Podcasts about Subgroup

N Engl J Med 2017;377:2419-2432Background: A small fraction of patients with acute myocardial infarction (5-10%) have cardiogenic shock. These patients have a high baseline mortality. Early revascularization had been established as better than initial stabilization with medical therapy. Many patients with cardiogenic shock due to acute myocardial infarction (AMI) have multivessel disease. The question arises about whether to do culprit-only percutaneous coronary intervention (PCI) or more complete PCI at the time of the initial intervention.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.The Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) trial was designed to test the hypothesis that PCI of the culprit lesion only, with the option of staged revascularization of nonculprit lesions, would result in better clinical outcomes than immediate multivessel PCI among patients who have multivessel coronary artery disease and acute myocardial infarction with cardiogenic shock.Patients: The trial enrolled 706 patients with acute myocardial infarction (ST-segment elevation or non-ST-segment elevation) complicated by cardiogenic shock who had multivessel coronary artery disease. Cardiogenic shock was defined as SBP < 90 mmHg for more than 30 minutes or requiring pressors, clinical signs of pulmonary congestion, and signs of organ hypoperfusion (altered mental status, cold/clammy skin, oliguria, or lactate > 2 mmol/L).Exclusion criteria were extensive and designed to exclude patients with extremely poor prognosis: prolonged resuscitation, no intrinsic heart action, fixed dilated pupils, an indication for urgent CABG, a mechanical cause of shock, age > 90 years, massive pulmonary embolism, or severe renal insufficiency at baseline.Baseline Characteristics: The median age was 70 years, and approximately 75% were male. About 63% of patients had three-vessel disease. More than half the patients had ST-segment elevation myocardial infarction (about 62%), and anterior ST-segment elevation MI accounted for approximately 54% of these cases. About 53% of patients required resuscitation before randomization. The median left ventricular ejection fraction was between 30-33%.Procedures: In the culprit-lesion-only PCI group, only the culprit lesion was treated during the initial procedure, with staged revascularization encouraged based on residual ischemic lesions. In the multivessel PCI group, PCI of all major coronary arteries with >70% stenosis was performed, including attempts to recanalize chronic total occlusions. Crossover from the culprit-lesion-only PCI group to the multivessel PCI group occurred in 12.5% of patients, while crossover in the opposite direction happened in 9.4% of patients. The overall dose of contrast material was significantly higher and the duration of fluoroscopy significantly longer in the multivessel PCI group. Other interventional therapeutic measures were allowed, independent of the assigned treatment strategy.Endpoints: The primary endpoint was a composite of death from any cause or severe renal failure leading to renal-replacement therapy within 30 days after randomization. Secondary endpoints included the individual components of the primary endpoint, recurrent myocardial infarction, rehospitalization for heart failure, repeat revascularization, time to hemodynamic stabilization, catecholamine therapy duration, ICU stay duration, and measurements of renal and myocardial injury. Safety end points included bleeding, which was defined as type 2, 3, or 5 on the Bleeding Academic Research Consortium (BARC) scale.Trialists estimated an event rate of the composite primary endpoint of 38% in the culprit-only group vs 50% in the complete group. Using a global type I error level of 0.05, the authors calculated that a sample of 684 patients would give the trial 80% power to rule out the null hypothesis of no difference between the two treatment groups in the event rate for the primary end point.Results: At 30 days, the composite primary endpoint occurred in 45.9% of patients in the culprit-lesion-only PCI group versus 55.4% in the multivessel PCI group (relative risk, 0.83; 95% CI, 0.71 to 0.96; P=0.01). Death occurred in 43.3% of the culprit-lesion-only PCI group versus 51.6% of the multivessel PCI group (relative risk, 0.84; 95% CI, 0.72 to 0.98; P=0.03). The rate of renal-replacement therapy was 11.6% in the culprit-lesion-only PCI group and 16.4% in the multivessel PCI group (relative risk, 0.71; 95% CI, 0.49 to 1.03; P=0.07).Rates of recurrent myocardial infarction, rehospitalization for heart failure, bleeding, and stroke did not differ significantly between groups. Subgroup analyses showed consistent results across all prespecified subgroups. The time to hemodynamic stabilization, the use of catecholamine therapy and the duration of such therapy, the duration of the ICU stay, and the use of mechanical ventilation and the duration of such therapy also did not differ significantly between the two groups.Conclusion: In patients with myocardial infarction and cardiogenic shock, culprit-only PCI was superior to multivessel PCI. Both components of the primary endpoint, death and severe renal failure were lower in the culprit-only arm. The authors and editorialists speculate why these findings contrast with trials in hemodynamically stable myocardial infarction patients, where early multivessel PCI showed benefit over culprit-only PCI.If you accept the thesis that multi-vessel PCI was superior to culprit-only PCI in stable AMI patients, the likely reason for the disparate results are that patients with cardiogenic shock differ substantially from stable patients. The sicker patients with cardiogenic shock benefit from a less-is-more approach where culprit-only PCI reduces treatment harm relative to multivessel PCI.We at CardiologyTrials, however, find the evidence for complete revascularization in stable AMI patients less than clear. The COMPLETE trial found benefit from multivessel PCI over culprit-only, but both composite endpoints were driven largely by non-fatal MI. CV death was not substantially different. The difference in MI could have been related to excluding procedure-related MI.What's more, the FULL-REVASC trial, which also compared culprit-only and multivessel PCI, failed to replicate the COMPLETE trial results. In FULL-REVASC the rates of the composite primary outcome of death, MI or unplanned revascularization were not significantly different. Sadly, FULL-REVASC was stopped early when COMPLETE results were published, which led to a possible loss of power.It's possible, likely even, that the null results of CULPRIT-SHOCK are not really that disparate from prior trials in patients with more stable AMI.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Commentary by Dr. Jian'an Wang.

The Lancet 2002;360:743-751Background: The TACTICS-TIMI 18 trial showed that an early invasive strategy in beneficial in selected patients with unstable angina or non-ST-elevation myocardial infarction (NSTEMI). These positive findings contrasted the findings from some earlier studies.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.The British Heart Foundation RITA 3 randomized trial sought to compare invasive vs conservative strategy in patients with unstable angina or NSTEMI, similar to the trial question of TACTICS-TIMI 18.Patients: Eligible patients had suspected cardiac chest pain at rest with at least one of the following: Evidence of ischemia on electrocardiogram (ST depression, transient ST elevation, old left bundle branch block, or T wave inversion), pathologic Q waves suggesting previous myocardial infarction, or documented coronary artery disease on prior coronary angiogram.Patients were excluded if they had evolving myocardial infarction in which reperfusion therapy was indicated. Patients were also excluded if creatine kinase or creatine kinase MB concentrations were twice the upper limit of normal before randomization, if they had myocardial infarction within a month, had percutaneous coronary intervention (PCI) in the previous 12 months, or coronary artery bypass grafting (CABG) at any time.Baseline characteristics: The trial randomized 1,810 patients – 895 randomized to the invasive strategy and 915 randomized to conservative strategy. Patients were recruited from 45 hospitals in England and Scotland.The average age of patients was 63 years and 62% were men. Approximately 35% had hypertension on drugs, 13% had diabetes and 28% had prior myocardial infarction.The majority (92%) of the patients were enrolled because they met the criteria for evidence of ischemia on electrocardiogram.Procedures: Patients were randomly assigned in a 1:1 ratio to undergo invasive vs conservative strategy.In the conservative arm, patients received aspirin and enoxaparin 1mg/kg subcutaneously twice a day for 2-8 days. Beta-blockers, other antiplatelets and glycoprotein IIb/IIIa inhibitors could also be used. Coronary angiography could be performed if patients had anginal symptoms at rest or with minimal exertion despite appropriate therapy or if they had ischemia on stress testing.Patients in the invasive strategy arm received similar medical therapy to the conservative arm. Coronary angiogram was to be performed as soon as possible after randomization and ideally within 72 hours. Revascularization was recommended for lesions of at least 70% stenosis or 50% or more if left main.Endpoints: The trial had two co-primary outcomes. The first was a composite of death from any cause, nonfatal myocardial infarction, or refractory angina at 4 months. The second was a composite of death from any cause or nonfatal myocardial infarction at 1 year.Analysis was performed based on the intention-to-treat principle. The estimated sample size to provide 80% power at 5% alpha, was 1,770 patients. This assumed that 12% of the patients in the conservative arm would experience the outcome of death or non-fatal myocardial infarction at 1-year, and that the invasive strategy would result in 33% relative risk reduction in this outcome.Results: In the invasive strategy, 97% of the patients underwent coronary angiogram at a median of 2 days after randomization, and 55.3% underwent PCI or CABG. In the conservative arm, 10.3% had revascularization during the index admission, and 17.3% had revascularization at 1-year. The median follow time was 2 years and 97% of the patients had at least 1-year of follow up.The first primary composite outcome of death from any cause, nonfatal myocardial infarction, or refractory angina at 4 months was lower with the invasive strategy (9.6% vs 14.5%, HR: 0.66, 95% CI: 0.51 – 0.85; p= 0.001). The second primary composite outcome of death from any cause or nonfatal myocardial infarction at 1 year was not significantly different between both groups (7.6% with invasive vs 8.3% with conservative, HR: 0.91, 95% CI: 0.67 – 1.25; p= 0.58). At 1-year, 4.6% patients died in the invasive arm compared to 3.9% in the conservative arm, and this was not statistically significant. Myocardial infarction at 1-year occurred in 3.8% of the patients in the invasive arm compared to 4.8% in the conservative arm, and this was not statistically significant as well.All bleeding occurred in 8.2% in the invasive arm and 3.5% in the conservative arm.Subgroup analysis showed that men benefited from an invasive strategy while women did not (p for interaction= 0.011). The endpoint of death or myocardial infarction at 1-year, in women, was 5.1% in the conservative arm and 8.6% in the invasive arm, while in men, the incidence of this endpoint was 10.1% in the conservative arm and 7.0% in the invasive arm.Conclusion: In patients with unstable angina or NSTEMI, an invasive strategy compared to conservative strategy, reduced refractory angina but not myocardial infarction or death at 1-year.The reduction in angina is a subjective endpoint, prone to bias and faith healing, as we have previously discussed in other trials of PCI. The reduction in this endpoint alone should not justify widespread adoption of invasive strategy for unstable angina or NSTEMI.A key distinction between this trial and TACTICS-TIMI 18—which demonstrated a reduction in myocardial infarction with an invasive approach—is that this study included patients with smaller myocardial infarctions. Only 41% of participants had ST depression or transient ST elevation, and patients were excluded if creatine kinase or creatine kinase MB levels were more than twice the upper limit of normal before randomization. This highlights the heterogeneity among patients with unstable angina and NSTEMI, where baseline risk and the extent of myocardial necrosis influence treatment effects. We encourage you to read again the subgroup interactions of TACTICS-TIMI 18.Additionally, in the current era, high-sensitivity troponin assays enable the detection of smaller myocardial infarctions, potentially limiting the applicability of older trial results to all present NSTEMI patients.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Featuring an interview with Dr Komal Jhaveri, including the following topics: Imlunestrant, an oral selective estrogen receptor degrader (SERD), with and without abemaciclib for ER-positive, HER2-negative advanced or metastatic breast cancer (0:00) Jhaveri KL et al. Imlunestrant, an oral selective estrogen receptor degrader (SERD), as monotherapy & combined with abemaciclib, for patients with ER+, HER2- advanced breast cancer (ABC), pretreated with endocrine therapy (ET): Results of the phase 3 EMBER-3 trial. San Antonio Breast Cancer Symposium 2024;Abstract GS1-01. Jhaveri KL et al. Imlunestrant with or without abemaciclib in advanced breast cancer. N Engl J Med 2024;[Online ahead of print]. Abstract Rugo HS et al. Elacestrant abemaciclib (abema) combination in patients (pts) with estrogen receptor-positive (ER+), HER2-negative (HER2-) advanced or metastatic breast cancer (mBC). San Antonio Breast Cancer Symposium 2024; Abstract PS7-07. Elacestrant for ER-positive, HER2-negative metastatic breast cancer with ESR1-mutated tumors: Subgroup analyses from the Phase III EMERALD trial by duration of prior endocrine therapy with a CDK4/6 inhibitor and in clinical subgroups (7:40) Bardia A et al. Elacestrant in ER+, HER2- MBC with ESR1-mutated tumors: Subgroup analyses from the phase III EMERALD trial by prior duration of endocrine therapy plus CDK4/6 inhibitor and in clinical subgroups. Clin Cancer Res 2024;30(19):4299-309. Abstract Pharmacokinetics and safety of imlunestrant in patients with hepatic impairment (11:25) Wang XA et al. Evaluation of pharmacokinetics and safety of imlunestrant in participants with hepatic impairment. San Antonio Breast Cancer Symposium 2024;Abstract P4-10-07. Precision therapeutics and emerging strategies for HR-positive metastatic breast cancer (13:15) Lloyd MR et al. Precision therapeutics and emerging strategies for HR-positive metastatic breast cancer. Nat Rev Clin Oncol 2024;21(10):743-61. Abstract CME information and select publications

Dr. Neeraj Agarwal and Dr. Peter Hoskin discuss key abstracts in GU cancers from the 2025 ASCO Genitourinary Cancers Symposium, including novel therapies in prostate, bladder, and kidney cancer and the impact of combination therapies on patient outcomes. TRANSCSRIPT Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, the director of the Genitourinary Oncology Program and professor of medicine at the Huntsman Cancer Institute at the University of Utah, and editor-in-chief of ASCO Daily News. Today, we'll be discussing practice-informing abstracts and other key advances in GU oncology featured at the 2025 ASCO Genitourinary Cancers Symposium. Joining me for this discussion is Dr. Peter Hoskin, the chair of this year's ASCO GU Symposium. Dr. Hoskin is a professor in clinical oncology in the University of Manchester and honorary consultant in clinical oncology at the Christie Hospital, Manchester, and University College Hospital London, in the United Kingdom. Our full disclosures are available in the transcript of this episode. Peter, thank you for joining us today. Dr. Peter Hoskin: Thank you so much, Neeraj. I am very pleased to be here. Dr. Neeraj Agarwal: The GU meeting highlighted remarkable advancements across the spectrum of GU malignancies. What stood out to you as the most exciting developments at the ASCO GU Symposium?  Dr. Peter Hoskin: The theme of this year's meeting was "Driving Innovation, Improving Patient Care," and this reflected ASCO GU's incredible milestone in GU cancer research over the years. We were thrilled to welcome almost 6,000 attendees on this occasion from over 70 countries, and most of them were attending in person and not online, although this was a hybrid meeting. Furthermore, we had more than 1,000 abstract submissions. You can imagine then that it fostered fantastic networking opportunities and facilitated valuable knowledge and idea exchanges among experts, trainees, and mentees. So, to start I'd like to come back to you for a second because the first day started with a focus on prostate cancer and some of the key clinical trials. And congratulations to you, Neeraj, on sharing the data from the TALAPRO-2 trial, which we were eagerly awaiting. I'd love to get your thoughts on the data that you presented. Could you tell us more about that trial, Abstract LBA18?  Dr. Neeraj Agarwal: Yes, Peter, I agree with you. It was such an exciting conference overall and thank you for your leadership of this conference. So, let's talk about the TALAPRO-2 trial. First of all, I would like to remind our audience that the combination of talazoparib plus enzalutamide was approved by the U.S. FDA in June 2023 in patients with metastatic castration-resistant prostate cancer harboring HRR gene alterations, after this combination improved the primary endpoint of radiographic progression-free survival compared to enzalutamide alone in the randomized, double-blind, placebo-controlled, multi-cohort phase 3 TALAPRO-2 trial. In the abstract I presented at ASCO GU 2025, we reported the final overall survival data, which was a key alpha-protected secondary endpoint in cohort 1, which enrolled an all-comer population of patients with mCRPC. So, at a median follow-up of around 53 months, in the intention-to-treat population, the combination of talazoparib plus enzalutamide significantly reduced the risk of death by 20% compared to enzalutamide alone, with a median OS of 45.8 months in the experimental arm versus 37 months in the control arm, which was an active control arm of enzalutamide. This improvement was consistent in patients with HRR alterations with a hazard ratio of 0.54 and in those with non-deficient or unknown HRR status, with a hazard ratio of 0.87. In a post hoc analysis, the hazard ratio for OS was 0.78 favoring the combination in those patients who did not have any HRR gene alteration in their tumors by both tissue and ctDNA testing. Consistent with the primary analysis, the updated rPFS data also favored the experimental arm with a median rPFS of 33.1 compared to 19.5 months in the control arm, and a hazard ratio of 0.667. No new safety signals were identified with extended follow-up. Thus, TALAPRO-2 is the first PARP inhibitor plus ARPI study to show a statistically significant and a clinically meaningful improvement in OS compared to standard-of-care enzalutamide as first-line treatment in patients with mCRPC unselected for HRR gene alterations. Dr. Peter Hoskin: Thank you, Neeraj. That's a great summary of the data presented and very important data indeed. There was another abstract also featured in the same session, Abstract 20, titled “Which patients with metastatic hormone-sensitive prostate cancer benefit more from androgen receptor pathway inhibitors? STOPCAP meta-analyses of individual participant data.” Neeraj, could you tell us more about this abstract? Dr. Neeraj Agarwal: Absolutely, I would be delighted to. So, in this meta-analysis, Dr. David Fischer and colleagues pooled individual participant data from different randomized phase 3 trials in the mHSPC setting to assess the potential ARPI effect modifiers and determine who benefits more from an ARPI plus ADT doublet. The primary outcome was OS for main effects and PFS for subgroup analyses. Prostate cancer specific survival was a sensitivity outcome. The investigators pooled data from 11 ARPI trials and more than 11,000 patients. Overall, there was a clear benefit of adding an ARPI on both OS and PFS, with hazard ratios of 0.66 and 0.51, respectively, representing a 13% and 21% absolute improvement at 5 years, respectively, with no clear difference by the class of agent. When stratifying the patients by age group, the effects of adding an ARPI on OS and PFS were slightly smaller in patients older than 75, than in those younger than 65, or aged between 65 and 75 years. Notably, in the trials assessing the use of abiraterone, we saw very little OS effects in the group of patients older than 75, however there was some benefit maintained in prostate-cancer specific survival, suggesting that other causes of death may be having an impact. The effects of the other ARPIs, or ‘lutamides' as I would call them, were similar across all three age subgroups on both OS and PFS. Therefore, the majority of patients with mHSPC benefit from the addition of ARPIs, and the benefits/risks of abiraterone and other ‘amides' must be considered in older patients.  Dr. Peter Hoskin: Thanks, Neeraj. Another great summary relevant to our day-to-day practice. Of course, there's ongoing collection of individual patient data from other key trials, which will allow robust comparison of ARPI doublet with triplet therapy (including docetaxel), guiding more personalized treatment.   Dr. Neeraj Agarwal: I agree with you, Peter, we need more data to help guide personalized treatment for patients with mHSPC and potentially guide de-escalation versus escalation strategies. Now, moving on to a different setting in prostate cancer, would you like to mention Abstract 17 titled, “Overall survival and quality of life with Lu-PSMA-617 plus enzalutamide versus enzalutamide alone in poor-risk, metastatic, castration-resistant prostate cancer in ENZA-p (ANZUP 1901),” presented by Dr. Louise Emmett? Dr. Peter Hoskin: Of course I will. So, ENZA-p was a multicenter, open-label, randomized, phase 2 trial conducted in Australia. It randomized 163 patients into adaptive doses (2 or 4 cycles) of Lu-PSMA-617 plus enzalutamide versus enzalutamide alone as first-line treatment in PSMA-PET-CT-positive, poor-risk, mCRPC. The interim analysis of ENZA-p with median follow-up 20 months showed improved PSA-progression-free survival with the addition of Lu-PSMA-617 to enzalutamide. Here, the investigators reported the secondary outcomes, overall survival, and health-related quality of life (HRQOL). After a median follow up of 34 months, overall survival was longer in the combination arm compared to the enzalutamide arm, with a median OS of 34 months compared to 26 months; with an HR of 0.55. Moreover, the combination improved both deterioration-free survival and health-related quality of life indicators for pain, fatigue, physical function, and overall health and quality of life compared to the control arm. Consistent with the primary analysis, the rPFS also favored the experimental arm with a median rPFS of 17 months compared to 14 months with a HR of 0.61. So, the addition of LuPSMA improved overall survival, and HRQOL in patients with high-risk mCRPC. Dr. Neeraj Agarwal: Thank you, Peter. Great summary, and promising results with Lu-177 and ARPI combination in first line treatment for mCRPC among patients who had two or more high risk features associated with early enzalutamide failure. Before we move on to bladder cancer, would you like to tell us about Abstract 15 titled, “World-wide oligometastatic prostate cancer (omPC) meta-analysis leveraging individual patient data (IPD) from randomized trials (WOLVERINE): An analysis from the X-MET collaboration,” presented by Dr. Chad Tang?  Dr. Peter Hoskin: Sure. So, with metastatic-directed therapy (MDT), we have a number of phase 2 studies making up the database, and the X-MET collaboration aimed to consolidate all randomized data on oligometastatic solid tumors. This abstract presented pooled individual patient data from all the published trials involving patients with oligometastatic prostate cancer who received MDT alongside standard of care (SOC) against SOC alone. The analysis included data from five trials, encompassing 472 patients with oligometastatic prostate cancer, and followed for a median of 41 months. Patients were randomly assigned in a 1:1 ratio to receive either MDT plus SOC or SOC alone. The addition of MDT significantly improved PFS. The median PFS was 32 months with MDT compared to 14.9 months with SOC alone, with an HR of 0.45. Subgroup analyses further confirmed the consistent benefits of MDT across different patient groups. Regardless of factors like castration status, receipt of prior primary treatment, stage, or number of metastases, MDT consistently improved PFS. In patients with mHSPC, MDT significantly delayed the time to castration resistance by nine months, extending it to a median of 72 months compared to 63 months in the SOC group with an HR of 0.58. In terms of OS, the addition of MDT improved the 48-month survival rate by 12%, with OS rates of 87% in the MDT+SOC group compared to 75% in the SOC alone group. Dr. Neeraj Agarwal: Thank you, Peter. These data demonstrate that adding MDT to systemic therapy significantly improves PFS, rPFS, and castration resistance-free survival, reinforcing its potential role in the treatment of oligometastatic prostate cancer. So, let's switch gears to bladder cancer and start with Abstract 658 reporting the OS analysis of the CheckMate-274 trial. Would you like to tell us about this abstract?  Dr. Peter Hoskin: Yes, sure, Neeraj. This was presented by Dr. Matt Milowsky, and it was additional efficacy outcomes, including overall survival, from the CheckMate-274 trial which evaluated adjuvant nivolumab versus placebo in patients with high-risk muscle-invasive bladder cancer after radical surgery. The phase 3 trial previously demonstrated a significant improvement in disease-free survival with nivolumab. With a median follow-up of 36.1 months, disease-free survival was longer with nivolumab compared to placebo across all patients with muscle-invasive bladder cancer, reducing the risk of disease recurrence or death by 37%. Among patients who had received prior neoadjuvant cisplatin-based chemotherapy, nivolumab reduced this risk by 42%, whilst in those who had not received chemotherapy, the risk was reduced by 31%. Overall survival also favored nivolumab over placebo, reducing the risk of death by 30% in all patients with muscle-invasive bladder cancer and by 52% in those with tumors expressing PD-L1 at 1% or higher. Among patients who had received prior neoadjuvant chemotherapy, nivolumab reduced the risk of death by 26%, whilst in those who had not received chemotherapy, the risk was reduced by 33%. Alongside this, the safety profile remained consistent with previous findings. Dr. Neeraj Agarwal: Thank you, Peter, for such a nice overview of this abstract. These results reinforce adjuvant nivolumab as a standard of care for high-risk muscle-invasive bladder cancer, offering the potential for a curative outcome for our patients. Dr. Peter Hoskin: I agree with you Neeraj. Perhaps you would like to mention Abstract 659 titled, “Additional efficacy and safety outcomes and an exploratory analysis of the impact of pathological complete response (pCR) on long-term outcomes from NIAGARA.” Dr. Neeraj Agarwal: Of course. Dr. Galsky presented additional outcomes from the phase 3 NIAGARA study, which evaluated perioperative durvalumab combined with neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer. The study previously demonstrated a significant improvement in event-free survival and overall survival with durvalumab compared to chemotherapy alone, with a manageable safety profile and no negative impact on the ability to undergo radical cystectomy. Among the 1,063 randomized patients, those who received durvalumab had a 33% reduction in the risk of developing distant metastases or death and a 31% reduction in the risk of dying from bladder cancer compared to those who received chemotherapy alone. More patients who received durvalumab achieved a pathological complete response at the time of surgery with 37% compared to 28% in the chemotherapy-alone group. Patients who achieved a pathological complete response had better event-free survival and overall survival compared to those who did not. In both groups, durvalumab provided additional survival benefits, reducing the risk of disease progression or death by 42% and the risk of death by 28% in patients with a pathological complete response, while in those patients without a pathological complete response, the risk of disease progression or death was reduced by 23% and the risk of death by 16% when durvalumab was added to the chemotherapy. Immune-mediated adverse events occurred in 21% of patients in the durvalumab group compared to 3% in the chemotherapy-alone group, with grade 3 or higher events occurring in 3% compared to 0.2%. The most common immune-related adverse events included hypothyroidism in 10% of patients treated with durvalumab compared to 1% in the chemotherapy-alone group, and hyperthyroidism in 3% versus 0.8%. At the time of the data cutoff, these adverse events had resolved in 41% of affected patients in the durvalumab group and 44% in the chemotherapy-alone group. Dr. Peter Hoskin: Thank you, Neeraj, for the great summary. These findings further support the role of perioperative durvalumab as a potential standard of care for patients with muscle-invasive bladder cancer. Dr. Neeraj Agarwal: I concur with your thoughts, Peter. Before wrapping up the bladder cancer section, would you like to mention Abstract 664 reporting updated results from the EV-302 trial, which evaluated enfortumab vedotin in combination with pembrolizumab compared to chemotherapy as first-line treatment for patients with previously untreated locally advanced or metastatic urothelial carcinoma? Dr. Peter Hoskin: Yes, of course. Dr. Tom Powles presented updated findings from the EV-302 study, and in this abstract presented 12 months of additional follow-up for EV-302 (>2 y of median follow-up) and an exploratory analysis of patients with confirmed complete response (cCR). The study had a median follow-up of 29.1 months and previously demonstrated significant improvements in progression-free survival and overall survival with enfortumab vedotin and pembrolizumab. This is now the standard of care in global treatment guidelines. Among the 886 randomized patients, enfortumab vedotin and pembrolizumab reduced the risk of disease progression or death by 52% and the risk of death by 49% compared to chemotherapy. The survival benefit was consistent regardless of cisplatin eligibility or the presence of liver metastases. The confirmed objective response rate was higher with enfortumab vedotin and pembrolizumab at 67.5% compared to 44.2% with chemotherapy. The median duration of response was 23.3 months with enfortumab vedotin and pembrolizumab compared to 7.0 months with chemotherapy. A complete response was achieved in 30.4% of patients in the enfortumab vedotin and pembrolizumab group compared to 14.5% in the chemotherapy group, with the median duration of complete response not yet reached in the enfortumab vedotin and pembrolizumab group compared to 15.2 months in the chemotherapy group. Severe treatment-related adverse events occurred in 57.3% of patients treated with enfortumab vedotin and pembrolizumab compared to 69.5% in the chemotherapy group, while in patients who achieved a complete response, severe adverse events occurred in 61.7% of those treated with enfortumab vedotin and pembrolizumab compared to 71.9% with chemotherapy. Treatment-related deaths were reported in 1.1% of patients treated with enfortumab vedotin and pembrolizumab compared to 0.9% with chemotherapy, with no treatment-related deaths occurring in those who achieved a complete response. These findings clearly confirm the durable efficacy of enfortumab vedotin and pembrolizumab, reinforcing its role as the standard of care for the first-line treatment of patients with locally advanced or metastatic urothelial carcinoma, and no new safety concerns have been identified. Dr. Neeraj Agarwal: Thank you for this great summary. Moving on to kidney cancer, let's talk about Abstract 439 titled, “Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Final follow-up results from the CheckMate-9ER trial.” Dr. Peter Hoskin: Sure. Dr. Motzer presented the final results from the phase 3 CheckMate-9ER trial, which compared the combination of cabozantinib and nivolumab against sunitinib in previously untreated advanced renal cell carcinoma. The data after more than five years follow-up show that the combination therapy provided sustained superior efficacy compared to sunitinib. In terms of overall survival, we see an 11-month improvement in median OS, 46.5 months for the cabo-nivo versus 35.5 months for sunitinib and a 42% reduction in the risk of disease progression or death, with median progression-free survival nearly doubling – that's 16.4 months in the combination group and 8.3 months with sunitinib. Importantly, the safety profile was consistent with the known safety profiles of the individual medicines, with no new safety concerns identified. Dr. Neeraj Agarwal: Great summary, Peter. These data further support the efficacy of cabo-nivo combination therapy in advanced renal cell carcinoma, which is showing a 11-month difference in overall survival. Dr. Peter Hoskin: Neeraj, before wrapping up this podcast, would you like to tell us about Abstract 618? This is titled “Prospective COTRIMS (Cologne trial of retroperitoneal lymphadenectomy in metastatic seminoma) trial: Final results.” Dr. Neeraj Agarwal: Sure, Peter. I would be delighted to. Dr Heidenrich from the University of Cologne in Germany presented the COTRIMS data evaluating retroperitoneal LN dissection in patients with clinical stage 2A/B seminomas. Seminomas are classified as 2A or B when the disease spreads to the retroperitoneal lymph nodes of up to 2 cm (CS IIA) or of more than 2 cm to up to 5 cm (CS 2B) in maximum diameter, respectively. They account for 10-15% of seminomas and they are usually treated with radiation and chemotherapy. However, radiation and chemo can be associated with long-term toxicities such as cardiovascular toxicities, diabetes, solid cancers, leukemia, particularly for younger patients. From this standpoint, Dr Heidenrich and colleagues evaluated unilateral, modified template, nerve-sparing retroperitoneal lymph node dissection as a less toxic alternative compared to chemo and radiation. They included 34 patients with negative AFP, beta-HCG, and clinical stage 2A/B seminomas. At a median follow-up of 43.2 months, the trial demonstrated great outcomes: a 99.3% treatment-free survival rate and 100% overall survival, with only four relapses. Antegrade ejaculation was preserved in 88% of patients, and severe complications such as grade 3 and 4 were observed in 12% of patients. Pathological analysis revealed metastatic seminoma in 85% of cases, with miR371 being true positive in 23 out of 24 cases and true negative in 100% of cases. It appears to be a valid biomarker for predicting the presence of lymph node metastases. These findings highlight retroperitoneal lymph node dissection is feasible; it has low morbidity, and excellent oncologic outcomes, avoiding overtreatment in 80% of patients and sparing unnecessary chemotherapy or radiotherapy in 10-15% of cases. Dr. Peter Hoskin: Great summary and important data on retroperitoneal lymphadenectomy in metastatic seminoma. These findings will help shape clinical practice. Any final remarks before we conclude today's podcast? Dr. Neeraj Agarwal: Before wrapping up this podcast, I would like to say that we have reviewed several abstracts addressing prostate, bladder, kidney cancers, and seminoma, which are impacting our medical practices now and in the near future. Peter, thank you for sharing your insights with us today. These updates are undoubtedly exciting for the entire GU oncology community, and we greatly appreciate your valuable contribution to the discussion and your leadership of the conference. Many thanks. Dr. Peter Hoskin: Thank you, Neeraj. Thank you for the opportunity to share this information more widely. I'm aware that whilst we have nearly 6,000 delegates, there are many other tens of thousands of colleagues around the world who need to have access to this information. And it was a great privilege to chair this ASCO GU25. So, thank you once again, Neeraj, for this opportunity to share more of this information that we discussed over those few days. Dr. Neeraj Agarwal: Thank you, Peter. And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.  Find out more about today's speakers:   Dr. Neeraj Agarwal    @neerajaiims    Dr. Peter Hoskin Follow ASCO on social media:      @ASCO on Twitter      ASCO on Bluesky  ASCO on Facebook      ASCO on LinkedIn      Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas Dr. Peter Hoskin: Research Funding (Institution): Varian Medical Systems, Astellas Pharma, Bayer, Roche, Pfizer, Elekta, Bristol Myers  

This week James and Jeff delve into one (...of the many) subgroup analyses of the DREAM study. What is better surgery or Physiotherapy for meniscal tears?How can we predict which patients will do well in each group? Why does Jeff hate the world of research?

LATE BREAKING CLINICAL SCIENCE: Benefits of Dynamx Bioadaptor Versus DES in Patients With Dyslipidemia: Subgroup Analysis Results from the BIOADAPTOR RCT

Why you should listenLearn how Google Ads work specifically for tech and consulting businesses, including different types of campaigns and their effectiveness.Discover why Google remains a dominant player in digital advertising and how to leverage its strengths even in a competitive landscape.Gain insights into the power of retargeting ads and how to create effective campaigns that resonate with your audience.Are you struggling to generate leads beyond referrals and partnerships? In this episode, we tackle this common challenge with expert insights from John Horn, CEO of the StubGroup. With over 11 years of experience in digital marketing, John reveals how Google Ads can be a game-changer for tech consultants and businesses seeking to attract more clients. He discusses the mechanics of Google Ads, the platform's enduring relevance despite emerging AI competitors, and effective strategies for retargeting ads to engage potential customers who have already shown interest in your services.About John HornJohn Horn is the CEO of StubGroup, a digital advertising agency and a premier Google ad agency. Subgroup has helped over 2000 clients, across 15k campaigns, with their paid ads and suspension issues. They have generated over half a billion dollars in revenue for their clients across many different verticals including ecommerce, lead generation, B2B, B2C, local services, and more.John has also taught digital advertising to over 100,000 students via online courses and the videos he produces through StubGroup's YouTube channel have received millions of views. When he's not marketing, John loves spending time with his wife and two little boys and exploring the Texas countryside he calls home.Resources and Linksstubgroup.comJohn's LinkedIn profileStubGroup Youtube channel: @StubgroupPrevious episode: 585 - The LinkedIn Assistant That Helps Users Save Time and Make Money with Joe ApfelbaumCheck out more episodes of The Paul Higgins ShowSubscribe to our YouTube channel: @PaulHigginsMentoringThe Tech Consultant's RoadmapJoin our newsletterJoin the Tech CollectiveSuggested resources

In this episode, we dive into the hottest updates in myeloma and amyloidosis at ASH 2024 annual meeting with Dr. Rakesh Popat. Here are the abstracts we discussed: 1. AQUILA Trial in High-Risk SMMOverview of the AQUILA trial testing single-agent daratumumab for high-risk smoldering multiple myeloma (HR-SMM) versus active monitoring. Discussion on patient characteristics, primary endpoints, and results showing significant progression-free survival (PFS) benefit with Dara. Insights into modes of progression, adequacy of active surveillance, and post-protocol therapy in control arm. Read the abstract. Read the simultaneous publication at NEJM. 2. Anito-Cel: New BCMA CAR T Therapy Early data from the iMMagine-1 trial showing strong efficacy and a promising safety profile for Anito-Cel, a novel BCMA CAR T. Discussion of its potential to rival cilta-cel while avoiding neurotoxicity concerns. Read the abstract.3. CARTITUDE-4 Update Updates on MRD-negativity rates and survival outcomes for cilta-cel in relapsed myeloma, with significant benefits over standard care. Read the abstract.4. ANDROMEDA OS Data in AL Amyloidosis Long-term data showing an overall survival (OS) benefit of Dara-VCd over VCd in AL amyloidosis. Insights into cardiac responses and crossover impact. Read the abstract.5. OPTIMUM Trial in Ultra-High-Risk NDMMFive-year follow-up of a tailored approach for ultra-high-risk newly diagnosed myeloma patients with continuous therapy incorporating multiple active agents. Subgroup outcomes highlighting both challenges and exceptional results. Read the abstract6. GMMG-HD7 Trial PFS Update Phase 3 trial results on Isa-VRD vs. VRD induction and risk-adapted tandem ASCT. Discussion on the role of CD38 in maintenance therapy. Read the abstract Read the simultaneous publication at JCO7. Exciting New Drugs Review of three innovative therapies: inobrodib, a BCMA-CD38 trispecific antibody, and cevostamab, a FcRH5-targeted bispecific antibody. Expert insights into their efficacy and potential to reshape myeloma care. Read the abstract

Episode 112: Grab the Ultimate Ad Script right HERE - https://join.digitaltrailblazer.com/ultimate-ad-scriptGoogle ads work for a lot of businesses, but do they actually work for selling online courses, coaching programs, or agency services?At first, it seems like you should be able to find very high-intent buyers if you target the right keywords… if someone is searching for “best fitness coach”, you would think that running ads for that keyword would give you “ready-to-buy” leads, right?The answer is more complicated than one might think.In this episode, Google Ads expert John Horn breaks down the pros and cons of Google ads for coaches and course creators and explains when it might make sense and when it doesn't. He also gives us a bunch of tips on how to make different types of paid ads work for online businesses.About John Horn: John Horn is the CEO of StubGroup, a digital advertising agency and a premier Google ad agency. Subgroup has helped over 2000 clients, across 15k campaigns, with their paid ads and suspension issues. They have generated over half a billion dollars in revenue for their clients across many different verticals including ecommerce, lead generation, B2B, B2C, local services, and more.John has also taught digital advertising to over 100,000 students via online courses and the videos he produces through StubGroup's YouTube channel have received millions of views. When he's not marketing, John loves spending time with his wife and two little boys and exploring the Texas countryside he calls home.Grab John's Free Resources Here: https://stubgroup.com/free/Connect with John: Website: https://stubgroup.com/ LinkedIn: https://www.linkedin.com/in/johnjhorn1/ Youtube: https://www.youtube.com/@Stubgroup Facebook: https://www.facebook.com/StubGroup/ Instagram: https://www.instagram.com/stubgroupadvertising/ TikTok: https://www.tiktok.com/@stubgroup Twitter: https://twitter.com/stubgroup LinkedIn: https://www.linkedin.com/company/stub-group/Grab our Ultimate Ad Script for Coaches, Agencies, and Course Creators.Learn the exact 5-step script we teach our clients that allows them to generate targeted, high-quality leads at ultra-low cost, so you can land paying customers and clients without breaking the bank on ad spend.Grab the Ultimate Ad Script right HERE - https://join.digitaltrailblazer.com/ultimate-ad-script✅ Connect With Us:Website - https://DigitalTrailblazer.comFacebook - https://www.facebook.com/digitaltrailblazer/TikTok: https://www.tiktok.com/@digitaltrailblazerTwitter: https://twitter.com/DgtlTrailblazerInstagram: https://www.instagram.com/DigitalTrailblazer

Instead of grouping together people with autism based on traditional severity scores, what if groupings were done based on functional outcome? Would this help better understand the broad spectrum of autism and why some people with autism are so different than others? Researchers at the University of Minnesota led by Kyle Sterrett, together with UCLA … Continue reading "Profound Autism: The first meaningful autism subgroup"

Lancet 1982;320:1173-1180Background: The first coronary artery bypass graft surgery (CABG) was performed in 1964 and by the 1970's it was commonly used for relief of angina. However, whether it improved survival was unknown. The European Coronary Surgery Study (ECSS) sought to test the hypothesis that CABG compared to medical therapy improved survival at 5 years.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Note to readers: Several preliminary reports of ECSS results were published at earlier time points (2 and 3-5 years). We are reporting the 5-year results since this was the prespecified hypothesis the investigators sought to test.Patients: Men under 65 years of age with angina pectoris of more than 3 months duration, a left ventricular ejection fraction >50%, and angiographic obstruction of >/=50% in at least 2 major coronary vessels with at least 1 vessel suitable for grafting. Patients with severe angina that could not be controlled with medical therapy were excluded.Baseline characteristics: No information is provided in the main paper on the number or characteristics of individuals screened to enrolled. There were 768 patients enrolled in the study. They were recruited from September, 1973 to March, 1976. The average age of patients was 50 years and the left ventricular ejection fraction was 65%. Approximately, 46% had a previous heart attack, 43% smoked, 35% had a high cholesterol, 15% had hypertension and 6% had diabetes. In terms of coronary anatomy, 53% had 3-vessel disease, 40% had 2-vessel disease, and 7% had left main disease.Procedures: Patients were randomly assigned to receive medical or surgical treatment. Medical measures varied based on location. The authors reported that strict standardization was not felt to be practical or necessary. Surgical treatment was either with saphenous-vein graft or internal mammary artery and was performed as soon as possible following randomization. The average time from randomization to surgery was approximately 4 months.Follow-up evaluations were performed 6 months after randomization and annually thereafter. Graft angiography was planned at 6 and 12 months after operation.Endpoints: The primary endpoint was all-cause death. The prespecified minimum follow-up time, set at the start of the trial, for all patients was 5 years. At the time of this report, some patients had been followed up to 8 years. A strict hypothesis was not tested (i.e., CABG would reduce death by X% compared to medical therapy). The primary analysis was a traditional intention to treat analysis and medical patients who crossed over to surgery and surgical patients who died prior to receiving surgery or refused surgery after randomization were retained within their original groups.Results: There were 767 patients included in the final analysis; 373 patients in the medical group and 394 in the surgical group (1 patient was lost from the surgical group immediately following randomization and was not counted in the group). At 5 years, 90 patients (24%) of the medical group had crossed over to surgery and 26 (7%) of the surgical patients were not operated on. An average of 1.9 grafts per patient were performed in the 2-vessel disease subgroup and 2.4 grafts per patient in the 3-vessel disease subgroup. The graft patency rate was 90% within 9 months and 77% between 9 and 18 months.Compared to medical therapy, surgery significantly reduced death at 5 years by 53% (7.6% vs 16.4%; p=0.00025). Operative (in-hospital) mortality was 3.6% for a total of 494 operations and 7.7% for 26 reoperations. Seven of 27 prespecified variables recorded at the time of randomization were found to be associated with significant treatment effect heterogeneity. They included: (i) extent of disease; (ii) location of lesion(s) in the proximal third of the left anterior descending artery (proximal LAD); (iii) resting ECG suggestive of previous possible or probable myocardial infarction and/or with other specified abnormalities (iv) ischemic ST-segment response predominantly in lead V5 during maximum level of a multistage symptom/sign-limited bicycle exercise test; (v) history of peripheral arterial disease; (vi) age; and (vii) mode of treatment.Subgroup analysis on the basis of coronary anatomy supported a significant advantage of surgery for patients with left main disease (14.3% vs 32.1%; p=0.11) and 3-vessel disease (6% vs 17.6%; p=0.003) but not in 2-vessel disease (8.8% vs 11.8%; p>0.20). The left main subgroup could have had 2- or 3-vessel disease and the p-value was insignificant due to the small sample size.Surgery significantly reduced death in patients with proximal LAD disease (7.3% vs 18%; p=0.0004) but not in those without it (6.7% vs 7.9%; p>0.20). In the subset of patients with 2-vessel disease and without proximal LAD disease, surgery caused a numerical increase in death at 5 years, attributed to operative mortality.Surgery significantly reduced death in patients with >/= 1.5mm exertional ST depression on bicycle testing (8.3% vs 21%; p=0.003) but not in those without it (5.1% vs 9.7%; p>0.20).Angina and exercise performance were significantly improved in the surgery group compared to medicine. Conclusions: Compared to medical therapy, bypass surgery using internal mammary arteries and saphenous vein grafts significantly reduced mortality at 5 years in men under 65 years of age with normal left ventricular function. Approximately 11 men would need to be treated with CABG to prevent 1 death. This represents a large benefit for bypass surgery in well-selected patients at the time the study was undertaken. Contemporary caveats to this interpretation include improvements in medical therapy since the publication of ECSS mainly involving aspirin and cholesterol lowering drugs for patients with CAD as well as an improvement in the general management of conditions like hypertension and diabetes. Also, smoking rates have significantly declined at the population level.Despite the impressive benefit of bypass surgery seen in this study, important treatment effect heterogeneity was identified for certain lower risk patient groups including those with 2-vessel disease, absence of proximal LAD disease, and minimal ST depression on symptom limited bicycle testing. Theoretically, such patients would be expected to benefit from bypass surgery even less today given the improvements in medical therapy mentioned above.Finally, it is worth pointing out the difference in treatment effects seen in this study compared to the Veterans Administration Cooperative Study that we reviewed earlier this week, which was a negative trial. In the Veterans Administration Cooperative Study, coronary bypass was performed primarily with saphenous vein grafting whereas ECSS used internal mammary arteries and saphenous vein grafts. Internal mammary arteries are superior conduits compared to vein grafts. They have improved long-term patency rates, which is attributed to their striking resistance to the development of atherosclerosis. Furthermore, they are used almost exclusively on the LAD, which is the most important vessel.In conclusion, ECSS demonstrated that CABG surgery dramatically reduced death at 5 years compared to medical treatment; however, we should be aware of the caveats mentioned above and appreciate that the trial was limited to highly selected male patients under the age of 65.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

At the 2024 European Hematology Association (EHA) Congress, CancerNetwork® spoke with a variety of experts in the hematologic oncology space about optimizing outcomes across different patient populations and subgroups based on updated research they presented at the meeting.  Manali Kamdar, MD, an associate professor of medicine-hematology and clinical director of Lymphoma Services at the University of Colorado Anschutz Medical Campus, in Colorado, spoke about data from the phase 1 TRANSCEND NHL 001 trial (NCT02631044) supporting the use of lisocabtagene maraleucel (liso-cel; Breyanzi) in earlier lines of therapy for patients with relapsed/refractory mantle cell lymphoma (MCL).1  Specifically, Kamdar highlighted how research should continue to focus on the potential utility of liso-cel in MCL subgroups such as those with TP53 mutations or blastoid morphology. Additionally, she stated that liso-cel may need to be further tested in earlier lines of therapy for patients with diffuse large B-cell lymphoma, including those with double-hit lymphoma. Michael R. Grunwald, MD, chief of the Leukemia Division and director of the Transplantation and Cellular Therapy Program at Atrium Health's Levine Cancer Institute, in North Carolina, discussed findings from the Prospective Observational Study of Patients With Polycythemia Vera (PV) in US Clinical Practices Trial (REVEAL) exploring risk factors for disease progression in patients with polycythemia vera (PV).2 According to Grunwald, a history of thromboembolic events, elevated white blood cell counts, and higher variant allele frequencies may contribute to a patient's likelihood of experiencing progression to myelofibrosis or acute myeloid leukemia (AML). Additionally, he highlighted ongoing research into the potential molecular factors that may prognosticate disease transformation in PV among a small cohort of patients enrolled on the REVEAL trial.3 Harry P. Erba, MD, PhD, a professor of medicine in the Division of Hematologic Malignancies and Cellular Therapy and the director of the Leukemia Program and Phase I Development in Hematologic Malignancies at Duke Cancer Institute, in North Carolina, discussed the clinical implications of data from the phase 3 QuANTUM-First study (NCT02668653).4  Specifically, findings demonstrated that continuation therapy with quizartinib (Vanflyta) elicited a more pronounced survival benefit vs placebo in patients with newly diagnosed FLT3-ITD–positive AML who did not undergo allogeneic hematopoietic stem cell transplant (allo-HSCT). However, Erba noted that survival outcomes were not significantly different in the quizartinib and placebo arms among patients who received allo-HSCT. References 1.        Palomba ML, Siddiqi T, Gordon LI, et al. Subgroup analyses in patients with R/R MCL treated with lisocabtagene maraleucel by prior lines of therapy and response to Bruton tyrosine kinase inhibitor from the TRANSCEND NHL 001 MCL cohort. Presented at the European Hematology Association (EHA) 2024 Congress; Madrid, Spain; June 13-16, 2024. P1126. 2.        Grunwald M, Zwicker J, Gerds A, et al. A real-world evaluation of risk factors for disease progression in patients with polycythemia vera (PV) enrolled in REVEAL. Presented at the 2024 European Hematology Association (EHA) Congress; June 13-16, 2024; Madrid, Spain. Abstract P1047. 3.        Crowgey E, Timmers C, Xue Z, et al. Analysis of molecular mechanisms and predictive biomarkers of disease transformation in polycythemia vera. Presented at the 2024 European Hematology Association (EHA) Congress; June 13-16, 2024; Madrid, Spain. Abstract S217. 4.        Sekeres MA, Erba H, Montesinos P, et al. QuANTUM-First: efficacy in newly diagnosed patients with FMS-like tyrosine kinase 3-internal tandem duplication–positive (FLT3-ITD+) acute myeloid leukemia (AML) who received continuation therapy. Presented at the 2024 European Hematology Association (EHA) Congress; June 13-16, 2024; Madrid, Spain. Abstract S142.

N Engl J Med 2013;369:999-1010Background: Adding P2Y12 inhibitors to aspirin improves outcomes in patients with acute coronary syndrome. Yet, debate persisted regarding the optimal timing for administering these drugs in patients undergoing percutaneous coronary intervention (PCI). The ATLANTIC trial showed that pre-hospital administration of ticagrelor did not improve outcomes compared to in-hospital administration, in patients with ST elevation myocardial infarction.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.The ACCOAST trial sought to test the hypothesis that administering the P2Y12 inhibitor, prasugrel, 2-48 hours before angiography in non-ST elevation myocardial infarction patients is superior to administering it during PCI.Patients: Patients were enrolled if they had non-ST elevation myocardial infarction. Patients were scheduled to undergo angiography with possible PCI within 2-48 hours after randomization. Patients were excluded if they had cardiogenic shock, refractory ventricular arrhythmias, prior hemorrhagic or ischemic stroke or TIA, history of intracranial neoplasms, history of intracranial AV malformations or aneurysm, surgery within 4 weeks, active bleeding or history of bleeding diathesis or had high risk of bleeding based on the judgement of the investigator.Baseline characteristics: The average age of patients was 64 years with 72% being men. The average weight was 82 kg. About 20% had diabetes, 45% had hyperlipidemia, 62% had hypertension and 33% were current smokers. Creatinine clearance was ≤ 30 ml/min in 3% of the patients and GRACE score was < 140 in 77% of them. Beta-blockers were given in 84% of the patients, statins in 90%, angiotensin-receptor blockers in 13% and ACE inhibitors in 70%.After randomization, 68.7% of the patients underwent PCI while 25.1% were treated medically. CABG within 7 days was performed in 6.2% of the patients.Procedures: Patients were randomized 1:1 to receive pretreatment with prasugrel or matching placebo (control group). Those in the pretreatment group received a 30 mg loading dose of prasugrel before coronary angiography with an additional 30 mg if angiography confirmed the need for PCI. Patients in the control group received placebo before coronary angiography and a 60 mg loading dose of prasugrel in patients undergoing PCI. Only the initial 30 mg loading dose of prasugrel or placebo were administered, if a decision, after coronary angiography, was made to pursue CABG or medical therapy.Endpoints: The primary efficacy end point was a composite endpoint of death from cardiovascular causes, myocardial infarction, stroke, urgent revascularization, or the need for rescue therapy with glycoprotein IIb/IIIa inhibitors. Follow up for the primary endpoint was 7 days post randomization. Secondary endpoints included death from any cause, stent thrombosis and a composite endpoint of death from cardiovascular causes, myocardial infarction, or stroke.Safety end points were major or minor bleeding according to Thrombolysis in Myocardial Infarction (TIMI) criteria.Statistical analysis was performed on the intention-to-treat principle. To achieve 80% power with two-sided alpha of 0.05 for detecting 24% relative risk reduction in the pretreatment compared to the control group, 400 patients with the primary outcome and approximately 4,100 enrolled patients would be needed.Results: The trial randomized 2,037 patients to the pre-treatment group and 1,996 to the control group. The median time from the initial loading dose to PCI was 4.3 hours.The incidence of the composite primary end point was similar between both treatment groups (10.0% in the pre-treatment group vs 9.8% in the control group, HR: 1.02, 95% CI: 0.84 – 1.25; p= 0.81). There was no significant difference between both treatment groups in any of the components of the primary end point, death from any cause, or stent thrombosis. Results were similar for patients who underwent PCI (about two thirds of study participants).There were more major bleeding events at 7 days in the pretreatment group (2.6% vs 1.4%, HR: 1.90, 95%: 1.19 – 3.02; p= 0.006). Major bleeding events not related to CABG were also higher in the pre-treatment group (1.3% vs 0.5%; p= 0.003). In the PCI cohort, 12 patients in the pre-treatment group had life-threatening bleeding compared to 2 in the control group. Most bleedings in this cohort were access site bleeding, pericardial bleeding and retroperitoneal bleeding.Subgroup analysis for the primary efficacy endpoint did not identify any subgroup who would benefit from pre-treatment with prasugrel.Conclusion: In patients with non-ST elevation myocardial infarction undergoing coronary angiography within 48 hours of admission, pre-treatment with prasugrel did not improve ischemic events and resulted in more major bleeding.The results of this trial led to the recommendation that prasugrel should be used after coronary anatomy is defined and PCI is chosen as the treatment strategy. This approach will reduce the risk of bleeding complications without increasing the risk of ischemic events.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

JAMA. 2013;309(12):1241-1250Background Case reports as early as the 1950s suggested chelation of lead might reduce angina. The popularity of chelation accelerated around the turn of the century. Small underpowered trials of chelation were inconclusive. Mainstream medicine considered chelation unproven and potentially hazardous.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.Chelation with disodium EDTA binds divalent and some trivalent cations, including calcium, magnesium, lead, cadmium, zinc, iron, aluminum, and copper, which facilitates their urinary excretion. High dose vitamins are often co-administered with chelation.The NIH-funded Trial to Assess Chelation Therapy (TACT) trial was conducted to respond to the public health problem posed by EDTA chelation therapy: namely, that large numbers of patients could be exposed to undefined risks for unproven benefits. TACT was a double-blind placebo-controlled 2x2 factorial randomized trial enrolling 1708 patients to test chelation therapy.Patients Eligibility for TACT required patients be older than 50 years, have a creatinine of < 2 mg/dl, and have survived a previous myocardial infarction. Exclusion criteria included platelet count less than 100 000/μL, abnormal liver function, BP > 160/100 mm Hg, past intolerance to the chelation or vitamin components, chelation therapy within 5 years, coronary or carotid revascularization planned or having taken place within 6 months, cigarette smoking within 3 months, active heart failure or heart failure hospitalization within 6 months, or inability to tolerate 500-mL infusions weekly. Enrollment began in 2003 and follow-up continued until 2011. There were 134 sites; 60% of which were established chelation centers.Baseline Characteristics The median age of patients was 65 years, 18% were women and the median body mass index was 30. More than 90% of patients had had either percutaneous coronary intervention or coronary bypass surgery. Approximately 31% of patients had diabetes. Use of guideline directed medications was typical of a well-treated population of post-MI patients. Procedures The active 10-component chelation solution consisted of up to 3 g of disodium EDTA; 7 g of ascorbic acid; 2 g of magnesium chloride; 100 mg of procaine; 2500 U of unfractionated heparin; 2 mEq of potassium chloride; 840 mg of sodium bicarbonate; 250 mg of pantothenic acid; 100 mg of thiamine; 100 mg of pyridoxine; and sterile water to make up 500 mL of solution. The identical-appearing placebo solution consisted of 500 mL of normal saline and 1.2% dextrose (2.5 g total).The chelation or placebo infusions were administered through a peripheral intravenous line, weekly for the first 30 infusions, followed by an additional 10 infusions 2 to 8 weeks apart. Patient also received an oral vitamin-mineral regimen vs an oral placebo. In this review, we focus on the intention-to-treat comparison of EDTA chelation vs placebo.Endpoints The primary endpoint was a composite of death, reinfarction, stroke, coronary revascularization, or hospitalization for angina.TACT trialists had planned to enroll 2300 patients over three years with a follow-up of one year. Enrollment was slow, and with permission from the data safety monitoring board (DSMB) enrollment was decreased to 1700 patients and follow-up was extended. The resultant power was 85% to detect a 25% reduction in the primary endpoint assuming a 2.5% per year event rate in the placebo arm.Over the course of the trial, the DSMB requested 11 interim analyses of the data. Because of the increased monitoring, the level of statistical significance required for the primary endpoint was enhanced to a P value of less than 0.036.Results After a median follow-up of 55 months, a primary end point occurred in 222 (26%) of the chelation group and 261 (30%) of the placebo group (hazard ratio [HR]: 0.82 [95% CI: 0.69-0.99]; p= .035). There was no effect on total mortality (10% vs 11%, HR: 0.93, 95% CI: 0.70-1.25; p= 0.64). Myocardial infarction and coronary revascularization favored chelation (6% vs 8% and 15% vs 18%, respectively), however this did not reach statistical significance for either endpoints.Subgroup analysis revealed a potentially important heterogenous treatment effect. In patients with diabetes (about a third of patients) there was an approximate 40% reduction in the primary endpoint (HR: 0.61, 95% CI: 0.45-0.83; p= 0.002).There were no significant differences in adverse effects between the two groups.The trialists did sensitivity analyses centering on patients who withdrew from the trial or were lost to follow-up. The comparison of the 2 groups remained significant even if the percentage of events among withdrawn/lost patients in the active group was 25% higher than in the placebo group.Conclusions The results of the TACT trial surprised the cardiology community. Prior beliefs were pessimistic because heavy metals was not a proven causal factor in atherosclerosis. What's more, the majority of patients were enrolled from non-traditional medical centers.Yet the effect size was both clinically important and statistically significant. The effect size in the diabetes subgroup, which was pre-specified, was even larger and more robust statistically than the general results. In fact, there was essentially no signal of benefit from chelation in non-diabetic patients. If this was confirmed, it would be a major finding both therapeutically and scientifically, as it would have discovered heavy metal exposure as an important cause of atherosclerosis.The Journal of the American Medical Association published the manuscript along with an explanatory letter from the editors, and an accompanying editorial from Dr. Steve Nissen, which challenged the internal validity of the trial.The results of TACT did not lead to widespread adoption of chelation, but it did lead primary investigator Gervasio Lamas to seek (and obtain) funding for a TACT 2 trial to study chelation in patients with diabetes. Experts often refer to subgroup findings as “hypothesis-generating” and so it was with the TACT 1 and TACT 2 trials.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

N Engl J Med 2010;363:930-942Background By 2010, dual antiplatelet therapy had been established as beneficial during and after percutaneous coronary intervention for acute coronary syndromes. Optimal dosing however remained unknown. This included the best loading dose of clopidogrel and optimal dose of aspirin.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.The Clopidogrel and Aspirin Optimal Dose Usage to Reduce Recurrent Events−Seventh Organization to Assess Strategies in Ischemic Syndromes (CURRENT–OASIS 7) trial was designed to determine whether a doubling of the loading and initial maintenance doses of clopidogrel is superior to the standard-dose regimen and whether higher-dose aspirin (300 to 325 mg daily) is superior to lower-dose aspirin (75 to 100 mg daily) in patients with acute coronary syndromes referred for an early invasive strategy.Patients Adult patients who presented with a non-ST-segment elevation acute coronary syndrome (ACS) or an ST-segment elevation myocardial infarction. Patients had to have had coronary angiography with a plan to perform PCI within 72 hours. Major exclusion criteria were an increased risk of bleeding or active bleeding and a known allergy to clopidogrel or aspirin. Baseline Characteristics Nearly all patients had angiography. About 68% had PCI and 32% did not have PCI due to lack of significant (≤70%) stenosis. About a quarter of patients had coronary-artery bypass surgery. The average age of patients was 61 years; 27% female sex, and 70% had a diagnosis of unstable angina or NSTEMI. The median time to randomization in patients with unstable angina/NSTEMI was 3.4 days vs 0.6 days in patients with STEMI. About 60% of patients were white, and 22% were Asian. The co-existing cardiac risk factors, such as smoking, hypertension, diabetes and previous MI were similar in all the trial arms, and typical of most trials at the time.Procedures The CURRENT-OASIS 7 trial had 2x2 factorial design. First, comparing in a double-blind fashion, a double dose vs standard dose clopidogrel regimen. In the second component, patients were randomly assigned in an open-labeled fashion to higher- or lower-dose aspirin.Immediately after randomization and before coronary angiography, patients randomly assigned to double-dose clopidogrel received a loading dose of 600 mg on day 1, followed by 150 mg once daily on days 2 through 7. Patients assigned to standard-dose clopidogrel received a 300-mg loading dose on day 1 before angiography, followed by 75 mg once daily on days 2 through 7. On days 8 through 30, both the double-dose and standard-dose groups received 75 mg of clopidogrel once daily.Patients randomly assigned to lower-dose aspirin received 75 to 100 mg daily on days 2 through 30, and those randomly assigned to higher-dose aspirin received 300 to 325 mg daily on days 2 through 30. An initial loading dose of aspirin 300 mg was used in both arms on day 1. Other therapies, such as anti-thrombotics were left to the discretion of the treating doctors. Endpoints The primary endpoint was cardiovascular death, myocardial infarction, or stroke at 30 days. The sample-size calculation estimated an event rate of 11% at 30 days with standard-dose clopidogrel or lower-dose aspirin. That would have led to 14,000 patients to have 90% power to detect a 16% reduction in the primary endpoint. Lower-than expected event rates required an increase in sample size to 25,000 patients. This allowed for an 80% power to detect a 16% reduction in the primary endpoint.Results  A primary outcome event occurred in 4.2% of patients in the double-dose clopidogrel group at 30 days, as compared with 4.4% in the standard-dose group (hazard ratio, 0.94, 95% confidence interval [CI], 0.83 to 1.06; P=0.30). The rate of death from any cause did not differ significantly between the double-dose and standard-dose groups (2.3% and 2.4%, respectively; hazard ratio with the double dose, 0.96; 95% CI, 0.82 to 1.13; P=0.61). Major bleeding occurred more often in the double-dose arm (2.5 vs 2.0% HR 1.24; 95% CI 1.05-1.46).For the aspirin comparison, the rate of primary outcome events did not differ: 4.2% in the higher-dose arm vs 4.4% in the lower-dose arm. Death from any cause was not statistically different in either arm. Major bleeding rates were also similar in the two aspirin arms (2.3% in both arms).The authors described a “nominally significant” interaction between clopidogrel dose and aspirin dose for the primary outcome. Among patients assigned to higher-dose aspirin, the primary outcome occurred in 3.8% of patients in the double-dose clopidogrel group, as compared with 4.6% of patients in the standard-dose clopidogrel group (hazard ratio, 0.82; 95% CI, 0.69 to 0.98; P=0.03). But in the lower dose aspirin group, there were no significant differences in the primary outcome between double-dose and standard-dose clopidogrel (4.5% vs 4.2% HR 1.07 95% CI 0.90-1.26, respectively). The p-value for the interaction here was 0.04. Subgroup analyses showed generally consistent results. One possible heterogenous treatment effect in the double- vs standard-dose clopidogrel comparison turned on whether the patient had PCI or did not have PCI. In the 68% (≈17,000) of patients who had PCI, double dose clopidogrel reduced the primary outcome by 15% (3.9% vs 4.5%) vs increasing it by 14% in the no PCI group (4.9% vs 4.3%). The p-value for interaction was 0.03. There were no indications of heterogenous treatment effects depending on aspirin.Conclusions In patients with ACS, double dose clopidogrel or aspirin compared to standard dose did not significantly reduce the composite endpoint of cardiovascular death, MI or stroke. Double dose clopidogrel did increase major bleeding with a NNH of approximately 200 patients. Treatment effect heterogeneity, favoring the double dose clopidogrel strategy, was suggested for patients undergoing PCI.This trial serves as a good example of the limitations of surrogate endpoints in predicting hard outcomes. Previous studies had demonstrated that higher doses of clopidogrel led to faster and more substantial platelets inhibition. The observed increase in bleeding events with double-dose clopidogrel supported these findings. Nonetheless, it did not correspond to better ischemic outcomes.As for the dose of aspirin, there was no added benefit (or increase in bleeding) with higher dose aspirin beyond 75-100 mg. Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: What should you do when you want to escape negative people of the community/subgroup you're in (but don't want to hamper your career)?, published by Polkashell on April 8, 2024 on The Effective Altruism Forum. I'm talking specifically of an EA group. Anyone have experiences or thoughts on if their local EA group became super toxic and was full of people that they thought were super questionable? What do you do when for instance, that group has a few people who are working on the same things you are (I.e, same career area) and so you feel that if you chose to work on your career separate from this community (instead of forcing yourself within it) your career would be hampered in some way? (Eg having to interact with them, not work with each other, same network where they might be community builders hosting events so you feel so unwelcome in those) I've for a while now felt a couple groups (not all) I've been in EA can be quite toxic, especially certain individuals. So it feels right to stay far away and not work with them at all. But you're worried since the talent pool is quite small it would be negative to not join forces in someway. I guess further, I've been feeling more disenthused with EA groups the past year, the group I was part of definitely had a lot of toxic community builders and members who said bad things, very red flag type things. It scares me to feel this way because it feels like it leaves me more alone among people who should care about things I do but they would actually seem not to (not all of them) and I think I could hamper my impact and career because I would be alone. It has made me seriously consider quitting EA and even the area I'm working on now just to be away from them because it's impossible not to interact with them if not. What advice does anyone have for me? Does anyone have similar experiences? How do you thrive in an EA career outside of EA when the network is so strong within EA? For instance if I want to work on X cause area but do not want to involve myself with EA specifically anymore, how can I be successful especially if the talent pool from where I'm from is quite small for that particular cause area? I keep thinking, if I distance myself from this pool then I might also distance myself from opportunity. Some people I think who are not super directly "EA" but are doing good work are Jess Whittlestone, Jaime Yassif, etc. (correct me if I'm wrong) Thoughts here? I'm really struggling with how I feel in this community and it's been really awful for my mental health. I feel like the community I was part of has been very unfair and yeah, toxic and if other people around the community I know not part of this group heard what they were doing or what they said they would think it were red flaggy. I might been roundabout there but this is a raw post/Q. I don't feel so comfortable talking to community health at the moment. I don't currently feel comfortable talking to the CH of my group too. But to be open, some of these experiences revolve: 1) intentionally sabotaging specifically people in the community 2) spreading false information about people in the community 3) badmouthing people in the community unfairly 4) being questionable in their EA intentions 5) showing signs of strong arrogance (entitled to someone's life information, throwing some mini tantrums when they're not chosen for job, etc. there are more but I don't think I should disclose that). If these people were to go around doing stuff would people recommend they be reported or flagged or not? Would people who might work with them want to know this stuff? It might look weird if I proactively told people this stuff, might make me a hypocrite. I'm not here to ruin people's careers or anything. But sometimes I feel very uneasy that I've just been quiet dealing with these pe...

Lancet 1996;347:561-68.Background In most of the prior AMI trials presented here, patients with non_ST-segment myocardial infarction (NSTEMI) and/or unstable angina were included with patients with ST-segment myocardial infarction (STEMI). Patients with NSTEMI usually represented about 1/3 of trial participants. It had become clear based on subgroup analyses from the previous trials that NSTEMI patients did not benefit from thrombolysis. So, while intravenous anticoagulation with heparin was not found to be beneficial in GISSI-2 or ISIS-3, where thrombolysis was also used, there remained the possibility that it may benefit patients with unstable coronary syndromes who were not candidates for thrombolytic therapy. This smaller trial represents a departure from the general eligibility criteria for the AMI trials that we have already reviewed. The Fragmin During Instability in Coronary Artery Disease (FRISC) study group sought to test the hypothesis that subcutaneous low-molecular-weight heparin, in combination with aspirin, reduces death and new cardiac events in patients with unstable CAD. For the purposes of this study, unstable CAD represents unstable angina and NSTEMI.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients Patients had to be men older than 40 years and women at least 1 year after menopause admitted to the hospital for chest pain within the previous 72 hours. All patients had to have either newly developed or increased angina symptoms during the previous 2 months or persisting chest pain with suspicion for AMI and at least one of the following ECG criteria: transient or persistent ST depression of ≥ 0.1 mV or T-wave inversion of ≥ 0.1 mV in at least 2 adjacent leads without pathological Q waves in the ischemic leads. Essentially, the authors were selecting patients with unstable angina or NSTEMIs and not STEMIs or completed infarcts. There were many exclusion criteria for the trial including the presence of conditions with an increased risk of bleeding, known renal or liver insufficiency, indications for thrombolysis, suspected myocarditis and many others; however, it is worth noting there was no upper age limit.Baseline characteristics There were 5,137 patients who met eligibility criteria and 1,506 (29%) were randomized. The 3 most common reasons for exclusion were risk of bleeding (20%), compliance problems (15%), and Q waves or bundle branch block (14%). Patients with other severe disease accounted for 4% of exclusions and those with renal or liver insufficiency accounted for 2%.The median age of participants was 69 years and approximately 65% were men. 20% of participants were active smokers, 13% had diabetes and nearly 30% had a previous heart attack. Patients with NSTEMI accounted for close to 40% of participants and the remainder had unstable angina.Procedures Treatment was started as soon as possible after admission. During the first 6 days (acute phase), 120 IU per kg bodyweight (maximum dose of 10,000 IU) of dalteparin or placebo was injected every 12 hr. There was then a home treatment phase. For the next 35-45 days—at home— 7,500 IU of dalteparin or placebo was injected once daily. Patients stayed in the hospital during the acute phase for at least 5 days and on day 5-8 were discharged with the lower home dose. On day 40-50, the treatment was stopped and the final follow-up visit was scheduled 5-7 months after trial enrollment.Endpoints The primary endpoint was the rate of death and new myocardial infarction during the first 6 days. Secondary endpoints were the rates of death and new MI after 40 and 150 days, the frequency of revascularization procedures and need for heparin infusion, and a composite endpoint. Cause of death and myocardial infarction were verified by the independent endpoint committee who had to differentiate a new event from an inclusion event. Safety endpoints included major and minor bleeding. Major bleeding was defined by a drop of ≥2 g/dL in hemoglobin with associated signs or symptoms of bleeding, and minor bleeding was any other bleeding not meeting the former criteria. A sample size of 1,500 was based on a power of 0.80 to detect a reduction in the primary composite endpoint from 6% to 3% at a 2-sided alpha of 5%. Subgroup analyses were prespecified and a “high-risk group” was defined by the presence of at least 2 of the following variables: age >70, previous MI, medically treated heart failure, or diabetes.Results 1,506 patients were included in the final analysis; 757 in the placebo group and 741 in the dalteparin group. At 6 days, dalteparin significantly reduced the occurrence of the primary endpoint (RR 0.37; 1.8% vs 4.8%; 95% CI 0.20-0.68), which was driven by myocardial infarction (RR 0.33; 1.4% vs 4.4%; 95% CI 0.16-0.60). There was no difference in death between groups (RR 0.88; 0.9% vs 1.1%; 95% CI 0.32-2.48) and minor bleeding events were much more common in the dalteparin group (8.2% vs 0.3%).At 40 (8.0% vs 10.7%) and 150 (14.0% vs 15.5%) days, differences between groups were less pronounced for the primary endpoint and the results, in favor of dalteparin, were not statistically significant. Bleeding events, driven by minor bleeding, continued to be much higher for the dalteparin group.Subgroup analyses are presented at 6 and 40 days and are generally concordant across subgroups, meaning the treatment effect goes in the same direction, but these analyses should be viewed skeptically as they represent small sample sizes, particularly compared to subgroups in the earlier mega trials. Subgroup data suggests concordant results for patients less than or greater than 70 years of age and for patients meeting high risk criterion compared to those not meeting it.Conclusions In patients with unstable angina and NSTEMI, dalteparin reduced the primary endpoint of death or nonfatal MI compared to placebo at 6 days and was associated with a NNT of 33 patients. This was driven by a reduction in nonfatal MI. The results were no longer significant at 40 or 150 days. This trial is limited by small sample size and highly selected patient population.Thank you for reading Cardiology Trial's Substack. This post is public so feel free to share it. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Claire chatted to Maria Jose (Marisé) Galvez Trigo from Cardiff University all about human-robot interaction, machine learning, and accessibility. Maria Jose Galvez Trigo (Marisé) is a Lecturer in the School of Computer Science and Informatics at Cardiff University, and part of the Human-centred Computing (HCC) Research Section and its Subgroup in Computational and Human-centred Robotics. Marisé is interested in Robotics, Human-Robot Interaction, Human-Computer Interaction and applications of Machine Learning in those areas, with accessibility and co-design as key aspects of her research. Within those areas, her research explores how the uptake of robotics systems can be improved. Win a Robot Talk T-shirt For a chance to win your very own organic cotton Robot Talk t-shirt, all you have to do is: Sign up to our newsletter Share our competition post on social media: Twitter, LinkedIn, Facebook, BlueSky, Threads or Mastodon You can enter across multiple platforms. One lucky winner will be randomly selected each month!  Find out more: https://www.robottalk.org/t-shirt-competition/.

In this episode of Carbless Conversations, we venture into the surprising intersection of Oreos, cholesterol, and statins in a bold experiment that challenges conventional wisdom. We will dive deep into a groundbreaking study conducted by Harvard medical student Nick Norwitz.  As we peel back the layers of this metabolic demonstration, the episode illuminates the nuances of this new "Lipid Energy Model" (LEM), the role of saturated fats, and the surprising efficacy of Oreos in lowering LDL cholesterol more dramatically than high-intensity statin therapy in people with a specific phenotype, namely the Lean Mass Hyper Responder (LMHR).  But it's not all cookies and cream; the conversation takes a critical look at the pharmaceutical industry's reliance on statins and the broader implications for those following a ketogenic diet.  With a blend of science and skepticism, this episode invites your brain to explode and for you to rethink everything you thought you knew about diet, cholesterol, saturated fat, and carbohydrates. Oreos Vs. Statins Study: https://www.mdpi.com/2218-1989/14/1/73 Keto/Low Carb/Carnivore recipes: https://trinakrug.com Keto/Low Carb/Carnivore/Diabetes Community: https://www.facebook.com/groups/335715249100159 Keto/Low Carb Recipes and Support Community: https://www.facebook.com/groups/1993303330779537 Email: trina@trinakrug.com   Please note that the content provided in this podcast is for informational purposes only and is not intended as professional advice. The views expressed by the hosts and guests are their own and should not be taken as expert guidance. While we strive to provide accurate and up-to-date information, we do not guarantee the completeness, reliability, or accuracy of this information. Listeners are encouraged to consult with a professional in the relevant field for any specific advice or information they may need. The creators of this podcast disclaim any liability for actions taken based on the content of this podcast.

This week we discuss the chronic neurological condition Multiple Sclerosis. Samantha Joseph BA (Hons), DipBCNH, mBANT, CNHC, is a Nutritional Therapist. Her husband Danny was diagnosed with MS in 2002 which led her to specialise in this area. She has been a guest lecturer for colleges of Integrative Nutrition covering modules on MS, Parkinson's disease, mental & behavioural health. In 2018 she joined the charity Overcoming MS as a senior facilitator. Samantha also worked together with the MS Academy (www.neurologyacademy.org) giving nutritional advice for their Healthy Living Services clinics and collaborated on the a paper pending in Frontiers of Neurology, highlighting holistic management of MS, https://linktr.ee/nutritionista_uk Karen Lee, previously intensive care nurse and practising registered nutritionist, combines her love of food with her professional background to inspire others to experience the powerful effects of food as medicine.  As ‘The Sensitive Foodie', Karen has run courses, workshops and cooking classes, and has a blog – The Sensitive Foodie Kitchen. In 2019, Karen published her first book Eat Well Live Well with The Sensitive Foodie and is currently working on her second. Karen is an Ambassador for Overcoming MS and helped to create The PBHP-UK factsheet on MS. She was co-author on a case study in The American Journal of Lifestyle Medicine. She is also Events Manager for Plant-Based Health Professionals UK. Website: https://thesensitivefoodiekitchen.com Facebook: https://facebook.com/thesensitivefoodie Instagram: https://Instagram.com/the.sensitive.foodie Historical Swank Evidence:  Swank RL, Dugan BB. Effect of low saturated fat diet in early and late cases of multiple sclerosis. Lancet. 1990 Jul 7;336(8706):37-9. Swank, RL. MS: a correlation of its incidence with dietary fat. Am J Med Sci. 1950;220:421-30  Bjørnevik, K. Polyunsaturated fatty acids and the risk of multiple sclerosis.  Multiple Sclerosis Journal,  2017. 23(14), 1830–1838  Jelinek GA, et al. Association of fish consumption and Ω 3 supplementation with quality of life, disability and disease activity in an international cohort of people with multiple sclerosis. Int J Neurosci. 2013 Nov;123(11):792-800 Esparza ML, et al. A brief original contribution: Nutrition, Latitude, and Multiple Sclerosis Mortality: An Ecologic Study. American Journal of Epidemiology, 1995. 142(7):733–737  Simpson-Yap S, et al. Longitudinal associations between quality of diet and disability over 7.5 years in an international sample of people with multiple sclerosis. Eur J Neurol. 2023 Jul 11. doi: 10.1111/ene.15980  Ayroza Galvão Ribeiro Gomes AB, et al. Immunoglobulin A Antibodies Against Myelin Oligodendrocyte Glycoprotein in a Subgroup of Patients With Central Nervous System Demyelination. JAMA Neurol. 2023 Aug 7:e232523 Agranoff BW & Goldberg D. Diet and the geographical distribution of multiple sclerosis. Lancet. 1974; 2:1061-6 Munger KL, et al. Vitamin D intake and incidence of MS. Neurology. 2004;62:60-5 Richards JB. Vitamin D and Risk of Multiple Sclerosis: A Mendelian Randomization Study., 2015. PLoS Medicine. Aug 25;12(8):e1001866 Hadgkiss EJ et al. The association of diet with quality of life, disability, and relapse rate in an international sample of people with multiple sclerosis. Nutritional Neuroscience. 2015;18(3):125-136. Fitzgerald KC, Tyry T, Salter A, Cofield SS, Cutter G, Fox R, Marrie RA. Diet quality is associated with disability and symptom severity in multiple sclerosis. Neurology. 2018 Jan 2;90(1):e1-e11. Simpson-Yap S, et al. Longitudinal associations between quality of diet and disability over 7.5 years in an international sample of people with multiple sclerosis. Eur J Neurol. 2023 Jul 11. doi: 10.1111/ene.15980 Evers I, et al. Adherence to dietary guidelines is associated with better physical and mental quality of life: results from a cross-sectional survey among 728 Dutch MS patients. Nutr Neurosci. 2022 Aug;25(8):1633-1640

Lancet 1988;349-360Background The introduction to the ISIS-2 manuscript opens with a remarkable statement from the authors:Reductions in mortality that are realistically moderate (eg, “only” 20-25%) are important, especially if produced by widely practicable treatments for common causes of death.At the time of this posting, January 2024, it's amazing to think, how in 1988, a 20-25% reduction in mortality was considered moderate for a “widely practicable treatment for a common cause of death” and now the profession seems to grasp at almost anything, at nearly any cost, that reduces some composite of hard, soft and, in some cases, completely meaningless endpoints by the same amount. Regardless, ISIS-2 sought to test the hypothesis that streptokinase and aspirin, either alone or together, would reduce vascular mortality in patients with MI.Patients Patients with suspected myocardial infarction, who the responsible physician thought were within 24 hours of symptom onset and had no clear indication for, or contraindication to, streptokinase or aspirin. Absolute contraindications included: any history of stroke or of gastrointestinal ulcer. Possible contraindications included: recent arterial puncture, recent severe trauma, severe persistent hypertension, allergy to streptokinase or aspirin, low risk of cardiac death, or some other life-threatening disease. ECG changes at entry were not required.The design was meant to be pragmatic to facilitate patient enrollment; however, exclusion criteria was more extensive for ISIS-2 compared to ISIS-1, which reflects concern about hemorrhagic side effects associated with use of these agents. Like ISIS-1, there were no special procedures dictating patient follow-up after the hospitalization ended.Baseline characteristics Basic demographic information is not provided in the main manuscript but we can infer from the subgroup Forest plots that more than two thirds of patients were men, the overwhelming majority were less than 70 years of age, and nearly half were less than 60. Less than 20% had a previous MI and only around 7% had diabetes. Patients with inferior and anterior STEMI's composed more than half of the cohort. About 43% of patients presented within 4 hours of symptom onset, another 42% presented between 5 and 12 hours, and the remaining 15% presented between 13 and 24 hours.Procedures A 2x2 factorial study design was used. All patients were randomly assigned to receive either streptokinase or a matching placebo. All patients were also randomly assigned to receive either aspirin or a matching placebo. This led to 4 distinct treatment groups: 1) streptokinase + aspirin placebo, 2) aspirin + streptokinase placebo, 3) streptokinase + aspirin, or 4) placebo onlyPatients allocated to receive streptokinase were immediately given 1.5 MU of ‘Streptase' over 1 hour. Patients allocated to receive aspirin were immediately given 162.5 mg of an enteric coated tablet that was crushed, sucked, or chewed for a rapid anti-platelet effect. Thereafter, they took a 162.5 mg tablet daily for 1 month.Endpoints Vascular mortality over 5 weeks was the primary endpoint. Follow-up after discharge involved only mortality, through government records wherever possible.Results 17,187 participants were randomized from 417 hospitals in 16 countries. Compliance with the assigned treatments was estimated to be between 90-95%.The results of ISIS-2 are not reported in a standard results table, making vascular mortality as well as all-cause mortality impossible to infer over the duration of the trial. The number of non-vascular deaths are presented in a table but vascular deaths beyond 5 weeks are not formally provided in the original publication. The only evidence of vascular deaths beyond 5 weeks is presented in survival curves.Over 5 weeks, Streptokinase alone reduced vascular mortality compared to placebo by approximately 25% (9.2% vs 12.0%) and these results were highly significant. The difference remained highly significant over the course of the trial. Non-vascular deaths accounted for a tiny fraction of all deaths (3.5%) and were unchanged between groups. Subgroup analysis of streptokinase efficacy based on time from pain onset showed it was more effective if given within 4 hours (8.2% vs 12.3%) vs between 5-24 hours (10.0% vs 11.8%).Streptokinase use was associated with higher rates of hypotension and bradycardia (10% vs 2.0%), allergic reactions (4.4% vs 0.9%), minor bleeding (3.5% vs 1.0%) and major bleeding (0.5% vs 0.2%). The bleeding excess appeared similar whether streptokinase was used with aspirin or not. Streptokinase was also associated with a small but significant risk of cerebral hemorrhage (7 vs 0 events) all of which were followed by death or severe disability. However, overall, streptokinase was not associated with an increase in stroke (0.7% vs 0.8%) or in the risk of disabling/fatal stroke (0.5% vs 0.6%).Aspirin alone reduced vascular mortality compared to placebo by 23%, approximately the same amount as streptokinase alone over 5 weeks (9.4% vs 11.8%), and these results were highly significant and remained so over the course of the trial. There were fewer non-vascular deaths among aspirin allocated patients, so all-cause deaths were also significantly reduced but like with streptokinase, non-vascular death accounted for a tiny fraction of all deaths. Unlike Streptokinase alone, the treatment effect of aspirin was unchanged regardless of when it was started relative to the onset of pain.Aspirin significantly increased minor bleeds (2.5% vs 1.9%) but there were no major differences in any other side effects.Streptokinase and aspirin compared to double placebo reduced vascular mortality nearly twice as much as either agent alone (8.0% vs 13.2%) and these results were highly significant and remained so over the course of the trial. Non-vascular deaths were the same between groups and so all-cause mortality was also significantly reduced by streptokinase and aspirin. Subgroup analysis based on time from pain onset demonstrated greater efficacy for those receiving treatment in under 4 hours (6.4% vs 13.1%) compared to those receiving treatment between 5-24 hours (9.2% vs 13.3%).Streptokinase and aspirin together were associated with increases in major and minor bleeding as well as cerebral hemorrhage that were similar to streptokinase alone both in terms of their relative and absolute differences.Additional subgroup analyses suggest that patients presenting with anterior STEMI's derived the greatest benefit from streptokinase alone and in combination with aspirin. The risk of death was about twice as high for patients presenting with an anterior vs inferior STEMI (15% vs 8%). Patient's presenting with ST depression on their ECGs experienced a similar overall risk of death compared to patients with anterior STEMI's but did not appear to derive a significant benefit from any combination of treatment.Conclusions Streptokinase alone and aspirin alone reduced death over 5 weeks compared to placebo. 30 to 40 patients would need to be treated with either agent alone to prevent 1 person from dying, which was very similar to the effect noted in the GISSI trial that tested Streptokinase alone. In ISIS-2, the combination of the 2 agents (Streptokinase and Aspirin) reduced death even further (nearly twice the effect of either agent alone) compared to double placebo controls and this was associated with an NNT of 20 or less. Streptokinase, whether alone or in combination with aspirin, exerted the greatest effect when given to patients presenting within 4 hours from pain onset but was still effective when given outside this window (subgroup stratification was not the same as GISSI, which showed that the benefit waned and possibly reversed after 6-9 hours). In ISIS-2 there was no evidence to suggest that sicker patients or those with larger MI's did worse (i.e, lower SBP, higher HR, or anterior STEMI) but again, not all subgroups presented were the same as in the GISSI trial, which did show less benefit for some higher risk groups. Like GISSI, ISIS-2 provided evidence that patients presenting with NSTEMI's did not benefit from streptokinase.In summation, ISIS-2, like the GISSI trial that preceded it, demonstrated the significant impact of early revascularization via thrombolysis on mortality in patients presenting with STEMI. It also demonstrated the significant benefit of aspirin and the additive effect of both agents together. To this day, the pillars of STEMI management involve aspirin and prompt revascularization, whether done via thrombolysis or PCI.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Featuring an interview with Dr Joseph Mikhael, including the following topics: Daratumumab, carfilzomib, lenalidomide, and dexamethasone with minimal residual disease response-adapted therapy for newly diagnosed multiple myeloma (MM) (0:00) KRd versus elotuzumab and KRd for transplant-eligible patients with newly diagnosed MM (10:47) Subgroup analysis of patients with 1q21 and other cytogenetic abnormalities in the Phase III IKEMA and ICARIA-MM studies (15:12) Results with ciltacabtagene autoleucel among patients with relapsed/refractory (R/R) MM in the CARTITUDE-1 study (26:59) CARTITUDE-4 study: Ciltacabtagene autoleucel in earlier lines of treatment for patients with lenalidomide-refractory MM (34:56) KarMMa-3 trial: Idecabtagene vicleucel for patients with R/R MM (44:20) GPRC5D-targeted CAR (chimeric antigen receptor) T-cell therapy for patients with R/R MM (49:09) Efficacy of teclistamab for R/R MM in the MajesTEC-1 trial (53:45) Efficacy of elranatamab for R/R MM in the MagnetisMM-3 trial (58:43) Efficacy of linvoseltamab for R/R MM in the LINKER-MM1 trial (1:02:01) Talquetamab for patients with R/R MM in the MonumenTAL-1 trial (1:04:16) Future directions in the first-line management of MM (1:06:03) Strategies to improve diversity and inclusion in clinical trials (1:10:53) CME information and select publications

There is a new subgroup being added to SIN 541611 for Program Evaluation Services.  They have created a technical board to review all applicants to the new category, find out the details in the episode!As always if you have any questions, or if you'd like direct support from a GSA consultant to help with a specific project please feel free to reach out to us at podcast@elevategsa.com 

Welcome to the NeurologyLive® Mind Moments® podcast. Tune in to hear leaders in neurology sound off on topics that impact your clinical practice. In this episode, Thomas Crawford, MD, a pediatric neurologist at Johns Hopkins Medicine, spoke on the recently published 5-year analysis of the NURTURE study (NCT02386553), a long-term trial assessing the efficacy and safety of nusinersen (Spinraza; Biogen) in presymptomatic infants with spinal muscular atrophy (SMA). Crawford discussed the significance of the positive findings, the shift in conversations around treatment optimization in SMA, and how subgroup data may factor into the design of future trials. Looking for more Neuromuscular Disorders discussion? Check out the NeurologyLive® neuromuscular clinical focus page. Episode Breakdown: 1:20 – Benefits seen with nusinersen in NURTURE  4:10 – Changes in goals for treating SMA 6:05 – Complexities with getting infants therapy days after diagnosis 9:40 – Neurology News Minute 12:30 – Subgroup findings from NURTURE 15:20 – Ways to improve treatment optimization in SMA This episode is brought to you by Medical World News, a streaming channel from MJH Life Sciences®. Check out new content and shows every day, only at medicalworldnews.com. The stories featured in this week's Neurology News Minute, which will give you quick updates on the following developments in neurology, are further detailed here: World Health Organization Adds Several MS Treatments to List of Essential Medicines Ceribell's Status Epilepticus Software Receives FDA Clearance With CMS NTAP Coverage Included FDA Accepts New Drug Application for Long-Acting Form of Glatiramer Acetate Essential Tremor Agent Ulixacaltamide Continues to Show Positive Results in Essential1 Study Thanks for listening to the NeurologyLive® Mind Moments® podcast. To support the show, be sure to rate, review, and subscribe wherever you listen to podcasts. For more neurology news and expert-driven content, visit neurologylive.com.

The Mission of St. Stephen's United Methodist Church is to make disciples of Jesus Christ for the transformation of the world. To learn more about St. Stephen's or to view our full online services please visit wwww.ststephensfairfax.org

This episode is sponsored by Charm Economics– data-driven solutions for digital health & MedTech businesses. Dr. Block and his guest, Dr. Ken Milne, delve into the concept of knowledge translation and the time it takes for new information to be integrated into clinical practice. They reference a famous paper that found it takes an average of 17 years for clinically relevant information to reach the patient's bedside.  However, the hosts believe that this time frame can be shortened with the help of social media and evidence-based medicine. They emphasize the importance of evidence-based medicine but also note that it should not be the only factor in decision-making. The hosts also discuss their checklist for evaluating the validity of studies and how they use their podcast to share new information with their audience. Overall, the hosts believe that shortening the time it takes for new information to be integrated into clinical practice can lead to improved patient outcomes. The episode also touches on the potential benefits of vitamin C in treating sepsis patients. One study conducted at Dr. Paul Merrick's Institution showed a significant mortality benefit in patients who were given a cocktail of thiamine, Vitamin C, and hydrocortisone. However, the study was not a randomized control trial and was before-and-after observational, leading to skepticism about the conclusions. Over the next few years, properly designed randomized control trials were conducted and found that vitamin C had no significant impact on sepsis patients. Therefore, while there was initial interest in the potential benefits of vitamin C in treating sepsis, further research has shown that it is not an effective treatment. Looking for something specific within the show? Here you go! [00:00:00] Evidence-based medicine in practice.  [00:05:27] Knowledge translation takes 17 years.  [00:07:26] Randomized control trial questions.  [00:10:59] Shared decision-making in medicine.  [00:14:53] Evidence-based medicine in emergency room.  [00:18:18] Physicians' big egos.  [00:22:20] TXA: The Duct Tape.  [00:24:01] Health interventions and cost.  [00:27:46] Subgroup analysis in studies.  [00:31:12] Epistemology and scientific bias.  [00:34:32] Vitamin C and its benefits.  [00:38:17] Losing to get better. Guest bio: Dr. Milne is a staff physician at Staff at South Huron Hospital Association in Exeter, Ontario, Canada. He has been doing medical research for over 35 years publishing on a variety of topics. Dr. Milne has been working clinically for 25 years and is an adjunct professor in the Department of Medicine (Division of Emergency Medicine) and Department of Family Medicine at the Schulich School of Medicine and Dentistry. He teaches evidence-based medicine, clinical epidemiology, critical appraisal and biostatistics at Western University in London, Ontario. Dr. Milne is passionate about skepticism and critical thinking. He is the creator of the knowledge translation project, The Skeptics' Guide to Emergency Medicine (TheSGEM). Ken is married to Barb and has three amazing children. Dr. Milne serves as a senior editor of Academic Emergency Medicine. He has no funding from the pharmaceutical or biomedical device industry. He is on faculty for the Center for Medical Education and EMRAP. Dr. Milne does partake in medical malpractice reviews and does hold a patent on a pediatric resuscitation device. Connect with Dr. Milne on his LinkedIn.  Did ya know…  You can also be a guest on our show? Please email me at brad@physiciansguidetodoctoring.com to connect.  Socials: @physiciansguidetodoctoring on FB  @physicianguidetodoctoring on YouTube @physiciansguide on Instagram and Twitter

Dr. Deidre O'Connor is an Assistant Professor and Chair of the Disability Subgroup at the University College Dublin in Dublin Ireland. Today she'll be telling us about the subgroup's work. Learn more about University College Dublin's Disability Subgroup by checking out their website via the link below: https://www.ucd.ie/equality/groups/disabilitysub-group/ We mentioned the "Atelier für Alle" disability-oriented art program: https://www.atelierfuralle.org If you have any questions about this show please send them to: atelierfuralle@gmail.com Feel free to leave a review of this show.

The authors report that applicants to undergraduate health professions education prefer selection methods that provide a sense of control and allow the demonstration of more than just academic ability.   Read the accompanying article to this podcast:  https://onlinelibrary.wiley.com/doi/10.1111/medu.14949

The JournalFeed podcast for the week of Feb 6 to 10, 2023.These are summaries from just 2 of the 5 article we cover every week! For access to more, please visit JournalFeed.org for details about becoming a member.Zinc Vs. COVID Spoon FeedZinc supplementation for patients with COVID-19 decreased 30-day ICU admission rate and led to shorter symptom duration. Subgroup analysis showed these effects were especially pronounced for elderly patients and those with comorbid conditions.Tubing in Angioedema Spoon FeedIn patients presenting with angioedema, history of hypertension, shortness of breath, drooling, and anterior tongue or pharyngeal swelling were risk factors for eventual need for intubation.

For patients with ER+/HER2- advanced breast cancer, current treatment guidelines recommend the use of endocrine therapy plus a CDK 4/6 inhibitor as a first-line treatment. And while the guidelines recommend sequential endocrine therapy for disease progressions, this progression can lead to ESR1 mutations and resistance to endocrine therapy. Could a novel oral selective estrogen receptor have more efficacy in preventing ESR1 mutations associated with endocrine resistance? That's the exact question the EMERALD trial sought to answer, and what this study found in its subgroup analyses is the focus of this Audio Abstract.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.06.519361v1?rss=1 Authors: Broeren, B. O., Hundepool, C. A., Kumas, A. H., Duraku, L. S., Walbeehm, E. T., Hooijmans, C. R., Power, D. M., Zuidam, J. M., De Jong, T. Abstract: Background: Treatment of nerve injuries proves to be a worldwide clinical challenge. Acellular nerve allografts are suggested to be a promising alternative for bridging a nerve gap to the current gold standard, an autologous nerve graft. Objective: To systematically review the efficacy of the acellular nerve allograft, its difference from the gold standard (the nerve autograft) and to discuss its possible indications. Material and methods: PubMed, Embase and Web of Science were systematically searched until the 4th of January 2022. Original peer reviewed paper that presented 1) distinctive data; 2) a clear comparison between not immunologically processed acellular allografts and autologous nerve transfers; 3) was performed in laboratory animals of all species and sex. Meta analyses and subgroup analyses (for graft length and species) were conducted for muscle weight, sciatic function index, ankle angle, nerve conduction velocity, axon count diameter, tetanic contraction and amplitude using a Random effects model. Subgroup analyses were conducted on graft length and species. Results: Fifty articles were included in this review and all were included in the meta-analyses. An acellular allograft resulted in a significantly lower muscle weight, sciatic function index, ankle angle, nerve conduction velocity, axon count and smaller diameter, tetanic contraction compared to an autologous nerve graft. No difference was found in amplitude between acellular allografts and autologous nerve transfers. Post hoc subgroup analyses of graft length showed a significant reduced muscle weight in long grafts versus small and medium length grafts. All included studies showed a large variance in methodological design. Conclusion: Our review shows that the included studies, investigating the use of acellular allografts, showed a large variance in methodological design and are as a consequence difficult to compare. Nevertheless, our results indicate that treating a nerve gap with an allograft results in an inferior nerve recovery compared to an autograft in seven out of eight outcomes assessed in experimental animals. In addition, based on our preliminary post hoc subgroup analyses we suggest that when an allograft is being used an allograft in short and medium (0-1cm, greater than 1-2cm) nerve gaps is preferred over an allograft in long ( greater than 2cm) nerve gaps. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.20.513105v1?rss=1 Authors: Purcell, E., Nguyen, T., Smith, M., Penny, T., Paton, M., Zhou, L., Jenkin, G., Miller, S., McDonald, C., Malhotra, A. Abstract: Introduction: We previously described preclinical literature, which supports umbilical cord blood-derived cell (UCBC) therapy use for perinatal brain injury. However, efficacy of UCBCs may be influenced by different patient populations and intervention characteristics. Objectives: To systematically review effects of UCBCs on brain outcomes in animal models of perinatal brain injury across subgroups to better understand contribution of model type (preterm versus term), brain injury type, UCB cell type, route of administration, timing of intervention, cell dosage and number of doses. Methods: A systematic search of MEDLINE and Embase databases was performed to identify studies using UCBC therapy in animal models of perinatal brain injury. Subgroup differences were measured by chi2 test where possible. Results: Differential benefits of UCBCs were seen in a number of subgroup analyses including intraventricular haemorrhage (IVH) vs. hypoxia ischaemia (HI) model (apoptosis white matter (WM): chi2=4.07; P=0.04, neuroinflammation-TNF-: chi2=5.99; P=0.01), UCB-derived mesenchymal stromal cells (MSCs) vs. UCB-derived mononuclear cells (MNCs) (oligodendrocyte WM: chi2=5.01; P=0.03, neuroinflammation-TNF-: chi2=3.93; P=0.05, apoptosis grey matter (GM), astrogliosis WM) and intraventricular/intrathecal vs. systemic routes of administration (microglial activation GM: chi2=7.51; P=0.02, astrogliosis WM: chi2=12.44; P=0.002). We identified a serious risk of bias and overall low certainty of evidence. Conclusions: Preclinical evidence suggests greater efficacy for UCBCs in IVH compared to HI injury model, use of UCB-MSCs compared to UCB-MNCs, and use of local administrative routes compared to systemic routes in animal models of perinatal brain injury. Further research is needed to improve certainty of evidence found and address knowledge gaps. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

https://psychiatry.dev/wp-content/uploads/speaker/post-9677.mp3?cb=1663308057.mp3 Playback speed: 0.8x 1x 1.3x 1.6x 2x Download: Increased immune cell and altered microglia and neurogenesis transcripts in an Australian schizophrenia subgroup with elevated inflammation – PubMed Hayley FFull EntryIncreased immune cell and altered microglia and neurogenesis transcripts in an Australian schizophrenia subgroup with elevated inflammation – PubMed

In this podcast, we discuss the article 'Perioperative critical events and morbidity associated with anesthesia in early life: Subgroup analysis of United Kingdom participation in the Neonate and Children audit of Anaesthesia Practice IN Europe (NECTARINE) prospective multicenter observational study'. We hope you enjoy.

In this episode, Jubilee Brown, MD, and Elisabeth Diver, MD, provide expert insights on new data presented at ASCO 2022 for ovarian, endometrial, and cervical cancers regarding:Subgroup analyses from KEYNOTE-826 evaluating pembrolizumab in combination with chemotherapy with or without bevacizumab in persistent, recurrent, or metastatic cervical cancerPreliminary subgroup analyses from phase III ENGOT-EN5/GOG-3055 SIENDO trial of selinexor vs placebo maintenance in recurrent endometrial cancerUpdated analyses from phase I GARNET trial of dostarlimab in dMMR/MSI-H and pMMR/MSS advanced/recurrent endometrial cancer (cohorts A1 and A2)EndoBARR trial of atezolizumab, bevacizumab, and rucaparib in previously treated recurrent and progressive endometrial cancerPhase III ATHENA-MONO trial of first-line rucaparib vs placebo maintenance after platinum-based chemotherapy in patients with advanced ovarian cancerPresenters:Jubilee Brown, MDProfessor and Division DirectorGynecologic OncologyLevine Cancer Institute, Atrium HealthCharlotte, North CarolinaElisabeth Diver, MDClinical Assistant ProfessorDivision of Gynecologic OncologyDepartment of Obstetrics and GynecologyStanford UniversityStanford Cancer InstituteStanford University Hospital and ClinicsStanford, CaliforniaContent supported by educational grants from AstraZeneca, GlaxoSmithKline, Karyopharm Therapeutics, and Merck Sharp & Dohme Corp.Link to full program, including a downloadable highlights slideset, and ClinicalThought commentaries:https://bit.ly/3ufB8Js

Guest host Dr. Vamsi Velcheti, of the NYU Langone Perlmutter Cancer Center, and Dr. Brian Henick, of the Columbia University Herbert Irving Comprehensive Cancer Center, discuss advances in KRAS-mutated lung cancer in the KRYSTAL-1 trial, and the association of ctDNA with overall survival in the NADIM trial, as well as other key advances in lung cancer presented at the 2022 ASCO Annual Meeting.   TRANSCRIPT   Dr. Vamsi Velcheti: Hello, everyone! This is Dr. Vamsi Velcheti, I'm your guest host for the ASCO Daily News podcast, today. I'm an associate professor and medical director for the Thoracic Oncology Program at Perlmutter Cancer Center at NYU Langone Health. My guest today is Dr. Brian Henick, an associate director of the Experimental Therapeutics Program, and assistant professor of Medicine at Columbia University's Herbert Irving Comprehensive Cancer Center. We'll be discussing key abstracts in lung cancer that were featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the notes and disclosures of all guests on the podcast can be found on the transcripts at asco.org/podcasts. Brian, it's great to speak with you today. Dr. Brain Henick: Thank you so much, Vamsi, and ASCO Daily News for letting me join you to discuss these abstracts. Dr. Vamsi Velcheti: So, let's dive in. So, it's an exciting ASCO Annual Meeting. And I hope you had a great time at the Meeting. So, let's start off with the LBA9009 and KRYSTAL-1 clinical trial. The study showed the activity of adagrasib in patients with KRAS-G12C mutant non-small cell lung cancer and active untreated brain mets. So, what is the key takeaway from this trial? Dr. Brain Henick: Well, Dr. Sabari presented some encouraging data on this important population. As we know, patients with active central nervous system (CNS) metastases represent a population of unmet medical need who are often excluded from clinical trials. So, it's a credit to the investigators for including this cohort. As Dr. Sabari noted, and as Dr. Goldberg emphasized in her discussion of the abstract, the measured CNS penetration of adagrasib compares favorably with other CNS active compounds from other settings. The overall response rate was 35%, with a disease control rate of 80%. But impressively, the median duration of intracranial response and progression-free survival (PFS) wasn't reached. This certainly seems to be a CNS active compound, and we'll need to see how sotorasib stacks up in their comparable cohort. Ideally, we'd have randomized data to prove superiority over the standard of care, but we may be a few steps away from that. Dr. Vamsi Velcheti: So, Brian, in terms of CNS mets, how big of a problem is it in patients with KRAS G12C mutant lung cancers? Dr. Brian Henick: We know that CNS metastases are a big problem for G12C mutant lung cancer. The rates have been quoted as high as up to 42% of patients. And in particular, as you know, Vamsi, a lot of times trials often don't include, specifically, cohorts with active untreated brain metastases. And so, this is a very unique cohort in that sense. Dr. Vamsi Velcheti: I just want to highlight that we really don't know the differential efficacy of sotorasib and adagrasib in the CNS met population because the trials were CodeBreak 100 and other trials and data readouts from sotorasib did not include patients with untreated brain mets. We did, however, [see] CNS progression-free survival data that go in line with sotorasib. So, it's really important to see that data from sotorasib. Dr. Brain Henick: I definitely look forward to seeing that. Dr. Vamsi Velcheti: So, let's talk about Abstract 8501. The primary endpoint that was presented at ASCO [Annual Meeting] was the pathologic complete response to chemotherapy and nivo vs. chemotherapy as a new adjuvant treatment for resectable stage 3, a non-small cell lung cancer. This was the phase 2 NADIM trial. So, what do you think about this study? And what's your key takeaway from the study? Dr. Brain Henick: Dr. Provencio from Spain presented data from this randomized study as you said, of nivo plus carbo taxol compared to carbo taxol as neoadjuvant therapy for potentially resectable stage 3-A and B non-small cell lung cancer. So, I did want to compare this to the randomized data that we have from Checkmate 816, which interestingly allowed for earlier-stage disease as low as 1-B. And they also allowed for more flexibility in the choice of platinum doublet regimens. This study, NADIM 2, employs 2:1 versus 1:1 randomization, which we saw in Checkmate 816. Another important difference was that NADIM 2 required adjuvant nivolumab for 6 months in the study arm, whereas Checkmate 816 didn't include any immunotherapy in the adjuvant setting, but they allowed for a standard of care chemotherapy. In NADIM 2, the control arm didn't include any adjuvant therapy. In keeping with the impressive improvements over historical pathologic complete response rates of about 5%, this chemotherapy-IO regimen yielded a path complete response (CR) rate of 36.8%. It also showed a major pathological response, which again is defined as less than 10% viable tumor of 52.6%, and an overall response rate of 75.4%. So, it looks like there's a benefit that's happening upfront with the immunotherapy and chemotherapy as opposed to this just being an adjuvant phenomenon. This is also in keeping with data that we saw with Checkmate 816, as well as neoadjuvant atezo plus chemotherapy in the phase 2 study that was led by Catherine Shu and colleagues here at Columbia a few years ago. Overall, this is more encouraging data for the neoadjuvant use of immunotherapy. The earlier immunotherapy marches into the treatment course of patients with lung cancer, the greater the cost of toxicity. So, I think an important thing for us to focus on going forward is trying to develop strategies to better identify the patients that are most likely to benefit. Dr. Vamsi Velcheti: So, Brian, I think from a practical standpoint, now that we have approval for neoadjuvant immunotherapy and adjuvant immunotherapy, we have some practical challenges in terms of how we manage our patients. Of course, the new adjuvant is very appealing because it's only 3 cycles of chemoimmunotherapy, but the challenge though, is a majority of the patients don't have a CR, or a significant proportion of the patients have an ongoing response or significant residual disease at the time of surgery. So, the question then would be what do you do after surgery if they're having an ongoing response? Do you think 3 cycles of immunotherapy are inadequate systemic therapy for these patients? Dr. Brian Henick: It's a really important question, Vamsi. I think until the data is mature, we're just kind of limited by the extent of what the data tells us so far, and then we have to kind of do our best as the treating doctor to navigate the patient's situation. So, tools that we'd still have available to us in the adjuvant setting that are approved are things like chemotherapy and radiation, leveraging things like circulating tumor DNA, I think maybe a promising path forward, as well to help guide strategies there, but I think until the data is mature, it has to be highly patient-focused to figure out what seems to be most appropriate there. How are you navigating those situations, Vamsi? Dr. Vamsi Velcheti: Yeah, as you said, it is very challenging. I think we need more data. And of course, the challenge now is like, if you use immunotherapy in the new adjuvant setting, it's very likely you're not going to get insurance authorization for 1 year of adjuvant atezolizumab. So, we really need studies to optimize treatment paradigms here. As you suggested, maybe circulating tumor DNA (ctDNA)-based approaches to look at residual disease, I think, that would be one great way to do it. Let's move on to the next abstract, Brian. I found Abstract 9001 really interesting. It's a U.S. Food and Drug Administration (FDA) pooled analysis that looked at outcomes of first-line immune checkpoint inhibitors, with or without chemotherapy based on the KRAS mutation status and PD-L1 expression. So, what is your take on this abstract and how do you think this is going to impact our practice? Dr. Brian Henick: So, Dr. Nakajima and colleagues explored the observation from individual trials that patients with KRAS-mutant lung cancer seem to have better responses than wild type with immunotherapy (IO) alone. But the favorability of these responses seems to be abrogated with chemotherapy-IO. We know that KRAS accounts for 25% of oncogene-driven non-small cell lung cancer predominantly at amino acid 12. And with the emergence of direct inhibitors of G12C, understanding the clinical features of these tumors may be critical to inform optimal integration of this new class of drugs and also to make sure that we've optimized treatment algorithms for KRAS patients in general. So, this study's authors at the FDA pulled data from 12 registrational clinical trials that were investigating first-line checkpoint inhibitor-containing regimens and they found no significant difference between KRAS wild type and mutant for overall survival regardless of the regimen used. The best outcomes were seen with chemoimmunotherapy regardless of KRAS status. This retrospective analysis does suggest that the notion of there being lesser benefit from chemoimmunotherapy from Dr. Gadgeel's study might not hold up in the overall population, but I think it raises important questions, like, are all KRAS mutations alike? The absence of KRAS mutation status for a majority of patients included in these studies limits the interpretation of the data. And also, the absence of commutation status makes it a little harder to interpret. And other important questions remain such as how G12C inhibitors will factor in? What were your thoughts, Vamsi? Dr. Vamsi Velcheti: No, I completely agree with you, Brian. I think we need more data and we know that commutation status is a very important aspect in terms of KRAS-directed therapies. And of course, with a lot of promising data from these KRAS inhibitors, there's an interest in moving these drugs into the front-line therapy for patients with KRAS mutations. But I think it's going to be quite challenging to incorporate them into the front-line therapies and we clearly will need better characterization of these patients with KRAS mutant [lung cancer] to further personalize treatment in the frontline setting for these patients. So, let's move on to the next abstract. This is the lung map study, Abstract 9004. This is a study sponsored by the National Cancer Institute (NCI), the lung map study, looking at overall survival from a phase 2 randomized study of ramucirumab and pembrolizumab, what's the standard of care in patients with advanced non—small cell lung cancer previously treated with immunotherapy. So, what were your key takeaway points here from this study? Dr. Brian Henick: So first of all, it's very exciting to see data from this very ambitious long map sub-study yield a positive result. Whereas many of the arms of this study were biomarker-guided, Dr. Reckamp presented the results from pembro plus ramucirumab as compared to the standard of care in unmarked patients with non-small cell lung cancer who had progressed after prior treatment with chemotherapy and immunotherapy. The data seems to suggest that pembro plus ramucirumab may be better tolerated than the standard of care chemo-containing regimens, as the experimental regimen had fewer serious adverse events. Pembro plus ramucirumab had a median overall survival of 14.6 months as compared to 11.6 months in the control arm and this was statistically significant. The PFS difference wasn't significant, but there was a late divergence in the curves. Dr. Bestvina nicely summarized some of the study's limitations such as the mixture of control regimens used, and there were really interesting signals that were found on subgroup analysis, such as benefit in those with mixed histology tumors, STK11 mutant tumors, and those who received chemotherapy prior to immunotherapy. The subgroups deserve further attention in the future. For now, this regimen may be an appealing option as an alternative to chemotherapy for the right patients. What do you think? Dr. Vamsi Velcheti: Yeah, I agree, Brian. I think it's a really promising combination. We've always seen some synergy with VEGF inhibitors and immunotherapy in multiple studies and multiple tumor types. So, we really need to develop better ways to select patients for VEGF combination-based approaches in lung cancer. So, let's move on to another interesting study. This is Abstract 9000. This explores the outcomes of anti-PD-L1 therapy with or without chemotherapy for first-line, metastatic non-small cell lung cancer with a PD-L1 score of greater than 50%. So, this is an FDA pooled analysis. So, what were your key takeaways from this abstract? Dr. Brain Henick: I thought this question was really well suited for a large pooled retrospective analysis and our colleagues at the FDA didn't let us down here. The question really was what's the optimal approach for patients with non-small cell lung cancer with greater than 50% PD-L1 in view of the absence of direct comparisons between these arms in prospective studies? I thought one of the most striking findings from Dr. Akinboro's presentation was the dismally low rate of underrepresented minority patients that were included in these registration trials. As far as the findings for the patients who were studied, although the Kaplan-Meier curves for overall survival showed early separation, the difference wasn't statistically significant. Subgroup analysis revealed a trend towards better outcomes for immunotherapy alone among patients who are [age] 75 and above, suggesting that this may need to be parsed out as a unique population in subsequent studies. But in all, our equipoise as a field on whether to include chemoimmunotherapy-based first-line regimens should persist and should be guided, in my opinion, largely by clinical considerations. Can the patient tolerate chemotherapy? Do you need a rapid response? Are there other things that you thought in hearing all this, Vamsi? Dr. Vamsi Velcheti: Yeah, absolutely. I think I am still struggling with the decision of whether to add chemotherapy for patients with greater than 50%. To a large extent, it's actually a clinical decision. In some patients who have a large disease burden, I tend to kind of opt for adding chemotherapy to immunotherapy in the front-line setting. But of course, we need more data here. And this is actually a very helpful piece of information from the FDA. And as you pointed out briefly, Brian, I think the fact that there are very few underrepresented patients in the pooled analysis, I think kind of speaks to the need for addressing increased diversity in clinical trial accruals. I think this is a great segue to also talk about Abstract 9012, talking about disparities in access to immunotherapy globally. This is a study from India looking at 15,000 patients who were checkpoint inhibitor eligible and who have very low rates of uptake of immunotherapy. This is something that reflects the global team of the ASCO Annual Meeting talking about disparities and improving access to treatments in underserved minority populations here in the United States, and also globally, in the developing world, the disparities in terms of access to care are humongous. So, what are your thoughts, Brian? And also, if you could highlight some of the work that you're doing at Columbia about disparities, I think that would be great. Dr. Brain Henick: Absolutely! I think access to medications is a really humbling topic for those of us who are involved in developmental therapeutics, particularly with the transformational impact we've seen with the advent of immunotherapy over the last decade-plus. Dr. Ravikrishna's presentation is therefore extremely important. He described very low rates of uptake of immunotherapy by indication. And perhaps most strikingly, the discrepancy in uptake by patients' ability to pay for therapy with the vast majority of immunotherapy received by those who are private is very concerning. Even if the definition of restricted access was permissive, for example, I didn't see mention of the cancer stage as an eligibility factor, the fact that this represents a single referral center's data doesn't bode well for uptake elsewhere. So, I think we need to continue to work as a field on prioritizing strategies to help overcome these gaps, but good quality data such as this study is an important first step. And to that point, Vamsi, I'm very excited to be working with you in collaboration on an observational study for patients with lung cancer from underserved minority populations with lung cancer in New York City so that we can better characterize access to care, efficacy, and toxicity in this population. Dr. Vamsi Velcheti: Thank you, Brian. I'd really like to thank you for sharing your valuable insights with us today on the ASCO Daily News Podcast. We really appreciate it. Brian, thank you so much for joining us. Dr. Brain Henick: My pleasure. Thanks for having me. Dr. Vamsi Velcheti: And thank you to all our listeners for joining in today. You will find links to all the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. Thank you so much.     Disclosures: Dr. Vamsi Velcheti: Honoraria: Honoraria Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline Dr. Brain Henick: None disclosed. Disclaimer: The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Show Notes:The Art of Gathering: How we meet and why it matters by Priya Parker The Essential Guide for Small Group Leaders by Bill SearchWhy does a group get tired? •Leader begins to coast•Meeting becomes routine•Relationships hit a plateau•Purpose is lost#1 Leader Coasting Am I practicing “Generous Authority”? – [Priya Parker] “'Chill' is selfishness disguised as kindness.” - Priya Parker Generous Authority Serves others by: 1.Protecting group members 2.Equalizing group members 3.Inter-Connecting group members We practice Generous Authority by:1.Practicing good MANNERS in the group 2.Reminding all of the “RULES” 3.Encourage “Sprout” Speeches not “Stump” Speeches Now What?1. Re-affirm Covenant 2. Have tough conversations3. Re-up as the leader or get out 4. Share Leadership #2 Meeting Routine “The room is doing 80% of the job” – Jerry Seinfeld Venue Matters 1.The space should be a symbol of reason for meeting 2.The space should bring out desired behaviors and discourage those you don't 3.Consider density Format Matters 1.Mix it up2.Curtail the dull parts 3.Try different curriculum Now What? 1. Rotate Hosting 2. Share testimony3. Serve together4. Choose an unlikely meeting place #3 Relationships Plateaued Why does this happen? 1.We stop being curious about others 2.We decide how far we will go relationally3.Potential conflict zones are avoided 4.We don't feel safe What can you do about it? 1.Don't avoid the awkward – embrace it 2.Utilize GOOD ice-breakers 3.Encourage people to share what no one in the group would guess/ know about them4.Talk about the forbidden subjects of politics, sex, and religion 5.Don't stop conflict but guide it 6.Navigate underlying conflicts Now What? 1. Split by gender 2. Subgroup for prayer3. Retreat4. Day trip, local restaurants, or local tourism #4 Lost Purpose “A good gathering purpose should be ‘disputable'” – The Art of Gathering by Parker Start by asking “WHY are we meeting?” 1.First, ask the church leadership 2.Reverse engineer current meeting and compare to stated goal 3.Who is this for? Second ask “Why are WE meeting?” 1.Is our goal the same as the leadership's goal? 2.Do we have a different goal? Third, re-state and re-affirm your purpose 1.Discuss the purpose as a group 2.Arrive at consensus3.Everyone has to re-up That didn't work. Now what? How to End Your Group (Page 87, Essential Guide for Small Group Leaders) 1.Understand all groups come to a natural end 2.Get input from group members3.Ask everyone to make a personal plan 4.Plan a final meeting and put it on the calendar5.End the group in a prayer circle6.Don't forget to tell your pastor or small group coach that your group has ended Recommended Resources: Dare to Lead by Brene BrownThe Art of Gathering By ParkerEssential Guide for Small Group Leaders by Search Questions? 

Show Notes:The Art of Gathering: How we meet and why it matters by Priya Parker The Essential Guide for Small Group Leaders by Bill SearchWhy does a group get tired? •Leader begins to coast•Meeting becomes routine•Relationships hit a plateau•Purpose is lost#1 Leader Coasting Am I practicing “Generous Authority”? – [Priya Parker] “'Chill' is selfishness disguised as kindness.” - Priya Parker Generous Authority Serves others by: 1.Protecting group members 2.Equalizing group members 3.Inter-Connecting group members We practice Generous Authority by:1.Practicing good MANNERS in the group 2.Reminding all of the “RULES” 3.Encourage “Sprout” Speeches not “Stump” Speeches Now What?1. Re-affirm Covenant 2. Have tough conversations3. Re-up as the leader or get out 4. Share Leadership #2 Meeting Routine “The room is doing 80% of the job” – Jerry Seinfeld Venue Matters 1.The space should be a symbol of reason for meeting 2.The space should bring out desired behaviors and discourage those you don't 3.Consider density Format Matters 1.Mix it up2.Curtail the dull parts 3.Try different curriculum Now What? 1. Rotate Hosting 2. Share testimony3. Serve together4. Choose an unlikely meeting place #3 Relationships Plateaued Why does this happen? 1.We stop being curious about others 2.We decide how far we will go relationally3.Potential conflict zones are avoided 4.We don't feel safe What can you do about it? 1.Don't avoid the awkward – embrace it 2.Utilize GOOD ice-breakers 3.Encourage people to share what no one in the group would guess/ know about them4.Talk about the forbidden subjects of politics, sex, and religion 5.Don't stop conflict but guide it 6.Navigate underlying conflicts Now What? 1. Split by gender 2. Subgroup for prayer3. Retreat4. Day trip, local restaurants, or local tourism #4 Lost Purpose “A good gathering purpose should be ‘disputable'” – The Art of Gathering by Parker Start by asking “WHY are we meeting?” 1.First, ask the church leadership 2.Reverse engineer current meeting and compare to stated goal 3.Who is this for? Second ask “Why are WE meeting?” 1.Is our goal the same as the leadership's goal? 2.Do we have a different goal? Third, re-state and re-affirm your purpose 1.Discuss the purpose as a group 2.Arrive at consensus3.Everyone has to re-up That didn't work. Now what? How to End Your Group (Page 87, Essential Guide for Small Group Leaders) 1.Understand all groups come to a natural end 2.Get input from group members3.Ask everyone to make a personal plan 4.Plan a final meeting and put it on the calendar5.End the group in a prayer circle6.Don't forget to tell your pastor or small group coach that your group has ended Recommended Resources: Dare to Lead by Brene BrownThe Art of Gathering By ParkerEssential Guide for Small Group Leaders by Search Questions? 

Ministry doesn't have to be a mystery. Attend an ALIGN workshop this March and get the basic and next steps of Small Group ministry. ALIGN will give you a foundational understanding of small groups and a plan for taking your church to the next level. But the most valuable part of an ALIGN workshop are the connections you'll make. Because no one should have to do ministry alone.ALIGN Irvine in Orange County, California is March 24thALIGN Atlanta at 1st Baptist Woodstock in Woodstock Georgia is March 31stFor more details, go to https://smallgroupnetwork.com/align-workshops/We can't wait to see you there!Show Notes:The Art of Gathering: How we meet and why it matters by Priya Parker The Essential Guide for Small Group Leaders by Bill SearchWhy does a group get tired? •Leader begins to coast•Meeting becomes routine•Relationships hit a plateau•Purpose is lost#1 Leader Coasting Am I practicing “Generous Authority”? – [Priya Parker] “'Chill' is selfishness disguised as kindness.” - Priya Parker Generous Authority Serves others by: 1.Protecting group members 2.Equalizing group members 3.Inter-Connecting group members We practice Generous Authority by:1.Practicing good MANNERS in the group 2.Reminding all of the “RULES” 3.Encourage “Sprout” Speeches not “Stump” Speeches Now What?1. Re-affirm Covenant 2. Have tough conversations3. Re-up as the leader or get out 4. Share Leadership #2 Meeting Routine “The room is doing 80% of the job” – Jerry Seinfeld Venue Matters 1.The space should be a symbol of reason for meeting 2.The space should bring out desired behaviors and discourage those you don't 3.Consider density Format Matters 1.Mix it up2.Curtail the dull parts 3.Try different curriculum Now What? 1. Rotate Hosting 2. Share testimony3. Serve together4. Choose an unlikely meeting place #3 Relationships Plateaued Why does this happen? 1.We stop being curious about others 2.We decide how far we will go relationally3.Potential conflict zones are avoided 4.We don't feel safe What can you do about it? 1.Don't avoid the awkward – embrace it 2.Utilize GOOD ice-breakers 3.Encourage people to share what no one in the group would guess/ know about them4.Talk about the forbidden subjects of politics, sex, and religion 5.Don't stop conflict but guide it 6.Navigate underlying conflicts Now What? 1. Split by gender 2. Subgroup for prayer3. Retreat4. Day trip, local restaurants, or local tourism #4 Lost Purpose “A good gathering purpose should be ‘disputable'” – The Art of Gathering by Parker Start by asking “WHY are we meeting?” 1.First, ask the church leadership 2.Reverse engineer current meeting and compare to stated goal 3.Who is this for? Second ask “Why are WE meeting?” 1.Is our goal the same as the leadership's goal? 2.Do we have a different goal? Third, re-state and re-affirm your purpose 1.Discuss the purpose as a group 2.Arrive at consensus3.Everyone has to re-up That didn't work. Now what? How to End Your Group (Page 87, Essential Guide for Small Group Leaders) 1.Understand all groups come to a natural end 2.Get input from group members3.Ask everyone to make a personal plan 4.Plan a final meeting and put it on the calendar5.End the group in a prayer circle6.Don't forget to tell your pastor or small group coach that your group has ended Recommended Resources: Dare to Lead by Brene BrownThe Art of Gathering By ParkerEssential Guide for Small Group Leaders by Search Questions? 

Subgroup analyses in combination with data visualisation is one of the hottest topics I can think about. And it hits us as statisticians during our careers again and again. We need to understand subgroups for efficacy reasons and safety reasons and it's a common question in terms of how consistent your drug works across the different subgroups. It gets even more complicated if you want to review it across multiple studies.

Dr. Neeraj Agarwal, ASCO Daily News editor-in-chief, and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, shares key takeaways from the practice-changing ARASENS trial in mHSPC, featured at the 2022 ASCO Genitourinary Cancers Symposium.   Transcript: ASCO Daily News: Hello, and welcome to the ASCO Daily News podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. Today in our continuing coverage of the 2022 ASCO Genitourinary (GU) Cancer Symposium. Dr. Neeraj Agarwal, the editor in chief of the ASCO Daily News will share key takeaways from the practice-changing ARASENS trial, which showed promising results in metastatic hormone-sensitive prostate cancer. Dr. Agarwal has no conflicts relating to the topic of this episode and his full disclosures are available in this show notes. Disclosures of all guests on the podcast can be found in our transcripts at asco.org/podcasts. Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News podcast. I'm Dr. Neeraj Agrawal, the director of the Genitourinary Cancers Program and professor of medicine at the University of Utah Huntsman Cancer Institute. Let's discuss the results of the practice-changing ARASENS trial in patients with metastatic castration-sensitive prostate cancer as presented at the 2022 ASCO GU Symposium. This abstract, Abstract 13, was presented by Dr. Matthew Smith from the Massachusetts General Hospital and Hartford Medical School. ARASENS is a randomized phase 3 trial evaluating the efficacy and safety of darolutamide, a novel hormonal therapy, plus ADT (antiandrogen therapy) plus docetaxel versus placebo plus ADT plus docetaxel in patients with metastatic castration-sensitive prostate cancer. Randomization was stratified by the extent of disease and alkaline phosphatase levels, below versus upper limit of normal or above. It is important to know that this study only included patients that were eligible for ADT and docetaxel chemotherapy, to begin with. The primary endpoint was overall survival with multiple secondary endpoints, including time to CRPC (castration-resistant prostate cancer), time to pain progression, time to first symptomatic skeletal event, and time to start off the next anti-neoplastic therapy, and safety. A total of 1,306 patients were randomly assigned to triplet therapy with darolutamide plus ADT plus docetaxel versus placebo plus ADT plus docetaxel. Baseline characteristics were well balanced between the treatment arms. Analysis of the primary endpoint was pre-specified. After, 533 events had occurred results show the primary endpoint of this study was met with a significant improvement in overall survival and a 32.5% reduction in risk of death for patients on the triplet therapy on for darolutamide plus ADT plus docetaxel versus placebo plus ADT plus docetaxel. It is important to know that the triplet therapy improved overall survival, despite 76% of patients in the control arm having received the next life-prolonging therapy. Subgroup analysis indicates consistent benefit across the 3 specified groups. Secondary endpoints also were favored by the triplet therapy combination over the control arm. While this study offers an additional excellent option for our patients with metastatic cancer-sensitive prostate cancer in older populations, the use of docetaxel may be a significant limitation to this triplet combination. In addition, and importantly, this study did not answer the question of whether adding docetaxel chemotherapy to the ADT plus novel hormonal therapy backbone will also improve survival. With the advent of multiple doublets and triplet combinations in recent years, as we saw in the form of ADT plus enzalutamide ADT plus apalutamide in the recent years, it is very important to find biomarkers that may predict response to these treatment options, which will allow personalization of therapy with that. I would like to conclude this podcast on the ARASENS trial. Thank you very much for your kind attention. ASCO Daily News: You've been listening to Dr. Neeraj Agarwal of the University of Utah's Huntsman Cancer Institute. Thanks for joining us today. If you're enjoying the content on the podcast, please take a moment to rate and review us wherever you get your podcasts. Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Merck, Novartis, lily, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, ORIC Pharmaceuticals, CRISPR therapeutics, and Arvinas Disclaimer: The purpose of this podcast is to educate and to inform this is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Show Notes:The Art of Gathering: How we meet and why it matters by Priya Parker The Essential Guide for Small Group Leaders by Bill Search Why does a group get tired? •Leader begins to coast •Meeting becomes routine •Relationships hit a plateau •Purpose is lost #1 Leader Coasting Am I practicing “Generous Authority”? – [Priya Parker] “'Chill' is selfishness disguised as kindness.” - Priya Parker Generous Authority Serves others by: 1.Protecting group members 2.Equalizing group members 3.Inter-Connecting group members We practice Generous Authority by:1.Practicing good MANNERS in the group 2.Reminding all of the “RULES” 3.Encourage “Sprout” Speeches not “Stump” Speeches Now What?1. Re-affirm Covenant 2. Have tough conversations3. Re-up as the leader or get out 4. Share Leadership #2 Meeting Routine “The room is doing 80% of the job” – Jerry Seinfeld Venue Matters 1.The space should be a symbol of reason for meeting 2.The space should bring out desired behaviors and discourage those you don't 3.Consider density Format Matters 1.Mix it up2.Curtail the dull parts 3.Try different curriculum Now What? 1. Rotate Hosting 2. Share testimony3. Serve together4. Choose an unlikely meeting place #3 Relationships Plateaued Why does this happen? 1.We stop being curious about others 2.We decide how far we will go relationally3.Potential conflict zones are avoided 4.We don't feel safe What can you do about it? 1.Don't avoid the awkward – embrace it 2.Utilize GOOD ice-breakers 3.Encourage people to share what no one in the group would guess/ know about them4.Talk about the forbidden subjects of politics, sex, and religion 5.Don't stop conflict but guide it 6.Navigate underlying conflicts Now What? 1. Split by gender 2. Subgroup for prayer3. Retreat4. Day trip, local restaurants, or local tourism #4 Lost Purpose “A good gathering purpose should be ‘disputable'” – The Art of Gathering by Parker Start by asking “WHY are we meeting?” 1.First, ask the church leadership 2.Reverse engineer current meeting and compare to stated goal 3.Who is this for? Second ask “Why are WE meeting?” 1.Is our goal the same as the leadership's goal? 2.Do we have a different goal? Third, re-state and re-affirm your purpose 1.Discuss the purpose as a group 2.Arrive at consensus3.Everyone has to re-up That didn't work. Now what? How to End Your Group (Page 87, Essential Guide for Small Group Leaders) 1.Understand all groups come to a natural end 2.Get input from group members 3.Ask everyone to make a personal plan 4.Plan a final meeting and put it on the calendar5.End the group in a prayer circle 6.Don't forget to tell your pastor or small group coach that your group has ended Recommended Resources: Dare to Lead by Brene Brown The Art of Gathering By Parker Essential Guide for Small Group Leaders by Search Questions? 

People Group Details https://joshuaproject.net/people_groups/10482/MO Listen to "A Third of Us" podcast with Greg Kelley, produced by the Alliance for the Unreached: https://alliancefortheunreached.org/podcast/ Watch "Stories of Courageous Christians" w/ Mark Kordic https://storiesofcourageouschristians.com/stories-of-courageous-christians

When I hear the word " change ", I hear HAVING THE CHOICE. ... _______________________ CONNECT on Facebook https://www.facebook.com/groups/503166600709551/?ref=share ________________________ CONNECT on Instagram https://instagram.com/survivingtheodds_thepodcast?utm_medium=copy_link _________________________ CONNECT on YouTube https://youtube.com/channel/UCUDx2Q2iEZXEeCsZmM4WkHw ________________________ MENTOR Facebook@Spiritual Success Sorrority https://www.facebook.com/groups/SpiritualSuccessSorority/?ref=share _________________________ MENTOR on Facebook @Shessobossmindsetincubator https://www.facebook.com/groups/shessobossmindsetincubator/?ref=share _______________________ CONNECT on Facebook @Om Vision https://www.facebook.com/groups/122399858477116/?ref=share ___________________________________________________________________________ SUPPORT THIS PODCAST @https://linktr.ee/strokesto _________________________ JOIN MY TRAUMA WARRIOR TRIBE, SUBGROUP on Facebook https://www.facebook.com/groups/1140238053097474/?ref=share _________________________ Medical Disclaimer The content shared here is not intended to be a substitute for professional medical advice, care, diagnosis, or treatment. Always seek the advice of a qualified & licensed Healthcare professional. ■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■ I'm a Survival coach specializing in Stroke survivors. 1- helping to find & accept the new identity. 2-Readdapt in day to day life. 3- Heal from this trauma. CALL WHAT'S APP 1-514-993-4454

The Gary Null Show Notes – 08.25.21 American Medical Association Calls for Covid-19 Vaccine Mandates China, 2049 The Leak That ‘Exposed the True Afghan War' Fauci Dismisses “Freedom” In Call For Vaccine Mandates: “The Time Has Come. Enough Is Enough.” A New Low for the FDA Eight Key Points on America's Defeat in Afghanistan 2 Things Mainstream Media Didn't Tell You About FDA's Approval of Pfizer Vaccine America in an Age of Faucism Today's Videos 1.  Dave Cullen Video on Mandating Vaccines: ” Vaccination: They're Becoming Desperate” 2. The Dunning-Kruger Effect – Cognitive Bias – Why Incompetent People Think They Are Competent 3. Dr. Malone Sounds Alarm On Liability Coverage Of Pfizer Vax Start this clip at 5.00 in when Dr. Malone begins to speak. 4. Dr. Ryan Cole #StoptheMandate (start at 1:25) Study suggests vitamin D supplementation may serve as part of strategy for autoimmune and infectious diseases associated with leaky gut MacKay Children's Hospital (Taiwan), August 15, 2021 According to news reporting from Taipei, Taiwan, research stated, “Vitamin D (VD) plays an important role not only in mineral balance and skeletal maintenance but also in immune modulation. VD status was found correlated with the pathophysiology and severity of inflammatory bowel diseases and other autoimmune disorders. Epithelial barrier function is primarily regulated by the tight-junction (TJ) proteins.” The news reporters obtained a quote from the research from MacKay Children's Hospital: “In this study, we try to establish an animal model by raising mice fed VD-deficient diet and to investigate the effects of VD-deficient diet on gut integrity and zonulin expression. Male C57BL/6 mice were administered either VD-deficient [VDD group, 25(OH)2D3 0 IU/per mouse] or VD-sufficient [VDS group, 25(OH)2D3 37.8 IU/per mouse] special diets for 7 weeks. Body weight and diet intake were recorded weekly. Serum VD levels were detected. After sacrifice, jejunum and colon specimens were collected. The villus length and crypt depth of the jejunum as well as mucosa thickness of the colon were measured. Various serum pro-inflammatory cytokines and intestinal TJ proteins were assessed. The serum level of zonulin and the mRNA expression of jejunum zonulin were also investigated. We found that mice fed a VDD diet had a lower serum level of VD after 7 weeks (p < 0.001). VDD mice gained significant less weight (p = 0.022) and took a similar amount of diet (p = 0.398) when compared to mice raised on a VDS diet. Significantly decreased colon mucosa thickness was found in VDD mice compared with the VDS group (p = 0.022). A marked increase in serum pro-inflammatory cytokine levels was demonstrated in VDD mice. All relative levels of claudin (CLD)-1 (p = 0.007), CLD-3 (p < 0.001), CLD-7 (p < 0.001), and zonulin-1 (ZO-1, p = 0.038) protein expressions were significantly decreased in the VDD group when compared to the VDS group. A significant upregulation of mRNA expression of jejunum zonulin (p = 0.043) and elevated serum zonulin (p = 0.001) were found in the VDD group.” According to the news editors, the research concluded: “We successfully demonstrated that VDD could lead to impaired barrier properties. We assume that sufficient VD could maintain intestinal epithelial integrity and prevent mucosal barrier dysfunction. VD supplementation may serve as part of a therapeutic strategy for human autoimmune and infectious diseases with intestinal barrier dysfunction (leaky gut) in the future. To our knowledge, this is the first study to demonstrate that VDD could lead to a significant upregulation in mRNA expression of the jejunum zonulin level and also a marked elevation of serum zonulin in a mouse model.” Investigating the anti-hypertensive effects of pumpkin seed oil Marymount University (US) and University of Guilan (China), August 24, 2021 In a study, researchers from Iran and the U.S. found that pumpkin seed oil can potentially treat hypertension in postmenopausal women. Their report was published in Complementary Therapies in Clinical Practice. Postmenopausal women are more likely to develop hypertension than men of the same age. In vivo studies reveal that pumpkin seed oil has anti-hypertensive activity. The team investigated the effects of pumpkin seed oil supplementation on vascular function and heart rate variability in postmenopausal women with elevated blood pressure. Participants were assigned to take either a pumpkin seed oil supplement or a placebo for the six-week study. Those in the experimental group took 3 grams of pumpkin seed oil every day. Brachial and central blood pressure, wave reflection (augmentation index, AIx), arterial stiffness (SI) and various HRV parameters were measured at baseline and at the end of the study. Those who took pumpkin seed oil had significantly lower AIx, brachial and systolic blood pressure after treatment. SI and HRV parameters remained unchanged for the treatment group and the placebo group at the end of the study. In sum, taking pumpkin seed oil may improve arterial hemodynamics in postmenopausal women.   Lack of exercise and poor nutrition could increase the risk of diseases like dementia Kings College London, August 23, 2021 New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King's College London has found that both diet and exercise can influence the risk of cognitive decline (CD) and dementia by potentially influencing hippocampal neurogenesis (the process by which the brain produces new brain cells) long before their onset. The study, published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, suggests that altered neurogenesis in the brain could potentially represent an early biomarker for both CD and dementia. The investigation studied how the blood of participants with and without CD and dementia could influence hippocampal neurogenesis in laboratory settings and whether diet and exercise were important factors. Specifically, blood samples of 418 French adults over the age of 65 were collected 12-years prior to CD and dementia diagnosis and tested on human hippocampal stems cells. Additionally, information on each participant's sociodemographic, lifestyle, and clinical data were collected and incidence cognition status and dementia were measured every two to three years over a 12-year period. Over the course of the study, the researchers established that 12 years prior to diagnosis, both CD and Alzheimer's were associated with levels of neural stem cell death. The team also found that exercise, nutrition, vitamin D levels, carotenoid and lipid levels are all associated with the rate at which cells die off. Furthermore, physical activity and nutrition were key factors that then also determined CD status. Specifically, researchers found that reduced physical activity and increased malnutrition both increased cell death which in turn increased the risk for future CD. While previous studies have established that diet and exercise have some protective effects against CD and dementia, these roles have been poorly understood at the neurobiological level. To date, studies on animals have shown how diet and exercise can directly influence hippocampal neurogenesis, potentially explaining how exercise and diet may biologically exert their effects, but this study sheds further light on this in the context of a human model. Dr. Sandrine Thuret, the study's lead investigator said, “Our study has demonstrated not only that there are individual markers of hippocampal neurogenesis associated with CD and dementia 12 years later, but also that there is some degree of specificity with respect to diagnoses of dementia subtypes. If an individual displays an increase in their levels of cell death during differentiation (when neural stem cells are becoming neurons), we can look at this as a potential warning sign of CD. Conversely, a decrease in levels of cell death during proliferation (the process by which a single cell divides into a pair) and reduced hippocampal progenitor cell integrity could be viewed as a predictor for Alzheimer's Disease and Vascular dementia, respectively.” According to Alzheimer's Research UK, there were a total of 525,315 people living with a dementia diagnosis in the UK in 2020. Rates of cognitive decline and dementia are expected to triple in prevalence by 2040. Dr. Andrea du Preez, the study's first author from King's IoPPN said, “While more work is undoubtedly needed to fully understand how diet and exercise might modulate hippocampal neurogenesis, our findings may represent an effective early preventative strategy against CD and dementia.” Mindfulness may improve cognition in older adults University College London, August 23, 2021 Mindfulness may provide modest benefits to cognition, particularly among older adults, finds a new review of evidence led by UCL researchers. The systematic review and meta-analysis, published in Neuropsychology Review, found that, while mindfulness is typically geared towards improving mental health and well-being, it may also provide additional benefits to brain health. The study's lead author, PhD student Tim Whitfield (UCL Psychiatry) said that “the positive effects of mindfulness-based programs on mental health are already relatively well-established. Here, our findings suggest that a small benefit is also conferred to cognition, at least among older adults.” The researchers reviewed previously published studies of mindfulness, and identified 45 studies that fit their criteria, which incorporated a total of 2,238 study participants. Each study tested the effects of a mindfulness-based intervention delivered by a facilitator in a group setting, over at least four sessions, while excluding mindfulness retreats in order to have a more homogenous set of studies. The majority of studies involved a certified instructor teaching participants techniques such as sitting meditation, mindful movement and body scan, generally on a weekly basis across six to 12 weeks, while also asking participants to continue the practices in their own time. The researchers found that overall, mindfulness conferred a small but significant benefit to cognition. Subgroup analysis revealed that the effect was slightly stronger for people over 60, while there was not a significant effect for people under 60. Tim Whitfield commented that “executive function is known to decline with age among older adults; the improvement in people over 60 suggests that mindfulness may help guard against cognitive decline, by helping to maintain or restore executive function in late adulthood. It might be easier to restore cognitive functions to previous levels, rather than to improve them beyond the developmental peak.” When they investigated which aspects of cognition were affected, the researchers found that mindfulness was beneficial only to executive function, and more specifically, there was strong evidence of a small positive effect on working memory (which is one facet of executive function). The researchers also analyzed whether mindfulness outperformed other ‘active interventions' (such as brain training, relaxation, or other health or educational programs) or only when compared to people who were not offered any alternative treatment. They found that cognitive benefits of mindfulness were only significant compared with an ‘inactive' comparison, which means they cannot rule out that the benefits may have been at least partly derived from an expectation of treatment benefits, or social interactions. The researchers say that more research is needed into which characteristics of mindfulness training may be more likely to confer cognitive benefits, or whether delivering interventions over longer periods, or in intensive retreat settings, might yield greater cognitive benefits. Senior author Dr Natalie Marchant (UCL Psychiatry) said that they “know mindfulness-based programs benefit mental health, and our paper now suggests that mindfulness may also help to maintain cognitive faculties as people age. Mindfulness practices do not share much in common with cognitive test measures, so it is notable that mindfulness training's impact appears to transfer to other domains. While our review only identified a small benefit to executive function, it remains possible that some types of mindfulness training might deliver larger gains.” Major Depression Symptoms Improved with Chlorella University of Western Australia, August 23rd 2021    The symptoms of depression are often treated with drugs that can have long-term adverse side effects. A new study finds chlorella significantly reduces symptoms of major depression. Research from the University of Western Australia in Perth has found that chlorella can significantly improve symptoms of depression. The researchers tested 92 patients with major depressive disorder – a disorder that affects millions of people around the world. The researchers split the patients into two groups. They gave 42 of the patients 1,800 milligrams of Chlorella vulgaris extract per day. The other 50 patients continued their standard care. The researchers used a scale called the Hospital Anxiety and Depression Scale (HADS) to test the patients' symptoms of depression, along with the Beck Depression Inventory II (BDI-II) scale. Both of these have been used in clinical settings to establish the range of depressive symptoms and the severity of the diagnosis. After six weeks of treatment with either the standard pharmaceutical treatment or chlorella extract, the researchers found that those patients who had taken the chlorella had significantly reduced scores in both depression tests. The BDI-II scores went down by over four points and the HADS scores went down by 3.71 points. To give some reference, the HADS scale consists of 21 points, and anything over an 8 is considered symptomatic of anxiety or depression. In addition to reduced total scores, the researchers also saw significant reductions in some of the subset scores. For example, physical and cognitive symptoms were significantly improved in the chlorella group, and subscales for depression and anxiety were significantly lower among the chlorella group. The researchers concluded: “This pilot exploratory trial provides the first clinical evidence on the efficacy and safety of adjunctive therapy with CVE in improving physical and cognitive symptoms of depression as well as anxiety symptoms in patients who are receiving standard antidepressant therapy.” Chlorella is a microalga. It is a single-celled algae that is typically grown in controlled growth medium tanks. It is significantly high in protein, with over 40 percent protein, with all of the essential amino acids. It also contains proteins that stimulate growth hormone and brain neurotransmitters. Concentrated extract was used in this study due to the fact that whole chlorella can be difficult for the body to break down the cell wall. An extract provides the contents of the cell after the cell wall has been broken. Greater adherence to Mediterranean diet associated with decreased cardiometabolic risk during pregnancy University of Granada, August 20, 2021 According to news reporting out of Granada, Spain,research stated, “Studies regarding dietary patterns and cardiometabolic risk markers during pregnancy are scarce. The aim of the present study was to analyse whether different degrees of adherence to the Mediterranean diet (MD) and the MD components were associated with cardiometabolic markers and a clustered cardiometabolic risk during pregnancy.” Our news journalists obtained a quote from the research from the University of Granada, “This study comprised 119 pregnant women from the GEStation and FITness (GESTAFIT) project. Dietary habits were assessed with a food frequency questionnaire at the 16th and 34th gestational weeks (g.w.). The Mediterranean Diet Score was employed to assess MD adherence. The following cardiometabolic markers were assessed: pre-pregnancy body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, triglycerides and high-density lipoprotein cholesterol (HDL-C). A greater MD adherence was associated with a better cardiometabolic status in cross-sectional (16th g.w. and 34th g.w.) and prospective analyses (MD adherence at the 16th g.w. and cardiometabolic markers at the 34th g.w.; SBP, DBP and HDL-C; all, p< 0.05). Participants with the highest MD adherence (Tertile 3) had a lower clustered cardiometabolic risk than those with the lowest MD adherence (Tertile 1) at the 16th and 34th g.w. (both, p< 0.05). A higher intake of fruits, vegetables and fish and a lower intake of refined cereals and red meat and subproducts were associated with a lower cardiometabolic risk during pregnancy (all, p< 0.05).” According to the news editors, the research concluded: “A higher MD adherence, a greater intake of fruits, vegetables and fish and a lower intake of refined cereals and red meat and subproducts showed a cardioprotective effect throughout gestation.” Unhealthy diet during pregnancy could be linked to ADHD King's College London and the University of Bristol , August 20, 2021   New research led by scientists from King's College London and the University of Bristol has found that a high-fat, high-sugar diet during pregnancy may be linked to symptoms of ADHD in children who show conduct problems early in life. Published in the Journal of Child Psychology and Psychiatry, this study is the first to indicate that epigenetic changes evident at birth may explain the link between unhealthy diet, conduct problems and ADHD. Early onset conduct problems (e.g. lying, fighting) and attention-deficit/hyperactivity disorder (ADHD) are the leading causes of child mental health referral in the UK. These two disorders tend to occur in tandem (more than 40 per cent of children with a diagnosis of conduct disorder also have a diagnosis of ADHD) and can also be traced back to very similar prenatal experiences such as maternal distress or poor nutrition. In this new study of participants from the Bristol-based ‘Children of the 90s' cohort, 83 children with early-onset conduct problems were compared with 81 children who had low levels of conduct problems. The researchers assessed how the mothers' nutrition affected epigenetic changes (or DNA methylation) of IGF2, a gene involved in fetal development and the brain development of areas implicated in ADHD – the cerebellum and hippocampus. Notably, DNA methylation of IGF2 had previously been found in children of mothers who were exposed to famine in the Netherlands during World War II. The researchers from King's and Bristol found that poor prenatal nutrition, comprising high fat and sugar diets of processed food and confectionary, was associated with higher IGF2 methylation in children with early onset conduct problems and those with low conduct problems. Higher IGF2 methylation was also associated with higher ADHD symptoms between the ages of 7 and 13, but only for children who showed an early onset of conduct problems. Dr Edward Barker from King's College London said: ‘Our finding that poor prenatal nutrition was associated with higher IGF2 methylation highlights the critical importance of a healthy diet during pregnancy. These results suggest that promoting a healthy prenatal diet may ultimately lower ADHD symptoms and conduct problems in children. This is encouraging given that nutritional and epigenetic risk factors can be altered.' Dr Barker added: ‘We now need to examine more specific types of nutrition. For example, the types of fats such as omega 3 fatty acids, from fish, walnuts and chicken are extremely important for neural development. ‘We already know that nutritional supplements for children can lead to lower ADHD and conduct problems, so it will be important for future research to examine the role of epigenetic changes in this process.' Green tea may help protect against sunburn Taiyo Kagaku Co (Japan), August 24, 2021 A systematic review and meta-analysis published in a recent issue of Molecules found an association between oral intake or topical application of green tea catechins and a reduction in ultraviolet (UV) radiation-induced sunburn, which is an inflammatory reaction of the skin to UV exposure, clinically known as erythema.* Catechins are a type of flavonoid that occur in plants such as Camellia sinensis (tea). Green tea catechins include (-)-epigallocatechin-3-gallate (EGCG), well known for its anti-cancer and health-promoting effects, (-)-epicatechin, and many other similar molecules. These compounds have been recognized as having anti-inflammatory, antioxidant and photo-protective properties. “To our knowledge, this is the first meta-analysis to assess the effectiveness of green tea catechins specifically on measures of ultraviolet radiation-induced erythema and related pro-inflammatory mediators,” authors Mahendra P. Kapoor and colleagues wrote. “Regular intake of as low as 540 mg of green tea catechins per day could be beneficial for the protection against ultraviolet radiation-induced erythema, wherein green tea catechin metabolites are bioavailable at the dermis and epidermis levels of the skin, and thus increase the minimal dose of radiation (MED) required to induce erythema.” Dr Kapoor added that the study “suggests that green tea catechins can strengthen the skin's tolerance to ultraviolet radiation-induced skin damage from radiation through the prevention of the ultraviolet radiation-induced perturbation of epidermal barrier functions.” Study details: 12 weeks of green tea intake yields benefits The meta-analysis included three randomized, double-blind, placebo-controlled trials and one non-double-blind, non-placebo-controlled study that examined potential protective effects of orally administered capsules containing green tea catechins against sunburn (clinically known as erythema) induced by solar-simulated UV radiation. Two additional studies that involved a single dose of topically administered catechins were separately analyzed. Pooled analysis of data from three studies that evaluated erythema in skin exposed to UV radiation before and after 12 or more weeks of green tea catechin intake revealed a favorable effect in association with catechin intake. Both low and high doses of the green tea capsules were effective at decreasing low-dose UV radiation-induced erythema. It was also noted that a significant favorable effect was seen in the one study which assessed UV radiation-induced erythema after green tea intake for only six weeks, but as none of the other studies assessed this shorter duration of intake, further analysis was not performed. When green tea catechins' effects compared to a placebo were analyzed, pooling the data of two placebo-controlled trials confirmed their effectiveness against low-intensity UV radiation-induced erythema. Pooling data from participants in the studies involving topical green tea catechins revealed significant benefit for green tea at higher UV radiation doses.

Featuring an interview with Dr Sara M Tolaney, including the following topics: Role of the Breast Cancer Index® in predicting benefit from extended aromatase inhibitor therapy for hormone receptor (HR)-positive breast cancer  (0:00) ADAPT HR-positive/HER2-negative trial: Prognostic utility of genomic assays, clinical factors and response to endocrine therapy for patients with high-risk luminal breast cancer (5:43) De-escalation of neoadjuvant chemotherapy in the treatment of early breast cancer — Clinical outcomes from the ADAPT HR-negative/HER2-positive trial (9:49) Effect of dose escalation on the tolerability of neratinib — Results from the CONTROL study (15:02) Phase II GeparNuevo study: Addition of durvalumab to neoadjuvant anthracycline/taxane therapy for early triple-negative breast cancer (17:13) Neoadjuvant talazoparib for patients with HER2-negative early breast cancer with germline BRCA1/2 mutations — Results from the Phase II NEOTALA study (21:53) Results from the Phase III OlympiA trial assessing adjuvant olaparib for patients with high-risk HER2-negative early breast cancer with germline BRCA1/2 mutations (23:02) Updated survival results from Phase III studies of CDK4/6 inhibitors in combination with hormonal therapy for HR-positive, HER2-negative advanced breast cancer (27:23) Long-term outcomes with alpelisib and fulvestrant for patients with HR-positive advanced breast cancer with PIK3CA mutations (30:58) Trastuzumab with endocrine therapy or chemotherapy as first-line treatment for HR-positive, HER2-positive metastatic breast cancer: Results from the SYSUCC-002 trial (33:20) Subgroup analysis of the DESTINY-Breast01 trial: Efficacy and safety of trastuzumab deruxtecan in patients with HER2-positive breast cancer and stable brain metastases (36:29) BEGONIA: A Phase Ib/II study of durvalumab combinations for advanced triple-negative breast cancer (39:49) CME information and select publications

How do I take down property and make sure the numbers work? How do I own and manage that property and make sure I have cash flow? - Look no further, let Garrick O'Connell helps you here from acquisition to financing, to property management, to possibly disposition and networking. So... Get ready… It's time to get some deeper insights from our expert guest for this episode one of the Subgroup Leader with Garrick O'Connell.  __ Garrick O'Connell Bio: Originally from San Diego CA, Garrick O'Connell growing up near the ocean he enjoyed action sports such as ocean kayaking, deep-sea fishing, snorkeling,  and practiced martial arts that taught him to seek adventure and discipline. Before landing in Arizona he had been working for a successful architecture and construction consulting firm in San Diego actively helping real estate owners and investors fix everything that can go WRONG with real estate where he developed a love and appreciation for buildings and homes. After reaching his peak in consulting he decided to seek a new adventure and no longer watch from the sidelines so he could help with everything that can go RIGHT with real estate. I have now been in Tempe for 2 years enjoying all it has to offer and working in the Central and uptown phoenix corridor as well. New homeownership, home sales, helping homeowners become investors, and experienced investors expand their portfolios. -- 

Featuring an interview with Dr Arjun Balar, including the following topics: Phase III VISION study: Lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer (PC) (0:00) Updated safety outcomes from the EORTC 1333/PEACE III trial: Effect of adding bone-protecting agents (3:44) First results from the Phase III PEACE 1 study evaluating abiraterone acetate with prednisone and/or local radiation therapy for de novo metastatic castration-sensitive PC (5:09) Update on darolutamide tolerability: Outcomes with aggressive hormonal therapy for high-risk localized PC  (7:35) Bladder-sparing therapy with pembrolizumab, gemcitabine and concurrent hypofractionated radiation therapy for muscle-invasive bladder cancer (MIBC) (9:17) Results from the Phase II HCRN GU16-257 trial: Gemcitabine/cisplatin with nivolumab and selective bladder sparing for patients with MIBC (12:00) Long-term outcomes from the KEYNOTE-052 trial assessing first-line pembrolizumab for cisplatin-ineligible patients with advanced urothelial cancer (15:02) First-line maintenance therapy with avelumab for advanced urothelial cancer: Subgroup analysis of the JAVELIN Bladder 100 trial (17:19) Phase III CheckMate 9ER trial: Outcomes by baseline disease characteristics with nivolumab and cabozantinib for advanced renal cell carcinoma (RCC)  (18:29) Results from the Phase III KEYNOTE-564 study assessing pembrolizumab as postnephrectomy adjuvant therapy for patients with RCC  (20:16) Pembrolizumab with axitinib as first-line therapy for advanced RCC: Results from a 42-month follow-up of the KEYNOTE-426 trial (22:26) Updates on tyrosine kinase inhibitor and immune checkpoint inhibitor combination therapy and other novel agents for patients with RCC (24:07) Expert perspectives on advances in the treatment of genitourinary cancers (26:30) CME information and select publications

European Banking Authority's Slavka Eley joins host FNA's Isabella Ivanov to discuss her experience as a woman in finance and the role women will play in the industry in the future. ​ Slavka Eley joined the European Banking Authority in 2013 and currently leads the Banking Innovation and Products Unit, responsible for the EBA's work on financial Innovation, digital finance, capital market union and sustainable finance. As part of her current role, she leads the EBA project team on sustainable finance. Additionally, Slavka represents the EBA at European and international working groups, including the FSB Financial Innovation Network, the European Commission's Platform on Sustainable Finance and Basel Committee's Taskforce on Climate Risk. Over the past few years, Slavka has chaired different working groups at the EBA, such as the Network on Sustainable Finance, the Sub-group on Risk Assessment Systems, the mandate to develop the European Supervisory framework and the Subgroup on supervisory Effectiveness and Convergence. Before joining the EBA, Slavka worked for the National Bank of Slovakia as the Head of Supervisory Division for Banks with Advanced Risk Management Approach, responsible for supervising all large banks in Slovakia. Slavka holds an MBA in general management from the City University of Seattle and a Master's degree in Mathematics and Physics from the Comenius University Bratislava. 00:00:00 Introduction 00:00:26 Slavka's Role at EBA and Introduction to EBA 00:02:02: What topics are you focusing on under the Digital Finance work 00:03:31: Education and the background to your current role 00:07:40: Is diversity an issue in the industry anecdotally speaking 00:12:53: Importance of diversity in Technology and finance

Vegan and omnivorous diets promote equivalent muscle mass gain, study shows University of São Paulo (Brazil), May 19, 2021 Protein intake is more important than protein source if the goal is to gain muscle strength and mass. This is the key finding of a study that compared the effects of strength training in volunteers with a vegan or omnivorous diet, both with protein content considered adequate.  In the study, which was conducted by researchers at the University of São Paulo (USP) in Brazil, 38 healthy young adults, half of whom were vegans and half omnivores, were monitored for 12 weeks. In addition to performing exercises to increase muscle strength and mass, the volunteers followed either a mixed diet with both animal and plant protein, or an entirely plant-based diet, both with the recommended protein content (1.6 gram of protein per kilogram of body weight per day). At the end of three months, there was no difference between vegans and omnivores in terms of muscle strength and mass increase.  “Like any other protein in our organism, such as the proteins in our skin and hair cells, which die and are renewed, our muscles undergo synthesis and breakdown every day. Diet [protein intake] and exercise are the main protein balance regulators, favoring synthesis over breakdown,” said Hamilton Roschel, last author of the published study. Roschel is a University of São Paulo professor affiliated with both USP’s Sports and Physical Education School (EEEE) and Medical School (FM). He also heads the Applied Physiology and Nutrition Research Group jointly run by EEEE-USP and FM-USP. Protein sources are characterized primarily on the basis of essential amino acids, especially leukin, which plays a key role in anabolic stimulation of skeletal muscles. “Animal protein has more leukin than plant protein. Leukin is an essential amino acid in the anabolic stimulus signaling process. A plant-based diet is often thought to contain less leukin and hence trigger less anabolic stimulation, potentially affecting vegans’ capacity for muscle mass gain,” Roschel said. The study is published in Sports Medicine and resulted from the master’s research of Victoria Hevia-Larraín, with support from FAPESP.  The study innovated by including a clinical analysis of the effects of protein source quality on muscle adaptation in vegans as compared with omnivores, since most research on the topic to date has focused on the acute anabolic response of muscles to protein intake under laboratory conditions and not on muscle mass as such. “Our findings show that there is no impairment of muscle mass gain for young adult vegans if they ingest the right amount of protein. In fact, the outcome of both diets was the same in this respect,” Roschel said.  However, the researchers stress that, for the purposes of experimental control, protein intake was made the same in both diets by means of protein supplements. Omnivores and vegans were given milk serum protein isolate or soy protein respectively in accordance with individual dietary needs in order to attain the targeted protein intake.  “In clinical practice, we know foods of animal origin generally have a higher protein content,” Roschel said. “Meat, milk and eggs contain more protein per gram than rice and beans, for example. In a clinical application with plant-based foods as the sole protein source, vegans would need to ingest a large amount of food to obtain the same amount of protein. In some specific cases, this could be a major challenge.” The protein source (mixed or plant-based diet) made no difference, provided each subject received an adequate amount of protein. “This result corroborates other data in the literature showing that a vegan diet can absolutely be complete if it is properly planned and executed,” Roschel said. “Previous studies suggest it can even be healthier than an omnivorous diet. For this to be the case, however, it requires appropriate nutritional counseling and education regarding people’s choices in restricting their intake to plant-based sources.”  Another point noted by Roschel is that the subjects were healthy young adults, and the results might be different for older people or subjects with health problems. “Aging entails a phenomenon known as anabolic resistance, meaning a suboptimal anabolic response to the stimuli provided by diet and exercise compared with young people. Optimal response is possible in older people only if their protein intake is higher than that of the average healthy youngster. So we should be cautious about generalizing our findings for the entire population.”   Yoga and breathing exercises aid children with ADHD to focus Ural Federal University, May 17, 2021 Yoga and breathing exercises have a positive effect on children with attention deficit hyperactivity disorder (ADHD). After special classes, children improve their attention, decrease hyperactivity, they do not get tired longer, they can engage in complex activities longer. This is the conclusion reached by psychologists at Ural Federal University who studied the effect of exercise on functions associated with voluntary regulation and control in 16 children with ADHD aged six to seven years. The results of the study are published in the journal Biological Psychiatry. "For children with ADHD, as a rule, the part of the brain that is responsible for the regulation of brain activity - the reticular formation - is deficient," said Sergey Kiselev, head of the Laboratory of Brain and Neurocognitive Development at UrFU, head of the study. "This leads to the fact that they often experience states of inadequate hyperactivity, increased distraction and exhaustion, and their functions of regulation and control suffer a second time. We used a special breathing exercise based on the development of diaphragmatic rhythmic deep breathing - belly breathing. Such breathing helps to better supply the brain with oxygen and helps the reticular formation to better cope with its role. When the reticular formation receives enough oxygen, it begins to better regulate the child's state of activity". In addition to breathing exercises, psychologists used body-oriented techniques, in particular, exercises with polar states "tension-relaxation". The trainings took place three times a week for two to three months (depending on the program). "Exercise has an immediate effect that appears immediately, but there is also a delayed effect. We found that exercise has a positive effect on regulation and control functions in children with ADHD and one year after the end of the exercise. This happens because the child's correct breathing is automated, it becomes a kind of assistant that allows better supply of oxygen to the brain, which, in turn, has a beneficial effect on the behavior and psyche of a child with ADHD," says Sergey Kiselev. This technique was developed by the Russian neuropsychologist Anna Semenovich as part of a neuropsychological correction technique. UrFU psychologists tested how well this approach helps children with ADHD. But the study is pilot, says Kiselev. It showed that these exercises have a positive effect. However, more work needs to be done, involving more children with ADHD. This will also take into account factors such as gender, age, severity of the disease, concomitant problems in children (speech, regulatory, etc.).     Study findings suggest vitamin D deficiency may be associated with reduced arterial elasticity Guizhou Medical University (China), May 17, 2021   According to news reporting out of Guizhou, People’s Republic of China, research stated, “There is evidence that serum 25-hydroxyvitamin D [25-(OH) D] levels may be associated with cardiovascular disease and its risk factors. This study aimed to investigate the relationship between 25-(OH) D levels and blood pressure (BP), blood lipids, and arterial elasticity in middle-aged and elderly cadres in China.In this retrospective study, we included 401 civil servants and cadres aged >42 years who underwent medical examinations at Guiyang Municipal First People’s Hospital, China in 2018.” Our news journalists obtained a quote from the research from Guizhou Medical University, “The participants were assigned to deficiency ( 20 ng/mL), insufficiency (20-30 ng/mL), and sufficiency ( 30 ng/mL) groups according to 25-(OH) D levels in their blood. Demographics, brachial-ankle pulse wave velocity (baPWV), BP, ankle-brachial index (ABI), and blood lipids were compared among groups. The associations between 25-(OH) D and other parameters were evaluated using linear regression analysis.Median (range) 25-(OH) D levels in the deficiency (n = 162), insufficiency (n = 162), and sufficiency (n = 77) groups were 15.32 (2.93-19.88), 25.12 (20.07-29.91), and 33.91 (30.23-82.42) ng/mL, respectively. There were significant differences in systolic BP, pulse pressure, baPWV (left and right sides), ABI (left side), high-density lipoprotein-cholesterol, and triglycerides (TGs; all P< .05) among groups.” According to the news editors, the research concluded: “Multivariate linear regression revealed that TG, left baPWV, and right baPWV were significantly negatively correlated with 25-(OH) D levels (all P< .05).In this study, 25-(OH) D levels were found to be associated with TG, left baPWV, and right baPWV values. 25-(OH) D deficiency may be associated with reduced arterial elasticity.”     Icing muscle injuries may delay recovery Kobe University and Chiba Institute of Technology (Japan), May 19, 2021 A study using a mouse model of eccentric contraction (*1) has revealed that icing injured muscles delays muscle regeneration. The discovery was made by a research group including Associate Professor ARAKAWA Takamitsu and then PhD. Student KAWASHIMA Masato from Kobe University's Graduate School of Health Sciences, and Chiba Institute of Technology's Associate Professor KAWANISHI Noriaki et al. In addition, the researchers illuminated that this phenomenon may be related to pro-inflammatory macrophages' (*2, 3, 4) ability to infiltrate damaged cells. This research raises questions as to whether or not severe muscle injuries (such as torn muscles) should be iced. These research results were published online as one of the Journal of Applied Physiology's Articles in Press on March 25, 2021. Main points The research results revealed that applying an ice pack to a severe muscle injury resulting from eccentric contraction may prolong the time it takes to heal. The cause of this phenomenon is that icing delays the arrival of pro-inflammatory macrophages, which are responsible for the phagocytosis (*5), or removal, of damaged tissue. Furthermore, this makes difficult for the macrophages to sufficiently infiltrate the damaged muscle cells. Research Background Skeletal muscle injuries encompass a range of damage to muscles; from a microcellular level to a severe level. These injuries include not only those that happen during sports or schools' physical education lessons but also external injuries that occur as a result of accidents and disasters. 'RICE treatment' is a common approach for skeletal muscle injuries, regardless of the extent of the injury. This acronym stands for Rest, Ice, Compression and Elevation and is often used in physical education, sports and even medicine. Ice is commonly applied regardless of the type of muscle injury, yet little is known about the long-term effects of icing. Ice is used to suppress inflammation, however, inflammation in response to tissue injury is one of the body's healing mechanisms. This has come to be understood as a vital response for tissue regeneration. In other words, suppressing inflammation with ice may also inhibit the body's attempt to repair itself. Experiments investigating the effect of icing muscles after injury have produced conflicting results. Some have reported that it delays muscle regeneration while others have stated that it doesn't inhibit this process. However, none of the research up until now has investigated the effects of icing using an injury model that mimics common sports injuries caused by muscle contraction. Using a mouse model of eccentric contraction injury, the current research team decided to observe the effects of post-injury icing. In this mouse model, injuries were induced to resemble severe torn muscles. Research Methodology and Results Eccentric contraction was induced by electrically stimulating the leg muscles of the mice and then exerting a stronger force during this stimulation to make the leg muscles move in the opposite direction. After this, the muscles were harvested. Icing was performed by placing polyurethane bags of ice on top of the skin over three 30 minute sessions per day, with each session being 2 hours apart. This was continued until two days after the injury. The icing was based on the usual clinically recommended method. The researchers investigated the regenerated skeletal muscle two weeks after injury, comparing the icing group with the non-icing group. A significantly higher percentage of smaller regenerated muscle fibers were found in cross-sections from the icing group, with a greater number of medium to large fibers in the non-icing group (Figure 1). In other words, this revealed that skeletal muscle regeneration may be delayed as a result of icing. Next, the researchers periodically took samples of muscle from the icing and non-icing groups of animals in order to investigate what was happening in the regeneration process up until this point. In the regeneration process, inflammatory cells gather at the site of the injury, remove the debris from the damaged muscle and then begin to build new muscle. However, the results revealed that it is harder for inflammatory cells to enter the injured muscle cells if ice is applied (Figure 2). Macrophages are typical of the inflammatory cells that enter the injured muscle. These consist of pro-inflammatory macrophages, which phagocyte damaged tissue thus causing inflammation, and anti-inflammatory macrophages (*6), which suppress the inflammatory reaction and promote repair. It is thought that pro-inflammatory macrophages change their characteristics, becoming anti-inflammatory. The results of this research team's experiments showed that icing delays the arrival of pro-inflammatory macrophages at the site of the injury (Figure 3). These results indicate the possibility that macrophages are unable to sufficiently phagocyte the damaged muscle when ice is applied after severe muscle injuries caused by eccentric contraction, consequently delaying the formation of new muscle cells. Comment from Associate Professor Arakawa In sports, the mantra of immediately applying ice to an injury is commonplace, regardless of the injury's severity. However, the mechanism that we illuminated through this research suggests that not icing a severe muscle injury may lead to faster recovery. The idea of immediately cooling any type of injury is also entrenched in schools' physical education classes. I hope that in the future, the alternative option of speeding up recovery by not cooling severe muscle injuries will become known. However, even though icing may disrupt the recovery process for severe muscle injuries, there is no denying the possibility that there are degrees of mild muscle injuries that can be iced. The next issue is to work out where to draw the line. We are now in the middle of investigating what effect icing has on slight muscle injuries. Next, we will continue to investigate how icing should be carried out according to the extent of the muscle injury. We aim to contribute guidelines that will enable people in sports and clinical rehabilitation to make accurate judgements about whether or not to ice an injury.     Probiotics associated with fewer respiratory symptoms in overweight and older people Findings provide further evidence of relationship between the gut and lungs Imperial College London, May 14, 2021 Daily probiotic use was associated with fewer upper respiratory symptoms in overweight and older people, according to a study that suggests a potential role for probiotics in preventing respiratory infections. The study was selected for presentation at Digestive Disease Week® (DDW) 2021.  "This is not necessarily the most intuitive idea, that putting bacteria into your gut might reduce your risk of respiratory infection," said Benjamin Mullish, MD, a lead researcher on the study and clinical lecturer in the Division of Digestive Diseases, Imperial College London, England, "but it's further evidence that the gut microbiome has a complex relationship with our various organ systems. It doesn't just affect how our gut works or how our liver works, it affects aspects of how our whole body works." Researchers re-analyzed detailed daily diaries of 220 patients who participated in an earlier double-blind placebo-controlled study on probiotics and weight loss. Reviewing the entries for common symptoms of upper respiratory infection, including cough, sore throat and wheezing, researchers found that participants who took probiotics during the six-month study had a 27 percent lower overall incidence of upper respiratory tract symptoms compared to the placebo group. The effect was largest among participants who were aged 45 years or older, as well as those with obesity. People with obesity are at higher risk for respiratory infections. Previous research has shown that probiotics reduce upper respiratory infections in healthy adults and children, but little data exists on this vulnerable population of older, overweight and people with obesity. "These findings add to growing interest in the gut-lung axis -- how the gut and the lungs communicate with each other," Dr. Mullish said. "It's not just the gut sending out signals that affect how the lungs work. It works in both directions. It adds to the story that changes in the gut microbiome can affect large aspects of our health." The researchers did not measure immune response, only respiratory symptoms. Future randomized clinical trials could help identify the mechanisms related to the reduction in respiratory symptoms and explore the possible impact of probiotics on the immune system, Dr. Mullish said.     Fruit discovery could provide new treatments for obesity, type 2 diabetes and cardiovascular disease University of Warwick (UK), May 11, 2021    A combination of two compounds found in red grapes and oranges could be used to improve the health of people with diabetes, and reduce cases of obesity and heart disease. The find has been made by University of Warwick researchers who now hope that their discovery will be developed to provide a treatment for patients.   Professor Thornalley who led research said: "This is an incredibly exciting development and could have a massive impact on our ability to treat these diseases. As well as helping to treat diabetes and heart disease it could defuse the obesity time bomb."   The research 'Improved glycemic control and vascular function in overweight and obese subjects by glyoxalase 1 inducer formulation' has been published in the journal Diabetes, and received funding from the UK's innovation agency, Innovate UK. The project was a collaboration between the University of Warwick and University Hospitals Coventry and Warwickshire (UHCW) NHS Trust.   A team led by Paul Thornalley, Professor in Systems Biology at Warwick Medical School, studied two compounds found in fruits but not usually found together. The compounds are trans-resveratrol (tRES) - found in red grapes, and hesperetin (HESP) - found in oranges. When given jointly at pharmaceutical doses the compounds acted in tandem to decrease blood glucose, improve the action of insulin and improve thehealth of arteries.   The compounds act by increasing a protein called glyoxalase 1 (Glo1) in the body which neutralises a damaging sugar-derived compound called methylglyoxal (MG). MG is a major contributor to the damaging effects of sugar. Increased MG accumulation with a high energy diet intake is a driver of insulin resistance leading to type 2 diabetes, and also damages blood vessels and impairs handling of cholesterol associated with increased risk of cardiovascular diseases. Blocking MG improved health in overweight and obese people and will likely help patients with diabetes and high risk of cardiovascular disease too. It has already been proven experimentally that blocking MG improves health impairment in obesity and type 1 and type 2 diabetes.   Although the same compounds are found naturally in some fruits, the amounts and type required for health improvement cannot be obtained from increased fruit consumption. The compounds that increase Glo1 and are called a 'Glo1 inducer'. Pharmaceutical doses for patients with obesity, diabetes and high risk of heart disease could be given to patients in capsule form.   Professor Thornalley increased Glo1 expression in cell culture. He then tested the formulation in a randomised, placebo-controlled crossover clinical trial. Thirty-two overweight and obese people within the 18-80 age range who had a BMI between 25-40 took part in the trial. They were given the supplement in capsule form once a day for eight weeks. They were asked to maintain their usual diet and their food intake was monitored via a dietary questionnaire and they were also asked not to alter their daily physical activity. Changes to their sugar levels were assessed by blood samples, artery health measured by artery wall flexibility and other assessments by analysis of blood markers.   The team found that the highly overweight subjects who had BMIs of over 27.5 with treatment displayed increased Glo1 activity, decreased glucose levels, improved working of insulin, improved artery function and decreased blood vessel inflammation. There was no effect of placebo.   Professor Thornalley said: "Obesity, type 2 diabetes and cardiovascular disease are at epidemic levels in Westernised countries. Glo1 deficiency has been identified as a driver of health problems in obesity, diabetes and cardiovascular disease."   "Diabetic kidney disease will be the initial target to prove effective treatment for which we are currently seeking commercial investors and partners. Our new pharmaceutical is safe and expected to be an effective add-on treatment taken with current therapy.   "The key steps to discovery were to focus on increasing Glo1 and then to combine tRES and HESP together in the formulation for effective treatment. "As exciting as our breakthrough is it is important to stress that physical activity, diet, other lifestyle factors and current treatments should be adhered to."   Professor Martin O Weickert, Consultant in Diabetes and Endocrinology at UHCW NHS Trust, and co-applicant for the grant, said: "We were really excited to participate in this study with Warwick Medical School, as taking part in world-leading research makes a real difference to our patients both now and in the future. "As well as the positive effects for the UHCW patients who took part in the trial, we hope this study will lead to new treatments to help patients with diabetes and cardiovascular diseases all over the world."   Prof. Thornalley and his team are now hoping manufacturers will want to explore the use of the compound as pharmaceutical products.       Vitamin D supplementation associated with less time spent in ICU among critically ill patients Lishui People’s Hospital (China), May 18, 2021 According to news originating from Lishui, People’s Republic of China, research stated, “Vitamin D deficiency is a common scenario in critically ill patients and has been proven to be associated with poor outcomes. However, the effect of vitamin D supplementation for critically ill patients remains controversial.” Our news correspondents obtained a quote from the research from Lishui People’s Hospital: “Thus, we conducted a meta-analysis to evaluate the effect of vitamin D supplementation among critically ill patients. Electronic databases PubMed, Embase, Scopus, and the Cochrane Library were searched for eligible randomized controlled trials between 2000 and January 2021. The primary outcome was overall mortality, and the secondary ones were the length of intensive care unit stay, the length of hospital stay, as well as the duration of mechanical ventilation. Subgroup analyses were performed to explore the treatment effect by type of admission, route of administration, dose of supplemented vitamin D, and the degree of vitamin D deficiency. A total of 14 studies involving 2,324 patients were finally included. No effect on overall mortality was found between vitamin D supplementation and control group [odds ratio (OR), 0.73; 95% CI, 0.52-1.03; I2 = 28%]. The vitamin D supplementation reduced the length of intensive care unit stay [mean difference (MD), -2.25; 95% CI, -4.07 to -0.44, I2 = 71%] and duration of mechanical ventilation (MD, -3.47; 95% CI, -6.37 to -0.57, I2 = 88%). In the subgroup analyses, the vitamin D supplementation for surgical patients (OR, 0.67; 95% CI, 0.47-0.94; I2 = 0%) or through parenteral way (OR, 0.42; 95% CI, 0.22-0.82, I2 = 0%) was associated with reduced mortality.” According to the news reporters, the research concluded: “In critically ill patients, the supplementation of vitamin D has no effect on overall mortality compared to placebo but may decrease the length of intensive care unit stay and mechanical ventilation. Further trials are necessary to confirm our findings.”

In Today's episode, let's welcome our special guest Patrick Allen.  Patrick Allen is a licensed real estate agent who moved to Tucson in 2013 from Nashville, TN. A former ultra-endurance triathlon coach, Patrick has a passion for helping home buyers and real estate investors alike accomplish their goals of buying their first, or next, property. Patrick enjoys serving his community through outreach programs surrounding investing and financial independence. In his free time, Patrick enjoys playing kickball, traveling, drinking craft beer and morning walks with his dog Artemis.  Make sure to listen to the full episode as Patrick discusses finding deals, how newbies can get started, and the Tucson group curriculum. Whether you are an experienced investor with a large portfolio, or just getting started and looking to secure income and wealth through real estate investing the AZREIA Show is here for you. This podcast provides you with exceptional education, resources, and support to help you further your real estate career. Our community consists of independent real estate investors who utilize a myriad of investment strategies. If you're looking to learn from the most successful investors in the industry then you have found your new home.   KEY TAKEAWAYS IN THIS EPISODE: 03: 14 Get to know Patrick Allen  06: 35 Real estate as a side hustle transition to full-time  07:47 The most straightforward ways to get started investing if you don't have a lot of capital. 13:13 Patrick provides service to the residents of Tucson  14:32 Patrick's primarily looking at Tucson market right now 15:49 Connect with Patrick  18:06 Benefits of being a member of Patrick's Subgroup in Tucson. 21:20 The beginning of Patrick's Subgroups in Tucson area (story revealed) 22:17 What is “Deal funnel at the top” 23:26 Newbie investors curriculum to learn real estate investing with Patrick (pretty polished) 27:42 Patrick's most intriguing part about being a Sub Group Leader. 28:49 Philosophy of “Why is this the next step?” 30:56 Characteristics that a newbie  investor should have in order to reach the level of success. 34:13 Azreia Calendar of Events.  Find out more about our guest at: https://www.biggerpockets.com/users/pat_allen Email: patrick@teamintegritytucson.com  Phone: 520.275.7368   ----- Thanks for listening to the AZREIA SHOW Podcast with Marcus Maloney and Michael Del Prete. Don't forget to subscribe to the show on iTunes and leave a rating and review. See you on our next episode!   To learn more about investing and to understand your investor identity to the free Entrepreneur Self Assessment at: https://azreia.org/entrepreneurial-self-assessment/  Azreia Real Estate Investing Entrepreneurial Self Assessment Who is if for? Anyone who wants to know if Real Estate Investing is right for them BEFORE spending time or money on education and training. Everyone new to Real Estate Investing Our Entrepreneurial Self Assessment is designed for you to understand if Real Estate Investing is right for you and if so, you are best suited for active or passive investing.   Join our conversation at: Facebook:   Twitter:  Instagram:  Website: LinkedIn:        

Whether you are an experienced investor with a large portfolio, or just getting started and looking to secure income and wealth through real estate investing the AZREIA Show is here for you. This podcast provides you with exceptional education, resources, and support to help you further your real estate career. Our community consists of independent real estate investors who utilize a myriad of investment strategies. If you're looking to learn from the most successful investors in the industry then you have found your new home. In today's episode, our special guest is Allan Woodruff he a Design Engineer, an Investor, an Electrical Contractor, an MBA, or a sales manager in the Asia Pacific region? These are all steps along the path. In 1968, Allan Woodruff left graduate school, moved to California, and started a career in technology. Within four months he bought his first duplex and was off and running as a part-time investor. His goal was simple: acquire enough properties that would pay themselves off over the next 30 years, so that they would then generate enough cash flow to allow him to break free. With this mission in mind, he was able to enjoy his high-tech career, and casually invest in real estate with a buy-hold strategy. He still enjoys the sport of the game. It's not all about the money... it's an art form, it's providing housing, it's improving the community. And it's fun. As a believer in building body, mind, and spirit, he's conscious of putting being into his doing. KEY TAKEAWAYS: 2:23 Get to know Alan Woodruff 7:03 How did Allan get his first duplex 30 days after he read a book? 12:50 The joy of providing housing to tenants kept Allan's passion & mission burning throughout the years 21:50  Allan's investment in different cities was a product of his market research & extensive analysis 29:04 Investing out of state as a result of ‘Serendipity' 30:27 Tips about finding contractors on both local or outside markets—REVEALED! 33:19 How did Allan bounce back after a mistake? 35:10 Allan bought deals out of state through CASH. How did he do that?       ----- Thanks for listening to the AZREIA SHOW Podcast with Marcus Maloney and Michael Del Prete. Don't forget to subscribe to the show on iTunes and leave a rating and review. See you on our next episode! To learn more about investing and to understand your investor identity to the free Entrepreneur Self Assessment at: https://azreia.org/entrepreneurial-self-assessment/  Azreia Real Estate Investing Entrepreneurial Self Assessment Who is if for? Anyone who wants to know if Real Estate Investing is right for them BEFORE spending time or money on education and training. Everyone new to Real Estate Investing Our Entrepreneurial Self Assessment is designed for you to understand if Real Estate Investing is right for you and if so, you are best suited for active or passive investing.   Join our conversation at: Facebook:   Twitter:  Instagram:  Website: LinkedIn:  

Introduction: In the U.S. A., there are many subgroups existing within all racial and ethnic groups. To make America truly a great/united nation under God, we need to be sensitive to individual differences and avoid over-generalization or stereotyping of any group. Not everyone is the same within one racial or ethnic group; everyone is different as an individual. Better not assume everyone in a racial group is the same.

Guest: Xiaohong Wang, MD, PhD Association of Biomarker Cutoffs and Endoscopic Outcomes in Crohn's Disease: A Post Hoc Analysis From the CALM Study Walter Reinisch, Remo Panaccione, Peter Bossuyt, Filip Baert, Alessandro Armuzzi, Xavier Hébuterne, Simon Travis, Silvio Danese, William J Sandborn, Stefan Schreiber, Sofie Berg, Qian Zhou, Kristina Kligys, Ezequiel Neimark, Ahmed A Suleiman, Geert D'Haens, Jean-Frederic Colombel Background: CALM was a randomized phase 3 trial in patients with Crohn's disease (CD) that demonstrated improved endoscopic outcomes when treatment was escalated based on cutoffs for inflammatory biomarkers, fecal calprotectin (FC), C-reactive protein (CRP), and CD Activity Index (CDAI) remission vs CDAI response alone. The purpose of this post hoc analysis of CALM was to identify drivers of treatment escalation and evaluate the association between biomarker cutoff concentrations and endoscopic end points. Methods: The proportion of patients achieving CD Endoscopic Index of Severity (CDEIS)

Guest: Xiaohong Wang, MD, PhD Association of Biomarker Cutoffs and Endoscopic Outcomes in Crohn's Disease: A Post Hoc Analysis From the CALM Study Walter Reinisch, Remo Panaccione, Peter Bossuyt, Filip Baert, Alessandro Armuzzi, Xavier Hébuterne, Simon Travis, Silvio Danese, William J Sandborn, Stefan Schreiber, Sofie Berg, Qian Zhou, Kristina Kligys, Ezequiel Neimark, Ahmed A Suleiman, Geert D'Haens, Jean-Frederic Colombel Background: CALM was a randomized phase 3 trial in patients with Crohn's disease (CD) that demonstrated improved endoscopic outcomes when treatment was escalated based on cutoffs for inflammatory biomarkers, fecal calprotectin (FC), C-reactive protein (CRP), and CD Activity Index (CDAI) remission vs CDAI response alone. The purpose of this post hoc analysis of CALM was to identify drivers of treatment escalation and evaluate the association between biomarker cutoff concentrations and endoscopic end points. Methods: The proportion of patients achieving CD Endoscopic Index of Severity (CDEIS)

Surveys can be used to learn a lot about your target market’s attitudes, behaviors and perceptions. But only if you analyze this market research data correctly. In this real-world example, we see an-all-too common error. Don’t let this happen to you! See the case study origin here: https://bit.ly/3cgQ7KU

Date: March 31st, 2021 Guest Skeptic: Prof Daniel Fatovich is an emergency physician and clinical researcher based at Royal Perth Hospital, Western Australia. He is Head of the Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research; Professor of Emergency Medicine, University of Western Australia; and Director of Research for Royal Perth […]

Chaga mushrooms, a natural way to regrow hair?  Tokushima University (Japan), February 28 2021 Alopecia areata is a condition characterized by hair falling out in patches. Research suggests it is caused by the immune system attacking the hair follicles, causing them to shrink and slow down hair production. Because of this, alopecia is called an autoimmune disorder. According to statistics, alopecia is a common autoimmune disorder that affects about 6.8 million people in the U.S. alone. One in five people who suffer from alopecia has a family member with the same condition. Hair loss, however, can vary from nothing more than a few patches to complete loss of hair on the scalp or the entire body. There are currently no mainstream cures for alopecia, and the reason why the immune system attacks hair follicles is still unknown. But in a recent study, researchers at Tokushima University in Japan reported a natural medicine that can potentially reverse the effects of alopecia. Inonotus obliquus, commonly known as chaga, is a parasitic fungus that grows on birch and other trees. It is traditionally used to treat gastrointestinal diseases as well as to maintain healthy hair in many countries in Asia. The researchers screened chaga mushrooms for useful phytochemicals and found that it contains plenty of potential anti-alopecia agents. They discussed their findings in detail in an article published in the Journal of Natural Medicines. Compounds in chaga mushroom promote proliferation of hair follicles Chaga mushrooms refer to the resting body, or sclerotium, of I. obliquus. In countries like China, Korea, Japan and Russia, these mushrooms are known for their favorable effects on lipid metabolism and cardiac function. Research has also found that they possess antibacterial, anti-inflammatory, antioxidant and anti-tumor properties, and even exhibit antiviral properties against the hepatitis C virus and the human immunodeficiency virus. On the other hand, phytochemical analysis of chaga mushrooms reveal that they are rich in polysaccharides, triterpenes and polyphenols. They also contain two components commonly derived from birch trees, namely, betulin (or betulinol) and betulinic acid. Studies show that betulin can help lower cholesterol levels and increase insulin sensitivityin mice, while betulinic acid can activate signaling pathways that lead to cancer cell death. According to Japanese researchers, chaga mushrooms are used in Mongolia to make shampoo that helps with the maintenance of strong, healthy hair. This prompted them to investigate whether chaga mushrooms can be used for the treatment of alopecia. Bioassay-guided fractionation of chaga mushroom extracts allowed them to identify five lanostane-type triterpenes whose structures they confirmed using spectroscopy. The researchers then conducted proliferation assays using human follicle dermal papilla cells (HFDPCs) and found that four of the five triterpenes can promote the proliferation of HFDPCs. The compounds were identified as lanosterol, inotodiol, lanost-8,24-diene-3B,21-diol and trametenolic acid. The researchers also reported that these lanostane-type triterpenes were more potent than minoxidil, a conventional treatment for male-pattern baldness that’s used to promote hair growth. Based on these findings, the researchers concluded that the lanostane-type triterpenes in chaga mushrooms are potent anti-alopecia agents that can be used to stimulate hair growth naturally.      Association of serum folate, vitamin A and vitamin C levels with greater bone mineral density Tiajin Fifth Central Hospital (China), February 22, 20221 According to news originating from the Tianjin Fifth Central Hospital research stated, “The conclusions on the associations of specific vitamin levels with bone mineral density (BMD) were controversial. Therefore, the aims of this study were to examine the associations of serum vitamins levels with BMD and the modified effect of race/ ethnicity on these associations in the US adults.” The news editors obtained a quote from the research from Tianjin Fifth Central Hospital: “This study was from the third National Health and Nutrition Examination Survey. All participants aged 18 years with complete data were eligible. Serum vitamins A, B9, B12, C, and E levels were assayed using the Quantaphase II Radioassay Kit (Bio-Rad). Dual-energy X-ray absorptiometry was employed to measure BMD, including femur neck and the total hip. There were 6023 participants included in the final analysis. Serum folate, vitamins A and C levels were positively associated with BMD. No significant associations of serum vitamins B12 and E levels with BMD were observed. There were positive associations of serum folate level (b = 0.00027 and 0.00032; and 95% CI: 0.00002-0.00057 and 0.00002-0.00063, respectively), vitamin A level (b = 0.01132 and 0.01115; and 95% CI: 0.00478-0.01787 and 0.00430-0.01799, respectively), and vitamin C level (b = 0.00027 and 0.00029; and 95% CI: 0.00012-0.00042 and 0.00013-0.00045, respectively) with BMD at femur neck and the total hip only in the Not Hispanic participants.” According to the news editors, the research concluded: “Elevated serum folate, vitamins A and C levels were associated with a higher BMD. Furthermore, sex and race/ ethnicity modified the associations of serum vitamins levels with BMD.”     Study shows mother's diet may boost immune systems of premature infants Johns Hopkins University, February 25, 2021 Medical researchers have long understood that a pregnant mother's diet has a profound impact on her developing fetus's immune system and that babies -- especially those born prematurely -- who are fed breast milk have a more robust ability to fight disease, suggesting that even after childbirth, a mother's diet matters. However, the biological mechanisms underlying these connections have remained unclear. Now, in a study published Feb. 15, 2021, in the journal Nature Communications, a Johns Hopkins Medicine research team reports that pregnant mice fed a diet rich in a molecule found abundantly in cruciferous vegetables -- such as broccoli, Brussels sprouts and cauliflower -- gave birth to pups with stronger protection against necrotizing enterocolitis (NEC). NEC is a dangerous inflammatory condition that destroys a newborn's intestinal lining, making it one of the leading causes of mortality in premature infants. The team also found that breast milk from these mothers continued to confer immunity against NEC in their offspring.  Seen in as many as 12% of newborn babies weighing less than 3.5 pounds at birth, NEC is a rapidly progressing gastrointestinal emergency in which normally harmless gut bacteria invade the underdeveloped wall of the premature infant's colon, causing inflammation that can ultimately destroy healthy tissue at the site. If enough cells become necrotic (die) so that a hole is created in the intestinal wall, the bacteria can enter the bloodstream and cause life-threatening sepsis. In earlier mouse studies, researchers at Johns Hopkins Medicine showed that NEC results when the underdeveloped intestinal lining in premature infants produces higher-than-normal amounts of a protein called toll-like receptor 4 (TLR4). TLR4 in full-term babies binds with bacteria in the gut and helps keep the microbes in check. However, in premature infants, TLR4 can act like an immune system switch, with excess amounts of the protein mistakenly directing the body's defense mechanism against disease to attack the intestinal wall instead. "Based on this understanding, we designed our latest study to see if indole-3-carbinole, or I3C for short, a chemical compound common in green leafy vegetables and known to switch off the production of TLR4, could be fed to pregnant mice, get passed to their unborn children and then protect them against NEC after birth," says study senior author David Hackam, M.D., Ph.D., surgeon-in-chief at Johns Hopkins Children's Center and professor of surgery at the Johns Hopkins University School of Medicine. "We also wanted to determine if I3C in breast milk could maintain that protection as the infants grow."  In the first of three experiments, Hackam and his colleagues sought to induce NEC in 7-day old mice, half of which were born from mothers fed I3C derived from broccoli during their pregnancies and half from mothers fed a diet without I3C. They found that those born from mothers given I3C throughout gestation were 50% less likely to develop NEC, even with their immune systems still immature at one week after birth. The second experiment examined whether breast milk with I3C could continue to provide infant mice with protection against NEC. To do this, the researchers used mice genetically bred without the binding site on intestinal cells for I3C known as the aryl hydrocarbon receptor (AHR). When AHR-lacking pups were given breast milk from mice fed a diet containing I3C, they could not process the compound. Therefore, they developed severe NEC 50% more frequently than infant mice that had the I3C receptor.  The researchers say this shows in mice -- and suggests in humans -- that AHR must be activated to protect babies from NEC and that what a mother eats during breastfeeding -- in this case, I3C -- can impact the ability of her milk to bolster an infant's developing immune system.  In confirmatory studies, Hackam and his colleagues looked at the amounts of AHR in human tissue obtained from infants undergoing surgery for severe NEC. They found significantly lower than normal levels of the receptor, suggesting that reduced AHR predisposes infants to the disease. Finally, the researchers searched for a novel drug that could be given to pregnant women to optimize AHR's positive effect and reduce the risk of NEC in the event of premature birth. After screening in pregnant mice a variety of compounds already approved by the U.S. Food and Drug Administration for other clinical uses, the researchers observed that one, which they called A18 (clinically known as lansoprazole, a drug approved for the treatment of gastrointestinal hyperacidity), activates the I3C receptor, limits TLR4 signaling and prevents gut bacteria from infiltrating the intestinal wall.  To show the relevance of what they saw in mice, the researchers tested A18 in the laboratory on human intestinal tissue removed from patients with NEC and found the drug produced similar protective results. "These findings enable us to imagine the possibility of developing a maternal diet that can not only boost an infant's overall growth, but also enhance the immune system of a developing fetus and, in turn, reduce the risk of NEC if the baby is born prematurely," says Hackam.   Plant-based diets improve cardiac function, cognitive health Boston University Medical School, February 25, 2021 What if you could improve your heart health and brain function by changing your diet? Boston University School of Medicine researchers have found that by eating more plant-based food such as berries and green leafy vegetables while limiting consumption of foods high in saturated fat and animal products, you can slow down heart failure (HF) and ultimately lower your risk of cognitive decline and dementia. Heart failure (HF) affects over 6.5 million adults in the U.S. In addition to its detrimental effects on several organ systems, presence of HF is associated with higher risk of cognitive decline and dementia. Similarly, changes in cardiac structure and function (cardiac remodeling) that precede the appearance of HF are associated with poor cognitive function and cerebral health.  The adoption of diets, such as the Mediterranean diet (MIND) and the Dietary Approaches to Stop Hypertension (DASH), which are characterized by high intakes of plant-based foods are among lifestyle recommendations for the prevention of HF. However, whether a dietary pattern that emphasizes foods thought to promote the maintenance of neurocognitive health also mitigates changes in cardiac structure and function (cardiac remodeling) has been unclear until now. The researchers found the MIND diet, which emphasizes consumption of berries and green leafy vegetables while limiting intakes of foods high in saturated fat and animal products, positively benefited the hearts' left ventricular function which is responsible for pumping oxygenated blood throughout the body. The researchers evaluated the dietary and echocardiographic data of 2,512 participants of the Framingham Heart Study (Offspring Cohort), compared their MIND diet score to measures of cardiac structure and function and observed that a dietary pattern that emphasizes foods thought to promote the maintenance of neurocognitive health also mitigates cardiac remodeling. According to the researchers previous studies have highlighted the importance of diet as a modifiable risk factor for cognitive decline and dementia. "Our findings highlight the importance of adherence to the MIND diet for a better cardiovascular health and further reduce the burden of cardiovascular disease in the community," explained corresponding author Vanessa Xanthakis, PhD, assistant professor of medicine and biostatistics at BUSM and an Investigator for the Framingham Heart Study. Although Xanthakis acknowledges that following a healthy diet may not always be easy or fit with today's busy schedules, people should make a concerted effort to adhere to healthy eating to help lower risk of disease and achieve better quality of life.         Fear of memory loss impacts well-being and quality of life Trinity College Dublin, February 23, 2021 Research from the Global Brain Health Institute (GBHI) at Trinity College suggests that experiencing high levels of fear about dementia can have harmful effects on older adults' beliefs about their memory and general well-being. To date, few studies have measured the impact of dementia-related fear on daily functioning, despite its clinical relevance. In this new study, published in the journal Aging and Mental Health, researchers investigated if fear of memory decline predicted increased memory failures and poorer quality of life in older adults. Dr. Francesca Farina, Atlantic Fellow for Equity in Brain Health at GBHI, in collaboration with researchers at the University of Cambridge, University of Maastricht and Northwestern University developed a novel scale—known as the Fear of Memory Loss (FAM) scale—to capture different components of fear related to memory loss. Using the scale, healthy older adults aged 55+ were assessed with respect to the different dimensions of fear. Questions probed specific fears like becoming dependent on others, being treated differently by friends or colleagues, and loss of identity, as well as coping strategies like avoiding social situations for fear of embarrassment. Findings from the study showed that having higher levels of fear about dementia was associated with reporting more memory lapses and a lower quality of life. Notably, these results were independent of performance on memory tests and the level of reported anxiety. That is, fears about dementia had a negative influence on peoples' beliefs regardless of how they performed on an objective lab-based memory test, or how they rated their anxiety levels. Key findings: Heightened fear of memory loss significantly predicted lower quality of life and increased self-reported memory failures, after controlling for objective memory performance and general anxiety. There was no difference in the level of fear expressed between those with and without a family history of dementia. Though surprising, this result is consistent with evidence of widespread fear of dementia among the general population. Over half of respondents (57%) said they worried about losing their memory and feared how people would treat them if this happened. The novel FAM scale highlights the important role played by avoidance behaviors in maintaining fear, along with subjective experiences and cognitions. Findings also have important healthcare implications. Fear of dementia is a psychological process that can be modified using interventions such as psycho-education and psychotherapy. The researchers propose a preliminary fear-avoidance model, where perceived changes in memory result in fear, which over time, creates avoidance and social withdrawal. This combination of fear and avoidance has a negative impact on everyday functioning, which then impairs mood and sense of self. Identifying effective ways to challenge fears about dementia could prove beneficial to individuals and society. On the individual level, reducing fear could lead to improvements in how people view their memory function and quality of life. At the societal level, acknowledging and addressing fears about dementia would help to eliminate stigma associated with the condition. Dr. Francesca Farina, Atlantic Fellow at GBHI, and lead author said: "Almost 80% of the general public are concerned about developing dementia, according to the World Alzheimer Report 2019. Evidence also suggests that these fears increase with age. Given global population aging and the increased visibility of dementia, it is crucial that we find ways to address peoples' fears. Understanding and tackling these fears will serve to promote brain health and well-being, and reduce societal stigma for people living with disease and their carers." Tackling Fear and Stigma Through Art Data from the study inspired "Remembering What I Have Forgotten': a fictional diary written from the perspective of someone experiencing symptoms of dementia. Created by Irish artist Aoibheann Brady, student at the National College of Art and Design, the diary aims to capture the feelings and perspectives of people experiencing memory loss. Through the medium of a diary, "Remembering What I Have Forgotten' offers a realistic insight into the experience of dementia, with entries such as "I feel more withdrawn and am not going out or connecting" and "I am anxious that I will make mistakes." This diary, however, was not written by a person—but by a software application known as a chatbot, which had been trained on anonymous interviews with healthcare professionals and carers of people living with dementia. Aoibheann Brady, creator of "Remembering What I Have Forgotten' said: "With this project, I aimed to create work that is a crossover between art and science. I hope it helps demonstrate, to younger generations and members of the art world, that dementia is something that should be considered more in artistic practices."     Diet of fish and olive oils beneficially modifies membrane properties in striatal rat synaptosomes National Institute of Neurology & Neurosurgery (Mexico), February 25, 2021 According to news reporting originating in Mexico City, Mexico, research stated, “Essential fatty acids (EFAs) and non-essential fatty acids (nEFAs) exert experimental and clinical neuroprotection in neurodegenerative diseases. The main EFAs, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), nEFAs, and oleic acid (OA) contained in olive and fish oils are inserted into the cell membranes, but the exact mechanism through which they exert neuroprotection is still unknown.” The news reporters obtained a quote from the research from the National Institute of Neurology & Neurosurgery, “In this study, we assessed the fatty acids content and membrane fluidity in striatal rat synaptosomes after fatty acid-rich diets (olive- or a fish-oil diet, 15% w/w). Then, we evaluated the effect of enriching striatum synaptosomes with fatty acids on the oxidative damage produced by the prooxidants ferrous sulfate (FeSO4) or quinolinic acid (QUIN). Lipid profile analysis in striatal synaptosomes showed that EPA content increased in the fish oil group in comparison with control and olive groups. Furthermore, we found that synaptosomes enriched with fatty acids and incubated with QUIN or FeSO4 showed a significant oxidative damage reduction.” According to the news reporters, the research concluded: “Results suggest that EFAs, particularly EPA, improve membrane fluidity and confer antioxidant effect.” This research has been peer-reviewed.     Soy intake is associated with lowering blood pressure in adults: A meta-analysis of randomized double-blind placebo-controlled trials Shiraz University of Medical Sciences (Iran), February 24, 2021 Soy has several beneficial effects on cardiovascular disease (CVD); however, results of clinical trial studies are equivocal. Thus, the present study sought to discern the efficacy of soy intake on blood pressure. Methods The search process was conducted in PubMed, Scopus, Web of Science, and Cochrane Library, to ascertain studies investigating the efficacy of soy intake on blood pressure in adults, published up to June 2020. A random-effects model was applied to pool mean difference and 95% confidence intervals (CIs). Meta-regression analysis was performed to discern potential sources of heterogeneity. Begg’s and Egger’s methods were conducted to assess publication bias. Results Pooled effects from 17 studies revealed a significant improvement in systolic blood pressure (SBP) (-1.64; -3.25 to -0.04 mmHg; I2 = 50.5 %) and diastolic blood pressure (DBP) (-1.21; -2.29 to -0.12 mmHg, I2 = 50.7 %) following soy consumption, in comparison with controls. Subgroup analysis demonstrated a reduction in both SBP and DBP in younger participants with lower baseline blood pressure and intervention durations of

The effects of lycopene supplementation on serum insulin-like growth factor 1 (IGF-1) levels and cardiovascular disease Ganzhou People’s Hospital (China), February 22, 2021   The results of human studies assessing the efficacy of lycopene on insulin-like growth factor 1 (IGF-1) levels are inconsistent. Thus, we performed a systematic review and meta-analysis to examine the effects of lycopene supplementation on serum IGF-1 levels and cardiovascular disease. Methods The literature published up to January 2020 was searched using the electronic databases Scopus, PubMed/Medline, Web of Science, Embase and Google Scholar. Results Seven qualified trials were included in the current meta-analysis. IGF-1 levels were non-significantly decreased in lycopene group compared to the control (WMD: −6.74 ng/mL, 95 % CI: −23.01 to 9.52, p = 0.42; I2 = 94.3 %). Subgroup analysis revealed a significantly decrease in IGF-1 levels upon lycopene supplementation at doses ≥15 mg/d (WMD: −6.40 ng/mL), intervention period 15 mg/d, for

Featuring an interview with Dr Ann S LaCasce on the following topics: Real-world prognostic biomarker testing, treatment patterns and dosing among patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) from the informCLL™ prospective observational registry (0:00) Outcomes with first-line ibrutinib among patients with CLL/SLL and high-risk genomic features: Integrated analysis of the RESONATE-2 and iLLUMINATE trials (3:09) Clinical outcomes among real-world patients with CLL initiating first-line ibrutinib or chemoimmunotherapy stratified by risk status: Results from a US retrospective chart review study (8:14) Pooled analysis of cardiovascular events from clinical trials evaluating acalabrutinib monotherapy in patients with CLL (10:31) Final results from the ASCEND trial comparing acalabrutinib to idelalisib/rituximab or bendamustine/rituximab for relapsed/refractory (R/R) CLL (12:31) Clonal dynamics after venetoclax-obinutuzumab therapy: Novel insights from the randomized, Phase III CLL14 trial (13:50) Enduring undetectable minimal residual disease in patients with R/R CLL after venetoclax/rituximab: Five-year analysis of the MURANO study (16:06) Efficacy of ibrutinib with venetoclax in the treatment of CLL and SLL (20:22) Acalabrutinib in combination with venetoclax and either obinutuzumab or rituximab for patients with treatment-naïve or R/R CLL (23:01) Results from the Phase I/II BRUIN study of LOXO-305, a highly selective noncovalent Bruton tyrosine kinase inhibitor, for previously treated CLL or SLL (26:45) Superiority of umbralisib with ublituximab compared to obinutuzumab with chlorambucil for patients with treatment-naïve or R/R CLL in the Phase III UNITY-CLL study (29:36) Updated results from a Phase I/II study of duvelisib and venetoclax in patients with R/R CLL/SLL or Richter’s syndrome (32:55) Lisocabtagene maraleucel alone or in combination with ibrutinib for R/R CLL or SLL on the TRANSCEND CLL 004 trial (34:34) Subgroup analyses of elderly patients aged ≥70 years in MAGNIFY: A Phase IIIb interim analysis of induction R2 followed by maintenance in R/R indolent non-Hodgkin lymphoma (NHL) (40:32) Efficacy and tolerability of tazemetostat for R/R follicular lymphoma (FL) (42:44) CITADEL-203: A Phase II study evaluating the efficacy and safety of parsaclisib in patients with R/R FL (49:11) Primary analysis of ZUMA-5: A Phase II study of axicabtagene ciloleucel for R/R indolent NHL (50:58) Efficacy and safety of tisagenlecleucel in adult patients with R/R FL: Interim analysis of the Phase II ELARA trial (52:36) Efficacy of mosunetuzumab in patients with multiple regimen-refractory FL: Updated data from a Phase I dose-escalation trial (57:19) Novel approaches under investigation for CLL and FL; management of Richter’s transformation (1:02:11) Impact of COVID-19 on the care of patients with CLL or FL (1:07:17) CME information and select publications

Drs. Ron Waksman and Pierre Amarenco discuss a subgroup analysis of the THALES study, which was presented at the American Heart Association Scientific Sessions 2020 virtual conference. This analysis showed that ticagrelor added to aspirin reduced the 30-day risk of recurrent stroke by 27% in transient ischemic attack (TIA) and minor ischemic stroke patients with ipsilateral atherosclerotic stenosis of cervicocranial vasculature.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.09.289827v1?rss=1 Authors: McGregor, H. R., Lee, J. K., Mulder, E., De Dios, Y., Beltran, N. E., Kofman, I. S., Bloomberg, J. J., Mulavara, A. P., Seidler, R. D. Abstract: Following long-duration missions onboard the International Space Station, some astronauts develop ophthalmic abnormalities collectively referred to as Spaceflight Associated Neuro-ocular Syndrome (SANS). Optic disc edema is a common sign of SANS. SANS presents significant potential risk to astronaut health and performance; however, the origin and effects of SANS are not understood as signs of SANS have not manifested in previous spaceflight analog studies. Here we investigated if development of optic disc edema during a spaceflight analog impacts resting-state functional connectivity. Eleven healthy volunteers participated in this 58-day longitudinal study conducted at the :envihab facility at the German Aerospace Center. Baseline data were collected during a 14-day ambulatory phase in standard ambient air. All participants then underwent a spaceflight analog intervention: 30 days of strict head-down tilt bed rest in elevated ambient carbon dioxide (HDBR+CO2). The elevated CO2 level (0.5%) was matched to the hypercapnic environment of the International Space Station. The intervention was followed by a 14-day ambulatory recovery phase in standard ambient air. During the HDBR+CO2 spaceflight analog, 5 participants developed optic disc edema (SANS subgroup) and 6 did not (NoSANS group). Using functional magnetic resonance imaging (fMRI), we acquired resting-state data at 6 time points throughout the study: before (2), during (2), and after (2) the HDBR+CO2 intervention. We assessed the time course of resting-state functional connectivity changes from before, during, to after the HDBR+CO2, and contrasted longitudinal changes between the SANS and NoSANS subgroups. We also assessed if the SANS and NoSANS subgroups exhibited differential patterns of resting-state functional connectivity prior to the HDBR+CO2 intervention. We foun that the SANS and NoSANS subgroups exhibited differential patterns of resting-state connectivity changes during the HDBR+CO2 spaceflight analog within visual and vestibular-related brain networks. We further found that the SANS and NoSANS subgroups exhibited differential resting-state brain activity prior to the spaceflight analog within a visual cortical network and within a large-scale network of brain areas involved in multisensory integration. Subgroup differences in resting-state functional connectivity changes may reflect differential patterns of visual and vestibular reweighting as optic disc edema develops during the HDBR+CO2 spaceflight analog. This finding suggests that SANS impacts not only neuro-ocular structures, but also brain function. Future prospective investigations incorporating sensory assessments are required to determine the functional significance of the observed connectivity differences. Copy rights belong to original authors. Visit the link for more info

The Bootstrap Marketing Subgroup chatted with Prof Dan Ariely, author of numerous books explaining the vagaries of human behavior and choice. Subgroup lead and BootRap Producer, Brian Massey interviewed Dan about his research and book, Predictably Irrational, and how these insights could be used in marketing and pricing. Brian provides a summary of the book in the first section and the interview begins at: 8:44. Topics covered include: Decoy Model, the power of comparison; social vs market exchange; price anchoring and Starbucks; TiVo v DVRs; fe/male differences in purchasing; the challenges of focus groups and bad data; anti-depressants vs placebos; the importance of moving marketing earlier in the product-creation process; design for physical AND cognitive differences; how the 2008 mortgage crisis was created by short-circuited human decision-making; how credit cards separate consumption from experience; Gucci, Prada & fakes; why consuming gas is stressful; the pain of pain; how lawyers should charge for their services; and much more. Dan also provides advice on how to appreciate the pain associated with the entrepreneurial journey. The conversation ends with a fascinating puzzle, the answer to which reveals our own proclivity to being "predictably irrational!" BootRap ATX is produced by Brian Massey of the Intended Consequences Podcast.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.19.255794v1?rss=1 Authors: Hmaied, C., Koulchitsky, S., Gladwyn-Ng, I., Seutin, V. Abstract: Although the fast antidepressant effect of ketamine is now well established clinically, neither its mechanism(s) nor its main site(s) of action is clearly defined. Because enhanced serotoninergic (5-HT) transmission is an important part of the antidepressant effect of various drug classes, we asked whether ketamine and one of its metabolites (hydroxynorketamine [HNK]), both used in their racemic form, may modulate the excitatory drive onto these neurons. Using whole-cell recordings from pharmacologically identified 5-HT and non-5-HT neurons in juvenile rat dorsal raphe slices, we found that both ketamine and HNK (10 microM) increase excitatory AMPA neurotransmission onto a subset (50%) of 5-HT neurons, whereas other 5-HT cells were unaffected. Both compounds increased the amplitude as well as the frequency of spontaneous excitatory post-synaptic currents (sEPSCs) mediated by AMPA receptors. The effect of ketamine was more robust than the one of HNK, since it significantly enhanced the charge transfer through AMPA channels, whereas HNK did not. The increase in the excitatory drive induced by ketamine was dependent on NMDA receptor blockade. In the presence of tetrodotoxin, the effect of ketamine was markedly reduced. Non-5-HT neurons, on the other hand, were unaffected by the drugs. We conclude that ketamine and HNK increase the excitatory drive onto a subset of 5-HT neurons by promoting glutamate release and possibly also through a postsynaptic action. The effect of ketamine is dependent on NMDA receptor modulation and appears to involve a network effect. These findings improve our understanding of the fast-acting antidepressant effect of ketamine. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.04.187401v1?rss=1 Authors: Yu, Q., Herold, F., Becker, B., KluGah-Brown, B., Zhang, Y., Perrey, S., Veronese, N., Muller, N. G., Zou, L., Kramer, A. F. Abstract: Despite a growing number of functional MRI studies reporting exercise-induced changes during cognitive processing, a systematic determination of the underlying neurobiological pathways is currently lacking. To this end, our neuroimaging meta-analysis included 20 studies and investigated the influence of exercise on cognition-related functional brain activation. The overall meta-analysis encompassing all experiments revealed exercise-induced changes in the left parietal lobe during cognitive processing. Subgroup analysis further revealed that in the younger-age group (

A new subgroup analysis of the VOYAGER-PAD trial revealed whether adding clopidogrel to the rivaroxaban and aspirin regime of a patient with peripheral artery disease (PAD) at the time of revascularization is beneficial. In this podcast, William R. Hiatt, MD, provides insight into the analysis results. The topic is one he presented about during a late-breaking clinical trial session, “The Benefit and Risk of Rivaroxaban Plus Aspirin in Patients With Peripheral Artery Disease After Lower Extremity Revascularization (LER) With and Without Concomitant Clopidogrel: a Key Subgroup Analysis From VOYAGER-PAD,” at ACC.20/WCC Virtual. For more, click here: www.consultant360.com/cardiology

It’s a worrying time out there at the moment, particularly for those who are vulnerable, immunosuppressed and older people. One organisation that is providing crucial support to older people is the charity ALONE.ALONE is a member organisation of the National Public Health Emergency COVID-19 Subgroup for Vulnerable People and is working in collaboration with the Department of Health and the HSE on a coordinated national response to support older people who have concerns, may be at risk or who have contracted the coronavirus, COVID-19.One of these critical supports is the operation of a national support line to complement the clinical advice and information being provided by the HSE through its website and helpline service. The ALONE support line is available seven days a week, 8am to 8pm on 0818 222 024 where professional staff will be available to answer questions in relation to the coronavirus, give advice and, where necessary, reassurance.In this podcast, the seventh in our Seminar Series, we will be revisiting our Annual Social Policy Conference from November 2019, and hearing from Seán Moynihan, CEO of ALONE, on revolutionising ageing at home together and the wonderful supports available from ALONE services.

As a follow up to the National Urban League’s report Standards of Equity and Excellence: A Lens on ESSA State Plans, we are hosting a webinar alongside our partners at the Alliance for Excellent Education to discuss an important part of state accountability systems: Subgroup Performance. Subgroup Performance is how well particular groups, divided by characteristics (gender, race/ethnicity, language status, socioeconomic status, etc.) perform in particular measurable areas including language arts, math, and many others. We invite you to join us for a brief discussion on what we are seeing in the field and how we can continue to hold states accountable as we move forward.

Sean and Nigel talk about the OSB ticketing sub group meeting See acast.com/privacy for privacy and opt-out information.

Dr Wang:             Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue.                                 In our first paper, Ying Tian and associates examine the effects and long-term outcomes of percutaneous stellate ganglion blockade in the setting of drug refractory electrical storm due to ventricular arrhythmia. They studied 30 consecutive patients over nearly a five-year period. They used bupivacaine alone, or in combination with lidocaine injected into the neck with good local anesthetic spread in the vicinity of the left stellate ganglion in 15 patients, or both stellate ganglion in 15 patients.                                 The mean left ventricular ejection fraction was 34%. At 24 hours, 60% of patients were free of ventricular arrhythmia. Patients whose ventricular arrhythmia was controlled had a lower hospital mortality rate than patients whose ventricular arrhythmia continued. 5.6 versus 50%, P equals 0.009. Implantable cardioverter-defibrillator interrogation showed a significant 92% reduction in ventricular arrhythmia episodes from 26 to 2 in the 72 hours after stellate ganglion blockade, P less than 0.001.                                 Patients who died during the same hospitalization, N equals 7, were more likely to have ischemic cardiomyopathy, 100% versus 43.5%. And recurrent ventricular arrhythmias within 24 hours, 85.7% versus 26.1%. There were no procedure related complications.                                 In our next paper, Zachi Attia and associates hypothesized that a convolutional neural network could be trained through a process called 'deep learning' to predict a person's age and gender using only 12-lead electrocardiogram signals. They trained convolutional neural network using 10 second samples of 12-lead ECG signals from 499,727 patients to predict gender and age. The networks were tested on a separate cohort of 275,056 patients. For gender classification, the model obtained 90.4% classification accuracy with an area under the curve of 0.97. In the independent test data, age was estimated as a continuous variable with an average error of 6.9 years, R squared equals 0.7.                                 Among 100 hundred patients with multiple ECGs over the course of at least two decades of life, most patients, 51%, had an average error between real age and convolutional neural network predicted age of less than seven years. Major factors seen amongst patients with convolutional neural network predicted age that exceeded chronologic age by greater than seven years included low ejection fraction, hypertension, and coronary disease, P less than 0.1. In the 27% of patients whose correlation was greater than 0.8, between convolutional neural network predicted and chronological age, no incident events occurred over follow up 30 years.                                 The authors concluded that applying artificial intelligence to the ECG allows prediction of patient, gender, and estimation of age. The ability of artificial intelligent algorithm to determine physiological age with further validation may serve as a measure of overall health.                                 In our next paper, Zain Ul Abideen Asad and associates performed a meta-analysis of randomized control trials in order to compare the efficacy and safety of catheter ablation with medical therapy for atrial fibrillation with the primary outcome being all-cause mortality. They examined 18 randomized controlled trials comprising 4,464 patients. Catheter ablation resulted in significant reduction in all-cause mortality, relative risk of 0.69 that was driven by patients with atrial fibrillation and heart failure in reduced ejection fraction, relative risk 0.52.                                 Catheter ablation resulted in significantly fewer cardiovascular hospitalizations, hazard ratio of 0.56, and fewer recurrences of atrial arrhythmia, relative risk 0.42. Subgroup analysis suggested that younger patients, age less than 65 years, and men derived more benefit from catheter ablation compared to medical therapy.                                 In our next paper, Felipe Kazmirczak, Ko-Hsuan Amy Chen, and associates examined patients with cardiac sarcoidosis meeting guideline criteria for implantable defibrillator implantation in a large retrospective cohort study of patients with biopsy proven sarcoidosis and known or suspected cardiac sarcoidosis undergoing cardiovascular magnetic resonance imaging. The authors found that in 290 patients, the class one and class 2A recommendation identified all patients who experienced a composite endpoint of significant ventricular arrhythmia or sudden cardiac death over a mean follow-up of three years.                                 Patients meeting class one recommendations had a significantly higher incidence of composite endpoint than those meeting class 2A recommendations. Left ventricular ejection fraction greater than 35% with greater than 5.7% late gadolinium enhancement and cardiovascular negative residence imaging was as sensitive as or significantly more specific than left trigger ejection frack greater than 35% with any late gadolinium enhancement. Patients meeting two class 2A recommendations left ventricular ejection fraction greater than 35% would need for a pacemaker, and left ventricle rejection at greater than 35% with late gadolinium enhancement. Greater than 5.7% had high annualized event rates. Excluding two class 2A recommendations, left ventricular ejection fraction greater than 35% with syncope, and left ventricular ejection fraction greater than 35% with inducible ventricular [inaudible] resulted in improved discrimination for the composite endpoint.                                 In our next paper, Kenji Okubo, Antonio Frontera, and associates examined the ability of a new grid mapping catheter for performing substrate and ventricular tachycardia activation mapping during ventricular tachycardia ablation procedures, identifying the low voltage areas and visualizing diastolic pathways. The authors studied 41 consecutive patients undergoing ventricular tachycardia ablation procedure. The grid mapping catheter was used to create three different maps with three bipolar configurations along the spine, across the spine, high density wave solution.                                 The median low voltage area drawn by the high-density wave configuration was 28.9 centimeters squared, but it was 13% and 15% smaller with a low voltage area identified by along and across. The late potential areas identified by the three configurations did not differ. Ventricular tachycardia activation mapping visualizes the full diastolic pathway in 22 out of 40, or 55%. The authors found that identifying the full diastolic pathway led to a higher ongoing VT termination rate during the ablation than in the case of partial recordings, 88% versus 45%, P equals 0.03. In addition, when the full diastolic pathway's identified, the targeted VTS were always non-inducible.                                 In our next paper, Masateru Takigawa, and associates examined whether the spacing orientation, the bipoles of high-density mapping catheters impacts the accuracy of scar detection. The authors analyze the electrograms using high-density HD grid catheter and determine the optimal cutoff for scar detection in six infarcted sheep. For using bipolar voltages to detect MRI defined scar, the area under the receiver operating curve dependent on the spacing and orientation of the bipoles and range from 0.89 to 0.923. The area under the receiver operating curve was significantly larger, P less than 0.01, when only the best points on each site were selected for analysis compared to when all points were used.                                 In our next paper, Darren Tsang and associates examine the impact of prior sternotomy on transvenous lead extraction outcomes. Of 1,480 patients, 455 had prior sternotomy. When compared to patient with no prior sternotomy, those with prior tsunami were more likely to be older, male, and present with more comorbidities and leads targeted for extraction. No statistical difference was identified in major and minor complication rates, clinical success rates, or in hospital mortality.                                 In patients with prior sternotomy, there were no instances of pericardial effusion following extraction. Patients with sternotomies prior to lead extraction experienced vascular cardiac perforation, presented clinically with hemothoraces rather than pericardial effusions.                                 In our next paper, Babak Nazer and associates highlight the electrophysiologic properties in sites of ablation for manifest nodofascicular and nodoventricular accessory pathways that connect the atrial ventricular node and the Purkinje system or ventricular myocardium respectively. Concealed nodoventricular and nodofascicular pathways participate as the retrograde limb of supraventricular tachycardia. Manifest nodofascicular and nodoventricular accessory pathways comprise the antegrade limb of wide complex supraventricular tachycardia but are quite rare.                                 The authors report on eight patients who underwent electrophysiologic studies for wide complex tachycardia three, narrow complex tachycardia one, and for pre-excitation in four patients. The authors found nodofascicular and nodoventricular accessory pathways were an integral part of the supraventricular tachycardia in three patients. In these three cases, cases one and two revealed wide complex tachycardia due to manifest supraventricular tachycardia. Case three with a bi-directional nodofascicular and nodoventricular accessory pathway that conducted retrograde during supraventricular tachycardia, and antegrade causing pre-excitation during atrial pacing.                                 The nodofascicular or nodoventricular accessory pathway with a bystander during AV nodal reentry and tachycardia, atrial fibrillation, atrial flutter, and orthodromic AV reentrant tachycardia in four cases, and caused only pre-excitation in one. Successful accessory pathway ablation was achieved empirically in the slow pathway region in one case. In five cases, the ventricular insertion was mapped to the slow pathway region in two cases, or septal right ventricle in three cases. The accessory pathway was not mapped in cases five and seven due to its bystander role. The QRS morphology of pre-excitation predicted the right ventricular insertion sites in four to five cases in which it was mapped. During follow-up, one patient noted recurrent palpitations but no documented supraventricular tachycardia. The authors recommend that ablation should initially target the slow pathway region with mapping of the right ventricular insertion site if slow pathway ablation is not successful, and that the QRS morphology of maximal pre-excitation may be used to predict the successful right ventricular ablation site.                                 In our next paper, Constanze Schmidt and associates sought to determine if gene therapy targeting TASK-1 atrial specific potassium channel gene would suppress atrial fibrillation and correct cellular electrophysiological modeling in a porcine model of atrial fibrillation. The authors induced atrial fibrillation in pigs using atrial burst stimulation via implanted pacemakers and injected into both atria adeno-associated viral vectors carrying anti TASK-1 SIRNA for gene transfer to suppress TASK-1 channel expression.                                 After 14 days, porcine cardiomyocytes were isolated from the right and left atrium. The authors found that anti TASK-1 adeno-associated viral vector application significantly reduced atrial fibrillation burden in comparison to pigs. Arrhythmic effects of anti TASK-1 SIRNA were associated with reduction of TASK-1 currents and prolongation of action potential durations in cardiomyocytes to sinus rhythm values. The authors concluded that suppression of atrial fibrillation through selective reduction of TASK-1 currents may represent a new option for anti-arrhythmic therapy.                                 We have two excellent research letters this month. Jordana Kron and associates reported the presence of Inflammasome within the granulomas in hearts of three cardiac sarcoidosis patients. Providing additional support for the role of IL-1 in the pathogenesis of cardiac sarcoidosis and raising the possibility of ion targeted therapies to treat cardiac sarcoidosis.                                 Walid Barake and associates examine 549 patients with left bundle branch block, left ventricular ejection fraction greater than 50% at baseline, and a follow-up echocardiogram. Of these, 134, 24.4% had a greater than 10% drop in left ventricular ejection fraction. The patients with possible left bundle branch block induced cardiomyopathy were more likely to be younger and male.                                 That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time.                                 This program is copyright American Heart Association 2019.  

Why do you think many of these “subgroup” projects are a headache for statisticians? Have you felt frustrations about such projects yourself? What are the steps to avoid or at least minimize these frustrations? Do you have the same questions in mind? These are some of the questions Necdet will be and sharing with us. This episode is based on a presentation at PSI 2019. Necdet won The Effective Statistician Best Presenter award for the amazing delivery of the presentation. But not only the delivery was excellent - the content will help you a lot.

One of the most common questions I got asked during my nearly 2 decades of being a statistician sounds similar to this: “Which patients have the best response to treatment?” I'm sure, we all face this situation sooner or later and not surprisingly lots of research has happened in the last years on this area. In todays episode, we will help you to understand one of the best approaches I have come across to solve this problem in a rigorous yet sophisticated way: the SIDES approach. Both Andy Nicholls and I have applied this approach in the past and we'll use an example, which he presented during a PSI webinar. Listen to this episode to learn step by step how to apply the SIDES method.

Dr Edward Livingston discusses How to Use a Subgroup Analysis with Dr Gordon Guyatt

Author: Aaron Lessen, MD Educational Pearls: Recent meta-analysis reviewed efficacy oseltamivir (Tamiflu) in pediatric populations treated for influenza, showing an 18 hour reduction in duration of illness for those with laboratory confirmed influenza Those with suspected influenza unsurprisingly had less effect Subgroup analysis showed most benefit in those treated within the first 24 hours of symptom onset Patients with confirmed influenza treated with oseltamivir had a 34% reduction in risk of otitis media Editor’s note:  Vomiting was higher in the treatment groups; There were no significantly different outcomes in regards to other endpoints, such as lower respiratory tract infections and hospitalizations References: Malosh RE, Martin ET, Heikkinen T, Brooks WA, Whitley RJ, Monto AS. Efficacy and Safety of Oseltamivir in Children: Systematic Review and Individual Patient Data Meta-analysis of Randomized Controlled Trials. Clin Infect Dis. 2018 May 2;66(10):1492-1500. doi: 10.1093/cid/cix1040. PubMed PMID: 29186364. Summarized by Travis Barlock, MS4 | Edited by Erik Verzemnieks, MD

My guest this week is Mark Micire, group lead for the Intelligent Robotics Group at NASA’s Ames Research Center. Previously Mark was a program manager at DARPA, an entrepreneur, and a volunteer firefighter. The topic of this conversation is how DARPA works and why it’s effective at generating game-changing technologies, the Intelligent Robotics Group at NASA, and developing Robotics and technology in high-stakes scenarios. Links Intelligent Robotics Group DARPA Camp Fire DARPA Defense Sciences Office First DARPA Grand Challenge Footage - looks like a blooper reel FEMA Robotics   Transcript Ben: [00:00:00] [00:00:00] Mark, welcome to the show.  I actually want to start let's start by talking about the campfire. [00:00:04]Camp Fire [00:00:04] So we have a unprecedented campfire going on right now. It's basically being fought primarily with people. I know you have a lot of experience dealing with natural disasters and Robotics for emergency situations. So I guess the big question is why don't we have more robots fighting the campfire right now? [00:00:26] Mark: [00:00:26] Well, so the believe it or not. There are a lot of efforts happening right now to bring robotics to bear on those kinds of problems. Menlo Park fire especially has one of the nation's leading. Groups, it's a small called kind of like a squad of folks that are actually on Menlo Park fire trained in their absolute career firefighters who are now learning how to leverage in their case. [00:00:57] They're [00:01:00] using a lot of uavs to to do Arrow aerial reconnaissance. It's been used on multiple disasters the we had the damn breakage up in almost the same area as campfire. And they were using the the uavs to do reconnaissance for for those kind of things. So so the the ability for fire rescue to begin adopting these two new technologies is always slow the inroads that I have seen in the last say five years is that they like that it has cameras. [00:01:32] They like that it can get overhead and can give them a view they wouldn't have been able to see otherwise the fact that now you can get these uavs. That have thermal imaging cameras is frighteningly useful, especially for structure fires. So that's so that's the baby steps that we've taken where we haven't gone yet that I'm hopeful we'll eventually see is the idea that you actually have some of [00:02:00] these robots deploying suppressant. [00:02:01] So the idea that they are helping to, you know, provide water and to help put out the fire that that's a long leap from where we are right now, but I would absolutely see that being within the realm of the possible. Sybil about gosh now friend 2008. So about 10 years ago NASA was leveraging a predator be that it had with some with some. [00:02:27] Imagery technology that was up underneath it. Um to help with the fire that was down in Big Sur and I helped with with that a little bit while I was back then I was just an intern here at Nasa and that's I think a really really good example of us using of the fire service leveraging larger government facilities and capabilities to use Robotics and usually these and other things in a way that the fire service itself frankly doesn't have the budget or R&D [00:03:00] resources to really do on their own. [00:03:00]Ben: [00:03:00] [00:03:00]So you think it's primarily a resources thing [00:00:00] Mark: [00:00:00] t it's a couple factors there's resources. So, you know outside of I'll say really outside of DHS. So the problem that homeland security has a science and technology division that does some technology development outside of that. There's not a whole lot of organizations outside of commercial entities that are doing R&D a for fire rescue the it just doesn't exist. [00:00:28] So that's so that's that's your first problem. The second problem is culturally the fire service is just very slow to adopt new technology. And that's not it. It's one part. You know, well, my daddy didn't need it in my daddy's daddy didn't need it. So why the heck do I need it right at that? [00:00:49] That's it's easy to blame it on that. What I guess I've learned over [00:04:00] time and after working within the fire service is that everything is life-critical? There's very few things that you're doing when you're in the field providing that service in this case Wildfire response where lives don't. Kind of hang in the balance. [00:01:09] And so the technologies that you bring to bear have to be proven because what you don't want to do is bring half-baked ideas or half-baked Technologies and frankly have your normal operations have have that technology in a fail in a way that your normal operations would have provided the right kind of service to protect those lives God. [00:01:33] So the evaluation and also kind of the acceptance criteria. For technology is much much higher in especially the fire service. Then the many other domains that I've worked in. I can only think of a few other ones and you know, like aircraft safety and automobile safety tend to be the same where [00:05:00] they're just very slow to roll in Technologies and other things like that, but those two areas that I just described have government and other groups that are providing R&D budgets to help push that technology forward. [00:02:06] So when you get the. You get the the combination of we don't have a lot of budget for R&D and we're very slow to accept new technology because we have to be risk adverse that those two tend to just make that domain of very slow-moving Target for new technologies. [00:02:21]Enabling Innovations in Risk Averse Domains [00:02:21] [00:02:21]Ben: [00:02:21] that actually strikes me as very similar to to NASA. [00:00:03] Actually. We're , there's always the the saying that you know, you can't fly it until you've flown it and do you see any ways for. Making Innovations happen faster in these risk-averse domains you have any thoughts about that? [00:00:16]Mark: [00:00:16] It's it's tough. I mean so short short answer is I don't know. I've been trying for the last 15 years and [00:06:00] I'm still still swinging at it the. [00:00:29] The trick is just to keep going and ultimately I think it just comes down to exposure and the folks the the decision makers within the respective Fields just being comfortable with the technology. So as we now have automobiles that are sharing the highways with us that are controlling themselves and I'm not even talking like fully autonomous, you know, driverless Vehicles, you know, the fact that we have, you know, Tesla's and other high-end cars. [00:00:59] They have Auto Pilots that are Auto steering and Lane keeping and stuff like that the ability for folks within the fire rescue domain to start becoming comfortable with the idea that machines can make decisions that are in life. Critical scenarios and if they can make the right decision on a regular basis, it sounds weird to say that something completely removed from the fire service may help improve the ability for fire service to adopt those [00:07:00] Technologies. [00:01:27] It seems weird to think that that's the case. It's absolutely the case and I you know, like I've been doing this for longer than well. I guess 10 or 15 years now as much as I hate to admit that and I've seen a dramatic change in that now I can go into a room and I can talk about. Averaging and unmanned air vehicle and I'm not laughed out of the room. [00:01:48] There's a comfortableness now that I see these domains accepting that they wouldn't before so, you know, hopefully we're making inroads. It's not going to be a fast path by any stretch. Yeah culturation is something that I don't think people think about very much when it comes to technology, but that's a really good point. [00:02:09] I have geek we don't and that's that's unfortunate. And the one thing I've learned over time. That as Geeks we have to realize that sometimes the technology isn't first that there's a lot of other factors that play in. [00:02:20]Mark's Mission [00:02:20] [00:02:20] Ben: [00:02:20] Yeah, absolutely.  something that I want people to hear about is I feel like you're one of the most [00:08:00] mission-driven people that I know and not to put you on the spot too much but could you tell folks what you do? [00:00:07] Like why you do what you do? [00:00:11] Mark: [00:00:11] Um well and it really depends. I'll say in yeah, you can appreciate this a depends on what it is. I'm doing so, you know for my day job. I work at Nasa have always been a space geek and an advocate for humans finding ways of working in space and one of the best ways that I have found that at least for my talents that I can help enable that is to leverage machines to do a lot of the precursor. [00:00:42] Work that allows us to put humans in those places. It turns out strangely enough of it a lot of the talents that I use for my day job here also help with work that I do on the side related to my role as search and rescue Personnel in FEMA [00:09:00] that a lot of the life safety critical things that we have to do to keep humans alive in the vacuum of space also apply to. [00:01:11] Women's Safe and finding humans at and around and after disasters and so I've always had this strange kind of bent for trying to find a technology that not only ties to a mission but then you can very clearly kind of Point your finger at that and say well that's that's really going to help someone stay safer or do their job more effectively if they had that piece of equipment. [00:01:39] Those are fun, you know. An engineering standpoint. Those are the kind of Base requirements that you want and and it always helps with there's a lot of other technology areas that I could have played in and I like the fact that when I'm when I'm making a design decision or an engineering trade that I can look at it and really grounded out [00:10:00] into okay. [00:02:02] Is that going to make that person safer? Is that going to make them do their job better? And it's really motivating to be able to. To have those as kind of your level one requirements as you as you try to design things that make the world better. [00:02:14] Intro to IRG [00:02:14] [00:02:14]Ben: [00:02:14] and So currently you're the head of IRG. [00:00:05] Yeah group lead is the official title. So I'm the group leader of the intelligent robotics group. Yeah, and I bet that many people haven't actually heard of the intelligent robotics for group at Ames which is kind of sad, but could you tell us a publicly shareable story that really captures IRG as an organization? [00:00:22]Mark: [00:00:22] [00:00:22] Serve, yeah, well, I would say that it is it is a an interesting Motley Crew of capabilities that that allow robots to go do things and all kinds of different domains. We have folks within our group. That specialize in ground robotic. So we have [00:11:00] Rovers that have quite literally gone to the ends of the Earth and that we've had them up in the northern Arctic. [00:00:49] We've had them in desert in Chile. We they've roamed around just about every crater or interesting Landmark that we have in California here and long story short. We have folks that not only work with and make ground robotics smart, but then. Of them and one of the things I adore about the team is that they're all filled capable. [00:01:13] So we all subscribe to the philosophy that if we're not taking this equipment out in the field and breaking it. We're probably not learning the right things. And so none of our robots are garage queens and stay inside inside of the lab that we love like to take our stuff outside and take them out into these domains where they're really really tested. [00:01:34] We have a group here. Subgroup within RG that's working on Technologies for the International Space [00:12:00] Station. So we have a free flyer and have worked with many of the free Flyers that are up on the International Space Station. Now, there's a new one that we are building. That should fly very soon here called Astro B, which is all you can think of it as in astronauts assistant. [00:02:01] So it's able to not only do things on its own but hopefully will be helpful to astronauts and also allow ground controllers to to have a virtual presence on the International Space Station in the way that they the way they haven't been able to. Let's see. We're turns out that when you're working with robots like this having very good maps and representations of the world's that you are exploring becomes important. [00:02:27] And so we have a sub grouped here.  That works with planetary mapping. So in the best, I guess most digestible way of describing that is that if you've ever opened up [00:13:00] Google Google Earth and kicked it into Google moon or Google Mars mode. That most of the especially the base in Ministry imagery and other products that are in that in that Google Earth We're actually generated by my group. [00:03:00] And so it turns out that when you get these pictures and imagery from satellites, they're not always right and they need a lot of kind of carrying and coercing to make them actually look correct. And so my group has a suite of software. Where that's all publicly available the that can be used to make that imagery more correct and more digestible by things like Google Earth and other systems like that and then you know in general we at any given time have, you know, north of 30 to 40 researchers that are here. [00:03:38] Doing all kinds of work that is relevant to robotics relative [00:14:00] relevant to space and yeah, and it's an awesome group and every single one of them is motivated and exactly the right kind of ways. [00:03:52]Organizational Nitty-Gritties: IRG [00:03:52] [00:03:52] Ben: [00:03:52] Yeah. I mean having having worked there I completely agree with that statement from personal experience. [00:03:58] And actually related to to the motivations something that I really like doing is digging into the nitty gritties of organizations that really generate Innovations. So so look what tell me about the incentives that are  at play in IRG like what really what motivates people like, how are people sort of rewarded for success and failure and how do those pieces work? [00:00:12] Mark: [00:00:12] Well, I and. I'm going to say this and it's going to sound super simple. But the IRG is one of the few places and it's one of the reasons why I wanted to when I was given the opportunity to be the group lead that I took it is I still feel like I RG is like one of the last one of the few places. [00:15:00] I guess I'll say where the research can kind of be up front. [00:00:34] We're creativity can be king and we can kind of focus on doing the good work in a way that I'll just say that is a little bit more difficult when you're out. A commercial world because you know chasing the next product sometimes has a whole bunch of things that come along with it. You know, what is the market doing what you know our is this going to be supported by Senior Management other things like that that we that we don't have to deal with that as much it has to align with NASA's Mission. [00:01:06] It has to align with what the focus is our of the agency, but I will. That because we have such good researchers here our ability to create a proposal. So we end up just like everyone else writing proposals to to NASA itself and winning those proposals that they that they were kind of ization is actually in the [00:16:00] fact that these researchers get to do the research that they're wanting to do and all the research that's being handed down to them by, you know, a marketing team or some corporate exec. [00:01:40] The other thing that is huge here and I know. Probably experienced it during your tenure when I say the folks are here for the right reasons. We all know every single person within IRG and I'll say that within especially NASA Ames out here in Silicon Valley every single one of us could go a thousand yards outside of the fence and be making two to three times what we make working for the government. [00:02:08] And that's not it's not so much a point of Pride. But what it does is it just helps relieve the the idea that folks are are are here for the money you're here for the research and you here for the science. I use the best analogy I make quite often is I used to. [00:17:00] I used to teach as an Adjunct professor at a community college doing and this is more than this is about 15 years ago in the courses were on like PC repair and other things it was this certification called A Plus and the I used to confound the other professors because I used to always take they had one section that they would do and it was 8 a.m. [00:02:52] On Saturday morning. It was like a it was like an 8 a.m. To 1 p.m. And it was just one day a week and I used to always take that one and the other professors were like, why are you taking an 8 a.m. Saturday course and I would smile at them and say. Because every single student it's in there. I know they want to be there. [00:03:14] I know that they are motivated and want to be there because no one in their right mind is other than a motivated student is going to get up at 8 a.m. On a Saturday morning to go learn about PC repair and to add in to everyone's surprise, but not my surprise. I had a [00:18:00] 100 percent pass rate on that test because it was independently tested outside out of out of the classroom and I. [00:03:39] So just smile because it was like wow, you must be a great professor and I'm like, no, I've got great students because they all are motivated to be there. So that's effectively what I have here within NASA sitting inside of you know, this Silicon Valley bubble is I have a whole bunch of frightening Lee smart people that are motivated to do good science and have absolute have financial reasons to go elsewhere and decided for themselves. [00:04:07] This is where they'd rather work. Yeah and do so the in terms of the majority. Let's break that down a little bit the way that projects happen is that you do a proposal to like, who do you propose projects to I guess [00:19:00] is the the correct question. Well the the fun part and this is one of the the freedoms and NASA has. [00:04:36] Can really propose to anybody we have projects here that our commercial so we work with like for instance. We're doing work with Nissan on autonomous vehicles. And and if actually done some really really interesting work there, you know related to visualization and other things like that which which borrows a lot from work that we do with the Rovers so so we can work with companies. [00:05:03] We work with Within. First so NASA itself. One of the ways that NASA works is that because we have multiple centers, you know, NASA Ames for instance in our group will propose to NASA headquarters. So we just pitched a couple of months ago we pitch to a program that was doing satellite-based Technologies and I flew to NASA headquarters in DC and we [00:20:00] pitched it to a much like you would do to a VC or any. [00:05:35] No any funding source, if you were a company doing it in the valley and you pitch it and we and we want it. We also work with other government agencies. So we have done work for DARPA. We've done work with the Marine Corps. It turns out that the dod Department of Defense is interested in a lot of the ways that we have worked with autonomous vehicles as the Department of Defense tries to figure out how they want to work with autonomous vehicles. [00:06:05] So it's easy for us to open a conversation with Department of Defense and say hey, here's what we did for our Rovers our uavs or whatever and this may be something that you know, you may want to consider and a lot of times they'll come back and say well look we not only want to consider that but we'd also like to go ahead and kind of put you on proverbial payroll here and how do you either do the work for us or help us [00:21:00] understand? [00:06:30] You know, what are the important parts of this we can work with Academia? And so we will often have projects where we partner with a university and we will go in and do a joint proposal either to NASA or all of the different funding sources that that are out there. And so NASA. Has a lot of flexibility in a way that you know myself having previously worked in the Department of Defense. [00:06:58] NASA can do something unique and that NASA can be a consult or NASA can do work for a private company. We have a thing called a space act agreement and like the Nissan workout was talking about there. It seems odd that that a government organization would be able to receive a paycheck if you will. [00:07:18] Yeah from a private Corporation. And it turns out that NASA has a very unique way of doing that and we leverage that frankly as often as we can. [00:22:00] So I realized that's probably a really long answer to a simple question and that's to say we can take money from just about anybody as long as it is legal and it benefits NASA in some way. [00:07:41] Those are the only two real catches that we have. We You Know It ultimately has to benefit and NASA's Mission as. You know being Shepherds of taxpayer dollars, but as long as we can justify that we can work with a lot of different funding sources. [00:07:58]Aligning with NASA's Mission [00:07:58] [00:07:58] Ben: [00:07:58] And what is NASA's mission right now? Like how do you know whether something is within the purview of NASA's Mission or not? [00:08:08] Mark: [00:08:08] Well, I NASA takes its guidance from from a lot of different places. I mean, we you know, there's the two A's. NASA, you know with respect to you know Aeronautics. I'm sorry, the what we have Aeronautics and we have space right and those are the two kind of built into the name, you know missions that are in there. [00:08:29] We [00:23:00] also you know, the we take direction from NASA headquarters. And they are putting out, you know, we have the science side, especially for space which is really driven a lot by the Decay deal surveys and other kind of Direction with respect to where we want to see and it sounds kind of funny to say but it's like where we want to see mankind go in terms of, you know, space exploration and other things like that, but we also have Earth Sciences, you know, some of the kind of flipping back to to the the. [00:09:02] It's up in Northern California some of the some of the best especially satellite imagery that is coming through there's actually being processed through NASA's Earth Sciences missions. And so, you know, there's a worldview and a bunch of other tools that are out there that as as the Earth Sciences. [00:09:24] With all of the different things that are affecting especially, you know, the climate and everything else. It turns out that [00:24:00] NASA's mission is also to benefit that and to help with Earth observations in a way that ultimately helps us understand how we might be impacting other worlds when were able to achieve going there [00:09:42] [00:09:42]NASA-> DARPA [00:09:42] [00:09:42] Ben: [00:09:42] Got it. I'm going to transition a little bit  from your time at Nasa to then your time at DARPA. And what I wanted to know is like what were some of the biggest shocks transitioning from NASA to DARPA and then now back from DARPA to NASA because they're both government agencies, but they feel like they have very different fields at least from the outside. [00:00:20] Mark: [00:00:20] Yeah. Um, gosh, that's there's especially from NASA to DARPA.  It was I guess the biggest things that come to mind one as a program manager. It is frightening Lee empowering to go to an organization where you know [00:25:00] where you're at Nasa here. We you know with Ed My Level and with the group kind of scenario that I just described to you. [00:00:51] We're in the trenches right? We're trying to do the science. We're doing the research and we're we're trying to make a kind of an impact at a kind of a ground level right when you go in as a program manager at DARPA your your. Trying to change a field. So you have your basically being given the power to say within this field within this field of let's say autonomous vehicles. [00:01:19] I see the following Gap and in stating that and in creating kind of the the request for proposals and other things that you do that bring researchers to darpa's door you're saying. You're not saying I'm going to go do this technology technological thing you're saying I think everyone needs to focus on this part of the [00:26:00] technology landscape. [00:01:44] That's a that's a different conversation at a very different level and it was startling to be frankly one of those program managers where you say. Hey, I don't think the field is doing this right and then to have an entire field turn to you and say oh, okay. Well then let's. From the thing that you want that you're suggesting that that's that isn't interesting and kind of empowering position to be in. [00:02:11] but has a NASA does too but DARPA specifically especially with Department of Defense type technologies that eventually roll out into civilian use your ability to just speak at such a different level and at a level that is. Accepting of risk in a way that NASA does not do that for DARPA. You almost have to have if it's not ready [00:27:00] yet. [00:02:43] If it's not risky enough that you can have a program not basically make the cut DARPA because it didn't have enough custo. It didn't have they call it and dark within DARPA. They called The Laugh ability test and that if your if your idea isn't just crazy enough that it's almost laughable. Then then then it didn't it didn't it's going to have to work a lot harder to get there. [00:03:07] And so I'd say the probably I guess in conclusion the risk and just the empowerment to move an entire field than a different Vector that that would probably be the biggest difference as I had between between my NASA world and then going over and being able to Moonlight as a program manager [00:03:26]Fields Impacted by DARPA [00:03:26] [00:00:00] Mark: [00:00:00] and what are some fields that you. All like DARPA has really moved that concept is incredible and makes sense. And I it hasn't been expressed. So concisely before  I'd love some [00:28:00] examples of that. [00:00:02] Mark: [00:00:02] What are the best and I think the most recent example that we can now see the impact for is is autonomous vehicles. [00:00:12] I mean you have to remember the that that now is over a decade ago that the original that the first DARPA Grand Challenge happened and what you know, I was reflecting on this while I was being chased down by a Tesla on the way into work this morning that clearly was autonomously driving itself. And I remembered that in most people forget that the first arpa Grand Challenge. [00:00:38] First of all was millions and millions of dollars in investment and no one won. Yeah one got to the finish line. And in thinking about risk and thinking about risk acceptance what I think that's one of the best data or a really good data point of darpa's not only saying this is really hard. We're going to call it a Grand Challenge and we're going to have these [00:29:00] vehicles basically racing across the desert that if that wasn't gutsy enough from a risk standpoint, but they also then failed and then did it again and said, you know what week we literally had. [00:01:16] Humvee flipped over on fire on in the desert and that was on the evening news for everyone to enjoy to the embarrassment of DARPA and the dod and everybody else and then they said you know, what? No, we're going to double down. This is really worth it. And we need to make this happen and the the impact for that is huge because that then became, you know kind of the ground floor. [00:01:46] Of the vehicles that we now have running around especially out here and you know in the Bay Area you got fully autonomous vehicles now that are able to navigate their way through, you know through all of the different difficulties in the complex situations [00:30:00] that can be presented. The folks that were that Noble Sebastian threatened and his Stanford team that won the the the Grand Challenge that those people went on to to work for you know, what was the Google autonomous car which eventually became way Mo and all of the different companies and talented is sprung out of all of that. [00:02:25] That was all born over a decade ago by an organization that is using your taxpayer dollars to do. Risky things and to say for this it's for this autonomy thing. We really think that vehicles are where the money needs to be spent and spent in a real way that that takes guts and it's still in my mind one of the only organizations that really able to kind of make an impact like that until that entire field. [00:02:53] Hey, I don't think you're doing this right and here's what I want you to do and I'm going to put money behind those words and we're going to go change the world and a [00:31:00] decade later. We've got autonomous vehicles quite literally beside you on the highway. That's pretty awesome. [00:03:07]Levels of Risk DARPA Shoots For [00:03:07] [00:03:07] Ben: [00:03:07] That is incredibly awesome. [00:03:09] Do you have a sense of what the level of risk that you're shooting for is I'm thinking just sort of. Like what is the the acceptable or even desired failure rate or is there a sense of how many fields per decade you're shooting for? Right because you think about it and even if it's changing one field per decade. [00:03:42] The amount of change that comes out of something like autonomous cars or even  the human computer interaction that came out came from the 60s might even make the whole thing worth it. So do does anybody even  think about it in terms of numbers at all? [00:32:00] [00:00:03] Mark: [00:00:03] So I never heard it framed that way the thing that the Mantra that was always drilled into US was that that it was that the way that you kept score was by the number of Transitions and how how DARPA and I guess that's more of a general DOD term. [00:00:25] That's to say for something you create how many times did. Someone take that technology and go use it for something and so, you know, we would count a transition as you know, well, you know Army decided to take our autonomous vehicle and use it for this but we also got contacted by Bosh and they are interested in leveraging that thing that we built with this new sensor that they're commercially making available and we provided the missing link that now allows them to use that safely. [00:00:59] Vehicles and so you kind of keep score internally on [00:33:00] that basis. The other thing though that darpa's doing is you got multiple horses in the race. So DARPA is organized into multiple floors that have different specializations. So they have like and just a couple examples. I have like the biological technology office and the micro technology office and each one of those. [00:01:29] Floors has a specialization in so the idea that you're bringing in these program managers, you're empowering them to go change their respective fields. And then you're doing that across multiple broad domains like biology and micro technology and other things like that. That's pretty that's pretty and that's awesome in a way that it provides overlap because when I was for instance where I work, What's called DSL which is the defense Sciences office, which is to say it works on [00:34:00] kind of first principle science and physics and Mathematics and other things like that the fact that you can as somebody who's working that go talk to somebody who was fundamental in the development of mems technology, which is what MTO the micro technology office. [00:02:21] That's what they work. And then you want to see how let's say that new chip that is leveraging mems technology might. By law might be able to parallel or be inspired by biology and go get one of the experts from the biotechnology office to you know to scrimmage on some new idea that you're having or whatever that that's that's awesome. [00:02:44] And what that does is that just ends up being kind of this this this multiplier this Catalyst for innovations that are then, you know, you've got multiple domains that are all kind of being affected in the same kind of positive feedback loop. So I would say that's the biggest thing to directly to your question that I don't ever remember anybody saying, okay. [00:03:03] We're not [00:35:00] hitting quote. We need you know, we need another six domain changing ideas organize, you know not have satisfied or obligation of Congress. I don't ever remember any kind of conversations like that. [00:03:16]Organizational Nitty Gritties: DARPA [00:03:16] [00:03:16]Ben: [00:03:16] Yeah that description of the like cross-disciplinary interactions is shockingly similar to some descriptions that I've heard of bell labs and it's the parallels that are really interesting. [00:03:32] And I want to dig into sort of the organizational nitty-gritties of DARPA as well. So all of the the program managers who are the sort of the the drivers of DARPA, you're all  basically temporary employees. And so how did the incentives their work? what are your goals as. Program manager and what drives people, what incentivizes them to do their work? [00:00:04]Mark: [00:00:04] [00:36:00] Well, so you're right you're there. So as a DARPA program manager you therefore it's. Typically to two-year renewable contracts. So you you go in you have basically two years at which point you're evaluated as to how well your programs are doing and then you may be renewed for typically another two years. [00:00:26] Most program managers are there for about three years and that that's kind of the the center of the bell curve is three years the motivation simple and that you're you're being. Given one of the largest.  within certainly within DOD. If not within just the overall research community and DARPA has a bit of a Swagger. [00:00:51] It has a bit of a like a brand recognition that when DARPA says that we are going to now going to focus on this particular type of sensor this particular type of technology that you as [00:37:00] a program manager. You have the ability to go talk to the best of the best the the the folks that are. Either changing or moving or working in those those respective technology bases that you can drop somebody an email and the fact that it's you at DARPA dot mil that that will probably get you a response that you might not have been able to get otherwise. [00:01:28] And so so that's you know, that's I would say one of the biggest kind of motivators that are incoming program manager has as they're going in and then the the other big motivator there is you're not you're there for a limited amount of time. So for years may sound like a lot of time it's not it's really is not because you it takes about to go from like idea on the back of a napkin. [00:01:57] To you know to kick off of a program it takes about a year. [00:38:00] There's a for as much as it looks like it's loose and free and a little crazy in terms of the ideas and stuff like that. It turns out that there's a pretty regimented all jokingly call it a hazing ritual that's on the backside that involves multiple pitches. [00:02:21] There's a level of. Programmatic oversight called a tech Council that you have to go present to that is extremely critical of whatever it is. It is that you're you're presenting and I'll admit it some of the toughest pitches and certainly the toughest like presentations that I ever prepared for. My first tech Council was way more difficult than anything I ever did like for my PhD dissertation or anything. [00:02:52] Like that and so yeah, and so, you know once the so if if you're on a let's say a three year time scale and it takes you a year to get a [00:39:00] program up and running you have got enough time to maybe make two or three dents in the universe, which is what you're hoping to probably do when you go in the door. [00:03:16] And then the other thing that could happen is as program managers are cycling out. So, you know you everybody's on kind of disorder. Even in their out after three years the other program managers have to then inherit the programs that are run up and running that some previous program manager, you know may have pitched in awarded but is now headed off to you know, make you know, buku bucks and industry or whatever and so it's another disc I'll say distraction that you have because program managers sometimes naively myself included go in thinking. [00:03:47] Okay. Well, I'm just going to go in and. Ditch my own ideas, and I don't even know what this inheriting other programs thing is but I'm going to try to avoid that as much as possible and now you've got three or four or five different programs that you're running and hopefully what you've done is you've built a good [00:40:00] staff because you're able to assemble your own staff and you can kind of keep keep the ball running but that's kind of a that's the cycle if I can give you kind of a you know, the the the day in the life kind of you is that you're going to go in. [00:04:19] You're going to be pitching and coming up with new ideas and trying to get them through Tech Council. Once they get through Tech Council, then you've got a program up and running in as soon as that programs up and running then you've got to be looking toward the next program while your staff. You know the ball rolling on your other on your other programs, then you rinse and repeat at least three or four times [00:04:43]What does success or failure look like at DARPA [00:04:43] [00:00:00] Ben: [00:00:00] and what does the end of a program look like either success failure or question? [00:00:11] Mark: [00:00:11] Um, it depends on the program and it depends on the objectives of the program, I guess, you know, the grand challenges always end with [00:41:00] a huge Fanfare and robots presumably in a running through Finish Lines and other things like that. There's other programs that end much much more quietly. We're a technology may have been built that is just dramatic. [00:00:37] We enabling and and the final tests occur and a lot of times DARPA may or may not have an immediate use for the technology. Are that the reasons for the Technology Building being built.  Innocence the program started and so you may see the companies basically take that technology back and continuing improving on it or incorporating it into their products and you know, and that's a very kind of quiet. [00:01:07] Quiet closure to what was a really really good runner really really good program and then presumably you would see that technology pop up and you know in the consumer world or in the, you [00:42:00] know our kind of our real world, you know in the next four to five years or so, and so there's a it's the full spectrum as you would probably imagine that that some of the program's some of them fail loudly some of them fail quietly. [00:01:35] And the successes are the same some of the successes are with great Fanfare and then other times and I'll say some of the most enabling Technologies are out there sometimes close their their time and their tenure at DARPA very quietly. And then some years later go on to do great things for the public. [00:01:53]How DARPA Innovations get into the world [00:01:53] [00:01:53] Ben: [00:01:53] That's something that I hadn't thought about so the sort of expectation of the model of how the the technology then gets. Into the world is just that the people who are working on it as part of the program are then the ones to go and take the ball and run with it. Is that accurate? [00:02:18] Mark: [00:02:18] Absolutely, and [00:43:00] I'd say that that's a difference so strictly speaking. [00:02:22] No research happens Within darpa's Walls, and I guess that's one of the things that that both Hollywood and the description of DARPA. Sometimes get confused is be. That you know DARPA is this this, you know, presumably the warehouse full of mad scientists and you go inside and everybody's in lab coats and it looks like something out of X-Files and that's not it's not the case at all that DARPA is there to to first, you know catalyzed Technologies for DOD purposes, but. [00:02:59] But those those folks that are working for DOD are also companies that are producing products made many of them are producing products that are very much outside of DOD and so the spillover and the fact that the DARPA can and I'll say relatively quietly create technology that [00:44:00] is that is just it's a catalyst for the greater good or the the greater use of Technology more broadly that that is a it's a wonderful. [00:03:28] Ability that DARPA has that a lot of other labs don't have that ability to do so you take and I'll give you an example. So let's take like either Air Force research Labs or Army research lab or any of the research Labs that are with the particular branches of the military that does have actual researchers much like NASA Ames here. [00:03:49] We have actual researchers that are inside of our four walls that are doing work and we can do work that you know is it can be exclusive to the government? But but in darpa's case because there is no research being done within its four walls that most of the contractors most of the what they would call the performers the folks that are performing the technology development that depending on the mostly depending on the contract and the contracts are usually written such that those companies can take those Technologies and and use them for [00:45:00] whatever they'd like after the the terms of the contract is done [00:04:26]Improving the Process of Getting DARPA Innovations into the world [00:04:26] [00:04:26]Ben: [00:04:26] something that I've always wondered is you try so many things at DARPA and there's there's no good way of sort of knowing all the things that have been tried and what the results were. Is there any there ever any thought. having it better knowledge base of what's been tried who tried it and what the result was because it feels like for  every technology that was developed by a company who then picks it up and runs with it. [00:00:04] Sometimes there's a something that's developed by a lab that. Is full of folks who just wanted to do the research and sort of have no desire to then push it out into the world so is there is there any effort to make that better make that [00:46:00] process better? [00:00:06] Mark: [00:00:06] Yes, and no but this is a bit of a trick question and I'll answer that. [00:00:12] Well, I'll answer the tricky part. First of all, let me ask let me back up. The obvious answer is that DARPA especially within the last five years or so on his been working much harder to be more open with the public about the work that's being done. You can hit darpa's website and. To the 80th percentile of an understanding of the work that's being done within within DARPA did that the balance of the twenty percent is stuff. [00:00:44] That's either classified or is of a nature where you would just need to do a little more digging or talking with the program manager to really understand what's happening. Okay. So that's a straightforward answer the trick. The trick answer here is that it's better sometimes. Have folks go in that don't know their [00:47:00] history. [00:01:05] The don't know why that previous program failed because since that previous program ran technology may have changed. There may be something that's different today that didn't exist 10 years ago. When that was when that program was also tried the there was this interesting effect within DARPA that because your. [00:01:31] Managers out about every three to four years and because I'll say it like this because DARPA didn't in the past had not done a very good job of documenting all of the programs that it had been running that there was a tendency for a program manager to come to the same Epiphany that a equivalent program integer had come up with a decade earlier. [00:01:56] But that doesn't mean that that program shouldn't be funded. Now. There were folks within DARPA that had been there for a long [00:48:00] time. So interestingly enough the caught the support contractors, so we call him sita's which is systems engineering technical assistance, and there are some CDs support staff that has been there for multiple decades. [00:02:20] So they were back at DARPA during the you know, roaring 80s and 90s, which is kind of, you know, some of the the Heyday for some of the more crazy DARPA stuff that was happening that you would have a program manager go and Pitch some idea. Timers in the back start, you know lean one would lean over to the other one in elbow on the you know, and pointed a slide and they both Giggle and then you would ask them later is like hey, what was the what was the weird body language? [00:02:48] He's like, yeah, you know, we tried this back in the 90s and and he didn't work out because Laser Technology was insufficiently precise in terms of its timing or you know, some other technical aspect or whatever, but it's good to see you doing this because I think it [00:49:00] actually has got a fight. [00:03:06] Chance of making it through this time and hearing that and watching that happen multiple times was interesting because we tend to We tend to say oh well if somebody already tried it and I you know, I'm probably not going to try it again. Whereas with DARPA that's built into the model. The the the ignorance is an essay. [00:03:26] It is ignorance. It's not necessarily it's ignorance of the fact that the idea and the Epiphany you just came up with may have been done before. For that is all I want to believe it's by design that then they will allow a program to be funded that may have been very similar to one that was funded earlier. [00:03:48] But because it's under a new it's under a whole new set of capabilities in terms of technology that if you do that intelligently that that's actually a blessing for for folks that are trying to come up with new programs. [00:04:04]The Heilmeier Catechism [00:04:04] [00:04:04] Ben: [00:04:04] The [00:50:00] concept of forgetting things that has been tried feels almost Blasphemous in the the face bright. [00:04:12] It's right. Like that's why I do wonder if there's sort of a middle ground where you say we tried this it failed for these reasons and then whenever someone wants to pick it up again, they can they can know that it's been tried and they have to make the argument of this is why the world is different now. [00:04:31]Mark: [00:04:31] yes. So that is actually part of within DARPA and one of the framings that they use for pitch is this thing called a Heilmeier catechism and and it's basically a framework that one of the previous DARPA directors made that said if you're going to pitch an idea pitch it within this Framing and that kind of helped that will help you kind of codify your argument and make it succinct one of the Lines within the. [00:00:27] Ism is why is this why can this happen now and that addresses that [00:51:00] kind of ignorance that I was talking about before as a program manager when you pitch that thing and you realize that some program manager did it back in 87 and you're all bummed because you're like, oh man, you can't come up with an original idea and these four walls that somebody hasn't done it previously that. [00:00:52] Then then you just after you get over, you know, the being hurt that you know that your idea is already been done. Then you go talk to some of the original contractors you go talk to some of the sita's you talk to the folks that were there and figure out what is different and then and that is part of the catechism that is part of the what is different. [00:01:13] Now that will enable this to work in a way that it didn't work previously. [00:01:18]Best ways to Enable Robotics [00:01:18] [00:01:18] Ben: [00:01:18] Yeah. The catechism is I think a. Our full set of questions that people don't ask enough outside of DARPA and I'll definitely put a link to it in the show notes. So I do know we're coming up on time. So as a final question, I want to ask [00:52:00] you've been involved in robotics in one way or another for quite some time in Academia and in governments and start. [00:01:42] And it's a notoriously tricky fueled in terms of the amount of hype and excitement and possibility versus the reality of robots coming into especially the the unstructured real world that we live in and why do you think of there? There's a better way to do it from sort of all the different systems that you've been a part of like is there an entirely different system. [00:02:10] What would you change to make to make some like more of that happen?   [00:02:16] Mark: [00:02:16] I this and I hate to say like this. I don't know that there's I don't know that there's much I would change. I think that right now especially working in robotics. That is I look at the. The capabilities the [00:53:00] sensors the all of the enabling work that we have right now in terms of machine learning and autonomy and everything else like it. [00:02:41] This is a great day to be alive and working in the field of Robotics in a way that you know, and I'll feel like the old man is I say this but you know, I started this back in the late 90s early 2000s and frankly when I think of the tools and the platforms and sensors that we had to work with. Um that that you spent especially my experience was a grad school grad student experience. [00:03:08] But when I remember how much time we would spend just just screwing around with sensors that didn't work right in platforms that weren't precise in their movements and you know, just all the other aspects that make robotics robotics and I now look at today the fact that you know, we've got kind of. [00:03:30] Bischoff platforms that we can go find that [00:54:00] you can use that that for these lower low-cost platforms. You can really dig deep into research areas that are still just wide open. The fact that now, you know in the mid-2000s if you wanted to do a Thomas car research you needed to be especially or basically. [00:04:03] They don't know how to work high power crazy high power servos and other things like that. Now you go buy a Prius like or Tesla or something, you know what I mean and you're off and the platforms built for you. We you know, the the lidar the computing power and everything else we have today. I might answer your question right now. [00:04:23] I don't know that I would change a thing. I maybe naively believe that we have all of the tools that we need to really really. Make dramatic impacts [00:55:00] and I believe we are making dramatic impacts in the world that we're living by enabling Automation and autonomy to do really really incredible things. [00:04:43] The biggest thing is is for folks to to go back and to kind of along the line of the last line of questioning the you would have had as far as you know, forgetting and remembering the things that we've done in the past. I find that some of the best ideas that I'm seeing that are coming forward into Robotics and autonomy are. [00:05:01] Ideas that were really born back in the 90s.  We just didn't have the computing power or the sensors to pull it off and now we do and so it's almost a go look back and look at you know, kind of create a Renaissance of us going back and looking at some of the really really great ideas. That just didn't have their day. [00:05:23] Back when you know when things were a little more scarce in terms of computing and algorithmic complexity and other things like that that we can now address in a really kind of powerful way that [00:56:00] is quite a note of optimism.  I really appreciate it mark, thank you so much for doing this. I want to let you get on with your day. [00:00:06]  I've learned a ton and I hope other folks have as well. Absolutely. Well, thank you for having me on I appreciate it.  

Biogen/Eisai to present updated subgroup analyses on their Phase 2 study looking at their Alzheimer's medicine, BAN2401. This antibody binds to amyloid beta protofibrils, reducing plaques in the brain. In this video, I go through Biogen's original data and talk about the problems parsing the Apoe E4+ patients. The options market is pricing in a 22 pt move in the stock by Oct 26th.The CTAD 2018 presentation schedule can be found here: https://www.eisai.com/news/2018/news201886.html (Note: I said 24th in the video but it's really the 25th)Other relevant links: https://www.eisai.com/ir/library/presentations/pdf/4523_180726.pdf https://alzres.biomedcentral.com/articles/10.1186/s13195-016-0181-2 https://www.ncbi.nlm.nih.gov/pubmed/29317609 https://www.ncbi.nlm.nih.gov/pubmed/27582220 https://www.ncbi.nlm.nih.gov/pubmed/23828104This is not investment advice Follow me @matthewlepoire www.breakingbiotech.com

Dr. Santiago Garcia and Dr. Srihari Naidu Discuss

Dr Baumert talks to ecancertv at ASCO 2015 about the results of her subgroup analysis of molecular markers of a randomised phase III study in patients with a high risk low-grade glioma. The analysis investigated how primary chemotherapy using temozolomide compares to standard radiotherapy, if it prolongs progression-free and overall survival, and whether prognostic molecular factors could be defined.

Prof Lancet presents at ASH 2016 to discuss CPX-351, a liposomal delivery of cytarabine and daunorubicin, for elderly patients with advanced AML following HSCT.

When treatments don't seem to work for a diagnosis we will often try to see if they work for particular subgroups. Sure, that's a thing, but that is a very difficult thing to determine that demands a very specific process. How have we done with subgroup analysis regarding low back pain? Have JW and Erik found the Ultimate Prime Number?! A systematic review reveals that the credibility of subgroup claims in low back pain trials was low. Saragiotto BT, Maher CG, Moseley AM, Yamato TP, Koes BW, Sun X, Hancock MJ. J Clin Epidemiol. 2016 Jun 10. pii: S0895-4356(16)30174-3. doi: 10.1016/j.jclinepi.2016.06.003. [Epub ahead of print] Due to copyright laws, unless the article is open source we cannot legally post the PDF on the website for the world to download at will. That said, if you are having difficulty obtaining an article, contact us. Music for PT Inquest: "The Science of Selling Yourself Short" by Less Than Jake Used by Permission  

Dr Escudier talks to ecancertv at ASCO GU 2016 about how patients with advanced kidney cancer live for nearly twice as long without their disease progressing if they are treated with cabozantinib, a small molecule tyrosine kinase inhibitor (TKI) that targets c-MET, VEGFR2 and AXL. In the interview he discusses the results of the open-label METEOR trial, which compared the TKI against everolimus, a standard of care in mRCC. The METEOR trial met its primary endpoint of improved progression free survival, and subgroup analyses of the endpoints progression free survival and overall response rate generally favoured cabozantinib over everolimus in patients with advanced RCC.

Audio Commentary by Dr. Valentin Fuster

At Engage for Success, the theme for March has been Wellbeing. During this month, the work of the Wellbeing Subgroup reaches its conclusion with a number of events and activities planned, as well as the finalisation of the evidence report looking at the linkages between wellbeing, engagement and organisational performance.   This month’s final Wellbeing event is with the E4S Guru Group community on 31 March. Tune into this radio show to hear from Julie Fidler and Vanessa King (both members of the Wellbeing Subgroup) who will talk about the Subgroup’s work and findings, and Bob Hughes (Chair of the Guru Group) who will give his take on what has emerged from the Guru’s Wellbeing event that very day. Host: Jo Moffatt  

Special Guest: Wendy Cartwright, Former HR Director of the Olympic Delivery Authority, Task Force Member and Chair of the Wellbeing Subgroup. In August last year, Engage for Success formed a subgroup looking at the links between wellbeing and engagement. A call for evidence was launched with the E4S Guru community and via the E4S website. Since then the Wellbeing subgroup have been busy reviewing the case studies and research papers provided in the call for evidence. In this radio show we hear from Wendy Cartwright, Chair of the Wellbeing Subgroup who discusses the findings so far from the evidence collected and the questions that still remain to be answered. Wendy is a member of the Engage for Success Task Force and she currently chairs the Engage for Success Wellbeing Sub-group, which is examining the links between employee engagement, wellbeing and organisational performance. She is the former HR Director for the Olympic Delivery Authority – the public body responsible for developing and building the new venues and infrastructure for London 2012, and prior to that held senior HR roles in central government, financial services, energy and retail sectors.. Wendy has a Masters degree in Employment Strategy and is a Chartered Fellow of the CIPD. She also chairs the Advisory Board of Global Diversity Practice and is a lead UK member of the European HRD Circle. Host: Jo Dodds

Editor's Audio Summary by Howard Bauchner, MD, Editor in Chief of JAMA, the Journal of the American Medical Association, for the January 22, 2014 issue