Podcasts about sequential

Dr. Deb Muth 0:00 Welcome back to Let’s Talk Wellness Now. I’m your host, Dr. Zab, and we are continuing our discussion this week on 0:08 peptides. And so, if you haven’t heard our first conversation about peptides, 0:13 please go back and look at that episode. We talk all about the manufacturing, the safety, the quality of peptides, and we 0:20 dove into GLP1s. And today we’re going to dive into peptides for sexual 0:26 wellness, immune function, growth hormone, and all the amazing fun things 0:32 we can do with peptides. So, as usual, grab your cup of coffee or tea, settle 0:37 in, and let’s talk wellness now. And we’re going to take a short pause from our sponsor. I know we’ve got to do 0:44 that, you guys. They’re who keep us on the air. So, I’m going to pause for just a minute and be right back after this 0:50 message from our sponsor. Ladies, it’s time to reignite your vitality. Primal 0:56 Queen supplements are clean, powerful formulas made for women like you who want balance, strength, and energy that 1:03 lasts. Get 25% off at primal queen.com. Serenity Health. That’s primalqueen.com. 1:10 Serenity Health. Because every queen deserves to feel in her prime. All 1:15 right, everybody. We are back. And are you ready? We are talking all things peptide and I am opening the show today 1:23 with sexual wellness. Yes, I’m going there, you guys. I am going there. You 1:29 know, this has really become a big issue for people um of all ages. It’s not just 1:3 4us older people. It’s younger people, too. And there’s a whole variety of reasons why we have sexual dysfunction. 1:42 And when we’re talking about sexual dysfunction, we’re not just talking about it doesn’t work, right? Or I can’t 1:48 reach orgasm. A lot of it is around desire and um the thought of it and 1:54 wanting to connect, wanting to be kinder to one another, wanting to be touching 2:00 one another. A lot of it resolves or revolves around that. And so there are some peptides that can help us and I’m 2:08 really excited to be able to talk about those today. So the first one is called PT-141. 2:14 This targets the brain not the periphery. Right? So for many women I 2:20 will always tell you sex starts between here. It is a brain thing for us. It is 2:26 not necessarily a physical thing. For guys that’s a little different. It’s very physical. For women it’s all in our 2:32 brain. So tip for you men that are listening. You have to prime your woman’s brain first if you want her to 2:38 have sex with you that night. You have to be nice to her. You have to bring her flowers. Do the dishes for her. Do 2:45 something kind. Bring her a cup of coffee or tea or a glass of wine. Take her to dinner. You have to woo her. And 2:51 I don’t care how long you’ve been married. That has to happen. And tip number two, don’t say anything stupid 2:57 that day. I’m just being honest. When you guys say things that make us upset, 3:03 that lingers with us for the rest of the day. And it’s it’s a turnoff for us. And 3:08 for a lot of women, we can’t get past that when it comes time to snuggle at night. And sex doesn’t always have to be 3:14 at night either. So, you can tell I really love talking about this conversation, but we’re going to get into the peptide part of it because this 3:21 is going to help people. So, um, PT-141 is marketed as I’m going to slaughter 3:28 this name, Vali, and it represents a fundamentally different approach to 3:34 sexual dysfunction than the PDE5s inhibitors like Slenden, Viagra, 3:40 Tedataphil, which is Seialis. And while the PDE5 inhibitors work specifically by 3:47 enhancing blood flow to the genital tissues, PT-141 works centrally in the brain by 3:54 modulating neural s neural circuits involved in the sexual desire and 4:00 arousal. Now PT-41 is a cyclic hpatipeptide. It’s seven amino acid 4:07 peptide arranged in a cyclic structure that acts as a melanoortin receptor 4:13 agonist and with particularly the infinity for MC3R and MC4R subtypes. 4:20 It’s actually a metabolite of the melanotan 2, a peptide originally 4:26 developed for tanning that was also found to enhance sexual desire in early 4:31 studies. Now the melanoortin system in the brain is involved in multiple functions including energy homeostasis 4:39 but it also is involved in sexual motivation and arousal behaviors. The FDA approved PT-141 in 2019 specifically 4:48 for the treatment of acquired generalized hypoactive sexual desire 4:54 HSDD in permenopausal women. So for the first time we have a medication that was 5:01 approved by the FDA to use for women for sexual dysfunction. We have had all of 5:07 these seialis tedataphil viagros for men but we had nothing for women. And so 5:12 this is amazing that this is available for women and approved by the FDA. It’s a big deal. This represents the first 5:19 and only FDA approved medication specifically targeting these circuits of sexual desire rather than the peripheral 5:27 arousal mechanisms. And this indication is quite specific, meaning it was developed at some point, not lifelong. 5:35 So I if you’ve had sexual dysfunction your entire life, this medication was 5:40 not approved for you. But if it’s something that you developed over time, like when you went through pmenopause or 5:46 menopause or some women have this experience happen after childirth, that’s what we’re talking about here. 5:53 Now, it’s also not just um supposed to be used if you dislike your partner, 5:59 right? If your relationship is bad and you dislike your partner, this probably isn’t going to fix a ton. It might help 6:05 a little bit, but that’s not what it’s meant for. So, you really have to know what you’re using it for and why. And 6:11 the other thing that I would say is this is something that we don’t go to if your hormones are not balanced properly. You 6:17 have to balance your hormones properly before using something like this because it still may not work. Now, the only 6:24 caveat to that is if you’re a woman that has a risk of breast cancer and can’t use hormones, then that’s a different 6:31 story and we would have that conversation about whether or not this medication would be appropriate for you. Now, the FDA label specifies PTA1 uh 6:39 PT-141 as it not being indicated for HSDD in causes where low sexual desire 6:46 is due to coexisting medical or psychiatric conditions, problems with relationships, like we had talked about, 6:53 side effects to medications or other substance use. This specifically reflects the importance of differential 6:59 diagnosis. Low sexual desire can have many root causes and PT-41 is only 7:05 appropriate when those causes have been ruled out. Now, I have I used PT41 in 7:10 people who have sexual dysfunction issues as a result of using 7:16 anti-depressants. Yes, I have. I’ve used Flynn in that effect as well. And it 7:21 does work sometimes, but it doesn’t work completely. But you need to know that that is not what the approval is for the 7:27 FDA. So that is done in something that we call off label use. So very important 7:33 to know. Now in these clinical trials leading to FDA approval, this was published by Kinsburg and colleagues in 7:40 obstetrics and gyne gynecology in 2019. PT-141 demonstrated statistically 7:46 significant improvements in sexual desire and decreases in distress related 7:51 to low desire compared to placebo. The effects manifest over 45 minutes to 7:56 several hours after the injection and the mechanisms involved modulation of dopamine and melanoorton pathways in the 8:04 hypothalamus and the brain regions that involved sexual motivation. Now cardiovascular effects of PT 141 require 8:12 careful attention. This drug causes transient increases in blood pressure about 3 to four points and transient 8:20 decreases in heart rate. And because of this, it is contraindicated in patients 8:25 with uncontrolled hypertension or known cardiovascular disease. And it has been studied in patients who’ve had recent 8:32 cardiovascular events or sorry hasn’t been studied hasn’t been studied in patients who’ve had recent 8:39 cardiovascular events. So patients need to have their blood pressures checked before starting therapy. Nausea is 8:45 extremely common. It is one of the biggest things I often will tell people to take an anti-nausea medicine if 8:52 they’re going to do this because the last thing you want to do is inject this medication and think it’s going to give 8:57 you this great time with your partner and you’re so nauseated that you can’t even perform, don’t want to kiss, don’t 9:05 want to do anything. It it can be pretty profound for some people. um it does affect about 40% of the patients in 9:12 clinical trials which is why many clinicians require or recommend an 9:17 anti-nausea medication like I had just said other common adverse effects include flushing injection site 9:24 reactions headache in about 13% of the population which I have seen worse if 9:30 people are prone to headaches and the headaches are pretty intense so I will also have them premedicate if they have 9:36 that um sensitivity ity with a Tylenol or Advil, Alie, whatever it is they 9:42 typically use for their headaches to help prevent that from occurring. Now, some patients also experience a 9:50 generalized hyperpigmentation of their skin, particularly in areas with chronic friction, and this may not be reversible 9:57 after discontinuation. So from an integrative perspective, PT-41 10:03 represents one tool in addressing female sexual dysfunction, but it should never be the first or only intervention. And 10:11 low sexual desire in women is complex. Multiffactorial involving hormonal imbalances, low testosterone, estrogen 10:18 deficiency, progesterone imbalances, thyroid dysfunction, adrenal dysfunction, and with elevated or 10:24 disregulated cortisol levels, sleep deprivation, relationship issues, unresolved trauma, including sexual 10:31 trauma, chronic pain, body image concerns, and medication side effects such as SSRIs are notorious for this. So 10:39 a comprehensive hormone panel including total and free testosterones, estradile, 10:45 progesterone, DHEA, thyroid function in cortisol assessment, ideally four-point 10:51 cortisol, salivary should precede any pharmacological intervention. And additionally, addressing the 10:57 psychological component and relationship dimensions through appropriate therapy is necessary. I have a lot of patients 11:03 that say, “This is just too much work for sex. I don’t want the side effects. I don’t want to deal with this.” and that’s totally fine. But for some 11:09 people, their sexual dysfunction is actually causing more problems on their 11:14 relationship and they want to do something to fix that. And just know that if you’re using a peptide like this 11:20 that comes with some of these side effects and you have to premedicate for it, it is not the end of the world. Um, 11:27 but it may be a possibility that you may need that. So, let’s dive into body composition and growth hormone access. 11:34 So Tesmarellin is the only FDA approved GH 11:40 analog. Tesarelin is marketed as Agrifta and Agria SV. It is a synthetic analog 11:48 of human growth hormone releasing hormone. So GH RH human growth hormone 11:53 releasing hormone. These things are such long names it’s confusing and it’s difficult to spit out, right? It 11:59 consists of 44 amino acids. The structure is identical to our own 12:05 body’s growth hormone GHR um with the addition of trans3 hexonol group which 12:14 stabilizes the molecule that extends its half-life compared to the native GHR. 12:19 The mechanism of tesmarellin is elegant in its preservation of physiological 12:24 growth hormone GH secretion patterns and rather than administering an exogenous 12:30 growth hormone directly, tesmarillin binds to the GH receptor in the anterior 12:36 pituitary gland stimulating the indogenous pulsatile release of GH. So 12:42 you know it it’s slower in that stimulation and it pulsates instead of a direct rise and fall. This pusile 12:49 pattern more closely mimics natural GH secretion which occurs in bursts 12:54 primarily during sleep. The GH then stimulates the liver to produce insulin-like growth factor IGF-1 which 13:01 exerts many of the downstream metabolic effects including lipolytic effects on 13:07 the atapost tissue. So fat atapose and how we break that down. The FDA approved 13:13 tesmarellin in 2010 for a very specific narrow indication, the reduction of 13:19 excess abdominal fat in HIV infected patients with lipodistrophe. This 13:25 condition characterized by abnormal fat redistribution with accumulation of visceral body fat and the loss of 13:32 subcutaneous fat in face and limbs developed as a complication of an 13:37 antiviral therapy particularly with older protease inhibitor reg uh 13:42 regimens. The visceral fat accumulation in patients is not just cosmetic. It’s associated with increased cardiovascular 13:49 risk, insulin resistance, and inflammatory markers. The pivotal trial that led to the FDA approval included 13:56 work by Stanley and colleagues published in the annuals of internal medicine in 2014. It demonstrated that tesmarillan 14:03 significantly reduced the visceral atapose measured by CT scan by approximately 15 to 20% which is a 14:10 significant difference to placebo over a short period of time only 26 weeks. Now, 14:16 interestingly, the total body uh weight typically remained stable or even 14:21 increased slightly as the reduction of visceral fat was sometimes offset by increases in lean body mass or 14:28 subcutaneous fat. This highlights an important point. Tesmearellin is not a weight loss drug in its conventional 14:34 sense. Its effects are specifically on body composition and fat redistribution. 14:40 Now the glucose metabolism effects of tesmarellin do require careful monitoring because GH and IGF1 can 14:47 induce insulin resistance. Tesmearellin can increase glucose levels and hemoglobin A1C and in these clinical 14:54 trials glucose tolerance and new onset diabetes occurred in some patients. So 14:59 this creates a therapeutic paradox while res reducing visceral fat we should theoretically improve metabolic health. 15:07 The GH mediated insulin resistance can worsen the glycemic control and patients 15:12 with diabetes require particularly close monitoring. The potential need for adjustment in diabetic medications can 15:19 occur. So I already know what you guys are thinking. Can I use Tesmarellin and 15:24 GLP1 at the same time? And the answer is yes. Especially in those people that we 15:30 know have an insulin resistance already or are prone to that, we can use lowd 15:36 dose micro doing GLP-1 along with tesmarellin to help prevent this from 15:42 occurring um or reduce the risk of it occurring. Now there are some other adverse related problems to growth 15:49 hormone access which include fluid retention which can uh manifest as uh 15:55 ankle swelling, joint pain, muscle pain, paristhesas, carpal tunnel syndrome is 16:01 common to see. Of course you can always see injection site reactions reported about 26 to 30% of the time in the trial 16:08 participants. And this also theoretically has a concern about IGF-1 elevation potentially promoting 16:14 malignancy through long-term data is limited. So we have to be cautious about 16:20 this but it is a growth hormone and anything that is a growth hormone can cause cells to grow and it cannot 16:26 necessarily differentiate between healthy cells and bad cells. So the drug is contraindicated is contraindicated in 16:33 patients with active cancer and in patients with the disruption of the HPA access from conditions like pituitary 16:40 tumors, pituitary surgery, head of radiation um and traumatic brain injury. 16:46 Now off label use of tesmarellin for general anti-aging or body composition 16:51 optimization in non-HIV population, it doesn’t have FDA approval. There is no 16:58 FDA studies. um that promote this, but practitioners do prescribe it for these 17:04 purposes under an experimental and not supported by FDA approved indications. 17:10 And um from an integrative medical standpoint, optimizing natural growth 17:15 hormone secretion through lifestyle interventions, high quality sleep is important. GH primarily is excreted 17:22 during sleep and deep sleep waves. So improving your deep sleep is important. Intermittent fasting can also increase 17:28 growth hormone by five-fold as demonstrated in a Hartman and colleagues uh study from the journal of clinical 17:35 endocrinology and metabolism in 1992. And highintensity interval training, adequate dietary protein, blood sugar 17:42 control, these all can help naturally increase your growth hormone. So, let’s 17:47 dive in now and talk about bone health. peptide hormones um such as oh I’m gonna 17:54 I’m gonna really slaughter this name. Terraparatide is a true bonebuilding 18:01 peptide. It’s marketed as forio. It’s a recumbent form of the first 34 amino 18:08 acids out of 85 of the human parathyroid hormone PTH. It represents a unique 18:13 approach to osteoporosis treatment because it’s one of the few truly anabolic anabolic bone therapies meaning 18:21 it actively binds new bone rather than simply preventing bone loss. The biology 18:26 of parathyroid is fascinating and seemly contraindicated or uh contradictory. 18:32 Continuously sustained elevations of PTH as occurs in hyperarathyroidism 18:37 is catabolic to bone. So people who have hyperarothyroidism typically have significant bone loss 18:44 especially before it’s diagnosed and it causes causes increased bone 18:49 reabsorption loss of bone density increased fracture risk and however 18:55 intermittent exposure to PTH as achieved with once daily uh injections of forio 19:01 has the opposite effect. This intermittent exposure preferentially stimulates osteoblasts bone building 19:08 cells over osteoclasts bone reabsorbing cells and it leads to 19:13 the net bone formation. So terraparatide binds to the PTH receptors on 19:20 osteoblasts and renal tubular cells in bone. It increases the number of 19:25 activity of osteoblasts stimulating the differentiation of osteoblast precursor cells and may 19:32 reduce osteoblast apoptosis basically programmed cell death allowing this bone 19:37 building cell to work longer. The result is increased bone formation, improved bone architecture and tbacular 19:45 connectivity and ultimately increased bone mineral density um particularly in the hip and the spine which is so 19:51 difficult to regain. The FDA approved this medication in 2002 based on pivotal 19:57 studies by Near and colleagues published in the New England Journal of Medicine in 2001 which demonstrated significant 20:05 reductions in vertebral and non-vebral fractures in post-menopausal women with 20:11 osteoporosis. specifically uh reduced new vertebral fractures by 20:17 65% and nonvettebral fragility fractures by 53% 20:23 compared to placebo over a median followup of 21 months. This is really 20:29 incredible because we have not seen this kind of um change uh in other 20:35 medications that we’ve used for osteoporosis. So current FDA approval 20:40 indicates uh this for post-menopausal women with osteoporosis at high risk for 20:46 fracture, men with primary or hypoconatal osteoporosis at high risk for fracture 20:53 and men and women with glucocord cord glucocordide 21:00 induced osteoporosis at high risk for fracture. The high risk qualifier is 21:05 important. uh terrapeptide is reserved for patients with severe osteoporosis, 21:11 multiple fractures, very low low bone density and those who have failed or are 21:16 intolerant of other therapies. The most significant concern for this medication 21:21 is highlighted in a boxed warning with rat toxicology studies where it caused 21:27 osteioaroma which is a bone cancer in a dose dependent and treatment duration dependent manner. The revolence of this 21:34 finding to humans is debated. Rats have fundamentally different bone biology than humans with continuous bone growth 21:41 throughout life and different PTH receptors. Now post marketing 21:46 surveillance in humans hasn’t shown a clear increase in osteocaroma risk but 21:51 theoretically concerns persist and because of this terapeptide is 21:57 contraindicated in patients at risk baseline risk for osteioaroma 22:02 including those with pageantss disease of the bone unexplained elevations of alkaline phosphate prior skeletal 22:10 radiations bone metastases or skeletal malignancies and pediatric patients or young adults 22:16 with open hyes. There’s also a lifetime treatment duration of only 2 years and 22:22 terrapeptide can cause transient hypercalcemia. So an elevated blood calcium and as PTH normally increases 22:31 calcium levels by enhancing bone reabsorption, increasing renal calcium 22:36 reabsorption and promoting activation of vitamin D which increases intestinal calcium absorption. Some patients 22:43 experience orthostatic hypotension within 4 hours of injecting requiring 22:48 caution in at risk populations for blood pressure. Common side effects include 22:53 muscle pain, joint pain, pain in the limbs, nausea, headache, and dizziness. So from an integrative bone health 23:00 perspective, terrapeptides should be part of a comprehensive strategy. Adequate calcium intake, 500 to a,000 23:08 milligrams of calcium a day from food and supplements combined. and vitamin D. 23:13 Getting vitamin D levels of at least 50 to 80 are essential for the drug to work 23:20 optimally. But beyond this, bone health requires vitamin K2, which directs calcium into the bones rather than soft 23:27 tissues, magnesium as a co-actor in bone metabolism, trace minerals like boron, 23:33 copper, silica, and of course, adequate protein intake, which many of us, especially as women, don’t do 0.8 8 to 1 23:42 gram of protein per kilogram of body weight, weightbearing exercise. Of 23:47 course, these all provide mechanical signals that complement the biochemical 23:52 symbol uh signals of terrapeptide. Sequential therapy is also critical. The 23:58 bone mass gains from terraparatide can be lost if patients don’t transition to 24:05 an anti-resorbbitive agent a bisphosphinate after completing this therapy and the anabolic effects to 24:12 build bone but maintaining the new bone requires preventing excess reabsorption. 24:18 So positive things about this but there are definitely some concerns as well. So 24:23 the next one we’re going to talk about is Lu Prolrooide. It is marketed under 24:29 the multiple brand names of Lupron, Depo, Eligard, and it’s a synthetic 24:34 nonapeptide analog of naturally occurring ginonadotropen releasing 24:39 hormone G&R, also called luteinizing hormone releasing hormone, LHR. 24:46 It’s a fascinating example of how manipulating natural hormonal feedback systems can create therapeutic effects. 24:53 So, G&RH is normally secreted in a pulsatile fashion by the hypothalamus 24:59 and travels to the anterior pituitary where it binds to G&R receptors and 25:05 stimulates the release of luteinizing hormone LH and follical stimulating hormone FSH. These ginatotropins signal 25:13 the ovaries or the testes to produce sex hormones, estrogen, progesterone in 25:18 women, testosterone in men. Uh, luoprololi lupron as a GNR agonist 25:26 initially mimics the action of natural G&R causing an acute flare response with 25:33 uh increased LHFSH secretion which temporarily increases sex hormone 25:38 production. However, the continuous administration which is in the depo 25:44 formulations, the GNR receptors in the pituitary become desensitized and 25:50 downregulated. And after about 2 to four weeks of continuous exposure, LH and FSH 25:56 secretion is profoundly suppressed, leading to what’s termed as chemical 26:01 castration. Testosterone levels in men drop to castrated levels less than 50 26:08 and estrogen production is marketkedly suppressed in women. This bifphasic 26:13 response creates both therapeutic applications and management challenges in prostate cancer where tumor growth is 26:20 typically androgen dependent and the ultimate goal is testosterone suppression. However, the initial 26:27 testosterone surge during the flare phase can temporarily worsen symptoms potentially causing increased bone pain, 26:34 urinary obstruction, or even spinal cord compression in patients with metastatic 26:40 disease. This is why uh luoprolide is often started with an anti-ad androgen 26:47 like bicladamide for the first two to four weeks to block the effects of the 26:52 testosterone surge. The FDA has approved lupalide for multiple indications across 26:59 formulations. In oncology, it’s used for palletive treatment of advanced prostate cancers. In gynecology, various 27:06 formulations are approved for endometriosis, for pain management and lesion reduction and for fibroids. 27:13 Typically for pre-operative uh hematological improvement in anemic patients. In pediatrics, it’s used for 27:20 central precocious p puberty basically to halt the premature sexual development of these young people. Now, there are 27:28 adex uh adverse effect profile that reflects profound hormonal suppression. 27:34 In men treated for prostate cancer, hot flashes affect about 59% of the patients. Other common effects include 27:41 general pain, swelling, bone pain. Um long-term use of these medications leads 27:47 to metabolic changes. It increases fat mass. It decreases lean mass. It worsens 27:53 insulin sensitivity, disrupts the cholesterol uh lipid panels, increases 27:59 diabetic risk, has some concerns over cardiovascular disease. And the metaanalysis have shown increased risks 28:06 of heart infarction, myocardial inffection, sudden cardiac death, and stroke in populations receiving 28:13 long-term androgen deprivation therapy. The bone effects are particularly dramatic. Without sex hormones, bone 28:20 density decreases significantly, typically 3 to 4% per year during the 28:26 first two to three years of therapy. And this bone loss may not fully be reversible after the the therapy 28:32 discontinues. The American Society of Clinical Oncology recommends bone density monitoring and consideration of 28:39 bisphosphinates uh in men receiving long-term androgen deprivation. In women treated for 28:46 endometriosis or fibroids, the estrogen suppression creates a hypoestrogenetic state similar 28:54 to menopause. Hot flashes affect 90% of patients with other common effects 29:00 including headaches, emotional irritability, decreased sex drive, vaginal dryness, bone density loss. And 29:08 because of these bone concerns and treatment duration with endometriosis, typically limited to six months, though 29:14 some formulations allow for longer use with adback hormonal therapy to 29:20 partially mitigate these side effects. The mood and cognitive effects can be s 29:25 significant. I’ve seen it over the years. the depression, the memory impairment, difficulty focusing and 29:31 concentrating. It can be very very traumatic and the quality of life that 29:37 happens for these uh women and men can be unbearing for many of them. Um, from 29:44 an integrative perspective, patients receiving this medication need comprehensive support care. Bone health 29:51 interventions using calcium, vitamin D, vitamin K2, weightbearing exercise, 29:58 cardiovascular risk management becomes critical, including blood pressure monitoring, lipid management, diabetes 30:05 screening. For hot flashes management, some patients respond to black coohos, 30:10 sage, or vitamin E. Though evidence is mixed and individual response varies, 30:16 omega-3s may help with the mood and the inflammation, resistance training becomes specifically important to 30:22 preserve lean muscle mass in the face of hormonal suppression. 30:27 Now there’s something called calcetonin salamon which is marketed as miaelin. 30:34 It is a nasal spray. It is now discontinued. And foral is the new 30:39 synthetic polyeptide hormone of 32 amino acids identical to calcetonin of salamon 30:47 origin. It represents an interesting case study in how initial promise gives 30:52 way to safety concerns that regulate a therapy to historical footnote status. 30:58 Calcetonin is naturally occurring hormone in humans. It’s secreted by the paraphalicular sea cells in the thyroid 31:04 gland. Its primary physiological role is to lower blood calcium levels by 31:10 directly inhibiting osteoclast activity, reducing bone reabsorption, increasing 31:16 renal calcium secretion or excretion, and possibly reducing the intestinal 31:21 calcium absorption. So, salamon calcetonin is used therapeutically because it’s more potent and longer 31:27 acting than human calcetonin. The FDA initially approved calceton and salmon 31:34 for several indications post-menopausal osteoporosis in women more than five 31:39 years post-menopausal when alternative treatments are not sustainable. Padet’s 31:44 disease for bone and hypercalcemium as emergency treatments. The nasal spray formulation is particularly popular for 31:53 osteoporosis because it offered a non-injectable alternative to bisphosphinates. 31:58 However, in 2012, the European Medicine’s Agency, EMA, conducted a 32:05 comprehensive safety safety review after a poolled analysis of 21 clinical trials 32:10 involving over 10,000 patients showed a statistically significant increase in 32:15 malignancy risk in patients treated with calceton salamon compared to compared to 32:21 placebo. The overall malignancy rate was 4.1% in calcetonin treated patients 32:28 versus 2.9% in placebo patients. The types of cancer 32:34 varied with no single cancer type predominating, making it difficult to establish a clear mechanistic link. 32:41 However, the signal was concerning enough that the EMA restricted the use of calcetonin containing medicines. In 32:48 the United States, the FDA issued communications about malignancy signal and conducted its own review. While they 32:56 didn’t fully withdraw the drug, the cons consensus shifted dramatically. The nasal spray formulations miaelson was 33:03 voluntarily discontinued by the manufacturer and current clinical practice guidelines now consider 33:10 calcetonin salamon as a second line or lower option for osteoporosis. While 33:15 behind bisphosphinates, dennism mob, uh, terrapeptide, the analesic effect of 33:21 calcetonin in bone pain, particularly in acute vitibbral, uh, compression 33:26 fractions from osteoporosis or pageantss disease may still provide a role for short-term use in these selected 33:32 patients. The mechanism of this pain relief is unclear, but may involve 33:38 effects of endorphin systems and/or direct actions on pathways. The history serves as an important reminder in 33:45 peptide medicine. Initial approval and early clinical use does not guarantee 33:50 long-term safety effects. Post marketing surveillance and poolled analysis of the clinical trial data can reveal adverse 33:58 effects that weren’t apparent in initial studies. It also underscores why newer 34:04 agents with better safety profiles um have largely replaced calcetonin in 34:10 clinical practice. So this is really an important thing. Not one thing stays the same forever. We have to change as we 34:18 identify new and better products as we identify problems and concerns. I will 34:24 always tell my patients if you are uncertain of taking a new drug which we 34:30 all should be wait five years. Within five years we are going to find the 34:36 problems that they didn’t find in the clinical studies. Remember, a lot of these clinical studies are small, small 34:43 groups, short periods of time. It’s expensive to do these trials. So, if you 34:49 wait for five years, in the first two to three years, you will see the problem start to emerge. And what are you going 34:55 to look for? You’re going to look for the the news um commercials from lawyers 35:02 suing a drug. And they will tell you what the problem is. and then you can decide, is this something that I want to 35:09 use or not. Don’t jump on bandwagon and be the first one to do this, especially 35:14 if you’re sensitive. You know, give it time so you can see exactly what’s going on. So, I’m going to end our show on 35:22 this and we are going to pick up on part three of peptide therapy in our next 35:28 segment where we’re going to talk about the investigational peptides and some 35:34 exciting things that are happening with that. So, I want to thank you for joining me today on Let’s Talk Wellness 35:39 Now. It’s always a pleasure having a conversation with you guys and I hope this brings value to you with what we’re 35:45 talking about. If you have ideas for topics that you want me to discuss, 35:51 please message us, you can share your comments on Facebook, you can email us, 35:58 um you can get a hold of us however you would like to share that. I do look at the comments below in the episodes as 36:04 well. So you can place your comments there. And once again, one of the best things you can do for me is like, 36:11 subscribe, and share so that we can spread the messages of what we’re doing. 36:16 I do this at no cost. I don’t make any money out of this. I do this as an 36:21 educational purpose for everybody else. I love doing it, but it really helps us 36:28 on the algorithms if you would be just willing to like, subscribe, and share. 36:33 So, thank you for spending your time with me. I know time is important.The post Episode 257 – Peptides for Sexual Wellness & Hormonal Health: PT-141, Growth Hormones, Bone Health & More! first appeared on Let's Talk Wellness Now.

Interview with Philip Williams, CEO, IsoEnergy Ltd.Our previous interview: https://www.cruxinvestor.com/posts/isoenergy-tsxiso-production-advancement-with-exploration-upside-commencing-winter-drill-program-8967Recording date: 1st of March 2026IsoEnergy is a diversified uranium developer and near-term producer operating across Canada, the United States, and Australia — three jurisdictions deliberately chosen for their strong regulatory and mining track records. The company is gaining significant attention from institutional investors as the uranium sector enters what many believe is a sustained structural bull market.Earlier in 2026, IsoEnergy raised $50 million in a capital round that attracted over $300 million in demand — more than six times oversubscribed — from 45 global institutional investors, roughly half of whom were new to the company. CEO Philip Williams, speaking at PDAC 2026, described it as a signal of a meaningful shift: where uranium investing was once the domain of a handful of specialists, generalist funds and large institutions are now actively deploying capital into quality names. IsoEnergy's scale and track record position it to capture that wave.IsoEnergy's flagship asset, the Hurricane deposit in Saskatchewan's Athabasca Basin, holds 48.6 million pounds of U₃O₈ at an average grade of 34.5% — the highest-grade uranium resource on earth. The deposit sits adjacent to Cameco and Orano's Dawn Lake project, whose operators have publicly confirmed high-grade mineralisation comparable to Cigar Lake and McArthur River, the two largest uranium mines in the world. IsoEnergy is currently running an expanded winter drill program and believes significant additional pounds remain to be discovered.The Tony M Mine in Utah is the company's most advanced production asset. A bulk sample program is currently underway underground, generating the data needed for a final restart decision. With approximately $150 million in cash, the company is fully funded for that decision without needing new equity or debt.IsoEnergy stages its portfolio deliberately — advancing Tony M first, then Daneros and Rim in Utah, then its Australian assets — allowing a core technical team to transfer expertise sequentially rather than spreading it thin. This matters because experienced uranium mine builders are globally scarce. The company is also well-positioned to access US government capital, with agencies including the Department of Energy and the Export-Import Bank actively advertising critical minerals funding at industry events.With multiple catalysts converging in 2026 — Hurricane drill results, a Tony M production decision, and broad institutional tailwinds — IsoEnergy is structurally positioned as one of the uranium sector's most compelling development stories.Learn more: https://www.cruxinvestor.com/companies/isoenergySign up for Crux Investor: https://cruxinvestor.com

A high calcium score, a stack of prescriptions, and the nagging sense that “healthy eating” wasn't working—David Etheridge's story captures what millions feel but rarely decode. When he shifted from chasing calories to controlling insulin, everything changed: he moved from a 12:12 rhythm to a 16:8 fasting window, led meals with protein and natural fats, saved carbs for later on the plate, and watched both cravings and brain fog fade. The scale moved, but the labs told the real story—A1C from 5.8 to 5.1, triglycerides from 285 to 72, and a dramatically improved lipid ratio.We dig into why this works. Intermittent fasting gives insulin time to fall, reigniting fat mobilization and cellular repair. Sequential eating blunts glucose spikes and steadies appetite. And building plates around eggs, meat, dairy, and vegetables respects how satiety actually functions. Along the way we confront the legacy of “low fat” guidance that pushed sugar and seed oils into everyday foods, trained us to graze, and stretched ingredient lists while shrinking satiety. David argues for flipping the pyramid: prioritize protein and real fats, add non-starchy vegetables for fiber and micronutrients, treat sugar as an occasional indulgence, and skip the ultra-processed traps.This isn't anti-medicine; it's pro-data. With medical oversight, David watched his markers improve and discussed next steps with a supportive clinician focused on outcomes, not dogma. Even with a high coronary calcium score, the goal becomes halting progression by lowering inflammation and improving insulin sensitivity. We also touch on how AI can translate cryptic test reports into plain English so patients ask better questions and make calmer choices. If you've tried to white-knuckle your way through snack culture, this conversation offers a clear, humane alternative: fewer eating windows, protein-first plates, simpler ingredients, and measurable wins. If this resonated, follow the show, share it with a friend who needs hope, and leave a review to help more people find the path back to metabolic health.Continue this conversation on SubStack: https://robertlufkinmd.substack.com Get 120 Biomarkers for $99 and CT Calcium scans anywhere in the US. https://www.vitalsvault.com/ Lies I Taught In Medical School : Free sample chapter- https://www.robertlufkinmd.com/lies/ Web: https://robertlufkinmd.com/X: https://x.com/robertlufkinmdYoutube: https://www.youtube.com/robertLufkinmd Instagram: https://www.instagram.com/robertlufkinmd/LinkedIn: https://www.linkedin.com/in/robertlufkinmd/TikTok: https://www.tiktok.com/@robertlufkinThreads: https://www.threads.net/@robertlufkinmdFacebook: https://www.facebook.com/robertlufkinmd Bluesky: ...

Empathy is pioneering bereavement care as an enterprise benefit, transforming how employers and financial institutions support employees during life's most challenging transitions. Working with 9 of the top 10 life insurance carriers in the US and Canada—covering over 40 million people—Empathy created a new category by combining grief support with practical logistics like probate navigation, account deactivation, and estate settlement. In a recent episode of BUILDERS, we sat down with Ron Gura, Co-Founder & CEO of Empathy, to learn how the company went from testing five verticals simultaneously to dominating life insurance, then leveraged the group life/employer overlap to expand into employee benefits. Topics Discussed: Testing five enterprise verticals simultaneously to find product-market fit Landing New York Life through their venture arm and innovation team Why life insurance carriers need to be risk-averse (and how to work with that reality) The strategic overlap between group life insurance and employee benefits Investing in brand at seed stage when your barrier to entry is psychological aversion Navigating dual audiences: decision-makers in their workday versus end users in crisis Expanding from loss to adjacent life transitions like disability leave and estate planning GTM Lessons For B2B Founders: Run parallel vertical tests with focus constraints, not sequential exploration: Ron identified 10+ potential verticals but intentionally tested exactly five simultaneously—hospices, funeral homes, employers, and two others before life insurance emerged as the winner at position five. This parallel testing with artificial constraints forces prioritization while dramatically compressing time-to-insight. Sequential testing would have meant potentially cycling through five failed pilots before discovering their strongest market. B2B founders with horizontal platforms should pick their top 3-5 verticals and run focused pilots in parallel, accepting that this burns more resources upfront but eliminates the risk of quitting before finding your wedge. Map the ecosystem overlap between buyer personas before choosing your wedge: Empathy's expansion from life insurance to employers wasn't growth strategy—it was recognizing an architectural reality. Half their carriers sell group life, meaning MetLife doesn't sell to consumers at metlife.com but exclusively to employer groups. When Amanda at Paramount loses her sister (not covered by insurance), she calls Paramount HR. When her husband dies (covered by MetLife group policy), the beneficiary calls MetLife. Same end user, two different enterprise entry points into the same moment. B2B founders should map these triangular relationships before choosing their wedge vertical. The question isn't just "who has budget?" but "who else touches this user in adjacent contexts?" Brand investment at seed stage is product strategy when fighting cognitive aversion: Ron's insight: "The barrier to entry isn't regulatory and isn't technology. It's us humans trying really hard not to think about our own mortality." This isn't a marketing problem—it's a fundamental go-to-market blocker. The company made what most would consider Series A investments (premium domain, design system, tone/voice framework) at seed stage specifically because brand reduces psychological friction to adoption. Contrast this with Monday.com starting as "daPulse" and rebranding years into success. B2B founders addressing taboo topics (death, mental health, financial distress, relationship issues) should model brand as a core distribution lever, not post-PMF polish. In deeply human categories, buyer's lived experience is your demo: Enterprise buyers at Citibank, MetLife, or Google aren't experiencing crisis during the sales cycle—they're evaluating ROI in their normal workday. But as Ron noted, "Everyone we're talking to...they're humans. They have parents, they had loss, they went through probate." The most common response after seeing the product: "Damn, I wish you called me a few months ago. I needed this a year ago with my mom." This turns product demo into personal recognition. B2B founders in universal human experience categories (caregiving, bereavement, parental leave, financial stress) should structure discovery and demo to activate buyer's memory of their own experience, not just their budget authority. Category creation is a resource-attraction strategy that trades speed for competitive exposure: Ron explicitly acknowledged: "There's pros and cons to defining a category. It's helpful when you attract resources, talent, capital. It also creates very fertile ground for a number two sympathy.com to come along and learn from this podcast...what to go after." Category leadership accelerates recruiting and fundraising by providing narrative clarity, but it simultaneously publishes your playbook. Every hiring blog post, podcast appearance, and positioning document teaches future competitors which verticals to target and which to avoid. B2B founders should treat category creation as a conscious bet: trade competitive opacity for talent/capital velocity. If you're not ready to defend your position, stay in stealth longer. Bridge new categories to existing budget lines through analogous benefits: When entering new verticals beyond life insurance, Ron doesn't educate from zero. With employers, he positions bereavement care alongside caregiving solutions, fertility programs, and parental leave: "This is a life transition happening in my own intimate house. Just like a new baby. I have new duties now." This isn't metaphor—it's budget mapping. Bereavement care gets evaluated against existing family benefits spending, not created from scratch. B2B founders in new categories should identify which existing line item their solution logically extends, then structure ROI narratives around reallocation, not net-new budget creation. // Sponsors: Front Lines — We help B2B tech companies launch, manage, and grow podcasts that drive demand, awareness, and thought leadership. www.FrontLines.io The Global Talent Co. — We help tech startups find, vet, hire, pay, and retain amazing marketing talent that costs 50-70% less than the US & Europe. www.GlobalTalent.co // Don't Miss: New Podcast Series — How I Hire Senior GTM leaders share the tactical hiring frameworks they use to build winning revenue teams. Hosted by Andy Mowat, who scaled 4 unicorns from $10M to $100M+ ARR and launched Whispered to help executives find their next role. Subscribe here: https://open.spotify.com/show/53yCHlPfLSMFimtv0riPyM

How early in process development should you address glycosylation? This episode presents the case for co-optimizing glycan profiles with productivity from initial process characterization. Deferring glycosylation characterization until after titer targets are met introduces risk: quality attribute gaps discovered late in development force process re-optimization, extended timelines, and potential cell line reselection. Media supplementation enables earlier intervention—tuning glycan distribution as a process parameter from the beginning of cell line and media development rather than as a remediation strategy.David Brühlmann outlines the experimental protocol for validating raffinose supplementation, including decision criteria for proceeding or terminating at each development stage. The discussion addresses process design space requirements, analytical monitoring strategy, and the experimental variables that determine when media-based glycan tuning is appropriate versus when alternative approaches are needed.Highlights from the episode:When to use (and not use) raffinose in your development program, including limitations and effectiveness windows (00:30)Essential protocol: three experiments over eight weeks to validate raffinose for your process, with clear go/no-go criteria (04:09)Why individualized mannose tracking (Man5, Man6, Man7, Man8) is crucial for meaningful results (01:06)Managing osmolality: why it matters and how to control it in your experiment (04:36)Advice on scaling up: moving from small-scale screens to benchtop bioreactors and stress-testing your process (07:48)Three key mistakes to avoid when implementing raffinose, including lessons from analytical oversight, incomplete design mapping, and feed interference (09:08)Integrating glycosylation as a core part of process design, not just a secondary consideration after titer optimization (13:10)Strategic insight:Sequential optimization of productivity followed by glycosylation introduces development risk: quality attribute deviations discovered after process lockdown require costly re-optimization cycles. Parallel development of titer and glycan specifications from initial cell line characterization reduces this risk by establishing feasible operating windows early in the development timeline.Are you planning your next recombinant protein scale-up? Hear how David's rule-of-three protocol and battle-tested lessons can help you optimize faster and avoid painful late-stage surprises.Resources: Journal of Biotechnology, 2017, volume 252, pages 32 to 42Next step:Need fast CMC guidance? → Get rapid CMC decision support hereSupport the show

Let me start with a confession. Classifiers are hard. Not hard in the way vocabulary is hard, where you simply need more exposure, more repetition, more time. Classifiers are hard because they require signers to think spatially while signing temporally, to track multiple referents while producing new content, to select among productive options while maintaining discourse coherence. That mouthful of a sentence appears in the opening of Depicting Space, and I want to unpack it for you, because hidden inside that description is something important about human cognition. When you speak English, your words unfold in time. One after another. Linear. Sequential. The sentence has a beginning, a middle, an end. You cannot say two words simultaneously. The channel is narrow. But when you sign ASL, something different happens. Your hands can represent two entities at once. Your face carries grammatical information independent of your hands. Your body can shift to become a character while your hands continue to manipulate objects in observer space. The channel is wide. Parallel processing becomes possible.

In this solo episode of Building Better, I explore a pattern I see everywhere. In engineering, in leadership, and in life.Most systems are built sequentially. One decision at a time. One optimization at a time. One fix after another. That approach works. It is safe. It prevents disasters.But it rarely produces truly great outcomes.Using product development and APQP as a starting point, I contrast sequential design with parallel processing. Learning late versus pulling understanding forward. Optimizing parts versus optimizing the system.I then zoom out beyond engineering to show how the same pattern shows up in home projects, health, parenting, and how we design our lives and organizations.This episode is about capability, foresight, and the difference between reacting your way to “good enough” and designing for something better from the start.Music creditSlow Burn by Kevin MacLeod

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/EBAH/AAPA information, and to apply for credit, please visit us at PeerView.com/JGX865. CME/MOC/EBAH/AAPA credit will be available until January 4, 2027.Many Roads to Myeloma Remission: Making Sequential Choices With BCMA and Non-BCMA Immunotherapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and HealthTree Foundation for Multiple Myeloma. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported by independent medical educational grants from Arcellx, Inc. and Kite, a Gilead Company; GSK; Johnson & Johnson; and Regeneron Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/EBAH/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PWK865. CME/MOC/EBAH/AAPA/IPCE credit will be available until January 4, 2027.Pathways to Personalized Remission in CLL: Leveraging Targeted Standards & Next-Gen Advances for Upfront and Sequential Care In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and CLL Society. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, BeOne Medicines, and Lilly.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/EBAH/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PWK865. CME/MOC/EBAH/AAPA/IPCE credit will be available until January 4, 2027.Pathways to Personalized Remission in CLL: Leveraging Targeted Standards & Next-Gen Advances for Upfront and Sequential Care In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and CLL Society. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, BeOne Medicines, and Lilly.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/EBAH/AAPA information, and to apply for credit, please visit us at PeerView.com/JGX865. CME/MOC/EBAH/AAPA credit will be available until January 4, 2027.Many Roads to Myeloma Remission: Making Sequential Choices With BCMA and Non-BCMA Immunotherapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and HealthTree Foundation for Multiple Myeloma. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported by independent medical educational grants from Arcellx, Inc. and Kite, a Gilead Company; GSK; Johnson & Johnson; and Regeneron Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/EBAH/AAPA information, and to apply for credit, please visit us at PeerView.com/JGX865. CME/MOC/EBAH/AAPA credit will be available until January 4, 2027.Many Roads to Myeloma Remission: Making Sequential Choices With BCMA and Non-BCMA Immunotherapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and HealthTree Foundation for Multiple Myeloma. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported by independent medical educational grants from Arcellx, Inc. and Kite, a Gilead Company; GSK; Johnson & Johnson; and Regeneron Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/EBAH/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PWK865. CME/MOC/EBAH/AAPA/IPCE credit will be available until January 4, 2027.Pathways to Personalized Remission in CLL: Leveraging Targeted Standards & Next-Gen Advances for Upfront and Sequential Care In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and CLL Society. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, BeOne Medicines, and Lilly.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/EBAH/AAPA information, and to apply for credit, please visit us at PeerView.com/JGX865. CME/MOC/EBAH/AAPA credit will be available until January 4, 2027.Many Roads to Myeloma Remission: Making Sequential Choices With BCMA and Non-BCMA Immunotherapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and HealthTree Foundation for Multiple Myeloma. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported by independent medical educational grants from Arcellx, Inc. and Kite, a Gilead Company; GSK; Johnson & Johnson; and Regeneron Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/EBAH/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PWK865. CME/MOC/EBAH/AAPA/IPCE credit will be available until January 4, 2027.Pathways to Personalized Remission in CLL: Leveraging Targeted Standards & Next-Gen Advances for Upfront and Sequential Care In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and CLL Society. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, BeOne Medicines, and Lilly.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/EBAH/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PWK865. CME/MOC/EBAH/AAPA/IPCE credit will be available until January 4, 2027.Pathways to Personalized Remission in CLL: Leveraging Targeted Standards & Next-Gen Advances for Upfront and Sequential Care In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and CLL Society. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, BeOne Medicines, and Lilly.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/EBAH/AAPA information, and to apply for credit, please visit us at PeerView.com/JGX865. CME/MOC/EBAH/AAPA credit will be available until January 4, 2027.Many Roads to Myeloma Remission: Making Sequential Choices With BCMA and Non-BCMA Immunotherapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and HealthTree Foundation for Multiple Myeloma. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported by independent medical educational grants from Arcellx, Inc. and Kite, a Gilead Company; GSK; Johnson & Johnson; and Regeneron Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/EBAH/AAPA information, and to apply for credit, please visit us at PeerView.com/JGX865. CME/MOC/EBAH/AAPA credit will be available until January 4, 2027.Many Roads to Myeloma Remission: Making Sequential Choices With BCMA and Non-BCMA Immunotherapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and HealthTree Foundation for Multiple Myeloma. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported by independent medical educational grants from Arcellx, Inc. and Kite, a Gilead Company; GSK; Johnson & Johnson; and Regeneron Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/EBAH/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PWK865. CME/MOC/EBAH/AAPA/IPCE credit will be available until January 4, 2027.Pathways to Personalized Remission in CLL: Leveraging Targeted Standards & Next-Gen Advances for Upfront and Sequential Care In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and CLL Society. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, BeOne Medicines, and Lilly.Disclosure information is available at the beginning of the video presentation.

Beijing's Sequential Strategy to Break the Coalition: Colleague Elbridge Colby explains that Beijing has abandoned "hide and bide" for a focused and sequential strategy designed to dismantle the anti-hegemonic coalition, targeting vulnerable US partners to demonstrate American hollowness, hoping to erode regional confidence and achieve dominance without fighting a total, catastrophic war.

Building a $2.5 million portfolio is hard. Spending it without running out? That's even harder. Welcome to the 700th episode of the BiggerPockets Money Podcast! To mark this milestone, hosts Mindy Jensen and Scott Trench are tackling one of the most critical—and most overlooked—aspects of financial independence: decumulation. Most people obsess over building wealth but stumble when it's time to actually spend it. The withdrawal strategy you choose can mean the difference between a comfortable 40-year retirement and running out of money at the worst possible time. In this episode, we cover: Sequential vs. blended vs. cyclical withdrawal strategies—which is right for you? How to create a tax-efficient drawdown plan that could save you hundreds of thousands The role of Roth accounts, traditional IRAs, and taxable brokerage accounts in your withdrawal strategy When to do Roth conversions and how to time them for maximum benefit Healthcare planning in early retirement and how it affects your withdrawal strategy Estate planning considerations and maximizing what you leave behind Real-world scenarios: what withdrawal strategies look like in practice The biggest mistakes retirees make in the decumulation phase Whether you're just starting your FI journey or you're ready to retire next year, this comprehensive guide will help you spend your money strategically, minimize taxes, and make your nest egg last. Learn more about your ad choices. Visit megaphone.fm/adchoices

"Eliminate frustration and speed ahead." Who doesn't want this?  When it comes to strength training - and calisthenics in particular - many ambitious and well-meaning enthusiasts jump right into a laundry list of progressions... And fall flat on their tushes.  If you want to feel like you're positively speeding through the various and sundry progressions that lay at the heart of each and every advanced calisthenics movement, you must first dominate their prerequisite movements.  This is the sure-fire path to things such as:  One-arm pushups Pistol squats Nigh on effortless pullups much, much more In this episode I dish on:  [0:00:28] Natural Movement and Standardized Exercises Discussion about learning basic movement patterns, balancing standardized exercises with natural human movements, and recommendations such as crawling, carries, and gait pattern work. [0:02:36] Handstand & Prerequisite Example from Social Media [0:05:00] Personal Anecdote: Prerequisites in Practice [0:06:27] Progress with Handstands and Sequential vs. Simultaneous Training [0:09:16] Lunge Program Leading to Improved Pistol Squats [0:10:32] Embracing the Foundations Valuing foundational, repetitive practice (particularly of prerequisites) across fitness skills.  [0:11:06] Closing   If you like training that: · Gives you more strength than it takes from you · Improves your stamina and resilience simultaneously · Powers-up every nook, cranny, crevice, and corner of your Soft Machine Then you just might like my 9-Minute Kettlebell and Bodyweight Challenge. As the name indicates, it's just 9 minutes long, and it's designed to be done WITH your current workouts – NOT instead of them. Even cooler: Many find that it actually amplifies their strength in their favorite kettlebell and bodyweight moves, like presses, squats, pullups, and more. And best of all, it's free. How free? I'm talkin' freer than the 4th of July, my friend. Get thee thine own copy here:  http://www.9MinuteChallenge.com  Have fun and happy training! Aleks Salkin

Are you using the wrong retirement withdrawal strategy? Sequential drawdown—draining one account before touching the next—is the most common approach to early retirement, but it could be costing you tens of thousands in unnecessary taxes. In this episode of the BiggerPockets Money Podcast, hosts Mindy Jensen and Scott Trench sit down with Enrolled Agent Mark to break down tax-efficient withdrawal strategies that maximize your retirement savings. Discover blended drawdown strategies and cyclical drawdown methods that optimize which accounts you tap first—Traditional IRA, Roth IRA, taxable brokerage, HSA—to minimize your lifetime tax burden. This episode covers: Sequential vs. blended vs. cyclical retirement drawdown strategies How to optimize withdrawal order from retirement accounts (401k, IRA, Roth, taxable accounts) Tax-efficient retirement planning for early retirees and FIRE followers How to leverage today's historically low tax rates before they expire Healthcare costs in early retirement (ACA subsidies, Medicare planning) Asset protection and estate planning considerations Roth conversion strategies during low-income years How to avoid costly tax mistakes in the decumulation phase Whether you're planning for financial independence, already retired early, or managing multiple retirement accounts, this tax optimization masterclass will help you keep more of your money and make your nest egg last longer. Learn more about your ad choices. Visit megaphone.fm/adchoices

Peter Jones, who heads up Revenue at Premion, returns to Insider Interviews (see Ep 38) to educate us on the shifts in local TV advertising in a streaming-first world -- and how small businesses can compete with national brands, with greater access to sports inventory, and why measurement actually matters! Learn what "context" really means for advertisers (spoiler: consumers don't experience media in silos), how the collapse of some Regional Sports Networks has created opportunities for local advertisers, and why "smart curation" is more than an industry buzzword. But it's not just the small business that needs to adapt: it's agencies and brands, too. Peter breaks down what full-funnel capabilities now available to SMBs—from maxing out brand awareness across Premion's 210 DMAs, to measurable sales transactions, tapping 1st and 3rd party data.  And, as we gear up for playoff sports, he reminds us how technology has leveled the playing field and that local advertisers can get in the game, too! So, sports puns are pervasive in Episode 44 since part of our conversation is about Premion's new(ish) programmatic options to enable more inventory for all in live sports. Talk about a “game changer...!” Understand how local car dealerships and furniture stores can now leverage the same targeting, data, and attribution tools that Fortune 500 companies use, all while reaching their specific communities with precision. But for everyone, it's key to understand the importance of creative in driving outcomes, and omnichannel strategies (because yes, we're all scrolling during halftime), and why advertisers need to embrace data-driven decisions over personal platform preferences. "The first thing to realize is that big tech has leveled the playing field for local advertisers..." Whether you're a media buyer, agency leader, or local business owner trying to navigate the CTV landscape, this conversation delivers practical guidance on inventory, data, and measurement—the three pillars every advertiser should evaluate when choosing a CTV partner. Bottom line? The local advertising opportunity in streaming TV has never been bigger—but only for those willing to adapt, measure outcomes over impressions, and follow consumers wherever they are. Key Highlights [01:15] CTV's double-digit growth, challenges and opportunities for advertisers [02:14] What Premion does – Nine years of helping local advertisers navigate CTV [03:33] Leveling the playing field – Educating SMBs on using the same tools as national brands [05:25] Challenges and Strategies for Outcomes in Omnichannel Advertising [08:26] Tools and tactics – First-party data, pixels, attribution, and what SMBs need to track [10:48] The role of creative – Sequential messaging, AI tools, and "message to market match" [12:52] How Premion's programmatic access to sports inventory is opening doors for local advertisers [15:39] Smart Curation Explained and Full Funnel Options in 200+ markets [20:22] The dynamic nature of live sports – Why planning can be tricky but opportunity is massive [21:45] What to look for in a CTV partner – Hint: Inventory, data, measurement (plus the TAG seal of approval!) [23:41] Emerging Trends and AI in Advertising Connect with Peter Jones and Premion Connect with E.B. Moss and Insider Interviews: With Media & Marketing Experts            LinkedIn: https://www.linkedin.com/in/mossappeal Instagram: https://www.instagram.com/insiderinterviews Facebook: https://www.facebook.com/InsiderInterviewsPodcast/ Threads: https://www.threads.net/@insiderinterviews If you enjoyed this episode, follow Insider Interviews, share with another smart business leader, and leave a comment on @Apple or @Spotify… or a tip in my jar!: https://buymeacoffee.com/mossappeal! 

Program notes:0:40 CVD risk factors and texting1:40 How many undergo screening?2:41 Impact of personalized messaging3:25 Decentralized trials versus centralized 4:25 Decentralized much larger5:25 Does the trial move in one way or another?6:15 Two studies related to use of peripregnancy GLP-1 use7:15 Stopping at pregnancy8:15 Is overweight worse than stopping?9:00 Machine learning model, tissues, genetics and age10:00 Practical for assessing genetic basis11:00 Sequential tissue samples11:57 End

Drs. Lewiecki and Camacho discuss sequential therapy in osteoporosis as a critical strategy that involves strategically switching between anabolic and antiresorptive treatments to maximize bone mineral density and reduce fracture risk. By carefully transitioning between different drug classes (eg, romosozumab; teriparatide; denosumab), clinicians can optimize patient outcomes and address the evolving needs of individuals with bone health challenges.

Matthew Cassidy of Partners Wealth Group has just taken the top spot in this year's Barron's Top 150 Advisers List. He offers a unique perspective on what you need to know about advice, and how to deal with an investment market that is clearly at the top of the cycle. Matthew Cassidy of Partners Wealth Group joins Associate Editor - Wealth, James Kirby in this episode. In today's show, we cover: What you should expect from a top financial adviser How to prepare for a sharemarket downturn Sequential risk - The biggest financial threat to the pre-retiree Taking profits off the table See omnystudio.com/listener for privacy information.

Creepy Adaptations: In a belated Halloween episode of Panel Borders, Alex Fitch talks to a trio of creators about their work on creepy adaptations. Graphic novelist, Lucy Sullivan, and film director, Dylan Southern, have worked together on The Thing With Feathers, an adaptation to screen of Max Porter’s award-winning 2015 novella. Lucy has created new […]

The full story behind our 2025 Grid Life Street Mod Championship season. After the struggles of 2024, we came back with a vengeance - 8 events, 5 straight wins, 7 lap records, and the most reliable car in Street Mod.In this extended season recap, Dewey, Dylan, Graham (Boosted Performance Tuning), and Forklift break down everything that happened behind the scenes: building our first sequential transmission, solving the turbo issues at Road Atlanta, the data analysis systems that changed everything, and that incredible rain-soaked victory at Pitt Race.Topics covered:Sequential transmission development and tuning challengesEvery event breakdown from CMP to Pitt RaceTechnical upgrades: suspension geometry, power steering, front diffThe criticism we faced and how we proved everyone wrongBehind-the-scenes logistics and team dynamicsOur systematic approach to data analysis and driver feedbackPlans for 2026: electronic wastegate, motorsport ABS, and morePlus: Terrible steak dinners in castles with Bucky Lasek, windshield explosions, trailer disasters, and why 38°F is the perfect temperature for Pitt Race.This isn't just about winning - it's about the work, the team, and the process that made it possible.#GridLife #TimeAttack #StreetMod #Subaru #Championship #Motorsports

SOFA-2, validated in more than 3 million intensive care unit (ICU) patients, incorporates contemporary organ support treatments, showing strong predictive validity for ICU mortality in diverse international settings. Coauthor Mervyn Singer, MD, joins JAMA Associate Editor Christopher W. Seymour, MD, MSc, to discuss. Related Content: Rationale and Methodological Approach Underlying the Development of the Sequential Organ Failure Assessment (SOFA)–2 Score Development and Validation of the Sequential Organ Failure Assessment (SOFA)-2 Score A Revision to Organ Failure Assessment in Critically Ill Patients

Midjourney Fast Hours — Episode 51: “Sora 2, Veo 3 & The AI Video Gold Rush”Drew and Rory crawl out of their creative caves after a month-long “break” (read: total burnout) and immediately get smacked in the face by Sora 2, Veo 3, and Midjourney Style Explorer updates that make everything they said last episode obsolete.They break down what's actually working in Sora 2 (full edits, audio, dialogue, even IP?), why Veo 3 can't seem to go fast anymore, and how keyframes are quietly becoming the holy grail of AI video.Expect rants about IP chaos, Mr. Rogers cameos, and why OpenAI's guerilla launch strategy might be the smartest marketing move of 2025.It's equal parts therapy session, tech panic, and creative caffeine rush — exactly how they like it.Keywords: Sora 2 update, Google Veo 3 review, Midjourney V8, AI video generation tools, Luma AI, keyframes, AI video editing, AI marketing trends 2025, generative video, Style Explorer Midjourney---⏱️ Midjourney Fast Hour00:00 – Intro + return from creative hibernation00:42 – Sora 2 drops: “the floodgates just opened”01:27 – Sora 2's new tricks: editing, sound, dialogue, and IP02:17 – Veo 3 vs Sora 2 vs Ray 303:20 – Rory's South Park AI episode + the “bar-only” friend05:00 – Why dedicated AI-only spaces actually matter05:48 – Remix culture, Mr. Rogers AI, and the rise of comedic timing07:00 – The “Remix” button, mass adoption, and kids using Sora08:43 – The IP gray area: Minecraft meets Mr. Rogers09:43 – Cameos, access codes, and mobile vs desktop creation12:25 – Sequential storytelling: AI understands chronology now13:29 – Toyota ads, guerrilla launches, and OpenAI's flood strategy15:00 – IP risk vs reward — how far can brands push it18:00 – AI performance comparisons23:00 – Fight scenes, motion control, and why keyframes matter27:50 – Workflow troubleshooting and micro-decision fatigue34:50 – Too many tools? Runway, Aleph, and the Weavy advantage35:45 – Shout-out to Weavy + tool consolidation predictions36:00 – Higgsfield pivots, Pika memes, and the marketing gap37:00 – Visual Electric's acquisition and the coming consolidation wave38:20 – Midjourney updates: Style Explorer, Smart Search, and new unlocks40:30 – Playing with EXP mode + hidden color/style refinements42:30 – Style Finder, Style Creator, and mood-board personalization43:57 – Style ranking feature + --r 40 nostalgia meltdown46:00 – Midjourney V8 speculation & dataset rumors50:30 – Google's product chaos: Gemini, Nano Banana, Flow, and Veo 353:00 – Why Google can fail (and still win)55:10 – ChatGPT's image text features & the next AI video wave59:30 – The Weavy renaissance and workflow automation discussion1:02:00 – New creative problems worth solving1:06:00 – Why “easy” AI creation still stings for creatives1:08:30 – Closing banter + “hit the button” outro

Robaux's serving pie, Teenage Engineering's cooking dub, and Sequential's back with poly aftertouch.

Inspired by the Twentieth Century: Alex Fitch looks at the work of cartoonists influenced by the culture of the Twentieth Century. In a Q and A recorded at the Lakes International Comic Art Festival, artist Juanjo Guarnido discusses his much loved anthropormophic graphic novel series Blacksad, and in a conversation recorded at Cartoon County, Digital […]

Cunningcast is back and Tony is kicking off his new series with one of his favourite subjects, Stonehenge, where new discoveries show that once again this ancient site is throwing up new evidence. Tony has invited his old friend, leading archaeologist Mike Parker Pearson, to discuss the Altar Stone's Scottish origins and its implications for understanding the monument's significance.Also joining the chat is top geologist Jane Evans, whose new research has revealed the fascinating story of an ancient cow's journey from Wales to Stonehenge. Through isotope analysis, Jane has uncovered insights about the Stonehenge cow's diet and origins, leading to broader implications about our ancient communities and their interactions.Hosted by Sir Tony Robinson | Instagram @sirtonyrobinsonProducer: Melissa FitzGerald With Mike Parker Pearson Professor of British Later Prehistory, University College London. He specialises in British and European prehistory from the Neolithic to the Iron Age; Stonehenge and the British Neolithic; the Beaker people of Bronze Age Europe; the archaeology of the Western Isles (Outer Hebrides); the archaeology of Madagascar and the Indian Ocean; the archaeology of death and burial; public archaeology and heritage. Parker Pearson, M. 2023. Stonehenge: a brief history. London: Bloomsbury Publishing | https://www.bloomsburycollections.com/monograph?docid=b-9781350192263 Parker Pearson, M., Bevins, R.I., Bradley, R., Ixer, R.E., Pearce, N.J.G. and Richards, C. 2024. ‘Stonehenge and its Altar Stone: the significance of distant stone sources'. Archaeology International 27: 113–37 | https://journals.uclpress.co.uk/ai/article/id/3293/ Professor Jane Evans Geologist whose early career focused on using isotope methods for dating rocks. She later turned her expertise toward archaeology, pioneering the use of isotopes to study past human migration. Now retired, she holds honorary professorships in archaeology at the Universities of Nottingham and Leicester and is an Honorary Research Associate at the British Geological Survey. Throughout her career, Jane has used the chemical signatures preserved in human remains to reveal where people came from and how they moved across landscapes. Her work has been central to major discoveries — from uncovering stories at Stonehenge and identifying Viking remains near Weymouth, to contributing to the investigation of King Richard III. Evans, J., Pashley, V., Wagner, D., Savickaite, K., Buckley, M., Madgwick, R. and Parker Pearson, M. In press. Sequential multi-isotope sampling through a Bos taurus tooth to assess comparative sources in strontium and lead. Journal of Archaeological Science | https://www.sciencedirect.com/science/article/pii/S0305440325001189Follow us:Instagram @cunningcastpod | X @cunningcastpod | YouTube @cunningcast Hosted on Acast. See acast.com/privacy for more information.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/WMD865. CME credit will be available until August 20, 2026.At the Nexus of Sequential Care in Myeloma: Interprofessional and Patient Perspectives on GPRC5D-Directed Therapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and HealthTree Foundation for Multiple Myeloma. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Johnson & Johnson.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/WMD865. CME credit will be available until August 20, 2026.At the Nexus of Sequential Care in Myeloma: Interprofessional and Patient Perspectives on GPRC5D-Directed Therapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and HealthTree Foundation for Multiple Myeloma. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Johnson & Johnson.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/WMD865. CME credit will be available until August 20, 2026.At the Nexus of Sequential Care in Myeloma: Interprofessional and Patient Perspectives on GPRC5D-Directed Therapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and HealthTree Foundation for Multiple Myeloma. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Johnson & Johnson.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/WMD865. CME credit will be available until August 20, 2026.At the Nexus of Sequential Care in Myeloma: Interprofessional and Patient Perspectives on GPRC5D-Directed Therapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and HealthTree Foundation for Multiple Myeloma. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Johnson & Johnson.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/WMD865. CME credit will be available until August 20, 2026.At the Nexus of Sequential Care in Myeloma: Interprofessional and Patient Perspectives on GPRC5D-Directed Therapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and HealthTree Foundation for Multiple Myeloma. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Johnson & Johnson.Disclosure information is available at the beginning of the video presentation.

As an independent musician, diving into the world of MIDI controllers and studio gear can feel intimidating, especially if you're unsure where to start or which tools best suit your creative process. In this episode, Xylo chats with Alex Godfrey, Product Specialist at the Focusrite Group, about what MIDI controllers actually are, how they work, and how to choose the right one for your music.With over 10 years at Focusrite and hands-on experience representing brands like Novation, Sequential, Oberheim, Focusrite, Adam Audio, and Sonnox, Alex breaks down the essentials of MIDI technology in a clear and practical way. From testing music tech as part of Focusrite's QA Engineering team to producing experimental tracks as Psychedalex, he brings both technical expertise and creative insight. Whether you're just setting up your first home studio or looking to expand your gear, this conversation will help you make confident, informed choices.Distrokid has kindly offered all MPW listeners a 30% discount off the first year of their annual subscription! Use the following link to redeem the discount: http://distrokid.com/vip/mpw

Clay Stephens of 6XD Gearbox joins us to teach us a bit about their product, sequential transmissions, the creation of the 6XD standard gearbox, the XTD gearbox, and the MTX transaxle. In addition to a bit about himself as well. High Performance Academy: https://hpcdmy.co/Minnoxide Use code "MINNOX" for 55% off ANY course Use Code "MINVIP" for $300 of the MINVIP Package Tuned By Shawn: https://www.tunedbyshawn.com Code "Minnoxide" for 5% off! Sure Things Logistics: https://www.surethinglogistics.net MORE BIGGER Turbo T-Shirts:  https://www.minnoxide.com/products/more-bigger-t-shirt

In this week's episode, we'll learn more about how exogenous CD19 stimulation affects CAR T-cell persistence in B-cell acute lymphoblastic leukemia treated with CD19 CAR T-cell therapy; new algorithms that incorporate sequential rapid immune-assays, intended to improve diagnosis of heparin-induced thrombocytopenia, and resource-adaptive survival prediction models to help guide management of patients with chronic myelomonocytic leukemia.Featured Articles:Outcomes of PLAT-02 and PLAT-03: evaluating CD19 CAR T-cell therapy and CD19-expressing T-APC support in pediatric B-ALLSequential combinations of rapid immunoassays for prompt recognition of heparin-induced thrombocytopeniaBLAST: a globally applicable and molecularly versatile survival model for chronic myelomonocytic leukemia

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PAT865. CME/MOC/NCPD/AAPA/IPCE credit will be available until August 10, 2026.The Power Sequence in RRMM: Collaborative Approaches for Optimizing Sequential Treatment With Cellular and Off-the-Shelf Immunotherapy In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported by independent medical education grants from GSK, Johnson & Johnson, and Regeneron Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PAT865. CME/MOC/NCPD/AAPA/IPCE credit will be available until August 10, 2026.The Power Sequence in RRMM: Collaborative Approaches for Optimizing Sequential Treatment With Cellular and Off-the-Shelf Immunotherapy In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported by independent medical education grants from GSK, Johnson & Johnson, and Regeneron Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PAT865. CME/MOC/NCPD/AAPA/IPCE credit will be available until August 10, 2026.The Power Sequence in RRMM: Collaborative Approaches for Optimizing Sequential Treatment With Cellular and Off-the-Shelf Immunotherapy In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis educational activity is supported by independent medical education grants from GSK, Johnson & Johnson, and Regeneron Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

The revelation that shattered systems thinking: Replacing every combustion car with electric vehicles improves urban efficiency by only 6%—revealing why isolated optimizations fail in complex ecosystems.Dr. Parfait Atchadé from MIT Media Lab discovered this through quantum-enhanced urban modeling in Boston's Kendall Square. His breakthrough: humanized AI agents with emotional architectures that "live" in virtual cities for decades of compressed time, then vote on configurations—exposing the systematic failure of single-variable optimization. Paradigm Shifts:→ The Single-Solution Trap: Complex systems require the vast majority of improvements from interconnected changes—individual optimizations create illusion of progress while missing systemic impact→ Quantum Superposition Planning: Test multiple city configurations simultaneously rather than sequential scenarios—compress 40 years of urban experience into months of simulation→ Agents with Feelings: AI agents embedded with emotional models (joy, fear, anger, sadness) provide qualitative experience data impossible to capture from human stakeholders→ Portfolio Voting Revolution: Beyond binary decisions—split voting percentages across options like investment portfolios, enabling nuanced collective optimization→ Traditional systems modeling: Sequential scenario testing vs. Quantum approach: Parallel reality simulation with dramatic efficiency gainsThe Innovation: Humanized Agent-Based Modeling (h-ABM) creates digital beings with memory, perception, and emotional responses that navigate virtual systems, accumulating experiences and providing stakeholder insights traditional analytics cannot capture.Strategic Application: Any complex ecosystem requiring multi-stakeholder optimization—from organizational transformation to supply chain design—can leverage quantum-enhanced modeling with emotionally-intelligent agents.Strategic Reframe: The most adaptive ecosystems will shift from asking "How do we optimize individual components?" to understanding: "How do we architect systems where quantum-enhanced agents can help us reveal the hidden interdependencies that single-solution approaches systematically miss?"#EcosystemicFutures #QuantumComputing #SystemsThinking #UrbanPlanning #MIT #ComplexSystems #AgentBasedModelingGuest: Dr. Parfait Atchadé, Research Affiliate, MIT Media Lab | Strategic Business Officer, Lighthouse DIGHost: Marco Annunziata, Co-founder, Annunziata & Desai AdvisorsSeries Hosts: Vikram Shyam, Lead Futurist, NASA Glenn Research Center Dyan Finkhousen, Founder & CEO, Shoshin WorksEcosystemic Futures is provided by NASA Convergent Aeronautics Solutions Project in collaboration with Shoshin Works.