Podcasts about Univariate

In this installment of the Longevity & Aging Series, Dr. Jon Berner from the Woodinville Psychiatric Associates in Woodinville, WA, joined host Dr. Evgeniy Galimov to discuss a research paper he co-authored that was published in Volume 16, Issue 14 of Aging (Aging-US), entitled, “mTORC1 activation in presumed classical monocytes: observed correlation with human size variation and neuropsychiatric disease.” DOI - https://doi.org/10.18632/aging.206033 Corresponding author - Jon Berner - jonbernermd@gmail.com Video interview - https://www.youtube.com/watch?v=45L89MaJ7qA Abstract Background: Gain of function disturbances in nutrient sensing are likely the largest component in human age-related disease. Mammalian target of rapamycin complex 1 (mTORC1) activity affects health span and longevity. The drugs ketamine and rapamycin are effective against chronic pain and depression, and both affect mTORC1 activity. Our objective was to measure phosphorylated p70S6K, a marker for mTORC1 activity, in individuals with psychiatric disease to determine whether phosphorylated p70S6K could predict medication response. Methods: Twenty-seven females provided blood samples in which p70S6K and phosphorylated p70S6K were analyzed. Chart review gathered biometric measurements, clinical phenotypes, and medication response. Questionnaires assessed anxiety, depression, autism traits, and mitochondrial dysfunction, to determine neuropsychiatric disease profiles. Univariate and multivariate statistical analyses were used to identify predictors of medication response. Results: mTORC1 activity correlated highly with both classical biometrics (height, macrocephaly, pupil distance) and specific neuropsychiatric disease profiles (anxiety and autism). Across all cases, phosphorylated p70S6K was the best predictor for ketamine response, and also the best predictor for rapamycin response in a single instance. Conclusions: The data illustrate the importance of mTORC1 activity in both observable body structure and medication response. This report suggests that a simple assay may allow cost-effective prediction of medication response. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206033 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, ketamine, lithium, monocyte, mTORC1, rapamycin About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) Please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.29.534696v1?rss=1 Authors: Goltermann, J., Winter, N. R., Gruber, M., Fisch, L., Richter, M., Grotegerd, D., Dohm, K., Meinert, S., Leehr, E. J., Böhnlein, J., Kraus, A., Thiel, K., Winter, A., Flinkenflügel, K., Leenings, R., Barkhau, C., Ernsting, J., Berger, K., Minnerup, H., Straube, B., Alexander, N., Jamalabadi, H., Stein, F., Brosch, K., Wroblewski, A., Thomas-Odenthal, F., Usemann, P., Teuteberg, L., Pfarr, J., Jansen, A., Nenadic, I., Kircher, T., Gaser, C., Opel, N., Hahn, T., Dannlowski, U. Abstract: Introduction: Statistical effect sizes are systematically overestimated in small samples, leading to poor generalizability and replicability of findings in all areas of research. Due to the large number of variables, this is particularly problematic in neuroimaging research. While cross-validation is frequently used in multivariate machine learning approaches to assess model generalizability and replicability, the benefits for mass-univariate brain analysis are yet unclear. We investigated the impact of cross-validation on effect size estimation in univariate voxel-based brain-wide associations, using body mass index (BMI) as an exemplary predictor. Methods: A total of n=3401 adults were pooled from three independent cohorts. Brain-wide associations between BMI and gray matter structure were tested using a standard linear mass-univariate voxel-based approach. First, a traditional non-cross-validated analysis was conducted to identify brain-wide effect sizes in the total sample (as an estimate of a realistic reference effect size). The impact of sample size (bootstrapped samples ranging from n=25 to n=3401) and cross-validation on effect size estimates was investigated across selected voxels with differing underlying effect sizes (including the brain-wide lowest effect size). Linear effects were estimated within training sets and then applied to unseen test set data, using 5-fold cross-validation. Resulting effect sizes (explained variance) were investigated. Results: Analysis in the total sample (n=3401) without cross-validation yielded mainly negative correlations between BMI and gray matter density with a maximum effect size of R2p=.036 (peak voxel in the cerebellum). Effects were overestimated exponentially with decreasing sample size, with effect sizes up to R2p=.535 in samples of n=25 for the voxel with the brain-wide largest effect and up to R2p=.429 for the voxel with the brain-wide smallest effect. When applying cross-validation, linear effects estimated in small samples did not generalize to an independent test set. For the largest brain-wide effect a minimum sample size of n=100 was required to start generalizing (explained variance greater than 0 in unseen data), while n=400 were needed for smaller effects of R2p=.005 to generalize. For a voxel with an underlying null effect, linear effects found in non-cross-validated samples did not generalize to test sets even with the maximum sample size of n=3401. Effect size estimates obtained with and without cross-validation approached convergence in large samples. Discussion: Cross-validation is a useful method to counteract the overestimation of effect size particularly in small samples and to assess the generalizability of effects. Train and test set effect sizes converge in large samples which likely reflects a good generalizability for models in such samples. While linear effects start generalizing to unseen data in samples of n greater than 100 for large effect sizes, the generalization of smaller effects requires larger samples (n greater than 400). Cross-validation should be applied in voxel-based mass-univariate analysis to foster accurate effect size estimation and improve replicability of neuroimaging findings. We provide open-source python code for this purpose (https://osf.io/cy7fp/?view_only=a10fd0ee7b914f50820b5265f65f0cdb). Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.21.533634v1?rss=1 Authors: Martel, A., Bruno, N., Robertson, I. H., Dockree, P. M., Sitt, J. D., Valero-Cabre, A. Abstract: Mind-wandering is typically characterized by the common experience wherein attention veers off into thoughts unrelated to the task at hand. Recent research highlights the intentionality dimension of mind-wandering as a key predictor of adverse functional outcomes with intentional and unintentional task-unrelated thought (TUT) differentially linked to neural, behavioral, clinical, and functional correlates. We here aimed to elucidate the electrophysiological underpinnings of intentional and unintentional TUT by systematically examining the individual and collective discriminative power of a large set of EEG markers to distinguish between attentional states. Univariate and multivariate analyses were conducted on 54 predefined markers belonging to four conceptual families: ERP, spectral, information theory and connectivity measures, extracted from scalp EEG recordings prior to multidimensional reports of ongoing thought from participants performing a sustained attention task. We report here that on-task, intentional and unintentional TUT exhibit distinct electrophysiological signatures in the low frequency range. More specifically, increased features of the theta frequency range were found to be most discriminative between on-task and off-task states, while features within the alpha band were characteristic of intentional TUT when compared to unintentional TUT. This result is theoretically well aligned with contemporary accounts describing alpha activity as an index of internally oriented attention and a potential mechanism to shield internal processes from sensory input. Our study verifies the validity of the intentionality dimension of mind-wandering and represents a step forward towards real-time detection and mitigation of maladaptive mind-wandering. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.01.530578v1?rss=1 Authors: Walton-Doyle, C., Heim, B., Sinclair, E., Hollywood, K., Milne, J., Holzknecht, E., Stefani, A., Hogl, B., Seppi, K., Silverdale, M., Poewe, W., Barran, P., Trivedi, D. K. Abstract: Background: Parkinson's Disease (PD) has been associated with a distinct odour, strongest in sebum-rich areas. Thermal Desorption Gas Chromatography Mass Spectrometry (TDGCMS) has revealed volatile signatures that distinguish individuals with Parkinson's Disease (PD) from healthy controls. Here, we applied the same method, including subjects with isolated REM sleep behaviour disorder (iRBD) to examine the volatiles in sebum and compare this with that found in PD subjects and control participants. Participants with iRBD have a high likelihood for conversion to overt clinical synucleinopathies like PD, Dementia with Lewy Bodies (DLB) or (less commonly) Multiple System Atrophy (MSA). Methods: Subjects with clinically established PD (n=16) or iRBD (n=9) as well as healthy controls (n=9) were included. Following methods established in our laboratory, sebum was sampled from each participant using cotton gauze and the headspace from these swabs, analysed directly with TDGCMS. Univariate and multivariate analysis was employed to probe the differences between volatile metabolites found for each phenotype. Putative identifications were assigned using spectral matching against the Golm metabolome and NIST spectral databases. Findings: We can completely classify each phenotype using the sampled volatilome from which we built models with logistic regression analysis. The classification between PD and control improved on previously published work, from 85% to 100%. Putatively annotated molecules include alkanes, aldehydes, fatty acid methyl esters (FAMEs), and three metabolites namely purine, tropinone and oleamide. Investigation of highly ranked features revealed 18 features that showed intermediate expression in samples from iRBD participants. Interpretation: TDGCMS can differentiate volatile metabolite signatures from sebum between PD, RDB and control samples. More than 70% of the identifiable metabolites that 2 permit this discrimination were putatively annotated as hydrocarbons and fatty acid methyl esters (FAMEs). Our prior work indicates that these components arise from larger lipid molecules that decompose during the experiment. Features putatively annotated as tropinone, oleamide and purine, have previously been linked with neuroprotection, sleep induction and antioxidation, respectively, are significantly different between the three groups of participants, along with FAMEs and hydrocarbons. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.14.519204v1?rss=1 Authors: DeRosa, J., Kim, H., Lewis-Peacock, J., Banich, M. Abstract: Recently multi-voxel pattern analysis has verified the removal of information from working memory (WM) via three distinct operations replacement, suppression, or clearing compared to information being maintained (Kim et al., 2020). Univariate analyses and classifier importance maps indicate that some brain regions commonly contribute to these operations. This study aimed to use multivariate approaches to determine whether, within these commonly activated brain regions, each of these operations is being represented in a similar or distinct manner. To do so, we used Leiden community detection to identify brain networks that are characterized by similar multi-voxel patterns of activity with regard to these WM operations. Four networks were identified. The Visual Network shows similar multi-voxel patterns for maintain and replace, which are highly dissimilar from suppress and clear, suggesting this network differentiates whether an item is held in WM or not. The Somatomotor Network shows distinct multi-voxel patterns for clear relative to the other operations, suggesting that this network diff in clearing information from WM. The Default Mode Network has distinct patterns for suppress and clear, also suggesting that clearing information from WM is distinct from suppressing it. The Frontoparietal Control Network displays distinct multi-voxel patterns for each of the four operations, suggesting that this network has high involvement in regulating the flow of information within WM. These results indicate that how information is removed from WM depends on distinct brain networks that each have a particular manner in which their co-activation patterns represent these operations. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In this JCO Article Insights episode, Davide Soldato summarizes two articles from the January 10th, 2023 Journal of Clinical Oncology issue: “Low-Intensity Chemotherapy for Early Breast Cancer in Older Women: Results From the Prospective Multicenter HOPE Trial” and “Inflammation and Clinical Decline After Adjuvant Chemotherapy: Results From the Hurria Older Patients Prospective Study .” Both articles report on clinical outcomes of elderly patients treated with chemotherapy for early-stage breast cancer. TRANSCRIPT Davide Soldato: Thank you for joining JCO Article Insights. I'm Davide Soldato. Today I will be providing summaries for two different articles focused on elderly patients treated for early-stage breast cancer. Both articles are reported from the Hurria Older Patients With Breast Cancer Study. This study is also known as the HOPE Study, and it was a multicenter, prospective, study of patients aged 65 years and older treated with current standard (Neo)adjuvant chemotherapy regimens for early-stage breast cancer. The study captured several detailed geriatric clinical and treatment data from 500 patients that were recruited between September 2011 and May 2017 in 16 sites across the United States. The first article is titled ‘Low-intensity Adjuvant Chemotherapy for Breast Cancer in Older Women'. In this article, Dr. Sedrak and colleagues used data from the HOPE Study to investigate the incidence of chemotherapy administration with low relative dose intensity, associated risk factors, and relationship with survival outcomes. Previous data already showed that the receipt of chemotherapy with a low relative dose intensity is associated with inferior survival outcomes, and the commonly used threshold to define a low relative dose intensity is 85%. And this same threshold was used inside of the study that I am reporting. Elderly patients that are treated with chemotherapy are at higher risk of receiving chemotherapy with low relative dose intensity because of toxicity. However, previous data on the topic was mainly retrospective in nature and reported heterogeneous rates of low relative dose intensity up to 75%. And also, little information was available on risk factors and on the impact on survival outcomes. So, considering the paucity and the quality of the previous data and the potential clinical implication for survival outcomes, results of the HOPE Study are extremely relevant to clinical practice as they provide novel insight on the topic from a prospective multicenter study. In the analysis that was reported in the January issue of JCO, the authors excluded patients with HER-2 positive disease, those receiving nonstandard chemotherapy regimens, and those with upfront chemotherapy dose reduction. The final analytic cohort included 322 patients with a median age of 70 years, 44% with stage II, and 22% with stage III disease. Docetaxel and cyclophosphamide, and anthracycline-based chemotherapy, and this one, either alone or with subsequent paclitaxel, were the most commonly used chemotherapy regimens. Additionally, 85% of patients received a primary prophylaxis with G-CSF. Relative dose intensity was variable in the study. More than half of the patients received full course chemotherapy with 100% relative dose intensity. However, the incidence of low relative dose intensity in the HOPE study was still 21%, thus identifying a subset of patients who received chemotherapy with a suboptimal dose intensity. The rates of low relative dose intensity were higher for patients receiving either anthracycline-based chemotherapy and those with a planned treatment duration over 12 weeks. The authors developed a multivariable logistic regression model with stepwise selection to identify risk factors associated with low relative dose intensity. The results of this analysis showed that an age higher than 76 years, administration of anthracycline and CMF-based regimens, and a physician-rated Karnofsky Performance Status under 90 were associated with higher risk of low relative dose intensity ranging from 3 to 5 times greater compared to reference categories. Then the authors realized another model where they used the previously mentioned three variables, but they also adjusted for relevant clinical characteristics, including age, stage, liver and renal function, and also previous cardiovascular disease. And in this model, the three variables that were observed previously— age, type of chemotherapy, and Karnofsky Performance Status—remained significantly associated with higher risk of receiving chemotherapy with a low relative dose intensity. Finally, the Authors evaluated the association between a low relative dose intensity and survival outcomes, specifically breast cancer-specific mortality, non-breast cancer-specific mortality, and overall survival. Patients who received the chemotherapy with a low relative dose intensity had a significantly lower overall survival, and this association persisted even after excluding patients older than 76 years. A higher risk of both breast cancer and non-breast cancer mortality was observed in patients with low relative dose intensity chemotherapy. However, the number of cause-specific events was too low to obtain statistical significance for both these endpoints. In conclusion, the study by Dr. Sedrak and colleagues provides several relevant information for clinical practice. First, the HOPE study demonstrates that the administration of chemotherapy to elderly patients while maintaining an appropriate relative dose intensity is feasible. However, 1 in 5 patients received chemotherapy with a low relative dose intensity. So the results of this study reinforced the need to identify upfront patients most likely to require dose reduction. And these patients should be proactively supported during the administration of chemotherapy to ensure that appropriate toxicity management can reduce the risk of low relative dose intensity. Second, in the study, the authors observed a significant association between a low relative dose intensity and the CARG and CARG-BC scores. These scores were previously validated to predict chemotherapy toxicity. The presence of this association is important because it suggests that these validated scores can be used routinely in clinical practice to identify patients that might benefit from a comprehensive geriatric assessment to optimize comorbidities treatments and assure optimal delivery of chemotherapy. Finally, longer follow-up will provide the opportunity to establish if the higher mortality that was observed in the HOPE study in patients receiving chemotherapy with a low relative dose intensity is consequent to the low chemotherapy efficacy or to a clinical decline that might be consequent to chemotherapy itself. I will now move to the second article titled ‘Inflammation and Clinical Decline After Adjuvant Chemotherapy in Older Adults With Breast Cancer'. This article was published by Dr. Ji and colleagues, and it describes a secondary analysis of the HOPE study. In this specific manuscript, the authors wanted to evaluate the potential predictive role of baseline inflammatory biomarkers on the risk of clinical decline after administration of chemotherapy. In the HOPE study, the authors collected information on frailty stages, pre and post-chemotherapy using the Deficit-Accumulation Index (DAI): this is a 50-item scale that evaluates deficits in physical activity of daily living, instrumental activities of daily living, psychosocial status, nutrition, frequency of falls, number of medications, comorbid conditions, social support, and laboratory values. The inflammatory biomarkers that were evaluated in the current study were CRP and IL-6, and their levels were determined on pre-chemotherapy blood specimens. Using the deficit accumulation index score, patients were categorized pre-chemotherapy as being robust, pre-frail, or frail; this is important because previous studies already demonstrated that there is a significant association between this categorization and morbidity and mortality outcomes in older adults. The primary outcome of the study was a chemotherapy-induced clinical decline that was defined as a decline from a robust stage pre-chemotherapy to a pre-frail or frail status after chemotherapy. The overall analytic cohorts included 295 robust women. The median age was 69, 62% of patients had stage II or III disease, median number of comorbidities was 1.9, and mean BMI was 28.5. One in 4 older women included in the study experienced a chemotherapy-induced decline in frailty status, so this means that they transitioned from a robust status pre-chemotherapy to a pre-frail or frail status after chemotherapy. This decline in frailty status was more frequent among patients with a higher BMI, those with more comorbidities, and those with stage II and III disease. Additionally, the patients who experienced chemotherapy-induced decline had higher baseline levels of both IL-6 and CRP. Univariate analysis also showed that patients with high IL-6 and CRP had a threefold higher risk of experiencing chemotherapy-induced decline in frailty stages. This association between higher inflammation and the decline in frailty status remained significant in a multivariable logistic regression analysis that was adjusted for relevant clinical and demographic characteristics, including age, stage, race, education, BMI, breast cancer surgery, anti-inflammatory medication, and number of comorbidities. Specifically, the results of these models showed that patients who had both high CRP and IL-6 at baseline had a threefold higher risk of experiencing a decline in frailty status. So, in conclusion, this study shows a significant association between systemic inflammation and a decline in frailty status in elderly patients receiving chemotherapy for early-stage breast cancer. From a biological perspective, these higher levels of systemic inflammation might be a direct byproduct of a more advanced biological aging following the accumulation of senescent cells. There are several intriguing future perspectives that come from this study. First, if validated in additional cohorts, these findings might lead to higher treatment personalization thanks to the identification of patients at risk of clinical decline based on clinical characteristics but also on systemic inflammation. And these patients could be then proactively supported during chemotherapy to try and reduce the appearance of the clinical decline. Second, we know that inflammation is a potentially targetable pathway, and previous data obtained in breast cancer patients showed the potential of behavioral, exercise, and dietary interventions in modulating systemic inflammation. So, based on this new information, if validated in additional cohorts, future research should then evaluate if this interventions can be used to treat and eventually prevent the decline in frailty status in patients with high baseline systemic inflammation before receiving chemotherapy. This is Davide Soldato in this episode of JCO Article Insights. We discussed two publications: ‘Low-intensity Adjuvant Chemotherapy for Breast Cancer in Older Women: Results from the Prospective Multicenter HOPE Trial',  and the second one, ‘Inflammation and Clinical Decline After Adjuvant Chemotherapy in Older Adults with Breast cancer: Results from the Hurria Older Patients Prospective Study'. Thank you for your attention, and stay tuned for the next episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.   Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.    Like, share and subscribe so you never miss an episode and leave a rating or review. Articles Low-intensity Adjuvant Chemotherapy for Breast Cancer in Older Women Inflammation and Clinical Decline After Adjuvant Chemotherapy in Older Adults With Breast Cancer Find more articles from the January 10 issue.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.08.515495v1?rss=1 Authors: Turney, I. C., Chamberlain, J. D., Hakun, J. G., Steinkrauss, A. C., Ross, L. A., Kirchhoff, B. A., Dennis, N. A. Abstract: The growing population of older adults emphasizes the need to develop interventions that prevent or delay some of the cognitive decline that accompanies aging. In particular, as memory impairment is the foremost cognitive deficit affecting older adults, it is vital to develop interventions that improve memory function. This study addressed the problem of false memories in aging by training older adults to use details of past events during memory retrieval to distinguish targets from related lures. We examined the neural basis of a retrieval-based monitoring strategy by assessing changes in univariate BOLD activity and discriminability of targets and lures pre and post training. Results showed training-related decreases in false memory rates with no alterations to hit rates. Training and practice were associated with altered recruitment of a frontoparietal monitoring network as well as benefits to neural discriminability within network regions. Participants with lower baseline neural discriminability between target and lure items exhibited the largest changes in neural discriminability. Collectively, our results highlight the benefits of training for reductions of false memories in aging. They also provide an understanding of the neural mechanisms that support these reductions. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Evaluating the efficacy of sonification for signal detection in univariate, evenly sampled light curves using astronify by J. Tucker Brown et al. on Monday 12 September Sonification is the technique of representing data with sound, with potential applications in astronomy research for aiding discovery and accessibility. Several astronomy-focused sonification tools have been developed; however, efficacy testing is extremely limited. We performed testing of astronify, a prototype tool for sonification functionality within the Barbara A. Mikulski Archive for Space Telescopes (MAST). We created synthetic light curves containing zero, one, or two transit-like signals with a range of signal-to-noise ratios (SNRs=3-100) and applied the default mapping of brightness to pitch. We performed remote testing, asking participants to count signals when presented with light curves as a sonification, visual plot, or combination of both. We obtained 192 responses, of which 118 self-classified as experts in astronomy and data analysis. For high SNRs (=30 and 100), experts and non-experts performed well with sonified data (85-100% successful signal counting). At low SNRs (=3 and 5) both groups were consistent with guessing with sonifications. At medium SNRs (=7 and 10), experts performed no better than non-experts with sonifications but significantly better (factor of ~2-3) with visuals. We infer that sonification training, like that experienced by experts for visual data inspection, will be important if this sonification method is to be useful for moderate SNR signal detection within astronomical archives and broader research. Nonetheless, we show that even a very simple, and non-optimised, sonification approach allows users to identify high SNR signals. A more optimised approach, for which we present ideas, would likely yield higher success for lower SNR signals. arXiv: http://arxiv.org/abs/http://arxiv.org/abs/2209.04465v1

A bite-sized episode where we each share 1 brain-related thing we learnt that you can use so level up your life...in less than 5 (maybe 6) minutes. Think biases, mental models, thinking tools and the latest science on how to live a better life.  If you're loving the show, please do us a teeny tiny favour and subscribe/follow on your favourite podcast platform. It helps us massively and we help you get the latest BrainTools episode as soon as it drops.  Where can you connect with us? Instagram: @braintoolspodcast TikTok: @braintools Website: www.braintools.com.au    

Host: Esteban Figueroa, MD Exploring the ACE Index in Acute Ulcerative Colitis Rebecca K Grant, Gareth-Rhys Jones, Nikolas Plevris, Ruairi W Lynch, Philip W Jenkinson, Charlie W Lees, Thomas A Manship, Fiona A M Jagger, William M Brindle, Mrithula Shivakumar, Jack Satsangi, Ian D R Arnott Background: Intravenous (IV) steroids remain the first-line treatment for patients with acute ulcerative colitis (UC). However, 30% of patients do not respond to steroids, requiring second-line therapy and/or surgery. There are no existing indices that allow physicians to predict steroid nonresponse at admission. We aimed to determine if admission biochemical and endoscopic values could predict response to IV steroids. Methods: All admissions for acute UC (ICD-10 K51) between November 1, 2011, and October 31, 2016 were identified. Case note review confirmed diagnosis; clinical, endoscopic, and laboratory data were collected. Steroid response was defined as discharge home with no further therapy for active UC. Nonresponse was defined as requirement for second-line therapy or surgery. Univariate and binary logistic regression analyses were employed to identify factors associated with steroid nonresponse. Results: Two hundred and thirty-five acute UC admissions were identified, comprising both acute severe and acute nonsevere UC; 155 of the 235 patients (66.0%) …

Host: Esteban Figueroa, MD Exploring the ACE Index in Acute Ulcerative Colitis Rebecca K Grant, Gareth-Rhys Jones, Nikolas Plevris, Ruairi W Lynch, Philip W Jenkinson, Charlie W Lees, Thomas A Manship, Fiona A M Jagger, William M Brindle, Mrithula Shivakumar, Jack Satsangi, Ian D R Arnott Background: Intravenous (IV) steroids remain the first-line treatment for patients with acute ulcerative colitis (UC). However, 30% of patients do not respond to steroids, requiring second-line therapy and/or surgery. There are no existing indices that allow physicians to predict steroid nonresponse at admission. We aimed to determine if admission biochemical and endoscopic values could predict response to IV steroids. Methods: All admissions for acute UC (ICD-10 K51) between November 1, 2011, and October 31, 2016 were identified. Case note review confirmed diagnosis; clinical, endoscopic, and laboratory data were collected. Steroid response was defined as discharge home with no further therapy for active UC. Nonresponse was defined as requirement for second-line therapy or surgery. Univariate and binary logistic regression analyses were employed to identify factors associated with steroid nonresponse. Results: Two hundred and thirty-five acute UC admissions were identified, comprising both acute severe and acute nonsevere UC; 155 of the 235 patients (66.0%) …

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Even if you have a nail, not all hammers are the same, published by PhilGoetz on the AI Alignment Forum. (Related to Over-ensapsulation and Subtext is not invariant under linear transformation) Between 2004 and 2007, Goran Bjelakovic et al. published 3 famous meta-analysis of vitamin supplements, concluding that vitamins don't help people but instead kill people. This is now the accepted dogma; and if you ask your doctor about vitamins, she's likely to tell you not to take them, based on reading either one of these articles, or one of the many summaries of these articles made in secondary sources like The Mayo Clinic Journal. The 2007 study claims that beta-carotene and vitamins A and E are positively correlated with death - the more you take, the more likely you are to die. Therefore, vitamins kill. The conclusion on E requires a little explanation, but the data on beta-carotene and A is simple and specific: Univariate meta-regression analyses revealed significant influences of dose of beta carotene (Relative Risk (RR), 1.004; 95% CI, 1.001-1.007; P = .012), dose of vitamin A (RR, 1.000006; 95% CI, 1.000002-1.000009; P = .003), ... on mortality. This appears to mean that, for each mg of beta carotene that you take, your risk of death increases by a factor (RR) of 1.004; for each IU of vitamin A that you take, by a factor of 1.000006. "95% CI, 1.001-1.007" means that the standard deviation of the sample indicates a 95% probability that the true RR lies somewhere between 1.001 and 1.007. "P = .012" means that there's only a 1.2% chance that you would be so unlucky as to get a sample giving that result, if in fact the true RR were 1. A risk factor of 1.000006 doesn't sound like much; but I'm taking 2,500 IU of vitamin A per day. That gives a 1.5% increase in my chance of death! (Per 3.3 years.) And look at those P-values: .012, .003! So why do I still take vitamins? What all of these articles do, in excruciating detail with regard to sample selection (though not so much with regard to the math), is to run a linear regression on a lot of data from studies of patients taking vitamins. A linear regression takes a set of data where each datapoint looks like this: Y = a1X1 + c and a multiple linear regression takes a set of data where each datapoint usually looks like this: Y = a1X1 + a2X2 + ... anXn + c where Y and all the Xi's are known. In this case, Y is a 1 for someone who died and a 0 for someone who didn't, and each Xi is the amount of some vitamin taken. In either case, the regression finds the values for a1, ... an, c that best fit the data (meaning they minimize the sum, over all data points, of the squared error of the value predicted for Y, (Y - (a1X1 + a2X2 + ... anXn + c)2). Scientists love linear regression. It's simple, fast, and mathematically pure. There are lots of tools available to perform it for you. It's a powerful hammer in a scientists' toolbox. But not everything is a nail. And even for a nail, not every hammer is the right hammer. You shouldn't use linear regression just because it's the "default regression analysis". When a paper says they performed "a regression", beware. A linear analysis assumes that if 10 milligrams is good for you, then 100 milligrams is ten times as good for you, and 1000 milligrams is one-hundred times as good for you. This is not how vitamins work. Vitamin A is toxic in doses over 15,000 IU/day, and vitamin E is toxic in doses over 400 IU/day (Miller et al. 2004, Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality; Berson et al. 1993, Randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa.). The RDA for vitamin A is 2500 IU/day for adults. Good dosage levels for vitamin A appear to be under 10,000 IU/day, and for E, less than 300 IU/day. (Sadly, studies rarel...

19. How can you define outlier? The sample answer is A data analyst interview question and answers guide will not complete without this question. An outlier is a term commonly used by data analysts when referring to a value that appears to be far removed and divergent from a set pattern in a sample. There are two kinds of outliers – Univariate and Multivariate. The two methods used for detecting outliers are: · Box plot method – According to this method, if the value is higher or lesser than 1.5*IQR (interquartile range), such that it lies above the upper quartile (Q3) or below the lower quartile (Q1), the value is an outlier. · Standard deviation method – This method states that if a value is higher or lower than mean ± (3*standard deviation), it is an outlier. --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.22.393199v1?rss=1 Authors: Pistono, A., Senoussi, M., Guerrier, L., Rafiq, M., Gimeno, M., Peran, P., Jucla, M., Pariente, J. Abstract: Language production deficits occur early in the course of Alzheimer's disease (AD); however, only few studies have focused on language functional networks in prodromal AD. The current study aims to uncover the extent of language alteration at a prodromal stage, on a behavioral, structural and functional level, using univariate and multivariate analyses. Twenty-four AD participants and 24 matched healthy controls underwent a comprehensive language evaluation, a structural T1-3D MRI and resting-state fMRI. We performed seed-based analyses, using the left inferior frontal gyrus and left posterior temporal gyrus as seeds. Then, we analyzed connectivity between executive control networks and language network in each group. Finally, we used multivariate pattern analyses to test whether the two groups could be distinguished based on the pattern of atrophy within the language network; atrophy within the executive control networks, as well as the pattern of functional connectivity within the language network; and functional connectivity within executive control networks. AD participants had language impairment during standardized language tasks and connected-speech production. Univariate analyses were not able to discriminate participants at this stage, while multivariate pattern analyses could significantly predict the group membership of prodromal patients and healthy controls, both when classifying atrophy patterns or connectivity patterns of the language network. Language functional networks could discriminate AD participants better than executive control networks. Most notably, they revealed an increased connectivity at a prodromal stage. Multivariate analyses represent a useful tool for investigating the functional and structural (re-)organization of the neural bases of language. Copy rights belong to original authors. Visit the link for more info

Towards improved characterization of immune-related adverse events in the setting of pre-existing autoimmune disease. TRANSCRIPT This JCO Podcast provides observations and commentary on the JCO article “Immune Checkpoint Inhibitor Therapy in Patients with Preexisting Inflammatory Bowel Disease”, by Abu-Sbeih et al. My name is Katy Tsai, and I am Assistant Professor of Medicine in the Division of Hematology/Oncology at the University of California, San Francisco. My oncologic specialty is the treatment of advanced melanoma and non-melanoma skin cancers.   Immune checkpoint inhibitors, referred to as ICIs in this podcast, have transformed the landscape of treatment options in oncology. While ICIs were first approved for the treatment of advanced melanoma in 2011, since that time, ICIs have shown activity in a variety of other histologies. Anti-PD-1 or anti-PD-L1, with or without anti-CTLA-4, are now approved for the treatment of lung cancer, head and neck squamous cell carcinoma, renal cell carcinoma, and many others. While ICIs can result in durable responses, their continued use can be limited by the development of immune-related adverse eventsimmune-related adverse events. Because these events are believed to be autoimmune in nature, there are intuitive safety concerns about ICI use in patients with known autoimmune disease. Can patients with pre-existing autoimmune disease be safely treated with ICI? Are these patients more likely to experience immune-related adverse events related to their autoimmune disease? Is this risk increased if their autoimmune disease is severe, with a history of required immunosuppression? These are all important questions faced by healthcare providers, questions which are not well studied due to the exclusion of patients with known autoimmune disease from pivotal ICI clinical trials.   To address these questions, Abu-Sbeih and colleagues chose to focus on ICI use in patients with pre-existing inflammatory bowel disease. This is a clinically relevant population of interest, given the relatively high incidence of immune-related diarrhea and colitis with ICI use; these immune-related adverse events occur in almost half of patients receiving combination anti-CTLA-4 and anti-PD-1 or PD-L1, about one-third of patients receiving anti-CTLA-4, and less frequently in patients receiving anti-PD-1 or PD-L1 alone. Abu-Sbeih and colleagues conducted a retrospective, multicenter study in which 102 patients – half with Crohn’s disease, half with ulcerative colitis – received ICI between 2010 and 2019. 17 patients received anti-CTLA-4, and 85 received anti-PD-1 or anti-PD-L1. This is a notable cohort of patients, as previous meta-analyses have reported on the safety of ICI use in much smaller numbers of patients with inflammatory bowel disease, and with less detailed clinical characterization of their inflammatory bowel disease. Univariate and multivariate logistic regression were used to assess the risk of gastrointestinal, or GI, adverse events, and was compared to a control population of 11,377 ICI-treated patients without inflammatory bowel disease, from the same participating institutions.   An important observation made by the authors was that the rate of GI immune-related adverse events in the inflammatory bowel disease cohort was significantly higher at 41%, compared to 11% in the non-inflammatory bowel disease cohort. Univariate analysis identified anti-CTLA-4 (given as monotherapy or in combination) as a risk factor for GI immune-related adverse events compared to anti-PD-1/L1 therapy but showed only a tendency toward significance in multivariate analysis, as did inflammatory bowel disease involving the colon. Although none of the collected clinical variables reached significance in multivariate analysis, the authors’ analysis of outcomes in the inflammatory bowel disease cohort is illuminating. Of the 41 inflammatory bowel disease patients who developed diarrhea, 51% had peak grade 3 or 4 diarrhea, 76% received glucocorticoids, and 29% required additional immunosuppression with infliximab or vedolizumab. 4% developed colonic perforation, with half of those patients requiring surgical intervention. Also of note, patients who were identified as having active inflammatory bowel disease within 3 months of ICI start had higher grade diarrhea compared to patients with inactive inflammatory bowel disease. Endoscopy data were also available for 48 inflammatory bowel disease patients. Interestingly, of the 41 patients who were noted to have normal or mild inflammatory findings, 18 (43%) developed any GI immune-related adverse events, 5 (12%) of which were grades 3-4. In the 7 patients with moderate/severe inflammatory findings, 5 (71%) had GI immune-related adverse events of any grade, 2 (29%) of which were grades 3-4.   Despite the higher rate of GI immune-related adverse events and associated complications in the inflammatory bowel disease cohort compared to the non-inflammatory bowel disease cohort, there were no fatalities. Additionally, 48% of patients in the inflammatory bowel disease cohort were identified as having complete response, partial response, or stable disease to ICI therapy, a clinical benefit rate similar to those reported in ICI clinical trials. It seems, then, that the benefits of ICI therapy in this population may well outweigh the risks, particularly for patients with inflammatory bowel disease who may have no viable alternative therapy available for their malignancy.   Overall, despite the inherent limitations of retrospective analysis, this work represents the largest study to date investigating the risk of GI immune-related adverse events in patients with cancer and comorbid inflammatory bowel disease who were treated with ICIs. It provides evidence for increased incidence and severity of GI immune-related adverse events, and complications thereof, in a well-annotated cohort of patients with inflammatory bowel disease. As these patients continued to receive clinical benefit from their ICI therapy, these findings can help better inform pre-ICI treatment counseling in patients with preexisting inflammatory bowel disease, and better prepare them for expected risks of treatment. At the same time, this work also raises a number of questions for further investigation. Is anti-CTLA-4 truly safe to use in this population, or was this limited by the small number of patients receiving anti-CTLA-4 in this study? Should ICI therapy be delayed to allow for optimal treatment of active inflammatory bowel disease, to decrease the risk of severe GI immune-related adverse events? What additional guidance can be given to providers regarding when to initiate additional immunosuppressive therapy, and should this be driven by endoscopic findings? These questions and more can and should be investigated in future larger-scale prospective studies. For the time being, based on the data presented, I would certainly be more cautious about giving a more aggressive immunotherapy regimen – that is, combination anti-CTLA-4 and anti-PD-1/L-1 – in a patient with highly symptomatic inflammatory bowel disease. Also, while numbers in this study were small, it seems that endoscopic evaluation prior to ICI start could be helpful in risk stratifying for severe GI IRAE. While inflammatory findings on endoscopy may not necessarily be an absolute contraindication to use of ICI, it seems these results would certainly be helpful in shared decision-making with the patient regarding their risk of developing GI IRAE and weighing other potential treatment options. Finally, and most importantly, this data demonstrates that some patients with inflammatory bowel disease who receive ICI for their malignancy can derive clinical benefit with manageable toxicities, suggesting that the mere presence of comorbid inflammatory bowel disease should not be a blanket exclusion criterion for ICI clinical trials.   This concludes this JCO Podcast. Thank you for listening.

This JCO Podcast provides observations and commentary on the JCO article “Resumption of Immune Checkpoint Inhibitor Therapy After Immune-Mediated Colitis” by Abu-Sbeih et al. My name is David Oh, and I am an Assistant Professor at the University of California, San Francisco. My oncologic specialty is genitourinary medical oncology and cancer immunotherapy.                                   While immune checkpoint inhibitors, or ICIs, can lead to durable responses even when other standard therapies have failed, their therapeutic window is often limited by immune-related adverse events or IRAEs which are thought to be autoimmune in nature. Immune-mediated diarrhea and colitis are a frequent IRAE with ICIs, affecting up to a third of patients receiving anti-CTLA-4, approaching half of patients receiving anti-CTLA-4 in combination with anti-PD-1 or anti-PD-L1, and less frequently patients receiving anti-PD-1 or anti-PD-L1 alone. Since there is often overlap between IRAEs and response or survival with ICIs, and IRAEs such as colitis can require interruption of treatment and immunosuppression in patients who may have failed other treatment options, many providers are faced with an important question: is it safe to resume ICIs after patients have initial diarrhea and colitis, and what are the risk factors for another episode of diarrhea and colitis? To address this question, which has not been well studied, Abu-Sbeih and colleagues in this issue of JCO performed a retrospective multicenter analysis of patients who had initial immune-mediated diarrhea and colitis requiring ICI interruption, and then subsequently resumed ICI from 2010 to 2018. From a starting population of 550 patients with initial diarrhea and colitis with ICI, they identified 167 patients who subsequently resumed ICI for a re-treatment rate of 30%. This represents a notable cohort with this degree of clinical annotation. For their initial therapy leading to diarrhea and colitis, about half of these patients had initially received anti-PD-1 or PD-L1 therapy, and a quarter each had initially received either anti-CTLA-4 therapy or combination. The majority of these patients had melanoma, with a smaller proportion of non-small cell lung and genitourinary cancer patients. At the time of re-treatment, 80% of these patients received an anti-PD-1 or anti-PD-L1 alone, while the others were re-treated with anti-CTLA-4 alone.   An important observation by the authors was that upon re-treatment of the 167 patients, 57 patients, or about a third, experienced recurrent diarrhea and colitis requiring permanent discontinuation of therapy. The grade of diarrhea and colitis most frequently seen was less severe, graded as less than or equal to Grade 2. As expected, 81% of these patients with recurrent diarrhea and colitis received steroids, while 12% of patients required further immunosuppression with either infliximab or vedolizumab which blocks the integrin alpha-4-beta-7.   Univariate and multivariate analyses were used to identify risk factors for recurrent diarrhea and colitis upon ICI resumption. Univariate analysis identified more severe initial diarrhea and colitis as a risk factor for having recurrent diarrhea and colitis on ICI re-challenge. Initial severity was determined either by longer duration of initial symptoms or requirement for initial immunosuppression. Multivariate analysis confirmed initial severity as a risk factor, and also found that a lower risk of recurrent diarrhea and colitis was associated with initial anti-CTLA-4 use, as well as with choice of anti-PD-1 or anti-PD-L1 therapy at the time of re-challenge regardless of their initial therapy. Importantly, even though resumption of anti-CTLA-4 was associated with a higher risk of recurrent diarrhea and colitis, the severity of recurrence, as determined by frequency of immunosuppression and grading of diarrhea and colitis, were actually similar to when anti-PD-1 or anti-PD-L1 were resumed.   Overall, then, despite the limitations of retrospective analysis, this work provides evidence from a substantial patient cohort across tumor and treatment types that recurrent diarrhea and colitis with ICI retreatment following initial interruption for diarrhea and colitis may occur in less than half of patients and is generally less severe. Furthermore, the risk of recurrent diarrhea and colitis is less likely in patients who had less severe episodes of initial diarrhea and colitis, who previously received initial anti-CTLA-4, or who are re-challenged with anti-PD-1 or anti-PD-L1 therapy. Although the choice of anti-PD-1 or anti-PD-L1 for re-treatment reduces the risk of recurrent diarrhea and colitis, the actual severity of recurrent episodes is similar to re-treatment with anti-CTLA-4 therapy. As a practical matter this can provide guidance to providers about whether to consider ICI resumption, and which agents to consider, based in part of characteristics of their initial treatment and IRAE. This will be particularly important for patients who experienced clinical benefit from their initial ICI therapy, or have limited other treatment options. At the same time, this work also prompts a number of questions for further investigation. Why does prior anti-CTLA-4 therapy leading to initial diarrhea and colitis yield a lower risk of recurrent episodes? Is there an association between recurrent diarrhea and colitis after ICI re-challenge and ongoing response to therapy? Finally, do different ICI-responsive cancer types exhibit higher or lower risk for recurrent diarrhea and colitis? These and other questions can be addressed by future studies involving larger and well-annotated patient cohorts at multiple centers.                                                                                              This concludes this JCO Podcast. Thank you for listening.

Background: Stigma can be detrimental to the quality of life, as well as the treatment and rehabiltation process of people with mental illness. The purpose of this study was to measure the extent and determine correlates of public and self-stigma against people with mental illness (PWMI) and their families in Jimma Zone, Southwest Ethiopia. Methods: Community and institution based quantitative and qualitative cross-sectional studies were conducted among 845 randomly selected community members at GGFRC, consecutive 422 PWMI and 422 family members of PWMI at Jimma University Specialized Hospital. Univariate, bivariate and multivariate linear regression analyses were done. Results: The mean scores of public stigma against PWMI and their family members were 2.62 (+0.34) and 2.16 (+0.49), respectively, on a range of 1 to 5. The mean self-stigma score among PWMI, on a range of 1 to 4, was 2.32 (+0.30). Place of residence, belief in the supernatural, psychosocial and biological explanations of mental illness were associated with stigma towards PWMI and family members of PWMI. Level of education and income predicted PWMI public stigma. A higher number of perceived signs of mental illness was correlated with lower stigma against family members of PWMI. Females, individuals with history of traditional treatment, individuals experiencing higher number of drug side-effects, and individuals who subscribed to more signs and supernatural explanations had significantly higher levels of self-stigma. In contrast, patients with higher education level and higher self esteem showed significantly lower levels of self-stigma. Supporting supernatural explanations of mental illness was associated with greater care-givers’ self-stigmatization. Conclusion: High public stigma against PWMI and high levels of patients’ self-stigma were found. Care-givers demonstrated reluctance to be identified with PWMI. Systematic forms of discrimination against PWMI and their family members were identified. PWMI and their family members faced behavioral and structural challenges. Thus, reducing stigma against patients may help to reduce stigma against family members. Developing strategies to improve patients’ self esteem, and developing policies and guidelines about mental illness may be helpful in reducing stigma. Effective intervention strategies that target patients, their families, as well as the public need to be designed to reduce stigma.

Background: Cytopenias are the most common HIV-associated hematological abnormality. Cytopenias have been associated with several factors including sex, race/ethnicity, geographical location and comorbidities such as tuberculosis, hepatitis B infection, fever and oral candidiasis. Cytopenias become more prevalent as HIV progresses and are often fatal. Data from resource-limited settings about the prevalence and correlates of cytopenia are limited. Therefore we conducted this cross-sectional study to assess the prevalence and correlates of cytopenia among adult AIDS patients at initiation of HAART in Uganda. Methods: 400 HIV-infected subjects who were HAART-naive or on HAART for

Background: The pattern of obesity in relation to socioeconomic status is of public health concern. This study investigates whether the association between height and obesity in children is affected by their socioeconomic background. It also explores the relationship between high birth weight and obesity. Methods: School children, (N = 557; 5 to 12 years old) were recruited from randomly selected primary schools in a cross-sectional study including 173 rural and 384 urban children in the North West Region of Cameroon. Socioeconomic status (SES) and birth weight were obtained using a self administered questionnaire. Anthropometric measures included height, weight, BMI, waist circumference and percentage body fat. These measures were transformed into age and sex-standardized variables. Then participants were divided according to quartiles of height SDS. Results: The highest frequencies of overweight/obesity (18.8%), abdominal overweight/obesity (10.9%) and high body fat/obesity (12.3%) were observed among the tallest children from a high socioeconomic background. Univariate analyses indicate that children of high SES (39.9%), fourth height quartile (33.1%) and of high birth weight (54.8%) were significantly (p

Background: In the present study factors affecting survival and toxicity in cerebral metastasized patients treated with stereotactic radiosurgery (SRS) were analyzed with special focus on radiation necrosis. Patients and methods: 340 patients with 1-3 cerebral metastases having been treated with SRS were retrospectively analyzed. Radiation necrosis was diagnosed by MRI und PET imaging. Univariate and multivariate analysis using a Cox proportional hazards regression model and log-rank test were performed to determine the prognostic value of treatment-related and individual factors for outcome and SRS-related complications. Results: Median overall survival was 282 days and median follow-up 721 days. 44% of patients received WBRT during the course of disease. Concerning univariate analysis a significant difference in overall survival was found for Karnofsky Performance Status (KPS

Background: There is partially conflicting evidence on the influence of the steroid hormones estrogen (E) and progesterone (P) on the development of ovarian cancer (OC). The aim of this study was to assess the expression of the receptor isoforms ER-alpha/-beta and PR-A/-B in OC tissue and to analyze its impact on clinical and pathological features and patient outcome. Methods: 155 OC patients were included who had been diagnosed and treated between 1990 and 2002. Patient characteristics, histology and follow-up data were available. ER-alpha/-beta and PR-A/-B expression were determined by immunohistochemistry. Results: OC tissue was positive for ER-alpha/-beta in ER-alpha/-beta and 60.1% and PR-A/-B in 36.2% and 33.8%, respectively. We identified significant differences in ER beta expression related to the histological subtype (p=0.041), stage (p=0.002) and grade (p=0.011) as well as PR-A and tumor stage (p=0.03). Interestingly, median receptor expression for ER-alpha and PR-A/-B was significantly higher in G1 vs. G2 OC. Kaplan Meier analysis revealed a good prognosis for ER-alpha positive (p=0.039) and PR-B positive (

Background: The present study examined whether craving as measured by the obsessive-compulsive drinking scale (OCDS) predict long-term outcome in alcohol-dependent inpatients. Methods: This was a 24-month prospective, observational study in 198 alcohol-dependent inpatients treated under standardized conditions. The primary outcome criterion was abstinence, defined as no subjective report or objective indication of alcohol consumption since discharge from treatment. The patients self-rated their craving for alcohol at the 6- and 12-month follow-ups by using the German version of the OCDS, which measures obsessive and compulsive aspects of craving. Univariate and logistic regression analyses with covariates were performed. Results: Of the 104 patients interviewed at the 24-month follow-up, 60% (n = 62) were abstinent. We found significant associations between total OCDS scores at 6 months and outcome at 12 months and between total OCDS scores at 12 months and outcome at 24 months: the higher the OCDS total score at one follow-up evaluation, the less likely patients were to be abstinent at the subsequent one. The same association was found for each of the two OCDS subscales, control and consequences and drinking obsessions. Conclusions: These results support earlier findings that OCDS scores can predict outcome in alcohol-dependent patients. This information can be used for the timely development of protective resources. Hence, decisions over the use of resources can be made on the basis of objectified parameters to develop a personalized treatment concept. Consequently, economic considerations can induce a reduction of high medical costs.

Background: Colonoscopy in combination with endoscopic polypectomy has been shown to be an efficient measure for reducing colorectal cancer incidence. In Germany, a colorectal cancer screening program based on colonoscopy for individuals aged 55 and above was introduced in 2002. However, for largely unknown reasons, participation rates remain low. The purpose of this study was to identify factors influencing compliance with colorectal cancer screening. Methods: A structured survey of 239 individuals aged 55-79 years ;was performed. Statistical analysis included chi(2) test, t test, principal component analysis, and logistic regression. Results: 56% of previously screened, but only 26% of non-screened individuals had received a recommendation to undergo screening colonoscopy. 50% of the non-screened believed a screening colonoscopy should only be performed in case of complaints. Univariate analysis identified participation in any secondary prevention measures (p < 0.001), concerns about colonoscopy (p < 0.012), and knowledge about colorectal cancer (p < 0.001) as critical issues distinguishing between groups. Multivariate analysis revealed that secondary prevention (p < 0.001) and concerns about colonoscopy (p = 0.026) were independent predictors of compliance with screening recommendations. Conclusion: Our survey has identified critical factors deterring compliance with colorectal cancer screening recommendations. This will help to direct future campaigns in order to increase participation in colorectal cancer screening. Copyright (C) 2010 S. Karger AG, Basel

Despite significant research efforts aimed at understanding the neurobiological underpinnings of psychiatric disorders, the diagnosis and the evaluation of treatment of these disorders are still based solely on relatively subjective assessment of symptoms. Therefore, biological markers which could improve the current classification of psychiatry disorders, and in perspective stratify patients on a biological basis into more homogeneous clinically distinct subgroups, are highly needed. In order to identify novel candidate biological markers for major depression and schizophrenia, we have applied a focused proteomic approach using plasma samples from a large case-control collection. Patients were diagnosed according to DSM criteria using structured interviews and a number of additional clinical variables and demographic information were assessed. Plasma samples from 245 depressed patients, 229 schizophrenic patients and 254 controls were submitted to multi analyte profiling allowing the evaluation of up to 79 proteins, including a series of cytokines, chemokines and neurotrophins previously suggested to be involved in the pathophysiology of depression and schizophrenia. Univariate data analysis showed more significant p-values than would be expected by chance and highlighted several proteins belonging to pathways or mechanisms previously suspected to be involved in the pathophysiology of major depression or schizophrenia, such as insulin and MMP-9 for depression, and BDNF, EGF and a number of chemokines for schizophrenia. Multivariate analysis was carried out to improve the differentiation of cases from controls and identify the most informative panel of markers. The results illustrate the potential of plasma biomarker profiling for psychiatric disorders, when conducted in large collections. The study highlighted a set of analytes as candidate biomarker signatures for depression and schizophrenia, warranting further investigation in independent collections.

Objectives: To study the value of demographic and alcohol-related variables for predicting 24-month treatment outcome in an outpatient setting. Methods: Prospective observational study with 92 alcohol-dependent patients. Assessments were made by personal interviews at the beginning and end of therapy, and at the 24-month follow-up. Univariate and logistic regression analyses were performed. Results: The mean age was 46.0 (SD = 9.9) years. There were 58 males (65.2%) and 31 females (34.8%). Of the 67 patients interviewed at 2-year follow-up, 58% were abstinent and 79% improved. Differences between abstainers and non-abstainers were found for number of previous detoxifications, and number of patients attempted suicides. In addition, female gender and a higher number of prior treatments predicted negative treatment outcome. Conclusion: Matching patients to different types of treatment by means of empirically based characteristics may help to improve outcome but research has failed to establish reliable predictors in that area. Data from this follow-up study confirm the role of certain clinical outcome predictors. Additionally, results give further evidence for outpatient treatment as an effective setting for alcohol-dependent patients as indicated by a favourable retention rate (84%) and outcome (minimum abstinence rate 44%).

The rate of axis II disorders in alcohol-dependent individuals is suggested to be high. The aim of this investigation is to assess the rate of DSM-IV axis II diagnoses in alcohol-dependent inpatients and their correlation with clinical characteristics of alcohol dependence (AD). 1,079 inpatients with DSM-IV AD from three inpatient addiction treatment centers ('qualified detoxification', open psychiatric university hospital wards) were included. Characteristics of AD were obtained using standardized structured interviews. Diagnoses of DSM-IV personality disorders (PDs) were generated with SCID-II-PQ and SCID-II interviews. Alcoholism severity was measured using the number of DSM-IV criteria endorsed and age at first drinking. Approximately 60% of the sample had at least one PD. However, rates of Axis II disorders differed significantly across centers. The most frequent PDs were obsessive-compulsive, borderline, narcissistic and paranoid PD. Diagnosis of any PD was related to a more severe clinical profile of AD. Regression analyses revealed that obsessive-compulsive PD was related to the number of DSM-IV criteria endorsed while antisocial PD was related to early age at first drinking. The majority of alcohol-dependent individuals had one or more comorbid axis II disorders. Univariate and multivariate analyses indicate that different PDs are related to age at first dinking and alcoholism severity. Copyright (c) 2009 S. Karger AG, Basel

Purpose: Ileal carcinoids are gut epithelial tumors originating from serotonin-containing enterochromaffin (EC) cells. Therapeutic options for effectively inhibiting the growth and spread of metastatic carcinoids are still limited. We aimed to identify the role of matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) during tumor development and metastasis. Patients and Methods: Tissue samples were obtained from surgically treated patients. Expression of the EC-cell marker, vesicular monoamine transporter-1 (VMAT-1), was used to verify ileal carcinoids. We investigated the differential expression of MMP-2, 7, 9, 11, and 13 and their endogenous inhibitors (TIMP-1, 2, and 3) by quantitative real-time RT-PCR in 25 primary tumors, their corresponding lymph node metastases and/or liver metastases and matched normal mucosa. Results: Significantly increased expression of VMAT-1, MMP-2, MMP-11, TIMP-1 and TIMP-3 was determined by quantitative RT-PCR in EC-cell carcinoids compared to normal intestinal mucosa (p < 0.05). In contrast, MMP-2 and MMP-9 as well as TIMP-1, TIMP-2, and TIMP-3 expression in primary tumors of patients with liver metastases (M1) was significantly lower than in patients lacking liver metastases (M0). EC-cell tumors were significantly larger in the M1 group of tumors, while VMAT-1 expression was significantly decreased. We found an inverse correlation between tumor size and prognosis. Univariate analysis further revealed that decreased expression of VMAT-1, MMP-2 and TIMP-3 in primary tumors was significantly associated with a reduced survival time of the patients. Conclusion: Our data reveal that MMP-2 and TIMP-3 expression together with VMAT-1 expression are of potential prognostic and clinical value in ileal carcinoids. Copyright (C) 2008 S. Karger AG, Basel

Objective: To validate the prognostic value of preoperative levels of CYFRA 21-1, CEA and the corresponding tumor marker index (TMI) in patients with stage I non-small cell lung cancer (NSCLC). Methods: Two hundred forty stage I NSCLC patients (80 in pT1 and 160 in pT2; 100 squamous cell carcinomas, 91 adenocarcinomas, 32 large-cell carcinomas, 17 with other histologies; 171 males and 69 females) who had complete resection (R0) between 1986 and 2004 were included in the analysis. CYFRA 21-1 and CEA were measured using the Elecsys system (Roche) and AxSym-System (Abbott), respectively. Univariate analysis was performed using the Kaplan-Meier method to identify potential associations between survival and age, gender, CYFRA 21-1, CEA and TMI. Results: Overall 3- and 5-year survival rates were 74 and 64%, respectively. Male gender (p = 0.0009) and age 1 70 years (p = 0.0041) were associated with a worse prognosis; there were no differences between pT1 and pT2 nor between histological subtypes. Three- year survival was 72% for CYFRA 21-1 levels > 3.3 ng/ml versus 75% for levels 6.7 ng/ ml versus 75% for CEA 70 years were associated with a worse outcome, but elevated levels of CEA and CYFRA 21-1, and TMI risk were not. Copyright (C) 2008 S. Karger AG, Basel.