POPULARITY
N Engl J Med 1986; 314:1547-52Background Into the mid-1980's, digoxin and diuretics were the mainstay of chronic disease management for congestive heart failure. Vasodilator agents were also commonly used based on limited data of their favorable hemodynamic effects. No sufficiently powered trials in this space had been performed to assess whether administration of vasodilators or any other agents improved long-term morbidity or mortality for heart failure patients. The V-HEFT trial was undertaken to test the hypotheses that 2 widely used vasodilator regimens (prazosin or a combination of hydralazine and isosorbide dinitrate) were superior for reducing death versus placebo. The trial was sponsored by the Veterans Administration and only enrolled men.Patients Men between the ages of 18 and 75 were recruited from 11 participating Veterans Administration hospitals and had to have chronic congestive heart failure based on either evidence of cardiac dilatation or left ventricular dysfunction (EF 0.7 ng/mL and euvolemic volume status. Clinical evaluations and exercise-tolerance tests on 2 consecutive visits, two weeks apart, had to reveal clinical and exercise stability before randomization could occur. Following randomization, patients continued to receive the optimal dose of digoxin and diuretic along with 1 of 3 study regimens. The placebo group was given placebo tablets and placebo capsules and instructed to take them 4 times a day. The prazosin group took 2.5 mg prazosin capsules and placebo tablets 4 times a day. The hydralazine-isosorbide dinitrate group took 37.5 mg hydralazine capsules and 20 mg isosorbide dinitrate tablets 4 times a day.In all groups, therapy began with 1 capsule and 1 tablet to be taken 4 times a day. In the absence of side effects, this was increased to 2 capsules and 2 tablets 4 times a day for a total of 20 mg of prazosin or 300-160 mg of hydralazine-isosorbide dinitrate. If drug-related side effects occurred, the dose could be reduced to half a tablet 4 times per day or to one capsule 2 times per day. If the dose was reduced, an attempt was made later to reinstitute the full dose.In order to limit dropouts, rigorous criteria were established for “treatment failures.” Physicians were advised to hospitalize patients with worsening symptoms, and, if appropriate, to use temporary intravenous vasodilator or inotropic interventions for stabilization. Physicians were encouraged to resume study medications upon discharge. At least 2 such hospitalizations were required, along with objective evidence of deterioration, before the study medications were discontinued and replaced with known therapy.Endpoints The primary endpoint was all-cause mortality.Results 642 patients were enrolled (273 in placebo group, 183 in prazosin group and 186 in the hydralazine-isosorbide dinitrate group). Excluding discontinuations that took place within 1 month before death, 47 patients (17%) discontinued one or both types of placebos, 43 patients (23%) discontinued prazosin, and 60 patients (32%) discontinued either one or both drugs in the hydralazine-isosorbide group. Six months after randomization, the average prescribed doses were 18.6 mg per day of prazosin, 270 mg per day of hydralazine, and 136 mg per day of isosorbide dinitrate. More than 85% of the prescribed drugs were taken in each treatment group.The mean follow-up was 2.3 years (range 6 months to 5.7 years). Only 4 patients were lost to follow up (2 in placebo group, 1 in prazosin group, and 1 in hydralazine-dinitrate group). There were 120 deaths in placebo group (44%; 19 per 100 patient years), 91 in the prazosin group (50%; 22 per 100 patient years), 72 in the hydralazine-dinitrate group (39%; 17 per 100 patient years). A reduction in mortality over the entire follow-up period was observed in the hydralazine-nitrate group compared with placebo (p = 0.093 on the log-rank test and p = 0.046 on the generalized Wilcoxon test, which gives more weight to treatment differences occurring in the earlier part of the mortality curves and less weight to the latter part, where the numbers are smaller). The absolute difference in mortality between these groups increased during three years and then began to diminish. The absolute difference in mortality between the placebo group and hydralazine-isosorbide groups at years 1 through 4 was 7%, 9%, 11% and 4%, respectively.Prespecified subgroup analysis in CAD vs no CAD stratification showed no significant treatment effect heterogeneity for hydralazine-nitrate among those with CAD although the absolute difference in mortality between groups was numerically higher for patients with CAD.At 8 weeks and 1 year, SBP (-4.1 and -4.6 mmHg) and DBP (-3.2 and -2.7 mmHg) decreased the most in the prazosin group compared to placebo. Hydralazine-nitrate was not associated with a statistically significant nor clinically significant difference in BP with exception of DBP at 8 weeks. The EF rose significantly at 8 weeks and 1 year in the hydralazine-nitrate group (+2.9 and +4.2) compared to placebo but not in the prazosin group.Side effects were reported in 4.0% of placebo patients, 11% of prazosin patients and 19% of hydralazine-nitrate patients, respectively. The most common side effects were headache and dizziness. Headache was reported in 12% of hydralazine-nitrate patients.Conclusions This study compared the combination of hydralazine-isosorbide dinitrate or prazosin to placebo in patients with chronic congestive heart failure who were optimized on digoxin and diuretic therapy. In what appears to be a young (58 years) and highly selected population of clinically stable, male veterans with dilated cardiomyopathies and low symptom burdens, the combination of hydralazine-isosorbide reduced death by 2 per 100 patient years, increased EF by 4% at 1 year and did not significantly alter BP compared to placebo. Side effects were reported in approximately 1 out of 5 patients with the most common being headache and approximately 1 out of 3 discontinued 1 or both study drugs. Prasozin did not reduce death or increase EF but did reduce BP compared to placebo. The internal validity of the study is high with only a few minor imbalances in baseline characteristics, which do not appear clinically relevant nor to consistently favor any one group. Less than 1% of patients were lost to follow up with no significant imbalances between groups. The external validity is limited by the fact that this is a population of male veterans and the etiologic distribution of cardiomyopathy and heart failure is likely different from a general heart failure population; etiologic causes of death are also likely to be different. Furthermore, the population is highly selected and its unclear how many patients from the general heart failure population would meet study criteria.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe
Als ich vor kurzen Alex in der Stadt traf, frug er, ob ich Sperie Karas kennen würde - Sperie: 94 Jahre alt, als Jugendlicher Schüler von Wilcoxon und später sowohl langjähriger Drummer der WDR Big Band als auch Dozent für Jazz und Big Band Drumming an der Folkwang Hochschule in Essen. "Den musst du interviewen!" Ich sagte natürlich sofort zu Diese Chance durfte ich mir nicht entgehen lassen. Ein paar Tage später eine NAchricht von Alex: "Sperie ist dabei. Er hat allerdings keine Vorstellung, was ein Podcast ist und ihm wäre am liebsten, wenn wir dort zusammen hinfahren könnten, Ok für dich?" ALEX, was eine Frage. Das ist nicht OK, das ist MEGA OK. Ich begann also zu recherchieren: Sperie als Kind auf der Flucht vor dem Nazi Regime, verliebte er sich auf der Überseefähre nach Amerika unsterblich: In das Schlagzeug. Zurück in den USA ging die wilde Fahrt aber erst so richtig los: Unterricht bei Wilcoxon, mit der eigenen Band Auftritte im legendären Birdland Club, Charlie Parkers Hand lobend auf der Schulter... Ich traute meinen Augen nicht. Ich konnte es nicht erwarten Sperie zu treffen und ihn nach all den Dingen zu fragen und schließlich auch die Frage zu klären, wie er nach Deutschland kam. Herausgekommen ist eine wundervolle, warmherzige, spannende Podcast-Folge, die ich zusammen mit Alex Vesper moderieren durfte. Prädikat: Sofort archivieren, um sie immer wieder hören zu können! Mehr zu Sperie findest du hier: https://de.wikipedia.org/wiki/Sperie_Karas Seine Bücher gibt es hier: https://www.amazon.de/s?i=stripbooks&rh=p_27%3ASperie+Karas&s=relevancerank&text=Sperie+Karas&ref=dp_byline_sr_book_1 Ein Video, wie Sperie mit 92 Jahren spielt: https://youtu.be/Yhx6nsvqZEU?feature=shared Und das besagte Video seiner Schüler: https://youtu.be/FHovHOx5BK0?feature=shared Ich freu mich tierisch, wenn du auf der Seite von Einfach Schlagzeug mal unter https://einfachschlagzeug.de/ oder bei Instagram vorbeischaust: https://www.instagram.com/krafftfelix/?hl=de Kapitelmarken 0:00:09 - Start 0:02:15 - Made in the USA 0:11:41 - Unterricht bei Charley Wilcoxon 0:23:24 - Sperie als Lehrer 0:28:08 - Das Leben geht weiter 0:34:20 - Ab nach Deutschland 0:43:33 - Schnellfragerunde 0:45:17 - Das gute Gefühl 0:53:59 - Noch einmal nachgehakt 1:00:28 - Die Musik steht immer im Zentrum 1:04:58 - Hidden Track
Bariatric surgery is an evolving field with new procedures, or variations of old ones, being developed to meet the needs of patients with obesity. The single anastomosis duodenoileal bypass (SADI) and one anastomosis gastric bypass (OAGB) are two such procedures which have recently entered the mainstream conversation. In this episode we will give a brief overview of the SADI and OAGB, go over some short and long term studies evaluating safety and efficacy, and discuss current sentiments about these options and how they may fit into bariatric practice. Show Hosts: Matthew Martin, MD Adrian Dan, MD Crystal Johnson-Mann, MD Paul Wisniowski, MD Article #1: Chao 2024 - Outcomes of SADI and OAGB Compared to RYGB from the Metabolic and Bariatric Surgery Quality Improvement Program: The North American Experience Roux-en-Y gastric bypass (RYGB) and duodenal switch are well described procedure for weight loss; however, associated postoperative complications have led to the development of simpler techniques Single anastomosis duodenoileal bypass (SADI) - modification of the duodenal switch where by a loop of ileum of the bilopancreatic limb approximately 200-300cm from the ileal cecal valve is anastomosed to the distal duodenal cuff of a tubularized stomach One anastomosis gastric bypass (OAGB) – modification of the RYGB where a loop of jejunum of the bilopancreatic limb approximately 150-200cm from the ligament of treitz is anastomosed to the distal end of a gastric pouch. There is increasing interest in these procedures given the perceived reduced risk reduction associated with one fewer anastomosis Currently, there is insufficient data on the safety of these procedures compared to the established RYGB. The article utilizes the MBSAQIP database to evaluate each procedure against the RYGB Matched groups: SADI vs RYGB and OAGB vs RYGB Matched against age, sex, BMI, operative time, and ASA classification 30-day outcomes included complications and health care utilization Results were analyzed with univariate comparative analysis, and significant outcomes were examined with logistic regression SADI vs RYGB: SADI independently associated INCREASED odds with staple line leak, sepsis, organ space infection, and pneumonia. OAGB vs RYGB: OAGB independently associated with REDUCED odds of SSI, transfusion requirement/GI bleed, ICU admission, bowel obstruction, and healthcare utilization (reoperation, readmissions, and reinterventions) No significant differences in mortality Limitation: Article generally reviews technical complications of procedures. Unable to address significant bariatric outcomes such as weight loss and metabolic profile, as well as long term outcomes. https://pubmed.ncbi.nlm.nih.gov/38170422/ Article #2: Maud 2019 - Efficacy and safety of OAGB vs RYGB for obesity (YOMEGA trial): A multicentre, randomized, open label, non-inferiority trial Limited long-term evidence on OAGB Mostly arising from retrospective analyses and one meta-analysis Two randomized clinical trials but with poor power and questionable methodology. This is a randomized non-inferiority trial of in patients undergoing bariatric surgery Randomized into 2 groups: OAGB vs RYGB with 117 patients per group Patients were followed for 2 years with a loss to follow up of 21% in OAGB and 24% in RYGB cohorts The primary outcome was weight loss with a noninferiority threshold of 7% assuming 60% weight loss at 2 years. Secondary outcomes included complications and metabolic outcomes Groups were compared with Student's T and Wilcoxon tests for quantitative data, and chi-squared and Fischer's exact for qualitative endpoints. Cohorts were analyzed with the intention to treat, and missing data on the primary endpoint was imputed with prediction-based modeling. Highlighted Outcomes Mean percent excess BMI loss of 87.9% in OAGB group compared to 85.8% in RYGB group demonstrating non-inferiority in terms of weight loss Increased number of serious adverse events (SAE) in the OAGB group, but no difference in the proportion of patients with at least 1 SAE OAGB demonstrated 70% complete or partial remission of diabetes compared to 44% in RYGB but underpowered to demonstrate significant difference. Equal rates of gastritis and esophagitis based on endoscopic biopsy results at 2 years. There were increased nutritional complications in the OAGB groups with 21% vs 0% in RYGB and high rates of diarrhea/anal fissures 14% vs 0%, respectively. This suggests a greater malabsorptive effect of OAGB. There was equal satisfaction in quality of life between RYGB and OAGB on two validated surveys with >80% satisfaction rates. Limitations Data was imputed for the primary end point High rates of loss to follow up in both cohorts Use of “severe adverse events” instead of Clavien-Dindo classification Comparison of specific institutional/surgeon technique of OAGB vs RYGB https://pubmed.ncbi.nlm.nih.gov/30851879/ Please visit https://behindtheknife.org to access other high-yield surgical education podcasts, videos and more. If you liked this episode, check out our recent episodes here: https://app.behindtheknife.org/listen
Dr. Masaya Koshizaka from the Department of Endocrinology, Hematology, and Gerontology at Chiba University Graduate School of Medicine, details a research paper he co-authored that was published by Aging (Aging-US) in Volume 15, Issue 9, entitled, “Renal dysfunction, malignant neoplasms, atherosclerotic cardiovascular diseases, and sarcopenia as key outcomes observed in a three-year follow-up study using the Werner Syndrome Registry.” DOI - https://doi.org/10.18632/aging.204681 Corresponding authors - Masaya Koshizaka - overslope@chiba-u.jp, and Koutaro Yokote - kyokote@faculty.chiba-u.jp Transcription - https://aging-us.net/2023/06/09/behind-the-study-key-outcomes-observed-in-follow-up-study-using-the-werner-syndrome-registrybehind-the-study/ Video - https://www.youtube.com/watch?v=HFqPvtYYTGE Abstract Werner syndrome is an adult-onset progeria syndrome that results in various complications. This study aimed to clarify the profile and secular variation of the disease. Fifty-one patients were enrolled and registered in the Werner Syndrome Registry. Their data were collected annually following registration. A cross-sectional analysis at registration and a longitudinal analysis between the baseline and each subsequent year was performed. Pearson's chi-squared and Wilcoxon signed-rank tests were used. Malignant neoplasms were observed from the fifth decade of life (mean onset: 49.7 years) and were observed in approximately 30% of patients during the 3-year survey period. Regarding renal function, the mean estimated glomerular filtration rate calculated from serum creatinine (eGFRcre) and eGFRcys, which were calculated from cystatin C in the first year, were 98.3 and 83.2 mL/min/1.73 m2, respectively, and differed depending on the index used. In longitudinal analysis, the average eGFRcre for the first and fourth years was 74.8 and 63.4 mL/min/1.73 m2, showing a rapid decline. Secular changes in Werner syndrome in multiple patients were identified. The prevalence of malignant neoplasms is high, and renal function may decline rapidly. It is, therefore, necessary to carry out active and detailed examinations and pay attention to the type and dose of the drugs used. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204681 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, disease profile, long-term follow-up, malignant neoplasm, renal function, Werner syndrome About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - 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/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM
Patterns and Possibilities - Thriving in Uncertainty with Miss Handie
In this episode, we're continuing our pattern of inquiry with active members of the HSD community. Our special guest is Antonia Wilcoxon. Antonia Maria Apolinário-Wilcoxon, Ed.D., Equity Strategies, LLC, founder, president, and principal consultant provides direction and leadership in efforts of private, public, and collaborative efforts working to improve the lives of disenfranchised and vulnerable persons impacted by inequities. Dr. Apolinário-Wilcoxon obtained her doctorate degree in educational leadership focusing on critical studies informed by Critical Pedagogy theorists. An African-Brazilian, she brings experiences in education, corporate, privatenonprofits, and government to lead efforts that bring agency, voice, and liberation in spaces where the presence of Oppression, bias and other barriers, silence those most valuable voices to find solutions to problems in their world. Dr. Apolinário-Wilcoxon's approach is one of listening deeply, exercising inquiry to enable wisdom and insights to emerge. Her facilitation is participatory, inclusive, resourceful, caring, and thoughtful. She is a volunteer member of several advisory boards, including board of directors: President-Elect, Minnesota Public Health Association (2023) Member, Senior Community Services Board of Directors Chair (2022), People's Center Clinics and Services Board of Directors Chair, Center for Resilient Families, University of Minnesota/Arizona, Federal Grant Member, African American Registry Board of Directors Member, Public Health Administration and Policy Community/Alumni Advisory Board, U of MN Member, Program in Health Disparities Research Advisory Board, U of MN/Medical School Member, National Association of Black Social Workers Member, ICHRP (Integrated Care for High-Risk Pregnancy/Healthy Black Pregnancy Board) --- Send in a voice message: https://podcasters.spotify.com/pod/show/hsdpatterns-possibilities/message
Today's podcast is very special as I have the distinct pleasure of introducing a wonderful friend and mentor Pastor Gerald Wilcoxon and First Lady Janice Wilcoxon, of Mount Sanai Institutional Baptist Church, in North Chicago. Biography Pastor Wilcoxon is a graduate of Lakeland College, Wisconsin, with a Bachelor of Religion, and a graduate of Milwaukee Theological Institute with a Bachelor of Ministry. He was called into the ministry and Licensed to Preach on February 5, 1989, and was ordained on March 17, 1991 at Friendship Baptist Church under the leadership of the Pastor Joseph L. Thomas. Pastor Wilcoxon served as Interim Pastor at United Faith Baptist Church for nine months before being called to serve the Mount Sinai Institutional Baptist Church family, in North Chicago, Illinois. Pastor Wilcoxon has served the Mount Sinai Family for 27 years, and has received numerous awards and recognitions for his service to the community. A native of Chicago, Pastor Wilcoxon, is a United States Marine Corps Vietnam Veteran, and for 51 years has been married to his lovely wife Janice. From their union God has blessed them with three beautiful daughters Tamecca, Tamarra, and Trinae, four wonderful granddaughters, and a grandson, and one great granddaughter. Biography Evangelist Janice Wilcoxon, aka “Lady J”, Motivational Speaker and Philanthropist, has been the First Lady of the Mount Sinai Institutional Baptist Church for 27 years. A devoted and loving wife, she has been married to Pastor Gerald for 51 years. She attended the University of Wisconsin Oshkosh, and retired after 37 years with Alfa Laval Incorporated, a Pharmaceutical Company. In 1999 Evangelist Wilcoxon was inspired by God to organize the Mt. Sinai Women's Retreat, an annual event that attracts more than 400 women from across the nation. As the First Lady, she started the Mount Sinai Women for Christ and Ministers and Deacons Wives Ministry; as well as hosting the Seasons of a Woman's Life Series. In 2013, Evangelist Wilcoxon was called into the ministry, allowing God to user her fully. In 2004, she was awarded the “Women in the Spirit” award by the People's Voice newspaper, and in 2011, Evangelist Janice Wilcoxon, along with her husband Pastor Gerald Wilcoxon, were awarded Most Influential African Americans of Lake County, Illinois. The Lord is continuing to use Evangelist Wilcoxon to lead those that are lost to Christ and constantly encourage women on their faith's journey. Today's Podcast is titled. A Conversation With Pastor Gerald and First Lady (Evangelist) Janice Wilcoxon Ladies and Gentlemen, please join me in welcoming today's guests. Pastor Gerald and First Lady Janice Wilcoxon. --- Send in a voice message: https://anchor.fm/david66634/message
Sarah is an associate professor of dance at MSU. We chat about her involvement in Humanities, volume 2: an exhibit at the Springfield Art Museum. We also talk about the Spring Dance Concert, and this episode features a shout-out from the COM department about the Vicki Stanton Public Speaking Showcase. SGF Art Museum: https://sgfmuseum.org/266/Humanities-Vol-2
Get to know Khaila Wilcoxon, Jasmine Forsberg, Storm Lever, Olivia Donalson, and Gabriela Carrillo from the first national tour of SIX THE MUSICAL as they share their journey from auditioning for the show to joining the Aragon tour. They talk about the different and interesting auditioning processes each of them went through and the stress and difficulties that came along with it as the pandemic hit. The queens discuss about what it's like being on a tour have been so far, how special the show is for having a diverse cast—an opportunity some of them have never had before, and how the group auditions helped in forming a camaraderie with the other casts, and the sisterhood that was formed along the way. Gabriela talks about her successful YouTube channel and why acting and vlogging are important for her. Khaila and Olivia share their Broadway experience, the physical and mental aspects of it versus doing Six now. From receiving gifts to meeting the audience after the show, they reflect on the widespread fame of the show and what it means to them. Khaila is currently playing Catherine of Arogan in the Aragon leg of the 2022-23 North American Tour production of Six the Musical. Her stage credits include Company (University of Wisconsin), Ruben and Clay's First Annual Christmas Carol Family Fun Pageant Spectacular Reunion Show (Imperial Theatre), and Hadestown (Walter Kerr Theatre). Jasmine is currently Jane Seymour in the Aragon leg of the 2022-23 North American Tour production of Six the Musical. Her stage credits include Shrek the Musical (Orlando Repertory Theatre), Legally Blonde (Penn State Centre Stage), A Grand Night for Singing (Goodspeed Opera House), and The Lucky Boy (Penn State Center Stage) Storm is currently playing Anne Boleyn in the Aragon leg of the 2022-23 North American Tour production of Six the Musical. Her stage credits include Romeo and Juliet (Arthur Miller Theatre), Freaky Friday (Signature Theatre), Almost Famous (The Old Globe), and Hair (The Old Globe) Olivia is currently playing Anna of Cleves in the Aragon leg of the 2022-23 North American Tour production of Six the Musical. Her stage credits include Tangle the Musical (The Disney Magic), Disney Dream (The Disney Magic), and Aladdin (US Tour, New Amsterdam Theatre) Gabriela is currently playing Catherine Parr in the Aragon leg of the 2022-23 North American Tour production of Six the Musical. Her stage credits include Atlantis (Tuacahn Amphitheater), The Prince of Egypt (Tuacahn Amphitheater), Love Actually Live (Bram Goldsmith Theatre), Mamma Mia! (La Mirada Theatre for the Performing Arts) In this episode, we talk about: Their favorite moments in the show Gabriela's YouTube vlogs and why documenting her life is important for her How Olivia recorded her self-tape What it's like doing group auditions and seeing each other in the final callbacks Jasmine doing Broadway Bounty Hunter The ability to make dolphin sounds Connect with Khaila, Jasmine, Storm, Olivia, Gabriela: Twitter: @KhailaWilcoxon, @forsbergjasmine, @StormLever, @oliviadonalson, @officialgabrielacarrillo Instagram: @thekhailawilcoxon, @jasmine_forsberg, @stormlever, @oliviadonalson TikTok: @khaila.wilcoxon, @jasmineforsberg, @stormlever, @oliviadonalson YouTube: Gabriela Carrillo Website: jasmineforsberg.com Connect with The Theatre Podcast: Support us on Patreon: Patreon.com/TheTheatrePodcast Twitter & Instagram: @theatre_podcast TikTok: @thetheatrepodcast Facebook.com/OfficialTheatrePodcast TheTheatrePodcast.com Alan's personal Instagram: @alanseales Email me at feedback@thetheatrepodcast.com. I want to know what you think. Learn more about your ad choices. Visit megaphone.fm/adchoices
Factors affecting the choice of statistical test, including level of measurement (nominal, ordinal and interval) and experimental design. When to use the following tests: Spearman's rho, Pearson's r, Wilcoxon, Mann-Whitney, related t-test, unrelated t-test and Chi-Squared test.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.16.384479v1?rss=1 Authors: Vuong, H., Truong, T., Phan, T., Pham, S. Abstract: Most widely used tools for finding marker genes in single-cell data (SeuratT/NegBinom/Poisson, CellRanger, EdgeR, limmatrend) use a conventional definition of differentially expressed genes: genes with different mean expression values. However, in single-cell data, a cell population can be a mixture of many cell types/cell states, hence the mean expression of genes cannot represent the whole population. In addition, these tools assume that the gene expression of a population belongs to a specific family of distribution. This assumption is often violated in single-cell data. In this work, we define marker genes of a cell population as genes that can be used to distinguish cells in the population from cells in other populations. Besides log-fold change, we devise a new metric to classify genes into up-regulated, down-regulated, and transitional states. In a benchmark for finding up-regulated and down-regulated genes, our tool outperforms all compared methods, including Seurat, ROTS, scDD, edgeR, MAST, limma, normal t test, Wilcoxon and KolmogorovSmirnov test. Our method is much faster than all compared methods, therefore, enables interactive analysis for large single cell data sets in BioTuring Browser. Venice algorithm is available within Signac package: https://github.com/bioturing/signac Copy rights belong to original authors. Visit the link for more info
Michael Wilcoxon (the Keto Hulk) and I talk about all things hormones, and nutrition as well as dive DEEP into mindset and mentality. We talk about the difference between losing weight and actually being healthy while addressing that a diet can't fix all problems, and talk about what else can help you be the healthiest version of yourself. Enjoy!
Today we welcome Rev. Buz Wilcoxon from Mobile, Alabama. Buz talks with us about not getting caught up in the lists, the supplies, the baseball games, the Girl Scout campouts and making sure you don't miss the very important lessons you can learn from a four year old at bed time.
Canceled Ep. 164 - Profit eps 7, 8, & 9 w/ Carlton Wilcoxon See acast.com/privacy for privacy and opt-out information.
Canceled Ep. 163 - Profit eps 5 & 6 w/ Carlton Wilcoxon See acast.com/privacy for privacy and opt-out information.
Canceled Ep. 162 - Profit eps 3 & 4 w/ Carlton Wilcoxon See acast.com/privacy for privacy and opt-out information.
Canceled Ep. 161 - Profit eps 1 & 2 w/ Carlton Wilcoxon See acast.com/privacy for privacy and opt-out information.
With the coming of May also comes another installation of Accountability Thursday! In this mini-episode we are working on a solo dedicated to the legendary, William F. Ludwig. "Assault and Battery' by Tommy Bloomingdale from the NARD book is the subject of this week's practice. Unlike most of the NARD book (yet similar to the Wilcoxon books) this solo utilizes very specific stickings and rudiments. The first place where we need to use our traditional interpretation skills is the dotted quarter note roll in the first measure of the second half of the solo. Perform this roll as a 15 stroke roll over the dotted quarter note value. Try to play the roll evenly and smoothly while landing on the downbeat of the following measure. Also take note of the alternating drags three measures from the end. You may find that upon initial run through that you may want to use the opposite stickings that the author has dictated. Make sure you resist that temptation and play his intended stickings! Make sure you visit this link to see the YouTube video: https://youtu.be/yaT2TQ9KoJs You'll be able to view the sheet music as well as see a performance of "Assault and Battery". We want you to practice this solo and post your videos on our social media. Make sure you tag the show in your description. Also head over to our web site at: www.drummersweeklygroovecast.com You can subscribe to the show, listen to all our episodes, see our performance videos, interact with our social media, and get in touch with us there as well. We'll see you in a couple of weeks with our next mini-episode and every Monday with our full length feature shows. The next time you log into your Itunes account please take a moment to go by our page and leave us a short, written review. It helps us out tremendously and allows other people searching for podcasts of similar content find us more easily.
Welcome to the OMG Oh! Maura Gale Show with Special Guests: First Lady Janice Wilcoxon and Tamarra Coleman Topic: "Women who share" (There's wisdom in our words, stories and struggles) In this episode we'll share some of our setbacks, set ups as well as the steps we took to recover, renew and reposition ourselves for success. Discover why there's strength, sanity and solace in our sharing. We will also inform listeners about an annual women's retreat that's celebrating it's 20th year! Women travel from all over the world to be encouraged, enlightened and equipped by the Mt Sinai Women's Retreat in Wisconsin. This year the award winning Docudramedy "STEM the Movement" will be making it's midwest premiere on Friday night of the weekend retreat being held April 20-22, 2018. For info/registration Email: MtSinaiRetreat@yahoo.com or Call 847-612-0327 or 262-237-4810. The opinions expressed during this broadcast are for inspiration, information and motivational purposes. This show is a production of Up2Me Radio and to learn more about our network, shows, hosts and guests please visit us at www.up2meradio.com Enjoy the Conversation! You can like us on Facebook at Up2Me Radio and follow us on Twitter @Up2Meradio
Once again we are back with "Accountability Thursday". This is our first episode using the Wilcoxon "All American Drummer 150 Rudimental Solos". We've worked from the Swing Solos book previously but this is our first time working in the 150. I chose solo #9 because it uses several proprietary Wilcoxon notations that are not commonly found in other rudimental methods. One thing that helps with his interpretation is that Wilcoxon specifies the required stickings on every single note of the solo. This allows him to highlight specific rudiments that he wants to use in each solo. The first thing to notice is the different notations for the seven stroke roll. The introductory roll-off is a seven stroke ternary roll. That style of seven is the preferred and most common way to interpret 8th note rolls in most rudimental literature. We've seen it numerous times in previous NARD solos and you'll use this particular roll three times in the first line alone. The ternary seven stroke is used a total of five times throughout the entire piece. Wilcoxon also uses a binary seven stroke roll. It appears first in the third line, last measure. You'll notice that he notates that roll with two grace notes prior to the 8th note on the '& of 2'. You'll start that roll on the 'e of 2' and roll 32nd notes ending on count one of the following measure. You'll see this same grace note style notation on the 15 stroke roll in the third line, third measure. Again, start that roll on the 'e of 1' and roll 32nd notes over to count one of the next measure. Another tricky place that may need some clarification is the third line, second measure. Pay attention to the stickings because the drags do not start on the expected hands! The measure begins with a single stroke, accented R, immediately afterward the notated left handed drag forces you to play grace notes on the right when you might expect a L. Also notice the fourth line, first measure. Wilcoxon notates the 8th note rolls as five stroke rolls (not seven stroke rolls). However with the two alternating accents that follow the doubles they actually become six stroke rolls. For further clarification visit the Youtube video to view the sheet music and see a performance of Wilcoxon Solo #9. https://youtu.be/nqX1NamJiJ4 We want you to practice this solo and post your videos on our social media. Make sure you tag the show in your description. Also head over to our web site at: www.drummersweeklygroovecast.com You can subscribe to the show, listen to all our episodes, see our performance videos, interact with our social media, and get in touch with us there as well. We'll see you in a couple of weeks with our next mini-episode and every Monday with our full length feature shows.
Jeff Wilcoxon – Bobtail Ice Cream “Let Your Customers Drive Your Innovation” As both the co-founder of Bobtail Ice Cream in Chicago, and a product management professional at a large corporation, Jeff Wilcoxon shares the ultimate advice for product entrepreneurs. Tune in to learn about the inner workings of a legacy ice cream business and how those small business lessons can be translated into a large corporate product management environment. In this episode, Jeff talks about growth, customer service, innovation and so much more! Whether you’re a product manager in an established company or an aspiring business owner with an idea for a new product business, Making It Real will provide you with real tools and advice on how to be a successful product entrepreneur! Hosted by Bob Caporale and Tate Tegtmeier Original Music by Bob Caporale Note: No endorsement of any product or service featured on Making It Real is either expressed or implied by its hosts or producers.
Jeff Wilcoxon – Bobtail Ice Cream “Let Your Customers Drive Your Innovation” As both the co-founder of Bobtail Ice Cream in Chicago, and a product management professional at a large corporation, Jeff Wilcoxon shares the ultimate advice for product entrepreneurs. Tune in to learn about the inner workings of a legacy ice cream business and how those small business lessons can be translated into a large corporate product management environment. In this episode, Jeff talks about growth, customer service, innovation and so much more! Whether you’re a product manager in an established company or an aspiring business owner with an idea for a new product business, Making It Real will provide you with real tools and advice on how to be a successful product entrepreneur! Hosted by Bob Caporale and Tate Tegtmeier Original Music by Bob Caporale Note: No endorsement of any product or service featured on Making It Real is either expressed or implied by its hosts or producers.
Mathematik, Informatik und Statistik - Open Access LMU - Teil 03/03
Thu, 1 Jan 2015 12:00:00 +0100 https://epub.ub.uni-muenchen.de/25569/1/BA_Steinherr.pdf Steinherr, Tobias
Introduction: Circulating tumor cells (CTCs) have been studied in breast cancer with the CellSearch® system. Given the low CTC counts in non-metastatic breast cancer, it is important to evaluate the inter-reader agreement. Methods: CellSearch® images (N = 272) of either CTCs or white blood cells or artifacts from 109 non-metastatic (M0) and 22 metastatic (M1) breast cancer patients from reported studies were sent to 22 readers from 15 academic laboratories and 8 readers from two Veridex laboratories. Each image was scored as No CTC vs CTC HER2-vs CTC HER2+. The 8 Veridex readers were summarized to a Veridex Consensus (VC) to compare each academic reader using % agreement and kappa (.) statistics. Agreement was compared according to disease stage and CTC counts using the Wilcoxon signed rank test. Results: For CTC definition (No CTC vs CTC), the median agreement between academic readers and VC was 92% (range 69 to 97%) with a median. of 0.83 (range 0.37 to 0.93). Lower agreement was observed in images from M0 (median 91%, range 70 to 96%) compared to M1 (median 98%, range 64 to 100%) patients (P < 0.001) and from M0 and < 3CTCs (median 87%, range 66 to 95%) compared to M0 and >= 3CTCs samples (median 95%, range 77 to 99%), (P < 0.001). For CTC HER2 expression (HER2-vs HER2+), the median agreement was 87% (range 51 to 95%) with a median. of 0.74 (range 0.25 to 0.90). Conclusions: The inter-reader agreement for CTC definition was high. Reduced agreement was observed in M0 patients with low CTC counts. Continuous training and independent image review are required.
Purpose: The purpose of this study was the intraindividual comparison of a 1.0 M and two 0.5 M gadolinium-based contrast agents (GBCA) using equimolar dosing in dynamic and static magnetic resonance angiography (MRA) of the supra-aortic vessels. Materials and Methods: In this institutional review board-approved study, a total of 20 healthy volunteers (mean +/- SD age, 29 +/- 6 years) underwent 3 consecutive supra-aortic MRA examinations on a 3.0 T magnetic resonance system. The order of GBCA (Gadobutrol, Gadobenate dimeglumine, and Gadoterate meglumine) was randomized with a minimum interval of 48 hours between the examinations. Before each examination and 45 minutes after each examination, circulatory parameters were recorded. Total GBCA dose per MRA examination was 0.1 mmol/kg with a 0.03 mmol/kg and 0.07 mmol/kg split for dynamic and static MRA, respectively, injected at a rate of 2 mL/s. Two blinded readers qualitatively assessed static MRA data sets independently using pairwise rankings (superior, inferior, and equal). In addition, quantitative analysis was performed with signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) evaluation as well as vessel sharpness analysis of static MRA using an in-house-developed semiautomated tool. Dynamic MRA was evaluated for maximal SNR. Statistical analysis was performed using the Cohen kappa, the Wilcoxon rank sum tests, and mixed effects models. Results: No significant differences of hemodynamic parameters were observed. In static MRA, Gadobutrol was rated superior to Gadoterate meglumine (P < 0.05) and equal to Gadobenate dimeglumine (P = 0.06) with good to excellent reader agreement (kappa, 0.66-0.83). In static MRA, SNR was significantly higher using 1.0 M Gadobutrol as compared with either 0.5 M agent (P < 0.05 and P < 0.05) and CNR was significantly higher as compared with Gadoterate meglumine (P < 0.05), whereas CNR values of Gadobutrol data sets were not significantly different as compared with Gadobenate dimeglumine (P = 0.13). Differences in CNR between Gadobenate dimeglumine and Gadoterate meglumine were not significant (P = 0.78). Differences in vessel sharpness between the different GBCAs were also not significant (P > 0.05). Maximal SNR in dynamic MRA using Gadobutrol was significantly higher than both comparators at the level of the proximal and distal internal carotid artery (P < 0.05 and P < 0.05; P < 0.05 and P < 0.05). Conclusions: At equimolar doses, 1.0 M Gadobutrol demonstrates higher SNR/CNR than do Gadobenate dimeglumine and Gadoterate meglumine, with superior image quality as compared with Gadoterate meglumine for dynamic and static carotid MRA. Despite the shortened bolus with Gadobutrol, no blurring of vessel edges was observed.
Background and Aims: Exclusive enteral nutrition (EEN) induces remissionin patients with Crohn’s disease (CD). We investigated the short-termimpact of EEN on bone quality and muscle mass in children with CD.Methods: Ten newly diagnosed CD patients (7 male, 10.6-17.7 years ofage) were assessed by peripheral quantitative computed tomography (pQCT)at the forearm before starting an 8-weeks treatment with EEN, and after12 and 52 weeks. No steroids or biologicals were applied. Trabecular andcortical bone mineral density, total bone, and muscle cross-sectionalarea (CSA) were measured by pQCT and expressed as age- and sex-specificz-scores; size-dependent CSAs were corrected for low height for age.Wilcoxon rank sum test was applied. Results: Remission at week 12 wasachieved in 8 patients; 2 still had mild disease.
Background: To determine if black-blood 3 T cardiovascular magnetic resonance (bb-CMR) can depict differences between symptomatic and asymptomatic carotid atherosclerotic plaques in acute ischemic stroke patients. Methods: In this prospective monocentric observational study 34 patients (24 males; 70 +/- 9.3 years) with symptomatic carotid disease defined as ischemic brain lesions in one internal carotid artery territory on diffusion weighted images underwent a carotid bb-CMR at 3 T with fat-saturated pre- and post-contrast T1w-, PDw-, T2w- and TOF images using surface coils and Parallel Imaging techniques (PAT factor = 2) within 10 days after symptom onset. All patients underwent extensive clinical workup (lab, brain MR, duplex sonography, 24-hour ECG, transesophageal echocardiography) to exclude other causes of ischemic stroke. Prevalence of American Heart Association lesion type VI (AHA-LT6), status of the fibrous cap, presence of hemorrhage/thrombus and area measurements of calcification, necrotic core and hemorrhage were determined in both carotid arteries in consensus by two reviewers who were blinded to clinical information. McNemar and Wilcoxon's signed rank tests were use for statistical comparison. A p-value
Fakultät für Mathematik, Informatik und Statistik - Digitale Hochschulschriften der LMU - Teil 01/02
In biological research, diverse high-throughput techniques enable the investigation of whole systems at the molecular level. The development of new methods and algorithms is necessary to analyze and interpret measurements of gene and protein expression and of interactions between genes and proteins. One of the challenges is the integrated analysis of gene expression and the associated regulation mechanisms. The two most important types of regulators, transcription factors (TFs) and microRNAs (miRNAs), often cooperate in complex networks at the transcriptional and post-transcriptional level and, thus, enable a combinatorial and highly complex regulation of cellular processes. For instance, TFs activate and inhibit the expression of other genes including other TFs whereas miRNAs can post-transcriptionally induce the degradation of transcribed RNA and impair the translation of mRNA into proteins. The identification of gene regulatory networks (GRNs) is mandatory in order to understand the underlying control mechanisms. The expression of regulators is itself regulated, i.e. activating or inhibiting regulators in varying conditions and perturbations. Thus, measurements of gene expression following targeted perturbations (knockouts or overexpressions) of these regulators are of particular importance. The prediction of the activity states of the regulators and the prediction of the target genes are first important steps towards the construction of GRNs. This thesis deals with these first bioinformatics steps to construct GRNs. Targets of TFs and miRNAs are determined as comprehensively and accurately as possible. The activity state of regulators is predicted for specific high-throughput data and specific contexts using appropriate statistical approaches. Moreover, (parts of) GRNs are inferred, which lead to explanations of given measurements. The thesis describes new approaches for these tasks together with accompanying evaluations and validations. This immediately defines the three main goals of the current thesis: 1. The development of a comprehensive database of regulator-target relation. Regulators and targets are retrieved from public repositories, extracted from the literature via text mining and collected into the miRSel database. In addition, relations can be predicted using various published methods. In order to determine the activity states of regulators (see 2.) and to infer GRNs (3.) comprehensive and accurate regulator-target relations are required. It could be shown that text mining enables the reliable extraction of miRNA, gene, and protein names as well as their relations from scientific free texts. Overall, the miRSel contains about three times more relations for the model organisms human, mouse, and rat as compared to state-of-the-art databases (e.g. TarBase, one of the currently most used resources for miRNA-target relations). 2. The prediction of activity states of regulators based on improved target sets. In order to investigate mechanisms of gene regulation, the experimental contexts have to be determined in which the respective regulators become active. A regulator is predicted as active based on appropriate statistical tests applied to the expression values of its set of target genes. For this task various gene set enrichment (GSE) methods have been proposed. Unfortunately, before an actual experiment it is unknown which genes are affected. The missing standard-of-truth so far has prevented the systematic assessment and evaluation of GSE tests. In contrast, the trigger of gene expression changes is of course known for experiments where a particular regulator has been directly perturbed (i.e. by knockout, transfection, or overexpression). Based on such datasets, we have systematically evaluated 12 current GSE tests. In our analysis ANOVA and the Wilcoxon test performed best. 3. The prediction of regulation cascades. Using gene expression measurements and given regulator-target relations (e.g. from the miRSel database) GRNs are derived. GSE tests are applied to determine TFs and miRNAs that change their activity as cellular response to an overexpressed miRNA. Gene regulatory networks can constructed iteratively. Our models show how miRNAs trigger gene expression changes: either directly or indirectly via cascades of miRNA-TF, miRNA-kinase-TF as well as TF-TF relations. In this thesis we focus on measurements which have been obtained after overexpression of miRNAs. Surprisingly, a number of cancer relevant miRNAs influence a common core of TFs which are involved in processes such as proliferation and apoptosis.
Background: For several immune-mediated diseases, immunological analysis will become more complex in the future with datasets in which cytokine and gene expression data play a major role. These data have certain characteristics that require sophisticated statistical analysis such as strategies for non-normal distribution and censoring. Additionally, complex and multiple immunological relationships need to be adjusted for potential confounding and interaction effects. Objective: We aimed to introduce and apply different methods for statistical analysis of non-normal censored cytokine and gene expression data. Furthermore, we assessed the performance and accuracy of a novel regression approach in order to allow adjusting for covariates and potential confounding. Methods: For non-normally distributed censored data traditional means such as the Kaplan-Meier method or the generalized Wilcoxon test are described. In order to adjust for covariates the novel approach named Tobit regression on ranks was introduced. Its performance and accuracy for analysis of non-normal censored cytokine/gene expression data was evaluated by a simulation study and a statistical experiment applying permutation and bootstrapping. Results: If adjustment for covariates is not necessary traditional statistical methods are adequate for non-normal censored data. Comparable with these and appropriate if additional adjustment is required, Tobit regression on ranks is a valid method. Its power, type-I error rate and accuracy were comparable to the classical Tobit regression. Conclusion: Non-normally distributed censored immunological data require appropriate statistical methods. Tobit regression on ranks meets these requirements and can be used for adjustment for covariates and potential confounding in large and complex immunological datasets.
This Podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Interim Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Matthew Barrett interview Dr. Ergun Uc about his paper driving with Parkinson disease. In the next segment, Dr. Ryan Overman is reading our e-Pearl of the week about cervical MRI with anterior flexion in Hirayama disease. The podcast concludes where Dr. Casey Hall interviews Dr. Mark Conaway for the Lesson of the Week on Wilcoxon tests. The participants had nothing to disclose except for Dr. Uc.Dr. Uc received an honorarium from Current Medicine Group LLC for writing an invited article; serves on the NIH/NINDS VA Merit Review Board; and receives research support from the Parkinson disease Foundation (PI).
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 07/19
Purpose: To quantitatively evaluate the lateralizing significance of ictal head movements of patients with temporal lobe epilepsy (TLE). Methods: We investigated EEG-video recorded seizures of patients with TLE, in which the camera position was perpendicular to the head facing the camera in an upright position and bilateral head movement was recorded. Thirty-eight seizures (31 patients) with head movement in both directions were investigated. Ipsilateral and contralateral head movement were defined according to ictal EEG. Head movements were quantified by selecting the movement of the nose in relation to a defined point on the thorax (25/s) in a defined plane facing the camera. The duration of the head version was determined independently of the camera angle. The angle, duration and angular speed of the head movements were computed and inter- and intrasubject analyses were performed (Wilcoxon rank sum). Results: Ipsilateral movement always preceded contralateral movement. The positive predictive value (PPV) was 100% for movement in both directions. The duration of contralateral head version was significantly longer than ipsilateral head movement (6.4s ± 4.1s vs. 3.9s ± 3.1s, p
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 05/19
Fragestellung: Das Ziel der vorliegenden Studie ist es, die Assoziation zwischen einer Kolonisierung der Vagina mit Candida spp. und den Konzentrationen von vaginalen Interleukinen IL-1 beta, IL-1ra, IL-4, IL-6, IL-8, IL-10 und IL-12 in Relation zur Schwangerschaftsperiode zu beschreiben. Studiendesign: Diese prospektive longitudinale Beobachtungsstudie wurde in der Klinik und Poliklinik für Geburtshilfe und Frauenheilkunde des Universitätsklinikum Großhadern von März 2002 bis Oktober 2004 durchgeführt. Das Studienkollektiv bestand aus 134 Frauen mit Einlingsschwangerschaften. Alle Frauen wurden zwischen der 6. und 16. Schwangerschaftswoche (SSW) rekrutiert und zwischen der 24. und 28. sowie der 35. und 38. SSW nachuntersucht. Die entsprechenden Vaginalabstriche wurden mittels einer kulturellen Anzüchtung und PCR-Amplifizierung auf Candida spp. getestet. Mittels ELISA wurden im Vaginallavage und im Serum Zytokine IL-1 beta, IL-1ra, IL-4, IL-6, IL-8, IL-10 und IL-12 gemessen. Zusätzlich wurde das jeweilige IL-1ra:IL-1 beta Verhältnis berechnet. Darüber hinaus wurden anamnestische Daten und die Ergebnisse von mikrobiologischen Untersuchungen erhoben. In die Endauswertung wurden die Daten von 98 Frauen mit vollständigen Ergebnissen und ohne lost to follow up aufgenommen. Für die statistische Analyse wurden der t-Test für unverbundene Stichproben, der Mann-Whitney U Tests für unverbundene Stichproben und der Vorzeichen-Rangtests von Wilcoxon für verbundene Stichproben verwendet. Ergebnisse: Wir isolierten Candida spp. in 18 (18,3%) Fällen im 1. Trimester, in 25 (25,5%) Fällen im 2. Trimester und in 30 (30,6%) Fällen im 3. Trimester mittels einer kulturellen Anzüchtung bzw. in 25 (25,5%) Fällen im 1. Trimester, in 33 (33,7%) Fällen im 2. Trimester und in 41 (41,8%) Fällen im 3. Trimester mittels PCR-Amplifizierung. Dabei wurden C. albicans und C. glabrata identifiziert. Die Konzentrationen von IL-1 im Vaginallavage waren im 1. und 3. Trimester (p= 0,0002, p=0,0005) in der Candidagruppe signifikant höher als in der Kontrollgruppe. Im Serum konnten signifikante Unterschiede nur im 2. Trimester festgestellt werden, wo die Werte in der Kontrollgruppe höher lagen (p=0,036). In den Konzentrationen von IL-1ra wurden keine signifikanten Unterschiede im Vaginallavage sowie im Serum festgestellt, mit Ausnahme vom 1. Trimester, wo die Werte in der Candidagruppe höher lagen (p=0,0047). Das IL-1ra: IL-1 beta Verhältnis im Vaginallavage war jedoch in der Gruppe ohne Candida-Kolonisierung im Vergleich mit der Candidagruppe in allen drei Untersuchungszeitpunkten signifikant höher. Im Serum wurde kein Unterschied zwischen den Gruppen festgestellt. Eine signifikante Erhöhung der IL-4-Konzentrationen wurde im 2. und 3. Trimester im Vaginallavage in der Candidagruppe nachgewiesen (p=0,049, p=0,041). IL-6 war im 1. und 3. Trimester signifikant höher im Vaginallavage in der Candidagruppe (p=0,024, p=0,0053). Die Konzentrationen von IL-8 im Vaginallavage waren in der Candidagruppe in allen Untersuchungszeitpunkten signifikant höher als in der Kontrollgruppe. IL-10 war im 3. Trimester im Vaginallavage in der Candidagruppe signifikant höher. Im Serum ergab sich kein signifikanter Unterschied in den Konzentrationen von IL-4, IL-6, IL-8, IL-10 sowie IL-12 zwischen den beiden Gruppen. Ebenfalls konnten keine Unterschiede zwischen den Gruppen in den Konzentrationen von IL-12 im Vaginallavage festgestellt werden. Im Laufe der Schwangerschaft stieg die Konzentration von IL-1 beta und IL-8 in der Candidagruppe zum 3. Trimester, was in der Kontrollgruppe nicht beobachtet wurde. Schlussfolgerungen: Die steigende Prävalenz der Besiedlung der Vagina mit Candida spp. im Verlauf der Schwangerschaft kann aufgrund der Ergebnisse dieser Studie folgendermaßen erklärt werden: Einerseits spielen für die Schwangerschaft typische Veränderungen im Scheidenmilieau eine große Rolle. Andererseits begünstigen die Veränderungen der lokalen Immunantwort die Entstehung der Kolonisierung mit Candida spp. Die Erhöhung von IL-4 und IL-6 zeigt, dass in Anwesenheit von Candida spp. die Th-2 Immunantwort aktiviert wird. Dies trägt auch zu einer Suppression der lokalen zellvermittelten Immunität bei. Aufgrund signifikant höherer Werte von IL-1 beta und IL-8 im Vaginallavage in der Candidagruppe kann die frühzeitige Reifung der Zervix und dementsprechend eine Frühgeburt nicht ausgeschlossen werden. Die Erhöhung der IL-10 in der Candidagruppe und die Tatsache niedriger IL-12-Konzentrationen weist auf eine Senkung der natürlichen Immunabwehr in der Vagina und ein lokales Immundefizit während der Schwangerschaft hin. Unsere Ergebnisse bestätigen auch, dass es wichtig ist, das IL-1ra:IL-1 beta Verhältnis zu bestimmen, da bei einer erhöhten Produktion von IL-1 beta oder einer supprimierten Synthese von IL-1ra eine Kolonisierung der Scheide mit Candida spp. begünstigt wird.
Background: Intravenous methylprednisolone (IV-MP) is an established treatment for multiple sclerosis ( MS) relapses, accompanied by rapid, though transient reduction of gadolinium enhancing (Gd+) lesions on brain MRI. Intermittent IV-MP, alone or with immunomodulators, has been suggested but insufficiently studied as a strategy to prevent relapses. Methods: In an open, single-cross-over study, nine patients with relapsing-remitting MS (RR-MS) underwent cranial Gd-MRI once monthly for twelve months. From month six on, they received a single i.v.-infusion of 500 mg methylprednisolone ( and oral tapering for three days) after the MRI. Primary outcome measure was the mean number of Gd+ lesions during treatment vs. baseline periods; T2 lesion volume and monthly plasma concentrations of cortisol, ACTH and prolactin were secondary outcome measures. Safety was assessed clinically, by routine laboratory and bone mineral density measurements. Soluble immune parameters (sTNF-RI, sTNF-RII, IL1-ra and sVCAM-1) and neuroendocrine tests ( ACTH test, combined dexamethasone/CRH test) were additionally analyzed. Results: Comparing treatment to baseline periods, the number of Gd+ lesions/scan was reduced in eight of the nine patients, by a median of 43.8% ( p = 0.013, Wilcoxon). In comparison, a pooled dataset of 83 untreated RR-MS patients from several studies, selected by the same clinical and MRI criteria, showed a non-significant decrease by a median of 14% ( p = 0.32). T2 lesion volume decreased by 21% during treatment ( p = 0.001). Monthly plasma prolactin showed a parallel decline ( p = 0.027), with significant cross-correlation with the number of Gd+ lesions. Other hormones and immune system variables were unchanged, as were ACTH test and dexamethasone-CRH test. Treatment was well tolerated; routine laboratory and bone mineral density were unchanged. Conclusion: Monthly IV-MP reduces inflammatory activity and T2 lesion volume in RR-MS.
Mathematik, Informatik und Statistik - Open Access LMU - Teil 02/03
Background: The annual relapse rate has been commonly used as a primary efficacy endpoint in phase III multiple sclerosis (MS) clinical trials. The aim of this study was to determine the relative contribution of different possible prognostic factors available at baseline to the on-study relapse rate in MS. Methods: A total of 821 patients from the placebo arms of the Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR) database were available for this analysis. The univariate relationships between on-study relapse rate and the baseline demographic, clinical, and MRI-based predictors were assessed. The multiple relationships were then examined using a Poisson regression model. Two predictor subsets were selected. Subset 1 included age at disease onset, disease duration, gender, Expanded Disability Status Scale (EDSS) at baseline, number of relapses in the last 24 months prior to baseline, and the disease course (RR and SP). Subset 2 consisted of Subset 1 plus gadolinium enhancement status in MRI. The number of patients for developing the models with no missing values was 727 for Subset 1 and 306 for Subset 2. Results:The univariate relationships show that the on-study relapse rate was higher for younger and for female patients, for RR patients than for SP patients, and for patients with positive enhancement status at entry (Wilcoxon test, p
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 02/19
In einem prospektiven, hypothesengeleiteten Design mit zwei Messzeitpunkten wurde die Krankheitsverarbeitung (Bewältigungsstrategien, Kausal- und Kontrollattributionen) von Patienten mit malignen Lymphomen sowie deren Zusammenhänge mit Lebensqualität und emotionalem Befinden vor und sechs Monate nach Hochdosischemotherapie mit autologer Blutstammzelltransplantation untersucht. Neben soziodemographischen Daten wurden medizinische Parameter wie Karnofsky-Index und Remissionsstatus erhoben. Die Untersuchung stützte sich auf multidimensionale, standardisierte und normierte Testverfahren, deren Gütekriterien an verschiedenen Stichproben, großteils auch an Krebspatienten, überprüft worden waren. Im Erhebungszeitraum (März 1999 bis August 2001) konnte eine Stichprobe von n=69 Patienten akquiriert werden. Diese reduzierte sich aus Gründen von Tod, anderer medizinischer Behandlung und persönlicher Ablehnung auf n=45 zum zweiten Erhebungszeitpunkt. Im Hinblick auf soziodemographische und medizinische Parameter wurden die Patienten mit der Studie von Langenmayer, 1999 an autolog blutstammzelltransplantierten Lymphompatienten und mit Daten der Normalbevölkerung (Statistisches Bundesamt Wiesbaden) verglichen. Die statistische Auswertung erfolgte in Abhängigkeit vom Skalenniveau und den Verteilungscharakteristika der Daten mit Hilfe von parametrischen und nonparametrischen Verfahren. Neben t-Test-Vergleichen, dem U-Test nach Mann-Whitney und Wilcoxon, den χ2-Techniken, der Produkt-Moment-Korrelation nach Bravais-Pearson und Spearman’s Rangkorrelation, wurden ein- und mehrfaktorielle Varianzanalysen, multiple Regressionsanalysen und Clusteranalysen nach der Ward-Methode berechnet. Um Scheinsignifkanzen durch α-Fehler-Kumulierung zu vermeiden, wurden die Irrtumswahrscheinlichen nach der Bonferroni-Methode korrigiert. In der Krankheitsbewältigung (FKV) zeigte sich eine im Vergleich mit Muthny et al., 1992 geringere Tendenz zum sozialen Abwärtsvergleich, was möglicherweise mit der Schwere und Lebensbedrohlichkeit der Erkrankung in Zusammenhang steht. Bei den subjektiven Kausalattributionen (PUK) konnten im Hinblick auf Lebensqualität und emotionales Befinden adaptive und maladaptive Formen identifiziert werden. Dies spricht gegen die prinzipielle Maladaptivität subjektiver Krankheitstheorien (Riehl-Emde et al., 1989; Muthny et al., 1992; Faller et al., 1995). Die Attribution auf "Umweltverschmutzung" ist bei Krebspatienten häufig (vgl. Becker, 1984; Verres, 1986) und erwies sich als adaptiv; "Gesundheitsverhalten", "Alltagsstress", "Verarbeitungsdefizite", "eigene seelische Probleme" und "geringes Durchsetzungsvermögen" hingegen als maladaptiv. Der Autor vermutet Zusammenhänge mit Selbstbeschuldigungsprozessen, was durch eine multivariate Varianzanalyse gestützt wurde: die bislang noch nicht publizierte Differenzierung zwischen natur- und handlungskausalen Attributionen erwies sich als einzig signifikanter Einflussfaktor auf Lebensqualität und emotionales Befinden im multivariaten Vergleich. Naturkausal werden solche Attributionen bezeichnet, auf die der Patient intentional keinen Einfluss nehmen konnte (z.B. Zufall, Schicksal, Vererbung), während handlungskausale Ursachen prinzipiell veränderbar gewesen wären (z.B. hohe Anforderungen an sich selbst, Alttagsstress, berufliche Belastungen). Patienten mit handlungskausalen Attributionsmodellen hatten eine signifikant geringere Lebensqualität, geringere emotionale Funktion und erhöhte Werte an affektiven Belastungen: sie waren häufiger niedergeschlagen, müde und missmutig; auch gaben sie signifikant mehr Ursachen für ihre Erkrankung an, zudem in höherer Gewichtung. Es zeigte sich ein positiver Einfluss internaler Kontrollattributionen auf Lebensqualität und Rollenfunktion sechs Monate nach autologer Stammzelltransplantation, was die Untersuchungen von Baider & Sarell, 1983; Reynaert et al., 1995 und Eckhardt-Henn et al., 1997 bestätigt, unserer Hypothese aber widerspricht, dass sich im Setting der Hochdosischemotherapie mit Angewiesenheit auf Ärzte, Pflegepersonal und Angehörige sozial-externale Attributionen als adaptiver erweisen würden. Hinsichtlich des Remissionsstatus und einiger soziodemographischer Parameter ergaben sich geringe bis mittelstarke Zusammenhänge mit der Krankheitsbewältigung, Kausal- und Kontrollüberzeugungen. Diese hielten einer Bonferroni-Korrektur jedoch nicht stand, so dass sie lediglich als Tendenzen interpretiert werden dürfen. Keine Zusammenhänge zeigten sich in Bezug auf den Karnofsky-Index und die Diagnosegruppen. Mit Clusteranalysen nach der Ward-Methode wurden die untersuchten Patienten eindeutig differenzierbaren Clustern der Krankheitsbewältigung (FKV) bzw. Kontrollattribution (KKG) zugeordnet. Letztere entsprachen den von Wallston & Wallston, 1982 beschriebenen "rein internalen" bzw. "doppelt externalen" Typen, dem des "Nay-sayer" und "Type thought not to exist". Es zeigten sich wenig signifikante Unterschiede im Hinblick auf Lebensqualität oder emotionale Belastungen. Die Zusammenhänge zwischen emotionalem Befinden und Krankheitsverarbeitung wurden mit kreuzvalidierten, multiplen Regressionsanalysen untersucht. Dabei leistete der Autoregressor jeweils einen wesentlichen Beitrag zur Varianzaufklärung des Kriteriums. Insgesamt scheinen die Bewältigungsstrategien das emotionale Befinden vorwiegend in den distalen Modellen zu beeinflussen, während in den proximalen Modellen auch Einflüsse des Karnofsky-Indexes bestehen. Da sich in der vorliegenden Untersuchung wie auch bei Filipp et al., 1989 und Faller et al., 1994b die Zusammenhänge für die verschiedenen Kriterien und Prädiktoren unterschiedlich darstellten, sollten kausale Beziehungen zwischen Coping und Befinden für jede Krankheitsverarbeitungsform bzw. jedes Adaptationskriterium separat überprüft werden. Die Verarbeitungsmechanismen erwiesen sich im matched-pair-Vergleich als relativ änderungsinvariant im untersuchten Sechs-Monatszeitraum. Dies widerspricht der These von Faller, 1988, nach der es sich bei subjektiven Krankheitstheorien um situationsabhängige Argumentationsprozesse handelt, wie auch der von Lohaus, 1992 beschriebenen Variabilität von Kontrollüberzeugungen. Die Krankheitsverarbeitung könnte mit Persönlichkeitsmerkmalen in Verbindung stehen, was künftige Studien untersuchen sollten. Möglicherweise kann die Unterscheidung zwischen natur- und handlungskausalen Attributionen künftig sowohl bei der Skalierung als auch bei der Identifikation einer Risikogruppe von Patienten behilflich sein, die einer besonderen psychotherapeutischen Unterstützung bedürfen.
Background/Aims: Ursodeoxycholic acid ( UDCA) decreases biliary secretion of cholesterol and is therefore used for the dissolution of cholesterol gallstones. It remains unclear whether these changes in biliary cholesterol excretion are associated with changes in cholesterol synthesis and bile acid synthesis. We therefore studied the activities of rate-limiting enzymes of cholesterol synthesis and bile acid synthesis, 3-hydroxy-3-methyl-glutarylcoenzyme A reductase and cholesterol 7alpha-hydroxylase, respectively, in normal subjects during UDCA feeding. Methods: UDCA was given to 8 healthy volunteers ( 5 men, 3 women; age 24-44 years) in a single dose of 10-15 mg/kg body weight for 40 days. Before and during ( days 3, 5, 10, 20, 30 and 40) UDCA treatment, urinary excretion of mevalonic acid and serum concentrations of 7alpha-hydroxy-4-cholesten-3-one (7alpha-HCO) were determined as markers of cholesterol and bile acid synthesis, respectively. The Wilcoxon signed rank test and Spearman's rank correlation coefficient were used for statistical analysis. Results: Cholesterol synthesis and serum lipid concentrations remained unchanged during UDCA treatment for 40 days. However, synthesis of bile acids increased during long-term treatment with UDCA as reflected by an increase in 7alpha-HCO serum concentrations from 39.7 +/- 21.3 ng/ml (median 32.8 ng/ml) before treatment to 64.0 +/- 30.4 ng/ml (median 77.5 ng/ml) at days 30-40 of UDCA treatment ( p < 0.05). Conclusions: UDCA treatment does not affect cholesterol synthesis in the liver, but does increase bile acid synthesis after prolonged treatment. This may represent a compensatory change following decreased absorption of endogenous bile acids as observed with UDCA therapy.
Nucleosomes, which are typical cell death products, are elevated in the serum of cancer patients and are known to rapidly increase during radiotherapy. As both normal and malignant cells are damaged by irradiation, we investigated to which extent both cell types contribute to the release of nucleosomes. We cultured monolayers of normal bronchoepithelial lung cells (BEAS-2B, n = 18) and epithelial lung cancer cells (EPLC, n = 18), exposed them to various radiation doses (0, 10 and 30 Gy) and observed them for 5 days. Culture medium was changed every 24 h. Subsequently, nucleosomes were determined in the supernatant by the Cell Death Detection-ELISA(plus) ( Roche Diagnostics). Additionally, the cell number was estimated after harvesting the cells in a second preparation. After 5 days, the cell number of BEAS-2B cultures in the irradiated groups (10 Gy: median 0.03 x 10(6) cells/culture, range 0.02-0.08 x 10(6) cells/culture; 30 Gy: median 0.08 x 10(6) cells/culture, range 0.02-0.14 x 10(6) cells/culture) decreased significantly (10 Gy: p = 0.005; 30 Gy p = 0.005; Wilcoxon test) compared to the non-irradiated control group (median 4.81 x 10(6) cells/culture, range 1.50-9.54 x 10(6) cells/culture). Consistently, nucleosomes remained low in the supernatant of nonirradiated BEAS-2B. However, at 10 Gy, BEAS-2B showed a considerably increasing release of nucleosomes, with a maximum at 72 h ( before irradiation: 0.24 x 10(3) arbitrary units, AU, range 0.13-4.09 x 10(3) AU, and after 72 h: 1.94 x 10(3) AU, range 0.11-5.70 x 10(3) AU). At 30 Gy, the release was even stronger, reaching the maximum earlier (at 48 h, 11.09 x 10(3) AU, range 6.89-18.28 x 10(3) AU). In non-irradiated EPLC, nucleosomes constantly increased slightly. At 10 Gy, we observed a considerably higher release of nucleosomes in EPLC, with a maximum at 72 h (before irradiation: 2.79 x 10(3) AU, range 2.42-3.80 x 10(3) AU, and after 72 h: 7.16 x 10(3) AU, range 4.30-16.20 x 10(3) AU), which was more than 3.5 times higher than in BEAS-2B. At 30 Gy, the maximum (6.22 x 10(3) AU, range 5.13-9.71 x 10(3) AU) was observed already after 24 h. These results indicate that normal bronchoepithelial and malignant lung cancer cells contribute to the release of nucleosomes during irradiation in a dose-and time-dependent manner with cancer cells having a stronger impact at low doses. Copyright (C) 2004 S. Karger AG, Basel.
Reboxetine is a selective noradrenaline reuptake inhibitor, whereas mirtazapine acts as an antagonist at noradrenergic alpha(2), serotonin (5-HT2), 5-HT3 and histamine H-1 receptors. In a former study we could demonstrate an inhibitory impact of mirtazapine on cortisol secretion. In the present investigation, the influence of combined administration of 15 mg mirtazapine and 4 mg reboxetine on the cortisol ( COR), adrenocorticotropin ( ACTH), growth hormone (GH), and prolactin (PRL) secretion was examined in 12 healthy male subjects, compared to reboxetine alone ( 4 mg). In a randomized order, the subjects received reboxetine ( 4 mg) alone or the combination of reboxetine ( 4 mg) and mirtazapine ( 15 mg) at 8: 00 a. m. on two different days. After insertion of an intravenous catheter, blood samples were drawn 1 h prior to the administration of single reboxetine or the combination ( reboxetine and mirtazapine), at time of administration, and during the time of 5 h thereafter in periods of 30 min. Serum concentrations of COR, GH, and PRL as well as plasma levels of ACTH were determined in each blood sample by means of double antibody RIA, fluoroimmunoassay and chemiluminescence immunometric assay methods. The area under the curve (AUC) was used as parameter for the COR, ACTH, GH, and PRL response. For statistical evaluation, the Wilcoxon signed-ranks test was performed. There was a pronounced stimulation of COR, ACTH, GH, and PRL concentrations after single administration of reboxetine. When reboxetine was given in combination with mirtazapine, a significant reduction of the COR, ACTH, and PRL stimulation was observed whereas GH secretion patterns remained unchanged, compared to single administration of reboxetine. Apparently, the stimulatory effects of reboxetine on pituitary hormone secretion via noradrenergic mechanisms are counteracted in part by the alpha(2)-blocking properties of mirtazapine and its inhibitory influence on cortisol secretion. Copyright (C) 2004 S. Karger AG, Basel.
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 02/19
Background: Lymphocytes are recruited to sites of inflammation by chemokines. Accordingly, a number of chemokine receptors are differentially expressed on effector T cells. We hypothesized that selected T cells accumulate in inflammatory lung diseases involving different pulmonary compartments. To test this hypothesis the frequencies of chemokine receptor expressing T cells were compared in peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) of children with chronic bronchitis and interstitial lung diseases. Methods: BAL was performed in 70 children. According to clinical, macroscopic and cytological findings 37 children were selected for the study and classified as chronic bronchitis (CB, n=17, m=7, mean age 6.6 yrs.) or interstitial lung diseases (ILD, n=20, m=13, mean age 7.0 yrs.). Patients (n=33) with other diagnoses or without cells in BALF were excluded. CD4+ and CD8+ T cells were analyzed in PB (n=30) and BALF (n=37) by flow cytometry. The percentages of CCR5+and CXCR3+ cells were determined within each T cell subset. Results are expressed as medians. For statistical analyses non-parametric tests (Wilcoxon, Mann-Whitney U) were applied. Results: In peripheral blood, the percentage of CXCR3+ T cells (16.4%, range: 0-35.2%) was higher than the percentage of CCR5+ T cells (3.9%, range: 0-19.1%; p
Fakultät für Mathematik, Informatik und Statistik - Digitale Hochschulschriften der LMU - Teil 01/02
Categorizing continuous variables arises as an important task in statistical analysis, especially in analyzing dose-response relationships. Creating meaningful groups of the predictor variables regarding the outcome variable is desirable in many settings, especially if the form of the relationship is unknown. However it is not always obvious how many groups should be build and where the cutpoints should be placed. Usually more than one explanatory variable has to be included in the analysis, and therefore one has to apply an appropriate statistical model. For this purpose we need a simple approach to model the data without many requirements. Another important issue in statistical analysis and especially in toxicology studies is proving a dose response relationship: increasing response probability with increasing predictor variable. This theses deals with cases where categorization of numerical or categorical predictor variables results as an effect of the dose-response relationship. Isotonic regression is an alternative proposal when one wishes to establish a dose-response relationship, categorize continuous variables and estimate threshold values. The only assumption for this approach is the monotonicity in the response variable. The isotonic regression summarizes the description of n observations to l categories (level sets or solution blocks) by automatically splitting the predictor in constant risk groups. The result is always a step function, and therefore the isotonic regression can be used to fit a changepoint model. The Pooled Adjacent Violators Algorithm (PAVA) is used to fit the data. In relation to model fitting and testing, some problems arise when the response is binary, and in the present work the difficulties are highlighted and some proposals to solve them are given. Regarding isotonic regression and binary response, the isotonic test for trend, the reduced isotonic model, multidimensional isotonic models and methods to assess threshold limit values are discussed. The isotonic framework provides a reliable test for trend which unlike other widely used tests (the Cochran-Armitage test for example) is independent of any monotonic transformation of the dose variable and does not assume a linear shape. However the proposed large sample approximation (a weighted chi-square distribution) does not hold when the overall response probability is less than 5% and thus exact methods are proposed in order to assess the correct p-value. In a simulation study it has been shown that the isotonic likelihood ratio test is more powerful than the Cochran-Armitage test, the Wilcoxon test and the Iso-chi-squared test. The model resulting from PAVA can become more parsimonious if the level sets which correspond to a non significant change for the response variable are eliminated. This model is called reduced isotonic regression. That can be accomplished by two means: a sequence of Fisher tests for the adjacent 2x2 tables or the application of a variation of a "closed testing" procedure. The correction for multiple comparisons is made for the first method by an a-priori estimation of the overall significance level in a permutation procedure. In the second method the control for the expense of the type I error is effected by the closure principal. To select between full isotonic and reduced model, a procedure based on parametric bootstrap is proposed. A simulation study proved that when the maximal coefficient of determination for the analyzed data set is at least 50% and the data can be represented by a step function, the reduced monotonic regression controls successfully the trade off between model complexity and goodness of fit. When more than one predictor is to be taken into account an additive isotonic model can be applied. Alternatively, an isotonic-surfaces model is proposed. This can be estimated by an iterative version of the Pooled Adjacent Violators Algorithm. The result is a sequence of surfaces which is monotonic in every dimension. This approach models interaction and categorizes the predictors in "multivariate" groups by combining them regarding restrictions to the outcome variable. This approach is very useful since, unlike the additive model, it can be easily combined with the reducing procedures to give a simple and interpretable model. However, for practical reasons a maximum of three predictors can be taken into account. A special aspect in analyzing dose-response relationships for a compound known to have harmful health effects, is to estimate a threshold limit value (TVL). On this regard a "hockey stick" threshold model is usually used. As alternative the use of a step function model by fitting the data using isotonic regression is proposed. A set of candidate threshold values is returned, and some threshold value estimation procedures are studied here. One of them starts from the isotonic model and applies the likelihood ratio test to detect the threshold value (method 1). Method 2 is based on the reduced isotonic regression. The performance of these two approaches is outlined in a simulation study under different scenarios and their properties are explored with categorical predictors. It is concluded that these methods possess a satisfactory power to reject the constant risk assumption, when a dose-response relationship exists as well as to estimate the actual threshold. Some limitations regarding the sample size and the force of trend are also discussed. A third method has also been presented. This modifies the closed testing procedure for the special case of thresholds, by setting one end of the regression line conditional to the other. All three threshold value estimation methods can be combined with the isotonic-surfaces model to provide thresholds, taking into account interactions between the predictor variables. The use of isotonic regression and its reduced version can also be extended to other settings. The capability of isotonic regression to be implemented in several models is outlined by describing how isotonic regression can model and test time-varying effects in Cox regression. The monotonic variation in the impact of a predictor included in the model during an observational period can be represented by a step function. An estimation of the time-dependent effect in the extended Cox model is presented based on isotonic regression framework. Smoothing the Schoenfeld residuals plotted against time applying PAVA, can reveal the changepoints without any a priori information about their location. The corresponding step function is then introduced in the model. The power of the Grambsch and Therneau test (which tests for time-variation in the effect of the predictors) can be improved if the isotonic transformation for the Schoenfeld residuals is used. Although this test appears to increase the type I error, its power is higher compared to conventional Grambsch and Therneau test and tests based on fractional polynomials. In summary it arises that isotonic framework is characterized by simplicity and stability. The main drawback underlying its application is the lack of asymptotic support in testing. This can make the use of isotonic models cumbersome since exact or bootstrap methods need to be used.
Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 01/07
Angesichts der zunehmenden Nachfrage nach Geflügelfleisch von Seiten des Verbrauchers wurde die Fragestellung behandelt, ob sich Masthähnchen aus unterschiedlichen Mast-/ bzw. Schlachtbetrieben im Hinblick auf die Qualität des rohen und zubereiteten Produktes unterscheiden. Die untersuchten Broiler stammten aus vier verschiedenen Schlachtbetrieben (A bis D), die jeweils von vertraglich gebundenen Mästern beliefert wurden. Alle Schlachtbetriebe entsprachen dem EU-Standard. Bei den Haltungsformen handelte es sich um konventionelle Bodenhaltung. Die Mäster von Betrieb C verfügten über ein BTS-Haltungssystem (Besonders Tierfreundliche Stallhaltung), welches den Tieren zusätzlich den Auslauf in einem überdachten Außenbereich ermöglicht. Die geschlachteten Tiere wurden von einem nordbayerischen Unternehmen direkt vom jeweiligen Schlachtbetrieb bezogen und frisch zur Untersuchung angeliefert. Die Broiler (n = 64) wurden im Hinblick auf ihre sensorischen Eigenschaften, ausgewählte chemische Parameter, ihren Brennwert sowie ihren Gehalt an auspreßbarem Gewebewasser analysiert. Die sensorische Untersuchung wurde an ungewürzten und an mit einer vorgefertigten Gewürzmischung gewürzten Hähnchen anhand einer bewertenden Prüfung mit 5-Punkte Skale durchgeführt. Die Zubereitung erfolgte mit einem speziellen „Grillhähnchen-Programm“ in einem Combi- Dämpfer. Die chemische Analyse sowie die Bestimmung des auspreßbaren Gewebewassers wurden in Anlehnung an die Amtliche Sammlung von Untersuchungsverfahren nach § 35 LMBG durchgeführt. Zur Berechnung der Brennwerte dienten einzelne Parameter aus der chemisch- physikalischen Analyse. Nach statistischer Auswertung der Ergebnisse der chemisch-physikalischen Untersuchung, der Ermittlung des ungebundenen Gewebewassers und der Brennwertuntersuchung, anhand des Wilcoxon‘schen-Rangsummentests, zeigte sich, daß die untersuchten Broiler der Chargen C signifikant weniger Fett und signifikant mehr Rohprotein enthielten. Das auspreßbare Gewebewasser war bei Charge A signifikant niedriger als bei den übrigen Chargen. Die Brennwerte waren bei allen Chargen weitgehend deckungsgleich, allerdings enthielt C im Vergleich zu den übrigen Chargen signifikant mehr Kilojoule aus Rohprotein als aus Fett. Die sensorische Untersuchung zeigte, daß alle Chargen über einen hohen Genußwert verfügten. Die besten sensorischen Ergebnisse wurden bei der hier gewählten Zubereitungsart allerdings bei einem mittleren Fettgehalt der Broiler erzielt. Aus den gewonnenen Ergebnissen läßt sich ableiten, daß sofern sich das Rohmaterial der Grillhähnchen innerhalb eines gewissen Qualitätsniveaus bewegt, bei gleicher Zubereitung keine bedeutenden Unterschiede in der Qualität des Endproduktes zu erwarten sind. Damit kommt den bromatologischen Aspekten wie Würzung, Zubereitung und Darreichungsform eine besondere Bedeutung zu.
Objectives: To determine the serum concentrations of procollagen type in peptide in severely injured patients with different outcomes and to evaluate the relationship between serum procollagen type III peptide concentrations, sources of increased posttraumatic fibrotic activity (wounds, lung, liver, kidney), and decreased elimination of procollagen type III peptide (liver). Design: Prospective study. Setting: Surgical ICU, university hospital. Patients: Fifty-seven patients (mean injury severity score: 38.5 points, range 13 to 75 points), between 16 and 70 yrs of age, treated in our institution within 6 hrs after the accident. Measurements: Serial measurements were started on admission and continued on a 6-hr basis. After 48 hrs, the monitoring interval was extended to 24 hrs until recovery (but at least until day 14) or death. At each point of evaluation, pulmonary and circulatory function parameters and chest radiographs (once a day) were evaluated, the results were recorded, and blood samples were drawn to determine procollagen type III peptide, total bilirubin, creatinine, [gamma]-glutamyl transferase, polymorphonuclear elastase, and other parameters. Statistic evaluation was done with the Wilcoxon test, Spearman rank correlation, and a multiple regression model. Results: Mean procollagen type m peptide serum concentrations (+/- sd) were significantly different in patients who died (8.0 +/- 3.8 U/mL) compared with those patients who survived with organ failure (2.7 +/- 1.3 U/mL) or without complications (1.4 +/- 0.5 U/mL), respectively. Significant correlations of procollagen type HI peptide concentrations with the serum bilirubin concentrations (r = .7), days with need of mechanical ventilation (r = .64), Pao2/Fio2 ratio (r = -.6), polymorphonuclear elastase (r = .6), serum creatinine concentrations (r = .55), and injury severity score (r = .33) were observed. There was a tendency toward higher serum procollagen type III peptide concentrations in patients with severe skeletal injuries. Conclusions: Serum procollagen type III peptide concentrations in severely injured patients may be considerably increased in correlation with injury severity and outcome. Procollagen type III peptide serum concentrations seem to reflect the sum of increased collagen formation from wound healing and fibrogenesis of mediator-related organ damage (especially lung) and decreased procollagen type HI peptide excretion due to impaired liver function. Further data are necessary to evaluate the role of hepatic elimination in these patients.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.15.043018v1?rss=1 Authors: Annink, K. V., van Leeuwen, I. C. E., van der Aa, N. E., Alderliesten, T., Groenendaal, F., Jellema, R. K., Nijboer, C. H. A., Nikkels, P. G. J., Lammens, M., Benders, M. J. N. L., Hoebeek, F. E., Dudink, J. Abstract: Introduction: In term neonates with hypoxic-ischemic encephalopathy (HIE), cerebellar injury is becoming more and more acknowledged. Animal studies demonstrated that Purkinje cells (PCs) are especially vulnerable for hypoxic-ischemic injury. In neonates, however, the extent and pattern of PC injury has not been investigated. The aim of this study was to determine the distribution of PC injury in the cerebellar vermis of term born neonates with HIE. Methods: Term born neonates with HIE that underwent post-mortem autopsy of the cerebellar vermis were included. Haematoxylin & Eosin (H&E) stained sections of the vermis were used to determine total PC count and morphology (normal, abnormal or non-classified) at the bases and crown of the folia and of the lobules in both the anterior and posterior lobes. Differences in PC count and PC morphology between the anterior and posterior lobe and between the bases and crown were calculated using the paired samples T-test or Wilcoxon-signed rank test. Results: The total number of PCs were significantly higher at the crown compared to the bases (p