An Implicitization Challenge for Binary Factor Analysis

We use tropical geometry to compute the multidegree and Newton polytope of the hypersurface of a statistical model with two hidden and four observed binary random variables, solving an open question stated by Drton, Sturmfels and Sullivant in "Lectures on Algebraic Statistics" (Problem 7.7). The model is obtained from the undirected graphical model of the complete bipartite graph $K_{2,4}$ by marginalizing two of the six binary random variables. We present algorithms for computing the Newton polytope of its defining equation by parallel walks along the polytope and its normal fan. In this way we compute vertices of the polytope. Finally, we also compute and certify its facets by studying tangent cones of the polytope at the symmetry classes vertices. The Newton polytope has 17214912 vertices in 44938 symmetry classes and 70646 facets in 246 symmetry classes.Comment: 25 pages, 5 figures, presented at Mega 09 (Barcelona, Spain

Cytotoxic Efficiency of Human CD8+ T Cell Memory Subtypes

Immunological memory is important to protect humans against recurring diseases. Memory CD8+ T cells are required for quick expansion into effector cells but also provide immediate cytotoxicity against their targets. Whereas many functions of the two main cytotoxic subtypes, effector memory CD8+ T cells (TEM) and central memory CD8+ T cells (TCM), are well defined, single TEM and TCM cell cytotoxicity has not been quantified. To quantify cytotoxic efficiency of TEM and TCM, we developed a FRET-based single cell fluorescent assay with NALM6 target cells which allows analysis of target cell apoptosis, secondary necrosis following apoptosis, and primary necrosis after TEM- or TCM-target cell contact. Both, single cell and population cytotoxicity assays reveal a higher cytotoxic efficiency of TEM compared to TCM, as quantified by target cell apoptosis and secondary necrosis. Perforin, granzyme B, FasL, but not TRAIL expression are higher in TEM compared to TCM. Higher perforin levels (likely in combination with higher granzyme levels) mediate higher cytotoxic efficiency of TEM compared to TCM. Both, TEM and TCM need the same time to find their targets, however contact time between CTL and target, time to induce apoptosis, and time to induce secondary necrosis are all shorter for TEM. In addition, immune synapse formation in TEM appears to be slightly more efficient than in TCM. Defining and quantifying single TEM and TCM cytotoxicity and the respective mechanisms is important to optimize future subset-based immune therapies

Understanding young people's transitions in university halls through space and time

This article contributes to the theoretical discussion about young people's transitions through space and time. Space and time are complex overarching concepts that have creative potential in deepening understanding of transition. The focus of this research is young people's experiences of communal living in university halls. It is argued that particular space-time concepts draw attention to different facets of experience and in combination deepen the understanding of young people's individual and collective transitions. The focus of the article is the uses of the space-time concepts 'routine', 'representation', 'rhythm' and 'ritual' to research young people's experiences. The article draws on research findings from two studies in the North of England. © 2010 SAGE Publications

Qualitative research in an international research program : maintaining momentum while building capacity in nurses

The article describes capacity building components that underpin the participatory action research (PAR) process for this international program. Although nurses are well positioned to lead positive change and advance health, barriers such as the dearth of nurse researchers with doctoral-level training prevent them from effectively responding to rapidly changing health care settings. This research program aimed to improve nursing practice in HIV care. The involvement of decision-makers was strategic, towards influencing policy, and changing nursing practice. The research program was developed with full participation of investigators who represented all participating countries: Canada, Barbados, Jamaica, Uganda, Kenya, and South Africa

The Ursinus Weekly, December 10, 1951

Feulner goes to convention in New York • Supply Store announces 40 percent reductions • Pi Gamma Mu sets initiation banquet for new members • Booster Committee doing art work • Messiah concert called credit to Philip\u27s directing ability • Harte and Lukens named \u2753 year book co-editors • Count to speak at 3rd Forum on January 9 • Y hears lecture on loyalty oath • Students dance at winter whirl • Inge Rudloff to speak • Pre-Christmas week of gay events arrives • Curtain Club may give play again • Candlelight Communion planned Thursday night • St. Nick furthers his education by paying visit to Ursinus College • Editorials: Christmas spirit; Thanks for paint job; New religion discovered • English dorm life described as much different from U.S. • I\u27m dreaming of a tight Christmas • Christmas spirits rise as caroling day draws near • Investment in dinner at Millers\u27 home pays high dividends • Bruin court squad scores 67-61 win over Lycoming team in extra period • Snell\u27s Belles practice for coming court season • Intramural basketball to start after Xmas vacation • Temple Pharmacy defeated by locals as 1951-52 basketball season begins • Twenty-seven report to Coach Kuhrt Wieneke for wrestling • Crusaders\u27 rally dies as Bears win thriller, 60-58 • French Club holds annual holiday soiree • Teacher to address FTA • Jones reads Galsworthy • Chest reaches half mark • Chess Club scores loss to Lansdale teamhttps://digitalcommons.ursinus.edu/weekly/1530/thumbnail.jp

Qualitative research in an international research program: maintaining momentum while building capacity in nurses

Sherpa Romeo green journal. Open access article. Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (CC BY-NC-SA 4.0) appliesNurses are knowledgeable about issues that affect quality and equity of care and are well qualified to inform policy, yet their expertise is seldom acknowledged and their input infrequently invited. In 2007, a large multidisciplinary team of researchers and decisionmakers from Canada and five low- and middle-income countries (Barbados, Jamaica, Uganda, Kenya, and South Africa) received funding to implement a participatory action research (PAR) program entitled “Strengthening Nurses’ Capacity for HIV Policy Development in sub-Saharan Africa and the Caribbean.” The goal of the research program was to explore and promote nurses’ involvement in HIV policy development and to improve nursing practice in countries with a high HIV disease burden. A core element of the PAR program was the enhancement of the research capacity, and particularly qualitative capacity, of nurses through the use of mentorship, role-modeling, and the enhancement of institutional support. In this article we: (a) describe the PAR program and research team; (b) situate the research program by discussing attitudes to qualitative research in the study countries; (c) highlight the incremental formal and informal qualitative research capacity building initiatives undertaken as part of this PAR program; (d) describe the approaches used to maintain rigor while implementing a complex research program; and (e) identify strategies to ensure that capacity building was locally-owned. We conclude with a discussion of challenges and opportunities and provide an informal analysis of the research capacity that was developed within our international team using a PAR approach.Ye

Strain-specific metastatic phenotypes in pheochromocytoma allograft mice

Somatostatin receptor-targeting endoradiotherapy offers potential for treating metastatic pheochromocytomas and paragangliomas, an approach likely to benefit from combination radiosensitization therapy. To provide reliable preclinical in vivo models of metastatic disease, this study characterized the metastatic spread of luciferase-expressing mouse pheochromocytoma (MPC) cells in mouse strains with different immunologic conditions. Bioluminescence imaging showed that, in contrast to subcutaneous non-metastatic engraftment of luciferase-expressing MPC cells in NMRI-nude mice, intravenous cell injection provided only suboptimal metastatic spread in both NMRI-nude mice and hairless SCID (SHO) mice. Treatment of NMRI-nude mice with anti-Asialo GM1 serum enhanced metastatic spread due to substantial depletion of natural killer (NK) cells. However, reproducible metastatic spread was only observed in NK cell-defective SCID/beige mice and in hairless immunocompetent SKH1 mice bearing disseminated or liver metastases, respectively. Liquid chromatography tandem mass spectrometry of urine samples showed that subcutaneous and metastasized tumor models exhibit comparable renal monoamine excretion profiles characterized by increasing urinary dopamine, 3-methoxytyramine, norepinephrine and normetanephrine. Metastases-related epinephrine and metanephrine were only detectable in SCID/beige mice. Positron emission tomography and immunohistochemistry revealed that all metastases maintained somatostatin receptor-specific radiotracer uptake and immunoreactivity, respectively. In conclusion, we demonstrate that intravenous injection of luciferase-expressing MPC cells into SCID/beige and SKH1 mice provides reproducible and clinically relevant spread of catecholamine-producing and somatostatin receptor-positive metastases. These standardized preclinical models allow for precise monitoring of disease progression and should facilitate further investigations on theranostic approaches against metastatic pheochromocytomas and paragangliomas

Hierarchisierung von Risikofaktoren für schwere COVID-19-Erkrankungsverläufe im Kontext der COVID-19-Schutzimpfungen

Angesichts der derzeitigen Impfstoffknappheit geht mit den bundesweiten Schutzimpfungen gegen COVID-19 die Notwendigkeit einer Priorisierung bestimmter Bevölkerungsgruppen einher. Basierend auf den Empfehlungen der STIKO sollen zunächst Personen mit besonders hohem Risiko für schwere oder tödliche COVID-19-Verläufe oder beruflicher Exposition geimpft werden. Diese Empfehlungen stützen sich überwiegend auf internationale Studien - für den deutschen Versorgungskontext steht nur begrenzt Evidenz zur Bedeutung relevanter Risikofaktoren für einen schweren COVID-19-Verlauf zur Verfügung. Das Ziel der im Epidemiologischen Bulletin 19/2021 vorgestellten Studie war es, die Relevanz ausgewählter Vorerkrankungen für einen schweren COVID-19-Verlauf in der in Deutschland lebenden Bevölkerung empirisch zu überprüfen, Erkrankungen hinsichtlich ihres Risikos für einen schweren COVID-19-Verlauf zu ordnen und damit eine einfache, im Versorgungsalltag unkompliziert umsetzbare und dabei möglichst effektive Grundlage für die Impfrangfolge in der ambulanten ärztlichen Versorgung bilden

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe