The Grizzly, January 26, 1979

Campus Life Committee to Replace SFARC • Quad Fire Brought Quickly Under Control • The Fabulous Greaseband Presents...Rock \u27N\u27 Roll Revue Tonight • Christmas Thefts Hit Women\u27s Dorms • Four-One-Four Proposed • Integrated Dining: An Interesting Proposal • Low Attendance Attracts Attention • Letters to the Editor: No static at all?; Big-name concert • Roving Reporter: Alcohol policy • Ritter Gift • Class Skiing Trips: Coming Up • Billy Joel: Isn\u27t One Elton John Enough? • Grateful Dead Rocks Spectrum • Operatic Forum • Audio Corner: Receivers • Token Tolkien • Financial aid night to be held; Meistersingers on tour; New sports editor; Gift collection received; William J. Phillip prize endowed • USGA Elections Near • Bears Sink Below .500 • Cagers Capture Only One Of Six • Flying Fish • Grapplers Groping • Girl\u27s B-Ballhttps://digitalcommons.ursinus.edu/grizzlynews/1010/thumbnail.jp

Evaluation of Handheld Assays for the Detection of Ricin and Staphylococcal Enterotoxin B in Disinfected Waters

Development of a rapid field test is needed capable of determining if field supplies of water are safe to drink by the warfighter during a military operation. The present study sought to assess the effectiveness of handheld assays (HHAs) in detecting ricin and Staphylococcal Enterotoxin B (SEB) in water. Performance of HHAs was evaluated in formulated tap water with and without chlorine, reverse osmosis water (RO) with chlorine, and RO with bromine. Each matrix was prepared, spiked with ricin or SEB at multiple concentrations, and then loaded onto HHAs. HHAs were allowed to develop and then read visually. Limits of detection (LOD) were determined for all HHAs in each water type. Both ricin and SEB were detected by HHAs in formulated tap water at or below the suggested health effect levels of 455 ng/mL and 4.55 ng/mL, respectively. However, in brominated or chlorinated waters, LODs for SEB increased to approximately 2,500 ng/mL. LODs for ricin increased in chlorinated water, but still remained below the suggested health effect level. In brominated water, the LOD for ricin increased to approximately 2,500 ng/mL. In conclusion, the HHAs tested were less effective at detecting ricin and SEB in disinfected water, as currently configured

International Pediatric Otolaryngology Group (IPOG) consensus recommendations: Hearing loss in the pediatric patient

Objective To provide recommendations for the workup of hearing loss in the pediatric patient. Methods Expert opinion by the members of the International Pediatric Otolaryngology Group. Results Consensus recommendations include initial screening and diagnosis as well as the workup of sensorineural, conductive and mixed hearing loss in children. The consensus statement discusses the role of genetic testing and imaging and provides algorithms to guide the workup of children with hearing loss. Conclusion The workup of children with hearing loss can be guided by the recommendations provided herein

Mid-term Body Mass Index increase among obese and non-obese individuals in middle life and deprivation status: A cohort study

BACKGROUND: In the UK, obesity is associated with a clear socioeconomic gradient, with individuals of lower socioeconomic status being more likely to be obese. Several previous studies, using individual measures of soecioeconomic status, have shown a more rapid increase in Body Mass Index (BMI) over time among adults of lower socioeconomic status. We conducted a study to further examine whether ecologically defined deprivation status influences within-individual BMI change during middle life, as the answer to this question can help determine optimal preventive strategies both for obesity per se, and its' associated socioeconomic disparities. METHODS: Anonymised records of participants to the Stockport population-based cardiovascular disease risk factor screening programme were analysed. Individuals aged 35–55 who had a first screening episode between 1989 and 1993, and a subsequent screening episode were included in the study. Deprivation status was defined using quintiles of the Townsend score. Mean annual BMI change by deprivation group was calculated using linear regression. Subsequently, deprivation group was included in the model as an ordinal variable, to test for trend. The modelling was repeated separately for individuals who were obese (BMI < 30) and non-obese at the time of first screening. In supplementary analysis, regression models were also adjusted for baseline BMI. RESULTS: Of 21,976 women and 19,158 men initially screened, final analysis included just over half of all individuals [11,158 (50.8%) women and 9,831 (51.3%) men], due to the combined effect of loss to follow-up and incomplete BMI ascertainment. In both sexes BMI increased by 0.19 kg/m(2 )annually (95% Confidence Intervals 0.15–0.24 for women and 0.16–0.23 for men). All deprivation groups had similar mean annual change, and there was no evidence of a significant deprivation trend (p = 0.801, women and 0.892, men). Restricting the analysis to individuals who were non-obese at baseline did not alter the results in relation to the lack of a deprivation effect. When restricting the analysis to individuals who were obese at baseline however, the findings were suggestive of an association of BMI increase with higher deprivation group, which was further supported by a significant association when adjusting for baseline BMI. CONCLUSION: In the study setting, the BMI of non-obese individuals aged 35–55 was increasing over time independently of deprivation status; among obese individuals a positive association with higher deprivation was found. The findings support that socioeconomic differences in mean BMI and obesity status are principally attained prior to 35 years of age. Efforts to tackle inequalities in mean BMI and obesity status should principally concentrate in earlier life periods, although there may still be scope for focusing inequality reduction efforts on obese individuals even in middle life

Neoadjuvant Chemotherapy Is Associated with Altered Immune Cell Infiltration and an Anti-Tumorigenic Microenvironment in Resected Pancreatic Cancer

PURPOSE: Neoadjuvant chemotherapy is increasingly administered to patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC), yet its impact on the tumor immune microenvironment is incompletely understood. DESIGN: We employed quantitative, spatially resolved multiplex immunofluorescence and digital image analysis to identify T-cell subpopulations, macrophage polarization states, and myeloid cell subpopulations in a multi-institution cohort of up-front resected primary tumors (n = 299) and in a comparative set of resected tumors after FOLFIRINOX-based neoadjuvant therapy (n = 36) or up-front surgery (n = 30). Multivariable-adjusted Cox proportional hazards models were used to evaluate associations between the immune microenvironment and patient outcomes. RESULTS: In the multi-institutional resection cohort, immune cells exhibited substantial heterogeneity across patient tumors and were located predominantly in stromal regions. Unsupervised clustering using immune cell densities identified four main patterns of immune cell infiltration. One pattern, seen in 20% of tumors and characterized by abundant T cells (T cell-rich) and a paucity of immunosuppressive granulocytes and macrophages, was associated with improved patient survival. Neoadjuvant chemotherapy was associated with a higher CD8:CD4 ratio, greater M1:M2-polarized macrophage ratio, and reduced CD15+ARG1+ immunosuppressive granulocyte density. Within neoadjuvant-treated tumors, 72% showed a T cell-rich pattern with low immunosuppressive granulocytes and macrophages. M1-polarized macrophages were located closer to tumor cells after neoadjuvant chemotherapy, and colocalization of M1-polarized macrophages and tumor cells was associated with greater tumor pathologic response and improved patient survival. CONCLUSIONS: Neoadjuvant chemotherapy with FOLFIRINOX shifts the PDAC immune microenvironment toward an anti-tumorigenic state associated with improved patient survival

Evaluating the health and economic impact of osteoarthritis pain in the workforce: results from the National Health and Wellness Survey

<p>Abstract</p> <p>Background</p> <p>There has been increasing recognition that osteoarthritis (OA) affects younger individuals who are still participants in the workforce, but there are only limited data on the contribution of OA pain to work productivity and other outcomes in an employed population. This study evaluated the impact of OA pain on healthcare resource utilization, productivity and costs in employed individuals.</p> <p>Methods</p> <p>Data were derived from the 2009 National Health and Wellness Survey. Univariable and multivariable analyses were used to characterize employed individuals (full-time, part-time, or self-employed) ≥20 years of age who were diagnosed with OA and had arthritis pain in the past month relative to employed individuals not diagnosed with OA or not experiencing arthritis pain in the past month. Work productivity was assessed using the Work Productivity and Activity Impairment (WPAI) questionnaire; health status was assessed using the physical (PCS) and mental component summary (MCS) scores from the SF-12v2 Health Survey and SF-6D health utilities; and healthcare utilization was evaluated by type and number of resources within the past 6 months. Direct and indirect costs were estimated and compared between the two cohorts.</p> <p>Results</p> <p>Individuals with OA pain were less likely to be employed. Relative to workers without OA pain (n = 37,599), the OA pain cohort (n = 2,173) was significantly older (mean age 52.1 ± 11.5 years vs 41.4 ± 13.2 years; <it>P </it>< 0.0001) and with a greater proportion of females (58.2% vs 45.9%; <it>P </it>< 0.0001). OA pain resulted in greater work impairment than among workers without OA pain (34.4% versus 17.8%; <it>P </it>< 0.0001), and was primarily due to presenteeism (impaired activity while at work). Health status, assessed both by the SF-12v2 and the SF-6D was significantly poorer among workers with OA pain (<it>P </it>< 0.0001), and healthcare resource utilization was significantly higher (<it>P </it>< 0.0001) than workers without OA pain. Total costs were higher in the OA pain cohort ($15,047 versus$8,175; <it>P </it>< 0.0001), driven by indirect costs that accounted for approximately 75% of total costs.</p> <p>Conclusions</p> <p>A substantial proportion of workers suffer from OA pain. After controlling for confounders, the impact of OA pain was significant, resulting in lower productivity and higher costs.</p

Health-related quality of life results from the phase III CheckMate 067 study

Background Nivolumab, a monoclonal antibody of immune checkpoint programmed death 1 on T cells (PD-1), combined with ipilimumab, an immune checkpoint cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor, as combination therapy on the one hand and nivolumab as monotherapy on the other, have both demonstrated improved efficacy compared with ipilimumab alone in the CheckMate 067 study. However, the combination resulted in a higher frequency of grade 3/4 adverse events (AEs), which could result in diminished health-related quality of life (HRQoL). Here we report analyses of HRQoL for patients with advanced melanoma in clinical trial CheckMate 067.Patients and methods HRQoL was assessed at weeks 1 and 5 per 6-week cycle for the first 6 months, once every 6 weeks thereafter, and at two follow-up visits using the European Organization for Research and Treatment of Care Core Quality of Life Questionnaire and the EuroQoL Five Dimensions Questionnaire. In addition to the randomised population, patient subgroups, including BRAF mutation status, partial or complete response, treatment-related AEs of grade 3/4, and those who discontinued due to any reason and due to an AE, were investigated.Results Nivolumab and ipilimumab combination and nivolumab alone both maintained HRQoL, and no clinically meaningful deterioration was observed over time compared with ipilimumab. In addition, similar results were observed across patient subgroups, and no clinically meaningful changes in HRQoL were observed during follow-up visits for patients who discontinued due to any cause.Conclusion These results further support the clinical benefit of nivolumab monotherapy and nivolumab and ipilimumab combination therapy in patients with advanced melanoma. The finding that the difference in grade 3/4 AEs between the arms did not translate into clinically meaningful differences in the reported HRQoL may be relevant in the clinical setting.Study number NCT01844505

Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities

Peer reviewe

Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 x 10(-8)) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.Peer reviewe