The Grizzly, October 26, 2017

History of Halloween • Senior English Majors go Gothic • SAO Plans Halloween Trip to Dorney • Senior Halloween Party: An Ursinus Tradition • Fright Night: Phoenixville Theatre Hosts Horror Film Series • Spooky Ursinus Folk • Something Wicked This Way Comes • Opinions: A Ghost Story Haunts with Quiet Pain and Loss; Trick-or-Treating Should End for Children Older than Thirteen • Superstitions Win Confidence for Ursinus Student Athletes • First Year Athletes Face Scary New Adjustmentshttps://digitalcommons.ursinus.edu/grizzlynews/1629/thumbnail.jp

The Grizzly, November 9, 2017

Department of Education Rolls Back Piece of Title IX • Joe DeSimone \u2786 Receives Heinz Award • New Education Major Created • Nadler Awarded Tow Fellowship • Dr. Kerr Appears on Full Frontal with Samantha Bee • History of a Historian • Opinions: Male Gun Violence Must End with Restrictive Gun Legislation; JFK\u27s Legacy Should be More Than Assassination Conspiracies • Senior Athletes Share Memories as Fall Sports Seasons Wind to a Close • Football Drops Three of Last Four Gameshttps://digitalcommons.ursinus.edu/grizzlynews/1631/thumbnail.jp

Malaria, Intestinal Helminths and Other Risk Factors for Stillbirth in Ghana

Objective. The objective of the study was to assess Plasmodium/intestinal helminth infection in pregnancy and other risk factors for stillbirth in Ghana. Methods. A cross-sectional study of women presenting for delivery in two hospitals was conducted during November-December 2006. Data collected included sociodemographic information, medical and obstetric histories, and anthropometric measures. Laboratory investigations for the presence of Plasmodium falciparum and intestinal helminths, and tests for hemoglobin levels were also performed. Results. The stillbirth rate was relatively high in this population (5%). Most of the stillbirths were fresh and 24% were macerated. When compared to women with no malaria, women with malaria had increased risk of stillbirth (OR = 1.9, 95% CI = 1.2–9.3). Other factors associated with stillbirth were severe anemia, low serum folate concentration, past induced abortion, and history of stillbirth. Conclusion. The fact that most of the stillbirths were fresh suggests that higher quality intrapartum care could reduce stillbirth rates

Physical Mechanisms for Vertical-CLVD Earthquakes at Active Volcanoes

Many volcanic earthquakes large enough to be detected globally have anomalous focal mechanisms and frequency content. In a previous study, we examined the relationship between active volcanism and the occurrence of a specific type of shallow, non-double-couple earthquake. We identified 101 earthquakes with vertical compensated-linear-vector-dipole (vertical-CLVD) focal mechanisms that took place near active volcanoes between 1976 and 2009. The majority of these earthquakes, which have magnitudes 4.3 less than or equal to MW less than or equal to 5.8, are associated with documented episodes of volcanic unrest. Here we further characterize vertical-CLVD earthquakes and explore possible physical mechanisms. Through teleseismic body-wave analysis and examination of the frequency content of vertical-CLVD earthquakes, we demonstrate that these events have longer source durations than tectonic earthquakes of similar magnitude. We examine the covariance matrix for one of the best-recorded earthquakes and confirm that the isotropic and pure vertical-CLVD components of the moment tensor cannot be independently resolved using our long-period seismic data set. Allowing for this trade-off, we evaluate several physical mechanisms that may produce earthquakes with deviatoric vertical-CLVD moment tensors. We find that physical mechanisms related to fluid flow and volumetric changes are incompatible with seismological, geological, and geodetic observations of vertical-CLVD earthquakes. However, ring-faulting mechanisms explain many characteristics of vertical-CLVD earthquakes, including their seismic radiation patterns, source durations, association with volcanoes in specific geodynamic environments, and the timing of the earthquakes relative to volcanic activity

Reducing emergency hospital admissions: A population health complex intervention of an enhanced model of primary care and compassionate communities

YesBackground: Reducing emergency admissions to hospital has been a cornerstone of health care policy. There is little evidence of systematic interventions which achieved this aim across a population. We report the impact on unplanned admissions to hospital through a complex intervention over a 44 month period in Frome, Somerset. Aim: A population health complex intervention of an enhanced model of primary care and compassionate communities to improve population health and reduce emergency admissions to hospital Design: A cohort retrospective study of a complex intervention on all emergency admissions in Frome compared to Somerset from April 2013 to December 2017. Setting: Frome Medical Practice, Somerset Methods: Patients were identified using broad criteria including anyone with cause for concern. Patient centred goal setting and care planning combined with a compassionate community social approach was implemented broadly across the population of Frome. Results: There was a progressive reduction, by 7.9 cases per quarter (95% CI: 2.8, 13.1; p=0.006) in unplanned hospital admissions across the whole population of Frome, over the study period from April 2014 to December 2017. At the same time, there was sharp increase in the number of admissions per quarter, within the Somerset, with an increase in the number of unplanned admissions of 236 per quarter (95% CI: 152, 320; p<0.001). Conclusion: The complex intervention in Frome was associated with highly significant reductions in unplanned admissions to hospital with reduction of healthcare costs across the whole population of From

Immunological insights into COVID-19 in Southern Nigeria

Introduction: One of the unexpected outcomes of the COVID-19 pandemic was the relatively low levels of morbidity and mortality in Africa compared to the rest of the world. Nigeria, Africa's most populous nation, accounted for less than 0.01% of the global COVID-19 fatalities. The factors responsible for Nigeria's relatively low loss of life due to COVID-19 are unknown. Also, the correlates of protective immunity to SARS-CoV-2 and the impact of pre-existing immunity on the outcome of the COVID-19 pandemic in Africa are yet to be elucidated. Here, we evaluated the natural and vaccine-induced immune responses from vaccinated, non-vaccinated and convalescent individuals in Southern Nigeria throughout the three waves of the COVID-19 pandemic in Nigeria. We also examined the pre-existing immune responses to SARS-CoV-2 from samples collected prior to the COVID-19 pandemic. Methods: We used spike RBD and N- IgG antibody ELISA to measure binding antibody responses, SARS-CoV-2 pseudotype assay protocol expressing the spike protein of different variants (D614G, Delta, Beta, Omicron BA1) to measure neutralizing antibody responses and nucleoprotein (N) and spike (S1, S2) direct ex vivo interferon gamma (IFNγ) T cell ELISpot to measure T cell responses. Result: Our study demonstrated a similar magnitude of both binding (N-IgG (74% and 62%), S-RBD IgG (70% and 53%) and neutralizing (D614G (49% and 29%), Delta (56% and 47%), Beta (48% and 24%), Omicron BA1 (41% and 21%)) antibody responses from symptomatic and asymptomatic survivors in Nigeria. A similar magnitude was also seen among vaccinated participants. Interestingly, we revealed the presence of preexisting binding antibodies (N-IgG (60%) and S-RBD IgG (44%)) but no neutralizing antibodies from samples collected prior to the pandemic. Discussion: These findings revealed that both vaccinated, non-vaccinated and convalescent individuals in Southern Nigeria make similar magnitude of both binding and cross-reactive neutralizing antibody responses. It supported the presence of preexisting binding antibody responses among some Nigerians prior to the COVID-19 pandemic. Lastly, hybrid immunity and heterologous vaccine boosting induced the strongest binding and broadly neutralizing antibody responses compared to vaccine or infection-acquired immunity alone

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival