Social workers and clients: Women at the Merrill-Palmer Institute, 1920-1970 (Michigan).

The Merrill-Palmer Motherhood and Home Training School was founded in 1919. It operated independently until the 1970\u27s, when it was absorbed by Wayne State University. Lizzie Merrill-Palmer founded the School with the intention of providing homemaking training to young girls, but over the years the School expanded its services. In my thesis I will focus on the Merrill-Palmer staff and their clients from 1920 to 1970. Through the years, the social workers and the clients both tried to achieve some measure of control or power in their relationship. This interaction was significantly influenced by the factors of race, class, and ethnicity. The social workers and their clients were affected by prevailing gender concepts in American society. The Merrill-Palmer staff justified their position as career women through their professional status. The staff, however, promoted traditional gender roles to their clients. In my thesis, I wish to demonstrate how changes in American society, combined with the factors of race, class, ethnicity and gender, affected the social worker/client relationship. (Abstract shortened by UMI.)Dept. of History, Philosophy, and Political Science. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis1993 .B455. Source: Masters Abstracts International, Volume: 32-04, page: 1130. Chair: Christina Simmons. Thesis (M.A.)--University of Windsor (Canada), 1993

Comparison of SST diurnal variation models over the Tropical Warm Pool region

Four sea surface temperature (SST) diurnal variation (DV) models have been compared against Multi-functional Transport Satellite - 1R (MTSAT-1R) SST measurements over the Tropical Warm Pool region (TWP, 90°E-170°E, 25°S-15°N) for four months from January to April 2010. The four models include one empirical model formulated by Chelle Gentemann (hereafter CG03), one physical model proposed by Zeng and Beljaars in 2005 (ZB05) and its updated version (ZB+T), and one air-sea coupled model (the Met Office Unified Model Global Coupled configuration 2, GC2) with ZB05 warm layer scheme added on top of the standard configuration. The sensitivity of the v3 MTSAT-1R data to the “true” changes in SST is first investigated using drifting buoys and is estimated to be 0.60 ± 0.05. This being significantly different from 1, the models are validated against MTSAT-1R data and the same data scaled by the inverse of the sensitivity (representing an estimate of the true variability). Results indicate that all models are able to capture the general DV patterns but with differing accuracies and features. Specifically, CG03 and ZB+T underestimate strong (> 2 K) DV events’ amplitudes especially if we assume that sensitivity-scaled MTSAT-1R variability is most realistic. ZB05 can effectively capture the DV cycles under most DV and wind conditions, as well as the DV spatial distribution. GC2 tends to overestimate small-moderate (< 2 K) DV events but can reasonably predict large DV events. 1-3 hr lags in warming start and peak times are found in GC2

TV Wars: Exclusive Content and Platform Competition in Pay TV

The article examines incentives for exclusive distribution of premium television programming. Static analysis shows that a vertically integrated operator with premium programming always supplies this content to the rival distributor, using per-subscriber fees to soften competition. In a dynamic setting with switching costs exclusivity confers a market share advantage, benefiting the operator in the future. Under certain conditions this future benefit outweighs the opportunity cost of forgone wholesale fees, making exclusivity the preferred choice. Alternative dynamic mechanisms are explored, identifying essential features. The analysis explains the observed incidence of content exclusivity in pay TV and provides guidance for policymakers

Machine learning for determining lateral flow device results for testing of SARS-CoV-2 infection in asymptomatic populations

Rapid antigen tests, in the form of lateral flow devices (LFD) allow testing of a large population for SARS-CoV-2. To reduce the variability seen in device interpretation, we show the design and testing of an AI algorithm based on machine learning. The machine learning (ML) algorithm is trained on a combination of artificially hybridised LFDs and LFD data linked to RT-qPCR result. Participants are recruited from assisted test sites (ATS) and health care workers undertaking self-testing and images analysed using the ML algorithm. A panel of trained clinicians are used to resolve discrepancies. In total, 115,316 images are returned. In the ATS sub study, sensitivity increased from 92.08% to 97.6% and specificity from 99.85% to 99.99%. In the self-read sub-study, sensitivity increased from 16.00% to 100%, and specificity from 99.15% to 99.40%. An ML-based classifier of LFD results outperforms human reads in asymptomatic testing sites and self-reading

Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were rising during early summer 2021 in many countries as a result of the Delta variant. We assessed reverse transcription polymerase chain reaction swab positivity in the Real-time Assessment of Community Transmission–1 (REACT-1) study in England. During June and July 2021, we observed sustained exponential growth with an average doubling time of 25 days, driven by complete replacement of the Alpha variant by Delta and by high prevalence at younger, less-vaccinated ages. Prevalence among unvaccinated people [1.21% (95% credible interval 1.03%, 1.41%)] was three times that among double-vaccinated people [0.40% (95% credible interval 0.34%, 0.48%)]. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination.The study was funded by the Department of Health and Social Care in England. Sequencing was provided through funding from the COVID-19 Genomics UK (COG-UK) Consortium. P.E. is Director of the Medical Research Council (MRC) Centre for Environment and Health (MR/L01341X/1, MR/S019669/1). P.E. acknowledges support from Health Data Research UK (HDR UK); the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre; NIHR Health Protection Research Units (HPRUs) in Chemical and Radiation Threats and Hazards, and Environmental Exposures and Health; the British Heart Foundation Centre for Research Excellence at Imperial College London (RE/18/4/34215); and the UK Dementia Research Institute at Imperial (MC_PC_17114). S.R., C.A.D. acknowledge support: MRC Centre for Global Infectious Disease Analysis, NIHR HPRU in Modelling and Health Economics, Wellcome Trust (200861/Z/16/Z, 200187/Z/15/Z), and Centres for Disease Control and Prevention (US, U01CK0005-01-02). G.C. is supported by an NIHR Professorship. H.War. acknowledges support from an NIHR Senior Investigator Award and the Wellcome Trust (205456/Z/16/Z). We thank The Huo Family Foundation for their support of our work on COVID-19. Quadram authors gratefully acknowledge the support of the Biotechnology and Biological Sciences Research Council (BBSRC); their research was funded by the BBSRC Institute Strategic Programme Microbes in the Food Chain BB/R012504/1 and its constituent project BBS/E/F/000PR10352. We thank members of the COVID-19 Genomics Consortium UK (COG-UK) for their contributions to generating the genomic data used in this study. COG-UK is supported by funding from the MRC, part of UK Research & Innovation (UKRI), NIHR and Genome Research Limited, operating as the Wellcome Sanger Institute

Oral and intravenous iron therapy differentially alter the on- and off-tumor microbiota in anemic colorectal cancer patients

© 2021 The Authors. Published by MDPI. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3390/cancers13061341Iron deficiency anemia is a common complication of colorectal cancer and may require iron therapy. Oral iron can increase the iron available to gut bacteria and may alter the colonic microbiota. We performed an intervention study to compare oral and intravenous iron therapy on the colonic tumor-associated (on-tumor) and paired non-tumor-associated adjacent (off-tumor) microbiota. Anemic patients with colorectal adenocarcinoma received either oral ferrous sulphate (n = 16) or intravenous ferric carboxymaltose (n = 24). On- and off-tumor biopsies were obtained post-surgery and microbial profiling was performed using 16S ribosomal RNA analysis. Off-tumor α- and β-diversity were significantly different between iron treatment groups. No differences in on-tumor diversity were observed. Off-tumor microbiota of oral iron-treated patients showed higher abundances of the orders Clostridiales, Cytophagales, and Anaeroplasmatales compared to intravenous iron-treated patients. The on-tumor microbiota was enriched with the orders Lactobacillales and Alteromonadales in the oral and intravenous iron groups, respectively. The on- and off-tumor microbiota associated with intravenous iron-treated patients infers increased abundances of enzymes involved in iron sequestration and anti-inflammatory/oncogenic metabolite production, compared to oral iron-treated patients. Collectively, this suggests that intravenous iron may be a more appropriate therapy to limit adverse microbial outcomes compared to oral iron.The Ferinject™ used in the original IVICA trial was donated to all study centers, except Nottingham University Hospitals NHS Trust, by Vifor Pharma (Glattbrugg, Switzerland). The study represents independent research funded by the National Institute for Health Research (NIHR) Research for Patient Benefit (RfPB) program (grant number PB-PG-0110-21041)

Exploiting differential Wnt target gene expression to generate a molecular biomarker for colorectal cancer stratification

OBJECTIVE Pathological Wnt pathway activation is a conserved hallmark of colorectal cancer. Wnt-activating mutations can be divided into: i) ligand-independent (LI) alterations in intracellular signal transduction proteins (, β-catenin), causing constitutive pathway activation and ii) ligand-dependent (LD) mutations affecting the synergistic R-Spondin axis (, -fusions) acting through amplification of endogenous Wnt signal transmembrane transduction. Our aim was to exploit differential Wnt target gene expression to generate a mutation-agnostic biomarker for LD tumours. DESIGN We undertook harmonised multi-omic analysis of discovery (n=684) and validation cohorts (n=578) of colorectal tumours collated from publicly available data and the Stratification in Colorectal Cancer Consortium. We used mutation data to establish molecular ground truth and subdivide lesions into LI/LD tumour subsets. We contrasted transcriptional, methylation, morphological and clinical characteristics between groups. RESULTS Wnt disrupting mutations were mutually exclusive. Desmoplastic stromal upregulation of may compensate for absence of epithelial mutation in a subset of stromal-rich tumours. Key Wnt negative regulator genes were differentially expressed between LD/LI tumours, with targeted hypermethylation of some genes (, ) occurring even in CIMP-negative LD cancers. mRNA expression was used as a discriminatory molecular biomarker to distinguish LD/LI tumours (area under the curve >0.93). CONCLUSIONS Epigenetic suppression of appropriate Wnt negative feedback loops is selectively advantageous in LD tumours and differential expression in LD/LI lesions can be exploited as a molecular biomarker. Distinguishing between LD/LI tumour types is important; patients with LD tumours retain sensitivity to Wnt ligand inhibition and may be stratified at diagnosis to clinical trials of Porcupine inhibitors

The analysis of gut microbiota in patients with bile acid diarrhoea treated with colesevelam

© 2023 The Authors. Published by Frontiers Media. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3389/fmicb.2023.1134105Introduction: Bile acid diarrhoea (BAD) is a common disorder that results from an increased loss of primary bile acids and can result in a change in microbiome. The aims of this study were to characterise the microbiome in different cohorts of patients with BAD and to determine if treatment with a bile acid sequestrant, colesevelam, can alter the microbiome and improve microbial diversity. Materials and methods: Patients with symptoms of diarrhoea underwent 75-selenium homocholic acid (75SeHCAT) testing and were categorised into four cohorts: idiopathic BAD, post-cholecystectomy BAD, post-operative Crohn’s disease BAD and 75SeHCAT negative control group. Patients with a positive 75SeHCAT (<15%) were given a trial of treatment with colesevelam. Stool samples were collected pre-treatment, 4-weeks, 8-weeks and 6–12 months post-treatment. Faecal 16S ribosomal RNA gene analysis was undertaken. Results: A total of 257 samples were analysed from 134 patients. α-diversity was significantly reduced in patients with BAD and more specifically, in the idiopathic BAD cohort and in patients with severe disease (SeHCAT <5%); p < 0.05. Colesevelam did not alter bacterial α/β-diversity but patients who clinically responded to treatment had a significantly greater abundance of Fusobacteria and Ruminococcus, both of which aid in the conversion of primary to secondary bile acids. Conclusion: This is the first study to examine treatment effects on the microbiome in BAD, which demonstrated a possible association with colesevelam on the microbiome through bile acid modulation in clinical responders. Larger studies are now needed to establish a causal relationship with colesevelam and the inter-crosstalk between bile acids and the microbiome.The research department of MB received project funding from Bowel and Cancer Research for part of this work. The research department of MB received project funding from an unrestricted grant from Tillotts Pharma for part of this work.Published versio