142 research outputs found
Banking Geography and Cross-Fertilization in the Productivity Growth of US Commercial Banks
The US banking industry offers a unique, natural and fertile environment to study geography's effects on banks' behavior and performance. The literature on banks' operating performance, while extensive, says little about the influence of spatial interactions on banks' performance. We compute and examine, using a physical distance-based spatio-temporal empirical model, the state-wide total factor productivity growth (TFPG) indices of US commercial banks for each state for the 1971-1995 period. We observe that the productivity growth of commercial banks in state i depends strongly, positively, and contemporaneously on the productivity growth of commercial banks located in state i's contiguous states. Further, “regulatory space” appears to induce frictions and lessen the documented spatial interactions. These findings support our plea that research on commercial banking sector's behavior need to pay a particular attention to the effects of banking geography.Spatial, Commercial Banks, Total Factor Productivity Growth, Kalman Filter
Banking geography and cross-fertilization in the productivity growth of US commercial banks
The US banking industry offers a unique, natural and fertile environment to study geography's effects on banks' behavior and performance. The literature on banks' operating performance, while extensive, says little about the influence of spatial interactions on banks' performance. We compute and examine, using a physical distance-based spatio-temporal empirical model, the state-wide total factor productivity growth (TFPG) indices of US commercial banks for each state for the 1971-1995 period. We observe that the productivity growth of commercial banks in state i depends strongly, positively, and contemporaneously on the productivity growth of commercial banks located in state i's contiguous states. Further, regulatory space appears to induce frictions and lessen the documented spatial interactions. These findings support our plea that research on commercial banking sector's behavior need to pay a particular attention to the effects of banking geography
Why do women not use antenatal services in low and middle income countries? A metasynthesis of qualitative studies
Background:
Almost 50% of women in low & middle income countries (LMIC’s) don’t receive adequate antenatal care. Women’s views can offer important insights into this problem. Qualitative studies exploring inadequate use of antenatal services have been undertaken in a range of countries, but the findings are not easily transferable. We aimed to inform the development of future antenatal care programmes through a synthesis of findings in all relevant qualitative studies.
Methods and Findings:
Using a pre-determined search strategy, we identified robust qualitative studies reporting on the views and experiences of women in LMIC’s who received inadequate antenatal care. We used meta-ethnographic techniques to generate themes and a line of argument synthesis. We derived policy relevant hypotheses from the findings.
We included 21 papers representing the views of more than 1230 women from 15 countries. Three key themes were identified: ‘Pregnancy as socially risky and physiologically healthy’; ‘Resource use and survival in conditions of extreme poverty’and ‘Not getting it right first time’. The line of argument synthesis describes a dissonance between programme design and cultural contexts that may restrict access and discourage return visits. We hypothesize that centralized, risk-focused antenatal care programmes may be at odds with the resources, beliefs and experiences of pregnant women who underuse antenatal services.
Conclusions:
Our findings suggest that there may be a mis-alignment between current antenatal provision and the social and cultural context of some women in LMIC’s. Antenatal care provision that is theoretically and contextually at odds with local contextual beliefs and experiences are likely to be underused, especially when attendance generates increased personal risks of lost family resource or physical danger during travel; when the promised care is not delivered due to resource constraints; and when women experience covert or overt abuse in care settings
The Impact of Advocacy Organizations on Low-Income Housing Policy in U.S. Cities
Financial support for affordable housing competes with many other municipal priorities. This work seeks to explain the variation in support for affordable housing among U.S. cities with populations of 100,000 or more. Using multivariate statistical analysis, this research investigates political explanations for the level of city expenditures on housing and community with a particular interest in the influence of housing advocacy organizations (AOs). Data for the model were gathered from secondary sources, including the U.S. Census and the National Center for Charitable Statistics. Among other results, the analysis indicates that, on average, the political maturity of AOs has a statistically significant, positive effect on local housing and community development expenditures
Clinical Ethics in Gabon: The Spectrum of Clinical Ethical Issues Based on Findings from In-Depth Interviews at Three Public Hospitals
Introduction Unlike issues in biomedical research ethics, ethical challenges arising in daily clinical care in Sub-Saharan African countries have not yet been studied in a systematic manner. However this has to be seen as a distinct entity as we argue in this paper. Our aim was to give an overview of the spectrum of clinical ethical issues and to understand what influences clinical ethics in the Sub-Saharan country of Gabon. Materials and Methods In-depth interviews with 18 health care professionals were conducted at three hospital sites in Gabon. Interview transcripts were analyzed using a grounded theory approach (open and axial coding),giving a qualitative spectrum of categories for clinical ethical issues. Validity was checked at a meeting with study participants and other health care experts in Gabon after analysis of the data. Results Twelve main categories (with 28 further-specified subcategories) for clinical ethical issues were identified and grouped under three core categories: A) micro level: "confidentiality and information","interpersonal, relational and behavioral issues","psychological strain of individuals",and "scarce resources";B) meso level: "structural issues of medical institutions","issues with private clinics","challenges connected to the family",and "issues of education, training and competence";and C) macro level: "influence of society, culture, religion and superstition","applicability of western medicine","structural issues on the political level",and "legal issues". Discussion Interviewees reported a broad spectrum of clinical ethical issues that go beyond challenges related to scarce financial and human resources. Specific socio-cultural, historical and educational backgrounds also played an important role. In fact these influences are central to an understanding of clinical ethics in the studied local context. Further research in the region is necessary to put our study into perspective. As many participants reported a lack of awareness of ethical issues amongst other health care professionals in daily clinical practice, we suggest that international organizations and national medical schools should consider infrastructure and tools to improve context-sensitive capacity building in clinical ethics for Sub-Saharan African countries like Gabon
Decellularized Matrix from Tumorigenic Human Mesenchymal Stem Cells Promotes Neovascularization with Galectin-1 Dependent Endothelial Interaction
BACKGROUND: Acquisition of a blood supply is fundamental for extensive tumor growth. We recently described vascular heterogeneity in tumours derived from cell clones of a human mesenchymal stem cell (hMSC) strain (hMSC-TERT20) immortalized by retroviral vector mediated human telomerase (hTERT) gene expression. Histological analysis showed that cells of the most vascularized tumorigenic clone, -BD11 had a pericyte-like alpha smooth muscle actin (ASMA+) and CD146+ positive phenotype. Upon serum withdrawal in culture, -BD11 cells formed cord-like structures mimicking capillary morphogenesis. In contrast, cells of the poorly tumorigenic clone, -BC8 did not stain for ASMA, tumours were less vascularized and serum withdrawal in culture led to cell death. By exploring the heterogeneity in hMSC-TERT20 clones we aimed to understand molecular mechanisms by which mesenchymal stem cells may promote neovascularization. METHODOLOGY/PRINCIPAL FINDINGS: Quantitative qRT-PCR analysis revealed similar mRNA levels for genes encoding the angiogenic cytokines VEGF and Angiopoietin-1 in both clones. However, clone-BD11 produced a denser extracellular matrix that supported stable ex vivo capillary morphogenesis of human endothelial cells and promoted in vivo neovascularization. Proteomic characterization of the -BD11 decellularized matrix identified 50 extracellular angiogenic proteins, including galectin-1. siRNA knock down of galectin-1 expression abrogated the ex vivo interaction between decellularized -BD11 matrix and endothelial cells. More stable shRNA knock down of galectin-1 expression did not prevent -BD11 tumorigenesis, but greatly reduced endothelial migration into -BD11 cell xenografts. CONCLUSIONS: Decellularized hMSC matrix had significant angiogenic potential with at least 50 angiogenic cell surface and extracellular proteins, implicated in attracting endothelial cells, their adhesion and activation to form tubular structures. hMSC -BD11 surface galectin-1 expression was required to bring about matrix-endothelial interactions and for xenografted hMSC -BD11 cells to optimally recruit host vasculature
Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity
The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)
Multi-ethnic genome-wide association study for atrial fibrillation
Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF
Genetic mechanisms of critical illness in COVID-19.
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 × 10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
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