2,653 research outputs found
An Annotated Bibliography of Recent Literature on Current Developments in Philanthropy
As philanthropic organizations play an increasingly important role in societies around the world, the research on philanthropy – from giving and volunteering practices to regulatory frameworks to digital innovations – has also evolved in recent decades. It is important to develop a thorough overview of the relevant scientific discourses and literature on current developments in philanthropy. This will allow researchers and practitioners to enhance the understanding of philanthropy and to improve its practice worldwide. This report provides new insights on current developments and important changes in the global philanthropic landscape, including trends in global philanthropy and its interaction with other sectors of society
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Syndemics and the PrEP Cascade: Results from a Sample of Young Latino Men Who Have Sex with Men.
Young Latino men who have sex with men (MSM) are a highly vulnerable population for HIV infection. Pre-exposure prophylaxis (PrEP) is a novel biomedical HIV prevention tool that may aid in reducing the disparity in HIV incidence among Latino MSM. However, PrEP use is disproportionally low among Latino MSM and, therefore, identifying barriers along the PrEP continuum of care (the "PrEP cascade") would provide insight into how to best deploy PrEP interventions. Syndemics theory is a prominent framework employed in HIV prevention; however, to date, no known studies have applied this theory to PrEP. Thus, the aim of the current study was to explore the association between syndemics and the PrEP cascade, including the degree to which psychosocial and structural syndemic constructs are related to the PrEP cascade. Participants were 151 young Latino MSM (M age = 24 years; SD = 3) residing in San Diego, California, who completed a battery of online self-report measures. Results indicated high levels of syndemic indicators and varying levels of engagement across the PrEP cascade. As syndemic indicators increased, the odds of engagement across the PrEP cascade were significantly lowered. Psychosocial and structural syndemic factors accounted for unique variance in the PrEP cascade. Results highlight the need for combination interventions that address both psychosocial and structural barriers to PrEP use and persistence among young Latino MSM
Influence of a Hypotensive Agent Upon Coronary Blood Flow and Cardiac Metabolism
There has been considerable doubt as to the direct relationship of coronary blood flow and the level of arterial or perfusing pressure forcing blood into the vessels of the heart muscle. Attempts to delineate clearly these relationships have been complicated by concomitant effects induced by circulating epinephrine. The drug dibenzyline2 makes it possible to evaluate the influence of hypotension on coronary blood flow. Dibenzyline injection induces a fall in blood pressure while maintaining essentially unchanged the cardiac output and the cerebral blood flow (1)
Validation of Envisat MERIS algorithms for chlorophyll retrieval in a large, turbid and optically-complex shallow lake
The 10-year archive of MEdium Resolution Imaging Spectrometer (MERIS) data is an invaluable resource for studies on lake system dynamics at regional and global scales. MERIS data are no longer actively acquired but their capacity for global scale monitoring of lakes from satellites will soon be re-established through the forthcoming Sentinel-3 Ocean and Land Colour Instrument (OLCI). The development and validation of in-water algorithms for the accurate retrieval of biogeochemical parameters is thus of key importance if the potential of MERIS and OLCI data is to be fully exploited for lake monitoring. This study presents the first extensive validation of algorithms for chlorophyll-a (chl-a) retrieval by MERIS in the highly turbid and productive waters of Lake Balaton, Hungary. Six algorithms for chl-a retrieval from MERIS over optically complex Case 2 waters, including band-difference and neural network architectures, were compared using the MERIS archive for 2007-2012. The algorithms were locally-tuned and validated using in situ chl-a data (n = 289) spanning the five year processed image time series and from all four lake basins. In general, both band-difference algorithms tested (Fluorescence Line Height (FLH) and Maximum Chlorophyll Index (MCI)) performed well, whereas the neural network processors were generally found to much less accurately retrieve in situ chl-a concentrations. The Level 1b FLH algorithm performed best overall in terms of chl-a retrieval (R2 = 0.87; RMSE = 4.19 mg m- 3; relative RMSE = 30.75%) and particularly at chl-a concentrations of ≥ 10 mg m- 3 (R2 = 0.85; RMSE = 4.81 mg m- 3; relative RMSE = 20.77%). However, under mesotrophic conditions (i.e., chl-a < 10 mg m- 3) FLH was outperformed by the locally-tuned FUB/WeW processor (relative FLH RMSE < 10 mg m- 3 = 57.57% versus relative FUB/WeW RMSE < 10 mg m- 3 = 46.96%). An ensemble selection of in-water algorithms is demonstrated to improve chl-a retrievals
Metabolic and Inflammatory Biomarkers are Associated with Epigenetic Aging Acceleration Estimates in the GOLDN Study
Background: Recently, epigenetic age acceleration-or older epigenetic age in comparison to chronological age-has been robustly associated with mortality and various morbidities. However, accelerated epigenetic aging has not been widely investigated in relation to inflammatory or metabolic markers, including postprandial lipids.
Methods: We estimated measures of epigenetic age acceleration in 830 Caucasian participants from the Genetics Of Lipid Lowering Drugs and diet Network (GOLDN) considering two epigenetic age calculations based on differing sets of 5′-Cytosine-phosphate-guanine-3′ genomic site, derived from the Horvath and Hannum DNA methylation age calculators, respectively. GOLDN participants underwent a standardized high-fat meal challenge after fasting for at least 8 h followed by timed blood draws, the last being 6 h postmeal. We used adjusted linear mixed models to examine the association of the epigenetic age acceleration estimate with fasting and postprandial (0- and 6-h time points) low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels as well as five fasting inflammatory markers plus adiponectin.
Results: Both DNA methylation age estimates were highly correlated with chronological age (r \u3e 0.90). We found that the Horvath and Hannum measures of epigenetic age acceleration were moderately correlated (r = 0.50). The regression models revealed that the Horvath age acceleration measure exhibited marginal associations with increased postprandial HDL (p = 0.05), increased postprandial total cholesterol (p = 0.06), and decreased soluble interleukin 2 receptor subunit alpha (IL2sRα, p = 0.02). The Hannum measure of epigenetic age acceleration was inversely associated with fasting HDL (p = 0.02) and positively associated with postprandial TG (p = 0.02), interleukin-6 (IL6, p = 0.007), C-reactive protein (C-reactive protein, p = 0.0001), and tumor necrosis factor alpha (TNFα, p = 0.0001). Overall, the observed effect sizes were small and the association of the Hannum residual with inflammatory markers was attenuated by adjustment for estimated T cell type percentages.
Conclusions: Our study demonstrates that epigenetic age acceleration in blood relates to inflammatory biomarkers and certain lipid classes in Caucasian individuals of the GOLDN study. Future studies should consider epigenetic age acceleration in other tissues and extend the analysis to other ethnic groups
Eta bound states in nuclei: a probe of flavour-singlet dynamics
We argue that eta bound states in nuclei are sensitive to the singlet
component in the eta. The bigger the singlet component, the more attraction and
the greater the binding. Thus, measurements of eta bound states will yield new
information about axial U(1) dynamics and glue in mesons. Eta - etaprime mixing
plays an important role in understanding the value of the eta-nucleon
scattering length.Comment: 8 pages, version to appear in PL
COL4A1-related autosomal recessive encephalopathy in 2 Turkish children.
OBJECTIVE: This study presents the neurologic phenotypes of 2 brothers with a novel homozygous COL4A1 mutation that was identified in a large Turkish consanguineous cohort of neurogenetic diseases. METHODS: Whole-exome sequencing and bioinformatic analysis of consanguineous families with children affected by early-onset, neurogenetic disorders was performed using the RD-Connect Genome-Phenome Analysis Platform. We also performed clinical, EEG, and neuroimaging analyses in unaffected siblings and parents. RESULTS: We have identified a homozygous missense mutation in COL4A1 (p.Gly1278Ser, NM_001845.5:c.3832G>T) in 2 siblings affected by small vessel brain disease with periventricular leukoencephalopathy and ocular defects. Presenting symptoms included mild weakness, hemiparetic gait, pyramidal findings, and seizures, whereas their intellectual and behavioral functions were normal. Both parents and 5 of the siblings (3 boys and 2 girls) were heterozygous for the variant. They did not show any clinical or laboratory signs of small vessel disease. CONCLUSIONS: COL4A1 has previously been associated with dominant small vessel disease of the brain and other organs, manifesting with high penetrance in heterozygous mutation carriers. Our findings provide evidence that COL4A1-related encephalopathy can be inherited in an autosomal recessive manner, which is important for counseling, prognosis, and treatment. Genotype-phenotype correlations remain to be established
Alternative Splicing Promotes Tumour Aggressiveness and Drug Resistance in African American Prostate Cancer.
linical challenges exist in reducing prostate cancer (PCa) disparities. The RNA splicing landscape of PCa across racial populations has not been fully explored as a potential molecular mechanism contributing to race-related tumour aggressiveness. Here, we identify novel genome-wide, race-specific RNA splicing events as critical drivers of PCa aggressiveness and therapeutic resistance in African American (AA) men. AA-enriched splice variants of PIK3CD, FGFR3, TSC2 and RASGRP2 contribute to greater oncogenic potential compared with corresponding European American (EA)-expressing variants. Ectopic overexpression of the newly cloned AA-enriched variant, PIK3CD-S, in EA PCa cell lines enhances AKT/mTOR signalling and increases proliferative and invasive capacity in vitro and confers resistance to selective PI3Kδ inhibitor, CAL-101 (idelalisib), in mouse xenograft models. High PIK3CD-S expression in PCa specimens associates with poor survival. These results highlight the potential of RNA splice variants to serve as novel biomarkers and molecular targets for developmental therapeutics in aggressive PCa
Alternative Splicing Promotes Tumour Aggressiveness and Drug Resistance in African American Prostate Cancer.
linical challenges exist in reducing prostate cancer (PCa) disparities. The RNA splicing landscape of PCa across racial populations has not been fully explored as a potential molecular mechanism contributing to race-related tumour aggressiveness. Here, we identify novel genome-wide, race-specific RNA splicing events as critical drivers of PCa aggressiveness and therapeutic resistance in African American (AA) men. AA-enriched splice variants of PIK3CD, FGFR3, TSC2 and RASGRP2 contribute to greater oncogenic potential compared with corresponding European American (EA)-expressing variants. Ectopic overexpression of the newly cloned AA-enriched variant, PIK3CD-S, in EA PCa cell lines enhances AKT/mTOR signalling and increases proliferative and invasive capacity in vitro and confers resistance to selective PI3Kδ inhibitor, CAL-101 (idelalisib), in mouse xenograft models. High PIK3CD-S expression in PCa specimens associates with poor survival. These results highlight the potential of RNA splice variants to serve as novel biomarkers and molecular targets for developmental therapeutics in aggressive PCa
Alternative Splicing Promotes Tumour Aggressiveness and Drug Resistance in African American Prostate Cancer.
linical challenges exist in reducing prostate cancer (PCa) disparities. The RNA splicing landscape of PCa across racial populations has not been fully explored as a potential molecular mechanism contributing to race-related tumour aggressiveness. Here, we identify novel genome-wide, race-specific RNA splicing events as critical drivers of PCa aggressiveness and therapeutic resistance in African American (AA) men. AA-enriched splice variants of PIK3CD, FGFR3, TSC2 and RASGRP2 contribute to greater oncogenic potential compared with corresponding European American (EA)-expressing variants. Ectopic overexpression of the newly cloned AA-enriched variant, PIK3CD-S, in EA PCa cell lines enhances AKT/mTOR signalling and increases proliferative and invasive capacity in vitro and confers resistance to selective PI3Kδ inhibitor, CAL-101 (idelalisib), in mouse xenograft models. High PIK3CD-S expression in PCa specimens associates with poor survival. These results highlight the potential of RNA splice variants to serve as novel biomarkers and molecular targets for developmental therapeutics in aggressive PCa
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