146 research outputs found

    Coronavirus Occurrence and Transmission Over 8 Years in the HIVE Cohort of Households in Michigan

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156082/1/jiaa161.pdfSEL

    Measures of happiness: Which to choose?

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    Happiness is defined as the subjective enjoyment of one’s life as a whole, also called ‘life-satisfaction.’ Two components of happiness are distinguished; an affective component (how well one feels most of the time) and a cognitive component (the degree to which one perceived to get what one wants from life). In this chapter, I present an overview of valid measures of these concepts, drawing on the ‘Collection of Happiness Measures’ of the ‘World Database of Happiness’. To date (2016), this collection includes more than twothousand measures of happiness, mostly single direct questions. Links in this text lead to detail about these measures and the studies in this chapter, I describe the differences and discuss their strengths and weaknesse

    Differential association of the Na+/H+ exchanger regulatory factor (NHERF) family of adaptor proteins with the raft- and the non-raft brush border membrane fractions of NHE3

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    Background/Aims: Trafficking, brush border membrane (BBM) retention, and signal-specific regulation of the Na+/H+ exchanger NHE3 is regulated by the Na+/H+ Exchanger Regulatory Factor (NHERF) family of PDZ-adaptor proteins, which enable the formation of multiprotein complexes. It is unclear, however, what determines signal specificity of these NHERFs. Thus, we studied the association of NHE3, NHERF1 (EBP50), NHERF2 (E3KARP), and NHERF3 (PDZK1) with lipid rafts in murine small intestinal BBM. Methods: Detergent resistant membranes ('lipid rafts') were isolated by floatation of Triton X-incubated small intestinal BBM from a variety of knockout mouse strains in an Optiprep step gradient. Acid-activated NHE3 activity was measured fluorometrically in BCECF-loaded microdissected villi, or by assessment of CO2/HCO3 - mediated increase in fluid absorption in perfused jejunal loops of anethetized mice. Results: NHE3 was found to partially associate with lipid rafts in the native BBM, and NHE3 raft association had an impact on NHE3 transport activity and regulation in vivo. NHERF1, 2 and 3 were differentially distributed to rafts and non-rafts, with NHERF2 being most raft-associated and NHERF3 entirely non-raft associated. NHERF2 expression enhanced the localization of NHE3 to membrane rafts. The use of acid sphingomyelinase-deficient mice, which have altered membrane lipid as well as lipid raft composition, allowed us to test the validity of the lipid raft concept in vivo. Conclusions: The differential association of the NHERFs with the raft-associated and the non-raft fraction of NHE3 in the brush border membrane is one component of the differential and signal-specific NHE3 regulation by the different NHERFs

    Benthic foraminifera living in Gulf of Mexico bathyal and abyssal sediments : community analysis and comparison to metazoan meiofaunal biomass and density

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    Author Posting. © Elsevier B.V., 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part II: Topical Studies in Oceanography 55 (2008): 2617-2626, doi:10.1016/j.dsr2.2008.07.011.Benthic foraminiferal biomass, density, and species composition were determined at ten sites in the Gulf of Mexico. During June 2001 and June 2002, sediment samples were collected with a GoMex boxcorer. A 7.5-cm diameter subcore was taken from a box core collected at each site and sliced into 1-cm or 2-cm sections to a depth of 2 or 3 cm; the >63-mm fraction was examined shipboard for benthic foraminifera. Individual foraminifers were extracted for adenosine triphosphate (ATP) using a luciferin-luciferase assay, which indicated the total ATP content per specimen; that data was converted to organic carbon. Foraminiferal biomass and density varied substantially (~2-53 mg C m-2; ~3,600-44,500 individuals m-2, respectively) and inconsistently with water depth. For example, although two ~1000-m deep sites were geographically separated by only ~75 km, the foraminiferal biomass at one site was relatively low (~9 mg C m-2) while the other site had the highest foraminiferal biomass (~53 mg C m-2). Although most samples from Sigsbee Plain (>3000 m) had low biomass, one Sigsbee site had >20 mg foraminiferal C m-2. The foraminiferal community from all sites (i.e., bathyal and abyssal locales) was dominated by agglutinated, rather than calcareous or tectinous, species. Foraminiferal density never exceeded that of metazoan meiofauna at any site. Foraminiferal biomass, however, exceeded metazoan meiofaunal biomass at five of the ten sites, indicating that foraminifera constitute a major component of the Gulf’s deep-water meiofaunal biomass.Funded by Minerals Management Service contract 1435-01-99-CT-30991 to G.T. Rowe (Texas A&M University)

    Phase II randomised discontinuation trial of brivanib in patients with advanced solid tumours

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    Background: Brivanib is a selective inhibitor of vascular endothelial growth factor and fibroblast growth factor (FGF) signalling. We performed a phase II randomised discontinuation trial of brivanib in 7 tumour types (soft-tissue sarcomas [STS], ovarian cancer, breast cancer, pancreatic cancer, non-small-cell lung cancer [NSCLC], gastric/esophageal cancer and transitional cell carcinoma [TCC]). Patients and methods: During a 12-week open-label lead-in period, patients received brivanib 800 mg daily and were evaluated for FGF2 status by immunohistochemistry. Patients with stable disease at week 12 were randomised to brivanib or placebo. A study steering committee evaluated week 12 response to determine if enrolment in a tumour type would continue. The primary objective was progression-free survival (PFS) for brivanib versus placebo in patients with FGF2-positive tumours. Results: A total of 595 patients were treated, and stable disease was observed at the week 12 randomisation point in all tumour types. Closure decisions were made for breast cancer, pancreatic cancer, NSCLC, gastric cancer and TCC. Criteria for expansion were met for STS and ovarian cancer. In 53 randomised patients with STS and FGF2-positive tumours, the median PFS was 2.8 months for brivanib and 1.4 months for placebo (hazard ratio [HR]: 0.58, p Z 0.08). For all randomised patients with sarcomas, the median PFS was 2.8 months (95% confidence interval [CI]: 1.4e4.0) for those treated with brivanib compared with 1.4 months (95% CI: 1.3e1.6) for placebo (HR Z 0.64, 95% CI: 0.38e1.07; p Z 0.09). In the 36 randomised patients with ovarian cancer and FGF2-positive tumours, the median PFS was 4.0 (95% CI: 2.6e4.2) months for brivanib and 2.0 months (95% CI: 1.2e2.7) for placebo (HR: 0.56, 95% CI: 0.26e1.22). For all randomised patients with ovarian cancer, the median PFS in those randomised to brivanib was 4.0 months (95% CI: 2.6e4.2) and was 2.0 months (95% CI: 1.2e2.7) in those randomised to placebo (HR Z 0.54, 95% CI: 0.25e1.17; p Z 0.11). Conclusion: Brivanib demonstrated activity in STS and ovarian cancer with an acceptable safety profile. FGF2 expression, as defined in the protocol, is not a predictive biomarker of the efficacy of brivanib

    Proof-of-concept of a data-driven approach to estimate the associations of comorbid mental and physical disorders with global health-related disability

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    Objective: The standard method of generating disorder-specific disability scores has lay raters make rankings between pairs of disorders based on brief disorder vignettes. This method introduces bias due to differential rater knowledge of disorders and inability to disentangle the disability due to disorders from the disability due to comorbidities. Methods: We propose an alternative, data-driven, method of generating disorder-specific disability scores that assesses disorders in a sample of individuals either from population medical registry data or population survey self-reports and uses Generalized Random Forests(GRF) to predict global (rather than disorder-specific) disability assessed by clinician ratings or by survey respondent self-reports. This method also provides a principled basis for studying patterns and predictors of heterogeneity in disorder-specific disability. We illustrate this method by analyzing data for 16 disorders assessed in the World Mental Health Surveys(n=53,645).Results: Adjustments for comorbidity decreased estimates of disorder-specific disability substantially. Estimates were generally somewhat higher with GRF than conventional multivariable regression models. Heterogeneity was nonsignificant. Conclusions: The results show clearly that the proposed approach is practical, and that adjustment is needed for comorbidities to obtain accurate estimates of disorder-specific disability. Expansion to a wider range of disorders would likely find more evidence for heterogeneity

    Incorporating field wind data to improve crop evapotranspiration parameterization in heterogeneous regions

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    Accurate parameterization of reference evapotranspiration ( ET0) is necessary for optimizing irrigation scheduling and avoiding costs associated with over-irrigation (water expense, loss of water productivity, energy costs, and pollution) or with under-irrigation (crop stress and suboptimal yields or quality). ET0 is often estimated using the FAO-56 method with meteorological data gathered over a reference surface, usually short grass. However, the density of suitable ET0 stations is often low relative to the microclimatic variability of many arid and semi-arid regions, leading to a potentially inaccurate ET0 for irrigation scheduling. In this study, we investigated multiple ET0 products from six meteorological stations, a satellite ET0 product, and integration (merger) of two stations’ data in Southern California, USA. We evaluated ET0 against lysimetric ET observations from two lysimeter systems (weighing and volumetric) and two crops (wine grapes and Jerusalem artichoke) by calculating crop ET ( ETc) using crop coefficients for the lysimetric crops with the different ET0. ETc calculated with ET0 products that incorporated field-specific wind speed had closer agreement with lysimetric ET, with RMSE reduced by 36 and 45% for grape and Jerusalem artichoke, respectively, with on-field anemometer data compared to wind data from the nearest station. The results indicate the potential importance of on-site meteorological sensors for ET0 parameterization; particularly where microclimates are highly variable and/or irrigation water is expensive or scarce

    Internet of Things in Agricultural Innovation and Security

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    The agricultural Internet of Things (Ag-IoT) paradigm has tremendous potential in transparent integration of underground soil sensing, farm machinery, and sensor-guided irrigation systems with the complex social network of growers, agronomists, crop consultants, and advisors. The aim of the IoT in agricultural innovation and security chapter is to present agricultural IoT research and paradigm to promote sustainable production of safe, healthy, and profitable crop and animal agricultural products. This chapter covers the IoT platform to test optimized management strategies, engage farmer and industry groups, and investigate new and traditional technology drivers that will enhance resilience of the farmers to the socio-environmental changes. A review of state-of-the-art communication architectures and underlying sensing technologies and communication mechanisms is presented with coverage of recent advances in the theory and applications of wireless underground communications. Major challenges in Ag-IoT design and implementation are also discussed

    Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.

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    To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesOver the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) <1.15).We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls).We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P = 9 × 10(-6)). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a 'neurodevelopmental hub' on chromosome 8p11.23.This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4.National Institutes of Mental Health (NIMH, USA) ACE Network Autism Genetic Resource Exchange (AGRE) is a program of Autism Speaks (USA) The Autism Genome Project (AGP) from Autism Speaks (USA) Canadian Institutes of Health Research (CIHR), Genome Canada Health Research Board (Ireland) Hilibrand Foundation (USA) Medical Research Council (UK) National Institutes of Health (USA) Ontario Genomics Institute University of Toronto McLaughlin Centre Simons Foundation Johns Hopkins Autism Consortium of Boston NLM Family foundation National Institute of Health grants National Health Medical Research Council Scottish Rite Spunk Fund, Inc. Rebecca and Solomon Baker Fund APEX Foundation National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD) endowment fund of the Nancy Pritzker Laboratory (Stanford) Autism Society of America Janet M. Grace Pervasive Developmental Disorders Fund The Lundbeck Foundation universities and university hospitals of Aarhus and Copenhagen Stanley Foundation Centers for Disease Control and Prevention (CDC) Netherlands Scientific Organization Dutch Brain Foundation VU University Amsterdam Trinity Centre for High Performance Computing through Science Foundation Ireland Autism Genome Project (AGP) from Autism Speak
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