156 research outputs found
KELVIN: A Software Package for Rigorous Measurement of Statistical Evidence in Human Genetics
This paper describes the software package KELVIN, which supports the PPL (posterior probability of linkage) framework for the measurement of statistical evidence in human (or more generally, diploid) genetic studies. In terms of scope, KELVIN supports two-point (trait-marker or marker-marker) and multipoint linkage analysis, based on either sex-averaged or sex-specific genetic maps, with an option to allow for imprinting; trait-marker linkage disequilibrium (LD), or association analysis, in case-control data, trio data, and/or multiplex family data, with options for joint linkage and trait-marker LD or conditional LD given linkage; dichotomous trait, quantitative trait and quantitative trait threshold models; and certain types of gene-gene interactions and covariate effects. Features and data (pedigree) structures can be freely mixed and matched within analyses. The statistical framework is specifically tailored to accumulate evidence in a mathematically rigorous way across multiple data sets or data subsets while allowing for multiple sources of heterogeneity, and KELVIN itself utilizes sophisticated software engineering to provide a powerful and robust platform for studying the genetics of complex disorders
Halpha Morphologies and Environmental Effects in Virgo Cluster Spiral Galaxies
We describe the various Halpha morphologies of Virgo Cluster and isolated
spiral galaxies, and associate the Halpha morphologies with the types of
environmental interactions which have altered the cluster galaxies. The spatial
distributions of Halpha and R-band emission are used to divide the star
formation morphologies of the 52 Virgo Cluster spirals into several categories:
normal (37%), anemic (6%), enhanced (6%), and (spatially) truncated (52%).
Truncated galaxies are further subdivided based on their inner star formation
rates into truncated/normal (37%), truncated/compact (6%), truncated/anemic
(8%), and truncated/enhanced (2%). The fraction of anemic galaxies is
relatively small (6-13%) in both environments, suggesting that starvation is
not a major factor in the reduced star formation rates of Virgo spirals. The
majority of Virgo spiral galaxies have their Halpha disks truncated (52%),
whereas truncated Halpha disks are rarer in isolated galaxies (12%). Most of
the Halpha-truncated galaxies have relatively undisturbed stellar disks and
normal-to-slightly enhanced inner disk star formation rates, suggesting that
ICM-ISM stripping is the main mechanism causing the reduced star formation
rates of Virgo spirals. In other galaxies, the Halpha morphologies are more
consistent with a tidal origin or perhaps outer cluster HI accretion. These
results indicate that most Virgo spiral galaxies experience ICM-ISM stripping,
many experience significant tidal effects, and many experience both.
(abridged).Comment: Accepted by Astrophysical Journal. 16 pages, 15 figures, including 9
in low-resolution jpg format. Higher resolution postscript versions of these
figures are available from http://www1.union.edu/~koopmanr/radfig.htm
UV/Optical Nuclear Activity in the gE Galaxy NGC 1399
Using HST/STIS, we have detected far-ultraviolet nuclear activity in the
giant elliptical galaxy NGC 1399, the central and brightest galaxy in the
Fornax I cluster. The source reached a maximum observed far-UV luminosity of
\~1.2 x 10e39 ergs/s in January 1999. It was detectable in earlier HST archival
images in 1996 (B band) but not in 1991 (V band) or 1993 (UV). It faded by a
factor of ~4x by mid-2000. The source is almost certainly associated with the
low luminosity AGN responsible for the radio emission in NGC 1399. The
properties of the outburst are remarkably similar to the UV-bright nuclear
transient discovered earlier in NGC 4552 by Renzini et al. (1995). The source
is much fainter than expected from its Bondi accretion rate (estimated from
Chandra high resolution X-ray images), even in the context of "radiatively
inefficient accretion flow" models, and its variability also appears
inconsistent with such models. High spatial resolution UV monitoring is a
valuable means to study activity in nearby LLAGNs.Comment: 18 pages, 2 figures, 1 table; accepted for publication in Ap
Insulin Resistance Exacerbates Genetic Predisposition to Nonalcoholic Fatty Liver Disease in Individuals Without Diabetes
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149741/1/hep41353.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149741/2/hep41353_am.pd
Participant Observation as Ethnography or Ethnography as Participant Observation in Organizational Research
There is a strong tradition of observational research in most areas of the social sciences, especially in Anthropology and Sociology. However, in business and management research observation is often seen as a poor relative to questionnaire surveys and qualitative interviewing. This chapter discusses the use of observational techniques especially for less experienced researchers planning their first major investigation, exploring the difference between participant and non-participant approaches, different techniques of data collection, recording and analysis. Rather than seeking to provide a full guide to conducting participant observation, an impractical task in a single chapter, this offering discusses some of the key issues facing researchers in Business and Management who choose to conduct this sort of research, exploring different approaches to participant observation and some of the ethical and practical challenges associated with the collection and analysis of observational data. The chapter draws on the authorâs experience of conducting participant observation in organizations with examples of both employee (Sandiford and Seymour, 2002; Seymour and Sandiford, 2013) and customer perspectives (Sandiford and Divers, 2011). It will also draw from âclassicâ observational studies such as Mars and Nicod (1984) and more recent examples such as Watson and Watson (2012).Peter John Sandifor
Genome-Wide Association Analysis of Ischemic Stroke in Young Adults
Ischemic stroke (IS) is among the leading causes of death in Western countries. There is a significant genetic component to IS susceptibility, especially among young adults. To date, research to identify genetic loci predisposing to stroke has met only with limited success. We performed a genome-wide association (GWA) analysis of early-onset IS to identify potential stroke susceptibility loci. The GWA analysis was conducted by genotyping 1 million SNPs in a biracial population of 889 IS cases and 927 controls, ages 15â49 years. Genotypes were imputed using the HapMap3 reference panel to provide 1.4 million SNPs for analysis. Logistic regression models adjusting for age, recruitment stages, and population structure were used to determine the association of IS with individual SNPs. Although no single SNP reached genome-wide significance (P < 5 Ă 10â8), we identified two SNPs in chromosome 2q23.3, rs2304556 (in FMNL2; P = 1.2 Ă 10â7) and rs1986743 (in ARL6IP6; P = 2.7 Ă 10â7), strongly associated with early-onset stroke. These data suggest that a novel locus on human chromosome 2q23.3 may be associated with IS susceptibility among young adults
Cosmological parameters from SDSS and WMAP
We measure cosmological parameters using the three-dimensional power spectrum
P(k) from over 200,000 galaxies in the Sloan Digital Sky Survey (SDSS) in
combination with WMAP and other data. Our results are consistent with a
``vanilla'' flat adiabatic Lambda-CDM model without tilt (n=1), running tilt,
tensor modes or massive neutrinos. Adding SDSS information more than halves the
WMAP-only error bars on some parameters, tightening 1 sigma constraints on the
Hubble parameter from h~0.74+0.18-0.07 to h~0.70+0.04-0.03, on the matter
density from Omega_m~0.25+/-0.10 to Omega_m~0.30+/-0.04 (1 sigma) and on
neutrino masses from <11 eV to <0.6 eV (95%). SDSS helps even more when
dropping prior assumptions about curvature, neutrinos, tensor modes and the
equation of state. Our results are in substantial agreement with the joint
analysis of WMAP and the 2dF Galaxy Redshift Survey, which is an impressive
consistency check with independent redshift survey data and analysis
techniques. In this paper, we place particular emphasis on clarifying the
physical origin of the constraints, i.e., what we do and do not know when using
different data sets and prior assumptions. For instance, dropping the
assumption that space is perfectly flat, the WMAP-only constraint on the
measured age of the Universe tightens from t0~16.3+2.3-1.8 Gyr to
t0~14.1+1.0-0.9 Gyr by adding SDSS and SN Ia data. Including tensors, running
tilt, neutrino mass and equation of state in the list of free parameters, many
constraints are still quite weak, but future cosmological measurements from
SDSS and other sources should allow these to be substantially tightened.Comment: Minor revisions to match accepted PRD version. SDSS data and ppt
figures available at http://www.hep.upenn.edu/~max/sdsspars.htm
Hundreds of variants clustered in genomic loci and biological pathways affect human height
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (Pâ<â0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
Comparison of 2 models for geneâenvironment interactions: an example of simulated geneâmedication interactions on systolic blood pressure in family-based data
Abstract Background Nearly half of adults in the United States who are diagnosed with hypertension use blood-pressure-lowering medications. Yet there is a large interindividual variability in the response to these medications. Two complementary geneâenvironment interaction methods have been published and incorporated into publicly available software packages to examine interaction effects, including whether genetic variants modify the association between medication use and blood pressure. The first approach uses a geneâenvironment interaction term to measure the change in outcome when both the genetic marker and medication are present (the âinteraction modelâ). The second approach tests for effect-size differences between strata of an environmental exposure (the âmed-diffâ approach). However, no studies have quantitatively compared how these methods perform with respect to 1 or 2 degree of freedom (DF) tests or in family-based data sets. We evaluated these 2 approaches using simulated genotypeâmedication response interactions at 3 single nucleotide polymorphisms (SNPs) across a range of minor allele frequencies (MAFs 0.1â5.4Â %) using the Genetic Analysis Workshop 19 family sample. Results The estimated interaction effect sizes were on average larger in the interaction model approach compared to the med-diff approach. The true positive proportion was higher for the med-diff approach for SNPs less than 1Â % MAF, but higher for the interaction model when common variants were evaluated (MAF >5Â %). The interaction model produced lower false-positive proportions than expected (5Â %) across a range of MAFs for both the 1DF and 2DF tests. In contrast, the med-diff approach produced higher but stable false-positive proportions around 5Â % across MAFs for both tests. Conclusions Although the 1DF tests both performed similarly for common variants, the interaction model estimated true interaction effects with less bias and higher true positive proportions than the med-diff approach. However, if rare variation (MAF <5Â %) is of interest, our findings suggest that when convergence is achieved, the med-diff approach may estimate true interaction effects more conservatively and with less variability
Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans
Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10â15âd after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection. Using sequential serum samples collected up to 94âd post onset of symptoms (POS) from 65 individuals with real-time quantitative PCR-confirmed SARS-CoV-2 infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) in >95% of cases and neutralizing antibody responses when sampled beyond 8âd POS. We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titres observed after an initial peak, and that the magnitude of this peak is dependent on disease severity. Although some individuals with high peak infective dose (ID50â>â10,000) maintained neutralizing antibody titres >1,000 at >60âd POS, some with lower peak ID50 had neutralizing antibody titres approaching baseline within the follow-up period. A similar decline in neutralizing antibody titres was observed in a cohort of 31 seropositive healthcare workers. The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection
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