54 research outputs found
Modelling interactions of acidâbase balance and respiratory status in the toxicity of metal mixtures in the American oyster Crassostrea virginica
Author Posting. © The Author(s), 2009. 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 Comparative Biochemistry and Physiology - Part A: Molecular & Integrative Physiology 155 (2010): 341-349, doi:10.1016/j.cbpa.2009.11.019.Heavy metals, such as copper, zinc and cadmium, represent some of the most common and
serious pollutants in coastal estuaries. In the present study, we used a combination of linear and
artificial neural network (ANN) modelling to detect and explore interactions among low-dose
mixtures of these heavy metals and their impacts on fundamental physiological processes in
tissues of the Eastern oyster, Crassostrea virginica. Animals were exposed to Cd (0.001 â 0.400
ÎŒM), Zn (0.001 â 3.059 ÎŒM) or Cu (0.002 â 0.787 ÎŒM), either alone or in combination for 1 to
27 days. We measured indicators of acid-base balance (hemolymph pH and total CO2), gas
exchange (Po2), immunocompetence (total hemocyte counts, numbers of invasive bacteria),
antioxidant status (glutathione, GSH), oxidative damage (lipid peroxidation; LPx), and metal
accumulation in the gill and the hepatopancreas. Linear analysis showed that oxidative
membrane damage from tissue accumulation of environmental metals was correlated with
impaired acid-base balance in oysters. ANN analysis revealed interactions of metals with
hemolymph acid-base chemistry in predicting oxidative damage that were not evident from
linear analyses. These results highlight the usefulness of machine learning approaches, such as
ANNs, for improving our ability to recognize and understand the effects of sub-acute exposure to
contaminant mixtures.This study was supported by NOAAâs Center of Excellence in Oceans and Human Health at HML and the National Science Foundation
Feasibility and results of a randomised pilot-study of pre-discharge occupational therapy home visits
BACKGROUND: Pre-discharge home visits aim to maximise independence in the community. These visits involve assessment of a person in their own home prior to discharge from hospital, typically by an occupational therapist. The therapist may provide equipment, adapt the home environment and/or provide education. The aims of this study were to investigate the feasibility of a randomised controlled trial in a clinical setting and the effect of pre-discharge home visits on functional performance in older people undergoing rehabilitation. METHODS: Ten patients participating in an inpatient rehabilitation program were randomly assigned to receive either a pre-discharge home visit (intervention), or standard practice in-hospital assessment and education (control), both conducted by an occupational therapist. The pre-discharge home visit involved assessment of the older person's function and environment, and education, and took an average of 1.5 hours. The hospital-based interview took an average of 40 minutes. Outcome data were collected by a blinded assessor at 0, 2, 4, 8 and 12 weeks. Outcomes included performance of activities of daily living, reintegration to community living, quality of life, readmission and fall rates. RESULTS: Recruitment of 10 participants was slow and took three months. Observed performance of functional abilities did not differ between groups due to the small sample size. Difference in activities of daily living participation, as recorded by the Nottingham Extended Activities of Daily Living scale, was statistically significant but wide confidence intervals and low statistical power limit interpretation of results. CONCLUSION: Evaluation of pre-discharge home visits by occupational therapists in a rehabilitation setting is feasible, but a more effective recruitment strategy for a main study is favored by application of a multi-centre setting
Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease
We identified rare coding variants associated with Alzheimerâs disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1Ă10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5Ă10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38Ă10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56Ă10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55Ă10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development
Association of NIPA1 repeat expansions with amyotrophic lateral sclerosis in a large international cohort
NIPA1 (nonimprinted in Prader-Willi/Angelman syndrome 1) mutations are known to cause hereditary spastic paraplegia type 6, a neurodegenerative disease that phenotypically overlaps to some extent with amyotrophic lateral sclerosis (ALS). Previously, a genomewide screen for copy number variants found an association with rare deletions in NIPA1 and ALS, and subsequent genetic analyses revealed that long (or expanded) polyalanine repeats in NIPA1 convey increased ALS susceptibility. We set out to perform a large-scale replication study to further investigate the role of NIPA1 polyalanine expansions with ALS, in which we characterized NIPA1 repeat size in an independent international cohort of 3955 patients with ALS and 2276 unaffected controls and combined our results with previous reports. Meta-analysis on a total of 6245 patients with ALS and 5051 controls showed an overall increased risk of ALS in those with expanded (>8) GCG repeat length (odds ratio = 1.50, p = 3.8Ă10-5). Together with previous reports, these findings provide evidence for an association of an expanded polyalanine repeat in NIPA1 and ALS
Searching for stochastic gravitational waves using data from the two colocated LIGO Hanford detectors
Searches for a stochastic gravitational-wave background (SGWB) using terrestrial detectors typically involve cross-correlating data from pairs of detectors. The sensitivity of such cross-correlation analyses depends, among other things, on the separation between the two detectors: the smaller the separation, the better the sensitivity. Hence, a colocated detector pair is more sensitive to a gravitational-wave background than a noncolocated detector pair. However, colocated detectors are also expected to suffer from correlated noise from instrumental and environmental effects that could contaminate the measurement of the background. Hence, methods to identify and mitigate the effects of correlated noise are necessary to achieve the potential increase in sensitivity of colocated detectors. Here we report on the first SGWB analysis using the two LIGO Hanford detectors and address the complications arising from correlated environmental noise. We apply correlated noise identification and mitigation techniques to data taken by the two LIGO Hanford detectors, H1 and H2, during LIGOâs fifth science run. At low frequencies, 40â460 Hz, we are unable to sufficiently mitigate the correlated noise to a level where we may confidently measure or bound the stochastic gravitational-wave signal. However, at high frequencies, 460â1000 Hz, these techniques are sufficient to set a 95% confidence level upper limit on the gravitational-wave energy density of Ω(f) < 7.7 Ă 10[superscript -4](f/900ââHz)[superscript 3], which improves on the previous upper limit by a factor of ~180. In doing so, we demonstrate techniques that will be useful for future searches using advanced detectors, where correlated noise (e.g., from global magnetic fields) may affect even widely separated detectors.National Science Foundation (U.S.)United States. National Aeronautics and Space AdministrationCarnegie TrustDavid & Lucile Packard FoundationAlfred P. Sloan Foundatio
Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign
Abstract: In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass âŒ6.5 Ă 109 M â. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87âs spectrum. We can exclude that the simultaneous Îł-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the Îł-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded
A novel Alzheimer disease locus located near the gene encoding tau protein
This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordAPOE Δ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE Δ4+ (10 352 cases and 9207 controls) and APOE Δ4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE Δ4 status. Suggestive associations (P<1 Ă 10-4) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE Δ4+: 1250 cases and 536 controls; APOE Δ4-: 718 cases and 1699 controls). Among APOE Δ4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 Ă 10-9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE Δ4+ subjects (CR1 and CLU) or APOE Δ4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 Ă 10-7) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (Pâ€1.3 Ă 10-8), frontal cortex (Pâ€1.3 Ă 10-9) and temporal cortex (Pâ€1.2 Ă 10-11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 Ă 10-6) and temporal cortex (P=2.6 Ă 10-6). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE Δ4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted
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