415 research outputs found
Direct Measurement of Nuclear Dependence of Charged Current Quasielastic-like Neutrino Interactions using MINERvA
Charged-current interactions on carbon, iron, and lead with a
final state hadronic system of one or more protons with zero mesons are used to
investigate the influence of the nuclear environment on quasielastic-like
interactions. The transfered four-momentum squared to the target nucleus,
, is reconstructed based on the kinematics of the leading proton, and
differential cross sections versus and the cross-section ratios of iron,
lead and carbon to scintillator are measured for the first time in a single
experiment. The measurements show a dependence on atomic number. While the
quasielastic-like scattering on carbon is compatible with predictions, the
trends exhibited by scattering on iron and lead favor a prediction with
intranuclear rescattering of hadrons accounted for by a conventional particle
cascade treatment. These measurements help discriminate between different
models of both initial state nucleons and final state interactions used in the
neutrino oscillation experiments
A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity
BACKGROUND: Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. METHODS: Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. RESULTS: Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). CONCLUSIONS: A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up
Visual ecology of aphids – a critical review on the role of colours in host finding
We review the rich literature on behavioural responses of aphids (Hemiptera: Aphididae) to stimuli of different colours. Only in one species there are adequate physiological data on spectral sensitivity to explain behaviour crisply in mechanistic terms.
Because of the great interest in aphid responses to coloured targets from an evolutionary, ecological and applied perspective, there is a substantial need to expand these studies to more species of aphids, and to quantify spectral properties of stimuli rigorously. We show that aphid responses to colours, at least for some species, are likely based on a specific colour opponency mechanism, with positive input from the green domain of the spectrum and negative input from the blue and/or UV region.
We further demonstrate that the usual yellow preference of aphids encountered in field experiments is not a true colour preference but involves additional brightness effects. We discuss the implications for agriculture and sensory ecology, with special respect to the recent debate on autumn leaf colouration. We illustrate that recent evolutionary theories concerning aphid–tree interactions imply far-reaching assumptions on aphid responses to colours
that are not likely to hold. Finally we also discuss the
implications for developing and optimising strategies
of aphid control and monitoring
CYP3A4 and CYP3A5 genotyping by Pyrosequencing
BACKGROUND: Human cytochrome P450 3A enzymes, particularly CYP3A4 and CYP3A5, play an important role in drug metabolism. CYP3A expression exhibits substantial interindividual variation, much of which may result from genetic variation. This study describes Pyrosequencing assays for key SNPs in CYP3A4 (CYP3A4*1B, CYP3A4*2, and CYP3A4*3) and CYP3A5 (CYP3A5*3C and CYP3A5*6). METHODS: Genotyping of 95 healthy European and 95 healthy African volunteers was performed using Pyrosequencing. Linkage disequilibrium, haplotype inference, Hardy-Weinberg equilibrium, and tag SNPs were also determined for these samples. RESULTS: CYP3A4*1B allele frequencies were 4% in Europeans and 82% in Africans. The CYP3A4*2 allele was found in neither population sample. CYP3A4*3 had an allele frequency of 2% in Europeans and 0% in Africans. The frequency of CYP3A5*3C was 94% in Europeans and 12% in Africans. No CYP3A5*6 variants were found in the European samples, but this allele had a frequency of 16% in the African samples. Allele frequencies and haplotypes show interethnic variation, highlighting the need to analyze clinically relevant SNPs and haplotypes in a variety of ethnic groups. CONCLUSION: Pyrosequencing is a versatile technique that could improve the efficiency of SNP analysis for pharmacogenomic research with the ultimate goal of pre-screening patients for individual therapy selection
Systemic-to-pulmonary collateral flow in patients with palliated univentricular heart physiology: measurement using cardiovascular magnetic resonance 4D velocity acquisition
Systematic evaluation and validation of reference and library selection methods for deconvolution of cord blood DNA methylation data
Background: Umbilical cord blood (UCB) is commonly used in epigenome-wide association studies of prenatal
exposures. Accounting for cell type composition is critical in such studies as it reduces confounding due to the cell
specificity of DNA methylation (DNAm). In the absence of cell sorting information, statistical methods can be
applied to deconvolve heterogeneous cell mixtures. Among these methods, reference-based approaches leverage
age-appropriate cell-specific DNAm profiles to estimate cellular composition. In UCB, four reference datasets
comprising DNAm signatures profiled in purified cell populations have been published using the Illumina 450 K and
EPIC arrays. These datasets are biologically and technically different, and currently, there is no consensus on how to
best apply them. Here, we systematically evaluate and compare these datasets and provide recommendations for
reference-based UCB deconvolution.
Results: We first evaluated the four reference datasets to ascertain both the purity of the samples and the potential
cell cross-contamination. We filtered samples and combined datasets to obtain a joint UCB reference. We selected
deconvolution libraries using two different approaches: automatic selection using the top differentially methylated
probes from the function pickCompProbes in minfi and a standardized library selected using the IDOL (Identifying
Optimal Libraries) iterative algorithm. We compared the performance of each reference separately and in
combination, using the two approaches for reference library selection, and validated the results in an independent
cohort (Generation R Study, n = 191) with matched Fluorescence-Activated Cell Sorting measured cell counts. Strict
filtering and combination of the references significantly improved the accuracy and efficiency of cell type estimates.
Ultimately, the IDOL library outperformed the library from the automatic selection method implemented in
pickCompProbes.
Conclusion: These results have important implications for epigenetic studies in UCB as implementing this method
will optimally reduce confounding due to cellular heterogeneity. This work provides guidelines for future referencebased UCB deconvolution and establishes a framework for combining reference datasets in other tissues
Effectiveness of Early Antiretroviral Therapy Initiation to Improve Survival among HIV-Infected Adults with Tuberculosis: A Retrospective Cohort Study
Molly Franke, Megan Murray, and colleagues report that early cART reduces
mortality among HIV-infected adults with tuberculosis and improves retention in
care, regardless of CD4 count
Amino Acid Similarity Accounts for T Cell Cross-Reactivity and for “Holes” in the T Cell Repertoire
Background: Cytotoxic T cell (CTL) cross-reactivity is believed to play a pivotal role in generating immune responses but the extent and mechanisms of CTL cross-reactivity remain largely unknown. Several studies suggest that CTL clones can recognize highly diverse peptides, some sharing no obvious sequence identity. The emerging realization in the field is that T cell receptors (TcR) recognize multiple distinct ligands. Principal Findings: First, we analyzed peptide scans of the HIV epitope SLFNTVATL (SFL9) and found that TCR specificity is position dependent and that biochemically similar amino acid substitutions do not drastically affect recognition. Inspired by this, we developed a general model of TCR peptide recognition using amino acid similarity matrices and found that such a model was able to predict the cross-reactivity of a diverse set of CTL epitopes. With this model, we were able to demonstrate that seemingly distinct T cell epitopes, i.e., ones with low sequence identity, are in fact more biochemically similar than expected. Additionally, an analysis of HIV immunogenicity data with our model showed that CTLs have the tendency to respond mostly to peptides that do not resemble self-antigens. Conclusions: T cell cross-reactivity can thus, to an extent greater than earlier appreciated, be explained by amino acid similarity. The results presented in this paper will help resolving some of the long-lasting discussions in the field of T cel
Methodological Issues Surrounding the Use of Baseline Health-Related Quality of Life Data to Inform Trial-Based Economic Evaluations of Interventions Within Emergency and Critical Care Settings: A Systematic Literature Review
Genetic polymorphisms in MDR1, CYP3A4 and CYP3A5 genes in a Ghanaian population: a plausible explanation for altered metabolism of ivermectin in humans?
<p>Abstract</p> <p>Background</p> <p>Ivermectin, a substrate of multidrug resistance (MDR1) gene and cytochrome P450 (CYP) 3A4, has been used successfully in the treatment of onchocerciasis in Ghana. However, there have been reports of suboptimal response in some patients after repeated treatment. Polymorphisms in host MDR1 and CYP3A genes may explain the observed suboptimal response to ivermectin. We genotyped relevant functional polymorphisms of MDR1 and CYP3A in a random sample of healthy Ghanaians and compared the data with that of ivermectin-treated patients with a view to exploring the relationship between suboptimal response to ivermectin and MDR1 and CYP3A allelic frequencies.</p> <p>Methods</p> <p>Using PCR-RFLP, relevant polymorphic alleles of MDR1 and CYP3A4 genes were analysed in 204 randomly selected individuals and in 42 ivermectin treated patients.</p> <p>Results</p> <p>We recorded significantly higher MDR1 (3435T) variant allele frequency in suboptimal responders (21%) than in patients who responded to treatment (12%) or the random population sample (11%). <it>CYP3A4*1B</it>, <it>CYP3A5*3 </it>and <it>CYP3A5*6 </it>alleles were detected at varied frequencies for the sampled Ghanaian population, responders and suboptimal responders to ivermectin. <it>CYP3A5*1/CYP3A5*1 </it>and <it>CYP3A5*1/CYP3A5*3 </it>genotypes were also found to be significantly different for responders and suboptimal responders. Haplotype (*1/*1/*3/*1) was determined to be significantly different between responders and suboptimal responders indicating a possible role of these haplotypes in treatment response with ivermectin.</p> <p>Conclusion</p> <p>A profile of pharmacogenetically relevant variants for MDR1, CYP3A4 and CYP3A5 genes has been generated for a random population of 204 Ghanaians to address the scarcity of data within indigenous African populations. In 42 patients treated with ivermectin, difference in MDR1 variant allele frequency was observed between suboptimal responders and responders.</p
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