Increasing the reference populations for the 55 AISNP panel: the need and benefits

Ancestry inference for an individual can only be as good as the reference populations with allele frequency data on the SNPs being used. If the most relevant ancestral population(s) does not have data available for the SNPs studied, then analyses based on DNA evidence may indicate a quite distantly related population, albeit one among the more closely related of the existing reference populations. We have added reference population allele frequencies for 14 additional population samples (with >1100 individuals studied) to the 125 population samples previously published for the Kidd Lab 55 AISNP panel. Allele frequencies are now publicly available for all 55 SNPs in ALFRED and FROG-kb for a total of 139 population samples. This Kidd Lab panel of 55 ancestry informative SNPs has been incorporated in commercial kits by both ThermoFisher Scientific and Illumina for massively parallel sequencing. Researchers employing those kits will find the enhanced set of reference populations useful

Categorization of compensatory motions in transradial myoelectric prosthesis users

Background: Prosthesis users perform various compensatory motions to accommodate for the loss of the hand and wrist as well as the reduced functionality of a prosthetic hand. Objectives: Investigate different compensation strategies that are performed by prosthesis users. Study Design: Comparative analysis Methods: 20 able-bodied subjects and 4 prosthesis users performed a set of bimanual activities. Movements of the trunk and head were recorded using a motion capture system, and a digital video recorder. Clinical motion angles were calculated to assess the compensatory motions made by the prosthesis users. The video recording also assisted in visually identifying the compensations. Results: Compensatory motions by the prosthesis users were evident in the tasks performed (slicing and stirring activities) as compared to the benchmark of able-bodied subjects. Compensations took the form of a measured increase in range of motion, an observed adoption of a new posture during task execution, and pre-positioning of items in the workspace prior to initiating a given task. Conclusion: Compensatory motions were performed by prosthesis users during the selected tasks. These can be categorized into three different types of compensations

Using an Ishikawa diagram as a tool to assist memory and retrieval of relevant medical cases from the medical literature

<p>Abstract</p> <p>Studying medical cases is an effective way to enhance clinical reasoning skills and reinforce clinical knowledge. An Ishikawa diagram, also known as a cause-and-effect diagram or fishbone diagram, is often used in quality management in manufacturing industries.</p> <p>In this report, an Ishikawa diagram is used to demonstrate how to relate potential causes of a major presenting problem in a clinical setting. This tool can be used by teams in problem-based learning or in self-directed learning settings.</p> <p>An Ishikawa diagram annotated with references to relevant medical cases and literature can be continually updated and can assist memory and retrieval of relevant medical cases and literature. It could also be used to cultivate a lifelong learning habit in medical professionals.</p

Process skill rather than motor skill seems to be a predictor of costs for rehabilitation after a stroke in working age; a longitudinal study with a 1 year follow up post discharge

<p>Abstract</p> <p>Background</p> <p>In recent years a number of costs of stroke studies have been conducted based on incidence or prevalence and estimating costs at a given time. As there still is a need for a deeper understanding of factors influencing these costs the aim of this study was to calculate the direct and indirect costs in a younger (<65) sample of stroke patients and to explore factors affecting the costs.</p> <p>Methods</p> <p>Fifty-eight patients included in a study of home rehabilitation and followed for 1 year after discharge from the rehabilitation unit, were interviewed about their use of health care services, assistance, medications and assistive devices. Costs (defined as the cost for society) were calculated. A linear regression of cost and variables of functioning, ability, community integration and health-related quality of life was done.</p> <p>Results</p> <p>Inpatient care contributed substantially to the direct cost with a mean length of stay of 92 days. Rehabilitation during the first year constituted of an average of 28 days in day clinics, 38 physiotherapy sessions and 20 occupational therapy sessions. The total direct mean cost was 80 020 € and the indirect cost 35 129 €. The direct costs were influenced by the process skill (the ability to plan and perform a given task and to adapt when needed) and presence of aphasia. Indirect costs for informal care giving increased for patients with a lower health-related quality of life as well as a low score on home integration.</p> <p>Conclusion</p> <p>Costs are high in this group of young (< 65 years) stroke patients compared to other studies, partly due to the length of the stay and partly to loss of productivity.</p

Mycobacterium tuberculosis-stimulated whole blood culture to detect host biosignatures for tuberculosis treatment response

Supplementary data are available online at https://www.sciencedirect.com/science/article/pii/S1472979221000329?via%3Dihub#appsec1 .Host markers to monitor the response to tuberculosis (TB) therapy hold some promise. We evaluated the changes in concentration of Mycobacterium tuberculosis (M.tb)-induced soluble biomarkers during early treatment for predicting short- and long-term treatment outcomes. Whole blood samples from 30 cured and 12 relapsed TB patients from diagnosis, week 1, 2, and 4 of treatment were cultured in the presence of live M.tb for seven days and patients followed up for 24 weeks after the end of treatment. 57 markers were measured in unstimulated and antigen-stimulated culture supernatants using Luminex assays. Top performing multi-variable models at diagnosis using unstimulated values predicted outcome at 24 months after treatment completion with a sensitivity of 75.0% (95% CI, 42.8–94.5%) and specificity of 72.4% (95% CI, 52.8–87.3%) in leave-one-out cross validation. Month two treatment responder classification was correctly predicted with a sensitivity of 79.2% (95% CI, 57.8–92.9%) and specificity of 92.3% (95% CI, 64.0–99.8%). This study provides evidence of the early M.tb-specific treatment response in TB patients but shows that the observed unstimulated marker models are not outperformed by stimulated marker models. Performance of unstimulated predictive host marker signatures is promising and requires validation in larger studies.Bill and Melinda Gates Foundation (TB Drug Accelerator Program, grant number 48941); Action TB by GSK; EDCTP (01.T.d1, Grant number 2004.1.R.d1); the South African Technology for Human Resources and Industry Program (THRIP); and an International Collaborations in Infectious Diseases Research grant from the National Institute of Allergy and Infectious Diseases (grant number 5U01IA115619). This research was also partially funded by the South African government through the South African Medical Research Council, through a grant from the Strategic Health Innovations Partnership (SHIP) unit, by the South African National Research Foundation through a South African Research Chair Initiative: Biomarkers for TB (grant number 86535) and a South African Department of Science and Innovation/National Research Foundation funded Centre of Excellence in Biomedical Tuberculosis Research

A Family-Wide RT-PCR Assay for Detection of Paramyxoviruses and Application to a Large-Scale Surveillance Study

Family-wide molecular diagnostic assays are valuable tools for initial identification of viruses during outbreaks and to limit costs of surveillance studies. Recent discoveries of paramyxoviruses have called for such assay that is able to detect all known and unknown paramyxoviruses in one round of PCR amplification. We have developed a RT-PCR assay consisting of a single degenerate primer set, able to detect all members of the Paramyxoviridae family including all virus genera within the subfamilies Paramyxovirinae and Pneumovirinae. Primers anneal to domain III of the polymerase gene, with the 3′ end of the reverse primer annealing to the conserved motif GDNQ, which is proposed to be the active site for nucleotide polymerization. The assay was fully optimized and was shown to indeed detect all available paramyxoviruses tested. Clinical specimens from hospitalized patients that tested positive for known paramyxoviruses in conventional assays were also detected with the novel family-wide test. A high-throughput fluorescence-based RT-PCR version of the assay was developed for screening large numbers of specimens. A large number of samples collected from wild birds was tested, resulting in the detection of avian paramyxoviruses type 1 in both barnacle and white-fronted geese, and type 8 in barnacle geese. Avian metapneumovirus type C was found for the first time in Europe in mallards, greylag geese and common gulls. The single round family-wide RT-PCR assay described here is a useful tool for the detection of known and unknown paramyxoviruses, and screening of large sample collections from humans and animals

The correlation between colorectal cancer rates of proliferation and apoptosis and systemic cytokine levels; plus their influence upon survival

Colorectal cancer development is associated with a shift in host immunity with suppression of the cell-mediated immune system (CMI) and a predominance of humoral immunity (HI). Tumour progression is also associated with increased rates of cell proliferation and apoptosis. The aim of this study was to investigate whether these factors correlate and have an influence upon prognosis. Long-term follow-up was performed on 40 patients with colorectal cancer who had levels of tumour necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-10 measured from stimulated blood cultures before surgery. Their archived tumour specimens were analysed to determine a Ki-67-derived proliferation index (PI) and a M30-derived apoptosis index (AI). Tumour necrosis factor-α levels negatively correlated to tumour proliferation (ρ=−0.697, P=0.01). Interleukin-10 levels had a positive correlation with tumour proliferation (ρ=0.452, P=0.05) and apoptosis (ρ=0.587, P=0.01). Patient survival correlates to tumour pathological stage (P=0.0038) and vascular invasion (P=0.0014). An AI⩽0.6% and TNF-α levels ⩾8148 pg ml−1 correlate to improved survival (P=0.032, P=0.021). Tumour proliferation and apoptosis correlate to progressive suppression of the CMI-associated cytokine TNF-α and to and higher levels of IL-10. Survival is dependent upon the histological stage of the tumour, vascular invasion, rates of apoptosis and proliferation and systemic immunity which are all interconnected

A pooling-based genome-wide analysis identifies new potential candidate genes for atopy in the European Community Respiratory Health Survey (ECRHS)

<p>Abstract</p> <p>Background</p> <p>Asthma and atopy are complex phenotypes with shared genetic component. In this study we attempt to identify genes related to these traits performing a two-stage DNA pooling genome-wide analysis in order to reduce costs. First, we assessed all markers in a subset of subjects using DNA pooling, and in a second stage we evaluated the most promising markers at an individual level.</p> <p>Methods</p> <p>For the genome-wide analysis, we constructed DNA pools from 75 subjects with atopy and asthma, 75 subjects with atopy and without asthma and 75 control subjects without atopy or asthma. In a second stage, the most promising regions surrounding significant markers after correction for false discovery rate were replicated with individual genotyping of samples included in the pools and an additional set of 429 atopic subjects and 222 controls from the same study centres.</p> <p>Results</p> <p><it>Homo sapiens </it>protein kinase-like protein SgK493 (<it>SGK493</it>) was found to be associated with atopy. To lesser extent mitogen-activated protein kinase 5 (<it>MAP3K5</it>), collagen type XVIII alpha 1 (<it>COL18A1</it>) and collagen type XXIX alpha 1 (<it>COL29A1</it>) were also found to be associated with atopy. Functional evidences points out a role for <it>MAP3K5</it>, <it>COL18A1 </it>and <it>COL29A1 </it>but the function of <it>SGK493 </it>is unknown.</p> <p>Conclusion</p> <p>In this analysis we have identified new candidate regions related to atopy and suggest <it>SGK493 </it>as an atopy locus, although these results need further replication.</p

Mink Farms Predict Aleutian Disease Exposure in Wild American Mink

BACKGROUND: Infectious diseases can often be of conservation importance for wildlife. Spillover, when infectious disease is transmitted from a reservoir population to sympatric wildlife, is a particular threat. American mink (Neovison vison) populations across Canada appear to be declining, but factors thus far explored have not fully explained this population trend. Recent research has shown, however, that domestic mink are escaping from mink farms and hybridizing with wild mink. Domestic mink may also be spreading Aleutian disease (AD), a highly pathogenic parvovirus prevalent in mink farms, to wild mink populations. AD could reduce fitness in wild mink by reducing both the productivity of adult females and survivorship of juveniles and adults. METHODS: To assess the seroprevalence and geographic distribution of AD infection in free-ranging mink in relation to the presence of mink farms, we conducted both a large-scale serological survey, across the province of Ontario, and a smaller-scale survey, at the interface between a mink farm and wild mink. CONCLUSIONS/SIGNIFICANCE: Antibodies to AD were detected in 29% of mink (60 of 208 mink sampled); however, seroprevalence was significantly higher in areas closer to mink farms than in areas farther from farms, at both large and small spatial scales. Our results indicate that mink farms act as sources of AD transmission to the wild. As such, it is likely that wild mink across North America may be experiencing increased exposure to AD, via disease transmission from mink farms, which may be affecting wild mink demographics across their range. In light of declining mink populations, high AD seroprevalence within some mink farms, and the large number of mink farms situated across North America, improved biosecurity measures on farms are warranted to prevent continued disease transmission at the interface between mink farms and wild mink populations