Identification of T-cell antigens specific for latent mycobacterium tuberculosis infection.

BACKGROUND: T-cell responses against dormancy-, resuscitation-, and reactivation-associated antigens of Mycobacterium tuberculosis are candidate biomarkers of latent infection in humans. METHODOLOGY/PRINCIPAL FINDINGS: We established an assay based on two rounds of in vitro restimulation and intracellular cytokine analysis that detects T-cell responses to antigens expressed during latent M. tuberculosis infection. Comparison between active pulmonary tuberculosis (TB) patients and healthy latently M. tuberculosis-infected donors (LTBI) revealed significantly higher T-cell responses against 7 of 35 tested M. tuberculosis latency-associated antigens in LTBI. Notably, T cells specific for Rv3407 were exclusively detected in LTBI but not in TB patients. The T-cell IFNgamma response against Rv3407 in individual donors was the most influential factor in discrimination analysis that classified TB patients and LTBI with 83% accuracy using cross-validation. Rv3407 peptide pool stimulations revealed distinct candidate epitopes in four LTBI. CONCLUSIONS: Our findings further support the hypothesis that the latency-associated antigens can be exploited as biomarkers for LTBI

The DINGO dataset: a comprehensive set of data for the SAMPL challenge

Part of the latest SAMPL challenge was to predict how a small fragment library of 500 commercially available compounds would bind to a protein target. In order to assess the modellers’ work, a reasonably comprehensive set of data was collected using a number of techniques. These included surface plasmon resonance, isothermal titration calorimetry, protein crystallization and protein crystallography. Using these techniques we could determine the kinetics of fragment binding, the energy of binding, how this affects the ability of the target to crystallize, and when the fragment did bind, the pose or orientation of binding. Both the final data set and all of the raw images have been made available to the community for scrutiny and further work. This overview sets out to give the parameters of the experiments done and what might be done differently for future studies

Mineral chemistry of igneous melanite garnets from analcite-bearing volcanic rocks, Alberta, Canada

The mineral chemistry of melanite garnets from the Crowsnest volcanic rocks of SW Alberta, Canada, has been investigated by using electron microprobe scans, quantitative analyses and multivariate statistical analysis. The garnets occur with aegirine-augite, sanidine, analcite and rare plagioclase as phenocrysts in trachyte and phonolite flows, agglomerates and tuffs. Wavelength dispersive microprobe scans reveal complex zonation patterns, both normal and oscillatory. The results of fifty quantitative analyses were subjected to R-mode factor analysis to delineate the chemical exchanges producing the zonation. The chemical zonation of the garnets may be attributed to four independent binary exchanges; Al-Fe3+, Si-Ti, Ca-Mn and Mg-Fe2+. The stoichiometry of these garnets, based on microprobe and wet chemical Fe analyses, combined with the strongly antithetic behavior of Si and Ti lead us to infer that the Ti in these garnets is dominantly tetravalent. It is clear from this study that quantitative modelling of the processes of crystal growth and zonation of melanite garnets in alkaline, undersaturated igneous rocks should be aimed at simulating the four chemical exchanges listed above

Aboriginal and Torres Strait Islander Suicide in Context

Aboriginal and Torres Strait Islander suicide has been an issue of national public health and mental health concern for only one decade, having increased dramatically from levels that were very low in the late 1980s to levels of young adult male suicide that are now substantially higher than for the non-indigenous population. In this review the authors socially and historically contextualize these changes, identifying the causal frameworks adopted in developing interventions, and present an explanation in narrative and pictorial form that draws on critical family-centered trauma

Health Industries in the Twentieth Century. Introduction

This article is the introduction to the special issue' Health Industries in the Twentieth Century'. It offers a broad literature review of scholarly works about the history of health and medicine, and stresses the opportunities for business historians to tackle the field of healthcare

Measurement of the Bovine Pancreatic Trypsin Inhibitors by Radioimmunoassay

Bovine pancreas contains two polypeptide trypsin inhibitors that are not homologous and differ in their inhibitory activity towards chymotrypsin, kallikrein, elastase, and other serine proteinases. The Kunitz inhibitor and the Kazal inhibitor are present in approximately equimolar concentrations in bovine pancreatic tissue, yet only the Kazal inhibitor is detectable in the pancreatic juice. The Kazal inhibitor has been named the pancreatic secretory trypsin inhibitor, PSTI because its concentration in the pancreatic juice parallels that of the exocrine secretory proteins. The Kunitz inhibitor is considered the intracellular inhibitor, however, no direct information is available concerning the intracellular localization of these inhibitors in the pancreas. The preparation of /sup 125/I-labeled derivatives of Kazal and Kunitz inhibitors by the lactoperoxidase method and a radioimmunoassay for each inhibitor are described. (auth

Comparing the health of low income and less well educated groups in the United States and Canada

<p>Abstract</p> <p>Background</p> <p>A limited number of health status and health-related quality of life (HRQL) measures have been used for inter-country comparisons of population health. We compared the health of Canadians and Americans using a preference-based measure.</p> <p>Methods</p> <p>The Joint Canada/United States Survey of Health (JCUSH) 2002–03 conducted a comprehensive cross-sectional telephone survey on the health of community-dwelling residents in Canada and the US (n = 8688). A preference-based measure, the Health Utilities Index Mark 3 (HUI3), was included in the JCUSH. Health status was analyzed for the entire population and white population only in both countries. Mean HUI3 overall scores were compared for both countries. A linear regression determinants of health model was estimated to account for differences in health between Canada and the US. Estimation with bootstraps was used to derive variance estimates that account for the survey's complex sampling design of clustering and stratification.</p> <p>Results</p> <p>Income is associated with health in both countries. In the lowest income quintile, Canadians are healthier than Americans. At lower levels of education, again Canadians are healthier than Americans. Differences in health among subjects in the JCUSH are explained by age, gender, education, income, marital status, and country of residence.</p> <p>Conclusion</p> <p>On average, population health in Canada and the US is similar. However, health disparities between Canadians and Americans exist at lower levels of education and income with Americans worse off. The results highlight the usefulness of continuous preference-based measures of population health such as the HUI3.</p

Identification of T-Cell Antigens Specific for Latent Mycobacterium Tuberculosis Infection

BACKGROUND: T-cell responses against dormancy-, resuscitation-, and reactivation-associated antigens of Mycobacterium tuberculosis are candidate biomarkers of latent infection in humans. METHODOLOGY/PRINCIPAL FINDINGS: We established an assay based on two rounds of in vitro restimulation and intracellular cytokine analysis that detects T-cell responses to antigens expressed during latent M. tuberculosis infection. Comparison between active pulmonary tuberculosis (TB) patients and healthy latently M. tuberculosis-infected donors (LTBI) revealed significantly higher T-cell responses against 7 of 35 tested M. tuberculosis latency-associated antigens in LTBI. Notably, T cells specific for Rv3407 were exclusively detected in LTBI but not in TB patients. The T-cell IFNgamma response against Rv3407 in individual donors was the most influential factor in discrimination analysis that classified TB patients and LTBI with 83% accuracy using cross-validation. Rv3407 peptide pool stimulations revealed distinct candidate epitopes in four LTBI. CONCLUSIONS: Our findings further support the hypothesis that the latency-associated antigens can be exploited as biomarkers for LTBI

Dual Use of Veterans Health Administration and Indian Health Service: Healthcare Provider and Patient Perspectives

Many American Indian and Alaska Native veterans are eligible for healthcare from Veterans Health Administration (VHA) and from Indian Health Service (IHS). These organizations executed a Memorandum of Understanding in 2003 to share resources, but little was known about how they collaborated to deliver healthcare. To describe dual use from the stakeholders’ perspectives, including incentives that encourage cross-use, which organization’s primary care is “primary,” and the potential problems and opportunities for care coordination across VHA and IHS. VHA healthcare staff, IHS healthcare staff and American Indian and Alaska Native veterans. Focus groups were conducted using a semi-structured guide. A software-assisted text analysis was performed using grounded theory to develop analytic categories. Dual use was driven by variation in institutional resources, leading patients to actively manage health-seeking behaviors and IHS providers to make ad hoc recommendations for veterans to seek care at VHA. IHS was the “primary” primary care for dual users. There was little coordination between VHA and IHS resulting in delays and treatment conflicts, but all stakeholder groups welcomed future collaboration. Fostering closer alignment between VHA and IHS would reduce care fragmentation and improve accountability for patient care