Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid: single biomarker re-derivation and external validation in three cohorts.

BACKGROUND: The original Manchester Acute Coronary Syndromes model (MACS) 'rules in' and 'rules out' acute coronary syndromes (ACS) using high sensitivity cardiac troponin T (hs-cTnT) and heart-type fatty acid binding protein (H-FABP) measured at admission. The latter is not always available. We aimed to refine and validate MACS as Troponin-only Manchester Acute Coronary Syndromes (T-MACS), cutting down the biomarkers to just hs-cTnT. METHODS: We present secondary analyses from four prospective diagnostic cohort studies including patients presenting to the ED with suspected ACS. Data were collected and hs-cTnT measured on arrival. The primary outcome was ACS, defined as prevalent acute myocardial infarction (AMI) or incident death, AMI or coronary revascularisation within 30 days. T-MACS was built in one cohort (derivation set) and validated in three external cohorts (validation set). RESULTS: At the 'rule out' threshold, in the derivation set (n=703), T-MACS had 99.3% (95% CI 97.3% to 99.9%) negative predictive value (NPV) and 98.7% (95.3%-99.8%) sensitivity for ACS, 'ruling out' 37.7% patients (specificity 47.6%, positive predictive value (PPV) 34.0%). In the validation set (n=1459), T-MACS had 99.3% (98.3%-99.8%) NPV and 98.1% (95.2%-99.5%) sensitivity, 'ruling out' 40.4% (n=590) patients (specificity 47.0%, PPV 23.9%). T-MACS would 'rule in' 10.1% and 4.7% patients in the respective sets, of which 100.0% and 91.3% had ACS. C-statistics for the original and refined rules were similar (T-MACS 0.91 vs MACS 0.90 on validation). CONCLUSIONS: T-MACS could 'rule out' ACS in 40% of patients, while 'ruling in' 5% at highest risk using a single hs-cTnT measurement on arrival. As a clinical decision aid, T-MACS could therefore help to conserve healthcare resources

Protective Role of Interleukin-10 in Ozone-Induced Pulmonary Inflammation

BackgroundThe mechanisms underlying ozone (O3)-induced pulmonary inflammation remain unclear. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is known to inhibit inflammatory mediators.ObjectivesWe investigated the molecular mechanisms underlying interleuken-10 (IL-10)–mediated attenuation of O3-induced pulmonary inflammation in mice.MethodsIl10-deficient (Il10−/−) and wild-type (Il10+/+) mice were exposed to 0.3 ppm O3 or filtered air for 24, 48, or 72 hr. Immediately after exposure, differential cell counts and total protein (a marker of lung permeability) were assessed from bronchoalveolar lavage fluid (BALF). mRNA and protein levels of cellular mediators were determined from lung homogenates. We also used global mRNA expression analyses of lung tissue with Ingenuity Pathway Analysis to identify patterns of gene expression through which IL-10 modifies O3-induced inflammation.ResultsMean numbers of BALF polymorphonuclear leukocytes (PMNs) were significantly greater in Il10−/− mice than in Il10+/+ mice after exposure to O3 at all time points tested. O3-enhanced nuclear NF-κB translocation was elevated in the lungs of Il10−/− compared with Il10+/+ mice. Gene expression analyses revealed several IL-10–dependent and O3-dependent mediators, including macrophage inflammatory protein 2, cathepsin E, and serum amyloid A3.ConclusionsResults indicate that IL-10 protects against O3-induced pulmonary neutrophilic inflammation and cell proliferation. Moreover, gene expression analyses identified three response pathways and several genetic targets through which IL-10 may modulate the innate and adaptive immune response. These novel mechanisms of protection against the pathogenesis of O3-induced pulmonary inflammation may also provide potential therapeutic targets to protect susceptible individuals

Induction of Asthma and the Environment: What We Know and Need to Know

The prevalence of asthma has increased dramatically over the last 25 years in the United States and in other nations as a result of ill-defined changes in living conditions in modern society. On 18 and 19 October 2004 the U.S. Environmental Protection Agency and the National Institute of Environmental Health Sciences sponsored the workshop “Environmental Influences on the Induction and Incidence of Asthma” to review current scientific evidence with respect to factors that may contribute to the induction of asthma. Participants addressed two broad questions: a) What does the science suggest that regulatory and public health agencies could do now to reduce the incidence of asthma? and b) What research is needed to improve our understanding of the factors that contribute to the induction of asthma and our ability to manage this problem? In this article (one of four articles resulting from the workshop), we briefly characterize asthma and its public health and economic impacts, and intervention strategies that have been successfully used to prevent induction of asthma in the workplace. We conclude with the findings of seven working groups that focus on ambient air, indoor pollutants (biologics), occupational exposures, early life stages, older adults, intrinsic susceptibility, and lifestyle. These groups found strong scientific support for public health efforts to limit in utero and postnatal exposure to cigarette smoke. However, with respect to other potential types of interventions, participants noted many scientific questions, which are summarized in this article. Research to address these questions could have a significant public health and economic impact that would be well worth the investment

Moving magnetoencephalography towards real-world applications with a wearable system

Imaging human brain function with techniques such as magnetoencephalography1 (MEG) typically requires a subject to perform tasks whilst their head remains still within a restrictive scanner. This artificial environment makes the technique inaccessible to many people, and limits the experimental questions that can be addressed. For example, it has been difficult to apply neuroimaging to investigation of the neural substrates of cognitive development in babies and children, or in adult studies that require unconstrained head movement (e.g. spatial navigation). Here, we develop a new type of MEG system that can be worn like a helmet, allowing free and natural movement during scanning. This is possible due to the integration of new quantum sensors2,3 that do not rely on superconducting technology, with a novel system for nulling background magnetic fields. We demonstrate human electrophysiological measurement at millisecond resolution whilst subjects make natural movements, including head nodding, stretching, drinking and playing a ball game. Results compare well to the current state-of-the-art, even when subjects make large head movements. The system opens up new possibilities for scanning any subject or patient group, with myriad applications such as characterisation of the neurodevelopmental connectome, imaging subjects moving naturally in a virtual environment, and understanding the pathophysiology of movement disorders

HIV Testing of At Risk Patients in a Large Integrated Health Care System

OBJECTIVE: Early identification of HIV infection is critical for patients to receive life-prolonging treatment and risk-reduction counseling. Understanding HIV screening practices and barriers to HIV testing is an important prelude to designing successful HIV screening programs. Our objective was to evaluate current practice patterns for identification of HIV. METHODS: We used a retrospective cohort analysis of 13,991 at-risk patients seen at 4 large Department of Veterans Affairs (VA) health-care systems. We also reviewed 1,100 medical records of tested patients. We assessed HIV testing rates among at-risk patients, the rationale for HIV testing, and predictors of HIV testing and of HIV infection. RESULTS: Of the 13,991 patients at risk for HIV, only 36% had been HIV-tested. The prevalence of HIV ranged from 1% to 20% among tested patients at the 4 sites. Approximately 90% of patients who were tested had a documented reason for testing. CONCLUSION: One-half to two-thirds of patients at risk for HIV had not been tested within our selected VA sites. Among tested patients, the rationale for HIV testing was well documented. Further testing of at-risk patients could clearly benefit patients who have unidentified HIV infection by providing earlier access to life-prolonging therapy