Thermo-viscoplastic analysis of hypersonic structures subjected to severe aerodynamic heating

A thermoviscoplastic computational method for hypersonic structures is presented. The method employs unified viscoplastic constitutive model implemented in a finite element approach for quasi-static thermal-structural analysis. Applications of the approach to convectively cooled hypersonic structures illustrate the effectiveness of the approach and provide insight into the transient inelastic structural behavior at elevated temperatures

Comparison of manual and semi-automated delineation of regions of interest for radioligand PET imaging analysis

BACKGROUND As imaging centers produce higher resolution research scans, the number of man-hours required to process regional data has become a major concern. Comparison of automated vs. manual methodology has not been reported for functional imaging. We explored validation of using automation to delineate regions of interest on positron emission tomography (PET) scans. The purpose of this study was to ascertain improvements in image processing time and reproducibility of a semi-automated brain region extraction (SABRE) method over manual delineation of regions of interest (ROIs). METHODS We compared 2 sets of partial volume corrected serotonin 1a receptor binding potentials (BPs) resulting from manual vs. semi-automated methods. BPs were obtained from subjects meeting consensus criteria for frontotemporal degeneration and from age- and gender-matched healthy controls. Two trained raters provided each set of data to conduct comparisons of inter-rater mean image processing time, rank order of BPs for 9 PET scans, intra- and inter-rater intraclass correlation coefficients (ICC), repeatability coefficients (RC), percentages of the average parameter value (RM%), and effect sizes of either method. RESULTS SABRE saved approximately 3 hours of processing time per PET subject over manual delineation (p 0.8) for both methods. RC and RM% were lower for the manual method across all ROIs, indicating less intra-rater variance across PET subjects' BPs. CONCLUSION SABRE demonstrated significant time savings and no significant difference in reproducibility over manual methods, justifying the use of SABRE in serotonin 1a receptor radioligand PET imaging analysis. This implies that semi-automated ROI delineation is a valid methodology for future PET imaging analysis

Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease.

Altered brain metabolism is associated with progression of Alzheimer's Disease (AD). Mitochondria respond to bioenergetic changes by continuous fission and fusion. To account for three dimensional architecture of the brain tissue and organelles, we applied 3-dimensional electron microscopy (3D EM) reconstruction to visualize mitochondrial structure in the brain tissue from patients and mouse models of AD. We identified a previously unknown mitochondrial fission arrest phenotype that results in elongated interconnected organelles, "mitochondria-on-a-string" (MOAS). Our data suggest that MOAS formation may occur at the final stages of fission process and was not associated with altered translocation of activated dynamin related protein 1 (Drp1) to mitochondria but with reduced GTPase activity. Since MOAS formation was also observed in the brain tissue of wild-type mice in response to hypoxia or during chronological aging, fission arrest may represent fundamental compensatory adaptation to bioenergetic stress providing protection against mitophagy that may preserve residual mitochondrial function. The discovery of novel mitochondrial phenotype that occurs in the brain tissue in response to energetic stress accurately detected only using 3D EM reconstruction argues for a major role of mitochondrial dynamics in regulating neuronal survival

Direct Selective Laser Sintering of Tool Steel Powders to High Density: Part A - Effects of Laser Beam Width and Scan Strategy

This paper describes progress on the Direct Selective Laser Sintering of M2 and H13 tool steel powders, comparing this with previous and further observations on stainless steel powders. The distinguishing feature is the melting of single tracks and layers in deep powder beds. The paper focuses on changing characteristics of the melt pool (mass, volume, aspect ratio, stability) and laser-powder interactivity as the laser beam width, power and scan speed change. It also compares the melt pool of neighbouring tracks during single layer construction. Simulations from a computer model to predict melt pool shape and dimension show reasonable agreement with experimental results at low scan speeds (0.5mm/s). But unexpected increases in melt depth above 1.0mm/s have been observed, suggesting higher values and more variability in laser absorptivity than expected, even approaching 1.0 for the CO2 laser radiation used in this work.Mechanical Engineerin

Lifestyle interventions for type 2 diabetes management among migrants and ethnic minorities living in industrialized countries : a systematic review and meta-analyses

The objective of this systematic review was to determine the effectiveness of lifestyle interventions to improve the management of type 2 diabetes mellitus (T2DM) among migrants and ethnic minorities. Major searched databases included MEDLINE (via PubMed), EMBASE (via Ovid) and CINAHL. The selection of studies and data extraction followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In the meta-analysis, significant heterogeneity was detected among the studies (I 2 >50%), and hence a random effects model was used. Subgroup analyses were performed to compare the effect of lifestyle interventions according to intervention approaches (peer-led vs community health workers (CHWs)-led). A total of 17 studies were included in this review which used interventions delivered by CHWs or peer supporters or combination of both. The majority of the studies assessed effectiveness of key primary (hemoglobin (HbA1c), lipids, fasting plasma glucose) and secondary outcomes (weight, body mass index, blood pressure, physical activity, alcohol consumption, tobacco smoking, food habits and healthcare utilization). Meta-analyses showed lifestyle interventions were associated with a small but statistically significant reduction in HbA1c level (-0.18%; 95% CI-0.32% to-0.04%, p=0.031). In subgroup analyses, the peer-led interventions showed relatively better HbA1c improvement than CHW-led interventions, but the difference was not statistically significant (p=0.379). Seven studies presented intervention costs, which ranged from US$131 to US$461 per participant per year. We conclude that lifestyle interventions using either CHWs or peer supporters or a combination of both have shown modest effectiveness for T2DM management among migrants of different background and origin and ethnic minorities. The evidence base is promising in terms of developing culturally appropriate, clinically sound and cost-effective intervention approaches to respond to the growing and diverse migrants and ethnic minorities affected by diabetes worldwide

Occupational asthma caused by cobalt chloride in a diamond polisher after cessation of occupational exposure: a case report

Objectives: The inspiration of cobalt containing dust leads to various respiratory symptoms, including asthma and interstitial lung disease. Occupational asthma caused by cobalt chloride has been diagnosed in a 35-year-old patient, who worked as a diamond polishing disc former. The patient presented a 2-year history of dyspnea, cough and symptoms of rhinitis. Materials and Methods: The patient underwent a medical history interview, skin prick tests with common and occupational allergens (cobalt and nickel chloride), and pulmonary function testing both before and after the nasal provocation with 0.05% cobalt chloride. Additionally, the authors analyzed morphological and biochemical changes before and after the specific nasal challenge test. Cell proliferation analysis was also carried out. Results: Skin prick tests (SPTs) with common environmental allergens were found to be negative, while SPTs with cobalt chloride were positive for all applied solutions. The provocation with cobalt chloride caused a significant increase in the proportion of eosinophils, basophils and albumin during the late allergic reaction. The positive lymphocyte transformation caused by cobalt was also observed. Conclusions: Cobalt salts may induce occupational asthma. The mechanism of this asthma may be IgE-mediated. The cobalt-sensitized lymphocytes may play an important role in this disease

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Cohort profile of BIOMArCS: The BIOMarker study to identify the Acute risk of a Coronary Syndrome-a prospective multicentre biomarker study conducted in the Netherlands

__Purpose:__ Progression of stable coronary artery disease (CAD) towards acute coronary syndrome (ACS) is a dynamic and heterogeneous process with many intertwined constituents, in which a plaque destabilising sequence could lead to ACS within short time frames. Current CAD risk assessment models, however, are not designed to identify increased vulnerability for the occurrence of coronary events within a precise, short time frame at the individual patient level. The BIOMarker study to identify the Acute risk of a Coronary Syndrome (BIOMArCS) was designed to evaluate whether repeated measurements of multiple biomarkers can predict such 'vulnerable periods'. __Participants:__ BIOMArCS is a multicentre, prospective, observational study of 844 patients presenting with ACS, either with or without ST-elevation and at least one additional cardiovascular risk factor. __Methods and analysis:__ We hypothesised that patterns of circulating biomarkers that reflect the various pathophysiological components of CAD, such as distorted lipid metabolism, vascular inflammation, endothelial dysfunction, increased thrombogenicity and ischaemia, diverge in the days to weeks before a coronary event. Divergent biomarker patterns, identified by serial biomarker measurements during 1-year follow-up might then indicate 'vulnerable periods' during which patients with CAD are at high short-Term risk of developing an ACS. Venepuncture was performed every fortnight during the first half-year and monthly thereafter. As prespecified, patient enrolment was terminated after the primary end point of cardiovascular death or hospital admission for nonfatal ACS had occurred in 50 patients. A case-cohort design will explore differences in temporal patterns of circulating biomarkers prior to the repeat ACS