126 research outputs found

    Thin-Skin Electromagnetic Fields Around Surface-Breaking Cracks in Metals

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    In situations where the electrical skin depth δ is small compared with a typical crack dimension l, substantial progress has been achieved in recent years in modeling surface electromagnetic fields and the perturbations that are produced in them by surface-breaking flaws [1,2,3]. The development of an unfolding theory at UCL for thin-skin surface fields was based on the approximation that the electric and magnetic field vectors E and H are essentially tangential to the surface of the material in the surface skin. It was motivated by the desire to measure fatigue cracks in ferrous materials used in large-scale steel structures such as offshore oil rigs [2], and the method to which it was applied was the a.c. field measurement technique. Auld et al [4,5] later adapted the unfolding approach in considering thin-skin field models for the eddy current method, and their major concern was with applications to non-ferrous materials used in airframe and aero-engine manufacture. For acfm work, the unfolding theory leads to a surface Laplacian field on both the metal surface and the crack face and information on the crack presence is deduced by measuring perturbations in the surface field. Auld’s model for eddy currents also has a plane Laplacian field on the crack face, but it is assumed that the crack produces no change in the field on the metal surface. Field lines in the unfolded plane for both models are shown schematically in Figure 1(b,c) for the case when the interrogating field is uniform and the crack is semi-circular. Auld’s model has been described as a Born type of approximation from an analogy with wave scattering theory which ignores the scattered field when calculating scattering cross-sections

    Disparities in the frequency of fruit and vegetable consumption by socio-demographic and lifestyle characteristics in Canada

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    <p>Abstract</p> <p>Background</p> <p>The health benefits of adequate fruit and vegetable (F&V) consumption are significant and widely documented. However, many individuals self-report low F&V consumption frequency per day. This paper examines the disparities in the frequency of F&V consumption by socio-demographic and lifestyle characteristics.</p> <p>Method</p> <p>This study uses a representative sample of 93,719 individuals from the Canadian Community Health Survey (2007). A quantile regression model is estimated in order to capture the differential effects of F&V determinants across the conditional distribution of F&V consumption.</p> <p>Results</p> <p>The conditional and unconditional analyses reveal the existence of a socioeconomic gradient in F&V consumption frequency, in which the low income-education groups consume F&V less frequently than the high income-education groups. We also find significant disparities in F&V consumption frequency by demographic and lifestyle characteristics. The frequency of F&V consumption is relatively lower among: males, those in middle age, singles, smokers, individuals with weak social interaction and households with no children. The quantile regression results show that the association between F&V consumption frequency, and socio-demographic and lifestyle factors varies significantly along the conditional F&V consumption distribution. In particular, individual educational attainment is positively and significantly associated with F&V consumption frequency across different parts of the F&V distribution, while the income level matters only over the lower half of the distribution. F&V consumption follows a U-shaped pattern across the age categories. Those aged 30-39, 40-49 and 50-59 years consume F&V less frequently than those aged 18-29 years. The smallest F&V consumption is among the middle aged adults (40-49).</p> <p>Conclusions</p> <p>Understanding the socio-demographic and lifestyle characteristics of individuals with low F&V consumption frequency could increase the effectiveness of policies aimed at promoting F&V consumption. The differential effects of individual characteristics along the F&V consumption distribution suggest the need for a multifaceted approach to address the variation in F&V consumption frequency.</p

    Differential Scanning Fluorometry Signatures as Indicators of Enzyme Inhibitor Mode of Action: Case Study of Glutathione S-Transferase

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    Differential scanning fluorometry (DSF), also referred to as fluorescence thermal shift, is emerging as a convenient method to evaluate the stabilizing effect of small molecules on proteins of interest. However, its use in the mechanism of action studies has received far less attention. Herein, the ability of DSF to report on inhibitor mode of action was evaluated using glutathione S-transferase (GST) as a model enzyme that utilizes two distinct substrates and is known to be subject to a range of inhibition modes. Detailed investigation of the propensity of small molecule inhibitors to protect GST from thermal denaturation revealed that compounds with different inhibition modes displayed distinct thermal shift signatures when tested in the presence or absence of the enzyme's native co-substrate glutathione (GSH). Glutathione-competitive inhibitors produced dose-dependent thermal shift trendlines that converged at high compound concentrations. Inhibitors acting via the formation of glutathione conjugates induced a very pronounced stabilizing effect toward the protein only when GSH was present. Lastly, compounds known to act as noncompetitive inhibitors exhibited parallel concentration-dependent trends. Similar effects were observed with human GST isozymes A1-1 and M1-1. The results illustrate the potential of DSF as a tool to differentiate diverse classes of inhibitors based on simple analysis of co-substrate dependency of protein stabilization

    Why Are There Social Gradients in Preventative Health Behavior? A Perspective from Behavioral Ecology

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    Background: Within affluent populations, there are marked socioeconomic gradients in health behavior, with people of lower socioeconomic position smoking more, exercising less, having poorer diets, complying less well with therapy, using medical services less, ignoring health and safety advice more, and being less health-conscious overall, than their more affluent peers. Whilst the proximate mechanisms underlying these behavioral differences have been investigated, the ultimate causes have not. Methodology/Principal Findings: This paper presents a theoretical model of why socioeconomic gradients in health behavior might be found. I conjecture that lower socioeconomic position is associated with greater exposure to extrinsic mortality risks (that is, risks that cannot be mitigated through behavior), and that health behavior competes for people’s time and energy against other activities which contribute to their fitness. Under these two assumptions, the model shows that the optimal amount of health behavior to perform is indeed less for people of lower socioeconomic position. Conclusions/Significance: The model predicts an exacerbatory dynamic of poverty, whereby the greater exposure of poor people to unavoidable harms engenders a disinvestment in health behavior, resulting in a final inequality in health outcomes which is greater than the initial inequality in material conditions. I discuss the assumptions of the model, and it

    Four-Year Treatment Outcomes of Adult Patients Enrolled in Mozambique's Rapidly Expanding Antiretroviral Therapy Program

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    BACKGROUND: In Mozambique during 2004-2007 numbers of adult patients (≥15 years old) enrolled on antiretroviral therapy (ART) increased about 16-fold, from <5,000 to 79,500. All ART patients were eligible for co-trimoxazole. ART program outcomes, and determinants of outcomes, have not yet been reported. METHODOLOGY/PRINCIPAL FINDINGS: In a retrospective cohort study, we investigated rates of mortality, attrition (death, loss to follow-up, or treatment cessation), immunologic treatment failure, and regimen-switch, as well as determinants of selected outcomes, among a nationally representative sample of 2,596 adults initiating ART during 2004-2007. At ART initiation, median age of patients was 34 and 62% were female. Malnutrition and advanced disease were common; 18% of patients weighed <45 kilograms, and 15% were WHO stage IV. Median baseline CD4(+) T-cell count was 153/µL and was lower for males than females (139/µL vs. 159/µL, p<0.01). Stavudine, lamivudine, and nevirapine or efavirenz were prescribed to 88% of patients; only 31% were prescribed co-trimoxazole. Mortality and attrition rates were 3.4 deaths and 19.8 attritions per 100 patient-years overall, and 12.9 deaths and 57.2 attritions per 100 patient-years in the first 90 days. Predictors of attrition included male sex [adjusted hazard ratio (AHR) 1.5; 95% confidence interval (CI), 1.3-1.8], weight <45 kg (AHR 2.1; 95% CI, 1.6-2.9, reference group >60 kg), WHO stage IV (AHR 1.7; 95% CI, 1.3-2.4, reference group WHO stage I/II), lack of co-trimoxazole prescription (AHR 1.4; 95% CI, 1.0-1.8), and later calendar year of ART initiation (AHR 1.5; 95% CI, 1.2-1.8). Rates of immunologic treatment failure and regimen-switch were 14.0 and 0.6 events per 100-patient years, respectively. CONCLUSIONS: ART initiation at earlier disease stages and scale-up of co-trimoxazole among ART patients could improve outcomes. Research to determine reasons for low regimen-switch rates and increasing rates of attrition during program expansion is needed

    Small molecule activators of the Trk receptors for neuroprotection

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    The neurotophin signaling network is critical to the development and survival of many neuronal populations. Especially sensitive to imbalances in the neurotrophin system, cholinergic neurons in the basal forebrain are progressively lost in Alzheimer's disease. Therapeutic use of neurotrophins to prevent this loss is hampered, however, by a number of pharmacological challenges. These include a lack of transport across the blood-brain barrier, rapid degradation in the circulation, and difficulty in production. In this review we discuss the evidence supporting the neurotrophin system's role in preventing neurodegeneration and survey some of the pharmacological strategies being pursued to develop effective therapeutics targeting neurotrophin function

    Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

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    Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability
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