Occupational lung diseases among former goldminers in two labour sending areas

Objectives. To compare and contrast the prevalence of pneumoconiosis in two groups of former migrant mineworkers in southern Africa, and to examine the effectiveness of the South African compensation system for occupational lung diseases.Design. Comparison of two cross-sectional studies and follow-up data on compensation results.Setting. The village of Thamaga, Botswana and the rural area of Libode, Eastern Cape, South Africa.Subjects. Two hundred and thirty-four former underground mineworkers in Thamaga, and 238 in Libode. Main outcome measures. Prevalence and severity of pneumoconiosis, prevalence of radiological signs of tuberculosis (TB), Medical Bureau for Occupational Diseases (MBOD) certification committee decisions, and compensation results.Results. Prevalence of pneumoconiosis ≥ 2/ 1 was 15.4% in Libode and 13.6% in Thamaga. Significantly more Libode than Thamaga subjects (51.1% versus 29.0%) reported past TB treatment Radiological signs of pulmonary TB were also more prevalent in Libode (33.3% v. 23.9%). Twenty-six per cent of Libode men and 16.1% of Thamaga men were certified with compensable disease. Libode payments were finalised within 30 months, whereas Thamaga cases only began receiving payments 52 months after medical  examination, with 11 cases still pending 66 months after medical examination.Conclusion. There was a high prevalence of pneumoconiosis in both study groups. Many men were eligible for compensation but were previously uncompensated. The higher rate of compensable disease in the Libode group may relate to the higher prevalence of TB, as well as more active follow-up by the study group, including a large number of appeals. Socio-political changes in South Africa between 1994 and 1996 may also have influenced compensation results

Micromechanical homogenization of a hydrogel-filled electrospun scaffold for tissue-engineered epicardial patching of the infarcted heart: a feasibility study

For tissue engineering applications, accurate prediction of the effective mechanical properties of tissue scaffolds is critical. Open and closed cell modelling, mean-field homogenization theory, and finite element (FE) methods are theories and techniques currently used in conventional homogenization methods to estimate the equivalent mechanical properties of tissue-engineering scaffolds. This study aimed at developing a formulation to link the microscopic structure and macroscopic mechanics of a fibrous electrospun scaffold filled with a hydrogel for use as an epicardial patch for local support of the infarcted heart. The macroscopic elastic modulus of the scaffold was predicted to be 0.287 MPa with the FE method and 0.290 MPa with the closed-cell model for the realistic fibre structure of the scaffold, and 0.108 MPa and 0.540 MPa with mean-field homogenization for randomly oriented and completely aligned fibres. The homogenized constitutive description of the scaffold was implemented for an epicardial patch in a FE model of a human cardiac left ventricle to assess the effects of patching on myocardial mechanics and ventricular function in the presence of an infarct. Epicardial patching was predicted to reduce maximum myocardial stress in the infarcted LV from 19 kPa (no patch) to 9.5 kPa (patch) and to marginally improve the ventricular ejection fraction from 40% (no patch) to 43% (patch). This study demonstrates the feasibility of homogenization techniques to represent complex multiscale structural features in a simplified but meaningful and effective manner

Evaluating the efficacy of thoracoscopy and talc poudrage versus pleurodesis using talc slurry (TAPPS trial): protocol of an open-label randomised controlled trial

INTRODUCTION: The management of recurrent malignant pleural effusions (MPE) can be challenging. Various options are available, with the most efficacious and widely used being talc pleurodesis. Talc can either be applied via a chest drain in the form of slurry, or at medical thoracoscopy using poudrage. Current evidence regarding which method is most effective is conflicting and often methodologically flawed. The TAPPS trial is a suitably powered, multicentre, open-label, randomised controlled trial designed to compare the pleurodesis success rate of medical thoracoscopy and talc poudrage with chest drain insertion and talc slurry. METHODS AND ANALYSIS: 330 patients with a confirmed MPE requiring intervention will be recruited from UK hospitals. Patients will be randomised (1:1) to undergo either small bore (<14 Fr) Seldinger chest drain insertion followed by instillation of sterile talc (4 g), or to undergo medical thoracoscopy and simultaneous poudrage (4 g). The allocated procedure will be performed as an inpatient within 3 days of randomisation taking place. Following discharge, patients will be followed up at regular intervals for 6 months. The primary outcome measure is pleurodesis failure rates at 3 months. Pleurodesis failure is defined as the need for further pleural intervention for fluid management on the side of the trial intervention. ETHICS AND DISSEMINATION: The trial has received ethical approval from the National Research Ethics Service Committee North West-Preston (12/NW/0467). There is a trial steering committee which includes independent members and a patient and public representative. The trial results will be published in a peer-reviewed journal and presented at international conferences, as well as being disseminated via local and national charities and patient groups. All participants who wish to know the study results will also be contacted directly on their publication. TRIAL REGISTRATION NUMBER: ISRCTN47845793

Continuity, Deconfinement, and (Super) Yang-Mills Theory

We study the phase diagram of SU(2) Yang-Mills theory with one adjoint Weyl fermion on R^3xS^1 as a function of the fermion mass m and the compactification scale L. This theory reduces to thermal pure gauge theory as m->infinity and to circle-compactified (non-thermal) supersymmetric gluodynamics in the limit m->0. In the m-L plane, there is a line of center symmetry changing phase transitions. In the limit m->infinity, this transition takes place at L_c=1/T_c, where T_c is the critical temperature of the deconfinement transition in pure Yang-Mills theory. We show that near m=0, the critical compactification scale L_c can be computed using semi-classical methods and that the transition is of second order. This suggests that the deconfining phase transition in pure Yang-Mills theory is continuously connected to a transition that can be studied at weak coupling. The center symmetry changing phase transition arises from the competition of perturbative contributions and monopole-instantons that destabilize the center, and topological molecules (neutral bions) that stabilize the center. The contribution of molecules can be computed using supersymmetry in the limit m=0, and via the Bogomolnyi--Zinn-Justin (BZJ) prescription in the non-supersymmetric gauge theory. Finally, we also give a detailed discussion of an issue that has not received proper attention in the context of N=1 theories---the non-cancellation of nonzero-mode determinants around supersymmetric BPS and KK monopole-instanton backgrounds on R^3xS^1. We explain why the non-cancellation is required for consistency with holomorphy and supersymmetry and perform an explicit calculation of the one-loop determinant ratio.Comment: A discussion of the non-cancellation of the nonzero mode determinants around supersymmetric monopole-instantons in N=1 SYM on R^3xS^1 is added, including an explicit calculation. The non-cancellation is, in fact, required by supersymmetry and holomorphy in order for the affine-Toda superpotential to be reproduced. References have also been adde

Power calculator for instrumental variable analysis in pharmacoepidemiology

Background: Instrumental variable analysis, for example with physicians' prescribing preferences as an instrument for medications issued in primary care, is an increasingly popular method in the field of pharmacoepidemiology. Existing power calculators for studies using instrumental variable analysis, such as Mendelian randomization power calculators, do not allow for the structure of research questions in this field. This is because the analysis in pharmacoepidemiology will typically have stronger instruments and detect larger causal effects than in other fields. Consequently, there is a need for dedicated power calculators for pharmacoepidemiological research. Methods and Results: The formula for calculating the power of a study using instrumental variable analysis in the context of pharmacoepidemiology is derived before being validated by a simulation study. The formula is applicable for studies using a single binary instrument to analyse the causal effect of a binary exposure on a continuous outcome. An online calculator, as well as packages in both R and Stata, are provided for the implementation of the formula by others. Conclusions: The statistical power of instrumental variable analysis in pharmacoepidemiological studies to detect a clinically meaningful treatment effect is an important consideration. Research questions in this field have distinct structures that must be accounted for when calculating power. The formula presented differs from existing instrumental variable power formulae due to its parametrization, which is designed specifically for ease of use by pharmacoepidemiologists.This work was supported by the Perros Trust and the Integrative Epidemiology Unit. The Integrative Epidemiology Unit is supported by the Medical Research Council and the University of Bristol [grant number MC_UU_12013/9]. S.B. is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 204623/Z/16/Z)

Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling

Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα(Thr172) and CREB-1(Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65(Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs

Cross-sectional analysis of educational inequalities in primary prevention statin use in UK Biobank.

OBJECTIVE: Identify whether participants with lower education are less likely to report taking statins for primary cardiovascular prevention than those with higher education, but an equivalent increase in underlying cardiovascular risk. METHODS: Using data from a large prospective cohort study, UK Biobank, we calculated a QRISK3 cardiovascular risk score for 472 097 eligible participants with complete data on self-reported educational attainment and statin use (55% female participants; mean age 56 years). We used logistic regression to explore the association between (i) QRISK3 score and (ii) educational attainment on self-reported statin use. We then stratified the association between QRISK3 score and statin use, by educational attainment to test for interactions. RESULTS: There was evidence of an interaction between QRISK3 score and educational attainment. Per unit increase in QRISK3 score, more educated individuals were more likely to report taking statins. In women with ≤7 years of schooling, a one unit increase in QRISK3 score was associated with a 7% higher odds of statin use (OR 1.07, 95% CI 1.07 to 1.07). In women with ≥20 years of schooling, a one unit increase in QRISK3 score was associated with an 14% higher odds of statin use (OR 1.14, 95% CI 1.14 to 1.15). Comparable ORs in men were 1.04 (95% CI 1.04 to 1.05) for ≤7 years of schooling and 1.08 (95% CI 1.08, 1.08) for ≥20 years of schooling. CONCLUSION: Per unit increase in QRISK3 score, individuals with lower educational attainment were less likely to report using statins, likely contributing to health inequalities

Consensus-based antimicrobial resistance and stewardship competencies for UK undergraduate medical students.

BACKGROUND: In the UK there is limited coverage of antimicrobial stewardship across postgraduate curricula and evidence that final year medical students have insufficient and inconsistent antimicrobial stewardship teaching. A national undergraduate curriculum for antimicrobial resistance and stewardship is required to standardize an adequate level of understanding for all future doctors. OBJECTIVES: To provide a UK national consensus on competencies for antimicrobial resistance and stewardship for undergraduate medical education. METHODS: Using the modified Delphi method over two online survey rounds, an expert panel comprising leads for infection teaching from 25 UK medical schools reviewed competency descriptors for antimicrobial resistance and stewardship education. RESULTS: There was a response rate of 100% with all 28 experts who agreed to take part completing both survey rounds. Following the first-round survey, of the initial 55 descriptors, 43 reached consensus (78%). The second-round survey included the 12 descriptors from the first round in which agreement had not been reached, four amended descriptors and 12 new descriptors following qualitative feedback from the panel members. Following the second-round survey, a total of 58 consensus-based competency descriptors within six overarching domains were identified. CONCLUSIONS: The consensus-based competency descriptors defined here can be used to inform standards, design curricula, develop assessment tools and direct UK undergraduate medical education

Early and efficient detection of Mycobacterium tuberculosis in sputum by microscopic observation of broth cultures.

Early, efficient and inexpensive methods for the detection of pulmonary tuberculosis are urgently needed for effective patient management as well as to interrupt transmission. These methods to detect M. tuberculosis in a timely and affordable way are not yet widely available in resource-limited settings. In a developing-country setting, we prospectively evaluated two methods for culturing and detecting M. tuberculosis in sputum. Sputum samples were cultured in liquid assay (micro broth culture) in microplate wells and growth was detected by microscopic observation, or in Löwenstein-Jensen (LJ) solid media where growth was detected by visual inspection for colonies. Sputum samples were collected from 321 tuberculosis (TB) suspects attending Bugando Medical Centre, in Mwanza, Tanzania, and were cultured in parallel. Pulmonary tuberculosis cases were diagnosed using the American Thoracic Society diagnostic standards. There were a total of 200 (62.3%) pulmonary tuberculosis cases. Liquid assay with microscopic detection detected a significantly higher proportion of cases than LJ solid culture: 89.0% (95% confidence interval [CI], 84.7% to 93.3%) versus 77.0% (95% CI, 71.2% to 82.8%) (p = 0.0007). The median turn around time to diagnose tuberculosis was significantly shorter for micro broth culture than for the LJ solid culture, 9 days (interquartile range [IQR] 7-13), versus 21 days (IQR 14-28) (p<0.0001). The cost for micro broth culture (labor inclusive) in our study was US $4.56 per sample, versus US$11.35 per sample for the LJ solid culture. The liquid assay (micro broth culture) is an early, feasible, and inexpensive method for detection of pulmonary tuberculosis in resource limited settings

Supersymmetric QCD: Exact Results and Strong Coupling

We revisit two longstanding puzzles in supersymmetric gauge theories. The first concerns the question of the holomorphy of the coupling, and related to this the possible definition of an exact (NSVZ) beta function. The second concerns instantons in pure gluodynamics, which appear to give sensible, exact results for certain correlation functions, which nonetheless differ from those obtained using systematic weak coupling expansions. For the first question, we extend an earlier proposal of Arkani-Hamed and Murayama, showing that if their regulated action is written suitably, the holomorphy of the couplings is manifest, and it is easy to determine the renormalization scheme for which the NSVZ formula holds. This scheme, however, is seen to be one of an infinite class of schemes, each leading to an exact beta function; the NSVZ scheme, while simple, is not selected by any compelling physical consideration. For the second question, we explain why the instanton computation in the pure supersymmetric gauge theory is not reliable, even at short distances. The semiclassical expansion about the instanton is purely formal; if infrared divergences appear, they spoil arguments based on holomorphy. We demonstrate that infrared divergences do not occur in the perturbation expansion about the instanton, but explain that there is no reason to think this captures all contributions from the sector with unit topological charge. That one expects additional contributions is illustrated by dilute gas corrections. These are infrared divergent, and so difficult to define, but if non-zero give order one, holomorphic, corrections to the leading result. Exploiting an earlier analysis of Davies et al, we demonstrate that in the theory compactified on a circle of radius beta, due to infrared effects, finite contributions indeed arise which are not visible in the formal limit that beta goes to infinity.Comment: 28 pages, two references added, one typo correcte