Geophysical characterization of derelict coalmine workings and mineshaft detection: a case study from Shrewsbury, United Kingdom

A study site of derelict coalmine workings near Shrewsbury, United Kingdom was the focus for multi‐phase, near‐surface geophysical investigations. Investigation objectives were: 1) site characterization for remaining relict infrastructure foundations, 2) locate an abandoned coalmine shaft, 3) determine if the shaft was open, filled or partially filled and 4) determine if the shaft was capped (and if possible characterize the capping material). Phase one included a desktop study and 3D microgravity modelling of the relict coalmine shaft thought to be on site. In phase two, electrical and electromagnetic surveys to determine site resistivity and conductivity were acquired together with fluxgate gradiometry and an initial microgravity survey. Phase three targeted the phase two geophysical anomalies and acquired high‐resolution self potential and ground penetrating radar datasets. The phased‐survey approach minimised site activity and survey costs. Geophysical results were compared and interpreted to characterize the site, the microgravity models were used to validate interpretations. Relict buildings, railway track remains with associated gravel and a partially filled coalmine shaft were located. Microgravity proved optimal to locate the mineshaft with radar profiles showing ‘side‐swipe’ effects from the mineshaft that did not directly underlie survey lines. Geophysical interpretations were then verified with subsequent geotechnical intrusive investigations. Comparisons of historical map records with intrusive geotechnical site investigations show care must be taken using map data alone, as the latter mineshaft locations was found to be inaccurate

Impact of eight weeks of repeated ischaemic preconditioning on brachial artery and cutaneous microcirculatory function in healthy males

Background Ischaemic preconditioning has well-established cardiac and vascular protective effects. Short interventions (one week) of daily ischaemic preconditioning episodes improve conduit and microcirculatory function. This study examined whether a longer (eight weeks) and less frequent (three per week) protocol of repeated ischaemic preconditioning improves vascular function. Methods Eighteen males were randomly allocated to either ischaemic preconditioning (22.4 ± 2.3 years, 23.7 ± 3.1 kg/m2) or a control intervention (26.0 ± 4.8 years, 26.4 ± 1.9 kg/m2). Brachial artery endothelial-dependent (FMD), forearm cutaneous microvascular function and cardiorespiratory fitness were assessed at zero, two and eight weeks. Results A greater improvement in FMD was evident following ischaemic preconditioning training compared with control at weeks 2 (2.24% (0.40, 4.08); p=0.02) and 8 (1.11% (0.13, 2.10); p=0.03). Repeated ischaemic preconditioning did not change cutaneous microcirculatory function or fitness. Conclusions These data indicate that a feasible and practical protocol of regular ischaemic preconditioning episodes improves endothelial function in healthy individuals within two weeks, and these effects persist following repeated ischaemic preconditioning for eight weeks

Parabolic oblique derivative problem in generalized Morrey spaces

We study the regularity of the solutions of the oblique derivative problem for linear uniformly parabolic equations with VMO coefficients. We show that if the right-hand side of the parabolic equation belongs to certain generalized Morrey space than the strong solution belongs to the corresponding generalized Sobolev-Morrey space

St George's Respiratory Questionnaire Score Predicts Outcomes in Patients with COPD: Analysis of Individual Patient Data in the COPD Biomarkers Qualification Consortium Database.

Background: We aimed to estimate the usefulness of a disease specific health status measure, the St George's Respiratory Questionnaire (SGRQ), to predict outcomes in patients with chronic obstructive pulmonary disease (COPD). Methods: Individual patient-data of 12043 patients from long-term randomized clinical trials (2-4 years' duration) in the COPD Biomarkers Qualification Consortium database were analyzed. The adverse COPD outcomes were: exacerbations of COPD, hospital admissions due to exacerbation and all-cause mortality. Cox proportional hazards regression was used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for quartiles of SGRQ scores at baseline and time to first event, and time from first to second event, where appropriate. Results: The risk of adverse COPD outcomes increased with each increasing quartile of SGRQ score for all time to first event analyses. When comparing the lowest versus the highest quartile, the event risk (HRs [95% CIs]) increased by 40% for exacerbations (1.40 [1.29, 1.51]); 2-fold for hospital admissions (2.01 [1.78, 2.28]) and more than 2-fold for all-cause mortality (2.30 [1.91, 2.78]). For second event analyses in a subset of eligible patients, these trends persisted albeit with reduced risk estimates for exacerbations. Conclusions: Among patients with COPD, health status measured by a SGRQ score predicted exacerbations of COPD, hospital admissions due to exacerbations and their recurrence and death after adjustment. These data support the rationale for a health status measure use as a drug development tool and suggest that a health status measure may also have a role in risk assessment for COPD patients in routine medical care

Socioeconomic Status as a Determinant of Health Status Treatment Response in COPD Trials.

Background: Randomized controlled trials (RCTs) often recruit patients from low and high socioeconomic status (SES) countries, but little is known about the effect of SES on clinical outcomes, particularly patient-centered measures of symptomatic benefit. Methods: Combined individual chronic obstructive pulmonary disease (COPD) patient data from the placebo and long-acting bronchodilator arms of 17 RCTs (from the COPD Biomarkers Qualification Consortium database) were analyzed. Health status was measured using the St George's Respiratory Questionnaire (SGRQ) (minimum clinically important difference [MCID]: 4 units). Trials were grouped into short-term (≤12 months) and medium-term (>12 months to 48 months). A participant's country of residence was categorized into Low/Medium or High SES using World Health Organization criteria. Results: Data from 19765 individuals (6109 Low/Medium SES) were available. Patients in Low/Medium SES countries had more severe disease at baseline. Improvement in SGRQ score with placebo was ≈2 units greater in Low/Medium than in High SES countries; at its greatest, the improvement from baseline exceeded the MCID in Low/Medium countries. This difference was maintained for at least 1 year. Improvement with bronchodilator was also greater in Low/Medium versus High SES countries; overall there was no evidence that the treatment effect versus placebo was different between countries of different SES status. Conclusions: Participants in Low/Medium SES countries experienced significantly larger treatment effects, irrespective of treatment group (placebo and bronchodilator). Despite this, COPD patients in Low/Medium SES countries experienced a health status gain from long-acting bronchodilator treatment that is similar to that seen in High SES countries

The COPD Biomarkers Qualification Consortium Database: Baseline Characteristics of the St George's Respiratory Questionnaire Dataset.

The COPD Biomarkers Qualification Consortium (CBQC) is a public-private partnership formed in 2010 with a goal of qualifying biomarkers and clinical assessment tools for use in clinical or nonclinical decision-making and particularly within the regulatory context. The St George's Respiratory Questionnaire (SGRQ) is a measure of health-related quality of life widely used in clinical research. The aim of the CBQC working group on SGRQ was to construct an individual patient level database of clinical trial data that included the SGRQ, to use this to confirm the reliability and validity of the SGRQ as an outcome measure of health status, and investigate its use as a predictor of future events (exacerbations and mortality). This manuscript describes the formulation of the CBQC database and presents the baseline demographic and clinical characteristics of the integrated SGRQ database overall, and by study type (short-term [≤1 year], medium-term [2-4 years] and observational studies). Distribution of baseline SGRQ scores varied little by demographic determinants except for income region in the observational data set (low-middle income countries +10 units compared with high income, p<0.0001) and this observation held across studies. SGRQ scores increased with increasing modified Medical Research Council dyspnea scores (mean differences ranged 6.9-17.9 units) and with increasing airflow limitations (Global initiative for chronic Obstructive Lung Disease grades 1 to 4; differences ranged 4.5-16.1 units), consistent across study types. As a method of cross-sectional comparison, the SGRQ appears to be relatively free of bias from demographic factors although care should be taken when making cross sectional comparisons of scores between patients in countries at different levels of socio-economic development/

Metabolically healthy and unhealthy obesity: differential effects on myocardial function according to metabolic syndrome, rather than obesity.

BACKGROUND: The term 'metabolically healthy obese (MHO)' is distinguished using body mass index (BMI), yet BMI is a poor index of adiposity. Some epidemiological data suggest that MHO carries a lower risk of cardiovascular disease (CVD) or mortality than being normal weight yet metabolically unhealthy. OBJECTIVES: We aimed to undertake a detailed phenotyping of individuals with MHO by using imaging techniques to examine ectopic fat (visceral and liver fat deposition) and myocardial function. We hypothesised that metabolically unhealthy individuals (irrespective of BMI) would have adverse levels of ectopic fat and myocardial dysfunction compared with MHO individuals. SUBJECTS: Individuals were categorised as non-obese or obese (BMI ⩾30 kg m(-2)) and as metabolically healthy or unhealthy according to the presence or absence of metabolic syndrome. METHODS: Sixty-seven individuals (mean±s.d.: age 49±11 years) underwent measurement of (i) visceral, subcutaneous and liver fat using magnetic resonance imaging and proton magnetic resonance spectroscopy, (ii) components of metabolic syndrome, (iii) cardiorespiratory fitness and (iv) indices of systolic and diastolic function using tissue Doppler echocardiography. RESULTS: Cardiorespiratory fitness was similar between all groups; abdominal and visceral fat was highest in the obese groups. Compared with age- and BMI-matched metabolically healthy counterparts, the unhealthy (lean or obese) individuals had higher liver fat and decreased early diastolic strain rate, early diastolic tissue velocity and systolic strain indicative of subclinical systolic and diastolic dysfunction. The magnitude of dysfunction correlated with the number of components of metabolic syndrome but not with BMI or with the degree of ectopic (visceral or liver) fat deposition. CONCLUSIONS: Myocardial dysfunction appears to be related to poor metabolic health rather than simply BMI or fat mass. These data may partly explain the epidemiological evidence on CVD risk relating to the different obesity phenotypes

REPEATED WARM WATER IMMERSION INDUCES SIMILAR CEREBROVASCULAR ADAPTATIONS TO 8-WEEKS OF MODERATE-INTENSITY EXERCISE TRAINING IN FEMALES

Exercise training has potential to positively impact cerebrovascular function in healthy and diseased individuals. Passive heat training using warm water immersion has recently been shown to enhance systemic vascular function including the cerebrovascular response to heating. We suggest that a passive heating intervention can be a useful adjunct or alternative to exercise training. Our aim was to directly compare the effects of exercise with warm water immersion training on cerebrovascular and thermoregulatory function. 18 females (25±5y) performed 8-weeks of moderate-intensity cycling (70% HRmax) or warm-water immersion (42°C) for 30 min three times per week. Brachial artery flow-mediated dilation (FMD) and cardiorespiratory fitness were measured prior to and following both interventions. A passive heat stress was employed to obtain temperature thresholds (Tb) and sensitivities for chest and forearm sweat rate (SR) and cutaneous vasodilation (CVC). Middle cerebral artery velocity (MCAv) was measured at rest and throughout heat stress. FMD (P=0.003) and VO2peak (P<0.001) improved following both interventions. MCAv and cerebrovascular conductance were higher at rest (P<0.001 and 0.05, respectively) and during passive heating (P<0.001 and <0.001, respectively) following both interventions. Chest and forearm SR occurred at a lower Tb post-intervention with no difference between interventions. Chest and forearm SR sensitivity were increased after both interventions with no differences between interventions at the forearm but a larger increase at the chest (P<0.001) following water immersion compared to exercise training. Chest and forearm CVC occurred at a lower Tb (P<0.001) following both interventions with no differences between interventions or over time. Warm water immersion training elicits favourable and similar cerebrovascular, conduit- and thermoregulatory adaptations compared to a period of moderate-intensity exercise training over 8-weeks

Health and lifestyle of Nepalese migrants in the UK

Background: The health status and lifestyle of migrants is often poorer than that of the general population of their host countries. The Nepalese represent a relatively small, but growing, immigrant community in the UK, about whom very little is known in term of public health. Therefore, our study examined the health and lifestyle of Nepalese migrants in the UK. Methods: A cross-sectional survey of Nepalese migrants in UK was conducted in early 2007 using a postal, self-administered questionnaire in England and Scotland (n = 312), and telephone interviews in Wales (n = 15). The total response rate was 68% (327 out of 480). Data were analyzed to establish whether there are associations between socio-economic and lifestyle factors. A multivariate binary logistic regression was applied to find out independent effect of personal factors on health status. Results: The majority of respondents was male (75%), aged between 30 and 45 (66%), married or had a civil partner (83%), had university education (47%) and an annual family income (69%) ranging from £5,035 to £33,300. More than one third (39%) of the respondents have lived in the UK for 1 to 5 years and approximately half (46%) were longer-term residents. Most (95%) were registered with a family doctor, but only 38% with a dentist. A low proportion (14%) of respondents smoked but more than half (61%) consumed alcohol. More than half (57%) did not do regular exercises and nearly one fourth (23%) of respondents rated their health as poor. Self reported 'good' health status of the respondents was independently associated with immigration status and doing regular exercise Conclusion: The self reported health status and lifestyle, health seeking behaviour of Nepalese people who are residing in UK appears to be good. However, the overall regular exercise and dentist registration was rather poor. Health promotion, especially aimed at Nepalese migrants could help encourage them to exercise regularly and assist them to register with a dentist

BAT117213: Ileal bile acid transporter (IBAT) inhibition as a treatment for pruritus in primary biliary cirrhosis: study protocol for a randomised controlled trial

Background: Pruritus (itch) is a symptom commonly experienced by patients with cholestatic liver diseases such as primary biliary cholangitis (PBC, previously referred to as primary biliary cirrhosis). Bile acids (BAs) have been proposed as potential pruritogens in PBC. The ileal bile acid transporter (IBAT) protein expressed in the distal ileum plays a key role in the enterohepatic circulation of BAs. Pharmacological inhibition of IBAT with GSK2330672 may reduce BA levels in the systemic circulation and improve pruritus. Methods: This clinical study (BAT117213 study) is sponsored by GlaxoSmithKline (GSK) with associated exploratory studies supported by the National Institute for Health Research (NIHR). It is a phase 2a, multi-centre, randomised, double bind, placebo controlled, cross-over trial for PBC patients with pruritus. The primary objective is to investigate the safety and tolerability of repeat doses of GSK2330672, and explore whether GSK2330672 administration for 14 days improves pruritus compared with placebo. The key outcomes include improvement in pruritus scores evaluated on a numerical rating scale and other PBC symptoms in an electronic diary completed twice daily by the patients. The secondary outcomes include the evaluation of the effect of GSK2330672 on total serum bile acid (BA) concentrations, serum markers of BA synthesis and steady-state pharmacokinetics of ursodeoxycholic acid (UDCA). Discussion: BAT117213 study is the first randomised controlled crossover trial of ileal bile acid transporter inhibitor, a novel class of drug to treat pruritus in PBC. The main strengths of the trial are utility of a novel, study specific, electronic symptom diary as patient reported outcome to measure the treatment response objectively and the crossover design that allows estimating the treatment effect in a smaller number of patients. The outcome of this trial will inform the trial design of future development phase of the IBAT inhibitor drug. The trial will also provide opportunity to conduct metabonomic and gut microbiome studies as explorative and mechanistic research in patients with cholestatic pruritus