A comparison of short-term and long-term air pollution exposure associations with mortality in two cohorts in Scotland

Air pollution–mortality risk estimates are generally larger at longer-term, compared with short-term, exposure time scales. We compared associations between short-term exposure to black smoke (BS) and mortality with long-term exposure–mortality associations in cohort participants and with short-term exposure–mortality associations in the general population from which the cohorts were selected. We assessed short-to-medium–term exposure–mortality associations in the Renfrew–Paisley and Collaborative cohorts (using nested case–control data sets), and compared them with long-term exposure–mortality associations (using a multilevel spatiotemporal exposure model and survival analyses) and short-to-medium–term exposure–mortality associations in the general population (using time-series analyses). For the Renfrew–Paisley cohort (15,331 participants), BS exposure–mortality associations were observed in nested case–control analyses that accounted for spatial variations in pollution exposure and individual-level risk factors. These cohort-based associations were consistently greater than associations estimated in time-series analyses using a single monitoring site to represent general population exposure {e.g., 1.8% [95% confidence interval (CI): 0.1, 3.4%] vs. 0.2% (95% CI: 0.0, 0.4%) increases in mortality associated with 10-μg/m3 increases in 3-day lag BS, respectively}. Exposure–mortality associations were of larger magnitude for longer exposure periods [e.g., 3.4% (95% CI: –0.7, 7.7%) and 0.9% (95% CI: 0.3, 1.5%) increases in all-cause mortality associated with 10-μg/m3 increases in 31-day BS in case–control and time-series analyses, respectively; and 10% (95% CI: 4, 17%) increase in all-cause mortality associated with a 10-μg/m3 increase in geometic mean BS for 1970–1979, in survival analysis]. After adjusting for individual-level exposure and potential confounders, short-term exposure–mortality associations in cohort participants were of greater magnitude than in comparable general population time-series study analyses. However, short-term exposure–mortality associations were substantially lower than equivalent long-term associations, which is consistent with the possibility of larger, more persistent cumulative effects from long-term exposures

Epidemiology of occupational hypersensitivity pneumonitis; reports from the SWORD scheme in the UK from 1996 to 2015

Objective To estimate the reported incidence of occupational hypersensitivity pneumonitis (OHP) in the UK and to consider whether the pattern of attributed causation has changed over time. Methods All cases of OHP reported to the SWORD scheme between January 1996 and December 2015 were classified into 1 of 10 categories of the suspected agent. Cases were grouped into four 5-year time periods to examine any changing pattern in incidence or suspected causation. For each time period, the annual incidence was calculated using the estimated number of reported cases and the working population of the UK. Results Between 1996 and 2015, there were 202 actual cases of OHP reported to SWORD, equating to an estimated 818 cases, when adjusting for the sampling ratio. Over this period, the annual UK incidence was 1.4 per million workers. The mean (SD) age of reported cases was 52 (13) years, and cases were four-times more likely to be men than women. Over the study period, there was a fall in the proportion of cases reported to be due to agricultural exposures (44–12%), and an increase in cases due to metalworking fluids (MWFs, 2–45%). Conclusions Over the last 20 years, the incidence of OHP in the UK has been ∼1–2 cases per million workers per year. Working with water-based MWFs is now the most commonly suspected causative exposure for OHP cases reported to the SWORD scheme in the UK

SD-208, a novel protein kinase D inhibitor, blocks prostate cancer cell proliferation and tumor Growth in Vivo by inducing G2/M cell cycle arrest

Protein kinase D (PKD) has been implicated in many aspects of tumorigenesis and progression, and is an emerging molecular target for the development of anticancer therapy. Despite recent advancement in the development of potent and selective PKD small molecule inhibitors, the availability of in vivo active PKD inhibitors remains sparse. In this study, we describe the discovery of a novel PKD small molecule inhibitor, SD-208, from a targeted kinase inhibitor library screen, and the synthesis of a series of analogs to probe the structure-activity relationship (SAR) vs. PKD1. SD-208 displayed a narrow SAR profile, was an ATP-competitive pan-PKD inhibitor with low nanomolar potency and was cell active. Targeted inhibition of PKD by SD-208 resulted in potent inhibition of cell proliferation, an effect that could be reversed by overexpressed PKD1 or PKD3. SD-208 also blocked prostate cancer cell survival and invasion, and arrested cells in the G2/M phase of the cell cycle. Mechanistically, SD-208-induced G2/M arrest was accompanied by an increase in levels of p21 in DU145 and PC3 cells as well as elevated phosphorylation of Cdc2 and Cdc25C in DU145 cells. Most importantly, SD-208 given orally for 24 days significantly abrogated the growth of PC3 subcutaneous tumor xenografts in nude mice, which was accompanied by reduced proliferation and increased apoptosis and decreased expression of PKD biomarkers including survivin and Bcl-xL. Our study has identified SD-208 as a novel efficacious PKD small molecule inhibitor, demonstrating the therapeutic potential of targeted inhibition of PKD for prostate cancer treatment

Satellite estimates of wide-range suspended sediment concentrations in Changjiang (Yangtze) estuary using MERIS data

The Changjiang (Yangtze) estuarine and coastal waters are characterized by suspended sediments over a wide range of concentrations from 20 to 2,500 mg l-1. Suspended sediment plays important roles in the estuarine and coastal system and environment. Previous algorithms for satellite estimates of suspended sediment concentration (SSC) showed a great limitation in that only low to moderate concentrations (up to 50 mg l-1) could be reliably estimated. In this study, we developed a semi-empirical radiative transfer (SERT) model with physically based empirical coefficients to estimate SSC from MERIS data over turbid waters with a much wider range of SSC. The model was based on the Kubelka–Munk two-stream approximation of radiative transfer theory and calibrated using datasets from in situ measurements and outdoor controlled tank experiments. The results show that the sensitivity and saturation level of remote-sensing reflectance to SSC are dependent on wavelengths and SSC levels. Therefore, the SERT model, coupled with a multi-conditional algorithm scheme adapted to satellite retrieval of wide-range SSC, was proposed. Results suggest that this method is more effective and accurate in the estimation of SSC over turbid water

The association of cold weather and all-cause and cause-specific mortality in the island of Ireland between 1984 and 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been made available through the Brunel Open Access Publishing Fund.Background This study aimed to assess the relationship between cold temperature and daily mortality in the Republic of Ireland (ROI) and Northern Ireland (NI), and to explore any differences in the population responses between the two jurisdictions. Methods A time-stratified case-crossover approach was used to examine this relationship in two adult national populations, between 1984 and 2007. Daily mortality risk was examined in association with exposure to daily maximum temperatures on the same day and up to 6 weeks preceding death, during the winter (December-February) and cold period (October-March), using distributed lag models. Model stratification by age and gender assessed for modification of the cold weather-mortality relationship. Results In the ROI, the impact of cold weather in winter persisted up to 35 days, with a cumulative mortality increase for all-causes of 6.4% (95%CI=4.8%-7.9%) in relation to every 1oC drop in daily maximum temperature, similar increases for cardiovascular disease (CVD) and stroke, and twice as much for respiratory causes. In NI, these associations were less pronounced for CVD causes, and overall extended up to 28 days. Effects of cold weather on mortality increased with age in both jurisdictions, and some suggestive gender differences were observed. Conclusions The study findings indicated strong cold weather-mortality associations in the island of Ireland; these effects were less persistent, and for CVD mortality, smaller in NI than in the ROI. Together with suggestive differences in associations by age and gender between the two Irish jurisdictions, the findings suggest potential contribution of underlying societal differences, and require further exploration. The evidence provided here will hope to contribute to the current efforts to modify fuel policy and reduce winter mortality in Ireland

The utility of information collected by occupational disease surveillance systems.

BACKGROUND: The Health and Occupation Research (THOR) network in the UK and the Republic of Ireland (ROI) is an integrated system of surveillance schemes collecting work-related ill-health (WRIH) data since 1989. In addition to providing information about disease incidence, trends in incidence and the identification of new hazards, THOR also operates an ad hoc data enquiry service enabling interested parties to request information about cases of WRIH reported to THOR. AIMS: To examine requests for information made to a network of surveillance schemes for WRIH in the UK. METHODS: Analysis via SPSS of data requests received by THOR between 2002 and 2014. RESULTS: A total of 631 requests were received by THOR between 2002 and 2014. Requests were predominantly submitted by participating THOR physicians (34%) and the main THOR funder-the UK Health & Safety Executive (HSE) (31%). The majority (67%) of requests were for information about work-related respiratory or skin disease with relatively few requests for other diagnoses, such as musculoskeletal or mental ill-health. Requests frequently related to a specific industry and/or occupation (42%) and/or a specific causal agent (58%). CONCLUSIONS: Data collected by occupational disease surveillance systems such as THOR are an extremely useful source of information, the use of which extends beyond informing government on disease incidence and trends in incidence. The data collected provide a framework that can assist a wide range of enquirers with clinical diagnoses, identification of suspected causative agents/exposures and to highlight growing risks in particular industrial and occupational sectors

Does a local financial incentive scheme reduce inequalities in the delivery of clinical care in a socially deprived community? A longitudinal data analysis.

BACKGROUND: Socioeconomic deprivation is associated with inequalities in health care and outcomes. Despite concerns that the Quality and Outcomes Framework pay-for-performance scheme in the UK would exacerbate inequalities in primary care delivery, gaps closed over time. Local schemes were promoted as a means of improving clinical engagement by addressing local health priorities. We evaluated equity in achievement of target indicators and practice income for one local scheme. METHODS: We undertook a longitudinal survey over four years of routinely recorded clinical data for all 83 primary care practices. Sixteen indicators were developed that covered five local clinical and public health priorities: weight management; alcohol consumption; learning disabilities; osteoporosis; and chlamydia screening. Clinical indicators were logit transformed from a percentage achievement scale and modelled allowing for clustering of repeated measures within practices. This enabled our study of target achievements over time with respect to deprivation. Practice income was also explored. RESULTS: Higher practice deprivation was associated with poorer performance for five indicators: alcohol use registration (OR 0.97; 95 % confidence interval 0.96,0.99); recorded chlamydia test result (OR 0.97; 0.94,0.99); osteoporosis registration (OR 0.98; 0.97,0.99); registration of repeat prednisolone prescription (OR 0.98; 0.96,0.99); and prednisolone registration with record of dual energy X-ray absorptiometry (DEXA) scan/referral (OR 0.92; 0.86,0.97); practices in deprived areas performed better for one indicator (registration of osteoporotic fragility fracture (OR 1.26; 1.04,1.51). The deprivation-achievement gap widened for one indicator (registered females aged 65-74 with a fracture referred for a DEXA scan; OR 0.97; 0.95,0.99). Two other indicators indicated a similar trend over two years before being withdrawn (registration of fragility fracture and over-75 s with a fragility fracture assessed and treated for osteoporosis risk). For one indicator the deprivation-achievement gap reduced over time (repeat prednisolone prescription (OR 1.01; 1.01,1.01). Larger practices and those serving more affluent areas earned more income per patient than smaller practices and those serving more deprived areas (t = -3.99; p =0.0001). CONCLUSIONS: Any gaps in achievement between practices were modest but mostly sustained or widened over the duration of the scheme. Given that financial rewards may not reflect the amount of work undertaken by practices serving more deprived patients, future pay-for-performance schemes also need to address fairness of rewards in relation to workload

Culminating Experience Grant Proposal to Fund a Resource Library for Current and Potential Adoptive Parents and Children Who Are Clients of the Kern County Department of Human Services Adoption Agency

The process of adoption is complex and is governed by state and federal law. There is currently substantial concern that the growth in the adoption of foster children will increase adoption disruption rates. Considerations of the pending or ongoing adjustment and issues of the child and family in the adoption are generally of secondary concern. Pre- and post-adoption services are generally limited to crisis intervention and placement stabilization. Little, if any, services, literature or resource provision is made to parents and children to cast light on the particular issues that may be facing that child or family before, during and after adoption finalization. The purpose of this grant proposal is to fund a resource library for pre- and post-adoptive parents and children. The resource library will contain book and DVD resources targeted at various age groups of children, common concerns that children have, and common issues facing adoptive parents

Variations in achievement of evidence-based, high-impact quality indicators in general practice : An observational study

BACKGROUND: There are widely recognised variations in the delivery and outcomes of healthcare but an incomplete understanding of their causes. There is a growing interest in using routinely collected 'big data' in the evaluation of healthcare. We developed a set of evidence-based 'high impact' quality indicators (QIs) for primary care and examined variations in achievement of these indicators using routinely collected data in the United Kingdom (UK). METHODS: Cross-sectional analysis of routinely collected, electronic primary care data from a sample of general practices in West Yorkshire, UK (n = 89). The QIs covered aspects of care (including processes and intermediate clinical outcomes) in relation to diabetes, hypertension, atrial fibrillation, myocardial infarction, chronic kidney disease (CKD) and 'risky' prescribing combinations. Regression models explored the impact of practice and patient characteristics. Clustering within practice was accounted for by including a random intercept for practice. RESULTS: Median practice achievement of the QIs ranged from 43.2% (diabetes control) to 72.2% (blood pressure control in CKD). Considerable between-practice variation existed for all indicators: the difference between the highest and lowest performing practices was 26.3 percentage points for risky prescribing and 100 percentage points for anticoagulation in atrial fibrillation. Odds ratios associated with the random effects for practices emphasised this; there was a greater than ten-fold difference in the likelihood of achieving the hypertension indicator between the lowest and highest performing practices. Patient characteristics, in particular age, gender and comorbidity, were consistently but modestly associated with indicator achievement. Statistically significant practice characteristics were identified less frequently in adjusted models. CONCLUSIONS: Despite various policy and improvement initiatives, there are enduring inappropriate variations in the delivery of evidence-based care. Much of this variation is not explained by routinely collected patient or practice variables, and is likely to be attributable to differences in clinical and organisational behaviour