Mesothelioma incidence surveillance systems and claims for workers’ compensation. Epidemiological evidence and prospects for an integrated framework

<p>Abstract</p> <p>Background</p> <p>Malignant mesothelioma is an aggressive and lethal tumour strongly associated with exposure to asbestos (mainly occupational). In Italy a large proportion of workers are protected from occupational diseases by public insurance and an epidemiological surveillance system for incident mesothelioma cases.</p> <p>Methods</p> <p>We set up an individual linkage between the Italian national mesothelioma register (ReNaM) and the Italian workers’ compensation authority (INAIL) archives. Logistic regression models were used to identify and test explanatory variables.</p> <p>Results</p> <p>We extracted 3270 mesothelioma cases with occupational origins from the ReNaM, matching them with 1625 subjects in INAIL (49.7%); 91.2% (1,482) of the claims received compensation. The risk of not seeking compensation is significantly higher for women and the elderly. Claims have increased significantly in recent years and there is a clear geographical gradient (northern and more developed regions having higher claims rates). The highest rates of compensation claims were after work known to involve asbestos.</p> <p>Conclusions</p> <p>Our data illustrate the importance of documentation and dissemination of all asbestos exposure modalities. Strategies focused on structural and systematic interaction between epidemiological surveillance and insurance systems are needed.</p

Identification of a large, fast-expanding HIV-1 subtype B transmission cluster among MSM in Valencia, Spain

We describe and characterize an exceptionally large HIV-1 subtype B transmission cluster occurring in the Comunidad Valenciana (CV, Spain). A total of 1806 HIV-1 protease-reverse transcriptase (PR/RT) sequences from different patients were obtained in the CV between 2004 and 2014. After subtyping and generating a phylogenetic tree with additional HIV-1 subtype B sequences, a very large transmission cluster which included almost exclusively sequences from the CV was detected (n = 143 patients). This cluster was then validated and characterized with further maximum-likelihood phylogenetic analyses and Bayesian coalescent reconstructions. With these analyses, the CV cluster was delimited to 113 patients, predominately men who have sex with men (MSM). Although it was significantly located in the city of Valencia (n = 105), phylogenetic analyses suggested this cluster derives from a larger HIV lineage affecting other Spanish localities (n = 194). Coalescent analyses estimated its expansion in Valencia to have started between 1998 and 2004. From 2004 to 2009, members of this cluster represented only 1.46% of the HIV-1 subtype B samples studied in Valencia (n = 5/143), whereas from 2010 onwards its prevalence raised to 12.64% (n = 100/791). In conclusion, we have detected a very large transmission cluster in the CV where it has experienced a very fast growth in the recent years in the city of Valencia, thus contributing significantly to the HIV epidemic in this locality. Its transmission efficiency evidences shortcomings in HIV control measures in Spain and particularly in Valencia

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

“I have no clue what I drunk last night” Using Smartphone technology to compare in-vivo and retrospective self-reports of alcohol consumption.

This research compared real-time measurements of alcohol consumption with retrospective accounts of alcohol consumption to examine possible discrepancies between, and contextual influences on, the different accounts.Building on previous investigations, a specifically designed Smartphone technology was utilized to measure alcohol consumption and contextual influences in de facto real-time. Real-time data (a total of 10,560 data points relating to type and number of drinks and current social / environmental context) were compared with daily and weekly retrospective accounts of alcohol consumption.Participants reported consuming more alcoholic drinks during real-time assessment than retrospectively. For daily accounts a higher number of drinks consumed in real-time was related to a higher discrepancy between real-time and retrospective accounts. This effect was found across all drink types but was not shaped by social and environmental contexts. Higher in-vivo alcohol consumption appeared to be related to a higher discrepancy in retrospectively reported weekly consumption for alcohol beverage types other than wine. When including contextual factors into the statistical models, being with two or more friends (as opposed to being alone) decreased the discrepancy between real-time and retrospective reports, whilst being in the pub (relative to being at home) was associated with greater discrepancies.Overall, retrospective accounts may underestimate the amount of actual, real-time alcohol consumed. Increased consumption may also exacerbate differences between real-time and retrospective accounts. Nonetheless, this is not a global effect as environmental and social contexts interact with the type of alcohol consumed and the time frame given for reporting (weekly vs. daily retrospective). A degree of caution therefore appears warranted with regards to the use of retrospective self-report methods of recording alcohol consumption. Whilst real-time sampling is unlikely to be completely error free, it may be better able to account for social and environmental influences on self-reported consumption

The PRO-AGE study: an international randomised controlled study of health risk appraisal for older persons based in general practice

BACKGROUND: This paper describes the study protocol, the recruitment, and base-line data for evaluating the success of randomisation of the PRO-AGE (PRevention in Older people – Assessment in GEneralists' practices) project. METHODS/DESIGN: A group of general practitioners (GPs) in London (U.K.), Hamburg (Germany) and Solothurn (Switzerland) were trained in risk identification, health promotion, and prevention in older people. Their non-disabled older patients were invited to participate in a randomised controlled study. Participants allocated to the intervention group were offered the Health Risk Appraisal for Older Persons (HRA-O) instrument with a site-specific method for reinforcement (London: physician reminders in electronic medical record; Hamburg: one group session or two preventive home visits; Solothurn: six-monthly preventive home visits over a two-year period). Participants allocated to the control group received usual care. At each site, an additional group of GPs did not receive the training, and their eligible patients were invited to participate in a concurrent comparison group. Primary outcomes are self-reported health behaviour and preventative care use at one-year follow-up. In Solothurn, an additional follow-up was conducted at two years. The number of older persons agreeing to participate (% of eligible persons) in the randomised controlled study was 2503 (66.0%) in London, 2580 (53.6%) in Hamburg, and 2284 (67.5%) in Solothurn. Base-line findings confirm that randomisation of participants was successful, with comparable characteristics between intervention and control groups. The number of persons (% of eligible) enrolled in the concurrent comparison group was 636 (48.8%) in London, 746 (35.7%) in Hamburg, and 1171 (63.0%) in Solothurn. DISCUSSION: PRO-AGE is the first large-scale randomised controlled trial of health risk appraisal for older people in Europe. Its results will inform about the effects of implementing HRA-O with different methods of reinforcement

Ultra-brief intervention for problem drinkers: research protocol

Background: Helping the large number of problem drinkers who will never seek treatment is a challenging issue. Public health initiatives employing educational materials or mass media campaigns have met with mixed success. However, clinical research has developed effective brief interventions to help problem drinkers. This project will employ an intervention that has been validated in clinical settings and then modified into an ultra-brief format suitable for use as a public health intervention. The major objective of this study is to conduct a randomized controlled trial to establish the effectiveness of an ultra-brief, personalized feedback intervention for problem drinkers. Methods/design: Problem drinkers recruited on a baseline population telephone survey conducted in a major metropolitan city in Canada will be randomized to one of three conditions - a personalized feedback pamphlet condition, a control pamphlet condition, or a no intervention control condition. In the week after the baseline survey, households in the two pamphlet conditions will be sent their respective pamphlets. Changes in drinking will be assessed post intervention at three-month and six-month follow-ups. Drinking outcomes will be compared between experimental conditions using Structural Equation Modeling. The primary hypothesis is that problem drinkers from households who receive the personalized feedback pamphlet intervention will display significantly improved drinking outcomes at three and six-month follow-ups as compared to problem drinkers from households in the no intervention control condition. Secondary hypotheses will test the impact of the intervention on help seeking, and explore the mediating or moderating role of perceived drinking norms, perceived alcohol risks and the problem drinker's social reasons for drinking. Discussion: This trial will provide information on the effectiveness of a pamphlet-based personalized feedback intervention for problem drinkers in a community setting. Trial registration: ClinicalTrials.gov registration #NCT00688584.This study is funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Grant #R01 AA015680-01A2

Magnesium Limitation Is an Environmental Trigger of the Pseudomonas aeruginosa Biofilm Lifestyle

Biofilm formation is a conserved strategy for long-term bacterial survival in nature and during infections. Biofilms are multicellular aggregates of cells enmeshed in an extracellular matrix. The RetS, GacS and LadS sensors control the switch from a planktonic to a biofilm mode of growth in Pseudomonas aeruginosa. Here we detail our approach to identify environmental triggers of biofilm formation by investigating environmental conditions that repress expression of the biofilm repressor RetS. Mg2+ limitation repressed the expression of retS leading to increased aggregation, exopolysaccharide (EPS) production and biofilm formation. Repression of retS expression under Mg2+ limitation corresponded with induced expression of the GacA-controlled small regulatory RNAs rsmZ and rsmY and the EPS biosynthesis operons pel and psl. We recently demonstrated that extracellular DNA sequesters Mg2+ cations and activates the cation-sensing PhoPQ two-component system, which leads to increased antimicrobial peptide resistance in biofilms. Here we show that exogenous DNA and EDTA, through their ability to chelate Mg2+, promoted biofilm formation. The repression of retS in low Mg2+ was directly controlled by PhoPQ. PhoP also directly controlled expression of rsmZ but not rsmY suggesting that PhoPQ controls the equilibrium of the small regulatory RNAs and thus fine-tunes the expression of genes in the RetS pathway. In summary, Mg2+ limitation is a biologically relevant environmental condition and the first bonafide environmental signal identified that results in transcriptional repression of retS and promotes P. aeruginosa biofilm formation

Activation of Akt by the Bacterial Inositol Phosphatase, SopB, is Wortmannin Insensitive

Salmonella enterica uses effector proteins translocated by a Type III Secretion System to invade epithelial cells. One of the invasion-associated effectors, SopB, is an inositol phosphatase that mediates sustained activation of the pro-survival kinase Akt in infected cells. Canonical activation of Akt involves membrane translocation and phosphorylation and is dependent on phosphatidyl inositide 3 kinase (PI3K). Here we have investigated these two distinct processes in Salmonella infected HeLa cells. Firstly, we found that SopB-dependent membrane translocation and phosphorylation of Akt are insensitive to the PI3K inhibitor wortmannin. Similarly, depletion of the PI3K regulatory subunits p85α and p85ß by RNAi had no inhibitory effect on SopB-dependent Akt phosphorylation. Nevertheless, SopB-dependent phosphorylation does depend on the Akt kinases, PDK1 and rictor-mTOR. Membrane translocation assays revealed a dependence on SopB for Akt recruitment to Salmonella ruffles and suggest that this is mediated by phosphoinositide (3,4) P2 rather than phosphoinositide (3,4,5) P3. Altogether these data demonstrate that Salmonella activates Akt via a wortmannin insensitive mechanism that is likely a class I PI3K-independent process that incorporates some essential elements of the canonical pathway

Effects of Vegetated Field Borders on Arthropods in Cotton Fields in Eastern North Carolina

The influence, if any, of 5m wide, feral, herbaceous field borders on pest and beneficial arthropods in commercial cotton, Gossypium hirsutum (L.) (Malvales: Malvaceae), fields was measured through a variety of sampling techniques over three years. In each year, 5 fields with managed, feral vegetation borders and five fields without such borders were examined. Sampling was stratified from the field border or edge in each field in an attempt to elucidate any edge effects that might have occurred. Early season thrips populations appeared to be unaffected by the presence of a border. Pitfall sampling disclosed no differences in ground-dwelling predaceous arthropods but did detect increased populations of crickets around fields with borders. Cotton aphid (Aphis gossypii Glover) (Hemiptera: Aphididae) populations were too low during the study to adequately assess border effects. Heliothines, Heliothis virescens (F.) and Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae), egg numbers and damage rates were largely unaffected by the presence or absence of a border, although in one instance egg numbers were significantly lower in fields with borders. Overall, foliage-dwelling predaceous arthropods were somewhat more abundant in fields with borders than in fields without borders. Tarnished plant bugs, Lygus lineolaris (Palisot de Beauvois) (Heteroptera: Miridae) were significantly more abundant in fields with borders, but stink bugs, Acrosternum hilare (Say), and Euschistus servus (Say) (Hemiptera: Pentatomidae) numbers appeared to be largely unaffected by border treatment. Few taxa clearly exhibited distributional edge effects relative to the presence or absence of border vegetation. Field borders like those examined in this study likely will have little impact on insect pest management in cotton under current insect management regimens

Rodent Models of TDP-43 Proteinopathy: Investigating the Mechanisms of TDP-43-Mediated Neurodegeneration

Since the identification of phosphorylated and truncated transactive response DNA-binding protein 43 (TDP-43) as a primary component of ubiquitinated inclusions in amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions, much effort has been directed towards ascertaining how TDP-43 contributes to the pathogenesis of disease. As with other protein misfolding disorders, TDP-43-mediated neuronal death is likely caused by both a toxic gain and loss of TDP-43 function. Indeed, the presence of cytoplasmic TDP-43 inclusions is associated with loss of nuclear TDP-43. Moreover, post-translational modifications of TDP-43, including phosphorylation, ubiquitination, and cleavage into C-terminal fragments, may bestow toxic properties upon TDP-43 and cause TDP-43 dysfunction. However, the exact neurotoxic TDP-43 species remain unclear, as do the mechanism(s) by which they cause neurotoxicity. Additionally, given our incomplete understanding of the roles of TDP-43, both in the nucleus and the cytoplasm, it is difficult to truly appreciate the detrimental consequences of aberrant TDP-43 function. The development of TDP-43 transgenic animal models is expected to narrow these gaps in our knowledge. The aim of this review is to highlight the key findings emerging from TDP-43 transgenic animal models and the insight they provide into the mechanisms driving TDP-43-mediated neurodegeneration