Long-term effects of flooding on mortality in England and Wales, 1994-2005: controlled interrupted time-series analysis

BACKGROUND: Limited evidence suggests that being flooded may increase mortality and morbidity among affected householders not just at the time of the flood but for months afterwards. The objective of this study is to explore the methods for quantifying such long-term health effects of flooding by analysis of routine mortality registrations in England and Wales. METHODS: Mortality data, geo-referenced by postcode of residence, were linked to a national database of flood events for 1994 to 2005. The ratio of mortality in the post-flood year to that in the pre-flood year within flooded postcodes was compared with that in non-flooded boundary areas (within 5 km of a flood). Further analyses compared the observed number of flood-area deaths in the year after flooding with the number expected from analysis of mortality trends stratified by region, age-group, sex, deprivation group and urban-rural status. RESULTS: Among the 319 recorded floods, there were 771 deaths in the year before flooding and 693 deaths in the year after (post-/pre-flood ratio of 0.90, 95% CI 0.82, 1.00). This ratio did not vary substantially by age, sex, population density or deprivation. A similar post-flood 'deficit' of deaths was suggested by the analyses based on observed/expected deaths. CONCLUSIONS: The observed post-flood 'deficit' of deaths is counter-intuitive and difficult to interpret because of the possible influence of population displacement caused by flooding. The bias that might arise from such displacement remains unquantified but has important implications for future studies that use place of residence as a marker of exposure

Cigarette smoke promotes dendritic cell accumulation in COPD; a Lung Tissue Research Consortium study

<p>Abstract</p> <p>Background</p> <p>Abnormal immune responses are believed to be highly relevant in the pathogenesis of chronic obstructive pulmonary disease (COPD). Dendritic cells provide a critical checkpoint for immunity by their capacity to both induce and suppress immunity. Although evident that cigarette smoke, the primary cause of COPD, significantly influences dendritic cell functions, little is known about the roles of dendritic cells in the pathogenesis of COPD.</p> <p>Methods</p> <p>The extent of dendritic cell infiltration in COPD tissue specimens was determined using immunohistochemical localization of CD83+ cells (marker of matured myeloid dendritic cells), and CD1a+ cells (Langerhans cells). The extent of tissue infiltration with Langerhans cells was also determined by the relative expression of the CD207 gene in COPD <it>versus </it>control tissues. To determine mechanisms by which dendritic cells accumulate in COPD, complimentary studies were conducted using monocyte-derived human dendritic cells exposed to cigarette smoke extract (CSE), and dendritic cells extracted from mice chronically exposed to cigarette smoke.</p> <p>Results</p> <p>In human COPD lung tissue, we detected a significant increase in the total number of CD83+ cells, and significantly higher amounts of CD207 mRNA when compared with control tissue. Human monocyte-derived dendritic cells exposed to CSE (0.1-2%) exhibited enhanced survival <it>in vitro </it>when compared with control dendritic cells. Murine dendritic cells extracted from mice exposed to cigarette smoke for 4 weeks, also demonstrated enhanced survival compared to dendritic cells extracted from control mice. Acute exposure of human dendritic cells to CSE induced the cellular pro-survival proteins heme-oxygenase-1 (HO-1), and B cell lymphoma leukemia-x(L) (Bcl-xL), predominantly through oxidative stress. Although activated human dendritic cells conditioned with CSE expressed diminished migratory CCR7 expression, their migration towards the CCR7 ligand CCL21 was not impaired.</p> <p>Conclusions</p> <p>These data indicate that COPD is associated with increased numbers of cells bearing markers associated with Langerhans cells and mature dendritic cells, and that cigarette smoke promotes survival signals and augments survival of dendritic cells. Although CSE suppressed dendritic cell CCR7 expression, migration towards a CCR7 ligand was not diminished, suggesting that reduced CCR7-dependent migration is unlikely to be an important mechanism for dendritic cell retention in the lungs of smokers with COPD.</p

DIA1R Is an X-Linked Gene Related to Deleted In Autism-1

Background: Autism spectrum disorders (ASDs) are frequently occurring disorders diagnosed by deficits in three core functional areas: social skills, communication, and behaviours and/or interests. Mental retardation frequently accompanies the most severe forms of ASDs, while overall ASDs are more commonly diagnosed in males. Most ASDs have a genetic origin and one gene recently implicated in the etiology of autism is the Deleted-In-Autism-1 (DIA1) gene. Methodology/Principal Findings: Using a bioinformatics-based approach, we have identified a human gene closely related to DIA1, we term DIA1R (DIA1-Related). While DIA1 is autosomal (chromosome 3, position 3q24), DIA1R localizes to the X chromosome at position Xp11.3 and is known to escape X-inactivation. The gene products are of similar size, with DIA1 encoding 430, and DIA1R 433, residues. At the amino acid level, DIA1 and DIA1R are 62 % similar overall (28 % identical), and both encode signal peptides for targeting to the secretory pathway. Both genes are ubiquitously expressed, including in fetal and adult brain tissue. Conclusions/Significance: Examination of published literature revealed point mutations in DIA1R are associated with X-linked mental retardation (XLMR) and DIA1R deletion is associated with syndromes with ASD-like traits and/or XLMR. Together, these results support a model where the DIA1 and DIA1R gene products regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-lik

Cardiac lymphatics in health and disease

The lymphatic vasculature, which accompanies the blood vasculature in most organs, is indispensable in the maintenance of tissue fluid homeostasis, immune cell trafficking, and nutritional lipid uptake and transport, as well as in reverse cholesterol transport. In this Review, we discuss the physiological role of the lymphatic system in the heart in the maintenance of cardiac health and describe alterations in lymphatic structure and function that occur in cardiovascular pathology, including atherosclerosis and myocardial infarction. We also briefly discuss the role that immune cells might have in the regulation of lymphatic growth (lymphangiogenesis) and function. Finally, we provide examples of how the cardiac lymphatics can be targeted therapeutically to restore lymphatic drainage in the heart to limit myocardial oedema and chronic inflammation.Peer reviewe

Homogeneous nucleation in water in microfluidic channels

It has been an experimental challenge to test the rupture of liquids with homogeneous nucleation of vapor bubbles. Many prior studies suffered from the ubiquitous presence of impurities in liquids or at container surfaces that spontaneously nucleate and grow under tension. Here, we propose a microfluidic approach to eliminate such impurities and obtain homogeneous bubble nucleation. We stretch the liquid dynamically via the interaction between a laser-induced shock and an air-liquid interface in a microchannel. Reproducible observations of the nucleation of vapor bubbles are obtained, supporting our claim of homogeneous nucleation. From comparisons of the distribution of vapor cavities with Euler flow simulations, the nucleation threshold for water at room temperature is predicted to be -60  MPa.Published versio