Descriptive Sets and the Topology of Nonseparable Banach Spaces

This paper was extensively circulated in manuscript form beginning in the Summer of 1989. It is being published here for the first time in its original form except for minor corrections, updated references and some concluding comments

Respiratory hospital admission risk near large composting facilities

AbstractBackgroundLarge-scale composting can release bioaerosols in elevated quantities, but there are few studies of health effects on nearby communities.MethodsA cross-sectional ecological small area design was used to examine risk of respiratory hospital admissions within 2500m of all 148 English large-scale composting facilities in 2008–10. Statistical analyses used a random intercept Poisson regression model at Census Output Area (COA) level (mean population 310). Models were adjusted for age, sex, deprivation and tobacco sales.ResultsAnalysing 34,963 respiratory hospital admissions in 4656 COAs within 250–2500m of a site, there were no significant trends using pre-defined distance bands of >250–750m, >750–1500m and >1500–2500m. Using a continuous measure of distance, there was a small non-statistically significant (p=0.054) association with total respiratory admissions corresponding to a 1.5% (95% CI: 0.0–2.9%) decrease in risk if moving from 251m to 501m. There were no significant associations for subgroups of respiratory infections, asthma or chronic obstructive pulmonary disease.ConclusionThis national study does not provide evidence for increased risks of respiratory hospital admissions in those living beyond 250m of an outdoor composting area perimeter. Further work using better measures of exposure and exploring associations with symptoms and disease prevalence, especially in vulnerable groups, is recommended to support regulatory approaches

In vitro and in vivo studies of the trypanocidal properties of WRR-483 against Trypanosoma cruzi.

BackgroundCruzain, the major cysteine protease of Trypanosoma cruzi, is an essential enzyme for the parasite life cycle and has been validated as a viable target to treat Chagas' disease. As a proof-of-concept, K11777, a potent inhibitor of cruzain, was found to effectively eliminate T. cruzi infection and is currently a clinical candidate for treatment of Chagas' disease.Methodology/principal findingsWRR-483, an analog of K11777, was synthesized and evaluated as an inhibitor of cruzain and against T. cruzi proliferation in cell culture. This compound demonstrates good potency against cruzain with sensitivity to pH conditions and high efficacy in the cell culture assay. Furthermore, WRR-483 also eradicates parasite infection in a mouse model of acute Chagas' disease. To determine the atomic-level details of the inhibitor interacting with cruzain, a 1.5 A crystal structure of the protease in complex with WRR-483 was solved. The structure illustrates that WRR-483 binds covalently to the active site cysteine of the protease in a similar manner as other vinyl sulfone-based inhibitors. Details of the critical interactions within the specificity binding pocket are also reported.ConclusionsWe demonstrate that WRR-483 is an effective cysteine protease inhibitor with trypanocidal activity in cell culture and animal model with comparable efficacy to K11777. Crystallographic evidence confirms that the mode of action is by targeting the active site of cruzain. Taken together, these results suggest that WRR-483 has potential to be developed as a treatment for Chagas' disease

Influences of Wind and Snow on Northern Tree-Line Environments at Churchill, Manitoba, Canada

The influences of wind and snow distribution at the tree line near Churchill, Manitoba, were studied. Wind profiles above the snow surface, snow crystal size and quantity were examined during abrasion experiments with white spruce branchlets. For white spruce, the abrasion zone was evidently within 80 cm above the snow surface, and needle removal by abrasion was strongly influenced by branch age. Removal by abrasion of similar-aged needles was highest in new branches and declined with branch age up to 7 or 8 years, and then increased again with older branches. Trees that grew 80 cm in height in 7 or 8 years were successful in passing through the abrasion zone. In forest-tundra environments the matted forms of trees were snow covered early in winter and received little abrasion. Sparsely needled islands of trees were largely covered with snow at the base. More densely needled trees and some trees within woodlands were less exposed to abrasion. The blockage of air flow resulted in high-speed jets, which cleared out snow within a "horseshoe-shaped vortex" around the base of the tree. Both in much of the woodlands and in the open forest, snow abrasion was minimal or non-existent and snow load on the branches (qali), becomes the prevalent stress. During winter, a large proportion of the snowfall was initially blown off the exposed surfaces of Hudson Bay and the coastal tundra regions, into the woodlands, and eventually across the tree line and into the open forest. As the woodlands filled up with snow in mid-winter, the rate of snow accumulation in the forest increased from double to triple the snowfall. Variations in the rate of accumulation occurred with wind speed and direction. ...Key words: tree line, wind, snow, white spruce, abrasionL'influence de la distribution du vent et de la neige à la limite forestière, près de Churchill, au Manitoba, constitue le thème de cette recherche. On a étudié le profil éolien au dessus de la surface de la neige, ainsi que la taille et la quantité des cristaux de neige au cours d'expériences d'abrasion faites sur des petites branches d'épinette blanche. Pour cette dernière, la zone d'abrasion se situait de toute évidence dans les 80 cm au-dessus de la surface de la neige et la disparition des aiguilles par abrasion était fortement influencée par l'âge de la branche. La disparition par abrasion des aiguilles d'âge semblable était plus élevée pour les nouvelles branches et diminuait avec l'âge de la branche, jusqu'à 7 ou 8 ans, pour augmenter à nouveau avec les branches plus vieilles. Les arbres qui poussaient de 80 cm en 7 ou 8 ans réussissaient à traverser la zone d'abrasion. Dans les environnements de toundra boisée, les arbres aux formes tassées et enchevêtrées étaient couverts de neige tôt en hiver et étaient peu sujets à l'abrasion. Les îlots d'arbres aux aiguilles clairsemées étaient largement couverts de neige à la base. Les arbres aux aiguilles plus fournies et quelques arbres de la forêt-parc étaient moins exposés à l'abrasion. Le blocage de la circulation d'air créait des courants très rapides qui soufflaient la neige en créant un tourbillon en fer à cheval au pied de l'arbre. Dans la plupart de la forêt-parc comme dans la forêt claire, l'abrasion par la neige était minime ou non existante et la charge nivale sur les branches (qali) était le principal agent de stress. Au cours de l'hiver, une grande quantité de la chute nivale était d'abord transportée par le vent, depuis la surface exposée des régions de la baie d'Hudson et de la toundra côtière, jusqu'à la forêt-parc, puis dépassait la limite forestière pour entrer dans la forêt claire. Comme la forêt-parc se remplissait de neige au milieu de l'hiver, le taux d'accumulation nivale dans la forêt passait du double au triple de la chute de neige. La vitesse et la direction du vent faisaient varier le taux d'accumulation. Durant le mois de mai, la fonte nivale se produisait d'abord dans la toundra et ruisselait en général sur la surface gelée. La fonte nivale se produisait environ 3 semaines plus tard dans la forêt claire et s'y caractérisait par une réduction du ruissellement, du fait que l'eau s'infiltrait plus facilement dans la tourbe en dégel. Les combes de neige tardives étaient caractéristiques de la toundra boisée de la forêt-parc et avaient généralement disparu au milieu de juillet. La forêt-parc était libre de neige pendant 1 mois et demi à 2 mois au cours d'une année, alors que la forêt claire était libre de neige durant environ 3 mois et la toundra pratiquement libre de neige durant au moins 6 mois.Mots clés : limite forestière, vent, neige, épinette blanche, abrasio

Dedekind order completion of C(X) by Hausdorff continuous functions

The concept of Hausdorff continuous interval valued functions, developed within the theory of Hausdorff approximations and originaly defined for interval valued functions of one real variable is extended to interval valued functions defined on a topological space X. The main result is that the set of all finite Hausdorff continuous functions on any topological space X is Dedekind order complete. Hence it contains the Dedekind order completion of the set C(X) of all continuous real functions defined on X as well as the Dedekind order completion of the set C_b(X) of all bounded continuous functions on X. Under some general assumptions about the topological space X the Dedekind order completions of both C(X) and C_b(X) are characterised as subsets of the set of all Hausdorff continuous functions. This solves a long outstanding open problem about the Dedekind order completion of C(X). In addition, it has major applications to the regularity of solutions of large classes of nonlinear PDEs

Birth weight, early childhood growth and lung function in middle to early old age: 1946 British birth cohort

Background Findings from previous studies investigating the relationship between birth weight and adult lung function have been inconsistent, and data on birth weight and adult lung function decline are lacking. Few studies have investigated the relation between early childhood growth and adult lung function. Methods FEV1 and FVC were measured at ages 43 years, 53 years and 60–64 years in the 1946 British birth cohort study. Multiple linear regression models were fitted to study associations with birth weight and weight gain at age 0–2 years. Multilevel models assessed how associations changed with age, with FEV1 and FVC as repeated outcomes. Results 3276 and 3249 participants were included in FEV1 and FVC analyses, respectively. In women, there was a decreasing association between birth weight and FVC with age. From the multilevel model, for every 1 kg higher birth weight, FVC was higher on average by 66.3 mL (95% CI 0.5 to 132) at 43 years, but significance was lost at 53 years and 60–64 years. Similar associations were seen with FEV1, but linear change (decline) from age 43 years lost statistical significance after full adjustment. In men, associations with birth weight were null in multilevel models. Higher early life weight gain was associated with higher FEV1 at age 43 years in men and women combined but not in each sex. Conclusions Birth weight is positively associated with adult lung function in middle age, particularly in women, but the association diminishes with age, potentially due to accumulating environmental influences over the life course

Inhibitors of SARS-CoV entry--identification using an internally-controlled dual envelope pseudovirion assay.

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged as the causal agent of an endemic atypical pneumonia, infecting thousands of people worldwide. Although a number of promising potential vaccines and therapeutic agents for SARS-CoV have been described, no effective antiviral drug against SARS-CoV is currently available. The intricate, sequential nature of the viral entry process provides multiple valid targets for drug development. Here, we describe a rapid and safe cell-based high-throughput screening system, dual envelope pseudovirion (DEP) assay, for specifically screening inhibitors of viral entry. The assay system employs a novel dual envelope strategy, using lentiviral pseudovirions as targets whose entry is driven by the SARS-CoV Spike glycoprotein. A second, unrelated viral envelope is used as an internal control to reduce the number of false positives. As an example of the power of this assay a class of inhibitors is reported with the potential to inhibit SARS-CoV at two steps of the replication cycle, viral entry and particle assembly. This assay system can be easily adapted to screen entry inhibitors against other viruses with the careful selection of matching partner virus envelopes

Health Technology Scenarios and Implications for Spectrum

Supporting Informatio

Are GPs under-investigating older patients presenting with symptoms of ovarian cancer? Observational study using General Practice Research Database

Background: Recent studies suggest that older patients in the United Kingdom are not benefiting as much from improvements in cancer treatments as their younger counterparts. We investigate whether this might be partly due to differential referral rates using ovarian cancer as an example. Methods: From the General Practice Research Database (GPRD), we identified all women aged 40–80 years on 1 June 2002 with a Read code for ovarian cancer between 1 June 2002 and 31 May 2007. Using these records, we compared the GPRD incidence of ovarian cancer with rates compiled from the UK cancer registries and investigated the relationship between age and coded investigations for suspected ovarian cancer. Results: The GPRD rates peaked earlier, at 70–74, and were lower than registry rates for nearly all ages particularly for patients over 59. The proportion investigated or referred by the GP decreased significantly with age and delays between first coded symptom and investigation showed a U-shaped distribution by age. Conclusions: GPs appear to be less likely to recognise and to refer patients presenting with ovarian cancer as they get older. If our findings extend to other cancers, lack of or delays in referral to secondary care may partly explain poor UK cancer mortality rates of older people

Теоретичні засади дослідження виборчих технологій в електоральному процесі України та проблеми їх ефективності

Здійснено політологічний аналіз ефективності виборчих технологій та проаналізо­вано їх вплив на електоральні процеси в Україні.Осуществлен политологический анализ эффективности избирательных технологий и проанализировано их влияние на электоральные процессы в Украине.Political analysis of electoral technologies effectiveness and analyzes of their impact on the electoral process in Ukraine are made