Coastal clustering of HEV; Cornwall, UK.

PublishedBACKGROUND AND AIMS: Autochthonous hepatitis E virus (HEV) infection is a porcine zoonosis and increasingly recognized in developed countries. In most cases the route of infection is uncertain. A previous study showed that HEV was associated geographically with pig farms and coastal areas. AIM: The aim of the present research was to study the geographical, environmental and social factors in autochthonous HEV infection. METHODS: Cases of HEV genotype 3 infection and controls were identified from 2047 consecutive patients attending a rapid-access hepatology clinic. For each case/control the following were recorded: distance from home to nearest pig farm, distance from home to coast, rainfall levels during the 8 weeks before presentation, and socioeconomic status. RESULTS: A total of 36 acute hepatitis E cases, 170 age/sex-matched controls and 53 hepatitis controls were identified. The geographical spread of hepatitis E cases was not even when compared with both control groups. Cases were more likely to live within 2000 m of the coast (odds ratio=2.32, 95% confidence interval=1.08-5.19, P=0.03). There was no regional difference in the incidence of cases and controls between west and central Cornwall. There was no difference between cases and controls in terms of distance from the nearest pig farm, socioeconomic status or rainfall during the 8 weeks before disease presentation. CONCLUSION: Cases of HEV infection in Cornwall are associated with coastal residence. The reason for this observation is uncertain, but might be related to recreational exposure to beach areas exposed to HEV-contaminated 'run-off' from pig farms. This hypothesis merits further study.The European Centre for the Environment and Human Health (part of the Peninsula College of Medicine and Dentistry which is a joint entity of the University of Exeter, the University of Plymouth and the NHS in the South West) is supported by investment from the European Regional Development Fund and the European Social Fund Convergence Programme for Cornwall and the Isles of Scilly

Rotation and Spin in Physics

We delineate the role of rotation and spin in physics, discussing in order Newtonian classical physics, special relativity, quantum mechanics, quantum electrodynamics and general relativity. In the latter case, we discuss the generalization of the Kepler formula to post-Newtonian order $(c^{-2}$) including spin effects and two-body effects. Experiments which verify the theoretical results for general relativistic spin-orbit effects are discussed as well as efforts being made to verify the spin-spin effects

Community ecology of the Middle Miocene primates of La Venta, Colombia: the relationship between ecological diversity, divergence time, and phylogenetic richness

It has been suggested that the degree of ecological diversity that characterizes a primate community correlates positively with both its phylogenetic richness and the time since the members of that community diverged (Fleagle and Reed in Primate communities. Cambridge University Press, New York, pp 92–115, 1999). It is therefore questionable whether or not a community with a relatively recent divergence time but high phylogenetic richness would be as ecologically variable as a community with similar phylogenetic richness but a more distant divergence time. To address this question, the ecological diversity of a fossil primate community from La Venta, Colombia, a Middle Miocene platyrrhine community with phylogenetic diversity comparable with extant platyrrhine communities but a relatively short time since divergence, was compared with that of modern Neotropical primate communities. Shearing quotients and molar lengths, which together are reliable indicators of diet, for both fossil and extant species were plotted against each other to describe the dietary “ecospace” occupied by each community. Community diversity was calculated as the area of the minimum convex polygon encompassing all community members. The diversity of the fossil community was then compared with that of extant communities to test whether the fossil community was less diverse than extant communities while taking phylogenetic richness into account. Results indicate that the La Ventan community was not significantly less ecologically diverse than modern communities, supporting the idea that ecological diversification occurred along with phylogenetic diversification early in platyrrhine evolution

Estimating the incidence of acute infectious intestinal disease in the community in the UK:A retrospective telephone survey

Objectives: To estimate the burden of intestinal infectious disease (IID) in the UK and determine whether disease burden estimations using a retrospective study design differ from those using a prospective study design. Design/Setting: A retrospective telephone survey undertaken in each of the four countries comprising the United Kingdom. Participants were randomly asked about illness either in the past 7 or 28 days. Participants: 14,813 individuals for all of whom we had a legible recording of their agreement to participate Outcomes: Self-reported IID, defined as loose stools or clinically significant vomiting lasting less than two weeks, in the absence of a known non-infectious cause. Results: The rate of self-reported IID varied substantially depending on whether asked for illness in the previous 7 or 28 days. After standardising for age and sex, and adjusting for the number of interviews completed each month and the relative size of each UK country, the estimated rate of IID in the 7-day recall group was 1,530 cases per 1,000 person-years (95% CI: 1135 – 2113), while in the 28-day recall group it was 533 cases per 1,000 person-years (95% CI: 377 – 778). There was no significant variation in rates between the four countries. Rates in this study were also higher than in a related prospective study undertaken at the same time. Conclusions: The estimated burden of disease from IID varied dramatically depending on study design. Retrospective studies of IID give higher estimates of disease burden than prospective studies. Of retrospective studies longer recall periods give lower estimated rates than studies with short recall periods. Caution needs to be exercised when comparing studies of self-reported IID as small changes in study design or case definition can markedly affect estimated rates

Methylation of hMLH1 promoter correlates with the gene silencing with a region-specific manner in colorectal cancer

Microsatellite instability is present in over 80% of the hereditary non-polyposis colorectal carcinoma and about 15–20% of the sporadic cancer. Microsatellite instability is caused by the inactivation of the mismatch repair genes, such as primarily hMLH1, hMSH2. To study the mechanisms of the inactivation of mismatch repair genes in colorectal cancers, especially the region-specific methylation of hMLH1 promoter and its correlation with gene expression, we analysed microsatellite instability, expression and methylation of hMLH1 and loss of heterozygosity at hMLH1 locus in these samples. Microsatellite instability was present in 17 of 71 primary tumours of colorectal cancer, including 14 of 39 (36%) mucinous cancer and three of 32 (9%) non-mucinous cancer. Loss of hMLH1 and hMSH2 expression was detected in nine and three of 16 microsatellite instability tumours respectively. Methylation at CpG sites in a proximal region of hMLH1 promoter was detected in seven of nine tumours that showed no hMLH1 expression, while no methylation was present in normal mucosa and tumours which express hMLH1. However, methylation in the distal region was observed in all tissues including normal mucosa and hMLH1 expressing tumours. This observation indicates that methylation of hMLH1 promoter plays an important role in microsatellite instability with a region-specific manner in colorectal cancer. Loss of heterozygosity at hMLH1 locus was present in four of 17 cell lines and 16 of 54 tumours with normal hMLH1 status, while loss of heterozygosity was absent in all nine cell lines and nine tumours with abnormal hMLH1 status (mutation or loss of expression), showing loss of heterozygosity is not frequently involved in the inactivation of hMLH1 gene in sporadic colorectal cancer

Mortality following Campylobacter infection: a registry-based linkage study

BACKGROUND: Campylobacteriosis is one of the most commonly identified causes of bacterial diarrheal disease and a common cause of gastroenteritis in travellers from developed nations. Despite the widespread occurrence, there is little information on Campylobacter mortality. METHODS: Mortality among a cohort of Campylobacter cases were compared with the general population 0–1, 1–3, 3–12 and more than 12 month after the onset of the illness. The cases were sub-grouped according to if they had been infected domestically or abroad. RESULTS: The standardized mortality ratio for cases infected domestically was 2.9 (95% CI: 1.9–4.0) within the first month following the illness. The risk then gradually diminished and approached 1.0 after one year or more have passed since the illness. This initial excess risk was not attributable to any particular age group (such as the oldest). In contrast, for those infected abroad, a lower standardized mortality ratio 0.3 (95% CI: 0.04–0.8) was shown for the first month after diagnosis compared to what would be expected in the general population. CONCLUSION: Infection with Campylobacter is associated with an increased short-term risk of death among those who were infected domestically. On the contrary, for those infected abroad a lower than expected risk of death was evident. We suggest that the explanation behind this is a "healthy traveler effect" among imported cases, and effects of a more frail than average population among domestic cases

Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK

The GTPases belonging to the Rho family control the actin cytoskeleton rearrangements needed for particle internalization during phagocytosis. ROCK and mDia1 are downstream effectors of RhoA, a GTPase involved in that process. Coxiella burnetii, the etiologic agent of Q fever, is internalized by the host´s cells in an actin-dependent manner. Nevertheless, the molecular mechanism involved in this process has been poorly characterized. This work analyzes the role of different GTPases of the Rho family and some downstream effectors in the internalization of C. burnetii by phagocytic and non-phagocytic cells. The internalization of C. burnetii into HeLa and RAW cells was significantly inhibited when the cells were treated with Clostridium difficile Toxin B which irreversibly inactivates members of the Rho family. In addition, the internalization was reduced in HeLa cells that overexpressed the dominant negative mutants of RhoA, Rac1 or Cdc42 or that were knocked down for the Rho GTPases. The pharmacological inhibition or the knocking down of ROCK diminished bacterium internalization. Moreover, C. burnetii was less efficiently internalized in HeLa cells overexpressing mDia1-N1, a dominant negative mutant of mDia1, while the overexpression of the constitutively active mutant mDia1-ΔN3 increased bacteria uptake. Interestingly, when HeLa and RAW cells were infected, RhoA, Rac1 and mDia1 were recruited to membrane cell fractions. Our results suggest that the GTPases of the Rho family play an important role in C. burnetii phagocytosis in both HeLa and RAW cells. Additionally, we present evidence that ROCK and mDia1, which are downstream effectors of RhoA, are involved in that processFil: Salinas Ojeda, Romina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Ortiz Flores, Rodolfo Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Distel, Jesús Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Aguilera, Milton Osmar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Colombo, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Beron, Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

Fires can benefit plants by disrupting antagonistic interactions

Fire has a key role in the ecology and evolution of many ecosystems, yet its effects on plant–insect interactions are poorly understood. Because interacting species are likely to respond to fire differently, disruptions of the interactions are expected. We hypothesized that plants that regenerate after fire can benefit through the disruption of their antagonistic interactions. We expected stronger effects on interactions with specialist predators than with generalists. We studied two interactions between two Mediterranean plants (Ulex parviflorus, Asphodelus ramosus) and their specialist seed predators after large wildfires. In A. ramosus we also studied the generalist herbivores. We sampled the interactions in burned and adjacent unburned areas during 2 years by estimating seed predation, number of herbivores and fruit set. To assess the effect of the distance to unburned vegetation we sampled plots at two distance classes from the fire perimeter. Even 3 years after the fires, Ulex plants experienced lower seed damage by specialists in burned sites. The presence of herbivores on Asphodelus decreased in burned locations, and the variability in their presence was significantly related to fruit set. Generalist herbivores were unaffected. We show that plants can benefit from fire through the disruption of their antagonistic interactions with specialist seed predators for at least a few years. In environments with a long fire history, this effect might be one additional mechanism underlying the success of fire-adapted plants

Quantum value indefiniteness

The indeterministic outcome of a measurement of an individual quantum is certified by the impossibility of the simultaneous, definite, deterministic pre-existence of all conceivable observables from physical conditions of that quantum alone. We discuss possible interpretations and consequences for quantum oracles.Comment: 19 pages, 2 tables, 2 figures; contribution to PC0

Comprehensive Audiometric Analysis of Hearing Impairment and Tinnitus After Cisplatin-Based Chemotherapy in Survivors of Adult-Onset Cancer.

PURPOSE: Cisplatin is widely used but highly ototoxic. Effects of cumulative cisplatin dose on hearing loss have not been comprehensively evaluated in survivors of adult-onset cancer. PATIENTS AND METHODS: Comprehensive audiological measures were conducted on 488 North American male germ cell tumor (GCT) survivors in relation to cumulative cisplatin dose, including audiograms (0.25 to 12 kHz), tests of middle ear function, and tinnitus. American Speech-Language-Hearing Association criteria defined hearing loss severity. The geometric mean of hearing thresholds (0.25 to 12 kHz) summarized overall hearing status consistent with audiometric guidelines. Patients were sorted into quartiles of hearing thresholds of age- and sex-matched controls. RESULTS: Increasing cumulative cisplatin dose (median, 400 mg/m(2); range, 200 to 800 mg/m(2)) was significantly related to hearing loss at 4, 6, 8, 10, and 12 kHz (P trends, .021 to \u3c .001): every 100 mg/m(2) increase resulted in a 3.2-dB impairment in age-adjusted overall hearing threshold (4 to 12 kHz; P \u3c .001). Cumulative cisplatin doses \u3e 300 mg/m(2) were associated with greater American Speech-Language-Hearing Association-defined hearing loss severity (odds ratio, 1.59; P = .0066) and worse normative-matched quartiles (odds ratio, 1.33; P = .093) compared with smaller doses. Almost one in five (18%) patients had severe to profound hearing loss. Tinnitus (40% patients) was significantly correlated with reduced hearing at each frequency (P \u3c .001). Noise-induced damage (10% patients) was unaffected by cisplatin dose (P = .59). Hypertension was significantly related (P = .0066) to overall hearing threshold (4 to 12 kHz) in age- and cisplatin dose-adjusted analyses. Middle ear deficits occurred in 22.3% of patients but, as expected, were not related to cytotoxic drug dosage. CONCLUSION: Follow-up of adult-onset cancer survivors given cisplatin should include routine inquiry for hearing status and tinnitus, referral to audiologists as clinically indicated, and hypertension control. Patients should be urged to avoid noise exposure, ototoxic drugs, and other factors that further damage hearing