Deficient Positive Selection of CD4 T Cells in Mice Displaying Altered Repertoires of MHC Class II–Bound Self-Peptides

AbstractThe role of self-peptides in positive selection of CD4+ T cells has been controversial. We show that some self-peptides are presented by the MHC class II molecule I-Ab in mice lacking Ii or H-2M but not in mice expressing a transgene-encoded peptide fused to I-Ab. In experiments using specific antibodies to block selection, these low-abundance self-peptides were implicated in the positive selection of some CD4+ T cells in H-2M−/− mice. However, all three mutant backgrounds failed to positively select two class II–restricted transgenic T cell receptors. Our findings suggest that minor components of the self-peptide repertoire can contribute to positive selection of a significant number of CD4+ T cells. In addition, the data suggest that T cell receptor repertoires selected in wild-type mice and in mice displaying limited spectra of self-peptides are distinct

Heat protection behaviour in the UK: Results of an online survey after the 2013 heatwave

Background: The Heatwave Plan for England provides guidance for personal and home protection measures during heatwaves. Although studies in the USA, Australia and Europe have surveyed heat-related behaviours during heatwaves, few have been conducted in the UK. This study assesses personal and housing (at-home) behaviour and housing characteristics of the UK population during the 2013 heatwave. Methods: This paper analyses data from 1497 respondents of an online survey on heat protection measures and behaviour. Participants were asked questions about their behaviour during the 2013 heatwave, the characteristics of their current housing as well as about any negative health outcomes experienced due to the hot weather. We used multinomial logit regression to analyse personal and home heat protection behaviour and logistic regression to analyse characteristics of participants' current home (installed air conditioner, curtains etc.). We stratified the outcomes by age, sex, ethnicity, income, education and regional location. Results: In 2013, for all heat-related illness (except tiredness), a higher proportion of those in the younger age groups reported symptoms compared with those in the older age groups. Women, higher income groups and those with higher education levels were found to be more likely to report always/often taking personal heat protective measures. The elderly were less likely to take some personal and home protective measures but were more likely to live in insulated homes and open windows at night to keep their home cool. Conclusion: Our study has found a high level of awareness of the actions to take during heatwaves in the UK, and has identified important demographic indicators of sections of the UK population that might benefit from additional or more targeted information. The health agencies should attempt to provide better information about heatwaves to those vulnerable (elderly, those at risk living in London, low income earners) or identify any barriers that might be preventing them from undertaking protective behaviour

The Impact of Heatwaves on Community Morbidity and Healthcare Usage: A Retrospective Observational Study Using Real-Time Syndromic Surveillance.

We investigated the impact of a moderate heatwave on a range of presenting morbidities in England. Asthma, difficulty breathing, cerebrovascular accident, and cardiovascular symptoms were analysed using general practitioner in hours (GPIH), out of hours (GPOOH) and emergency department (ED) syndromic surveillance systems. Data were stratified by age group and compared between a heatwave year (2013) and non-heatwave years (2012, 2014). Incidence rate ratios were calculated to estimate the differential impact of heatwave compared to non-heatwave summers: there were no apparent differences for the morbidities tested between the 2013 heatwave and non-heatwave years. A subset of GPIH data were used to study individuals at higher risk from heatwaves based on their pre-existing disease. Higher risk patients were not more likely to present at GPs or ED than other individuals. Comparing GPIH consultations and ED attendances for myocardial infarction/ischaemia (MI), there was evidence of a fall in the presentation of MI during the heatwave, which was particularly noted in the 65-74 years age group (and over 75 years in ED attendances). These results indicate the difficulty in identifying individuals at risk from non-fatal health effects of heatwaves and hot weather

The impact of climatic risk factors on the prevalence, distribution, and severity of acute and chronic trachoma.

BACKGROUND AND OBJECTIVES: Trachoma is the most common cause of infectious blindness. Hot, dry climates, dust and water scarcity are thought to be associated with the distribution of trachoma but the evidence is unclear. The aim of this study was to evaluate the epidemiological evidence regarding the extent to which climatic factors explain the current prevalence, distribution, and severity of acute and chronic trachoma. Understanding the present relationship between climate and trachoma could help inform current and future disease elimination. METHODS: A systematic review of peer-reviewed literature was conducted to identify observational studies which quantified an association between climate factors and acute or chronic trachoma and which met the inclusion and exclusion criteria. Studies that assessed the association between climate types and trachoma prevalence were also reviewed. RESULTS: Only eight of the 1751 papers retrieved met the inclusion criteria, all undertaken in Africa. Several papers reported an association between trachoma prevalence and altitude in highly endemic areas, providing some evidence of a role for temperature in the transmission of acute disease. A robust mapping study found strong evidence of an association between low rainfall and active trachoma. There is also consistent but weak evidence that the prevalence of trachoma is higher in savannah-type ecological zones. There were no studies on the effect of climate in low endemic areas, nor on the effect of dust on trachoma. CONCLUSION: Current evidence on the potential role of climate on trachoma distribution is limited, despite a wealth of anecdotal evidence. Temperature and rainfall appear to play a role in the transmission of acute trachoma, possibly mediated through reduced activity of flies at lower temperatures. Further research is needed on climate and other environmental and behavioural factors, particularly in arid and savannah areas. Many studies did not adequately control for socioeconomic or environmental confounders

The effectiveness of public health interventions to reduce the health impact of climate change:a systematic review of systematic reviews

Climate change is likely to be one of the most important threats to public health in the coming years. Yet despite the large number of papers considering the health impact of climate change, few have considered what public health interventions may be of most value in reducing the disease burden. We aimed to evaluate the effectiveness of public health interventions to reduce the disease burden of high priority climate sensitive diseases

The impact of climate on the abundance of Musca sorbens, the vector of trachoma

Background: To assess the extent to which climate may affect the abundance of Musca sorbens, a putative vector of trachoma. Data sources: Studies were identified by systematically searching online databases including CAB abstracts, Embase, Global Health, Medline, Web of Science and BIOS Online, references from key articles, and the websites of relevant international agencies. Methods: A systematic literature review was conducted of field and laboratory studies that reported the impact of climate factors (e.g., temperature, humidity) on the synanthropic fly Musca sorbens. Data were systematically extracted and studies assessed for quality by two readers. Study results were reported narratively. Results: A total of 16 studies met the inclusion criteria but only three evaluated associations between climatic/ abiotic factors and M. sorbens. Limited evidence indicates that M. sorbens abundance has an optimal temperature and humidity range. Thirteen studies reported seasonal patterns but no consistent pattern was found between season and the abundance of M. sorbens. Conclusions: The evidence base regarding the effect of climatic factors on M. sorbens is limited, so it is difficult to construct a biological model driven by climate for this species. A multivariate statistical approach based on the climate of sites where M. sorbens is found may better capture its complex relationship with climatic factors as well as aid in mapping the global range of M. sorbens

A comparison of weather variables linked to infectious disease patterns using laboratory addresses and patient residence addresses

Background: To understand the impact of weather on infectious diseases, information on weather parameters at patient locations is needed, but this is not always accessible due to confidentiality or data availability. Weather parameters at nearby locations are often used as a proxy, but the accuracy of this practice is not known. Methods: Daily Campylobacter and Cryptosporidium cases across England and Wales were linked to local temperature and rainfall at the residence postcodes of the patients and at the corresponding postcodes of the laboratory where the patient’s specimen was tested. The paired values of daily rainfall and temperature for the laboratory versus residence postcodes were interpolated from weather station data, and the results were analysed for agreement using linear regression. We also assessed potential dependency of the findings on the relative geographic distance between the patient’s residence and the laboratory. Results: There was significant and strong agreement between the daily values of rainfall and temperature at diagnostic laboratories with the values at the patient residence postcodes for samples containing the pathogens Campylobacter or Cryptosporidium. For rainfall, the R-squared was 0.96 for the former and 0.97 for the latter, and for maximum daily temperature, the R-squared was 0.99 for both. The overall mean distance between the patient residence and the laboratory was 11.9 km; however, the distribution of these distances exhibited a heavy tail, with some rare situations where the distance between the patient residence and the laboratory was larger than 500 km. These large distances impact the distributions of the weather variable discrepancies (i.e. the differences between weather parameters estimated at patient residence postcodes and those at laboratory postcodes), with discrepancies up to ±10 °C for the minimum and maximum temperature and 20 mm for rainfall. Nevertheless, the distributions of discrepancies (estimated separately for minimum and maximum temperature and rainfall), based on the cases where the distance between the patient residence and the laboratory was within 20 km, still exhibited tails somewhat longer than the corresponding exponential fits suggesting modest small scale variations in temperature and rainfall. Conclusion: The findings confirm that, for the purposes of studying the relationships between meteorological variables and infectious diseases using data based on laboratory postcodes, the weather results are sufficiently similar to justify the use of laboratory postcode as a surrogate for domestic postcode. Exclusion of the small percentage of cases where there is a large distance between the residence and the laboratory could increase the precision of estimates, but there are generally strong associations between daily weather parameters at residence and laboratory

Elucidating the aetiology of human Campylobacter coli infections

Peer reviewedPublisher PD

Sparse initial data indentification for parabolic pde and its finite element approximations

We address the problem of inverse source identification for parabolic equations from the optimal control viewpoint employing measures of minimal norm as initial data. We adopt the point of view of approximate controllability so that the target is not required to be achieved exactly but only in an approximate sense. We prove an approximate inversion result and derive a characterization of the optimal initial measures by means of duality and the minimization of a suitable quadratic functional on the solutions of the adjoint system. We prove the sparsity of the optimal initial measures showing that they are supported in sets of null Lebesgue measure. As a consequence, approximate controllability can be achieved efficiently by means of controls that are activated in a finite number of pointwise locations. Moreover, we discuss the finite element numerical approximation of the control problem providing a convergence result of the corresponding optimal measures and states as the discretization parameters tend to zero.The first author was supported by Spanish Ministerio de Economía y Competitividad under project MTM2011-22711. The third author was supported by the Advanced Grant NUMERIWAVES/FP7-246775 of the European Research Council Executive Agency, FA9550-14-1-0214 of the EOARD-AFOSR, FA9550-15-1-0027 of AFOSR, the BERC 2014-2017 program of the Basque Government, the MTM2011-29306 and SEV-2013-0323 Grants of the MINECO, the CIMI-Toulouse Excellence Chair in PDEs, Control and Numerics and a Humboldt Award at the University of Erlangen-Nürnberg