Causes of early-onset type 1 diabetes: toward data-driven environmental approaches

A new study reveals distinctive metabolic changes that precede the development of type 1 diabetes (T1D), tossing a stone into the quiet waters of T1D immunology and genetics. The causes of these metabolic changes and their relationship to autoimmunity and β cell destruction are not yet known, but the identification of a metabolic phenotype linked to susceptibility to type I diabetes may help pave the way to a new era of investigation of T1D causality

Modeling the Worldwide Spread of Pandemic Influenza: Baseline Case and Containment Interventions

We present a study of the worldwide spread of a pandemic influenza and its possible containment at a global level taking into account all available information on air travel. We studied a metapopulation stochastic epidemic model on a global scale that considers airline travel flow data among urban areas. We provided a temporal and spatial evolution of the pandemic with a sensitivity analysis of different levels of infectiousness of the virus and initial outbreak conditions (both geographical and seasonal). For each spreading scenario we provided the timeline and the geographical impact of the pandemic in 3,100 urban areas, located in 220 different countries. We compared the baseline cases with different containment strategies, including travel restrictions and the therapeutic use of antiviral (AV) drugs. We show that the inclusion of air transportation is crucial in the assessment of the occurrence probability of global outbreaks. The large-scale therapeutic usage of AV drugs in all hit countries would be able to mitigate a pandemic effect with a reproductive rate as high as 1.9 during the first year; with AV supply use sufficient to treat approximately 2% to 6% of the population, in conjunction with efficient case detection and timely drug distribution. For highly contagious viruses (i.e., a reproductive rate as high as 2.3), even the unrealistic use of supplies corresponding to the treatment of approximately 20% of the population leaves 30%-50% of the population infected. In the case of limited AV supplies and pandemics with a reproductive rate as high as 1.9, we demonstrate that the more cooperative the strategy, the more effective are the containment results in all regions of the world, including those countries that made part of their resources available for global use.Comment: 16 page

Risk Assessment of Transmission of Sporadic Creutzfeldt-Jakob Disease in Endodontic Practice in Absence of Adequate Prion Inactivation

BACKGROUND: Experimental results evidenced the infectious potential of the dental pulp of animals infected with transmissible spongiform encephalopathies (TSE). This route of iatrogenic transmission of sporadic Creutzfeldt-Jakob disease (sCJD) may exist in humans via reused endodontic instruments if inadequate prion decontamination procedures are used. METHODOLOGY/PRINCIPAL FINDINGS: To assess this risk, 10 critical parameters in the transmission process were identified, starting with contamination of an endodontic file during treatment of an infectious sCJD patient and ending with possible infection of a subsequent susceptible patient. It was assumed that a dose-risk response existed, with no-risk below threshold values. Plausible ranges of those parameters were obtained through literature search and expert opinions, and a sensitivity analysis was conducted. Without effective prion-deactivation procedures, the risk of being infected during endodontic treatment ranged between 3.4 and 13 per million procedures. The probability that more than one case was infected secondary to endodontic treatment of an infected sCJD patient ranged from 47% to 77% depending on the assumed quantity of infective material necessary for disease transmission. If current official recommendations on endodontic instrument decontamination were strictly followed, the risk of secondary infection would become quasi-null. CONCLUSION: The risk of sCJD transmission through endodontic procedure compares with other health care risks of current concern such as death after liver biopsy or during general anaesthesia. These results show that single instrument use or adequate prion-decontamination procedures like those recently implemented in dental practice must be rigorously enforced

Association of environmental markers with childhood type 1 diabetes mellitus revealed by a long questionnaire on early life exposures and lifestyle in a case–control study

First available in BioRxiv doi: http://dx.doi.org/10.1101/063438International audienceBackground. The incidence of childhood type 1 diabetes (T1D) incidence is rising in many countries, supposedly because of changing environmental factors, which are yet largely unknown. The purpose of the study was to unravel environmental markers associated with T1D.Methods. Cases were children with T1D from the French Isis-Diab cohort. Controls were schoolmates or friends of the patients. Parents were asked to fill a 845-item questionnaire investigating the child’s environment before diagnosis. The analysis took into account the matching between cases and controls. A second analysis used propensity score methods.Results. We found a negative association of several lifestyle variables, gastroenteritis episodes, dental hygiene, hazelnut cocoa spread consumption, wasp and bee stings with T1D, consumption of vegetables from a farm and death of a pet by old age.Conclusions. The found statistical association of new environmental markers with T1D calls for replication in other cohorts and investigation of new environmental areas.Trial registration. Clinical-Trial.gov NCT02212522. Registered August 6, 2014.

Toward unsupervised outbreak detection through visual perception of new patterns

<p>Abstract</p> <p>Background</p> <p>Statistical algorithms are routinely used to detect outbreaks of well-defined syndromes, such as influenza-like illness. These methods cannot be applied to the detection of emerging diseases for which no preexisting information is available.</p> <p>This paper presents a method aimed at facilitating the detection of outbreaks, when there is no a priori knowledge of the clinical presentation of cases.</p> <p>Methods</p> <p>The method uses a visual representation of the symptoms and diseases coded during a patient consultation according to the International Classification of Primary Care 2^ndversion (ICPC-2). The surveillance data are transformed into color-coded cells, ranging from white to red, reflecting the increasing frequency of observed signs. They are placed in a graphic reference frame mimicking body anatomy. Simple visual observation of color-change patterns over time, concerning a single code or a combination of codes, enables detection in the setting of interest.</p> <p>Results</p> <p>The method is demonstrated through retrospective analyses of two data sets: description of the patients referred to the hospital by their general practitioners (GPs) participating in the French Sentinel Network and description of patients directly consulting at a hospital emergency department (HED).</p> <p>Informative image color-change alert patterns emerged in both cases: the health consequences of the August 2003 heat wave were visualized with GPs' data (but passed unnoticed with conventional surveillance systems), and the flu epidemics, which are routinely detected by standard statistical techniques, were recognized visually with HED data.</p> <p>Conclusion</p> <p>Using human visual pattern-recognition capacities to detect the onset of unexpected health events implies a convenient image representation of epidemiological surveillance and well-trained "epidemiology watchers". Once these two conditions are met, one could imagine that the epidemiology watchers could signal epidemiological alerts, based on "image walls" presenting the local, regional and/or national surveillance patterns, with specialized field epidemiologists assigned to validate the signals detected.</p

Epidemiological evidence of higher susceptibility to vCJD in the young

BACKGROUND: The strikingly young age of new variant Creutzfeldt-Jacob disease (vCJD) cases remains unexplained. Age dependent susceptibility to infection has been put forward, but differential dietary exposure to contaminated food products in the UK population according to age and sex during the bovine spongiform encephalopathy (BSE) epidemic may provide a simpler explanation. METHODS: Using recently published estimates of dietary exposure in mathematical models of the epidemiology of the new variant Creutzfeldt Jacob disease (vCJD), we examine whether the age characteristics of vCJD cases may be reproduced. RESULTS: The susceptibility/exposure risk function has likely peaked in adolescents and was followed by a sharp decrease with age, evocative of the profile of exposure to bovine material consumption according to age. However, assuming that the risk of contamination was proportional to exposure, with no age dependent susceptibility, the model failed to reproduce the observed age characteristics of the vCJD cases: The predicted cumulated proportion of cases over 40 years was 48%, in strong disagreement with the observed 10%. Incorporating age dependent susceptibility led to a cumulated proportion of cases over 40 years old of 12%. CONCLUSIONS: This analysis provides evidence that differential dietary exposure alone fails to explain the pattern of age in vCJD cases. Decreasing age related susceptibility is required to reproduce the characteristics of the age distribution of vCJD cases