Avoiding Pandemic Fears in the Subway and Conquering the Platypus.

Metagenomics is increasingly used not just to show patterns of microbial diversity but also as a culture-independent method to detect individual organisms of intense clinical, epidemiological, conservation, forensic, or regulatory interest. A widely reported metagenomic study of the New York subway suggested that the pathogens Yersinia pestis and Bacillus anthracis were part of the "normal subway microbiome." In their article in mSystems, Hsu and collaborators (mSystems 1(3):e00018-16, 2016, http://dx.doi.org/10.1128/mSystems.00018-16) showed that microbial communities on transit surfaces in the Boston subway system are maintained from a metapopulation of human skin commensals and environmental generalists and that reanalysis of the New York subway data with appropriate methods did not detect the pathogens. We note that commonly used software pipelines can produce results that lack prima facie validity (e.g., reporting widespread distribution of notorious endemic species such as the platypus or the presence of pathogens) but that appropriate use of inclusion and exclusion sets can avoid this issue

Entropic measure of wave-packet spreading and ionization in laser-driven atoms

Published versio

Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders.

Common Variable Immunodeficiency Disorders (CVIDs) are the most prevalent cause of primary antibody failure. CVIDs are highly variable and a genetic causes have been identified in <5% of patients. Here, we performed whole genome sequencing (WGS) of 34 CVID patients (94% sporadic) and combined them with transcriptomic profiling (RNA-sequencing of B cells) from three patients and three healthy controls. We identified variants in CVID disease genes TNFRSF13B, TNFRSF13C, LRBA and NLRP12 and enrichment of variants in known and novel disease pathways. The pathways identified include B-cell receptor signalling, non-homologous end-joining, regulation of apoptosis, T cell regulation and ICOS signalling. Our data confirm the polygenic nature of CVID and suggest individual-specific aetiologies in many cases. Together our data show that WGS in combination with RNA-sequencing allows for a better understanding of CVIDs and the identification of novel disease associated pathways

Multi-Scale Simulation Modeling for Prevention and Public Health Management of Diabetes in Pregnancy and Sequelae

Diabetes in pregnancy (DIP) is an increasing public health priority in the Australian Capital Territory, particularly due to its impact on risk for developing Type 2 diabetes. While earlier diagnostic screening results in greater capacity for early detection and treatment, such benefits must be balanced with the greater demands this imposes on public health services. To address such planning challenges, a multi-scale hybrid simulation model of DIP was built to explore the interaction of risk factors and capture the dynamics underlying the development of DIP. The impact of interventions on health outcomes at the physiological, health service and population level is measured. Of particular central significance in the model is a compartmental model representing the underlying physiological regulation of glycemic status based on beta-cell dynamics and insulin resistance. The model also simulated the dynamics of continuous BMI evolution, glycemic status change during pregnancy and diabetes classification driven by the individual-level physiological model. We further modeled public health service pathways providing diagnosis and care for DIP to explore the optimization of resource use during service delivery. The model was extensively calibrated against empirical data.Comment: 10 pages, SBP-BRiMS 201

Chronic Oedema and the older person: The effects of ageing upon treatment outcomes

Chronic oedema (CO) and lymphoedema (LO) are long-term conditions that can become more complicated or are more likely to develop with age. The ageing process can involve alterations in the structures that support the normal function of the lymphatic system or put it at greater risk of damage. The main three components (skin care, exercise and compression therapy) within the management of CO/LO can become more difficult to apply with age. This is because of reduced healing rates, decreased cardiovascular capacity and deterioration in vascular and arterial structures. The impact of ageing and how this can affect patients and treatment outcomes requires careful consideration

Spontaneous Stratification in Granular Mixtures

Granular materials size segregate when exposed to external periodic perturbations such as vibrations. Moreover, mixtures of grains of different sizes spontaneously segregate in the absence of external perturbations: when a mixture is simply poured onto a pile, the large grains are more likely to be found near the base, while the small grains are more likely to be near the top. Here, we report a spontaneous phenomenon arising when we pour a mixture between two vertical plates: the mixture spontaneously stratifies into alternating layers of small and large grains whenever the large grains are rougher than the small grains. In contrast, we find only spontaneous segregation when the large grains are more rounded than the small grains. The stratification is related to the occurrence of avalanches; during each avalanche the grains comprising the avalanche spontaneously stratify into a pair of layers through a "kink" mechanism, with the small grains forming a sublayer underneath the layer of large grains.Comment: 4 pages, 6 figures, http://polymer.bu.edu/~hmakse/Home.htm

Diagnosing idiopathic learning disability: a cost-effectiveness analysis of microarray technology in the National Health Service of the United Kingdom

Array based comparative genomic hybridisation (aCGH) is a powerful technique for detecting clinically relevant genome imbalance and can offer 40 to > 1000 times the resolution of karyotyping. Indeed, idiopathic learning disability (ILD) studies suggest that a genome-wide aCGH approach makes 10–15% more diagnoses involving genome imbalance than karyotyping. Despite this, aCGH has yet to be implemented as a routine NHS service. One significant obstacle is the perception that the technology is prohibitively expensive for most standard NHS clinical cytogenetics laboratories. To address this, we investigated the cost-effectiveness of aCGH versus standard cytogenetic analysis for diagnosing idiopathic learning disability (ILD) in the NHS. Cost data from four participating genetics centres were collected and analysed. In a single test comparison, the average cost of aCGH was £442 and the average cost of karyotyping was £117 with array costs contributing most to the cost difference. This difference was not a key barrier when the context of follow up diagnostic tests was considered. Indeed, in a hypothetical cohort of 100 ILD children, aCGH was found to cost less per diagnosis (£3,118) than a karyotyping and multi-telomere FISH approach (£4,957). We conclude that testing for genomic imbalances in ILD using microarray technology is likely to be cost-effective because long-term savings can be made regardless of a positive (diagnosis) or negative result. Earlier diagnoses save costs of additional diagnostic tests. Negative results are cost-effective in minimising follow-up test choice. The use of aCGH in routine clinical practice warrants serious consideration by healthcare providers

Waiting time variation in Early Intervention Psychosis services: longitudinal evidence from the SEPEA naturalistic cohort study

PURPOSE: Early Intervention Psychosis [EIP] services have gained traction internationally, but are currently undergoing various forms of reconfiguration. In England, such services are now mandated to ensure 50% of accepted referrals commence care within 14 days, but no empirical evidence exists. We sought to estimate waiting times to EIP services in a large, representative epidemiological cohort in England, and investigate possible reasons for any variation. METHODS: We estimated median waiting time from referral to acceptance by EIP services and investigated whether this varied by clinical, demographic or neighbourhood-level factors, amongst 798 participants, 16-35 years old, presenting to six EIP services over 3.5 years in a defined catchment area serving 2.5 million people. We used parametric survival analysis to inspect variation in waiting times (in days). RESULTS: Median waiting time was 15 days (interquartile range 7-30), although this varied across services (p < 0.01). Waiting times increased over the case ascertainment period by an average of 4.3 days (95% CI 1.3, 6.2; p < 0.01). Longer waiting times were associated with greater diagnostic uncertainty, indexed by an organic presentation (+ 9.1 days; 95% CI 1.9, 16.6; p < 0.01), polysubstance abuse (+ 2.6; 0.6, 3.9; p < 0.01), absence of psychotic disorder (+1.8; -0.1, 3.0; p = 0.05) and insidious onset (+1.8; -0.1, 3.0; p = 0.06). Waiting times did not vary by most demographic or neighbourhood-level characteristics. CONCLUSIONS: EIP services operate close to new waiting time standards in England, with little systematic variation by sociodemographic position. However, waiting times increased over the study period, coinciding with substantial service reorganisation. Longer waiting times associated with greater diagnostic uncertainty highlight opportunities to reduce delays in certain clinical groups at initial referral.The work for this paper was supported by: a Sir Henry Wellcome Research Fellowship from the Wellcome Trust (Grant No. WT085540) to Dr James Kirkbride, a Sir Henry Dale Fellowship to Dr James Kirkbride, jointly funded by the Wellcome Trust and the Royal Society (Grant No. 101272/Z/13/Z), and an NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) grant for Cambridgeshire and Peterborough (Grant No. RP-PG-0606-1335) to Prof Peter Jones. The funders had no involvement in any aspect of the design of this study, preparation of results, or decision to submit for publication. We thank the Cambridgeshire and Peterborough (CPFT) and Norfolk and Suffolk Foundation Trusts (NSFT) for sponsoring this research