Development of a Cancer Risk Prediction Tool for Use in the UK Primary Care and Community Settings.

Several multivariable risk prediction models have been developed to asses an individual's risk of developing specific cancers. Such models can be used in a variety of settings for prevention, screening, and guiding investigations and treatments. Models aimed at predicting future disease risk that contains lifestyle factors may be of particular use for targeting health promotion activities at an individual level. This type of cancer risk prediction is not yet available in the UK. We have adopted the approach used by the well-established U.S.-derived "YourCancerRisk" model for use in the UK population, which allow users to quantify their individual risk of developing individual cancers relative to the population average risk. The UK version of "YourCancerRisk" computes 10-year cancer risk estimates for 11 cancers utilizing UK figures for prevalence of risk factors and cancer incidence. Because the prevalence of risk factors and the incidence rates for cancer are different between the U.S. and the UK population, this UK model provides more accurate estimates of risks for a UK population. Using an example of breast cancer and data from UK Biobank cohort, we demonstrate that the individual risk factor estimates are similar for the U.S. and UK populations. Assessment of the performance and validation of the multivariate model predictions based on a binary score confirm the model's applicability. The model can be used to estimate absolute and relative cancer risk for use in Primary Care and community settings and is being used in the community to guide lifestyle change. Cancer Prev Res; 10(7); 421-30. ©2017 AACR

Tapanuli orangutan endangered by Sumatran hydropower scheme

The Tapanuli orangutan survives today in less than 1,200 km of rainforest in northern Sumatra, Indonesia, in an area known as Batang Toru, where it was scientifically discovered in 1997. Teeming with endangered fauna and flora, the Batang Toru forest has been partially felled and fragmented and parts of the remainder allocated to agriculture, mining, hydropower and geothermal-energy production. The Tapanuli orangutan is estimated to number just 767 individuals, divided among three subpopulations. Its total remaining habitat 10 is merely a tenth the size of Sydney, Australia

A Proposal for a Three Detector Short-Baseline Neutrino Oscillation Program in the Fermilab Booster Neutrino Beam

A Short-Baseline Neutrino (SBN) physics program of three LAr-TPC detectors located along the Booster Neutrino Beam (BNB) at Fermilab is presented. This new SBN Program will deliver a rich and compelling physics opportunity, including the ability to resolve a class of experimental anomalies in neutrino physics and to perform the most sensitive search to date for sterile neutrinos at the eV mass-scale through both appearance and disappearance oscillation channels. Using data sets of 6.6e20 protons on target (P.O.T.) in the LAr1-ND and ICARUS T600 detectors plus 13.2e20 P.O.T. in the MicroBooNE detector, we estimate that a search for muon neutrino to electron neutrino appearance can be performed with ~5 sigma sensitivity for the LSND allowed (99% C.L.) parameter region. In this proposal for the SBN Program, we describe the physics analysis, the conceptual design of the LAr1-ND detector, the design and refurbishment of the T600 detector, the necessary infrastructure required to execute the program, and a possible reconfiguration of the BNB target and horn system to improve its performance for oscillation searches.Comment: 209 pages, 129 figure

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF

The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at the Fermilab Long-Baseline Neutrino Facility (LBNF) is described

Neurobiological Models of Two-Choice Decision Making Can Be Reduced to a One-Dimensional Nonlinear Diffusion Equation

The response behaviors in many two-alternative choice tasks are well described by so-called sequential sampling models. In these models, the evidence for each one of the two alternatives accumulates over time until it reaches a threshold, at which point a response is made. At the neurophysiological level, single neuron data recorded while monkeys are engaged in two-alternative choice tasks are well described by winner-take-all network models in which the two choices are represented in the firing rates of separate populations of neurons. Here, we show that such nonlinear network models can generally be reduced to a one-dimensional nonlinear diffusion equation, which bears functional resemblance to standard sequential sampling models of behavior. This reduction gives the functional dependence of performance and reaction-times on external inputs in the original system, irrespective of the system details. What is more, the nonlinear diffusion equation can provide excellent fits to behavioral data from two-choice decision making tasks by varying these external inputs. This suggests that changes in behavior under various experimental conditions, e.g. changes in stimulus coherence or response deadline, are driven by internal modulation of afferent inputs to putative decision making circuits in the brain. For certain model systems one can analytically derive the nonlinear diffusion equation, thereby mapping the original system parameters onto the diffusion equation coefficients. Here, we illustrate this with three model systems including coupled rate equations and a network of spiking neurons

Empirical Models of Transitions between Coral Reef States: Effects of Region, Protection, and Environmental Change

There has been substantial recent change in coral reef communities. To date, most analyses have focussed on static patterns or changes in single variables such as coral cover. However, little is known about how community-level changes occur at large spatial scales. Here, we develop Markov models of annual changes in coral and macroalgal cover in the Caribbean and Great Barrier Reef (GBR) regions

Tissue-specific alternative splicing of TCF7L2

Common variants in the transcription factor 7-like 2 (TCF7L2) gene have been identified as the strongest genetic risk factors for type 2 diabetes (T2D). However, the mechanisms by which these non-coding variants increase risk for T2D are not well-established. We used 13 expression assays to survey mRNA expression of multiple TCF7L2 splicing forms in up to 380 samples from eight types of human tissue (pancreas, pancreatic islets, colon, liver, monocytes, skeletal muscle, subcutaneous adipose tissue and lymphoblastoid cell lines) and observed a tissue-specific pattern of alternative splicing. We tested whether the expression of TCF7L2 splicing forms was associated with single nucleotide polymorphisms (SNPs), rs7903146 and rs12255372, located within introns 3 and 4 of the gene and most strongly associated with T2D. Expression of two splicing forms was lower in pancreatic islets with increasing counts of T2D-associated alleles of the SNPs: a ubiquitous splicing form (P = 0.018 for rs7903146 and P = 0.020 for rs12255372) and a splicing form found in pancreatic islets, pancreas and colon but not in other tissues tested here (P = 0.009 for rs12255372 and P = 0.053 for rs7903146). Expression of this form in glucose-stimulated pancreatic islets correlated with expression of proinsulin (r2 = 0.84–0.90, P < 0.00063). In summary, we identified a tissue-specific pattern of alternative splicing of TCF7L2. After adjustment for multiple tests, no association between expression of TCF7L2 in eight types of human tissue samples and T2D-associated genetic variants remained significant. Alternative splicing of TCF7L2 in pancreatic islets warrants future studies. GenBank Accession Numbers: FJ010164–FJ010174

French database of children and adolescents with Prader-Willi syndrome

<p>Abstract</p> <p>Background</p> <p>Prader-Willi syndrome (PWS) is a rare multisystem genetic disease leading to severe complications mainly related to obesity. We strongly lack information on the natural history of this complex disease and on what factors are involved in its evolution and its outcome. One of the objectives of the French reference centre for Prader-Willi syndrome set-up in 2004 was to set-up a database in order to make the inventory of Prader-Willi syndrome cases and initiate a national cohort study in the area covered by the centre.</p> <p>Description</p> <p>the database includes medical data of children and adolescents with Prader-Willi syndrome, details about their management, socio-demographic data on their families, psychological data and quality of life of the parents. The tools and organisation used to ensure data collection and data quality in respect of good clinical practice procedures are discussed, and main characteristics of our Prader-Willi population at inclusion are presented.</p> <p>Conclusion</p> <p>this database covering all the aspects of PWS clinical, psychological and social profiles, including familial psychological and quality of life will be a powerful tool for retrospective studies concerning this complex and multi factorial disease and could be a basis for the design of future prospective multicentric studies. The complete database and the Stata.do files are available to any researcher wishing to use them for non-commercial purposes and can be provided upon request to the corresponding author.</p

Staphylococcus aureus Induces Eosinophil Cell Death Mediated by α-hemolysin

Staphylococcus aureus, a major human pathogen, exacerbates allergic disorders, including atopic dermatitis, nasal polyps and asthma, which are characterized by tissue eosinophilia. Eosinophils, via their destructive granule contents, can cause significant tissue damage, resulting in inflammation and further recruitment of inflammatory cells. We hypothesised that the relationship between S. aureus and eosinophils may contribute to disease pathology. We found that supernatants from S. aureus (SH1000 strain) cultures cause rapid and profound eosinophil necrosis, resulting in dramatic cell loss within 2 hours. This is in marked contrast to neutrophil granulocytes where no significant cell death was observed (at equivalent dilutions). Supernatants prepared from a strain deficient in the accessory gene regulator (agr) that produces reduced levels of many important virulence factors, including the abundantly produced α-hemolysin (Hla), failed to induce eosinophil death. The role of Hla in mediating eosinophil death was investigated using both an Hla deficient SH1000-modified strain, which did not induce eosinophil death, and purified Hla, which induced concentration-dependent eosinophil death via both apoptosis and necrosis. We conclude that S. aureus Hla induces aberrant eosinophil cell death in vitro and that this may increase tissue injury in allergic disease

The SLUGGS Survey: kinematics for over 2500 globular clusters in twelve early-type galaxies

We present a spectrophotometric survey of 2522 extragalactic globular clusters (GCs) around 12 early-type galaxies, nine of which have not been published previously. Combining space-based and multicolour wide-field ground-based imaging, with spectra from the Keck/DEep Imaging Multi-Object Spectrograph (DEIMOS) instrument, we obtain an average of 160 GC radial velocities per galaxy, with a high-velocity precision of ∼15 km s−1 per GC. After studying the photometric properties of the GC systems, such as their spatial and colour distributions, we focus on the kinematics of metal-poor (blue) and metal-rich (red) GC subpopulations to an average distance of ∼8 effective radii from the galaxy centre. Our results show that for some systems the bimodality in GC colour is also present in GC kinematics. The kinematics of the red GC subpopulations are strongly coupled with the host galaxy stellar kinematics. The blue GC subpopulations are more dominated by random motions, especially in the outer regions, and decoupled from the red GCs. Peculiar GC kinematic profiles are seen in some galaxies: the blue GCs in NGC 821 rotate along the galaxy minor axis, whereas the GC system of the lenticular galaxy NGC 7457 appears to be strongly rotation supported in the outer region. We supplement our galaxy sample with data from the literature and carry out a number of tests to study the kinematic differences between the two GC subpopulations. We confirm that the GC kinematics are coupled with the host galaxy properties and find that the velocity kurtosis and the slope of their velocity dispersion profiles are different between the two GC subpopulations in more massive galaxies