A dynamical perspective on predictions of severe European cyclones: the role of large-scale conditions

Severe windstorms regularly inflict damage throughout Europe. This research examines a set of 31 midlatitude cyclones, investigating each in depth but encompassing a wide variety of such storms. The set is selected using the Storm Severity Index, and categorised using two methods. The first method is based on the relationship between the storm and the jet stream. Four groups emerge: storms that move along the edge of the jet; that cross the jet stream early; that cross later; or have a split jet. The second method is based on the Pressure Tendency Equation. This establishes whether horizontal temperature advection or diabatic processes dominate during storm development. These two approaches are linked: storms in the first two jet groups tend to be driven by horizontal temperature advection, and the other two groups by diabatic processes. This work then studies the storms’ forecast quality and spread using ECMWF data. It finds that storm intensity tends to be under-forecast, the forecast storms move too slowly and are too far south. Forecast quality improves and spread decreases earlier in storms that cross the jet early, compared to those that cross later, suggesting a link between jet interaction and forecast error. Storms where horizontal temperature advection dominates are on average less well forecast than their diabatic counterparts, but diabatically driven storms tend to have greater forecast spread. Finally, this study proposes metrics for storm-prone situations, examining the configuration of the atmosphere prior to the development of the storms. These describe a variety of key factors for cyclogenesis, such as baroclinicity, barotropicity and moist stability. Of the 31 storms, 29 are associated with a value greater than the 98th percentile of one or more metrics. There is a large overlap between storms where baroclinicity is strong and those where horizontal temperature advection dominates the deepening, confirming that the two approaches are dynamically linked. This relationship between the storms, the dynamics, and the metrics will allow future work to identify sources of uncertainty in modelling severe European windstorms

Atomic spectrometry update : a review of advances in environmental analysis

This is the 31st annual review of the application of atomic spectrometry to the chemical analysis of environmental samples. This update refers to papers published approximately between August 2014 and July 2015 and continues the series of Atomic Spectrometry Updates (ASUs) in Environmental Analysis that should be read in conjunction with other related ASUs in the series, namely: clinical and biological materials, foods and beverages; advances in atomic spectrometry and related techniques; elemental speciation; X-ray spectrometry; and metals, chemicals and functional materials. In the field of air analysis, highlights within this review period included: the development of a new laser fluorescence instrument for the ultratrace determination of mercury vapour; single particle ICP-MS studies and the coupling of elemental analysers to mass spectrometers for the improved characterisation of carbonaceous aerosols. In the arena of water analysis, methods continue to be developed: for the extraction and preconcentration of elements, As, Cr, Hg and Sb species and determination of elemental constituents in colloidal and NP fractions. Emerging elements of interest include Gd derived from MRI agents discharged at low level from medical facilities in water courses. Instrumental developments reported included the use of MC-ICP-MS for isotopic tracer studies and a review of TXRF techniques and associated preconcentration procedures for trace element analysis. In the period covered by this update several articles have explored the analysis of soil extracts for geochemical prospecting. There has been widening interest in the use of CS-AAS and in the application of techniques capable of direct sample analysis such as slurry sampling ETAAS and ETV-ICP-AES. Portable XRF instrumentation is now being used in many disciplines to quantify trace elements in soils – bringing a need for better transfer of analytical knowledge to non-specialist users – and the growing use of portable XRF in proximal sensing is also noteworthy. Recent research indicates that geological applications still drive many of the instrumental and methodological advances in LA-ICP-MS. Fundamental studies continued to shed light on the processes involved and hence ways of improving the analysis of laser-produced aerosols and to minimise matrix and fractionation effects. A new technique LA-DOF-MS (distance of flight) was described. The utility of LIBS and portable XRF for in situ survey work continues to show promise but issues such as appropriate calibration regimes and data processing protocols will still need to be addressed

Expression of KOC, S100P, mesothelin and MUC1 in pancreatico-biliary adenocarcinomas: development and utility of a potential diagnostic immunohistochemistry panel

<b>Background</b> Pancreatico-biliary adenocarcinomas (PBA) have a poor prognosis. Diagnosis is usually achieved by imaging and/or endoscopy with confirmatory cytology. Cytological interpretation can be difficult especially in the setting of chronic pancreatitis/cholangitis. Immunohistochemistry (IHC) biomarkers could act as an adjunct to cytology to improve the diagnosis. Thus, we performed a meta-analysis and selected KOC, S100P, mesothelin and MUC1 for further validation in PBA resection specimens.<p></p> <b>Methods</b> Tissue microarrays containing tumour and normal cores in a ratio of 3:2, from 99 surgically resected PBA patients, were used for IHC. IHC was performed on an automated platform using antibodies against KOC, S100P, mesothelin and MUC1. Tissue cores were scored for staining intensity and proportion of tissue stained using a Histoscore method (range, 0–300). Sensitivity and specificity for individual biomarkers, as well as biomarker panels, were determined with different cut-offs for positivity and compared by summary receiver operating characteristic (ROC) curve.<p></p> <b>Results</b> The expression of all four biomarkers was high in PBA versus normal ducts, with a mean Histoscore of 150 vs. 0.4 for KOC, 165 vs. 0.3 for S100P, 115 vs. 0.5 for mesothelin and 200 vs. 14 for MUC1 (p < .0001 for all comparisons). Five cut-offs were carefully chosen for sensitivity/specificity analysis. Four of these cut-offs, namely 5%, 10% or 20% positive cells and Histoscore 20 were identified using ROC curve analysis and the fifth cut-off was moderate-strong staining intensity. Using 20% positive cells as a cut-off achieved higher sensitivity/specificity values: KOC 84%/100%; S100P 83%/100%; mesothelin 88%/92%; and MUC1 89%/63%. Analysis of a panel of KOC, S100P and mesothelin achieved 100% sensitivity and 99% specificity if at least 2 biomarkers were positive for 10% cut-off; and 100% sensitivity and specificity for 20% cut-off.<p></p> <b>Conclusion</b> A biomarker panel of KOC, S100P and mesothelin with at least 2 biomarkers positive was found to be an optimum panel with both 10% and 20% cut-offs in resection specimens from patients with PBA.<p></p&gt

Automated eukaryotic gene structure annotation using EVidenceModeler and the Program to Assemble Spliced Alignments

EVidenceModeler (EVM) is an automated annotation tool that predicts protein-coding regions, alternatively spliced transcripts and untranslated regions of eukaryotic genes

mTORC2 signaling drives the development and progression of pancreatic cancer

mTOR signaling controls several critical cellular functions and is deregulated in many cancers, including pancreatic cancer. To date, most efforts have focused on inhibiting the mTORC1 complex. However, clinical trials of mTORC1 inhibitors in pancreatic cancer have failed, raising questions about this therapeutic approach. We employed a genetic approach to delete the obligate mTORC2 subunit Rictor and identified the critical times during which tumorigenesis requires mTORC2 signaling. Rictor deletion resulted in profoundly delayed tumorigenesis. Whereas previous studies showed most pancreatic tumors were insensitive to rapamycin, treatment with a dual mTORC1/2 inhibitor strongly suppressed tumorigenesis. In late-stage tumor-bearing mice, combined mTORC1/2 and PI3K inhibition significantly increased survival. Thus, targeting mTOR may be a potential therapeutic strategy in pancreatic cancer

Birthweight and risk markers for type 2 diabetes and cardiovascular disease in childhood: the Child Heart and Health Study in England (CHASE).

AIMS/HYPOTHESIS: Lower birthweight (a marker of fetal undernutrition) is associated with higher risks of type 2 diabetes and cardiovascular disease (CVD) and could explain ethnic differences in these diseases. We examined associations between birthweight and risk markers for diabetes and CVD in UK-resident white European, South Asian and black African-Caribbean children. METHODS: In a cross-sectional study of risk markers for diabetes and CVD in 9- to 10-year-old children of different ethnic origins, birthweight was obtained from health records and/or parental recall. Associations between birthweight and risk markers were estimated using multilevel linear regression to account for clustering in children from the same school. RESULTS: Key data were available for 3,744 (66%) singleton study participants. In analyses adjusted for age, sex and ethnicity, birthweight was inversely associated with serum urate and positively associated with systolic BP. After additional height adjustment, lower birthweight (per 100 g) was associated with higher serum urate (0.52%; 95% CI 0.38, 0.66), fasting serum insulin (0.41%; 95% CI 0.08, 0.74), HbA1c (0.04%; 95% CI 0.00, 0.08), plasma glucose (0.06%; 95% CI 0.02, 0.10) and serum triacylglycerol (0.30%; 95% CI 0.09, 0.51) but not with BP or blood cholesterol. Birthweight was lower among children of South Asian (231 g lower; 95% CI 183, 280) and black African-Caribbean origin (81 g lower; 95% CI 30, 132). However, adjustment for birthweight had no effect on ethnic differences in risk markers. CONCLUSIONS/INTERPRETATION: Birthweight was inversely associated with urate and with insulin and glycaemia after adjustment for current height. Lower birthweight does not appear to explain emerging ethnic difference in risk markers for diabetes

Changes in ponderal index and body mass index across childhood and their associations with fat mass and cardiovascular risk factors at age 15

Background: Little is known about whether associations between childhood adiposity and later adverse cardiovascular health outcomes are driven by tracking of overweight from childhood to adulthood and/or by vascular and metabolic changes from childhood overweight that persist into adulthood. Our objective is to characterise associations between trajectories of adiposity across childhood and a wide range of cardiovascular risk factors measured in adolescence, and explore the extent to which these are mediated by fat mass at age 15. Methods and Findings: Using data from the Avon Longitudinal Study of Parents and Children, we estimated individual trajectories of ponderal index (PI) from 0-2 years and BMI from 2-10 years using random-effects linear spline models (N = 4601). We explored associations between PI/BMI trajectories and DXA-determined total-body fat-mass and cardiovascular risk factors at 15 years (systolic and diastolic blood pressure, fasting LDL-and HDL-cholesterol, triglycerides, C-reactive protein, glucose, insulin) with and without adjustment for confounders. Changes in PI/BMI during all periods of infancy and childhood were associated with greater DXA-determined fat-mass at age 15. BMI changes in childhood, but not PI changes from 0-2 years, were associated with most cardiovascular risk factors in adolescence; associations tended to be strongest for BMI changes in later childhood (ages 8.5-10), and were largely mediated by fat mass at age 15. Conclusion: Changes in PI/BMI from 0-10 years were associated with greater fat-mass at age 15. Greater increases in BMI from age 8.5-10 years are most strongly associated with cardiovascular risk factors at age 15, with much of these associations mediated by fat-mass at this age. We found little evidence supporting previous reports that rapid PI changes in infancy are associated with future cardiovascular risk. This study suggests that associations between early overweight and subsequent adverse cardiovascular health are largely due to overweight children tending to remain overweight