TFTR 60 GHz alpha particle collective Thomson scattering diagnostic

A 60 GHz gyrotron collective Thomson Scattering alpha particle diagnostic has been implemented for the D-T period on TFM. Gyrotron power of 0.1-1 kW in pulses of up to 1 second can be launched in X-mode. Efficient corrugated waveguides are used with antennaes and vacuum windows of the TFTR Microwave Scattering system. A multichannel synchronous detector receiver system and spectrum analyzer acquire the scattered signals. A 200 Megasample/sec digitizer is used to resolve fine structure in the frequency spectrum. By scattering nearly perpendicular to the magnetic field, this experiment will take advantage of an enhancement of the scattered signal which results from the interaction of the alpha particles with plasma resonances in the lower hybrid frequency range. Significant enhancements are expected, which will make these measurements possible with gyrotron power less than 1 kW, while maintaining an acceptable signal to noise ratio. We hope to extract alpha particle density and velocity distribution functions from the data. The D and T fuel densities and temperatures may also be obtainable by measurement of the respective ion cyclotron harmonic frequencies

Interleaved Parton Showers and Tuning Prospects

General-purpose Monte Carlo event generators have become important tools in particle physics, allowing the simulation of exclusive hadronic final states. In this article we examine the Pythia 8 generator, in particular focusing on its parton-shower algorithms. Some relevant new additions to the code are introduced, that should allow for a better description of data. We also implement and compare with 2 to 3 real-emission QCD matrix elements, to check how well the shower algorithm fills the phase space away from the soft and collinear regions. A tuning of the generator to Tevatron data is performed for two PDF sets and the impact of first new LHC data is examined

Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: A comparative risk assessment

Background: High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. Methods: We used data for exposure to risk factors by country, age group, and sex from pooled analyses of population-based health surveys. We obtained relative risks for the effects of risk factors on cause-specific mortality from meta-analyses of large prospective studies. We calculated the population attributable fractions for each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the effects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specific population attributable fractions by the number of disease-specific deaths. We obtained cause-specific mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the final estimates. Findings: In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10·8 million deaths, 95% CI 10·1-11·5) of deaths from these diseases in 2010 were attributable to the combined effect of these four metabolic risk factors, compared with 67% (7·1 million deaths, 6·6-7·6) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined effects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. Interpretation: The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing effect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the global response to non-communicable diseases. Funding: UK Medical Research Council, US National Institutes of Health. © 2014 Elsevier Ltd

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Reproducibility of p53 Immunohistochemistry in Bladder Tumors

The National Cancer Institute Bladder Tumor Marker Network conducted a study to evaluate the reproducibility of immunohistochemistry for measuring p53 expression in bladder tumors. Fifty paraffin blocks (10 from each of the five network institutions) were chosen at random from among high-grade invasive primary bladder tumors. Two sections from each block were sent to each laboratory for staining and scoring, and then all sections were randomly redistributed among the laboratories for a second scoring. Intra- and interlaboratory reproducibility was assessed with regard to both staining and scoring. For overall assessments of p53 positivity, the results demonstrated that intralaboratory reproducibility was quite good. Concordance across the five participating laboratories was high for specimens exhibiting no or minimal nuclear immunostaining of tumor cells or high percentages of tumor cells with nuclear immunoreactivities. However, there was a reduced level of concordance on specimens with percentages of stained tumor cells in an intermediate range. The discordancies were due mainly to staining differences in one of the five laboratories and scoring differences in another laboratory. These results indicate that some caution must be used in comparing results across studies from different groups. Standardization of staining protocols and selection of a uniform threshold for binary interpretation of results may improve assay reproducibility between laboratories

Serum Iron Levels and the Risk of Parkinson Disease: A Mendelian Randomization Study

Background:Although levels of iron are known to be increased in the brains of patients with Parkinson disease (PD), epidemiological evidence on a possible effect of iron blood levels on PD risk is inconclusive, with effects reported in opposite directions. Epidemiological studies suffer from problems of confounding and reverse causation, and mendelian randomization (MR) represents an alternative approach to provide unconfounded estimates of the effects of biomarkers on disease. We performed a MR study where genes known to modify iron levels were used as instruments to estimate the effect of iron on PD risk, based on estimates of the genetic effects on both iron and PD obtained from the largest sample meta-analyzed to date.Methods and Findings:We used as instrumental variables three genetic variants influencing iron levels, HFE rs1800562, HFE rs1799945, and TMPRSS6 rs855791. Estimates of their effect on serum iron were based on a recent genome-wide meta-analysis of 21,567 individuals, while estimates of their effect on PD risk were obtained through meta-analysis of genome-wide and candidate gene studies with 20,809 PD cases and 88,892 controls. Separate MR estimates of the effect of iron on PD were obtained for each variant and pooled by meta-analysis. We investigated heterogeneity across the three estimates as an indication of possible pleiotropy and found no evidence of it. The combined MR estimate showed a statistically significant protective effect of iron, with a relative risk reduction for PD of 3% (95% CI 1%-6%; p = 0.001) per 10 μg/dl increase in serum iron.Conclusions:Our study suggests that increased iron levels are causally associated with a decreased risk of developing PD. Further studies are needed to understand the pathophysiological mechanism of action of serum iron on PD risk before recommendations can be made.Please see later in the article for the Editors' Summary