Phonon Quasidiffusion in Cryogenic Dark Matter Search Large Germanium Detectors

We present results on quasidiffusion studies in large, 3 inch diameter, 1 inch thick [100] high purity germanium crystals, cooled to 50 mK in the vacuum of a dilution refrigerator, and exposed with 59.5 keV gamma-rays from an Am-241 calibration source. We compare data obtained in two different detector types, with different phonon sensor area coverage, with results from a Monte Carlo. The Monte Carlo includes phonon quasidiffusion and the generation of phonons created by charge carriers as they are drifted across the detector by ionization readout channels.Comment: 13 pages, 12 figures, PHONONS201 conference proceedings; http://psroc.phys.ntu.edu.tw/cjp/download.php?d=4&pid=271

Rare and common genetic determinants of metabolic individuality and their effects on human health

Garrod’s concept of ‘chemical individuality’ has contributed to comprehension of the molecular origins of human diseases. Untargeted high-throughput metabolomic technologies provide an in-depth snapshot of human metabolism at scale. We studied the genetic architecture of the human plasma metabolome using 913 metabolites assayed in 19,994 individuals and identified 2,599 variant–metabolite associations (P < 1.25 × 10−11) within 330 genomic regions, with rare variants (minor allele frequency ≤ 1%) explaining 9.4% of associations. Jointly modeling metabolites in each region, we identified 423 regional, co-regulated, variant–metabolite clusters called genetically influenced metabotypes. We assigned causal genes for 62.4% of these genetically influenced metabotypes, providing new insights into fundamental metabolite physiology and clinical relevance, including metabolite-guided discovery of potential adverse drug effects (DPYD and SRD5A2). We show strong enrichment of inborn errors of metabolism-causing genes, with examples of metabolite associations and clinical phenotypes of non-pathogenic variant carriers matching characteristics of the inborn errors of metabolism. Systematic, phenotypic follow-up of metabolite-specific genetic scores revealed multiple potential etiological relationships

Doubtful outcome of the validation of the Rome II questionnaire: validation of a symptom based diagnostic tool

<p>Abstract</p> <p>Background</p> <p>Questionnaires are used in research and clinical practice. For gastrointestinal complaints the Rome II questionnaire is internationally known but not validated. The aim of this study was to validate a printed and a computerized version of Rome II, translated into Swedish. Results from various analyses are reported.</p> <p>Methods</p> <p>Volunteers from a population based colonoscopy study were included (n = 1011), together with patients seeking general practice (n = 45) and patients visiting a gastrointestinal specialists' clinic (n = 67). The questionnaire consists of 38 questions concerning gastrointestinal symptoms and complaints. Diagnoses are made after a special code. Our validation included analyses of the translation, feasibility, predictability, reproducibility and reliability. Kappa values and overall agreement were measured. The factor structures were confirmed using a principal component analysis and Cronbach's alpha was used to test the internal consistency.</p> <p>Results and Discussion</p> <p>Translation and back translation showed good agreement. The questionnaire was easy to understand and use. The reproducibility test showed kappa values of 0.60 for GERS, 0.52 for FD, and 0.47 for IBS. Kappa values and overall agreement for the predictability when the diagnoses by the questionnaire were compared to the diagnoses by the clinician were 0.26 and 90% for GERS, 0.18 and 85% for FD, and 0.49 and 86% for IBS. Corresponding figures for the agreement between the printed and the digital version were 0.50 and 92% for GERS, 0.64 and 95% for FD, and 0.76 and 95% for IBS. Cronbach's alpha coefficient for GERS was 0.75 with a span per item of 0.71 to 0.76. For FD the figures were 0.68 and 0.54 to 0.70 and for IBS 0.61 and 0.56 to 0.66. The Rome II questionnaire has never been thoroughly validated before even if diagnoses made by the Rome criteria have been compared to diagnoses made in clinical practice.</p> <p>Conclusion</p> <p>The accuracy of the Swedish version of the Rome II is of doubtful value for clinical practice and research. The results for reproducibility and reliability were acceptable but the outcome of the predictability test was poor with IBS as an exception. The agreement between the digital and the paper questionnaire was good.</p

Meeting the stakeholder needs and sustaining business through sustainability risk management practices: A case study of Malaysian environmentally sensitive companies

Sustainability issues such as climate change, carbon emissions, and energy consumption have become increasingly important issues among business organisations, academics and policy makers. Considering this complexity, stakeholders currently demanding companies to have a sound risk management that are aligned to their interest. Sustaining business requires a strong foundational on the economic, environmental and social aspects to address risks and capture value. Sustainability risk management (SRM) is a process that systematically integrates environmental, social, and economic aspects to address emerging risks and other non-quantifiable risk for company survival. This study aims to examine the impact of SRM practices on the company survival among the environmentally sensitive companies in Malaysia. A case study was carried out to examine the SRM implementation among the environmentally sensitive companies. The finding shows that leadership and compliance are considered as important factors in implementing SRM programme. Other factors such as sound risk culture, adequate risk management tools, and effective business continuity planning are crucial to support SRM implementation. Overall findings revealthat the companies are at the early stage implementing SRM programme and denote there is much room for improvement in the risk management process to create long-term value creation for the stakeholders. This study provides empirical evidence on the significance of SRM factors to the company survival. Given the huge environmental and social costs arising from sustainability issues, companies should intensify their effort to fully implement SRM programme across the organisation to sustain longer

SDSS spectroscopic survey of stars

In addition to optical photometry of unprecedented quality, the Sloan Digital Sky Survey (SDSS) is also producing a massive spectroscopic database. They discuss determination of stellar parameters, such as effective temperature, gravity and metallicity from SDSS spectra, describe correlations between kinematics and metallicity, and study their variation as a function of the position in the Galaxy. They show that stellar parameter estimates by Beers et al. show a good correlation with the position of a star in the g-r vs. u-g color-color diagram, thereby demonstrating their robustness as well as a potential for photometric parameter estimation methods. Using Beers et al. parameters, they find that the metallicity distribution of the Milky Way stars at a few kpc from the galactic plane is bimodal with a local minimum at [Z/Z{sub {circle_dot}}] {approx} -1.3. The median metallicity for the low-metallicity [Z/Z{sub {circle_dot}}] &lt; =1.3 subsample is nearly independent of Galactic cylindrical coordinates R and z, while it decreases with z for the high-metallicity [Z/Z{sub {circle_dot}}] &gt; -1.3 sample. they also find that the low-metallicity sample has {approx} 2.5 times larger velocity dispersion and that it does not rotate (at the {approx} 10 km/s level), while the rotational velocity of the high-metallicity sample decreases smoothly with the height above the galactic plane

Identification of rare loss-of-function genetic variation regulating body fat distribution

This is the final version. Available on open access from Oxford University Press via the DOI in this recordData Availability: This research was conducted using the UK Biobank resource (application Nos. 44448 and 9905). Access to the UK Biobank genotype and phenotype data is open to all approved health researchers (http://www.ukbiobank.ac.uk/).CONTEXT: Biological and translational insights from large-scale, array-based genetic studies of fat distribution, a key determinant of metabolic health, have been limited by the difficulty in linking predominantly non-coding variants to specific gene targets. Rare coding variant analyses provide greater confidence that a specific gene is involved, but do not necessarily indicate whether gain or loss-of-function (LoF) would be of most therapeutic benefit. OBJECTIVE, DESIGN AND SETTING: To identify genes/proteins involved in determining fat distribution, we combined the power of genome-wide analysis of array-based rare, non-synonymous variants in 450,562 individuals of UK Biobank with exome-sequence-based rare loss of function gene burden testing in 184,246 individuals. RESULTS: The data indicates that loss-of-function of four genes (PLIN1 [LoF variants, p=5.86×10 -7], INSR [LoF variants, p=6.21×10 -7], ACVR1C [LoF + Moderate impact variants, p=1.68×10 -7; Moderate impact variants, p=4.57×10 -7] and PDE3B [LoF variants, p=1.41×10 -6]) is associated with a beneficial impact on WHRadjBMI and increased gluteofemoral fat mass, whereas LoF of PLIN4 [LoF variants, p=5.86×10 -7] adversely affects these parameters. Phenotypic follow-up suggests that LoF of PLIN1, PDE3B and ACVR1C favourably affects metabolic phenotypes (e.g. triglyceride [TG] and HDL cholesterol concentrations) and reduces the risk of cardiovascular disease, whereas PLIN4 LoF has adverse health consequences. INSR LoF is associated with lower TG and HDL levels but may increase the risk of type 2 diabetes. CONCLUSION: This study robustly implicates these genes in the regulation of fat distribution, providing new and in some cases somewhat counter-intuitive insight into the potential consequences of targeting these molecules therapeutically.Medical Research Council (MRC)National Institute for Health Research (NIHR)Wellcome TrustResearch Englan

Performance of the PEP-II B-Factory Collider at SLAC

PEP-II is an e{sup +}e{sup -} asymmetric B-Factory Collider located at SLAC operating at the Upsilon 4S resonance (3.1 GeV x 9 GeV). It has reached a luminosity of 9.21 x 10{sup 33}/cm{sup 2}/s and has delivered an integrated luminosity of 710 pb{sup -1} in one day. PEP-II has delivered, over the past six years, an integrated luminosity to the BaBar detector of over 262 fb{sup -1}. PEP-II operates in continuous injection mode for both beams boosting the integrated luminosity. The peak positron current has reached 2.45 A in 1588 bunches. Steady progress is being made in reaching higher luminosity. The goal over the next several years is to reach a luminosity of 2.1 x 10{sup 34}/cm{sup 2}/s. The accelerator physics issues being addressed in PEP-II to reach this goal include the electron cloud instability, beam-beam effects, parasitic beam-beam effects, high RF beam loading, shorter bunches, lower {beta}*{sub y} interaction region operation, and coupling control. Figure 1 shows the PEP-II tunnel

Rare and common genetic determinants of metabolic individuality and their effects on human health

Garrod’s concept of ‘chemical individuality’ has contributed to comprehension of the molecular origins of human diseases. Untargeted high-throughput metabolomic technologies provide an in-depth snapshot of human metabolism at scale. We studied the genetic architecture of the human plasma metabolome using 913 metabolites assayed in 19,994 individuals and identified 2,599 variant–metabolite associations (P < 1.25 × 10−11) within 330 genomic regions, with rare variants (minor allele frequency ≤ 1%) explaining 9.4% of associations. Jointly modeling metabolites in each region, we identified 423 regional, co-regulated, variant–metabolite clusters called genetically influenced metabotypes. We assigned causal genes for 62.4% of these genetically influenced metabotypes, providing new insights into fundamental metabolite physiology and clinical relevance, including metabolite-guided discovery of potential adverse drug effects (DPYD and SRD5A2). We show strong enrichment of inborn errors of metabolism-causing genes, with examples of metabolite associations and clinical phenotypes of non-pathogenic variant carriers matching characteristics of the inborn errors of metabolism. Systematic, phenotypic follow-up of metabolite-specific genetic scores revealed multiple potential etiological relationships

Performance of a Nanometer Resolution BPM System

International Linear Collider (ILC) interaction region beam sizes and component position stability requirements will be as small as a few nanometers. It is important to the ILC design effort to demonstrate that these tolerances can be achieved ideally using beam-based stability measurements. It has been estimated that RF cavity beam position monitors (BPMs) could provide position measurement resolutions of less than one nanometer and could form the basis of the desired beam-based stability measurement. We have developed a high resolution RF cavity BPM system. A triplet of these BPMs has been installed in the extraction line of the KEK Accelerator Test Facility (ATF) for testing with its ultra-low emittance beam. The three BPMs are rigidly mounted inside an alignment frame on variable-length struts which allow movement in position and angle. We have developed novel methods for extracting the position and tilt information from the BPM signals including a calibration algorithm which is immune to beam jitter. To date, we have been able to demonstrate a resolution of approximately 20 nm over a dynamic range of +/- 20 microns. We report on the progress of these ongoing tests