Simulations of neutron background in a time projection chamber relevant to dark matter searches

Presented here are results of simulations of neutron background performed for a time projection chamber acting as a particle dark matter detector in an underground laboratory. The investigated background includes neutrons from rock and detector components, generated via spontaneous fission and (alpha, n) reactions, as well as those due to cosmic-ray muons. Neutrons were propagated to the sensitive volume of the detector and the nuclear recoil spectra were calculated. Methods of neutron background suppression were also examined and limitations to the sensitivity of a gaseous dark matter detector are discussed. Results indicate that neutrons should not limit sensitivity to WIMP-nucleon interactions down to a level of (1 - 3) x 10^{-8} pb in a 10 kg detector.Comment: 27 pages (total, including 3 tables and 11 figures). Accepted for publication in Nuclear Instruments and Methods in Physics Research - Section

Race, ethnicity and risk of second primary contralateral breast cancer in the United States

Breast cancer survivors have a high risk of a second primary contralateral breast cancer (CBC), but there are few studies of CBC risk in racial/ethnic minority populations. We examined whether the incidence and risk factors for CBC differed by race/ethnicity in the United States. Women with a first invasive Stage I-IIB breast cancer diagnosis at ages 20-74 years between 2000 and 2015 in the Surveillance, Epidemiology, and End Results Program (SEER) 18 registries were followed through 2016 for a diagnosis of invasive CBC ≥1 year after the first breast cancer diagnosis. We used cause-specific Cox proportional hazards models to test the association between race/ethnicity and CBC, adjusting for age, hormone receptor status, radiation therapy, chemotherapy and stage at first diagnosis, and evaluated the impact of contralateral prophylactic mastectomy, socioeconomic status, and insurance status on the association. After a median follow-up of 5.9 years, 9247 women (2.0%) were diagnosed with CBC. Relative to non-Hispanic (NH) White women, CBC risk was increased in NH Black women (hazard ratio = 1.44, 95% CI 1.35-1.54) and Hispanic women (1.11, 95% CI 1.02-1.20), with the largest differences among women diagnosed at younger ages. Adjustment for contralateral prophylactic mastectomy, socioeconomic status and health insurance did not explain the associations. Therefore, non-Hispanic Black and Hispanic women have an increased risk of CBC that is not explained by clinical or socioeconomic factors collected in SEER. Large studies of diverse breast cancer survivors with detailed data on treatment delivery and adherence are needed to inform interventions to reduce this disparity

Impact of the calcium form of β-hydroxy-β-methylbutyrate upon human skeletal muscle protein metabolism

Background & aims: β-hydroxy-β-methylbutyrate (HMB) is purported as a key nutritional supplement for the preservation of muscle mass in health, disease and as an ergogenic aid in exercise. Of the two available forms of HMB (calcium (Ca-HMB) salt or free acid (FA-HMB)) – differences in plasma bioavailability have been reported. We previously reported that ∼3 g oral FA-HMB increased muscle protein synthesis (MPS) and reduced muscle protein breakdown (MPB). The objective of the present study was to quantify muscle protein metabolism responses to oral Ca-HMB. Methods: Eight healthy young males received a primed constant infusion of 1,2 13C2 leucine and 2H5 phenylalanine to assess MPS (by tracer incorporation in myofibrils) and MPB (via arterio-venous (A-V) dilution) at baseline and following provision of ∼3 g of Ca-HMB; muscle anabolic (MPS) and catabolic (MPB) signalling was assessed via immunoblotting. Results: Ca-HMB led a significant and rapid (<60 min) peak in plasma HMB concentrations (483.6 ± 14.2 μM, p < 0.0001). This rise in plasma HMB was accompanied by increases in MPS (PA: 0.046 ± 0.004%/h, CaHMB: 0.072 ± 0.004%/h, p < 0001) and suppressions in MPB (PA: 7.6 ± 1.2 μmol Phe per leg min−1, Ca-HMB: 5.2 ± 0.8 μmol Phe per leg min−1, p < 0.01). Increases in the phosphorylation of mTORc1 substrates i.e. p70S6K1 and RPS6 were also observed, with no changes detected in the MPB targets measured. Conclusions: These findings support the pro-anabolic properties of HMB via mTORc1, and show that despite proposed differences in bioavailability, Ca-HMB provides a comparable stimulation to MPS and suppression of MPB, to FA-HMB, further supporting its use as a pharmaconutrient in the modulation of muscle mass

InBO3 and ScBO3 at high pressures: an ab initio study of elastic and thermodynamic properties

We have theoretically investigated the elastic properties of calcite-type orthoborates ABO(3) (A= Sc and In) at high pressure by means of ab initio total-energy calculations. From the elastic stiffness coefficients, we have obtained the elastic moduli (B, G and E), Poisson's ratio (nu), B/G ratio, universal elastic anisotropy index (A(U)), Vickers hardness, and sound wave velocities for both orthoborates. Our simulations show that both borates are more resistive to volume compression than to shear deformation (B > G). Both compounds are ductile and become more ductile, with an increasing elastic anisotropy, as pressure increases. We have also calculated some thermodynamic properties, like Debye temperature and minimum thermal conductivity. Finally, we have evaluated the theoretical mechanical stability of both borates at high hydrostatic pressures. It has been found that the calcite-type structure of InBO3 and ScBO3 becomes mechanically unstable at pressures beyond 56.2 and 57.7 GPa, respectively. (C) 2016 Elsevier Ltd. All rights reserved.This study is supported by the Spanish MICINN projects MAT2013-46649-C4-2-P/3-P and MAT2015-71070-REDC. H.M.O., A.M., and P.R-H. acknowledge computing time provided by Red Espanola de Supercomputacion (RES) and MALTA-Cluster. J.A.S. acknowledges Juan de la Cierva fellowship program for financial support.Gomis, O.; Ortiz, HM.; Sans Tresserras, JÁ.; Manjón Herrera, FJ.; Santamaría-Pérez, D.; Rodríguez-Hernández, P.; Muñoz, A. (2016). InBO3 and ScBO3 at high pressures: an ab initio study of elastic and thermodynamic properties. Journal of Physics and Chemistry of Solids. 98:198-208. https://doi.org/10.1016/j.jpcs.2016.07.002S1982089

The Sunrise Mission

The first science flight of the balloon-borne Sunrise telescope took place in June 2009 from ESRANGE (near Kiruna/Sweden) to Somerset Island in northern Canada. We describe the scientific aims and mission concept of the project and give an overview and a description of the various hardware components: the 1-m main telescope with its postfocus science instruments (the UV filter imager SuFI and the imaging vector magnetograph IMaX) and support instruments (image stabilizing and light distribution system ISLiD and correlating wavefront sensor CWS), the optomechanical support structure and the instrument mounting concept, the gondola structure and the power, pointing, and telemetry systems, and the general electronics architecture. We also explain the optimization of the structural and thermal design of the complete payload. The preparations for the science flight are described, including AIV and ground calibration of the instruments. The course of events during the science flight is outlined, up to the recovery activities. Finally, the in-flight performance of the instrumentation is discussed. © 2010 The Author(s)

Clinical, biochemical, and genetic spectrum of MADD in a South African cohort : an ICGNMD study

AVAILABILITY OF DATA AND MATERIALS : Previous data and samples were made available by the Centre for Human Metabolomics (NWU), SU, and UCT. New samples were collected with the help of paediatric and adult neurologists via Steve Biko Academic Hospital, Tygerberg Hospital, and Red Cross War Memorial Children’s Hospital. The datasets generated and/or analysed during the current study are not publicly available due to the data sharing policy of the ICGNMD study, but are available from the corresponding author on reasonable request.ADDITIONAL FILE 1 : Additional Clinical Information.ADDITIONAL FILE 2 : Additional Metabolic Information.ADDITIONAL FILE 3 : Additional Structural Information.BACKGROUND : Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder resulting from pathogenic variants in three distinct genes, with most of the variants occurring in the electron transfer flavoprotein-ubiquinone oxidoreductase gene (ETFDH). Recent evidence of potential founder variants for MADD in the South African (SA) population, initiated this extensive investigation. As part of the International Centre for Genomic Medicine in Neuromuscular Diseases study, we recruited a cohort of patients diagnosed with MADD from academic medical centres across SA over a three-year period. The aim was to extensively profile the clinical, biochemical, and genomic characteristics of MADD in this understudied population. METHODS : Clinical evaluations and whole exome sequencing were conducted on each patient. Metabolic profiling was performed before and after treatment, where possible. The recessive inheritance and phase of the variants were established via segregation analyses using Sanger sequencing. Lastly, the haplotype and allele frequencies were determined for the two main variants in the four largest SA populations. RESULTS : Twelve unrelated families (ten of White SA and two of mixed ethnicity) with clinically heterogeneous presentations in 14 affected individuals were observed, and five pathogenic ETFDH variants were identified. Based on disease severity and treatment response, three distinct groups emerged. The most severe and fatal presentations were associated with the homozygous c.[1067G > A];c.[1067G > A] and compound heterozygous c.[976G > C];c.[1067G > A] genotypes, causing MADD types I and I/II, respectively. These, along with three less severe compound heterozygous genotypes (c.[1067G > A];c.[1448C > T], c.[740G > T];c.[1448C > T], and c.[287dupA*];c.[1448C > T]), resulting in MADD types II/III, presented before the age of five years, depending on the time and maintenance of intervention. By contrast, the homozygous c.[1448C > T];c.[1448C > T] genotype, which causes MADD type III, presented later in life. Except for the type I, I/II and II cases, urinary metabolic markers for MADD improved/normalised following treatment with riboflavin and L-carnitine. Furthermore, genetic analyses of the most frequent variants (c.[1067G > A] and c.[1448C > T]) revealed a shared haplotype in the region of ETFDH, with SA population-specific allele frequencies of < 0.00067–0.00084%. CONCLUSIONS : This study reveals the first extensive genotype–phenotype profile of a MADD patient cohort from the diverse and understudied SA population. The pathogenic variants and associated variable phenotypes were characterised, which will enable early screening, genetic counselling, and patient-specific treatment of MADD in this population.Open access funding provided by North-West University. A Medical Research Council (MRC) strategic award; the National Research Foundation (NRF) of South Africa; the South African Medical Research Council (SAMRC); the Wellcome Centre for Mitochondrial Research; the Mitochondrial Disease Patient Cohort (UK); the Medical Research Council International Centre for Genomic Medicine in Neuromuscular Disease; the Lily Foundation; the UK NIHR Biomedical Research Centre for Ageing and Age-related Disease award to the Newcastle upon Tyne Foundation Hospitals NHS Trust; the UK NHS Highly Specialised Service for Rare Mitochondrial Disorders of Adults and Children; the MRC; Mito Foundation, and the Pathological Society (UK).https://ojrd.biomedcentral.comhj2024Paediatrics and Child HealthNon

Sputum and serum calprotectin are useful biomarkers during CF exacerbation

AbstractBackgroundAdequate monitoring of cystic fibrosis lung disease is difficult. CF exacerbation offers a unique setting to test the utility of biomarkers in the assessment of changing airways inflammation. We hypothesised that levels of calprotectin in sputum (and serum) would change informatively following treatment of an exacerbation.Methods27 patients with CF were recruited at onset of pulmonary exacerbation. Sputum and serum were collected at the start and end of anti-biotic therapy. Sputum calprotectin, interleukin-8 (IL8), and myeloperoxidase (MPO) were measured, as were serum calprotectin, CRP and vascular endothelial growth factor (VEGF).ResultsSputum calprotectin decreased following treatment of an exacerbation (p<0.05), and was superior to other sputum markers. Serum calprotectin, CRP, and VEGF also decreased significantly (p=0.002, p=0.002, p=0.013 respectively). Serum calprotectin level following treatment had predictive value for time to next exacerbation (p=0.032).ConclusionsThis study demonstrates the superiority of calprotectin (in sputum and serum) as a biomarker of CF exacerbation over better-established markers