Modelling the bimodal distribution of indoor gamma-ray dose-rates in Great Britain

Gamma radiation from naturally occurring sources (including directly ionizing cosmic-rays) is a major component of background radiation. An understanding of the magnitude and variation of doses from these sources is important, and the ability to predict them is required for epidemiological studies. In the present paper, indoor measurements of naturally occurring gamma-rays at representative locations in Great Britain are summarized. It is shown that, although the individual measurement data appear unimodal, the distribution of gamma-ray dose-rates when averaged over relatively small areas, which probably better represents the underlying distribution with inter-house variation reduced, appears bimodal. The dose-rate distributions predicted by three empirical and geostatistical models are also bimodal and compatible with the distributions of the areally averaged dose-rates. The distribution of indoor gamma-ray dose-rates in the UK is compared with those in other countries, which also tend to appear bimodal (or possibly multimodal). The variation of indoor gamma-ray dose-rates with geology, socio-economic status of the area, building type, and period of construction are explored. The factors affecting indoor dose-rates from background gamma radiation are complex and frequently intertwined, but geology, period of construction, and socio-economic status are influential; the first is potentially most influential, perhaps, because it can be used as a general proxy for local building materials. Various statistical models are tested for predicting indoor gamma-ray dose-rates at unmeasured locations. Significant improvements over previous modelling are reported. The dose-rate estimates generated by these models reflect the imputed underlying distribution of dose-rates and provide acceptable predictions at geographical locations without measurements

The prognostic significance of low-frequency somatic mutations in metastatic cutaneous melanoma

Background: Little is known about the prognostic significance of somatically mutated genes in metastatic melanoma (MM). We have employed a combined clinical and bioinformatics approach on tumor samples from cutaneous melanoma (SKCM) as part of The Cancer Genome Atlas project (TCGA) to identify mutated genes with potential clinical relevance. Methods: After limiting our DNA sequencing analysis to MM samples (n = 356) and to the CANCER CENSUS gene list, we filtered out mutations with low functional significance (snpEFF). We performed Cox analysis on 53 genes that were mutated in ≥3% of samples, and had ≥50% difference in incidence of mutations in deceased subjects versus alive subjects. Results: Four genes were potentially prognostic [RAC1, FGFR1, CARD11, CIITA; false discovery rate (FDR) 75% of the samples that exhibited corresponding DNA mutations. The low frequency, UV signature type and RNA expression of the 22 genes in MM samples were confirmed in a separate multi-institution validation cohort (n = 413). An underpowered analysis within a subset of this validation cohort with available patient follow-up (n = 224) showed that somatic mutations in SPEN and RAC1 reached borderline prognostic significance [log-rank favorable (p = 0.09) and adverse (p = 0.07), respectively]. Somatic mutations in SPEN, and to a lesser extent RAC1, were not associated with definite gene copy number or RNA expression alterations. High (>2+) nuclear plus cytoplasmic expression intensity for SPEN was associated with longer melanoma-specific overall survival (OS) compared to lower (≤ 2+) nuclear intensity (p = 0.048). We conclude that expressed somatic mutations in infrequently mutated genes beyond the well-characterized ones (e.g., BRAF, RAS, CDKN2A, PTEN, TP53), such as RAC1 and SPEN, may have prognostic significance in MM

νi13/2 structures in 155Sm and 159Gd: Supporting evidence of a Z=60 deformed subshell gap

Maximal ground-state deformation should occur when both proton and neutron Fermi surfaces are located at midshell. However, subshell gaps that stabilize large deformation can exist at proton or neutron values other than midshell. One such gap may occur at Z=60 in the rare-earth region, as the energy of the first 2+ states in even-even nuclei are often lowest in an isotonic chain for neodymium (Z=60) rather than the midshell isotopes of dysprosium (Z=66). Further evidence of this deformed gap has now been observed by investigating the signature splitting systematics of the νi13/2 bands found in the odd-N, rare-earth nuclei. These were aided by the present observation of the νi13/2 band in Gd159 and the confirmation of the same structure in Sm155 via the transfer of a neutron from a Gd160 beam to a Sm154 target

Possible quenching of static neutron pairing near the N=98 deformed shell gap: Rotational structures in Gd 160,161

A Gd160 beam was accelerated to an energy of 1000 MeV and, separately, bombarded thick targets of Sm154 and Dy164 in order to observe neutron-rich, rare-earth nuclei via deep-inelastic collision processes. Gammasphere was utilized to observe ?-ray emissions. Many new states and transitions were observed in Gd160 as a result of so-called unsafe Coulomb excitation. The ground-state band in Gd160 has been extended to Ip=20+ and a rotational band based on the Kp=4+ state, previously associated with a hexadecapole vibration, was observed up to 18+. The quasiparticle configuration of the Kp=4+ band has been determined, and its unusual alignment behavior may result from a possible quenching of static neutron pairing. In addition, the band based on the [523]5/2 quasineutron orbital in Gd161 was extended from 11/2- to 33/2- and also displays the same unusual alignment behavior

Evidence for Rigid Triaxial Deformation in Ge 76 from a Model-Independent Analysis

An extensive, model-independent analysis of the nature of triaxial deformation in Ge76, a candidate for neutrinoless double-beta (0νββ) decay, was carried out following multistep Coulomb excitation. Shape parameters deduced on the basis of a rotational-invariant sum-rule analysis provided considerable insight into the underlying collectivity of the ground-state and γ bands. Both sequences were determined to be characterized by the same β and γ deformation parameter values. In addition, compelling evidence for low-spin, rigid triaxial deformation in Ge76 was obtained for the first time from the analysis of the statistical fluctuations of the quadrupole asymmetry deduced from the measured E2 matrix elements. These newly determined shape parameters are important input and constraints for calculations aimed at providing, with suitable accuracy, the nuclear matrix elements relevant to 0νββ

Diabetic gastroparesis: Therapeutic options

Gastroparesis is a condition characterized by delayed gastric emptying and the most common known underlying cause is diabetes mellitus. Symptoms include nausea, vomiting, abdominal fullness, and early satiety, which impact to varying degrees on the patient’s quality of life. Symptoms and deficits do not necessarily relate to each other, hence despite significant abnormalities in gastric emptying, some individuals have only minimal symptoms and, conversely, severe symptoms do not always relate to measures of gastric emptying. Prokinetic agents such as metoclopramide, domperidone, and erythromycin enhance gastric motility and have remained the mainstay of treatment for several decades, despite unwanted side effects and numerous drug interactions. Mechanical therapies such as endoscopic pyloric botulinum toxin injection, gastric electrical stimulation, and gastrostomy or jejunostomy are used in intractable diabetic gastroparesis (DG), refractory to prokinetic therapies. Mitemcinal and TZP-101 are novel investigational motilin receptor and ghrelin agonists, respectively, and show promise in the treatment of DG. The aim of this review is to provide an update on prokinetic and mechanical therapies in the treatment of DG

Stress testing and non-invasive coronary angiography in patients with suspected coronary artery disease: time for a new paradigm

Diagnosis and management of coronary artery disease represents major challenges to our health care system, affecting millions of patients each year. Until recently, the diagnosis of coronary artery disease was possible only through cardiac catheterization and invasive coronary angiography. To avoid the risks of an invasive procedure, stress testing is often employed for an initial assessment of patients with suspected coronary artery disease, serving as a gatekeeper for cardiac catheterization. With the emergence of non-invasive coronary angiography, the question arises if such a strategy is still sensible, particularly, in view of only a modest agreement between stress testing results and the presence of coronary artery disease established by cardiac catheterization. Much data in support of the diagnostic accuracy and prognostic value of non-invasive coronary angiography by computed tomography have emerged within the last few years. These data challenge the role of stress testing as the initial imaging modality in patients with suspected coronary artery disease. This article reviews the clinical utility, limitations, as well as the hazards of stress testing compared with non-invasive coronary artery imaging by computed tomography. Finally, the implications of this review are discussed in relation to clinical practice

Manufacturing flow line systems: a review of models and analytical results

The most important models and results of the manufacturing flow line literature are described. These include the major classes of models (asynchronous, synchronous, and continuous); the major features (blocking, processing times, failures and repairs); the major properties (conservation of flow, flow rate-idle time, reversibility, and others); and the relationships among different models. Exact and approximate methods for obtaining quantitative measures of performance are also reviewed. The exact methods are appropriate for small systems. The approximate methods, which are the only means available for large systems, are generally based on decomposition, and make use of the exact methods for small systems. Extensions are briefly discussed. Directions for future research are suggested.National Science Foundation (U.S.) (Grant DDM-8914277