122 research outputs found
Operation of a high purity germanium crystal in liquid argon as a Compton suppressed radiation spectrometer
A high purity germanium crystal was operated in liquid argon as a Compton
suppressed radiation spectrometer. Spectroscopic quality resolution of less
than 1% of the full-width half maximum of full energy deposition peaks was
demonstrated. The construction of the small apparatus used to obtain these
results is reported. The design concept is to use the liquid argon bath to both
cool the germanium crystal to operating temperatures and act as a scintillating
veto. The scintillation light from the liquid argon can veto cosmic-rays,
external primordial radiation, and gamma radiation that does not fully deposit
within the germanium crystal. This technique was investigated for its potential
impact on ultra-low background gamma-ray spectroscopy. This work is based on a
concept initially developed for future germanium-based neutrinoless double-beta
decay experiments.Comment: Paper presented at the SORMA XI Conference, Ann Arbor, MI, May 200
Effects of Chronic Hepatitis B Infection on Pregnancy and Birth Outcomes in Ghana
Ghana is a known endemic area for hepatitis B virus (HBV) infections, yet the consequences of HBV infection on pregnancy outcomes are unknown. This prospective cohort study was thus conducted among 512 pregnant women attending antenatal clinic in the Cape Coast Teaching Hospital, Ghana, between January, 2011 and December, 2013 to determine the effects of hepatitis B during pregnancy on birth outcomes in Ghana. The HBsAg status of all pregnant women was determined by the latex agglutination test while a researcher administered semi-structured checklist was used to collect demographic/obstetric/medical data of respondents. We obtained 262 HBsAg positive and 250 HBsAg negative women most of whom were aged 20-29 (40%), classified themselves as low income earners (50%), and had attained primary education (42%). Logistic regression analysis showed that pregnant women who had chronic hepatitis B were more likely to develop PROM (p=0.008) and foul smelling liquor (p=0.024) at delivery. Moreover, neonatal consequences for chronic hepatitis B were; preterm babies (p=0.002), underweight (p\u3c0.001), Apgar score lower than 7 (p\u3c0.001), asphyxia at birth (p=0.006) and still birth (p=0.04). We conclude that babies born to mothers with positive HBsAg status have a higher risk for vertical transmission as well as adverse neonatal consequences
Chemical carcinogenicity revisited 2: Current knowledge of carcinogenesis shows that categorization as a carcinogen or non-carcinogen is not scientifically credible
Abstract Developments in the understanding of the etiology of cancer have undermined the 1970s concept that chemicals are either "carcinogens" or "non-carcinogens". The capacity to induce cancer should not be classified in an inflexible binary manner as present (carcinogen) or absent (non-carcinogen). Chemicals may induce cancer by three categories of mode of action: direct interaction with DNA or DNA replication including DNA repair and epigenetics; receptor-mediated induction of cell division; and non-specific induction of cell division. The long-term rodent bioassay is neither appropriate nor efficient to evaluate carcinogenic potential for humans and to inform risk management decisions. It is of questionable predicitiveness, expensive, time consuming, and uses hundreds of animals. Although it has been embedded in practice for over 50 years, it has only been used to evaluate less than 5% of chemicals that are in use. Furthermore, it is not reproducible because of the probabilisitic nature of the process it is evaluating combined with dose limiting toxicity, dose selection, and study design. The modes of action that lead to the induction of tumors are already considered under other hazardous property categories in classification (Mutagenicity/Genotoxicity and Target Organ Toxicity); a separate category for Carcinogenicity is not required and provides no additional public health protection
Chemical carcinogenicity revisited 3: Risk assessment of carcinogenic potential based on the current state of knowledge of carcinogenesis in humans
Abstract Over 50 years, we have learned a great deal about the biology that underpins cancer but our approach to testing chemicals for carcinogenic potential has not kept up. Only a small number of chemicals has been tested in animal-intensive, time consuming, and expensive long-term bioassays in rodents. We now recommend a transition from the bioassay to a decision-tree matrix that can be applied to a broader range of chemicals, with better predictivity, based on the premise that cancer is the consequence of DNA coding errors that arise either directly from mutagenic events or indirectly from sustained cell proliferation. The first step is in silico and in vitro assessment for mutagenic (DNA reactive) activity. If mutagenic, it is assumed to be carcinogenic unless evidence indicates otherwise. If the chemical does not show mutagenic potential, the next step is assessment of potential human exposure compared to the threshold for toxicological concern (TTC). If potential human exposure exceeds the TTC, then testing is done to look for effects associated with the key characteristics that are precursors to the carcinogenic process, such as increased cell proliferation, immunosuppression, or significant estrogenic activity. Protection of human health is achieved by limiting exposures to below NOEALs for these precursor effects. The decision tree matrix is animal-sparing, cost effective, and in step with our growing knowledge of the process of cancer formation
Statistical Characterization of the Chandra Source Catalog
The first release of the Chandra Source Catalog (CSC) contains ~95,000 X-ray
sources in a total area of ~0.75% of the entire sky, using data from ~3,900
separate ACIS observations of a multitude of different types of X-ray sources.
In order to maximize the scientific benefit of such a large, heterogeneous
data-set, careful characterization of the statistical properties of the
catalog, i.e., completeness, sensitivity, false source rate, and accuracy of
source properties, is required. Characterization efforts of other, large
Chandra catalogs, such as the ChaMP Point Source Catalog (Kim et al. 2007) or
the 2 Mega-second Deep Field Surveys (Alexander et al. 2003), while
informative, cannot serve this purpose, since the CSC analysis procedures are
significantly different and the range of allowable data is much less
restrictive. We describe here the characterization process for the CSC. This
process includes both a comparison of real CSC results with those of other,
deeper Chandra catalogs of the same targets and extensive simulations of
blank-sky and point source populations.Comment: To be published in the Astrophysical Journal Supplement Series (Fig.
52 replaced with a version which astro-ph can convert to PDF without issues.
Chronic Beryllium Disease and Sensitization at a Beryllium Processing Facility
We conducted a medical screening for beryllium disease of 577 former workers from a beryllium processing facility. The screening included a medical and work history questionnaire, a chest radiograph, and blood lymphocyte proliferation testing for beryllium. A task exposure and a job exposure matrix were constructed to examine the association between exposure to beryllium and the development of beryllium disease. More than 90% of the cohort completed the questionnaire, and 74% completed the blood and radiograph component of the screening. Forty-four (7.6%) individuals had definite or probable chronic beryllium disease (CBD), and another 40 (7.0%) were sensitized to beryllium. The prevalence of CBD and sensitization in our cohort was greater than the prevalence reported in studies of other beryllium-exposed cohorts. Various exposure measures evaluated included duration; first decade worked; last decade worked; cumulative, mean, and highest job; and highest task exposure to beryllium (to both soluble and nonsoluble forms). Soluble cumulative and mean exposure levels were lower in individuals with CBD. Sensitized individuals had shorter duration of exposure, began work later, last worked longer ago, and had lower cumulative and peak exposures and lower nonsoluble cumulative and mean exposures. A possible explanation for the exposure–response findings of our study may be an interaction between genetic predisposition and a decreased permanence of soluble beryllium in the body. Both CBD and sensitization occurred in former workers whose mean daily working lifetime average exposures were lower than the current allowable Occupational Safety and Health Administration workplace air level of 2 μg/m(3) and the Department of Energy guideline of 0.2 μg/m(3)
Chemical carcinogenicity revisited 1: A unified theory of carcinogenicity based on contemporary knowledge
Abstract Developments in the understanding of the etiology of cancer have profound implications for the way the carcinogenicity of chemicals is addressed. This paper proposes a unified theory of carcinogenesis that will illuminate better ways to evaluate and regulate chemicals. In the last four decades, we have come to understand that for a cell and a group of cells to begin the process of unrestrained growth that is defined as cancer, there must be changes in DNA that reprogram the cell from normal to abnormal. Cancer is the consequence of DNA coding errors that arise either directly from mutagenic events or indirectly from cell proliferation especially if sustained. Chemicals that act via direct interaction with DNA can induce cancer because they cause mutations which can be carried forward in dividing cells. Chemicals that act via non-genotoxic mechanisms must be dosed to maintain a proliferative environment so that the steps toward neoplasia have time to occur. Chemicals that induce increased cellular proliferation can be divided into two categories: those which act by a cellular receptor to induce cellular proliferation, and those which act via non-specific mechanisms such as cytotoxicity. This knowledge has implications for testing chemicals for carcinogenic potential and risk management
The Chandra Source Catalog
The Chandra Source Catalog (CSC) is a general purpose virtual X-ray
astrophysics facility that provides access to a carefully selected set of
generally useful quantities for individual X-ray sources, and is designed to
satisfy the needs of a broad-based group of scientists, including those who may
be less familiar with astronomical data analysis in the X-ray regime. The first
release of the CSC includes information about 94,676 distinct X-ray sources
detected in a subset of public ACIS imaging observations from roughly the first
eight years of the Chandra mission. This release of the catalog includes point
and compact sources with observed spatial extents <~ 30''. The catalog (1)
provides access to the best estimates of the X-ray source properties for
detected sources, with good scientific fidelity, and directly supports
scientific analysis using the individual source data; (2) facilitates analysis
of a wide range of statistical properties for classes of X-ray sources; and (3)
provides efficient access to calibrated observational data and ancillary data
products for individual X-ray sources, so that users can perform detailed
further analysis using existing tools. The catalog includes real X-ray sources
detected with flux estimates that are at least 3 times their estimated 1 sigma
uncertainties in at least one energy band, while maintaining the number of
spurious sources at a level of <~ 1 false source per field for a 100 ks
observation. For each detected source, the CSC provides commonly tabulated
quantities, including source position, extent, multi-band fluxes, hardness
ratios, and variability statistics, derived from the observations in which the
source is detected. In addition to these traditional catalog elements, for each
X-ray source the CSC includes an extensive set of file-based data products that
can be manipulated interactively.Comment: To appear in The Astrophysical Journal Supplement Series, 53 pages,
27 figure
The XMM Cluster Survey: X-ray analysis methodology
The XMM Cluster Survey (XCS) is a serendipitous search for galaxy clusters
using all publicly available data in the XMM-Newton Science Archive. Its main
aims are to measure cosmological parameters and trace the evolution of X-ray
scaling relations. In this paper we describe the data processing methodology
applied to the 5,776 XMM observations used to construct the current XCS source
catalogue. A total of 3,675 > 4-sigma cluster candidates with > 50
background-subtracted X-ray counts are extracted from a total non-overlapping
area suitable for cluster searching of 410 deg^2. Of these, 993 candidates are
detected with > 300 background-subtracted X-ray photon counts, and we
demonstrate that robust temperature measurements can be obtained down to this
count limit. We describe in detail the automated pipelines used to perform the
spectral and surface brightness fitting for these candidates, as well as to
estimate redshifts from the X-ray data alone. A total of 587 (122) X-ray
temperatures to a typical accuracy of < 40 (< 10) per cent have been measured
to date. We also present the methodology adopted for determining the selection
function of the survey, and show that the extended source detection algorithm
is robust to a range of cluster morphologies by inserting mock clusters derived
from hydrodynamical simulations into real XMM images. These tests show that the
simple isothermal beta-profiles is sufficient to capture the essential details
of the cluster population detected in the archival XMM observations. The
redshift follow-up of the XCS cluster sample is presented in a companion paper,
together with a first data release of 503 optically-confirmed clusters.Comment: MNRAS accepted, 45 pages, 38 figures. Our companion paper describing
our optical analysis methodology and presenting a first set of confirmed
clusters has now been submitted to MNRA
Human and mouse essentiality screens as a resource for disease gene discovery
The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery. Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery
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