408 research outputs found

    Astronomical Data Management

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    We present a summary of the major contributions to the Special Session on Data Management held at the IAU General Assembly in Prague in 2006. While recent years have seen enormous improvements in access to astronomical data, and the Virtual Observatory aims to provide astronomers with seamless access to on-line resources, more attention needs to be paid to ensuring the quality and completeness of those resources. For example, data produced by telescopes are not always made available to the astronomical community, and new instruments are sometimes designed and built with insufficient planning for data management, while older but valuable legacy data often remain undigitised. Data and results published in journals do not always appear in the data centres, and astronomers in developing countries sometimes have inadequate access to on-line resources. To address these issues, an 'Astronomers Data Manifesto' has been formulated with the aim of initiating a discussion that will lead to the development of a 'code of best practice' in astronomical data management.Comment: Proceedings of Special Session SPS6 (Astronomical Data Management) at the IAU GA 2006. To appear in Highlights of Astronomy, Volume 14, ed. K.A. van der Huch

    Identification and characterization of an irreversible inhibitor of CDK2

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    Irreversible inhibitors that modify cysteine or lysine residues within a protein kinase ATP binding site offer, through their distinctive mode of action, an alternative to ATP-competitive agents. 4-((6-(Cyclohexylmethoxy)- 9H-purin-2-yl)amino)benzenesulfonamide (NU6102) is a potent and selective ATP-competitive inhibitor of CDK2 in which the sulfonamide moiety is positioned close to a pair of lysine residues. Guided by the CDK2/NU6102 structure, we designed 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl)phenyl)-9H-purin-2-amine (NU6300), which binds covalently to CDK2 as shown by a co-complex crystal structure. Acute incubation with NU6300 produced a durable inhibition of Rb phosphorylation in SKUT-1B cells, consistent with it acting as an irreversible CDK2 inhibitor. NU6300 is the first covalent CDK2 inhibitor to be described, and illustrates the potential of vinyl sulfones for the design of more potent and selective compounds

    Incorporating Concern for Health Equity Into Resource Allocation Decisions: Development of a Tool and Population-Based Valuation for Uganda.

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    OBJECTIVES: Health economic analyses that simultaneously address the concerns of increasing population health and reducing health inequalities require information on public preferences for using healthcare resources to reduce health inequalities and how this is valued relative to improving total population health. Previous research has quantified this preference in the form of an inequality aversion parameter in a specified social welfare function. This study aimed to elicit general population's views on health inequality and to estimate an inequality aversion parameter in Uganda. METHODS: Adult respondents from the general population were recruited and interviewed using survey adapted from an existing questionnaire, including trade-off questions between 2 hypothetical healthcare programs. Data on participants' demographic and socioeconomic characteristics and health-related quality of life measured by 5-level version of EQ-5D were collected. RESULTS: A nationally representative sample of 165 participants were included, with mean age of 37.1 years and mean 5-level version of EQ-5D at 0.836. Most respondents indicated willingness to trade-off some total population health to reduce health inequality. Translating the preferences into an Atkinson inequality aversion parameter (14.70) implies that health gain to the poorest 20% of people should be given approximately 6 times the weight of health gains to the richest 20%. CONCLUSIONS: Our study suggests it is feasible to adapt questionnaires of this type for a Ugandan population and this approach could be used to measure public aversion to health inequality in other settings. The elicited inequality aversion parameter can be used to support the assessment of health inequality impact in economic evaluation in Uganda

    DNA methylation among firefighters

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    Firefighters are exposed to carcinogens and have elevated cancer rates. We hypothesized that occupational exposures in firefighters would lead to DNA methylation changes associated with activation of cancer pathways and increased cancer risk. To address this hypothesis, we collected peripheral blood samples from 45 incumbent and 41 new recruit nonsmoking male firefighters and analyzed the samples for DNA methylation using an Illumina Methylation EPIC 850k chip. Adjusting for age and ethnicity, we performed: 1) genome-wide differential methylation analysis; 2) genome-wide prediction for firefighter status (incumbent or new recruit) and years of service; and 3) Ingenuity Pathway Analysis (IPA). Four CpGs, including three in the YIPF6, MPST, and PCED1B genes, demonstrated above 1.5-fold statistically significant differential methylation after Bonferroni correction. Genome-wide methylation predicted with high accuracy incumbent and new recruit status as well as years of service among incumbent firefighters. Using IPA, the top pathways with more than 5 gene members annotated from differentially methylated probes included Sirtuin signaling pathway, p53 signaling, and 5' AMP-activated protein kinase (AMPK) signaling. These DNA methylation findings suggest potential cellular mechanisms associated with increased cancer risk in firefighters.US Federal Emergency Management Agency Assistance to Firefighters Grant program [EMW-2014-FP-00200]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

    Comparative Field Evaluation of Combinations of Long-Lasting Insecticide Treated Nets and Indoor Residual Spraying, Relative to Either Method Alone, for Malaria Prevention in an Area where the main Vector is Anopheles Arabiensis.

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    Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are commonly used together in the same households to improve malaria control despite inconsistent evidence on whether such combinations actually offer better protection than nets alone or IRS alone. Comparative tests were conducted using experimental huts fitted with LLINs, untreated nets, IRS plus untreated nets, or combinations of LLINs and IRS, in an area where Anopheles arabiensis is the predominant malaria vector species. Three LLIN types, OlysetÂź, PermaNet 2.0Âź and Icon LifeÂź nets and three IRS treatments, pirimiphos-methyl, DDT, and lambda cyhalothrin, were used singly or in combinations. We compared, number of mosquitoes entering huts, proportion and number killed, proportions prevented from blood-feeding, time when mosquitoes exited the huts, and proportions caught exiting. The tests were done for four months in dry season and another six months in wet season, each time using new intact nets. All the net types, used with or without IRS, prevented >99% of indoor mosquito bites. Adding PermaNet 2.0Âź and Icon LifeÂź, but not OlysetÂź nets into huts with any IRS increased mortality of malaria vectors relative to IRS alone. However, of all IRS treatments, only pirimiphos-methyl significantly increased vector mortality relative to LLINs alone, though this increase was modest. Overall, median mortality of An. arabiensis caught in huts with any of the treatments did not exceed 29%. No treatment reduced entry of the vectors into huts, except for marginal reductions due to PermaNet 2.0Âź nets and DDT. More than 95% of all mosquitoes were caught in exit traps rather than inside huts. Where the main malaria vector is An. arabiensis, adding IRS into houses with intact pyrethroid LLINs does not enhance house-hold level protection except where the IRS employs non-pyrethroid insecticides such as pirimiphos-methyl, which can confer modest enhancements. In contrast, adding intact bednets onto IRS enhances protection by preventing mosquito blood-feeding (even if the nets are non-insecticidal) and by slightly increasing mosquito mortality (in case of LLINs). The primary mode of action of intact LLINs against An. arabiensis is clearly bite prevention rather than insecticidal activity. Therefore, where resources are limited, priority should be to ensure that everyone at risk consistently uses LLINs and that the nets are regularly replaced before being excessively torn. Measures that maximize bite prevention (e.g. proper net sizes to effectively cover sleeping spaces, stronger net fibres that resist tears and burns and net use practices that preserve net longevity), should be emphasized

    Temperature dependence of magnetic resonance probes for use as embedded sensors in constructed wetlands

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    Constructed wetlands are now accepted as an environmentally friendly means of wastewater treatment however, their effectiveness can be limited by excessive clogging of the pores within the gravel matrix, making this an important parameter to monitor. It has previously been shown that the clog state can be characterised using magnetic resonance (MR) relaxation parameters with permanent magnet based sensors. One challenge with taking MR measurements over a time scale on the order of years is that seasonal temperature fluctuations will alter both the way that the sensor operates as well as the relaxation times recorded. Without an understanding of how the sensor will behave under different temperature conditions, meaningful information about the clog state cannot be successfully extracted from a wetland. This work reports the effect of temperature on a permanent magnet based MR sensor to determine if the received signal intensity is significantly compromised as a result of large temperature changes, and whether meaningful relaxation data can be extracted over the temperature range of interest. To do this, the central magnetic field of the sensor was monitored as a function of temperature, showing an expected linear relationship. Signal intensity was measured over a range of temperatures (5 °C to 44 °C) for which deterioration at high and low temperatures compared to room temperature was observed. The sensor was still operable at the extremes of this range and the reason for the signal loss has been studied and explained. Spin-lattice relaxation time measurements using the sensor at different temperatures have also been taken on a water sample and seem to agree with literature values. Further to this, measurements have been taken in an operational wetland over the course of 203 days and have shown a linear dependence with temperature as would be expected. This work concluded that the sensor can perform the task of measuring the spin-lattice relaxation time over the required temperature range making it suitable for long-term application in constructed wetlands

    Quality of Neonatal Healthcare in Kilimanjaro Region, Northeast Tanzania: Learning from Mothers' Experiences.

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    With a decline of infant mortality rates, neonatal mortality rates are striking high in development countries particularly sub Saharan Africa. The toolkit for high quality neonatal services describes the principle of patient satisfaction, which we translate as mother's involvement in neonatal care and so better outcomes. The aim of the study was to assess mothers' experiences, perception and satisfaction of neonatal care in the hospitals of Kilimanjaro region of Tanzania. A cross sectional study using qualitative and quantitative approaches in 112 semi structured interviews from 14 health facilities. Open ended questions for detection of illness, care given to the baby and time spent by the health worker for care and treatment were studied. Probing of the responses was used to extract and describe findings by a mix of in-depth interview skills. Closed ended questions for the quantitative variables were used to quantify findings for statistical use. Narratives from open ended questions were coded by colours in excel sheet and themes were manually counted. 80 mothers were interviewed from 13 peripheral facilities and 32 mothers were interviewed at a zonal referral hospital of Kilimanjaro region. 59 mothers (73.8%) in the peripheral hospitals of the region noted neonatal problems and they assisted for attaining diagnosis after a showing a concern for a request for further investigations. 11 mothers (13.8%) were able to identify the baby's diagnosis directly without any assistance, followed by 7 mothers (8.7%) who were told by a relative, and 3 mothers (3.7%) who were told of the problem by the doctor that their babies needed medical attention. 24 times mothers in the peripheral hospitals reported bad language like "I don't have time to listen to you every day and every time." 77 mothers in the periphery (90.6%) were not satisfied with the amount of time spent by the doctors in seeing their babies. Mothers of the neonates play great roles in identifying the illness of the newborn. Mother's awareness of what might be needed during neonatal support strategies to improve neonatal care in both health facilities and the communities

    The Impact of Pandemic Influenza H1N1 on Health-Related Quality of Life: A Prospective Population-Based Study

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    BACKGROUND: While the H1N1v influenza pandemic in 2009 was clinically mild, with a low case-fatality rate, the overall disease burden measured in quality-adjusted life years (QALY) lost has not been estimated. Such a measure would allow comparison with other diseases and assessment of the cost-effectiveness of pandemic control measures. METHODS AND FINDINGS: Cases of H1N1v confirmed by polymerase chain reaction (PCR) and PCR negative cases with similar influenza-like illness (ILI controls) in 7 regions of England were sent two questionnaires, one within a week of symptom onset and one two weeks later, requesting information on duration of illness, work loss and antiviral use together with EQ-5D questionnaires. Results were compared with those for seasonal influenza from a systematic literature review. A total QALY loss for the 2009 pandemic in England was calculated based on the estimated total clinical cases and reported deaths. A total of 655 questionnaires were sent and 296 (45%) returned. Symptoms and average illness duration were similar between confirmed cases and ILI controls (8.8 days and 8.7 days respectively). Days off work were greater for cases than ILI controls (7.3 and 4.9 days respectively, p  =  0.003). The quality-adjusted life days lost was 2.92 for confirmed cases and 2.74 for ILI controls, with a reduction in QALY loss after prompt use of antivirals in confirmed cases. The overall QALY loss in the pandemic was estimated at 28,126 QALYs (22,267 discounted) of which 40% was due to deaths (24% with discounting). CONCLUSION: Given the global public health significance of influenza, it is remarkable that no previous prospective study of the QALY loss of influenza using standardised and well validated methods has been performed. Although the QALY loss was minor for individual patients, the estimated total burden of influenza over the pandemic was substantial when compared to other infectious diseases

    Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

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    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∌8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD
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