170 research outputs found

    Mass hierarchy discrimination with atmospheric neutrinos in large volume ice/water Cherenkov detectors

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    Large mass ice/water Cherenkov experiments, optimized to detect low energy (1-20 GeV) atmospheric neutrinos, have the potential to discriminate between normal and inverted neutrino mass hierarchies. The sensitivity depends on several model and detector parameters, such as the neutrino flux profile and normalization, the Earth density profile, the oscillation parameter uncertainties, and the detector effective mass and resolution. A proper evaluation of the mass hierarchy discrimination power requires a robust statistical approach. In this work, the Toy Monte Carlo, based on an extended unbinned likelihood ratio test statistic, was used. The effect of each model and detector parameter, as well as the required detector exposure, was then studied. While uncertainties on the Earth density and atmospheric neutrino flux profiles were found to have a minor impact on the mass hierarchy discrimination, the flux normalization, as well as some of the oscillation parameter (\Delta m^2_{31}, \theta_{13}, \theta_{23}, and \delta_{CP}) uncertainties and correlations resulted critical. Finally, the minimum required detector exposure, the optimization of the low energy threshold, and the detector resolutions were also investigated.Comment: 23 pages, 16 figure

    Comparison of machine learning and semi-quantification algorithms for (I123)FP-CIT classification: the beginning of the end for semi-quantification?

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    Background Semi-quantification methods are well established in the clinic for assisted reporting of (I123) Ioflupane images. Arguably, these are limited diagnostic tools. Recent research has demonstrated the potential for improved classification performance offered by machine learning algorithms. A direct comparison between methods is required to establish whether a move towards widespread clinical adoption of machine learning algorithms is justified. This study compared three machine learning algorithms with that of a range of semi-quantification methods, using the Parkinson’s Progression Markers Initiative (PPMI) research database and a locally derived clinical database for validation. Machine learning algorithms were based on support vector machine classifiers with three different sets of features: Voxel intensities Principal components of image voxel intensities Striatal binding radios from the putamen and caudate. Semi-quantification methods were based on striatal binding ratios (SBRs) from both putamina, with and without consideration of the caudates. Normal limits for the SBRs were defined through four different methods: Minimum of age-matched controls Mean minus 1/1.5/2 standard deviations from age-matched controls Linear regression of normal patient data against age (minus 1/1.5/2 standard errors) Selection of the optimum operating point on the receiver operator characteristic curve from normal and abnormal training data Each machine learning and semi-quantification technique was evaluated with stratified, nested 10-fold cross-validation, repeated 10 times. Results The mean accuracy of the semi-quantitative methods for classification of local data into Parkinsonian and non-Parkinsonian groups varied from 0.78 to 0.87, contrasting with 0.89 to 0.95 for classifying PPMI data into healthy controls and Parkinson’s disease groups. The machine learning algorithms gave mean accuracies between 0.88 to 0.92 and 0.95 to 0.97 for local and PPMI data respectively. Conclusions Classification performance was lower for the local database than the research database for both semi-quantitative and machine learning algorithms. However, for both databases, the machine learning methods generated equal or higher mean accuracies (with lower variance) than any of the semi-quantification approaches. The gain in performance from using machine learning algorithms as compared to semi-quantification was relatively small and may be insufficient, when considered in isolation, to offer significant advantages in the clinical context

    Ethnic Differences in Leaving Home: Timing and Pathways

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    The dynamics of leaving home for youth from migrant families in the Netherlands are examined using individual administrative data on the 1977 and 1983 birth cohorts for the period 1999–2004. A competing-risks approach is applied to distinguish leaving home for union formation, to live independently, and to share with others. Migrant youth, and particularly Turkish and Moroccan youth, leave home at a significantly younger age than Dutch youth, given the relevant background variables. This is remarkable, given the older ages at which young people in the origin countries leave the parental home. The result may be seen as evidence of how the potential effects of cultural norms are counter-affected by other factors, such as the facilities of the welfare state and the awkward position of migrant youth between two cultures. Considering the pathways out of home, the analysis largely confirms the expected pattern: Turkish and Moroccan youth leave home more often for union formation and particularly marriage, while this pathway is of minor importance for Dutch youth at early ages

    Role of RecA and the SOS Response in Thymineless Death in Escherichia coli

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    Thymineless death (TLD) is a classic and enigmatic phenomenon, documented in bacterial, yeast, and human cells, whereby cells lose viability rapidly when deprived of thymine. Despite its being the essential mode of action of important chemotherapeutic agents, and despite having been studied extensively for decades, the basic mechanisms of TLD have remained elusive. In Escherichia coli, several proteins involved in homologous recombination (HR) are required for TLD, however, surprisingly, RecA, the central HR protein and activator of the SOS DNA–damage response was reported not to be. We demonstrate that RecA and the SOS response are required for a substantial fraction of TLD. We show that some of the Rec proteins implicated previously promote TLD via facilitating activation of the SOS response and that, of the roughly 40 proteins upregulated by SOS, SulA, an SOS–inducible inhibitor of cell division, accounts for most or all of how SOS causes TLD. The data imply that much of TLD results from an irreversible cell-cycle checkpoint due to blocked cell division. FISH analyses of the DNA in cells undergoing TLD reveal blocked replication and apparent DNA loss with the region near the replication origin underrepresented initially and the region near the terminus lost later. Models implicating formation of single-strand DNA at blocked replication forks, a SulA-blocked cell cycle, and RecQ/RecJ-catalyzed DNA degradation and HR are discussed. The data predict the importance of DNA damage-response and HR networks to TLD and chemotherapy resistance in humans

    Spatial Variation in Foraging Behaviour of a Marine Top Predator (Phoca vitulina) Determined by a Large-Scale Satellite Tagging Program

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    The harbour seal (Phoca vitulina) is a widespread marine predator in Northern Hemisphere waters. British populations have been subject to rapid declines in recent years. Food supply or inter-specific competition may be implicated but basic ecological data are lacking and there are few studies of harbour seal foraging distribution and habits. In this study, satellite tagging conducted at the major seal haul outs around the British Isles showed both that seal movements were highly variable among individuals and that foraging strategy appears to be specialized within particular regions. We investigated whether these apparent differences could be explained by individual level factors: by modelling measures of trip duration and distance travelled as a function of size, sex and body condition. However, these were not found to be good predictors of foraging trip duration or distance, which instead was best predicted by tagging region, time of year and inter-trip duration. Therefore, we propose that local habitat conditions and the constraints they impose are the major determinants of foraging movements. Specifically the distance to profitable feeding grounds from suitable haul-out locations may dictate foraging strategy and behaviour. Accounting for proximity to productive foraging resources is likely to be an important component of understanding population processes. Despite more extensive offshore movements than expected, there was also marked fidelity to the local haul-out region with limited connectivity between study regions. These empirical observations of regional exchange at short time scales demonstrates the value of large scale electronic tagging programs for robust characterization of at-sea foraging behaviour at a wide spatial scale

    The human capital transition and the role of policy

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    Along with information and communication technology, infrastructure, and the innovation system, human capital is a key pillar of the knowledge economy with its scope for increasing returns. With this in mind, the purpose of this chapter is to investigate how industrialized economies managed to achieve the transition from low to high levels of human capital. The first phase of the human capital transition was the result of the interaction of supply and demand, triggered by technological change and boosted by the demands for (immaterial) services. The second phase of the human capital transition (i.e., mass education) resulted from enforced legislation and major public investment. The state’s aim to influence children’s beliefs appears to have been a key driver in public investment. Nevertheless, the roles governments played differed according to the developmental status and inherent socioeconomic and political characteristics of their countries. These features of the human capital transition highlight the importance of understanding governments’ incentives and roles in transitions

    Smoking prevalence and attributable disease burden in 195 countries and territories, 1990-2015 : a systematic analysis from the Global Burden of Disease Study 2015

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    Background The scale-up of tobacco control, especially after the adoption of the Framework Convention for Tobacco Control, is a major public health success story. Nonetheless, smoking remains a leading risk for early death and disability worldwide, and therefore continues to require sustained political commitment. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) offers a robust platform through which global, regional, and national progress toward achieving smoking-related targets can be assessed. Methods We synthesised 2818 data sources with spatiotemporal Gaussian process regression and produced estimates of daily smoking prevalence by sex, age group, and year for 195 countries and territories from 1990 to 2015. We analysed 38 risk-outcome pairs to generate estimates of smoking-attributable mortality and disease burden, as measured by disability-adjusted life-years (DALYs). We then performed a cohort analysis of smoking prevalence by birth-year cohort to better understand temporal age patterns in smoking. We also did a decomposition analysis, in which we parsed out changes in all-cause smoking-attributable DALYs due to changes in population growth, population ageing, smoking prevalence, and risk-deleted DALY rates. Finally, we explored results by level of development using the Socio-demographic Index (SDI). Findings Worldwide, the age-standardised prevalence of daily smoking was 25.0% (95% uncertainty interval [UI] 24.2-25.7) for men and 5.4% (5.1-5.7) for women, representing 28.4% (25.8-31.1) and 34.4% (29.4-38.6) reductions, respectively, since 1990. A greater percentage of countries and territories achieved significant annualised rates of decline in smoking prevalence from 1990 to 2005 than in between 2005 and 2015; however, only four countries had significant annualised increases in smoking prevalence between 2005 and 2015 (Congo [Brazzaville] and Azerbaijan for men and Kuwait and Timor-Leste for women). In 2015, 11.5% of global deaths (6.4 million [95% UI 5.7-7.0 million]) were attributable to smoking worldwide, of which 52.2% took place in four countries (China, India, the USA, and Russia). Smoking was ranked among the five leading risk factors by DALYs in 109 countries and territories in 2015, rising from 88 geographies in 1990. In terms of birth cohorts, male smoking prevalence followed similar age patterns across levels of SDI, whereas much more heterogeneity was found in age patterns for female smokers by level of development. While smoking prevalence and risk-deleted DALY rates mostly decreased by sex and SDI quintile, population growth, population ageing, or a combination of both, drove rises in overall smoking-attributable DALYs in low-SDI to middle-SDI geographies between 2005 and 2015. Interpretation The pace of progress in reducing smoking prevalence has been heterogeneous across geographies, development status, and sex, and as highlighted by more recent trends, maintaining past rates of decline should not be taken for granted, especially in women and in low-SDI to middle-SDI countries. Beyond the effect of the tobacco industry and societal mores, a crucial challenge facing tobacco control initiatives is that demographic forces are poised to heighten smoking's global toll, unless progress in preventing initiation and promoting cessation can be substantially accelerated. Greater success in tobacco control is possible but requires effective, comprehensive, and adequately implemented and enforced policies, which might in turn require global and national levels of political commitment beyond what has been achieved during the past 25 years.Peer reviewe
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