2,705 research outputs found

    Demographic and epidemiological characteristics of major regions, 1990-2001

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    In an era when most societies are coping with greater demand for health resources, choices will have to be made about the provision of health services. Strategic health planning must take into account the comparative burden of diseases and injuries, and the risk factors that cause them, and how this burden is likely to change under various policies and interventions. The Global Burden of Disease (GBD) framework is the principal, if not the only, framework for integrating and analyzing information on population health and making it more relevant for health policy and planning purposes. The comprehensive findings of the 2001 GBD study represent a major update of the effort launched with the 1990 GBD study. The 1990 GBD study was a major advance in the quantification of the impact of diseases, injuries, and risk factors on population health globally and by region. Government and nongovernmental agencies alike have used its results to argue for more strategic allocation of health resources to programs that are likely to yield the greatest gains in population health. Publication of the 1990 results led to improvements in analytical methods and mortality data in a number of countries. In addition, critiques of methodological approaches used in the 1990 study prompted a new framework for risk factor assessment along with systematic attempts to quantify some of the uncertainty in national and global assessments of disease burden. The 2001 GBD provides a new and improved baseline for measuring progress in global health

    Nanoinformatics: developing new computing applications for nanomedicine

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    Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended ?nanotype? to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others

    A giant comet-like cloud of hydrogen escaping the warm Neptune-mass exoplanet GJ 436b

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    Exoplanets orbiting close to their parent stars could lose some fraction of their atmospheres because of the extreme irradiation. Atmospheric mass loss primarily affects low-mass exoplanets, leading to suggest that hot rocky planets might have begun as Neptune-like, but subsequently lost all of their atmospheres; however, no confident measurements have hitherto been available. The signature of this loss could be observed in the ultraviolet spectrum, when the planet and its escaping atmosphere transit the star, giving rise to deeper and longer transit signatures than in the optical spectrum. Here we report that in the ultraviolet the Neptune-mass exoplanet GJ 436b (also known as Gliese 436b) has transit depths of 56.3 +/- 3.5% (1 sigma), far beyond the 0.69% optical transit depth. The ultraviolet transits repeatedly start ~2 h before, and end >3 h after the ~1 h optical transit, which is substantially different from one previous claim (based on an inaccurate ephemeris). We infer from this that the planet is surrounded and trailed by a large exospheric cloud composed mainly of hydrogen atoms. We estimate a mass-loss rate in the range of ~10^8-10^9 g/s, which today is far too small to deplete the atmosphere of a Neptune-like planet in the lifetime of the parent star, but would have been much greater in the past.Comment: Published in Nature on 25 June 2015. Preprint is 28 pages, 12 figures, 2 table

    Clinical trial of laronidase in Hurler syndrome after hematopoietic cell transplantation.

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    BackgroundMucopolysaccharidosis I (MPS IH) is a lysosomal storage disease treated with hematopoietic cell transplantation (HCT) because it stabilizes cognitive deterioration, but is insufficient to alleviate all somatic manifestations. Intravenous laronidase improves somatic burden in attenuated MPS I. It is unknown whether laronidase can improve somatic disease following HCT in MPS IH. The objective of this study was to evaluate the effects of laronidase on somatic outcomes of patients with MPS IH previously treated with HCT.MethodsThis 2-year open-label pilot study of laronidase included ten patients (age 5-13 years) who were at least 2 years post-HCT and donor engrafted. Outcomes were assessed semi-annually and compared to historic controls.ResultsThe two youngest participants had a statistically significant improvement in growth compared to controls. Development of persistent high-titer anti-drug antibodies (ADA) was associated with poorer 6-min walk test (6MWT) performance; when patients with high ADA titers were excluded, there was a significant improvement in the 6MWT in the remaining seven patients.ConclusionsLaronidase seemed to improve growth in participants <8 years old, and 6MWT performance in participants without ADA. Given the small number of patients treated in this pilot study, additional study is needed before definitive conclusions can be made

    A rocky planet transiting a nearby low-mass star

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    M-dwarf stars -- hydrogen-burning stars that are smaller than 60 per cent of the size of the Sun -- are the most common class of star in our Galaxy and outnumber Sun-like stars by a ratio of 12:1. Recent results have shown that M dwarfs host Earth-sized planets in great numbers: the average number of M-dwarf planets that are between 0.5 to 1.5 times the size of Earth is at least 1.4 per star. The nearest such planets known to transit their star are 39 parsecs away, too distant for detailed follow-up observations to measure the planetary masses or to study their atmospheres. Here we report observations of GJ 1132b, a planet with a size of 1.2 Earth radii that is transiting a small star 12 parsecs away. Our Doppler mass measurement of GJ 1132b yields a density consistent with an Earth-like bulk composition, similar to the compositions of the six known exoplanets with masses less than six times that of the Earth and precisely measured densities. Receiving 19 times more stellar radiation than the Earth, the planet is too hot to be habitable but is cool enough to support a substantial atmosphere, one that has probably been considerably depleted of hydrogen. Because the host star is nearby and only 21 per cent the radius of the Sun, existing and upcoming telescopes will be able to observe the composition and dynamics of the planetary atmosphere.Comment: Published in Nature on 12 November 2015, available at http://dx.doi.org/10.1038/nature15762. This is the authors' version of the manuscrip

    Fractionation of parietal function in bistable perception probed with concurrent TMS-EEG

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    When visual input has conflicting interpretations, conscious perception can alternate spontaneously between these possible interpretations. This is called bistable perception. Previous neuroimaging studies have indicated the involvement of two right parietal areas in resolving perceptual ambiguity (ant-SPLr and post-SPLr). Transcranial magnetic stimulation (TMS) studies that selectively interfered with the normal function of these regions suggest that they play opposing roles in this type of perceptual switch. In the present study, we investigated this fractionation of parietal function by use of combined TMS with electroencephalography (EEG). Specifically, while participants viewed either a bistable stimulus, a replay stimulus, or resting-state fixation, we applied single pulse TMS to either location independently while simultaneously recording EEG. Combined with participant’s individual structural magnetic resonance imaging (MRI) scans, this dataset allows for complex analyses of the effect of TMS on neural time series data, which may further elucidate the causal role of the parietal cortex in ambiguous perception

    Terminus thinning drives recent acceleration of a Greenlandic lake-terminating outlet glacier

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    Ice-contact proglacial lakes affect ice dynamics and the transition of glacier termini from land- to lake-terminating has been shown to cause ice flow acceleration. In recent decades, the number and size of Greenlandic ice-marginal lakes has increased, highlighting the need to further understand these lake-terminating ice-margins as their influence on ice sheet mass balance increases. Here, time series of satellite-derived observations of ice velocity, surface elevation, and terminus position were generated at a lake-terminating outlet glacier, Isortuarsuup Sermia, and the nearby land-terminating Kangaasarsuup Sermia in south-west Greenland. At Isortuarsuup Sermia, annual surface velocity at the terminus increased by a factor of 2.5 to 214 ± 4 m yr ´1 (2013–2021), with the magnitude of this acceleration declining with distance up-glacier. Meanwhile, near-terminus surface elevation changed at a rate of -2.3 ± 1.1 m yr ´1 (2012–2021). Conversely, velocity change at Kangaasarsuup Sermia was minimal, while surface elevation change was approximately half at comparable elevations (-1.2 ± 0.3 m yr ´1). We attribute these dynamic differences to thinning at Isortuarsuup Sermia and subsequent retreat from a stabilising sublacustrine moraine, and emphasise the potential of proglacial lakes to enhance future rates of mass loss from the Greenland Ice Sheet.</p

    The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

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    The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future

    New Constraints (and Motivations) for Abelian Gauge Bosons in the MeV-TeV Mass Range

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    We survey the phenomenological constraints on abelian gauge bosons having masses in the MeV to multi-GeV mass range (using precision electroweak measurements, neutrino-electron and neutrino-nucleon scattering, electron and muon anomalous magnetic moments, upsilon decay, beam dump experiments, atomic parity violation, low-energy neutron scattering and primordial nucleosynthesis). We compute their implications for the three parameters that in general describe the low-energy properties of such bosons: their mass and their two possible types of dimensionless couplings (direct couplings to ordinary fermions and kinetic mixing with Standard Model hypercharge). We argue that gauge bosons with very small couplings to ordinary fermions in this mass range are natural in string compactifications and are likely to be generic in theories for which the gravity scale is systematically smaller than the Planck mass - such as in extra-dimensional models - because of the necessity to suppress proton decay. Furthermore, because its couplings are weak, in the low-energy theory relevant to experiments at and below TeV scales the charge gauged by the new boson can appear to be broken, both by classical effects and by anomalies. In particular, if the new gauge charge appears to be anomalous, anomaly cancellation does not also require the introduction of new light fermions in the low-energy theory. Furthermore, the charge can appear to be conserved in the low-energy theory, despite the corresponding gauge boson having a mass. Our results reduce to those of other authors in the special cases where there is no kinetic mixing or there is no direct coupling to ordinary fermions, such as for recently proposed dark-matter scenarios.Comment: 49 pages + appendix, 21 figures. This is the final version which appears in JHE
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