1,587 research outputs found

    Using a realist approach to evaluate smoking cessation interventions targeting pregnant women and young people

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    Background This paper describes a study protocol designed to evaluate a programme of smoking cessation interventions targeting pregnant women and young people living in urban and rural locations in Northeast Scotland. The study design was developed on so-called 'realist' evaluation principles, which are concerned with the implementation of interventions as well as their outcomes. Methods/design A two-phased study was designed based on the Theory of Change (TOC) using mixed methods to assess both process and outcome factors. The study was designed with input from the relevant stakeholders. The mixed-methods approach consists of semi-structured interviews with planners, service providers, service users and non-users. These qualitative interviews will be analysed using a thematic framework approach. The quantitative element of the study will include the analysis of routinely collected data and specific project monitoring data, such as data on service engagement, service use, quit rates and changes in smoking status. Discussion The process of involving key stakeholders was conducted using logic modelling and TOC tools. Engaging stakeholders, including those responsible for funding, developing and delivering, and those intended to benefit from interventions aimed at them, in their evaluation design, are considered by many to increase the validity and rigour of the subsequent evidence generated. This study is intended to determine not only the components and processes, but also the possible effectiveness of this set of health interventions, and contribute to the evidence base about smoking cessation interventions aimed at priority groups in Scotland. It is also anticipated that this study will contribute to the ongoing debate about the role and challenges of 'realist' evaluation approaches in general, and the utility of logic modelling and TOC approaches in particular, for evaluation of complex health interventions

    The Comparative Osteology of the Petrotympanic Complex (Ear Region) of Extant Baleen Whales (Cetacea: Mysticeti)

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    Anatomical comparisons of the ear region of baleen whales (Mysticeti) are provided through detailed osteological descriptions and high-resolution photographs of the petrotympanic complex (tympanic bulla and petrosal bone) of all extant species of mysticete cetaceans. Salient morphological features are illustrated and identified, including overall shape of the bulla, size of the conical process of the bulla, morphology of the promontorium, and the size and shape of the anterior process of the petrosal. We place our comparative osteological observations into a phylogenetic context in order to initiate an exploration into petrotympanic evolution within Mysticeti.The morphology of the petrotympanic complex is diagnostic for individual species of baleen whale (e.g., sigmoid and conical processes positioned at midline of bulla in Balaenoptera musculus; confluence of fenestra cochleae and perilymphatic foramen in Eschrichtius robustus), and several mysticete clades are united by derived characteristics. Balaenids and neobalaenids share derived features of the bulla, such as a rhomboid shape and a reduced anterior lobe (swelling) in ventral aspect, and eschrichtiids share derived morphologies of the petrosal with balaenopterids, including loss of a medial promontory groove and dorsomedial elongation of the promontorium. Monophyly of Balaenoidea (Balaenidae and Neobalaenidae) and Balaenopteroidea (Balaenopteridae and Eschrichtiidae) was recovered in phylogenetic analyses utilizing data exclusively from the petrotympanic complex.This study fills a major gap in our knowledge of the complex structures of the mysticete petrotympanic complex, which is an important anatomical region for the interpretation of the evolutionary history of mammals. In addition, we introduce a novel body of phylogenetically informative characters from the ear region of mysticetes. Our detailed anatomical descriptions, illustrations, and comparisons provide valuable data for current and future studies on the phylogenetic relationships, evolution, and auditory physiology of mysticetes and other cetaceans throughout Earth's history

    Predicting the impact of Lynch syndrome-causing missense mutations from structural calculations

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    Accurate methods to assess the pathogenicity of mutations are needed to fully leverage the possibilities of genome sequencing in diagnosis. Current data-driven and bioinformatics approaches are, however, limited by the large number of new variations found in each newly sequenced genome, and often do not provide direct mechanistic insight. Here we demonstrate, for the first time, that saturation mutagenesis, biophysical modeling and co-variation analysis, performed in silico, can predict the abundance, metabolic stability, and function of proteins inside living cells. As a model system, we selected the human mismatch repair protein, MSH2, where missense variants are known to cause the hereditary cancer predisposition disease, known as Lynch syndrome. We show that the majority of disease-causing MSH2 mutations give rise to folding defects and proteasome-dependent degradation rather than inherent loss of function, and accordingly our in silico modeling data accurately identifies disease-causing mutations and outperforms the traditionally used genetic disease predictors. Thus, in conclusion, in silico biophysical modeling should be considered for making genotype-phenotype predictions and for diagnosis of Lynch syndrome, and perhaps other hereditary diseases

    Assessment of BED HIV-1 Incidence Assay in Seroconverter Cohorts: Effect of Individuals with Long-Term Infection and Importance of Stable Incidence

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    BACKGROUND: Performance of the BED assay in estimating HIV-1 incidence has previously been evaluated by using longitudinal specimens from persons with incident HIV infections, but questions remain about its accuracy. We sought to assess its performance in three longitudinal cohorts from Thailand where HIV-1 CRF01_AE and subtype B' dominate the epidemic. DESIGN: BED testing was conducted in two longitudinal cohorts with only incident infections (a military conscript cohort and an injection drug user cohort) and in one longitudinal cohort (an HIV-1 vaccine efficacy trial cohort) that also included long-term infections. METHODS: Incidence estimates were generated conventionally (based on the number of annual serocoversions) and by using BED test results in the three cohorts. Adjusted incidence was calculated where appropriate. RESULTS: For each longitudinal cohort the BED incidence estimates and the conventional incidence estimates were similar when only newly infected persons were tested, whether infected with CRF01_AE or subtype B'. When the analysis included persons with long-term infections (to mimic a true cross-sectional cohort), BED incidence estimates were higher, although not significantly, than the conventional incidence estimates. After adjustment, the BED incidence estimates were closer to the conventional incidence estimates. When the conventional incidence varied over time, as in the early phase of the injection drug user cohort, the difference between the two estimates increased, but not significantly. CONCLUSIONS: Evaluation of the performance of incidence assays requires the inclusion of a substantial number of cohort-derived specimens from individuals with long-term HIV infection and, ideally, the use of cohorts in which incidence remained stable. Appropriate adjustments of the BED incidence estimates generate estimates similar to those generated conventionally

    Sensory substitution information informs locomotor adjustments when walking through apertures

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    The study assessed the ability of the central nervous system (CNS) to use echoic information from sensory substitution devices (SSDs) to rotate the shoulders and safely pass through apertures of different width. Ten visually normal participants performed this task with full vision, or blindfolded using an SSD to obtain information regarding the width of an aperture created by two parallel panels. Two SSDs were tested. Participants passed through apertures of +0%, +18%, +35%, and +70% of measured body width. Kinematic indices recorded movement time, shoulder rotation, average walking velocity across the trial, peak walking velocities before crossing, after crossing and throughout a whole trial. Analyses showed participants used SSD information to regulate shoulder rotation, with greater rotation associated with narrower apertures. Rotations made using an SSD were greater compared to vision, movement times were longer, average walking velocity lower and peak velocities before crossing, after crossing and throughout the whole trial were smaller, suggesting greater caution. Collisions sometimes occurred using an SSD but not using vision, indicating that substituted information did not always result in accurate shoulder rotation judgements. No differences were found between the two SSDs. The data suggest that spatial information, provided by sensory substitution, allows the relative position of aperture panels to be internally represented, enabling the CNS to modify shoulder rotation according to aperture width. Increased buffer space indicated by greater rotations (up to approximately 35% for apertures of +18% of body width), suggests that spatial representations are not as accurate as offered by full vision

    Measurement of the Z/gamma* + b-jet cross section in pp collisions at 7 TeV

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    The production of b jets in association with a Z/gamma* boson is studied using proton-proton collisions delivered by the LHC at a centre-of-mass energy of 7 TeV and recorded by the CMS detector. The inclusive cross section for Z/gamma* + b-jet production is measured in a sample corresponding to an integrated luminosity of 2.2 inverse femtobarns. The Z/gamma* + b-jet cross section with Z/gamma* to ll (where ll = ee or mu mu) for events with the invariant mass 60 < M(ll) < 120 GeV, at least one b jet at the hadron level with pT > 25 GeV and abs(eta) < 2.1, and a separation between the leptons and the jets of Delta R > 0.5 is found to be 5.84 +/- 0.08 (stat.) +/- 0.72 (syst.) +(0.25)/-(0.55) (theory) pb. The kinematic properties of the events are also studied and found to be in agreement with the predictions made by the MadGraph event generator with the parton shower and the hadronisation performed by PYTHIA.Comment: Submitted to the Journal of High Energy Physic

    Performance of the CMS Cathode Strip Chambers with Cosmic Rays

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    The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

    Highly structured slow solar wind emerging from an equatorial coronal hole

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    International audienceDuring the solar minimum, when the Sun is at its least active, the solar wind(1,2) is observed at high latitudes as a predominantly fast (more than 500 kilometres per second), highly Alfvenic rarefied stream of plasma originating from deep within coronal holes. Closer to the ecliptic plane, the solar wind is interspersed with a more variable slow wind(3) of less than 500 kilometres per second. The precise origins of the slow wind streams are less certain(4); theories and observations suggest that they may originate at the tips of helmet streamers(5,6), from interchange reconnection near coronal hole boundaries(7,8), or within coronal holes with highly diverging magnetic fields(9,10). The heating mechanism required to drive the solar wind is also unresolved, although candidate mechanisms include Alfven-wave turbulence(11,12), heating by reconnection in nanoflares(13), ion cyclotron wave heating(14) and acceleration by thermal gradients1. At a distance of one astronomical unit, the wind is mixed and evolved, and therefore much of the diagnostic structure of these sources and processes has been lost. Here we present observations from the Parker Solar Probe(15) at 36 to 54 solar radii that show evidence of slow Alfvenic solar wind emerging from a small equatorial coronal hole. The measured magnetic field exhibits patches of large, intermittent reversals that are associated with jets of plasma and enhanced Poynting flux and that are interspersed in a smoother and less turbulent flow with a near-radial magnetic field. Furthermore, plasma-wave measurements suggest the existence of electron and ion velocity-space micro-instabilities(10,16) that are associated with plasma heating and thermalization processes. Our measurements suggest that there is an impulsive mechanism associated with solar-wind energization and that micro-instabilities play a part in heating, and we provide evidence that low-latitude coronal holes are a key source of the slow solar wind

    A supermatrix analysis of genomic, morphological, and paleontological data from crown Cetacea

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    <p>Abstract</p> <p>Background</p> <p>Cetacea (dolphins, porpoises, and whales) is a clade of aquatic species that includes the most massive, deepest diving, and largest brained mammals. Understanding the temporal pattern of diversification in the group as well as the evolution of cetacean anatomy and behavior requires a robust and well-resolved phylogenetic hypothesis. Although a large body of molecular data has accumulated over the past 20 years, DNA sequences of cetaceans have not been directly integrated with the rich, cetacean fossil record to reconcile discrepancies among molecular and morphological characters.</p> <p>Results</p> <p>We combined new nuclear DNA sequences, including segments of six genes (~2800 basepairs) from the functionally extinct Yangtze River dolphin, with an expanded morphological matrix and published genomic data. Diverse analyses of these data resolved the relationships of 74 taxa that represent all extant families and 11 extinct families of Cetacea. The resulting supermatrix (61,155 characters) and its sub-partitions were analyzed using parsimony methods. Bayesian and maximum likelihood (ML) searches were conducted on the molecular partition, and a molecular scaffold obtained from these searches was used to constrain a parsimony search of the morphological partition. Based on analysis of the supermatrix and model-based analyses of the molecular partition, we found overwhelming support for 15 extant clades. When extinct taxa are included, we recovered trees that are significantly correlated with the fossil record. These trees were used to reconstruct the timing of cetacean diversification and the evolution of characters shared by "river dolphins," a non-monophyletic set of species according to all of our phylogenetic analyses.</p> <p>Conclusions</p> <p>The parsimony analysis of the supermatrix and the analysis of morphology constrained to fit the ML/Bayesian molecular tree yielded broadly congruent phylogenetic hypotheses. In trees from both analyses, all Oligocene taxa included in our study fell outside crown Mysticeti and crown Odontoceti, suggesting that these two clades radiated in the late Oligocene or later, contra some recent molecular clock studies. Our trees also imply that many character states shared by river dolphins evolved in their oceanic ancestors, contradicting the hypothesis that these characters are convergent adaptations to fluvial habitats.</p
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