Objective To measure the effect of free access to the scientific literature on article downloads and citations.Design Randomised controlled trial.Setting 11 journals published by the American ...Physiological Society.Participants 1619 research articles and reviews.Main outcome measures Article readership (measured as downloads of full text, PDFs, and abstracts) and number of unique visitors (internet protocol addresses). Citations to articles were gathered from the Institute for Scientific Information after one year.Interventions Random assignment on online publication of articles published in 11 scientific journals to open access (treatment) or subscription access (control).Results Articles assigned to open access were associated with 89% more full text downloads (95% confidence interval 76% to 103%), 42% more PDF downloads (32% to 52%), and 23% more unique visitors (16% to 30%), but 24% fewer abstract downloads (−29% to −19%) than subscription access articles in the first six months after publication. Open access articles were no more likely to be cited than subscription access articles in the first year after publication. Fifty nine per cent of open access articles (146 of 247) were cited nine to 12 months after publication compared with 63% (859 of 1372) of subscription access articles. Logistic and negative binomial regression analysis of article citation counts confirmed no citation advantage for open access articles.Conclusions Open access publishing may reach more readers than subscription access publishing. No evidence was found of a citation advantage for open access articles in the first year after publication. The citation advantage from open access reported widely in the literature may be an artefact of other causes.
Upgraded electronics, improved water system dynamics, better calibration and analysis techniques allowed Super-Kamiokande-IV to clearly observe very low-energy B8 solar neutrino interactions, with ...recoil electron kinetic energies as low as ∼3.5 MeV. Super-Kamiokande-IV data-taking began in September of 2008; this paper includes data until February 2014, a total livetime of 1664 days. The measured solar neutrino flux is (2.308±0.020(stat)−0.040+0.039(syst))×106/(cm2 sec) assuming no oscillations. The observed recoil electron energy spectrum is consistent with no distortions due to neutrino oscillations. An extended maximum likelihood fit to the amplitude of the expected solar zenith angle variation of the neutrino-electron elastic scattering rate in SK-IV results in a day/night asymmetry of (−3.6±1.6(stat)±0.6(syst))%. The SK-IV solar neutrino data determine the solar mixing angle as sin2θ12=0.327−0.031+0.026, all SK solar data (SK-I, SK-II, SK III and SK-IV) measures this angle to be sin2θ12=0.334−0.023+0.027, the determined mass-squared splitting is Δm212=4.8−0.8+1.5×10−5 eV2.
Networks of no-take reserves are important for protecting coral reef biodiversity from climate change and other human impacts. Ensuring that reserve populations are connected to each other and ...non-reserve populations by larval dispersal allows for recovery from disturbance and is a key aspect of resilience. In general, connectivity between reserves should increase as the distance between them decreases. However, enhancing connectivity may often tradeoff against a network's ability to representatively sample the system's natural variability. This “representation” objective is typically measured in terms of species richness or diversity of habitats, but has other important elements (e.g., minimizing the risk that multiple reserves will be impacted by catastrophic events). Such representation objectives tend to be better achieved as reserves become more widely spaced. Thus, optimizing the location, size and spacing of reserves requires both an understanding of larval dispersal and explicit consideration of how well the network represents the broader system; indeed the lack of an integrated theory for optimizing tradeoffs between connectivity and representation objectives has inhibited the incorporation of connectivity into reserve selection algorithms. This article addresses these issues by (1) updating general recommendations for the location, size and spacing of reserves based on emerging data on larval dispersal in corals and reef fishes, and on considerations for maintaining genetic diversity; (2) using a spatial analysis of the Great Barrier Reef Marine Park to examine potential tradeoffs between connectivity and representation of biodiversity and (3) describing a framework for incorporating environmental fluctuations into the conceptualization of the tradeoff between connectivity and representation, and that expresses both in a common, demographically meaningful currency, thus making optimization possible.
Genetic variation can affect drug response in multiple ways, although it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, ...collaborating with the Pharmacogenomics Research Network, began eMERGE‐PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of “precision medicine.” The February 2015 eMERGE‐PGx data release includes sequence‐derived data from ∼5,000 clinical subjects. We present the variant frequency spectrum categorized by variant type, ancestry, and predicted function. We found 95.12% of genes have variants with a scaled Combined Annotation‐Dependent Depletion score above 20, and 96.19% of all samples had one or more Clinical Pharmacogenetics Implementation Consortium Level A actionable variants. These data highlight the distribution and scope of genetic variation in relevant pharmacogenes, identifying challenges associated with implementing clinical sequencing for drug treatment at a broader level, underscoring the importance for multifaceted research in the execution of precision medicine.
Background. The sensitivity of the MVista Histoplasma antigen enzyme immunoassay (MiraVista Diagnostics) has been evaluated in disseminated histoplasmosis in patients with AIDS and in the "epidemic" ...form of acute pneumonia. Moreover, there has been no evaluation of the sensitivity of antigenemia detection in disseminated histoplasmosis after the implementation of methods to dissociate immune complexes and denature released antibodies. The goal of this study was to determine the sensitivity of the current antigen assay in different categories of histoplasmosis. Methods. Urine and serum specimens obtained from 218 patients with histoplasmosis and 229 control subjects, including 30 with blastomycosis, were tested. Results. Antigenuria was detected in 91.8% of 158 patients with disseminated histoplasmosis, 83.3% of 6 patients with acute histoplasmosis, 30.4% of 46 patients with subacute histoplasmosis, and 87.5% of 8 patients with chronic pulmonary histoplasmosis; antigenemia was present in 100% of 31 tested cases of disseminated histoplasmosis. Among patients with disseminated cases, antigenuria was detected more often and at higher concentrations in immunocompromised patients and those with severe disease. Specificity was 99.0% for patients with nonfungal infections (n = 130) and in healthy subjects (n = 69), but cross-reactivity occurred in 90% of patients with blastomycosis. Conclusions. The sensitivity of antigen detection in disseminated histoplasmosis is higher in immunocompromised patients than in immunocompetent patients and in patients with more severe illness. The sensitivity for detection of antigenemia is similar to that for antigenuria in disseminated infection.
To determine the frequency and significance of electrographic seizures and other EEG findings in patients with intracerebral hemorrhage (ICH).
We reviewed 102 consecutive patients with ICH who ...underwent continuous electroencephalographic monitoring (cEEG). Demographic, clinical, radiographic, and cEEG findings were recorded. Using multivariate logistic regression analysis, we determined factors associated with 1) electrographic seizures, 2) periodic epileptiform discharges (PEDs), and 3) poor outcome (death, vegetative or minimally conscious state) at hospital discharge.
Seizures occurred in 31% (n = 32) of patients with ICH, prior to cEEG in 19 patients. Eighteen percent (n = 18) of patients had electrographic seizures; only one of these patients also had clinical seizures while on cEEG. After controlling for demographic and clinical predictors, only an increase in ICH volume of 30% or more between admission and 24-hour follow-up CT scan was associated with electrographic seizures (33% vs 15%; OR 9.5, 95% CI 1.7 to 53.8). PEDs were less frequently seen in those with hemorrhages located at least 1 mm from the cortex (8% vs 29%; OR 0.2, 95% CI 0.1 to 0.7). PEDs were independently associated with poor outcome (65% vs 17%; OR 7.6, 95% CI 2.1 to 27.3). In patients with electrographic seizures, the first seizure was detected within the first hour of cEEG monitoring in 56% and within 48 hours in 94%.
Seizures occurred in one third of patients with intracerebral hemorrhage (ICH) and over half were purely electrographic. Electrographic seizures were associated with expanding hemorrhages, and periodic discharges with cortical ICH and poor outcome. Further research is needed to determine if treating or preventing seizures or PEDs might lead to improved outcome after ICH.
The exploration of near‐Earth asteroids has revealed dynamic surfaces characterized by mobile, unconsolidated material that responds to local geophysical gradients, resulting in distinct morphologies ...and boulder distributions. The OSIRIS‐REx (Origins, Spectral Interpretation, Resource Identification, and Security‐Regolith Explorer) mission confirmed that asteroid (101955) Bennu is a rubble pile with an unconsolidated surface dominated by boulders. In this work, we documented morphologies indicative of mass movement on Bennu and assessed the relationship to slope and other geologic features on the surface. We found globally distributed morphologic evidence of mass movement on Bennu up to ~70° latitude and on spatial scales ranging from individual boulders (meter scale) to a single debris flow ~100 m long and several meters thick. The apparent direction of mass movement is consistent with the local downslope direction and dominantly moves from the midlatitudes toward the equator. Mass movement appears to have altered the surface expression of large (≥30m diameter) boulders, excavating them in the midlatitudes and burying them in the equatorial region. Up to a 10 ± 1 m depth of material may have been transported away from the midlatitudes, which would have deposited a layer ~5 ± 1 m thick in the equatorial region assuming a stagnated flow model. This mass movement could explain the observed paucity of small (<50‐m diameter) craters and may have contributed material to Bennu's equatorial ridge. Models of changes in slope suggest that the midlatitude mass movement occurred in the past several hundred thousand years in regions that became steeper by several degrees.
Plain Language Summary
Mass movement is the flow of loose material such as rock fragments across the surface of a planetary body (for instance, a landslide). We searched images of the surface of asteroid (101955) Bennu for evidence of mass movement. We found that rocks of various sizes have moved downslope, and evidence of this movement is apparent at most locations on the asteroid. By measuring the distribution of, and surface elevation around, the largest boulders on the surface of Bennu, we also found that the downslope movement of material appears to have excavated large boulders from the subsurface in the midlatitudes and buried large boulders near the equator. Our observation that material on Bennu has moved in what is currently the local downslope direction is not necessarily expected, because the downslope direction can change based on how quickly the asteroid is rotating, which varies over time. Thus, we can infer that this movement happened in the geologically recent past—probably within the past several hundred thousand years. These results can help us understand how geologic features like craters are erased, how the equatorial ridge formed, and how Bennu (and potentially other asteroids) change shape over time.
Key Points
Signatures of mass movement on Bennu are globally distributed at multiple spatial scales
Mass movement may have removed a ~10‐m‐thick layer of material from the midlatitudes and deposited a ~5‐m‐thick layer near the equator
Mass movement that left visible evidence on Bennu occurred within the past several hundred thousand years
We describe here the design and initial implementation of the eMERGE‐PGx project. eMERGE‐PGx, a partnership of the Electronic Medical Records and Genomics Network and the Pharmacogenomics Research ...Network, has three objectives: (i) to deploy PGRNseq, a next‐generation sequencing platform assessing sequence variation in 84 proposed pharmacogenes, in nearly 9,000 patients likely to be prescribed drugs of interest in a 1‐ to 3‐year time frame across several clinical sites; (ii) to integrate well‐established clinically validated pharmacogenetic genotypes into the electronic health record with associated clinical decision support and to assess process and clinical outcomes of implementation; and (iii) to develop a repository of pharmacogenetic variants of unknown significance linked to a repository of electronic health record–based clinical phenotype data for ongoing pharmacogenomics discovery. We describe site‐specific project implementation and anticipated products, including genetic variant and phenotype data repositories, novel variant association studies, clinical decision support modules, clinical and process outcomes, approaches to managing incidental findings, and patient and clinician education methods.
Clinical Pharmacology & Therapeutics (2014); 96 4, 482–489. doi:10.1038/clpt.2014.137
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