672 research outputs found

    The Role of Data in an Emerging Research Community:

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    Open science data benefit society by facilitating convergence across domains that are examining the same scientific problem. While cross-disciplinary data sharing and reuse is essential to the research done by convergent communities, so far little is known about the role data play in how these communities interact. An understanding of the role of data in these collaborations can help us identify and meet the needs of emerging research communities which may predict the next challenges faced by science. This paper represents an exploratory study of one emerging community, the environmental health community, examining how environmental health research groups form, collaborate, and share data. Five key insights about the role of data in emerging research communities are identified and suggestions are made for further research

    Scapular deformity in obstetric brachial plexus palsy: a new finding

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    While most obstetric brachial plexus palsy patients recover arm and hand function, the residual nerve weakness leads to muscle imbalances about the shoulder which may cause bony deformities. In this paper we describe abnormalities in the developing scapula and the glenohumeral joint. We introduce a classification for the deformity which we term Scapular Hypoplasia, Elevation and Rotation. Multiple anatomic parameters were measured in bilateral CT images and three-dimensional CT reconstruction of the shoulder girdle of 30 obstetric brachial plexus palsy patients (age range 10 months–10.6 years). The affected scapulae were found to be hypoplastic by an average of 14% while the ratio of the height to the width of the body of scapula (excluding acromion) were not significantly changed, the acromion was significantly elongated by an average of 19%. These parameters as well as subluxation of the humeral head (average 14%) and downward rotation in the scapular plane were found to correlate with the area of scapula visible over the clavicle. This finding provides a classification tool for diagnosis and objective evaluation of the bony deformity and its severity in obstetric brachial plexus palsy patients

    Identification of Direct Target Engagement Biomarkers for Kinase-Targeted Therapeutics

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    Pharmacodynamic (PD) biomarkers are an increasingly valuable tool for decision-making and prioritization of lead compounds during preclinical and clinical studies as they link drug-target inhibition in cells with biological activity. They are of particular importance for novel, first-in-class mechanisms, where the ability of a targeted therapeutic to impact disease outcome is often unknown. By definition, proximal PD biomarkers aim to measure the interaction of a drug with its biological target. For kinase drug discovery, protein substrate phosphorylation sites represent candidate PD biomarkers. However, substrate phosphorylation is often controlled by input from multiple converging pathways complicating assessment of how potently a small molecule drug hits its target based on substrate phoshorylation measurements alone. Here, we report the use of quantitative, differential mass-spectrometry to identify and monitor novel drug-regulated phosphorylation sites on target kinases. Autophosphorylation sites constitute clinically validated biomarkers for select protein tyrosine kinase inhibitors. The present study extends this principle to phosphorylation sites in serine/threonine kinases looking beyond the T-loop autophosphorylation site. Specifically, for the 3′-phosphoinositide-dependent protein kinase 1 (PDK1), two phospho-residues p-PDK1Ser410 and p-PDK1Thr513 are modulated by small-molecule PDK1 inhibitors, and their degree of dephosphorylation correlates with inhibitor potency. We note that classical, ATP-competitive PDK1 inhibitors do not modulate PDK1 T-loop phosphorylation (p-PDK1Ser241), highlighting the value of an unbiased approach to identify drug target-regulated phosphorylation sites as these are complementary to pathway PD biomarkers. Finally, we extend our analysis to another protein Ser/Thr kinase, highlighting a broader utility of our approach for identification of kinase drug-target engagement biomarkers

    Whale, whale, everywhere: increasing abundance of western South Atlantic humpback whales (Megaptera novaeangliae) in their wintering grounds

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    The western South Atlantic (WSA) humpback whale population inhabits the coast of Brazil during the breeding and calving season in winter and spring. This population was depleted to near extinction by whaling in the mid-twentieth century. Despite recent signs of recovery, increasing coastal and offshore development pose potential threats to these animals. Therefore, continuous monitoring is needed to assess population status and support conservation strategies. The aim of this work was to present ship-based line-transect estimates of abundance for humpback whales in their WSA breeding ground and to investigate potential changes in population size. Two cruises surveyed the coast of Brazil during August-September in 2008 and 2012. The area surveyed in 2008 corresponded to the currently recognized population breeding area; effort in 2012 was limited due to unfavorable weather conditions. WSA humpback whale population size in 2008 was estimated at 16,410 (CV = 0.228, 95% CI = 10,563–25,495) animals. In order to compare abundance between 2008 and 2012, estimates for the area between Salvador and Cabo Frio, which were consistently covered in the two years, were computed at 15,332 (CV = 0.243, 95% CI = 9,595–24,500) and 19,429 (CV = 0.101, 95% CI = 15,958–23,654) whales, respectively. The difference in the two estimates represents an increase of 26.7% in whale numbers in a 4-year period. The estimated abundance for 2008 is considered the most robust for the WSA humpback whale population because the ship survey conducted in that year minimized bias from various sources. Results presented here indicate that in 2008, the WSA humpback whale population was at least around 60% of its estimated pre-modern whaling abundance and that it may recover to its pre-exploitation size sooner than previously estimated.Publisher PDFPeer reviewe

    CEO international experience and foreign IPOs

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    International audienceThis paper examines listing location as a managerial decision by using a sample of IPOs of Chinese entrepreneurial firms in mainland China, the United States and Hong Kong. We find that Chinese entrepreneurial firms managed by CEOs with international experience are more likely to undertake foreign IPOs, especially those returned from countries with more advanced legal institutions and those operating in high-tech industries. The credibility crisis for Chinese firms in 2010 switched the focus of foreign IPOs from the US to Hong Kong. These results are consistent across returnee CFOs and other senior executives with international experience

    Associations of Cardiorespiratory Fitness and Obesity With Risks of Impaired Fasting Glucose and Type 2 Diabetes in Men

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    OBJECTIVE—The purpose of this study was to examine the associations of cardiorespiratory fitness (hereafter fitness) and various obesity measures with risks of incident impaired fasting glucose (IFG) and type 2 diabetes

    Between Documentality and Imagination: Five Theses on Curating the Violent Past

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    This article considers the notion that to document or inscribe our lives not only leaves a trace of our creaturely presence, but may also become a form of juris-writing, a writing that concerns and aims at Justice. Employing an expanded notion of Justice that takes it beyond the institutions of law, therefore, it asks about forms of documentality (Ferraris) that put us ‘before memory’ in Derrida’s sense. How is it possible to think curation in relation to a violent past in such a way that neither attempts to deny the lacunae nor surrenders in the face of the difficulties of such attempts? How should we consider the relation between the delimited encounter with an ‘invitation to imagine’ (Didi-Huberman) and processes of institutionalisation that build a society? What about those things that it is not possible to show, including relations of power, that arise analytically? Reflecting on current memory spaces, especially within ex-clandestine centres for detention, torture and extermination (ex-ccdtyes) in Argentina, the article offers five theses in order to consider what is at stake in the encounters staged at these sites

    Arm rotated medially with supination – the ARMS variant: description of its surgical correction

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    <p>Abstract</p> <p>Background</p> <p>Patients who have suffered obstetric brachial plexus injury (OBPI) have a high incidence of musculoskeletal complications stemming from the initial nerve injury. The presence of muscle imbalances and contractures leads to typical bony changes affecting the shoulder, including the SHEAR (Scapular Hypoplasia, Elevation and Rotation) deformity. The SHEAR deformity commonly occurs in conjunction with Medial Rotation Contracture (MRC) of the arm. OBPI also causes muscle imbalances at the level of the forearm, that lead to a fixed supination deformity (SD) in a small number of patients. Both MRC and SD will cause severe functional limitations without surgical intervention.</p> <p>Methods</p> <p>Fourteen OBPI patients were diagnosed with MRC of the shoulder and SD of the forearm along with SHEAR deformity during a 16 month study period, with eight patients available to long-term follow-up (age range 2.2 – 18 years). Surgical correction of the MRC was performed as a triangle tilt or humeral osteotomy depending on the age of the child, after which, the patients were treated with a radial osteotomy to correct the fixed supination deformity. Function was assessed using the modified Mallet scale, examination of apparent supination and appearance of the extremity at rest.</p> <p>Results</p> <p>Significant functional improvements were observed in patients with surgical reconstruction. Mallet score increased by an average of 5.2 (p < 0.05). Overall forearm position was not significantly changed from an average of 5° to an average of 34° maximum apparent supination after both shoulder rotation and forearm rotation corrective surgeries.</p> <p>Conclusion</p> <p>The simultaneous presence of two opposing deformities in the same limb will visually offset each other at the level of the wrist and hand, giving the false impression of neutral positioning of the limb. In reality, the neutral-appearing position of the hand indicates a fixed supination posture of the forearm in the face of a medial rotation contracture of the shoulder. Both of these deformities require surgical attention, and the presence of concurrent MRC and SD should be monitored for in OBPI patients.</p

    Metabolic Factors Limiting Performance in Marathon Runners

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    Each year in the past three decades has seen hundreds of thousands of runners register to run a major marathon. Of those who attempt to race over the marathon distance of 26 miles and 385 yards (42.195 kilometers), more than two-fifths experience severe and performance-limiting depletion of physiologic carbohydrate reserves (a phenomenon known as ‘hitting the wall’), and thousands drop out before reaching the finish lines (approximately 1–2% of those who start). Analyses of endurance physiology have often either used coarse approximations to suggest that human glycogen reserves are insufficient to fuel a marathon (making ‘hitting the wall’ seem inevitable), or implied that maximal glycogen loading is required in order to complete a marathon without ‘hitting the wall.’ The present computational study demonstrates that the energetic constraints on endurance runners are more subtle, and depend on several physiologic variables including the muscle mass distribution, liver and muscle glycogen densities, and running speed (exercise intensity as a fraction of aerobic capacity) of individual runners, in personalized but nevertheless quantifiable and predictable ways. The analytic approach presented here is used to estimate the distance at which runners will exhaust their glycogen stores as a function of running intensity. In so doing it also provides a basis for guidelines ensuring the safety and optimizing the performance of endurance runners, both by setting personally appropriate paces and by prescribing midrace fueling requirements for avoiding ‘the wall.’ The present analysis also sheds physiologically principled light on important standards in marathon running that until now have remained empirically defined: The qualifying times for the Boston Marathon
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