bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deleterious protein‐altering mutations in the SCN10A voltage‐gated sodium channel gene are associated with prolonged QT
Authors: Abou Ziki M.D. , Seidelmann S.B. , Smith E. , Atteya G. , Jiang Y. , Fernandes R.G. , Marieb M.A. , Akar J.G. , Mani A. 
Published: April 2017

BackgroundLong QT syndrome (LQT) is a pro‐arrhythmogenic condition with life‐threatening complications. Fifteen genes have been associated with congenital LQT, however, the genetic causes remain unknown in more than 20% of cases.Materials and MethodsEighteen patients with history of palpitations, pre‐syncope, syncope and prolonged QT were referred to the Yale Cardiovascular Genetics Program. All subjects underwent whole‐exome sequencing (WES) followed by confirmatory Sanger sequencing. Mutation burden analysis was carried out using WES data from 16 subjects with no identifiable cause of LQT.ResultsDeleterious and novel SCN10A mutations were identified in 3 of the 16 patients (19%) with idiopathic LQT. These included 2 frameshifts and 1 missense variants (p.G810fs, p.R1259Q, and p.P1877fs). Further analysis identified 2 damaging SCN10A mutations with allele frequencies of approximately 0.2% (p.R14L and p.R1268Q) in 2 independent cases. None of the SCN10A mutation carriers had mutations in known arrhythmia genes. Damaging SCN10A mutations (p.R209H and p.R485C) were also identified in the 2 subjects on QT prolonging medications.ConclusionOur findings implicate SCN10A in LQT. The presence of frameshift mutations suggests loss‐of‐function as the underlying disease mechanism. The common association with atrial fibrillation suggests a unique mechanism of disease for this LQT gene.
From CCTs to a social investment welfare state? Brazil's ‘new’ pro‐poor strategy
Authors: Fenwick Tracy Beck 
Published: April 2017

AbstractThe changes in Brazil's pro‐poor strategy from the presidency of Luiz Inácio Lula da Silva to that of Dilma Roussef have received little analysis. Based on a qualitative research approach that includes media analysis, semi‐structured interviews with local level elites, NGO representatives and Brazilian policy experts, the central argument here is that, although it is true that this ‘new’ approach closely approximates a European‐style social investment agenda that goes beyond the policy intentions of Conditional Cash Transfers (CCTs), in reality it continues to prioritize ‘expanding access to complementary services’ over improving the ‘quality’ of publicly provided services. Using the example of Brasil Carinhoso, one of the federal government's priority programmes within the Brasil Sem Miséria programme designed to be complementary to Bolsa Família, the article outlines the initial challenges facing this emerging agenda, along with its key political constraints.
Recent Scholarship on Hume's Theory of Mental Representation
Authors: Landy David 
Published: April 2017

AbstractIn a recent paper, Karl Schafer argues that Hume's theory of mental representation has two distinct components, unified by their shared feature of having accuracy conditions. As Schafer sees it, simple and complex ideas represent the intrinsic imagistic features of their objects whereas abstract ideas represent the relations or structures in which multiple objects stand. This distinction, however, is untenable for at least two related reasons. Firstly, complex ideas represent the relations or structures in which the impressions that are the objects of their simple components stand. Secondly, abstract ideas are themselves instances of complex ideas. I draw two important conclusions from these facts. Firstly, contra Schafer and Garrett (to whom Schafer responds), the Copy Principle, properly emended, constitutes the entirety of Hume's theory of mental representation. Secondly, whereas paradigm examples of complex ideas, e.g. ideas of spatial and temporal complexes, are structured by relations of contiguity, abstract ideas are those complex ideas instead structured by relations of resemblance. As such, they represent their objects not as spatially or temporally contiguous but rather as resembling.
Accounting and the emergence of care pathways in the National Health Service
Authors: Gebreiter Florian 
Published: April 2017

AbstractThis paper examines the effects of New Public Management reforms on the information infrastructure underpinning the work of public service professionals. Focussing on the case of the British National Health Service (NHS), the paper argues that hospital accounting reforms played a significant role in the emergence of standardised models of clinical practice. The paper moreover argues that, under the label ‘care pathways’, such standardised models of clinical practice became embedded in the information infrastructure of the NHS and concludes by discussing their implications for the work of doctors and hospital accountants.
X‐ray computed tomography quantification of damage in concrete under compression considering irreversible mode‐II microcracks
Authors: Yu Z.W. , Tan S. , Shan Z. , Tian X.Q. 
Published: April 2017

AbstractA method for X‐ray computed tomography quantification of damage in concrete under compression considering irreversible mode‐II microcracks is developed. To understand damage behaviour in concrete, a micromechanical analysis of damage under biaxial compression is conducted focusing on random micro‐defects in micro‐cells isolated from the representative volume element. Furthermore, for stress–strain response prediction, a quantification is developed concerning the behaviours of the dominant macrocracks in multiaxial compression. Specifically, two crack types are taken into account: mode‐I cracks and irreversible deformation cracks (including mode‐II microcracks). Furthermore, mode‐I cracks generate compression‐induced tensile load (transverse) area reduction and further stiffness degradation, whereas the latter contribute to the development of irreversible strains. Additionally, by investigating the development of gradually converging dominant cracks, the procedure for quantifying damage is competently executed. In addition, distinguished from other approaches, the quantified damage can be applied directly to constitutive models to produce stress–strain response highly agrees with experimental results.
Monocyte/lymphocyte ratio as a better predictor of cardiovascular and all‐cause mortality in hemodialysis patients: A prospective cohort study
Authors: Xiang Fangfang , Chen Rongyi , Cao Xuesen , Shen Bo , Liu Zhonghua , Tan Xiao , Ding Xiaoqiang , Zou Jianzhou 
Published: April 2017

AbstractIntroduction: Patients with chronic kidney disease, especially those with end‐stage renal disease, have an increased risk of death. Previous studies have suggested neutrophil/lymphocyte ratio (NLR) was related to worse outcome in patients undergoing hemodialysis (HD). However, monocyte/lymphocyte ratio (MLR) has not been evaluated in HD patients. In this study, we prospectively studied the predictive value of MLR for all‐cause and cardiovascular mortality in HD patients and compared it with NLR.Methods: Patients who had been on a HD treatment for at least 6 months were enrolled. MLR was calculated by dividing the monocyte count by the lymphocyte count. Survival outcomes were estimated using the Kaplan‐Meier method and compared by the log‐rank test. Univariate and multivariate analyses were performed to evaluate the prognostic impact of MLR and other clinical factors on all‐cause and cardiovascular mortality.Results: Mortality rates for the lowest, middle, and highest MLR tertile group were 3.65, 7.02, and 11.15, respectively per 100 patient‐years. The Kaplan‐Meier analysis revealed that survival rates were significantly different among three MLR groups (P < 0.001). In multivariate Cox regression analyses, MLR was independently associated with all‐cause mortality (HR 4.842; 95% CI, 2.091–11.214; P < 0.001) and cardiovascular mortality (HR 6.985, 95% CI 1.943–25.115, P = 0.003) as continuous variables. NLR was not an independent predictor of all‐cause nor cardiovascular mortality after adjusted with MLR.Conclusions: The main finding of the study suggest that higher MLR was a strong and independent predictor of all‐cause and cardiovascular mortality and overwhelmed NLR among HD patients.
Towards satisfying performance of an O/W cosmetic emulsion: screening of reformulation factors on textural and rheological properties using general experimental design
Authors: Filipovic M. , Lukic M. , Djordjevic S. , Krstonosic V. , Pantelic I. , Vuleta G. , Savic S. 
Published: April 2017

AbstractObjectiveConsumers' demand for improved products' performance, alongside with the obligation of meeting the safety and efficacy goals, presents a key reason for the reformulation, as well as a challenging task for formulators. Any change of the formulation, whether it is wanted – in order to innovate the product (new actives and raw materials) or necessary – due to, for example legislative changes (restriction of ingredients), ingredients market unavailability, new manufacturing equipment, may have a number of consequences, desired or otherwise. The aim of the study was to evaluate the influence of multiple factors – variations of the composition, manufacturing conditions and their interactions, on emulsion textural and rheological characteristics, applying the general experimental factorial design and, subsequently, to establish the approach that could replace, to some extent, certain expensive and time‐consuming tests (e.g. certain sensory analysis), often required, partly or completely, after the reformulation.MethodsAn experimental design strategy was utilized to reveal the influence of reformulation factors (addition of new actives, preparation method change) on textural and rheological properties of cosmetic emulsions, especially those linked to certain sensorial attributes, and droplet size.ResultsThe general experimental factorial design revealed a significant direct effect of each factor, as well as their interaction effects, on certain characteristics of the system and provided some valuable information necessary for fine‐tuning reformulation conditions. Upon addition of STEM‐liposomes, consistency, index of viscosity, firmness and cohesiveness were decreased, as along with certain rheology parameters (elastic and viscous modulus), whereas maximal and minimal apparent viscosities and droplet size were increased. The presence of an emollient (squalene) affected all the investigated parameters in a concentration‐dependent manner. Modification of the preparation method (using Ultra Turrax instead of a propeller stirrer) produced emulsions with higher firmness and maximal apparent viscosity, but led to a decrease in minimal apparent viscosity, hysteresis loop area, all monitored parameters of oscillatory rheology and droplet size.ConclusionThe study showed that the established approach which combines a general experimental design and instrumental, rheological and textural measurements could be appropriate, more objective, repeatable and time and money‐saving step towards developing cosmetic emulsions with satisfying, improved or unchanged, consumer‐acceptable performance during the reformulation.
El auge del empleo precario en Europa. Conceptos, indicadores y efectos de la crisis económica mundial
Authors: GUTIÉRREZ BARBARRUSA Tomás 
Published: April 2017

ResumenDesde los años setenta y ochenta las economías occidentales experimentan un aumento de la precariedad laboral, consecuencia de la reorganización del proceso productivo y de las políticas neoliberales de flexibilización. El autor revisa el concepto atendiendo a su doble dimensión de inseguridad y pobreza, y documenta el impacto de la crisis económica mundial sobre su evolución y características en la UE‐15 con un indicador construido a partir de estas dos dimensiones y datos de Eurostat de 1995 a 2015. Se observa un aumento generalizado de la precariedad a partir de la crisis de 2008, debido a la pobreza en los mercados más desreglamentados y a la inseguridad en los meridionales.
Influencia del empleo temporal y por cuenta propia en la trayectoria laboral en la República de Corea
Authors: AHN Taehyun 
Published: April 2017

ResumenEn relación con el empleo estándar, es decir, permanente, los porcentajes de empleo temporal y por cuenta propia están aumentando en gran parte del mundo desarrollado. El autor examina la dinámica de esta tendencia en la República de Corea investigando las decisiones laborales de hombres y mujeres en plena edad de trabajar. Con datos de panel, modelos logit multinomiales y una especificación de análisis factorial de efectos aleatorios, encuentra que el empleo temporal no suele conducir al permanente y que el empleo por cuenta propia es el menos conducente a la situación sin empleo al año siguiente.
La proliferación de las pasantías y el reto de reglamentar en favor de una experiencia laboral decente
Authors: OWENS Rosemary , STEWART Andrew 
Published: April 2017

ResumenUna tendencia actual importante (aunque poco estudiada) en el ámbito laboral es la proliferación de las pasantías no remuneradas y otras formas de ≪adquisición de experiencia≫. Si bien responden al deseo comprensible de los solicitantes de empleo de afianzarse en mercados laborales muy competitivos, también posibilitan la explotación en empresas y organizaciones sin ánimo de lucro, al reemplazar puestos anteriormente remunerados para principiantes, y pueden reducir la movilidad social. Los autores analizan medidas jurídicas y políticas de países desarrollados seleccionados para tratar de sentar las bases de una respuesta más eficaz a un fenómeno que constituye ya un problema evidente para la consecución del trabajo decente.
Epigallocatechin gallate inhibits Streptococcus pneumoniae virulence by simultaneously targeting pneumolysin and sortase A
Authors: Song Meng , Teng Zihao , Li Meng , Niu Xiaodi , Wang Jianfeng , Deng Xuming 
Published: April 2017

AbstractStreptococcus pneumoniae (pneumococcus), the causative agent of several human diseases, possesses numerous virulence factors associated with pneumococcal infection and pathogenesis. Pneumolysin (PLY), an important virulence factor, is a member of the cholesterol‐dependent cytolysin family and has cytolytic activity. Sortase A (SrtA), another crucial pneumococcal virulence determinate, contributes greatly to the anchoring of many virulence‐associated surface proteins to the cell wall. In this study, epigallocatechin gallate (EGCG), a natural compound with little known antipneumococcal activity, was shown to directly inhibit PLY‐mediated haemolysis and cytolysis by blocking the oligomerization of PLY and simultaneously reduce the peptidase activity of SrtA. The biofilm formation, production of neuraminidase A (NanA, the pneumococcal surface protein anchored by SrtA), and bacterial adhesion to human epithelial cells (Hep2) were inhibited effectively when S. pneumoniae D39 was cocultured with EGCG. The results from molecular dynamics simulations and mutational analysis confirmed the interaction of EGCG with PLY and SrtA, and EGCG binds to Glu277, Tyr358, and Arg359 in PLY and Thr169, Lys171, and Phe239 in SrtA. In vivo studies further demonstrated that EGCG protected mice against S. pneumoniae pneumonia. Our results imply that EGCG is an effective inhibitor of both PLY and SrtA and that an antivirulence strategy that directly targets PLY and SrtA using EGCG is a promising therapeutic option for S. pneumoniae pneumonia.
Low glucose induces mitochondrial reactive oxygen species via fatty acid oxidation in bovine aortic endothelial cells
Authors: Kajihara Nobuhiro , Kukidome Daisuke , Sada Kiminori , Motoshima Hiroyuki , Furukawa Noboru , Matsumura Takeshi , Nishikawa Takeshi , Araki Eiichi 
Published: April 2017

AbstractAims/IntroductionOverproduction of reactive oxygen species (ROS) in endothelial cells (ECs) plays a pivotal role in endothelial dysfunction. Mitochondrial ROS (mtROS) is one of the key players in the pathogenesis of diabetic vascular complications. Hypoglycemia is linked to increased ROS production and vascular events; however, the underlying mechanisms remain unclear. In the present study, we aimed to determine whether and how low glucose (LG) mediates mtROS generation in ECs, and to examine the impact of LG‐induced mtROS on endothelial dysfunction.Materials and MethodsMetabolomic profiling, cellular oxygen consumption rate, mtROS, endothelial nitric oxide synthase phosphorylation, and the expression of vascular cell adhesion molecule‐1 or intercellular adhesion molecule‐1 were evaluated in bovine aortic ECs.ResultsWe found that LG increased mtROS generation in ECs; which was suppressed by overexpression of manganese superoxide dismutase. Comprehensive metabolic analysis using capillary electrophoresis‐mass spectrometry and oxygen consumption rate assessment showed that the pathway from fatty acid to acetyl‐CoA through fatty acid oxidation was upregulated in ECs under LG conditions. In addition, etomoxir, a specific inhibitor of the free fatty acid transporter, decreased LG‐induced mtROS production. These results suggested that LG increased mtROS generation through activation of fatty acid oxidation. We further revealed that LG inhibited endothelial nitric oxide synthase phosphorylation, and increased the expression of vascular cell adhesion molecule‐1 and intercellular adhesion molecule‐1. These effects were suppressed either by overexpression of manganese superoxide dismutase or by treatment with etomoxir.ConclusionsThe activation of fatty acid oxidation followed by mtROS production could be one of the causes for endothelial dysfunction during hypoglycemia.
A proposed scoring system for assessing the severity of actinic keratosis on the head: actinic keratosis area and severity index
Authors: Dirschka T. , Pellacani G. , Micali G. , Malvehy J. , Stratigos A.J. , Casari A. , Schmitz L. , Gupta G. ,   Athens AK Study Group
Published: April 2017

AbstractBackgroundActinic keratosis (AK) severity is currently evaluated by subjective assessment of patients.ObjectivesTo develop and perform an initial pilot validation of a new easy‐to‐use quantitative tool for assessing AK severity on the head.MethodsThe actinic keratosis area and severity index (AKASI) for the head was developed based on a review of other severity scoring systems in dermatology, in particular the psoriasis area and severity index (PASI). Initial validation was performed by 13 physicians assessing AK severity in 18 AK patients and two controls using a physician global assessment (PGA) and AKASI. To determine an AKASI score, the head was divided into four regions (scalp, forehead, left/right cheek ear, chin and nose). In each region, the percentage of the area affected by AKs was estimated, and the severities of three clinical signs of AK were assessed: distribution, erythema and thickness.ResultsThere was a strong correlation between AKASI and PGA scores (Pearson correlation coefficient: 0.86). AKASI was able to discriminate between different PGA categories: mean (SD) AKASI increased from 2.88 (1.18) for ‘light’ to 5.33 (1.48) for ‘moderate’, 8.28 (1.89) for ‘severe’, and 8.73 (3.03) for ‘very severe’ PGA classification. The coefficient of variation for AKASI scores was low and relatively constant across all PGA categories.ConclusionsActinic keratosis area and severity index is proposed as a new quantitative tool for assessing AK severity on the head. It may be useful in the future evaluation of new AK treatments in clinical studies and the management of AK in daily practice.
Comprehensive Geriatric Assessment for Prevention of Delirium After Hip Fracture: A Systematic Review of Randomized Controlled Trials
Authors: Shields Lynn , Henderson Victoria , Caslake Robert 
Published: April 2017

ObjectivesTo assess the efficacy of comprehensive geriatric assessment (CGA) in prevention of delirium after hip fracture.DesignSystematic review and metaanalysis.SettingWard based models on geriatrics wards and visiting team based models on orthopaedics wards were included.ParticipantsFour trials (three European, one U.S.; 973 participants) were identified. Two assessed ward‐based, and two assessed team‐based interventions.MeasurementsMEDLINE, EMBASE, CINAHL and PsycINFO databases; Clinicaltrials.gov; and the Central Register of Controlled Trials were searched. Reference lists from full‐text articles were reviewed. Incidence of delirium was the primary outcome. Length of stay, delirium severity, institutionalization, long‐term cognition and mortality were predefined secondary outcomes. Duration of delirium was included as a post hoc outcome.ResultsThere was a significant reduction in delirium overall (relative risk (RR) = 0.81, 95% confidence interval (CI) = 0.69–0.94) in the intervention group. Post hoc subgroup analysis found this effect to be preserved in the team‐based intervention group (RR = 0.77, 95% CI = 0.61–0.98) but not the ward‐based group. No significant effect was observed on any secondary outcome.ConclusionThere was a reduction in the incidence of delirium after hip fracture with CGA. This is in keeping with results of non‐randomized controlled trials and trials in other populations. Team‐based interventions appeared superior in contrast to the Ellis CGA paper, but it is likely that heterogeneity in interventions and population studied affected this.
Treatment of tibial diaphyseal fractures following plateless tibial tuberosity advancement to manage cranial cruciate disease
Authors: De Sousa R. , Egan P. , Parsons K. , Butterworth S. , Calvo I. , Roch S. , Moores A. P. 
Published: April 2017

ObjectiveTo report diaphyseal fractures of the proximal tibia following tibial tuberosity advancement without plate stabilisation for the management of cranial cruciate ligament rupture in dogs.MethodsMembers of the British Veterinary Orthopaedic Association's online discussion forum were invited to submit revision cases of tibial diaphyseal fracture following tibial tuberosity advancement without plate fixation. Data collected included signalment, surgical revision technique, pre‐ and postoperative revision radiographic findings, complications and veterinary assessment. Owners were invited to complete the Liverpool Osteoarthritis in Dogs questionnaire.ResultsA total of 17 dogs were included in the study. Eleven dogs had OrthoFoam‐wedge modified Maquet procedures and six had the tibial tuberosity advancement rapid procedure. Tibial tuberosity advancement was maintained in 14/17 cases. Postrevision surgery complications occurred in eight cases: minor complications in 3/17 dogs; major in 5/17 and no catastrophic complications. Surgical site infection was the most common complication (4/8). Final clinical outcome found 8/17 of dogs to have excellent, 8/17 satisfactory and 1/17 poor clinical outcome. The median Liverpool Osteoarthritis in Dogs score was 12/52 (range 2 to 28). Final outcome was 6/13 owners that were very satisfied, 2/13 owners indifferent and 5/13 owners very disappointed.Clinical SignificanceThis is the first case series reporting tibial diaphyseal fractures following tibial tuberosity advancement without plate stabilisation. The authors report here a wide spectrum of potential fixation strategies should one of these fractures occur.