1,426 research outputs found

    Contests with rank-order spillovers

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    This paper presents a unified framework for characterizing symmetric equilibrium in simultaneous move, two-player, rank-order contests with complete information, in which each player's strategy generates direct or indirect affine "spillover" effects that depend on the rank-order of her decision variable. These effects arise in natural interpretations of a number of important economic environments, as well as in classic contests adapted to recent experimental and behavioral models where individuals exhibit inequality aversion or regret. We provide the closed-form solution for the symmetric Nash equilibria of this class of games, and show how it can be used to directly solve for equilibrium behavior in auctions, pricing games, tournaments, R&D races, models of litigation, and a host of other contests

    Widespread loss of mammalian lineage and dietary diversity in the early Oligocene of Afro-Arabia

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    Diverse lines of geological and geochemical evidence indicate that the Eocene-Oligocene transition (EOT) marked the onset of a global cooling phase, rapid growth of the Antarctic ice sheet, and a worldwide drop in sea level. Paleontologists have established that shifts in mammalian community structure in Europe and Asia were broadly coincident with these events, but the potential impact of early Oligocene climate change on the mammalian communities of Afro-Arabia has long been unclear. Here we employ dated phylogenies of multiple endemic Afro-Arabian mammal clades (anomaluroid and hystricognath rodents, anthropoid and strepsirrhine primates, and carnivorous hyaenodonts) to investigate lineage diversification and loss since the early Eocene. These analyses provide evidence for widespread mammalian extinction in the early Oligocene of Afro-Arabia, with almost two-thirds of peak late Eocene diversity lost in these clades by ~30 Ma. Using homology-free dental topographic metrics, we further demonstrate that the loss of Afro-Arabian rodent and primate lineages was associated with a major reduction in molar occlusal topographic disparity, suggesting a correlated loss of dietary diversity. These results raise new questions about the relative importance of global versus local influences in shaping the evolutionary trajectories of Afro-Arabia‘s endemic mammals during the Oligocene

    A pilot study on the immunogenicity of dendritic cell vaccination during adjuvant oxaliplatin/capecitabine chemotherapy in colon cancer patients

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    Contains fulltext : 87604.pdf (publisher's version ) (Closed access)BACKGROUND: Dendritic cell (DC) vaccination has been shown to induce anti-tumour immune responses in cancer patients, but so far its clinical efficacy is limited. Recent evidence supports an immunogenic effect of cytotoxic chemotherapy. Pre-clinical data indicate that the combination of chemotherapy and immunotherapy may result in an enhanced anti-cancer activity. Most studies have focused on the immunogenic aspect of chemotherapy-induced cell death, but only few studies have investigated the effect of chemotherapeutic agents on the effector lymphocytes of the immune system. METHODS: Here we investigated the effect of treatment with oxaliplatin and capecitabine on non-specific and specific DC vaccine-induced adaptive immune responses. Stage III colon cancer patients receiving standard adjuvant oxaliplatin/capecitabine chemotherapy were vaccinated at the same time with keyhole limpet haemocyanin (KLH) and carcinoembryonic antigen (CEA)-peptide pulsed DCs. RESULTS: In 4 out of 7 patients, functional CEA-specific T-cell responses were found at delayed type hypersensitivity (DTH) skin testing. In addition, we observed an enhanced non-specific T-cell reactivity upon oxaliplatin administration. KLH-specific T-cell responses remained unaffected by the chemotherapy, whereas B-cell responses were diminished. CONCLUSION: The results strongly support further testing of the combined use of specific anti-tumour vaccination with oxaliplatin-based chemotherapy

    Epidemiology and reporting characteristics of preclinical systematic reviews

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    In an effort to better utilize published evidence obtained from animal experiments, systematic reviews of preclinical studies are increasingly more common-along with the methods and tools to appraise them (e.g., SYstematic Review Center for Laboratory animal Experimentation [SYRCLE's] risk of bias tool). We performed a cross-sectional study of a sample of recent preclinical systematic reviews (2015-2018) and examined a range of epidemiological characteristics and used a 46-item checklist to assess reporting details. We identified 442 reviews published across 43 countries in 23 different disease domains that used 26 animal species. Reporting of key details to ensure transparency and reproducibility was inconsistent across reviews and within article sections. Items were most completely reported in the title, introduction, and results sections of the reviews, while least reported in the methods and discussion sections. Less than half of reviews reported that a risk of bias assessment for internal and external validity was undertaken, and none reported methods for evaluating construct validity. Our results demonstrate that a considerable number of preclinical systematic reviews investigating diverse topics have been conducted; however, their quality of reporting is inconsistent. Our study provides the justification and evidence to inform the development of guidelines for conducting and reporting preclinical systematic reviews

    Including all voices in international data-sharing governance

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    Background Governments, funding bodies, institutions, and publishers have developed a number of strategies to encourage researchers to facilitate access to datasets. The rationale behind this approach is that this will bring a number of benefits and enable advances in healthcare and medicine by allowing the maximum returns from the investment in research, as well as reducing waste and promoting transparency. As this approach gains momentum, these data-sharing practices have implications for many kinds of research as they become standard practice across the world. Main text The governance frameworks that have been developed to support biomedical research are not well equipped to deal with the complexities of international data sharing. This system is nationally based and is dependent upon expert committees for oversight and compliance, which has often led to piece-meal decisionmaking. This system tends to perpetuate inequalities by obscuring the contributions and the important role of different data providers along the data stream, whether they be low- or middle-income country researchers, patients, research participants, groups, or communities. As research and data-sharing activities are largely publicly funded, there is a strong moral argument for including the people who provide the data in decision-making and to develop governance systems for their continued participation. Conclusions We recommend that governance of science becomes more transparent, representative, and responsive to the voices of many constituencies by conducting public consultations about data-sharing addressing issues of access and use; including all data providers in decision-making about the use and sharing of data along the whole of the data stream; and using digital technologies to encourage accessibility, transparency, and accountability. We anticipate that this approach could enhance the legitimacy of the research process, generate insights that may otherwise be overlooked or ignored, and help to bring valuable perspectives into the decision-making around international data sharing.</p

    The ILAE classification of seizures and the epilepsies: Modification for seizures in the neonate. Position paper by the ILAE Task Force on Neonatal Seizures

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    Seizures are the most common neurological emergency in the neonatal period and in contrast to those in infancy and childhood, are often provoked seizures with an acute cause and may be electrographic‐only. Hence, neonatal seizures may not fit easily into classification schemes for seizures and epilepsies primarily developed for older children and adults. A Neonatal Seizures Task Force was established by the International League Against Epilepsy (ILAE) to develop a modification of the 2017 ILAE Classification of Seizures and Epilepsies, relevant to neonates. The neonatal classification framework emphasizes the role of electroencephalography (EEG) in the diagnosis of seizures in the neonate and includes a classification of seizure types relevant to this age group. The seizure type is determined by the predominant clinical feature. Many neonatal seizures are electrographic‐only with no evident clinical features; therefore, these are included in the proposed classification. Clinical events without an EEG correlate are not included. Because seizures in the neonatal period have been shown to have a focal onset, a division into focal and generalized is unnecessary. Seizures can have a motor (automatisms, clonic, epileptic spasms, myoclonic, tonic), non‐motor (autonomic, behavior arrest), or sequential presentation. The classification allows the user to choose the level of detail when classifying seizures in this age group

    A broader role for AmyR in Aspergillus niger: regulation of the utilisation of d-glucose or d-galactose containing oligo- and polysaccharides

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    AmyR is commonly considered a regulator of starch degradation whose activity is induced by the presence of maltose, the disaccharide building block of starch. In this study, we demonstrate that the role of AmyR extends beyond starch degradation. Enzyme activity assays, genes expression analysis and growth profiling on d-glucose- and d-galactose-containing oligo- and polysaccharides showed that AmyR regulates the expression of some of the Aspergillus niger genes encoding α- and β-glucosidases, α- and β- galactosidases, as well as genes encoding α-amlyases and glucoamylases. In addition, we provide evidence that d-glucose or a metabolic product thereof may be the inducer of the AmyR system in A. niger and not maltose, as is commonly assumed

    Idiopathic central precocious puberty in girls: presentation factors

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    <p>Abstract</p> <p>Background</p> <p>It is sometimes difficult to distinguish between premature thelarche and precocious puberty in girls who develop breasts before the age of 8 years. We evaluated the frequencies of the signs associated with breast development and the factors influencing the presentation of girls with idiopathic central precocious puberty (CPP).</p> <p>Methods</p> <p>353 girls monitored 0.9 ± 0.7 year after the onset of CPP.</p> <p>Results</p> <p>The age at CPP was < 3 years in 2%, 3–7 years in 38% and 7–8 years in 60% of cases. Pubic hair was present in 67%, growth rate greater than 2 SDS in 46% and bone age advance greater than 2 years in 33% of cases. Breast development was clinically isolated in 70 (20%) cases. However, only 31 of these (8.8% of the population) had a prepubertal length uterus and gonadotropin responses to gonadotropin releasing hormone and plasma estradiol. The clinical picture of CPP became complete during the year following the initial evaluation.</p> <p>25% of cases were obese. The increase in weight during the previous year (3.7 ± 1.4 kg) and body mass index were positively correlated with the statural growth and bone age advance (P < 0.0001).</p> <p>There was no relationship between the clinical-biological presentation and the age at puberty, the interval between the onset of puberty and evaluation, or the presence of familial CPP.</p> <p>Conclusion</p> <p>The variation in presentation of girls with CPP does not depend on their age, interval between the onset and evaluation, or familial factors. This suggests that there are degrees of hypothalamic-pituitary-ovarian activation that are not explained by these factors.</p

    CT colonography with minimal bowel preparation: evaluation of tagging quality, patient acceptance and diagnostic accuracy in two iodine-based preparation schemes

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    PURPOSE: The aim of this study was to compare a 1-day with a 2-day iodine bowel preparation for CT colonography in a positive faecal occult blood test (FOBT) screening population. MATERIALS AND METHODS: One hundred consecutive patients underwent CT colonography and colonoscopy with segmental unblinding. The first 50 patients (group 1) ingested 7 50 ml iodinated contrast starting 2 days before CT colonography. The latter 50 patients (group 2) ingested 4 50 ml iodinated contrast starting 1 day before CT colonography. Per colonic segment measurements of residual stool attenuation and homogeneity were performed, and a subjective evaluation of tagging quality (grade 1-5) was done. Independently, two reviewers performed polyp and carcinoma detection. RESULTS: The tagging density was 638 and 618 HU (p = 0.458) and homogeneity 91 and 86 HU for groups 1 and 2, respectively (p = 0.145). The tagging quality was graded 5 (excellent) in 90% of all segments in group 1 and 91% in group 2 (p = 0.749). Mean per-polyp sensitivity for lesions >or=10 mm was 86% in group 1 and 97% in group 2 (p = 0.355). Patient burden from diarrhoea significantly decreased for patients in group 2. CONCLUSIONS: One-day preparation with meglumine ioxithalamate results in an improved patient acceptability compared with 2-day preparation and has a comparable, excellent image quality and good diagnostic performanc
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