619 research outputs found

    University of Strathclyde at TREC HARD

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    The motivation behind the University of Strathclyde's approach to this years HARD track was inspired from previous experiences by other participants, in particular research by [1], [3] and [4]. A running theme throughout these papers was the underlying hypothesis that a user's familiarity in a topic (i.e. their previous experience searching a subject), will form the basis for what type or style of document they will perceive as relevant. In other words, the user's context with regards to their previous search experience will determine what type of document(s) they wish to retrieve

    Ensemble Kalman filter versus ensemble smoother for assessing hydraulic conductivity via tracer test data assimilation

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    Abstract. Estimating the spatial variability of hydraulic conductivity K in natural aquifers is important for predicting the transport of dissolved compounds. Especially in the nonreactive case, the plume evolution is mainly controlled by the heterogeneity of K. At the local scale, the spatial distribution of K can be inferred by combining the Lagrangian formulation of the transport with a Kalman-filter-based technique and assimilating a sequence of time-lapse concentration C measurements, which, for example, can be evaluated on site through the application of a geophysical method. The objective of this work is to compare the ensemble Kalman filter (EnKF) and the ensemble smoother (ES) capabilities to retrieve the hydraulic conductivity spatial distribution in a groundwater flow and transport modeling framework. The application refers to a two-dimensional synthetic aquifer in which a tracer test is simulated. Moreover, since Kalman-filter-based methods are optimal only if each of the involved variables fit to a Gaussian probability density function (pdf) and since this condition may not be met by some of the flow and transport state variables, issues related to the non-Gaussianity of the variables are analyzed and different transformation of the pdfs are considered in order to evaluate their influence on the performance of the methods. The results show that the EnKF reproduces with good accuracy the hydraulic conductivity field, outperforming the ES regardless of the pdf of the concentrations

    Mitochondrial dysfunction increases fatty acid β-oxidation and translates into impaired neuroblast maturation

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    The metabolic transition from anaerobic glycolysis and fatty acid \u3b2-oxidation to glycolysis coupled to oxidative phosphorylation is a key process for the transition of quiescent neural stem cells to proliferative neural progenitor cells. However, a full characterization of the metabolic shift and the involvement of mitochondria during the last step of neurogenesis, from neuroblasts to neuron maturation, is still elusive. Here, we describe a model of neuroblasts, Neuro2a cells, with impaired differentiation capacity due to mitochondrial dysfunction. Using a detailed biochemical characterization consisting of steady-state metabolomics and metabolic flux analysis, we find increased fatty acid \u3b2-oxidation as a peculiar feature of neuroblasts with altered mitochondria. The consequent metabolic switch favors neuroblast proliferation at the expense of neuron maturation

    Efetividade das terapias em grupo na qualidade de vida de pacientes com fibromialgia: uma revisão sistemática

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    Introduction: Fibromyalgia is a very common pain syndrome in clinical practice, characterized mainly by chronic and generalized musculoskeletal pain, as well as fatigue, joint stiffness and sleep disorders. However, it has a very wide and heterogeneous clinical presentation, compromising several spheres of patients’ lives. The objective was to verify the effectiveness of group therapies on the quality of life of fibromyalgia patients. Method: This is a systematic review, which sought to analyze research related to the topic between 2010 and 2020. The search for articles took place in the VHL in the LILACS and MEDLINE databases, including only original articles available in full. Results: 86 scientific publications were found and, after exclusion of duplicates, application of filters and initial analysis, 6 articles were selected to compose the sample body. Subsequently, the articles were grouped according to their central theme in: 1) Positive effects of interdisciplinary group therapy on the physical and psychosocial symptoms of fibromyalgia; 2) Empowerment of the patient in coping with fibromyalgia; and 3) Quality of professional assistance and the social support network of group therapy. Conclusion: It was found that the application of therapies in groups positively impacted the quality of life of patients in their physical, psycho-emotional and social dimensions. In addition, it was concluded that including the patient as the protagonist of their treatment and building a support network are essential for coping with the disease.Introdução: A fibromialgia é uma síndrome dolorosa muito comum na prática clínica, caracterizada, principalmente, por dor musculoesquelética crônica e generalizada, bem como fadiga, rigidez articular e distúrbios do sono. No entanto, possui uma apresentação clínica bastante vasta e heterogênea, comprometendo diversas esferas da vida dos pacientes. O objetivo foi verificar a efetividade das terapias em grupo na qualidade de vida dos pacientes fibromiálgicos. Método: Trata-se de uma revisão sistemática, a qual buscou analisar as pesquisas relacionadas ao tema entre 2010 e 2020. A busca dos artigos ocorreu na BVS nas bases de dados LILACS e MEDLINE, sendo incluídos apenas artigos originais disponíveis na íntegra. Resultados: Foram encontradas 86 publicações científicas e, após exclusão de duplicados, aplicação de filtros e análise inicial, foram selecionados 6 artigos para compor o corpo amostral. Posteriormente, os artigos foram agrupados de acordo com a sua temática central em: 1) Efeitos positivos da terapia interdisciplinar em grupo nos sintomas físicos e psicossociais da fibromialgia; 2) Empoderamento do paciente no enfrentamento da fibromialgia; e 3) Qualidade da assistência profissional e a rede de apoio social da terapia em grupo. Conclusão: Verificou-se que a aplicação das terapias em grupos impactou, positivamente, a qualidade de vida dos pacientes em sua dimensão física, psicoemocional e social. Além disso, concluiu-se que incluir o paciente como protagonista do seu tratamento e construir uma rede de apoio são fundamentais para o enfrentamento da doença

    Astrogliosis in epilepsy leads to overexpression of adenosine kinase, resulting in seizure aggravation

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    Adenosine kinase (ADK) is considered to be the key regulator of the brain's endogenous anticonvulsant, adenosine. In adult brain, ADK is primarily expressed in a subpopulation of astrocytes and striking upregulation of ADK in these cells has been associated with astrogliosis after kainic acid-induced status epilepticus (KASE) in the kainic acid mouse model of temporal lobe epilepsy. To investigate the causal relationship between KASE-induced astrogliosis, upregulation of ADK and seizure activity, we have developed a novel mouse model [the Adktm1−/−-Tg(UbiAdk) mouse] lacking the endogenous astrocytic enzyme due to a targeted disruption of the endogenous gene, but containing an Adk transgene under the control of a human ubiquitin promoter. Mutant Adktm1−/−-Tg(UbiAdk) mice were characterized by increased brain ADK activity and constitutive overexpression of transgenic ADK throughout the brain, with particularly high levels in hippocampal pyramidal neurons. This ADK overexpression was associated with increased baseline levels of locomotion. Most importantly, two-thirds of the mutant mice analysed exhibited spontaneous seizure activity in the hippocampus and cortex. This was the direct consequence of transgene expression, since this seizure activity could be prevented by systemic application of the ADK inhibitor 5-iodotubercidin. Intrahippocampal injection of kainate in the mutant mice resulted in astrogliosis to the same extent as that observed in wild-type mice despite the absence of endogenous astrocytic ADK. Therefore, KASE-induced upregulation of endogenous ADK in wild-type mice is a consequence of astrogliosis. However, seizures in kainic acid-injected mutants displayed increased intra-ictal spike frequency compared with wild-type mice, indicating that, once epilepsy is established, increased levels of ADK aggravate seizure severity. We therefore conclude that therapeutic strategies that augment the adenosine system after astrogliosis-induced upregulation of ADK constitute a neurochemical rationale for the prevention of seizures in epileps

    Weight loss and outcomes in subjects with progressive pulmonary fibrosis: data from the INBUILD trial

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    BACKGROUND: Lower body mass index (BMI) and weight loss have been associated with worse outcomes in some studies in patients with pulmonary fibrosis. We analyzed outcomes in subgroups by BMI at baseline and associations between weight change and outcomes in subjects with progressive pulmonary fibrosis (PPF) in the INBUILD trial. METHODS: Subjects with PPF other than idiopathic pulmonary fibrosis were randomized to receive nintedanib or placebo. In subgroups by BMI at baseline (< 25, ≥ 25 to < 30, ≥ 30 kg/m2), we analyzed the rate of decline in FVC (mL/year) over 52 weeks and time-to-event endpoints indicating disease progression over the whole trial. We used a joint modelling approach to assess associations between change in weight and the time-to-event endpoints. RESULTS: Among 662 subjects, 28.4%, 36.6% and 35.0% had BMI < 25, ≥ 25 to < 30 and ≥ 30 kg/m2, respectively. The rate of decline in FVC over 52 weeks was numerically greater in subjects with baseline BMI < 25 than ≥ 25 to < 30 or ≥ 30 kg/m2 (nintedanib: - 123.4, - 83.3, - 46.9 mL/year, respectively; placebo: - 229.5; - 176.9; - 171.2 mL/year, respectively). No heterogeneity was detected in the effect of nintedanib on reducing the rate of FVC decline among these subgroups (interaction p = 0.83). In the placebo group, in subjects with baseline BMI < 25, ≥ 25 to < 30 and ≥ 30 kg/m2, respectively, 24.5%, 21.4% and 14.0% of subjects had an acute exacerbation or died, and 60.2%, 54.5% and 50.4% of subjects had ILD progression (absolute decline in FVC % predicted ≥ 10%) or died over the whole trial. The proportions of subjects with these events were similar or lower in subjects who received nintedanib versus placebo across the subgroups. Based on a joint modelling approach, over the whole trial, a 4 kg weight decrease corresponded to a 1.38-fold (95% CI 1.13, 1.68) increase in the risk of acute exacerbation or death. No association was detected between weight loss and the risk of ILD progression or the risk of ILD progression or death. CONCLUSIONS: In patients with PPF, lower BMI at baseline and weight loss may be associated with worse outcomes and measures to prevent weight loss may be required. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02999178

    Ketogenic Diet : a New Light Shining on Old but Gold Biochemistry

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    Diets low in carbohydrates and proteins and enriched in fat stimulate the hepatic synthesis of ketone bodies (KB). These molecules are used as alternative fuel for energy production in target tissues. The synthesis and utilization of KB are tightly regulated both at transcriptional and hormonal levels. The nuclear receptor peroxisome proliferator activated receptor \u3b1 (PPAR\u3b1), currently recognized as one of the master regulators of ketogenesis, integrates nutritional signals to the activation of transcriptional networks regulating fatty acid \u3b2-oxidation and ketogenesis. New factors, such as circadian rhythms and paracrine signals, are emerging as important aspects of this metabolic regulation. However, KB are currently considered not only as energy substrates but also as signaling molecules. \u3b2-hydroxybutyrate has been identified as class I histone deacetylase inhibitor, thus establishing a connection between products of hepatic lipid metabolism and epigenetics. Ketogenic diets (KD) are currently used to treat different forms of infantile epilepsy, also caused by genetic defects such as Glut1 and Pyruvate Dehydrogenase Deficiency Syndromes. However, several researchers are now focusing on the possibility to use KD in other diseases, such as cancer, neurological and metabolic disorders. Nonetheless, clear-cut evidence of the efficacy of KD in other disorders remains to be provided in order to suggest the adoption of such diets to metabolic-related pathologies

    Spatial Distribution of Dung in Integrated Dairy Systems

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    Animals in grazing work as catalyst in the nutrient cycling processes of the ecosystems. Part of biomass that animal intake returning to soil in the degraded way like faeces and urine. The return is around 90% of the mineral nutrients, including nitrogen. However, it is necessary to know how these dejects are distributed on the area by animals. The environment management affects directly spatial distribution of these dejects. Drinking fountain, salt and feed trough, portress, rest area and shadow are structures that change the way that animal graze. Sward structure and herbage morphology affect the grazing behaviour as well. So, the objective this experiment was evaluate the spatial distribution of dung from dairy heifers in integrated systems of production at Mato Grosso, Brazil. The experiment was accomplished at Embrapa (Sinop/Mato Grosso/ Brazil). The experimental area was 10 ha divided in three systems: full sun, marginal shadowing (300 trees per ha) and intensive shadowing (750 trees per ha). Each system had different sizes, but 2.4 ha was useful area for all systems divided in 10 paddocks each. The tree used was Eucalyptus urograndis, H13 clone and the pasture was piata Grass (Urochloa brizantha). The grazing was done when the sward reached 95% light interception. It was evaluated a group of 24 breed heifers with 350 kg in three periods of year. Each paddock was divided in 25 grids for count of faeces boards. The spatial faeces distribution was evaluated with GPS, by walking and capturing points where there was faeces boards in all steps for the grassland paddocks, in three periods of year (rainy, rainy-drought transition and dry period). The dataset was analysed by SAS 9.2 version, using PROC MIXED and PDIFF to 5% of significance. The spatial distribution of dung had significant difference only in rainy-drought transition period (P=0.0165) and interaction effect between shadowing and site (P=0.0025) in this period of year and dry period as well (P=0. 0465). In both periods, the distribution was the same. The full sun system promoted more concentration of faeces boards in sites next portress and border fence in site opposite to portress. In marginal shadowing system, the major concentration was in the central area and under shadow. In intensive shadowing system, the major concentration of dung boards was under shadow, sites preferred by heifers for rumination and leisure activities. The kind of shade and the year periods affected in spatial dung distribution. There were places with more dung concentration, in all kind of shade, but when the pasture had the intensive shade, the dispersion was more homogeneous. Unlike expected, the dung deposition didn?t happens only under treetops. The distribution is more homogeneous when trees are in large quantities. The shadow area available in the grassland affected the spatial dung distribution, and can be more homogeneous than no shadow
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