University of Strathclyde at TREC HARD

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

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

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

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

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

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

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

HDAC3 is a molecular brake of the metabolic switch supporting white adipose tissue browning.

White adipose tissue (WAT) can undergo a phenotypic switch, known as browning, in response to environmental stimuli such as cold. Post-translational modifications of histones have been shown to regulate cellular energy metabolism, but their role in white adipose tissue physiology remains incompletely understood. Here we show that histone deacetylase 3 (HDAC3) regulates WAT metabolism and function. Selective ablation of Hdac3 in fat switches the metabolic signature of WAT by activating a futile cycle of de novo fatty acid synthesis and β-oxidation that potentiates WAT oxidative capacity and ultimately supports browning. Specific ablation of Hdac3 in adipose tissue increases acetylation of enhancers in Pparg and Ucp1 genes, and of putative regulatory regions of the Ppara gene. Our results unveil HDAC3 as a regulator of WAT physiology, which acts as a molecular brake that inhibits fatty acid metabolism and WAT browning.Histone deacetylases, such as HDAC3, have been shown to alter cellular metabolism in various tissues. Here the authors show that HDAC3 regulates WAT metabolism by activating a futile cycle of fatty acid synthesis and oxidation, which supports WAT browning

Age-related changes in bile acid synthesis and hepatic nuclear receptor expression

BACKGROUND:Recent data highlighted the role of nuclear receptors in the transcriptional regulation of the limiting enzyme of bile acid synthesis, cholesterol 7alpha-hydroxylase, in cellular and animal models. This study was designed to analyze the effects of age on cholesterol 7alpha-hydroxylase and related nuclear receptor expression in human livers.DESIGN:Surgical liver biopsies were obtained in 23 patients requiring operation on the gastrointestinal tract. mRNA levels of cholesterol 7alpha-hydroxylase and related nuclear receptors and co-activators were assayed by quantitative real-time RT-PCR. Serum levels of 7alpha-hydroxy-4-cholesten-3-one, a marker of bile acid synthesis, were assayed by gas-liquid chromatography:mass spectrometry.RESULTS:Ageing was inversely correlated with serum 7alpha-hydroxy-4-cholesten-3-one and with cholesterol 7alpha-hydroxylase mRNA levels (r = -0.44 and r = -0.45 on a semi-log scale, respectively, P < 0.05). Among different nuclear factors, cholesterol 7alpha-hydroxylase mRNA best correlated with hepatocyte nuclear factor-4 (r = 0.55 on a log scale, P < 0.05); hepatocyte nuclear factor-4 levels were also inversely correlated with age (r = -0.64 on a semi-log scale, P < 0.05). Age was inversely correlated with serum insulin-like growth factor-I levels, which were directly correlated with hepatocyte nuclear factor-4 and cholesterol 7alpha-hydroxylase expression. No suppressive effect of short heterodimer partner expression on cholesterol 7alpha-hydroxylase was observed.CONCLUSIONS:Ageing associates with reduced bile acid synthesis, possibly related to decreased hepatic expression of hepatocyte nuclear factor-4 and consequently of cholesterol 7alpha-hydroxylase. Age-related modifications of the growth hormone/insulin-like growth factor axis might play a role. These findings may help to elucidate the pathophysiology of age-related modifications of cholesterol metabolism

Robotic-assisted, laparoscopic, and open radical cystectomy: surgical data of 1400 patients from The Italian Radical Cystectomy Registry on intraoperative outcomes

Introduction: The Italian Radical Cystectomy Registry (Registro Italiano Cistectomie - RIC) aimed to analyse outcomes of a multicenter series of patients treated with radical cystectomy (RC) for bladder cancer. Material and methods: An observational, prospective, multicenter, cohort study was performed to collect data from RC and urinary diversion via open (ORC), laparoscopic (LRC), or robotic-assisted (RARC) techniques performed in 28 Italian Urological Departments. The enrolment was planned from January 2017 to June 2020 (goal: 1000 patients), with a total of 1425 patients included. Chi-square and t-tests were used for categorical and continuous variables. All tests were 2-sided, with a significance level set at p &lt;0.05. Results: Overall median operative-time was longer in RARCs (390 minutes, IQR 335-465) than ORCs (250, 217-309) and LRCs (292, 228-350) (p &lt;0.001). Lymph node dissection (LND) was performed more frequently in RARCs (97.1%) and LRCs (93.5%) than ORCs (85.6%) (p &lt;0.001), with extended-LND performed 2-fold more frequently in RARCs (61.6%) (p &lt;0.001). The neobladder rate was significantly higher (more than one-half) in RARCs. The median estimated blood loss (EBL) rate was lower in RARCs (250 ml, 165-400) than LRCs (330, 200-600) and ORCs (400, 250-600) (p &lt;0.001), with intraoperative blood transfusion rates of 11.4%, 21.7% and 35.6%, respectively (p &lt;0.001). The conversion to open rate was slightly higher in RARCs (6.8%) than LRCs (4.3%). Intraoperative complications occurred in 1.3% of cases without statistically significant differences among the approaches. Conclusions: Data from the RIC confirmed the need to collect as much data as possible in a multicenter manner. RARCs proves to be feasible with perioperative complication rates that do not differ from the other approaches

DISTRIBUIÇÃO E BIOMASSA DE MACROALGAS EM UM MANGUEZAL DA BAÍA DA BABITONGA, SC: RESULTADOS PRELIMINARES

This work aims to assess distribution and biomass of epiphyte macroalgae of mangrove roots in the Babitonga Bay. The macroalgae were collected monthly in three topographyc levels into the mangrove (Places A, B and C). In each place the collect was stratified in the trees (0 to 10 cm high, 10 to 20 cm , etc). The observed Rhodophyta, from higher to smaller biomass, were: Bostrychia calliptera, Bostrychia pinnata, Bostrychia radicans f. radicans, Bostrychia montagnei, Catenella caespitosa, Caloglossa leprieurii, Bostrychia tenella, Caloglossa ogazawaraensis, Bostrychia radicans f. moniliforme, Bostrychia moritziana, Polysiphonia howei, Bostrychia binderi, Gelidium spp., Polysiphonia tepida. The observed Chlorophyta were: Bloodleopsis pusilla, Cladophoropsis membranacea, Rhizoclonium spp., Ulvaria oxysperma, Enteromorpha spp. There are strong variation on horizontal and vertical biomass and on contribution of each species to total biomass. In the mangrove fringe (place A) the algae occur from 0 to 60 cm high in the trees, the mean biomass along this high varies 30 and 45 g m-2 of substrate. Higher values of biomass occur between 10 and 30 cm high, rising to 75 g m-2. On place B (intermediate tidal flooding) the algae occur from 0 to 30 cm high in the trees, the mean biomass along this high varies 20 and 30 g m-2 of substrate. Higher values of biomass occur between 0 and 10 cm high (50 g m-2 of substrate), but high values may also occur between 10 and 20 cm high. In the inner mangrove (place C) the algae occur from 0 to 20 cm high in the trees, the mean biomass along this high varies 10 and 20 g m-2 of substrate. Like place B, higher values of biomass occur between 0 and 10 cm high (35 g m-2 of substrate), but high values may also occur between 10 and 20 cm high. The green algae, Bloodleopsis pusilla, Cladophoropsis membranacea, Rhizoclonium, and the red algae, Bostrychia montagnei, Caloglossa leprieurii and Caloglossa ogazawaraensis were mainly present from 0 to 10 cm high, and rarely occur above 20 cm. Bostrychia radicans f. radicans presents the most broad distribution, has the higher frequency of occurrence in all places and all strata, and it is the main algae in the upper strata. The higher values of biomass, specially on place A, are due to Bostrychia calliptera and Bostrychia pinnata. This two algae also have a broad vertical and horizontal distribution, but they have higher values from 10 to 30 cm high. The results found until now suggest that macroalgae may be an important component of mangrove primary production. Meanwhile, to evaluate the mangrove magroalgae biomass, we need to include algae epiphytic on pneumatophores. And to evaluate the contribution of these algae to the total primary production of the mangrove, it will be necessary to complement biomass data with ecophysiological experiments, including the responses of growth and photosynthetic rates to environmental factors.Este trabalho tem como objetivo determinar a distribuição e quantificar a biomassa de macroalgas presentes nas raízes e troncos das árvores de manguezal da Baía de Babitonga. Para tal, as macroalgas foram coletadas mensalmente (setembro/1997 a junho/1998) em 3 níveis topográficos dentro do manguezal (Linhas A, B e C). Em cada linha a coleta foi estratificada de acordo com a altura das algas no tronco (0 a 10 cm de altura, 10 a 20 cm , etc). As espécies de Rhodophyta observadas, em ordem decrescente de biomassa, foram: Bostrychia calliptera, Bostrychia pinnata, Bostrychia radicans f. radicans, Bostrychia montagnei, Catenella caespitosa, Caloglossa leprieurii, Bostrychia tenella, Caloglossa ogazawaraensis, Bostrychia radicans f. moniliforme, Bostrychia moritziana, Polysiphonia howei, Bostrychia binderi, Gelidium spp., Polysiphonia tepida. As Chlorophyta são Bloodleopsis pusilla, Cladophoropsis membranacea, Rhizoclonium spp., Ulvaria oxysperma, Enteromorpha spp. Há uma forte variação horizontal e vertical na biomassa e na contribuição de cada espécie para a biomassa total. Na franja do manguezal (linha A) as algas ocupam uma altura de 60 cm, e a biomassa média por tronco varia entre 30 e 45 g m-2 de tronco. A maior biomassa ocorre entre 10 e 30 cm, chegando a 75 g m-2 de tronco. Na porção intermediária (linha B) as algas ocupam uma altura de 30 cm e a biomassa média varia entre 20 e 30 g m-2 de tronco. A biomassa é maior nos primeiros 10 cm (50 g m-2 de tronco), mas pode atingir altos valores também entre 10 e 20 cm. Na porção interna do manguezal (linha C) as algas ocupam uma altura de 20 cm, e a biomassa média varia entre 10 e 20 g m-2 de tronco. Assim como na linha B, a biomassa é maior nos primeiros 10 cm (35 g m-2 de tronco), mas pode atingir altos valores também entre 10 e 20 cm. As algas verdes Bloodleopsis pusilla, Cladophoropsis membranacea, Rhizoclonium, e as algas vermelhas Bostrychia montagnei, Caloglossa leprieurii e Caloglossa ogazawaraensis estão presentes principalmente nos primeiros 10 cm de altura, raramente ocorrendo acima de 20 cm. Bostrychia radicans f. radicans é a alga mais amplamente distribuída, com maior freqüência de ocorrência e a mais abundante na região superior do tronco nas três linhas. As algas que apresentam a maior biomassa, especialmente na linha A, são Bostrychia calliptera e Bostrychia pinnata, que também apresentam distribuição vertical e horizontal ampla, mas são mais abundantes entre 10 e 30 cm de altura. Os resultados obtidos até o momento indicam que as macroalgas podem ser vistas como um componente produtor representativo dentro do manguezal. Entretanto, para uma avaliação da biomassa de macroalgas no manguezal como um todo, é necessário quantificar a biomassa de algas em pneumatóforos. Para avaliar a contribuição destas algas para a produção primária do manguezal, os dados de biomassa devem ser complementados com experimentos de crescimento e produtividade, com relação aos fatores ambientais