Brain Connectivity and Information-Flow Breakdown Revealed by a Minimum Spanning Tree-Based Analysis of MRI Data in Behavioral Variant Frontotemporal Dementia

Brain functional disruption and cognitive shortfalls as consequences of neurodegeneration are among the most investigated aspects in current clinical research. Traditionally, specific anatomical and behavioral traits have been associated with neurodegeneration, thus directly translatable in clinical terms. However, these qualitative traits, do not account for the extensive information flow breakdown within the functional brain network that deeply affect cognitive skills. Behavioural variant Frontotemporal Dementia (bvFTD) is a neurodegenerative disorder characterized by behavioral and executive functions disturbances. Deviations from the physiological cognitive functioning can be accurately inferred and modeled from functional connectivity alterations. Although the need for unbiased metrics is still an open issue in imaging studies, the graph-theory approach applied to neuroimaging techniques is becoming popular in the study of brain dysfunction. In this work, we assessed the global connectivity and topological alterations among brain regions in bvFTD patients using a minimum spanning tree (MST) based analysis of resting state functional MRI (rs-fMRI) data. Whilst several graph theoretical methods require arbitrary criteria (including the choice of network construction thresholds and weight normalization methods), MST is an unambiguous modeling solution, ensuring accuracy, robustness, and reproducibility. MST networks of 116 regions of interest (ROIs) were built on wavelet correlation matrices, extracted from 41 bvFTD patients and 39 healthy controls (HC). We observed a global fragmentation of the functional network backbone with severe disruption of information-flow highways. Frontotemporal areas were less compact, more isolated, and concentrated in less integrated structures, respect to healthy subjects. Our results reflected such complex breakdown of the frontal and temporal areas at both intra-regional and long-range connections. Our findings highlighted that MST, in conjunction with rs-fMRI data, was an effective method for quantifying and detecting functional brain network impairments, leading to characteristic bvFTD cognitive, social, and executive functions disorders

Splenic autoimplant and hyperbaric oxygen therapy in rats

OBJECTIVE: To study the functional and morphological features of splenic autoimplants in rats subjected, or not, to postoperative hyperbaric oxygen therapy. METHODS: One hundred and five male Wistar rats, weighing 251.6 g ± 29.5 g, were studied ot early (11th day) and late (70th day ) postoperative periods. For each period the animals were distributed in the following groups: A (n=40), splenic manipulation; B (n=65),splenic autoimplants, not treated (nt) (A11nt- n=10, B11nt- n=21, A70nt- n= 10, B70nt-n= 18) and treated with hyperbaric oxygen (t) ( A11t- n= 10, B11t- n=15, A70t - n=10, B70t- n=11). Blood was collected for measurement of lipids and immunoglobulins , platelet and Howell-Jolly body count before and after surgery. The spleen and autoimplants were removed for histologic analyses. RESULTS: There was an increase of total cholesterol (p=0.00068), LDL-cholesterol (p=0.002), VLDL-cholesterol and triglycerides (p=0.0033) in B11nt group. There was an increase of total cholesterol (p= 0.0007) and LDL-cholesterol (p=0.0000) in B70nt group, and no alterations were observed in the other groups. IgM decreased in B groups (p=0.0000) and no changes were observed in the splenic manipulation group. Number of Howell-Jolly bodies were lesser in Bt groups than in Bnt groups( p=0.03). Platelets were increased in B11t and B11nt groups (p=0.0000) and remained unchanged in the other groups. Autoimplants microscopic viability was better in Bt groups than in Bnt. CONCLUSION: The splenic autoimplants of rats treated with hyperbaric oxygen therapy showed a better functionality and viability than those subjected to other procedures.OBJETIVO: Estudar aspectos morfológicos e funcionais dos autoimplantes esplênicos de ratos submetidos ou não à oxigenioterapia hiperbárica (OHB). MÉTODOS: Foram estudados em dois períodos distintos 105 ratos Wistar. No período mediato (n= 56) os animais foram avaliados até o 11º dia de pós-operatório, e no período tardio (n= 49), até o 70º dia. Em cada período os ratos foram distribuídos nos grupos: A- Simulação, B- Autoimplante esplênico, tratados com oxigênio hiperbárico ou não. Nos animais do Grupo A realizou-se apenas manipulação do baço. Nos animais do Grupo B realizou-se esplenectomia total e a seguir quatro fragmentos do baço foram implantados no grande omento. Em todos os animais foram dosados os lípides e imunoglobulinas e contadas as plaquetas e os corpúsculos de Howell-Jolly no pré-operatório e no 11º ou 70º dia de pós-operatório. O baço dos animais do Grupo A e os autoimplantes dos animais do Grupo B foram retirados e enviados para avaliação morfológica. RESULTADOS: No grupo B11nt houve aumento do colesterol total, LDL-colesterol, VLDL-colesterol e triglicérides. No grupo B70nt houve aumento do colesterol total e LDL-colesterol. Nos grupos tratados não houve alterações lipídicas. A IgM caiu nos grupos B e não alterou nos grupos A. Os corpúsculos de Howell - Jolly foram menos freqüentes nos grupos Bt que nos grupos Bnt. As plaquetas aumentaram nos grupos B11t e B11nt e não se alteraram nos demais grupos. A viabilidade microscópica dos grupos Bt foi melhor que a dos grupos Bnt. CONCLUSÃO: Os autoimplantes esplênicos dos animais tratados com OHB apresentaram melhor função e viabilidade do que os autoimplantes dos animais não tratados.22623

Patients' perceptions of quality of care delivery by urology residents: A nationwide study

Objective To present the results of a nationwide survey among urological patients to evaluate their perception of the quality of care provided by residents. Methods An anonymous survey was distributed to patients who were referred to 22 Italian academic institutions. The survey aimed to investigate the professional figure of the urology resident as perceived by the patient. Results A total of 2587 patients were enrolled in this study. In all, 51.6% of patients were able to correctly identify a urology resident; however, almost 40% of respondents discriminated residents from fully trained urologists based exclusively on their young age. Overall, 98.2% patients rated the service provided by the resident as at least sufficient. Urology trainees were considered by more than 50% of the patients interviewed to have good communication skills, expertise and willingness. Overall, patients showed an excellent willingness to be managed by urology residents. The percentage of patients not available for this purpose showed an increasing trend that directly correlated with the difficulty of the procedure. Approximately 5-10% of patients were not willing to be managed by residents for simple procedures such as clinical visits, cystoscopy or sonography, and up to a third of patients were not prepared to undergo any surgical procedure performed by residents during steps in major surgery, even if the residents were adequately tutored. Conclusions Our data showed that patients have a good willingness to be managed by residents during their training, especially for medium- to low-difficulty procedures. Furthermore, the majority of patients interviewed rated the residents' care delivery as sufficient. Urology trainees were considered to have good communication skills, expertise and willingness

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Assessing the use of rainfall synthetic series to estimate rainfall erosivity in Brazil

Although it has been used in research or technical work, applying synthetic rainfall data series to estimate rainfall erosivity is still a tool that requires careful evaluation and validation. In this study we evaluate the potential use of synthetic data sets to estimate the rainfall erosivity index (R-factor) in order to validate the use of this tool throughout Brazil. Sub-hourly rainfall data from 141 pluviographic stations were used. Pluviographic synthetic series were generated from ClimaBR software. A computer routine was specifically developed to identify erosive rainfalls. R-factor was calculated from erosive rainfall events and from pluviographic synthetic series, as well as through regression equations proposed in the literature. It was observed that the method estimating rainfall erosivity from synthetic pluviographic series (SS) had satisfactory performance and was superior to the use of data based on empirical equations (EE). The results indicate that applying ClimaBR synthetic pluviographic series to estimate rainfall erosivity is a valid and potentially applicable alternative. Moreover, its application in Brazil showed no needs for calibration. Due to these results, we believe that R-factors can be calculated for each pluviographic station in the country by using SS, creating a useful rainfall erosivity map with wide distribution throughout Brazil

Critérios para Escolha de Distribuições de Probabilidades em Estudos de Eventos Extremos de Precipitação

Este estudo objetivou estabelecer um critério sobre qual teste de aderência deve ser preferido na escolha de funções de distribuição de probabilidades (fdp). Para tal, foram ajustadas as fdp: Gumbel (GUM), Generalizada de valores extremos (GEV) e Log-normal a 2 parâmetros (LN2), através dos métodos dos momentos, momentos-L e máxima verossimilhança, em séries de precipitação diária máxima anual de 11 estações localizadas na bacia hidrográfica do rio Sapucaí. A aderência dessas fdp aos dados foi feita pelos testes de Kolmogorov-Smirnov (KS), Qui-quadrado (χ2), Filliben (Fi) e Anderson-Darling (AD). Verificaram-se quais testes de aderência são mais rigorosos na seleção de distribuições de probabilidade e, ainda, os testes de aderência que convergem os resultados para a escolha da fdp com melhor desempenho na análise de incerteza e/ou nas estatísticas de ajuste. Os testes de aderência mais rigorosos no aceite da aderência da fdp aos dados são os testes de Fi e AD. O teste de Fi é o que mais converge para a escolha da fdp com melhor desempenho na análise de incerteza e nas estatísticas de ajuste, seguido pelo teste de χ2, portanto devem ser preferidos. As fdp GUM e GEV se destacaram em representar os dados de precipitação máxima anual.This study aimed to establish a criterion on which good of fit test should be preferred in the choice of probability distribution functions (pdf). For this, the Gumbel (GUM), Generalized Extreme Value (GEV) and 2-parameter Log-Normal (LN2) were fit Moments, L-moments and maximum likelihood methods, in annual maximum daily precipitation series of 11 rain gauges located in the hydrographic basin of the Sapucaí river. The adherence of these fdp to the data was made by the Kolmogorov-Smirnov (KS), Chi-square (χ2), Filliben (Fi) and Anderson-Darling (AD) tests. It was verified which good of fit tests are more rigorous in the selection of pdf and also the good of fit test that converge the results to the choice of the best performing fdp in the uncertainty analysis and/or statistics performance. The most stringent good of fit test on the adherence of fdp to the data are the Fi and AD tests. The Fi test, followed by the χ2 test showed best performance in terms of goodness of fit and convergence therefore, they should be preferred to others tests. The GUM and GEV are great pfd in representing the annual maximum precipitation data

Significance of topoisomerase III beta expression in breast ductal carcinomas: strong associations with disease-specific survival and metastasis

Topoisomerases are ubiquitous nuclear enzymes that regulate DNA structure in eukaryotic cells. The role of topoisomerase III beta, the newest member of the topoisomerase family, in the clinical outcome of breast cancer is still poorly understood. This study aims to investigate the immunoexpression of topoisomerase III beta in breast cancer and its relationships with clinicopathologic features and immunohistochemical markers of prognostic significance in breast pathology. Using tissue microarrays containing 171 cases of primary invasive breast cancer, we analyzed the immunoexpression of topoisomerase III beta, estrogen receptor, progesterone receptor, HER-2, BRCA-1, p53, and Ki67. Immunostaining for topoisomerase III beta was found in 33.9% of breast carcinomas, and immunopositivity was correlated with distant metastasis (P = .036) and death (P = .006). Decreased expression of topoisomerase III beta correlated with low expression of Ki67 (P < .001) and negativity for HER-2 (P < .001), BRCA-1 (P = .001), and p53 (P < .001). In the multivariate analysis, topoisomerase Hip expression was a significant predictor of survival (hazard ratio, 3.006 [95% confidence interval, 1.582-5.715]; P = .001). In conclusion, topoisomerase III beta expression can be a useful marker in assessing the prognosis of patients with breast cancer and is an independent predictor of survival. (C) 2010 Elsevier Inc. All rights reserved.National Council for Scientific and Technological Development (CNPq)[470412/07-0

Critérios para Escolha de Distribuições de Probabilidades em Estudos de Eventos Extremos de Precipitação

Resumo Este estudo objetivou estabelecer um critério sobre qual teste de aderência deve ser preferido na escolha de funções de distribuição de probabilidades (fdp). Para tal, foram ajustadas as fdp: Gumbel (GUM), Generalizada de valores extremos (GEV) e Log-normal a 2 parâmetros (LN2), através dos métodos dos momentos, momentos-L e máxima verossimilhança, em séries de precipitação diária máxima anual de 11 estações localizadas na bacia hidrográfica do rio Sapucaí. A aderência dessas fdp aos dados foi feita pelos testes de Kolmogorov-Smirnov (KS), Qui-quadrado (χ2), Filliben (Fi) e Anderson-Darling (AD). Verificaram-se quais testes de aderência são mais rigorosos na seleção de distribuições de probabilidade e, ainda, os testes de aderência que convergem os resultados para a escolha da fdp com melhor desempenho na análise de incerteza e/ou nas estatísticas de ajuste. Os testes de aderência mais rigorosos no aceite da aderência da fdp aos dados são os testes de Fi e AD. O teste de Fi é o que mais converge para a escolha da fdp com melhor desempenho na análise de incerteza e nas estatísticas de ajuste, seguido pelo teste de χ2, portanto devem ser preferidos. As fdp GUM e GEV se destacaram em representar os dados de precipitação máxima anual