phenix.mr_rosetta: molecular replacement and model rebuilding with Phenix and Rosetta.

The combination of algorithms from the structure-modeling field with those of crystallographic structure determination can broaden the range of templates that are useful for structure determination by the method of molecular replacement. Automated tools in phenix.mr_rosetta simplify the application of these combined approaches by integrating Phenix crystallographic algorithms and Rosetta structure-modeling algorithms and by systematically generating and evaluating models with a combination of these methods. The phenix.mr_rosetta algorithms can be used to automatically determine challenging structures. The approaches used in phenix.mr_rosetta are described along with examples that show roles that structure-modeling can play in molecular replacement

The Latent Class Structure of ADHD is stable across informants

Previous studies have looked at the structure of attention-deficit/ hyperactivity disorder (ADHD) using latent class analysis (LCA) of Child Behavior Checklist (CBCL) or Diagnostic and Statistical Manual of Mental Disorders (DSM) symptom structure. These studies have identified distinct classes of children with inattentive, hyperactive, or combined subtypes and have used these classes to refine genetic analyses. The objective of the current report is to determine if the latent class structure of ADHD subtypes is consistent across informant using the Conners' Rating Scales (CRS). LCA was applied to CRS forms from mother, father, and teacher reports of 1837, 1329 and 1048 latency aged Dutch twins, respectively. The optimal solution for boys was a 5-class solution for mothers, a 3-class solution for fathers, and a 4-class solution for teachers. For girls, a 4-class solution for mothers and a 3-class for fathers and teachers was optimal. Children placed into a class by one informant had markedly increased odds ratio of being placed into the same or similar class by the other informants. Results from LCA using Dutch twins with the CRS show stability across informants suggesting that more stable phenotypes may be accessible for genotyping using a multi-informant approach

Na mira do sucesso : estratégias de combate ao insucesso escolar de alunos estrangeiros

Trabalho de projeto de mestrado, Ciências da Educação (Área de especialização Formação de Adultos), Universidade de Lisboa, Instituto de Educação, 2017Considerando a importância da integração no contexto escolar e consequentemente no sucesso educativo, o presente trabalho projeto, desenvolvido no âmbito do Mestrado em Ciências da Educação, área de especialidade em Formação de Adultos, centra-se na integração de alunos estrangeiros no ensino português, assim como na dinamização de atividades de promoção do seu sucesso escolar. Deste modo, o relatório apresenta como principais temáticas a integração de estrangeiros em Portugal, o insucesso escolar dos alunos estrangeiros e as políticas educativas de combate a este fenómeno, culminando na definição e desenvolvimento de um projeto de combate ao insucesso escolar destinado a este público. O trabalho desenvolvido junto destes jovens nos últimos nove anos e o diagnóstico elaborado no Agrupamento de Escolas João de Barros permitiu compreender a importância de intervir junto da população estrangeira, fomentando o sucesso educativo e a integração no país de acolhimento, uma vez que a taxa de retenção destes jovens está muito acima dos seus colegas autóctones.Considering the importance of integration in the school context, and consequently in educational success, this project, developed in the scope of the master’s degree in Educational Sciences, specialization in Adult Education, focuses on foreign students’ integration at the Portuguese educational system and activities that could be developed to promote their school success. Therefore, the main themes of the report are the integration of foreigners in Portugal, the lack of academic experience from foreign students and educational policies to reduce this barrier, in order to define and develop a project to combat school failure among this cases. The work developed for the last nine years with this students, the diagnostic elaborated in João de Barros Group of Schools, allowed me to understand the importance of an intervention among foreign students, to foment educational success and integration in the host country, bearing in mind that the retention rate in those cases is far above the native students’ average

Clinical outcomes of EUS-guided drainage of debris-containing pancreatic pseudocysts: a large multicenter study

Background and study aims Data on clinical outcomes of endoscopic drainage of debris-free pseudocysts (PDF) versus pseudocysts containing solid debris (PSD) are very limited. The aims of this study were to compare treatment outcomes between patients with PDF vs. PSD undergoing endoscopic ultrasound (EUS)-guided drainage via transmural stents. Patients and methods Retrospective review of 142 consecutive patients with pseudocysts who underwent EUS-guided transmural drainage (TM) from 2008 to 2014 at 15 academic centers in the United States. Main outcome measures included TM technical success, treatment outcomes (symptomatic and radiologic resolution), need for endoscopic re-intervention at follow-up, and adverse events (AEs). Results TM was performed in 90 patients with PDF and 52 with PSD. Technical success: PDF 87 (96.7 %) vs. PSD 51 (98.1 %). There was no difference in the rates for endoscopic re-intervention (5.5 % in PDF vs. 11.5 % in PSD; P = 0.33) or AEs (12.2 % in PDF vs. 19.2 % in PSD; P = 0.33). Median long-term follow-up after stent removal was 297 days (interquartile range [IQR]: 59 - 424 days) for PDF and 326 days (IQR: 180 - 448 days) for PSD (P = 0.88). There was a higher rate of short-term radiologic resolution of PDF (45; 66.2 %) vs. PSD (21; 51.2 %) (OR = 0.30; 95 % CI: 0.13 - 0.72; P = 0.009). There was no difference in long-term symptomatic resolution (PDF: 70.4 % vs. PSD: 66.7 %; P = 0.72) or radiologic resolution (PDF: 68.9 % vs. PSD: 78.6 %; P = 0.72) Conclusions There was no difference in need for endoscopic re-intervention, AEs or long-term treatment outcomes in patients with PDF vs. PSD undergoing EUS-guided drainage with transmural stents. Based on these results, the presence of solid debris in pancreatic fluid collections does not appear to be associated with a poorer outcome

Testing assumptions for endophenotype studies in ADHD: Reliability and validity of tasks in a general population sample

BACKGROUND: Advances in both genetic and cognitive-experimental studies on attention deficit hyperactivity disorder (ADHD) have opened new opportunities for cognitive endophenotype research. In such genetic designs the focus is on individual differences in characteristics, associated with ADHD, that can be measured reliably over time. Genetic studies that take a 'quantitative trait loci' approach hypothesise that multiple susceptibility genes contribute to a continuous dimension of ADHD symptoms. As an important initial step, we aimed to investigate the underlying assumptions that (1) key cognitive-experimental tasks indicate adequate test-retest reliability and (2) ADHD symptom scores in a general population sample are associated with performance on these tasks. METHODS: Forty-nine children were assessed on a go/no-go task and a reaction time task (the 'fast task') that included manipulations with event rate and incentives. The children were assessed twice, with a test-retest interval of two weeks. RESULTS: The majority of the task variables demonstrated moderate-to-good test-retest reliability. The correlations between teacher ratings of ADHD symptoms and key task variables were .4–.6: ADHD symptoms were associated with poor performance (especially high reaction time variability) in a slow baseline condition, whereas there was low or no association in conditions with a faster event rate or incentives. In contrast, no clear pattern of findings emerged based on parent ratings of ADHD symptoms. CONCLUSION: The data support the usefulness of the go/no-go and fast tasks for genetic studies, which require reliable and valid indices of individual differences. The overall pattern of associations between teacher ratings of ADHD symptoms and task variables is consistent with effects of event rate and incentives on performance, as predicted by the model of activation and arousal regulation. The lack of a clear pattern of findings with parent ratings of ADHD symptoms warrants further study

Fatal alcohol intoxication in women: A forensic autopsy study from Slovakia

<p>Abstract</p> <p>Background</p> <p>Plenty of information related to alcoholism can be found in the literature, however, the studies have mostly dealt with the predominance of male alcoholism and data related to addiction in women are desperately scarce and difficult to find. Basic demographic data focusing on the impact of acute alcohol intoxication on the circumstances of death and social behaviour in the alcohol addicted female population are needed especially in the prevention of alcohol related mortality.</p> <p>Methods</p> <p>A retrospective forensic autopsy study of all accidental deaths due to alcohol intoxication over a 12-year period was performed in order to evaluate the locations, circumstances, mechanisms and causes of death.</p> <p>Results</p> <p>A sample of 171 cases of intoxicated women who died due to blood alcohol concentration (BAC) equal to or higher than 2 g/kg was selected. Among them 36.26% (62/171) of women died due to acute alcohol intoxication (AAI). We noted an increase in the number of deaths in women due to AAI from 2 in 1994 up to 5 in 2005 (an elevation of 150% between the years 1994-2005). The age structure of deaths in women due to BAC and AAI followed the Gaussian distribution with a dominant group of women aged 41-50 years (45.16% and 35.09% respectively). The most frequent place of death (98%) among women intoxicated by alcohol was their own home. The study suggests a close connection between AAI and violence against women.</p> <p>Conclusions</p> <p>The increasing number of cases of death of women suffering from AAI has drawn attention to the serious problem of alcoholism in women in the Slovak Republic during the process of integration into "western" lifestyle and culture.</p

Postoperative pericardial effusion, pericardiotomy, and atrial fibrillation: an explanatory analysis of the PALACS trial

BackgroundIn the Posterior left pericardiotomy for the prevention of atrial fibrillation after cardiac surgery (PALACS) trial, posterior pericardiotomy was associated with a significant reduction in postoperative atrial fibrillation (POAF) after cardiac surgery. We aimed to investigate the mechanisms underlying this effect.MethodsWe included PALACS patients with available echocardiographic data (n = 387/420, 92%). We tested the hypotheses that the reduction in POAF with the intervention was associated with 1) a reduction in postoperative pericardial effusion and/or 2) an effect on left atrial size and function. Spline and multivariable logistic regression analyses were used.ResultsMost patients (n = 307, 79%) had postoperative pericardial effusions (anterior 68%, postero-lateral 51.9%). The incidence of postero-lateral effusion was significantly lower in patients undergoing pericardiotomy (37% vs 67%; P P = .42), but there was a nonsignificant trend towards larger postero-lateral effusion in the POAF group (5.0 [IQR 3.0–9.0] vs 4.0 [IQR 3.0–6.4] mm; P = .06). There was a non-linear association between postero-lateral effusion and POAF at a cut-off at 10 mm (OR 2.70; 95% CI 1.13, 6.47; P = .03) that was confirmed in multivariable analysis (OR 3.5, 95% CI 1.17, 10.58; P = 0.02). Left atrial dimension and function did not change significantly after posterior pericardiotomy.ConclusionsReduction in postero-lateral pericardial effusion is a plausible mechanism for the effect of posterior pericardiotomy in reducing POAF. Measures to reduce postoperative pericardial effusion are a promising approach to prevent POAF.Graphical abstractPathophysiological mechanisms explaining the association between postoperative pericardial effusion and the occurrence of postoperative atrial fibrillation. Hb, hemoglobin; MetHb, methemoglobin; OxyHb, oxyhemoglobin; ROS, reactive oxygen species.Cardiolog

Lateral opening in the intact β-barrel assembly machinery captured by cryo-EM

The β-barrel assembly machinery (BAM) is a ~203 kDa complex of five proteins (BamA-E) which is essential for viability in E. coli. BAM promotes the folding and insertion of β-barrel proteins into the outer membrane via a poorly understood mechanism. Several current models suggest that BAM functions through a ‘lateral gating’ motion of the β-barrel of BamA. Here we present a cryo-EM structure of the BamABCDE complex, at 4.9 Å resolution. The structure is in a laterally open conformation showing that gating is independent of BamB binding. We describe conformational changes throughout the complex, and interactions between BamA, B, D, and E and the detergent micelle that suggest communication between BAM and the lipid bilayer. Finally, using an enhanced reconstitution protocol and functional assays, we show that for the outer membrane protein OmpT, efficient folding in vitro requires lateral gating in BAM

Transpapillary drainage has no added benefit on treatment outcomes in patients undergoing EUS-guided transmural drainage of pancreatic pseudocysts: a large multicenter study

Background and Aims The need for transpapillary drainage (TPD) in patients undergoing transmural drainage (TMD) of pancreatic fluid collections (PFCs) remains unclear. The aims of this study were to compare treatment outcomes between patients with pancreatic pseudocysts undergoing TMD versus combined (TMD and TPD) drainage (CD) and to identify predictors of symptomatic and radiologic resolution. Methods This is a retrospective review of 375 consecutive patients with PFCs who underwent EUS-guided TMD from 2008 to 2014 at 15 academic centers in the United States. Main outcome measures included TMD and CD technical success, treatment outcomes (symptomatic and radiologic resolution) at follow-up, and predictors of treatment outcomes on logistic regression. Results A total of 375 patients underwent EUS-guided TMD of PFCs, of which 174 were pseudocysts. TMD alone was performed in 95 (55%) and CD in 79 (45%) pseudocysts. Technical success was as follows: TMD, 92 (97%) versus CD, 35 (44%) (P = .0001). There was no difference in adverse events between the TMD (15%) and CD (14%) cohorts (P = .23). Median long-term (LT) follow-up after transmural stent removal was 324 days (interquartile range, 72-493 days) for TMD and 201 days (interquartile range, 150-493 days) (P = .37). There was no difference in LT symptomatic resolution (TMD, 69% vs CD, 62%; P = .61) or LT radiologic resolution (TMD, 71% vs CD, 67%; P = .79). TPD attempt was negatively associated with LT radiologic resolution of pseudocyst (odds ratio, 0.11; 95% confidence interval, 0.02-0.8; P = .03). Conclusions TPD has no benefit on treatment outcomes in patients undergoing EUS-guided TMD of pancreatic pseudocysts and negatively affects LT resolution of PFCs