From Easy to Hopeless - Predicting the Difficulty of Phylogenetic Analyses

Phylogenetic analyzes under the Maximum-Likelihood (ML) model are time and resource intensive. To adequately capture the vastness of tree space, one needs to infer multiple independent trees. On some datasets, multiple tree inferences converge to similar tree topologies, on others to multiple, topologically highly distinct yet statistically indistinguishable topologies. At present, no method exists to quantify and predict this behavior. We introduce a method to quantify the degree of difficulty for analyzing a dataset and present Pythia, a Random Forest Regressor that accurately predicts this difficulty. Pythia predicts the degree of difficulty of analyzing a dataset prior to initiating ML-based tree inferences. Pythia can be used to increase user awareness with respect to the amount of signal and uncertainty to be expected in phylogenetic analyzes, and hence inform an appropriate (post-)analysis setup. Further, it can be used to select appropriate search algorithms for easy-, intermediate-, and hard-to-analyze datasets

The Free Lunch is not over yet—systematic exploration of numerical thresholds in maximum likelihood phylogenetic inference

Maximum likelihood (ML) is a widely used phylogenetic inference method. ML implementations heavily rely on numerical optimization routines that use internal numerical thresholds to determine convergence. We systematically analyze the impact of these threshold settings on the log-likelihood and runtimes for ML tree inferences with RAxML-NG, IQ-TREE, and FastTree on empirical datasets. We provide empirical evidence that we can substantially accelerate tree inferences with RAxML-NG and IQ-TREE by changing the default values of two such numerical thresholds. At the same time, altering these settings does not significantly impact the quality of the inferred trees. We further show that increasing both thresholds accelerates the RAxML-NG bootstrap without influencing the resulting support values. For RAxML-NG, increasing the likelihood thresholds ϵLnL and ϵbrlen to 10 and 103, respectively, results in an average tree inference speedup of 1.9 ± 0.6 on Data collection 1, 1.8 ± 1.1 on Data collection 2, and 1.9 ± 0.8 on Data collection 2 for the RAxML-NG bootstrap compared to the runtime under the current default setting. Increasing the likelihood threshold ϵLnL to 10 in IQ-TREE results in an average tree inference speedup of 1.3 ± 0.4 on Data collection 1 and 1.3 ± 0.9 on Data collection 2

Discontinuous BPS spectra in N=2N = 2 gauge theory

We consider the spectrum of BPS saturated states in $N = 2$ gauge theories in four dimensions. This spectrum may be discontinuous across real codimension one submanifolds of marginal stability in the moduli space of vacua. An example, which can be treated with semiclassical methods in the weak coupling limit, is the decay of quark-soliton bound states. For a quark and a soliton of electric-magnetic charge vectors $Q$ and $Q^\prime$ respectively, we find that as the manifold of marginal stability is crossed, the number of soliton states changes by a factor of $2^{Q \cdot Q^\prime}$, where the dot denotes the symplectic product.Comment: 10 pages, uses harvma

Randomized controlled trial of S-1 maintenance therapy in metastatic esophagogastric cancer – the multinational MATEO study

Background: The optimal duration of firstline chemotherapy in metastatic esophagogastric cancer is unknown. In most clinical trials therapy was given until tumour progression or limiting toxicity. Maintenance concepts aiming to prolong the duration of response and maintain quality of life have been established in other tumour types but not in esophagogastric cancer. S-1 is an oral fluoropyrimidine with proven efficacy in metastatic esophagogastric cancer. Methods: The Maintenance Teysuno® (S-1) in esophagogastric cancer (MATEO) trial is a multinational, randomized phase II study that explores the role of S-1 maintenance therapy in Her-2 negative, advanced esophagogastric adenocarcinoma. After a 12-week firstline platinum-fluoropyrimidine-based chemotherapy patients without tumour progression are randomized in a 2:1 allocation to receive S-1 alone or continue with the same regimen as during the primary period. The primary endpoint is overall survival. Secondary endpoints include safety and toxicity, progression-free survival and quality of life. Correlative biomarker analyses focus on the identification of a subgroup of patients with a prolonged benefit from S-1 based maintenance therapy. Discussion: MATEO will be the first trial to define the role of a S-1 based maintenance therapy in patients having received a platinum-based firstline chemotherapy. Trial registration: NCT02128243 (date of registration: 29–04-2014)

Working from home and management controls

The Covid-19 pandemic and the corresponding shift toward working from home (WFH) amplifies control problems within organizations and poses severe challenges for management control as employees’ tasks are difficult to observe under WFH conditions. We examine the association between WFH and action controls. Based on a survey among employees in a large international corporation, we find that under WFH conditions the organization more intensively uses standardization and planning participation. We also examine the association between WFH and employee outcomes. The findings suggest that WFH is associated with more time employees spend in meetings and a higher job focus. Overall, the study adds to the literature by exploring the association between WFH and the use of management controls in organizations

Adaptive RAxML-NG: Accelerating Phylogenetic Inference under Maximum Likelihood using Dataset Difficulty

Phylogenetic inferences under the maximum likelihood criterion deploy heuristic tree search strategies to explore the vast search space. Depending on the input dataset, searches from different starting trees might all converge to a single tree topology. Often, though, distinct searches infer multiple topologies with large log-likelihood score differences or yield topologically highly distinct, yet almost equally likely, trees. Recently, Haag et al. introduced an approach to quantify, and implemented machine learning methods to predict, the dataset difficulty with respect to phylogenetic inference. Easy multiple sequence alignments (MSAs) exhibit a single likelihood peak on their likelihood surface, associated with a single tree topology to which most, if not all, independent searches rapidly converge. As difficulty increases, multiple locally optimal likelihood peaks emerge, yet from highly distinct topologies. To make use of this information, we introduce and implement an adaptive tree search heuristic in RAxML-NG, which modifies the thoroughness of the tree search strategy as a function of the predicted difficulty

Cardiac Repair and Regenerative Potential in the Goldfish (Carassius auratus) Heart

The remarkable ability of the heart to regenerate has been demonstrated in the zebrafish and giant danio, two fish members of the cyprinid family. Here we use light and electron microscopy to examine the repair response in the heart of another cyprinid, the goldfish (Carassius auratus), following cautery injury to a small portion of its ventricularmyocardium. We observed a robust inflammatory response in the first two weeks consisting primarily of infiltrating macrophages, heterophils, and melanomacrophages. These inflammatory cells were identified in the lumen of the spongy heart, within the site of the wound, and attached to endocardial cells adjacent to the site of injury. Marked accumulation of collagen fibers and increased connective tissue were also observed during the first and second weeks in a transition zone between healthy and injured myocardium as well as in adjacent sub-epicardial regions. The accumulation of collagen and connective tissue however did not persist. The presence of capillaries was also noted in the injured area during repair. The replacement of the cauterized region of the ventricle by myocardial tissue was achieved in 6 weeks. The presence of ethynyl deoxyuridinepositive cardiac myocytes and partially differentiated cardiac myocytes during repair suggest effective cardiac myocyte driven regeneration mechanisms also operate in the injured goldfish heart, and are similar to those observed in zebrafish and giant danio. Our data suggest the ability for cardiac regeneration may be widely conserved among cyprinids

Propriedades psicométricas do Inventário de Crescimento Pós-Traumático em uma amostra de estudantes universitários brasileiros

Objective: To examine psychometric properties of the Brazilian version of the Posttraumatic Growth Inventory (PTGI). Method: A total of 300 university students were evaluated though instruments that investigated trauma history, depression and posttraumatic symptoms, and personality traits through the Big Five model. Pearson's correlation was used to assess internal consistency, inter-item reliability and construct validity. Principal component analysis and confirmatory factor analysis were performed to investigate the factor structure of the PTGI. Results: Results confirmed the original five-factor structure. The results showed good internal consistency for the total scale (α = 0.91) and its subscales, ranging from α = 0.85 to α = 0.70. Also, evidence of construct and convergent validity was observed through correlations with posttraumatic and depression symptoms and personality measures. Conclusions: These preliminary results suggest that the Brazilian PTGI is reliable and showed adequate evidence of validity.Objetivo: O objetivo deste estudo é examinar as propriedades psicométricas da versão brasileira do Inventário de Crescimento Pós-Traumático (Posttraumatic Growth Inventory - PTGI). Método: Foram avaliados 300 estudantes universitários através de instrumentos que investigaram histórico de trauma, sintomas pós-traumáticos e de depressão e traços de personalidade através do modelo Big Five. A correlação de Pearson foi utilizada para investigar consistência interna, confiabilidade entre itens e procedimentos de validade de construto. Análise de componentes principais e análise de fatores confirmatórios foram realizadas para investigar a estrutura fatorial do PTGI. Resultados: Os resultados confirmaram a estrutura original de cinco fatores. Os resultados mostraram boa consistência interna para a escala total (α = 0.91) e suas subescalas, variando de α = 0.85 a α = 0.70. Além disso, evidências de validade de construto e convergente foram observadas através de correlações com sintomas pós-traumáticos e de depressão e medidas de personalidade. Conclusões: Os resultados preliminares sugerem que o PTGI brasileiro é confiável e apresentou evidência de validade adequada

ESCOLHA DA VIA DE PARTO: UMA QUESTÃO DE AUTONOMIA OU HETERONOMIA?

A cesárea surgiu como uma necessidade médica e foi se aprimorando com o passar do tempo (WEIDLE et al., 2014). Entretanto, a solução tornou-se um problema quando o número de cesáreas aumentou, intensificando os custos e a morbidez. Isso deveu-se ao desejo das mulheres e à conveniência do procedimento para os profissionais que o realizam. O objetivo neste trabalho foi descrever as vantagens e desvantagem dos tipos de parto, incluindo o motivo da preferência pelas cesáreas, além de demonstrar a influência dos profissionais de saúde e da sociedade na escolha da gestante. Quanto à metodologia, tratou-se de uma pesquisa com base em dados bibliográficos obtidos por meio de banco de dados referentes ao tema escolhido.  Segundo Silva (2014), durante o período gestacional cabe ao obstetra repassar as informações a respeito dos tipos de parto, esclarecendo as dúvidas da gestante durante as consultas pré-natais. Por outro lado, nem sempre essa escolha é respeitada e, muitas vezes, o médico acaba influenciando sua paciente na escolha do parto que mais o beneficie, tanto em questões financeiras quanto de comodidade. De acordo com Marchi (1998, p. 3-4), “Heteronomia [...] é o poder que se dá, ou que alguns profissionais pretendem ter, de determinar como seus pacientes devem se comportar, impondo sua vontade [...]” Para Weidle (2014), as taxas de cesariana sofrem variações em razão de fatores culturais e sociais ou da gestação de alto risco, e aumentam na população de maior poder aquisitivo. A indicação indiscriminada e incorreta da realização de cesarianas envolve diversos riscos para mães e recém-nascidos, podendo gerar complicações anestésicas, operatórias e resultantes em transfusões sanguíneas (WEIDLE, 2014). Um estudo mostrou mudança na escolha da via de parto do início para o final da gestação, em que a gestante opta pela cesárea por medo da dor e pela falta de atenção humanizada por parte dos médicos, além do despreparo e de fatores emocionais associados (WEIDLE, 2014, p. 47 e 53). Um estudo mostrou que a expectativa inicial da maioria das gestantes é pelo parto natural, e a dos médicos obstetras, pela cesárea, porém estes fariam tanto parto natural quanto cesárea se requisitado (LEGUIZAMON JÚNIOR et al., 2014).  Segundo o Ministério da Saúde (2005 apud SILVA et al., 2014), a vantagem do parto normal é a recuperação imediata. Contudo, alguns procedimentos não recomendados pela OMS são realizados em partos normais no SUS, como manipulação excessiva, confinamento e parto com o auxílio de episiotomia (WEIDLE, 2014).  Em conclusão, o tipo de parto deve ser escolhido cautelosamente, pois vai se refletir na saúde da mãe e do bebê. Para diversas gestantes, a dor é o principal motivo que as leva à desistência do parto normal no decorrer da gravidez. Contudo, as cesáreas, em que pese a diminuição de complicações, começaram a ser realizadas de forma excessiva nos últimos anos, tornando-se imprescindível que haja orientação adequada do profissional de saúde durante as consultas pré-natais no sentido de facilitar uma escolha consciente, sem influências externas e adequada ao tipo de gravidez.Palavras-chave: Parto. Cesárea. Autonomia. Gravidez. Influência

Terapia de Exposição com Realidade Virtual para Transtorno de Estresse Pós-Traumático para bancários: um estudo de caso com o banco virtual

Exposure Therapy (ET) is an established treatment for Posttraumatic Stress Disorder (PTSD), in which patients gradually confront trauma memories through mental imagery. Virtual Reality Exposure (VRE) is an alternative for those who have difficulties in recreating such memories. Most studies develop VRE scenarios of war or accidents; however, traumatic events in Brazil are mainly of urban violence. Objective: To evaluate the quality of the Virtual Bank scenario through a pilot case study of a banker with PTSD through a cognitive behavioral therapy protocol. Method: A 39-year-old bank employee diagnosed with PTSD through the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) took part on a Cognitive Behavioral Therapy (CBT) protocol including VRE. Patient’s symptoms were assessed through Beck’s anxiety and depression inventories, the Screen for Posttraumatic Stress Symptoms and Posttraumatic Cognitions Inventory. The therapy protocol was comprised of 16 sessions divided into three blocks: (i) psychoeducation; (ii) exposure and (iii) cognitive restructuring and relapse prevention. Reassessments were conducted at the end of each block. The sense of presence in the Virtual Bank was assessed through the Presence Questionnaire (PQ). Results: The patient presented at least 60% of reduction on all instruments and no longer met criteria for PTSD at posttreatment. The greatest reduction on PTSD symptoms scores occurred after the VRE block (-44.8%). The mean score of the PQ was 5.24. Conclusion: CBT protocol with VRE was effective in reducing all measures in this case study. Quality evaluation of the Virtual Bank was positive. Results are promising and similar to those of other innovative case studies using VRE for PTSD.Keywords: Posttraumatic Stress Disorder, Cognitive Behavioral Therapy, Virtual Reality, Trauma, Exposure Therapy.A Terapia de Exposição é um tratamento padrão-ouro para o Transtorno de Estresse Pós-Traumático (TEPT), na qual os pacientes confrontam gradualmente as memórias traumáticas por meio de imagens mentais. A Terapia de Exposição por Realidade Virtual é uma alternativa para aqueles que têm dificuldades na formação das imagens mentais. Embora a maioria dos cenários de Realidade Virtual seja de guerra ou acidentes, no Brasil, a maior parte dos eventos traumáticos está relacionado com a violência urbana. Objetivo: Avaliar a qualidade do cenário do Banco Virtual por meio de um estudo de caso piloto com uma bancária com TEPT, através de um protocolo de terapia cognitivo comportamental. Método: Uma bancária diagnosticada com TEPT pela Entrevista Clínica Estruturada para o DSM-IV (SCID) foi atendida em um protocolo de Terapia Cognitivo Comportamental (TCC) incluindo a Terapia de Exposição por Realidade Virtual. Os sintomas foram investigados por meio dos Inventários Beck de Ansiedade e Depressão, o Inventário de Cognições Pós-traumáticas e o Instrumento para Rastreio de Sintomas Pós-traumáticos. O protocolo foi composto por 16 sessões divididas em três blocos: (i) psicoeducação; (ii) exposição; e (iii) reestruturação cognitiva e prevenção à recaída. Foram conduzidas reavaliações ao final de cada bloco. A sensação de presença foi medida por meio do Questionário de Presença (QP). Resultados: A paciente apresentou redução de no mínimo 60% em todos os instrumentos e não fechava critério para TEPT ao final do tratamento. A maior redução nos sintomas de TEPT ocorreu após a exposição (-44,8%). A média do QP foi de 5,24. Conclusões: O protocolo foi efetivo na redução de todas as medidas nesse estudo de caso. A qualidade do Banco Virtual foi satisfatória. Os resultados são promissores e semelhantes aos de outros estudos de caso inovadores que usaram ERV para o TEPT.Palavras-chave: Transtorno de Estresse Pós-Traumático, Terapia Cognitivo Comportamental, Realidade Virtual, Terapia de Exposição