PhyloMissForest: a random forest framework to construct phylogenetic trees with missing data.

BACKGROUND: In the pursuit of a better understanding of biodiversity, evolutionary biologists rely on the study of phylogenetic relationships to illustrate the course of evolution. The relationships among natural organisms, depicted in the shape of phylogenetic trees, not only help to understand evolutionary history but also have a wide range of additional applications in science. One of the most challenging problems that arise when building phylogenetic trees is the presence of missing biological data. More specifically, the possibility of inferring wrong phylogenetic trees increases proportionally to the amount of missing values in the input data. Although there are methods proposed to deal with this issue, their applicability and accuracy is often restricted by different constraints. RESULTS: We propose a framework, called PhyloMissForest, to impute missing entries in phylogenetic distance matrices and infer accurate evolutionary relationships. PhyloMissForest is built upon a random forest structure that infers the missing entries of the input data, based on the known parts of it. PhyloMissForest contributes with a robust and configurable framework that incorporates multiple search strategies and machine learning, complemented by phylogenetic techniques, to provide a more accurate inference of lost phylogenetic distances. We evaluate our framework by examining three real-world datasets, two DNA-based sequence alignments and one containing amino acid data, and two additional instances with simulated DNA data. Moreover, we follow a design of experiments methodology to define the hyperparameter values of our algorithm, which is a concise method, preferable in comparison to the well-known exhaustive parameters search. By varying the percentages of missing data from 5% to 60%, we generally outperform the state-of-the-art alternative imputation techniques in the tests conducted on real DNA data. In addition, significant improvements in execution time are observed for the amino acid instance. The results observed on simulated data also denote the attainment of improved imputations when dealing with large percentages of missing data. CONCLUSIONS: By merging multiple search strategies, machine learning, and phylogenetic techniques, PhyloMissForest provides a highly customizable and robust framework for phylogenetic missing data imputation, with significant topological accuracy and effective speedups over the state of the art.

Take me where I want to go: Institutional prestige, advisor sponsorship, and academic career placement preferences.

Placement in prestigious research institutions for STEM (science, technology, engineering, and mathematics) PhD recipients is generally considered to be optimal. Yet some doctoral recipients are not interested in intensive research careers and instead seek alternative careers, outside but also within academe (for example teaching positions in Liberal Arts Schools). Recent attention to non-academic pathways has expanded our understanding of alternative PhD careers. However, career preferences and placements are also nuanced along the academic pathway. Existing research on academic careers (mostly research-centric) has found that certain factors have a significant impact on the prestige of both the institutional placement and the salary of PhD recipients. We understand less, however, about the functioning of career preferences and related placements outside of the top academic research institutions. Our work builds on prior studies of academic career placement to explore the impact that prestige of PhD-granting institution, advisor involvement, and cultural capital have on the extent to which STEM PhDs are placed in their preferred academic institution types. What determines whether an individual with a preference for research oriented institutions works at a Research Extensive university? Or whether an individual with a preference for teaching works at a Liberal Arts college? Using survey data from a nationally representative sample of faculty in biology, biochemistry, civil engineering and mathematics at four different Carnegie Classified institution types (Research Extensive, Research Intensive, Master's I & II, and Liberal Arts Colleges), we examine the relative weight of different individual and institutional characteristics on institutional type placement. We find that doctoral institutional prestige plays a significant role in matching individuals with their preferred institutional type, but that advisor involvement only has an impact on those with a preference for research oriented institutions. Gender effects are also observed, particularly in the role of the advisor in affecting preferred career placement.

Radiographic changes of cervical spine in rheumatoid arthritis.

INTRODUCTION: The involvement of the cervical spine is a common feature of rheumatoid arthritis (RA). OBJECTIVE: To study the prevalence of radiographic changes of the cervical spine in patients with RA and their association with clinical and serological profiles of the disease. METHODS: We analysed lateral (neutral position, hyperextension, hyperflexion) and transoral views of cervical spine radiographs from 80 individuals with RA to investigate the presence of atlanto-axial subluxation (AAS), basilar invagination (BI), and subaxial instability (SAI). Demographic, clinical (nodules, interstitial pneumonitis, secondary Sjögren's syndrome, medications etc.), and serologic (rheumatoid factor--RF, cyclic citrullinated peptide antibody--anti-CCP, and antinuclear factor--ANF) data were obtained from the clinical records. RESULTS: Cervical spine misalignments were identified in 26/80 (32.5%) participants; AAS occurred in 12/80 (15%) participants, BI in 6/80 (7.5%), and SAI in 13/80 (32.5%). Odontoid erosions were identified in 16/80 (20.0%) participants. Cervical spine misalignment exhibited associations with age at onset and disease duration (P = 0.03 and 0.02, respectively). No associations were identified between the cervical spine changes and the participants' ethnicity or gender, presence of nodules, interstitial pneumonitis, secondary Sjögren's syndrome, RF, ANF, or anti-CCP. The participants with cervical spine misalignment exhibited higher frequencies of odontoid erosion (P = 0.03). CONCLUSIONS: Cervical spine misalignment was a common radiographic finding and occurred more frequently in participants with earlier onset and longer length of RA.

Alterações radiográficas de coluna cervical em artrite reumatoide / Radiographic changes of cervical spine in rheumatoid arthritis

INTRODUÇÃO: O envolvimento da coluna cervical é comum na artrite reumatoide (AR). OBJETIVO: Estudar a prevalência das alterações radiológicas de coluna cervical em pacientes com AR e sua associação com perfil clinico e sorológico da doença. MÉTODOS: Analisaram-se as radiografias de coluna cervical em perfil neutro hiperextensão, hiperflexão e transoral de 80 pacientes com AR para presença de subluxação atlanto-axial (LAA), invaginação basilar (IB) e instabilidade subaxial (ISA). Dados de perfil demográfico, clínico (nódulos, pneumonite intersticial, síndrome Sjögren secundária, uso de medicamentos etc.) e sorológico (FR, anti-CCP e FAN) foram obtidos por revisão de prontuários. RESULTADOS: Havia alguma alteração de eixo de coluna cervical em 26/80 (32,5%); em 12/80 (15%) havia LAA; em 6/80(7,5%) existia IB; em 13/80 (16,2%) existia ISA. Erosões em odontoide foram vistas 16/80 (20,0%). As alterações do eixo cervical estavam associadas com idade de início da doença e duração da mesma (P = 0,03 e 0,02, respectivamente). Não se encontrou associação das alterações em coluna cervical com raça, gênero, nódulos, pneumonite intersticial, Sjögren secundário, FR, FAN ou anti-CCP. Pacientes com alterações do eixo cervical apresentavam mais erosões de odontoide (P = 0,03). CONCLUSÕES: Alterações radiológicas em eixo de coluna cervical são comuns e aparecem mais frequentemente em indivíduos com diagnóstico mais precoce de AR e maior tempo de doença.

INTRODUCTION: The involvement of the cervical spine is a common feature of rheumatoid arthritis (RA). OBJECTIVE: To study the prevalence of radiographic changes of the cervical spine in patients with RA and their association with clinical and serological profiles of the disease. METHODS: We analysed lateral (neutral position, hyperextension, hyperflexion) and transoral views of cervical spine radiographs from 80 individuals with RA to investigate the presence of atlanto-axial subluxation (AAS), basilar invagination (BI), and subaxial instability (SAI). Demographic, clinical (nodules, interstitial pneumonitis, secondary Sjögren's syndrome, medications etc.), and serologic (rheumatoid factor - RF, cyclic citrullinated peptide antibody - anti-CCP, and antinuclear factor - ANF) data were obtained from the clinical records. RESULTS: Cervical spine misalignments were identified in 26/80 (32.5%) participants; AAS occurred in 12/80 (15%) participants, BI in 6/80 (7.5%), and SAI in 13/80 (32.5%). Odontoid erosions were identified in 16/80 (20.0%) participants. Cervical spine misalignment exhibited associations with age at onset and disease duration (P = 0.03 and 0.02, respectively). No associations were identified between the cervical spine changes and the participants' ethnicity or gender, presence of nodules, interstitial pneumonitis, secondary Sjögren's syndrome, RF, ANF, or anti-CCP. The participants with cervical spine misalignment exhibited higher frequencies of odontoid erosion (P = 0.03). CONCLUSIONS: Cervical spine misalignment was a common radiographic finding and occurred more frequently in participants with earlier onset and longer length of RA.

Chaos in the square billiard with a modified reflection law.

The purpose of this paper is to study the dynamics of a square billiard with a non-standard reflection law such that the angle of reflection of the particle is a linear contraction of the angle of incidence. We present numerical and analytical arguments that the nonwandering set of this billiard decomposes into three invariant sets, a parabolic attractor, a chaotic attractor, and a set consisting of several horseshoes. This scenario implies the positivity of the topological entropy of the billiard, a property that is in sharp contrast with the integrability of the square billiard with the standard reflection law.

Ability of a synthetic coumestan to antagonize Bothrops snake venom activities.

We investigated a synthetic coumestan named LQB93 and similar compounds abilities to antagonize activities of Bothrops jararacussu and Bothrops jararaca crude venoms in different protocols. The antimyotoxic activity was evaluated in vitro by the rate of release of creatine kinase (CK) from isolated mouse extensor digitorum longus muscle (EDL) induced by B. jararacussu (25 g/ml). For in vivo studies, B. jararacussu venom (1.0 mg/kg) was preincubated with LQB93 (0.1-30 mg/kg), during 30 min, for later injection in mouse tight and evaluation of the antimyotoxic and anti-edematogenic effects. LQB93 antagonized in vitro, the increase of CK release from the EDL muscle (IC(50)=0.0291 M). It also showed in vivo, antimyotoxic and anti-edematogenic effects that were dose-dependent with ID50 of 0.17 mg/kg and 0.14 mg/kg, respectively. The hemorrhage induced by B. jararaca (1.0 mg/kg) venom in the mouse skin, was abolished by LQB93 (10.0 mg/kg) preincubated with venom. Like wedelolactone, LQB93 protected rat isolated heart on a Langendorff preparation, from the cardiotoxicity of B. jararacussu venom. LQB93 inhibit the effects of Bothrops venoms like wedelolactone, a natural compound isolated from the plant Eclipta prostrata.

Quality assurance in cervical screening of a high risk population: a study of 65,753 reviewed cases in Parana Screening Program, Brazil.

Epidemiological data from the Quality Assurance Unit (QAU) of the Cervical Cancer Screening Program of Paraná is discussed. Slides (65,753) reviewed by the QAU, from October 1997 to July 1999, were analyzed. Relations between agreement rate, diagnostic categories, and age groups were tested. The overall agreement rate was 97.04% (kappa +/- 95%, confidence interval = 0.888 +/- 0.003). Low-grade squamous intraepithelial lesion (LSIL) showed its peak prevalence in patients < or = 19 yr (8.3%). High-grade squamous intraepithelial lesion (HSIL) was more common in women between 40 and 49 yr (5.0%). Squamous-cell carcinoma (SCC) was almost exclusively seen in women > or = 40 yr. The lowest agreement rates were seen in adenocarcinoma (54.5%; kappa = 0.667) and LSIL cases (76.3%, kappa = 0.822), and in women < or = 19 yr (95.8%). It was concluded that constant monitoring to assess specific errors allows directed measures. The 10% rescreening model of quality assurance proved to be effective in a low resources setting with a positive overall financial impact.

Influence of specimen adequacy on the diagnosis of ASCUS.

The impact of specimen adequacy on the diagnosis of cervical cytology is not fully understood. Virtually, the greatest impact of smear quality limitation factors is on the diagnosis of atypical squamous cells of undetermined significance (ASCUS) because this category is more susceptible to interpretation mistake due to its criteria subjectivity. This study aims to evaluate the impact of smear quality impairing factors on the diagnosis of ASCUS. The 1,507 cases of ASCUS studied were obtained from the Cervical Cancer Screening Program of Paraná (CCSPP). The cases were reviewed by expert cytopathologists and the results were correlated to the specimen adequacy. The results showed that the presence of obscuring blood impairs the correct diagnosis and leads the pathologist to overdiagnose negative smears as ASCUS. The presence of adequate endocervical sampling contributes to a higher rate of correct ASCUS diagnoses but did not influence the pathologist to over- or underestimate the cytological findings.

Estudo de 11 casos de fibroelastose endocárdica primária / Primary endocardial fibroelastosis: study of 11 cases

INTRODUÇÃO: A fibroelastose endocárdica (FEE) é definida como espessamento difuso do endocárdio ventricular em função da proliferação de fibras colágenas e elásticas. Pode ser classificada como primária ou secundária. A FEE primária apresenta-se na forma dilatada, mais comum, ou na forma restritiva. Geralmente manifesta-se como insuficiência cardíaca inexplicada, em crianças com menos de 12 meses de idade. OBJEIVOS: Avaliar aspectos epidemiológicos, clínicos e anatomopatológicos da FEE primária. MATERIAL E MÉTODO: Foram pesquisadas, entre 1960 e 2000, 6.211 necropsias perinatais e pediátricas do Hospital de Clínicas da Universidade Federal do Paraná (UFPR), tendo sido verificados 11 casos de FEE. RESULTADOS: Em nove casos (81,8%), o surgimento dos sintomas ocorreu antes de 1 ano de idade. Em oito (72,7%), o óbito ocorreu antes de 1 ano de idade. Dentre os sinais clínicos, destacaram-se taquipnéia (54,5%), hepatomegalia (45,5%), tosse (36,4%), cianose (36,4%) e febre (36,4%). Todas as radiografias (n = 6) apresentavam cardiomegalia. O espessamento endocárdico predominou no coração esquerdo (90,9%). A causa de óbito foi insuficiência respiratória aguda em cinco casos (45,5%) e choque cardiogênico em quatro (36,4%). DISCUSSÃO E CONCLUSÕES: Os resultados mostram acometimento predominante de crianças com menos de 1 ano de idade e rápida progressão para óbito. Sinais clínicos freqüentes, como taquipnéia, tosse e febre, sugeriram infecção respiratória, que foi confirmada por necropsia em três casos (27,3%). Os exames complementares mostraram apenas achados sugestivos de insuficiência cardíaca. Os dados analisados neste estudo mostram que, em nosso meio, a FEE primária não difere significativamente do que é apresentado na literatura internacional em relação a características epidemiológicas, clínicas e anatomopatológicas.

BACKGROUND: Endocardial fibroelastosis (EFE) is a diffuse thickening of the ventricular endocardium resulting from proliferation of fibrous and elastic tissue. Primary and secondary forms have been described. Primary EFE occurs in the dilated and contracted forms. EFE usually manifests as unexplained congestive heart failure in infants younger than 1 year old. OBJECTIVES: To analyze the epidemiologic, clinical and anatomopathological aspects of primary EFE. METHODS: Eleven cases of histologically confirmed EFE were found in 6211 necropsies performed between 1960 and 2000 in the Hospital of the University of Paraná. Results: In nine cases (81.8%) the initial clinical presentation occurred before the age of 1 year. In eight cases (72.7%) patients died before the age of 1 year. The most common clinical findings were tachypnea (54.5%), hepatomegaly (45.5%), cough (36.4%) and fever (36.4%). Cardiomegaly was the main radiographic finding, present in all cases (n = 6). The endocardial thickening was more frequent at the left heart (90.9%). The death cause was acute respiratory failure in five cases (45.5%) and cardiogenic chock in four cases (36.4%). DISCUSSION AND CONCLUSIONS: The results showed that EFE affects usually infants younger than 1 year old that rapidly progress to death. Some common clinical findings like tachypnea, cough and fever suggested respiratory infection which was confirmed by necropsy in three cases (27.3%). The complementary tests showed only non-specific findings of congestive heart failure. The information analyzed here demonstrated no significant difference of the epidemiological, clinical and anatomopathological characteristics of primary EFE between Brazil and the international literature.

[Choroid plexus tumours: epidemiologic comparative study of 24 cases]. / Tumores de plexo coróide: estudo epidemiológico comparativo de 24 casos.

Tumours derived from choroid plexus are rare central nervous system neoplasms affecting mainly children. This study presents a series of 38 patients with neuroectodermal tumours. Twenty four of them had the histological and/or immunohistochemical diagnosis of choroid plexus carcinoma (CPC). Sixteen of these patients were male. The left lateral ventricle was affected in most cases. Main clinical features were: hydrocephalus, intracranial hypertension and convulsion. All the patients were treated by surgery. There were 2 deaths due to surgical complications. Nine patients had recurrence, dying in a intermediate time of 12.3 months and 7 patients remain alive. The other cases did not present available data. CPC is very prevalent in Curitiba when compared to other choroid plexus tumours and it might be related to some pathogenic agent.

Tumores de plexo coróide: estudo epidemiológico comparativo de 24 casos / Choroid plexus tumours: epidemiologic comparative study of 24 cases

Tumores derivados do plexo coróide são neoplasias raras do sistema nervoso central que acometem principalmente crianças. Este estudo apresenta uma série de 38 pacientes com tumores de origem neuroectodérmica, dentre os quais 24 possuem diagnóstico histológico e/ou imunoistoquímico de Carcinoma do Plexo Coróide (CPC). Destes, 16 eram do gênero masculino. O local predominantemente acometido foi o ventrículo lateral esquerdo. As manifestações clínicas mais freqüentes foram hidrocefalia, hipertensão intracraniana e crises convulsivas. Todos os pacientes foram submetidos a tratamento cirúrgico. Houve um óbito no per-operatório e outro no pós-operatório imediato. Nove pacientes tiveram recidiva, evoluindo a óbito em tempo médio de 12,3 meses. Sete estão vivos. Os demais casos não apresentavam dados disponíveis. Em Curitiba, o CPC tem uma alta prevalência em relação a outros tumores do plexo coróide, podendo estar relacionado a algum agente patogênico.

Synthesis and pharmacological evaluation of prenylated and benzylated pterocarpans against snake venom.

Edunol (3), a pterocarpan isolated from Harpalyce brasiliana, a plant used in the northeast of Brazil against snakebites, was obtained by synthesis and showed antimyotoxic, antiproteolytic and PLA2 inhibitor properties. These proprieties could be improved through the synthesis of a bioisoster (5), where the prenyl group was replaced by the benzyl group.