Correcting for the bias due to expression specificity improves the estimation of constrained evolution of expression between mouse and human.

MOTIVATION: Comparative analyses of gene expression data from different species have become an important component of the study of molecular evolution. Thus methods are needed to estimate evolutionary distances between expression profiles, as well as a neutral reference to estimate selective pressure. Divergence between expression profiles of homologous genes is often calculated with Pearson's or Euclidean distance. Neutral divergence is usually inferred from randomized data. Despite being widely used, neither of these two steps has been well studied. Here, we analyze these methods formally and on real data, highlight their limitations and propose improvements. RESULTS: It has been demonstrated that Pearson's distance, in contrast to Euclidean distance, leads to underestimation of the expression similarity between homologous genes with a conserved uniform pattern of expression. Here, we first extend this study to genes with conserved, but specific pattern of expression. Surprisingly, we find that both Pearson's and Euclidean distances used as a measure of expression similarity between genes depend on the expression specificity of those genes. We also show that the Euclidean distance depends strongly on data normalization. Next, we show that the randomization procedure that is widely used to estimate the rate of neutral evolution is biased when broadly expressed genes are abundant in the data. To overcome this problem, we propose a novel randomization procedure that is unbiased with respect to expression profiles present in the datasets. Applying our method to the mouse and human gene expression data suggests significant gene expression conservation between these species. CONTACT: marc.robinson-rechavi@unil.ch; sven.bergmann@unil.ch SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Pré-resfriamento de maçã (Malus domestica Borkh.), cv. Fuji, em função da temperatura e velocidade do ar

O objetivo do trabalho foi determinar o efeito de três velocidades e três temperaturas do ar, no pré-resfriamento de maçã, cv. Fuji, até 5ºC. Os tratamentos utilizados originaram-se da combinação de três temperaturas (-1,-2 ou -3ºC) e três velocidades do ar de resfriamento (1, 2 ou 3m.s-1). O decréscimo da temperatura dos frutos é maior e seu tempo de resfriamento diminui com o aumento da velocidade de 1m.s-1 para 3m.s-1 e a redução da temperatura do ar de refrigerado de -1ºC para -3ºC; sendo o decréscimo da temperatura e o tempo de resfriamento das maçãs mais dependentes da velocidade do ar de refrigeração do que da temperatura obtida na entrada do túnel. Existe uma relação direta entre o decréscimo de temperatura dos frutos e a posição das caixas no túnel pré-resfriador. Com uma velocidade de 3m.s-1 e temperatura de -3ºC foi possível resfriar maçãs de 25 para 5ºC, em 40 minutos.

Efeito do 1-metilciclopropeno na conservação de maçãs 'Royal Gala' em ar refrigerado e atmosfera controlada

Maçãs 'Royal Gala', colhidas em dois estádios de maturação, foram tratadas com 1-MCP (1-metilciclopropeno) nas concentrações de 0; 625 e 1250 nL.L-1, durante 48 horas, à temperatura de 20 ± 2 ºC. Após este tratamento, foram armazenadas em dois diferentes sistemas: em atmosfera controlada à temperatura de 0 ± 0,5 ºC, 2,1 a 2,3 kPa de CO2 , 1,8 a 2,0 kPa de O2 e umidade relativa de 95 ± 5 %, durante 9 meses. Em ar refrigerado a 0,5 ± 0,5 ºC e 95 ± 5 % de umidade relativa, durante 8 meses. As análises realizadas demonstraram a eficiência do 1-MCP em controlar a maturação das frutas durante o armazenamento em ambas as condições e pontos de colheita. A aplicação do 1-MCP reduziu drasticamente a produção de etileno, diminuiu a perda de firmeza, além de preservar a acidez total titulável.

Distribuição de líquido da ponta de pulverização com indução de ar e jato excêntrico AIUB 8502 sob diferentes condições

Objetivou-se com este trabalho avaliar a distribuição de líquido da ponta de pulverização com indução de ar e jato excêntrico AIUB 8502 sob diferentes condições operacionais. Foram avaliados perfil individual, vazão, ângulo de abertura do jato, faixa de aplicação e distribuição volumétrica simulada de duas pontas AIUB 8502 nas pressões de trabalho de 200, 300, 400 e 500 kPa, altura de 30, 40 e 50 cm em relação ao alvo e espaçamento entre pontas de 30 a 100 cm. Todas as análises foram realizadas seguindo a norma ISSO 5682-1, com algumas adaptações. A ponta apresentou distribuição de líquido excêntrica com um lado descontínuo e extremidade oposta excêntrica, com queda abrupta do volume de líquido. À medida que se aumentou a altura da barra e a pressão de trabalho, alongou-se o perfil do jato. O maior número de configurações uniformes foi obtido na altura de 50 cm, decrescendo nas alturas de 40 e 30 cm. A vazão e o ângulo do jato excêntrico aumentaram com o incremento na pressão, não havendo diferença entre o ângulo do jato descontínuo e o total entre as pressões de 400 e 500 kPa e de 200 e 300 kPa.

End-tidal carbon dioxide monitoring using a naso-buccal sensor is not appropriate to monitor capnia during non-invasive ventilation.

BACKGROUND: In acute respiratory failure, arterial blood gas analysis (ABG) is used to diagnose hypercapnia. Once non-invasive ventilation (NIV) is initiated, ABG should at least be repeated within 1 h to assess PaCO2 response to treatment in order to help detect NIV failure. The main aim of this study was to assess whether measuring end-tidal CO2 (EtCO2) with a dedicated naso-buccal sensor during NIV could predict PaCO2 variation and/or PaCO2 absolute values. The additional aim was to assess whether active or passive prolonged expiratory maneuvers could improve the agreement between expiratory CO2 and PaCO2. METHODS: This is a prospective study in adult patients suffering from acute hypercapnic respiratory failure (PaCO2 ≥ 45 mmHg) treated with NIV. EtCO2 and expiratory CO2 values during active and passive expiratory maneuvers were measured using a dedicated naso-buccal sensor and compared to concomitant PaCO2 values. The agreement between two consecutive values of EtCO2 (delta EtCO2) and two consecutive values of PaCO2 (delta PaCO2) and between PaCO2 and concomitant expiratory CO2 values was assessed using the Bland and Altman method adjusted for the effects of repeated measurements. RESULTS: Fifty-four datasets from a population of 11 patients (8 COPD and 3 non-COPD patients), were included in the analysis. PaCO2 values ranged from 39 to 80 mmHg, and EtCO2 from 12 to 68 mmHg. In the observed agreement between delta EtCO2 and deltaPaCO2, bias was -0.3 mmHg, and limits of agreement were -17.8 and 17.2 mmHg. In agreement between PaCO2 and EtCO2, bias was 14.7 mmHg, and limits of agreement were -6.6 and 36.1 mmHg. Adding active and passive expiration maneuvers did not improve PaCO2 prediction. CONCLUSIONS: During NIV delivered for acute hypercapnic respiratory failure, measuring EtCO2 using a dedicating naso-buccal sensor was inaccurate to predict both PaCO2 and PaCO2 variations over time. Active and passive expiration maneuvers did not improve PaCO2 prediction. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01489150.

Mapping Bias Overestimates Reference Allele Frequencies at the HLA Genes in the 1000 Genomes Project Phase I Data.

Next-generation sequencing (NGS) technologies have become the standard for data generation in studies of population genomics, as the 1000 Genomes Project (1000G). However, these techniques are known to be problematic when applied to highly polymorphic genomic regions, such as the human leukocyte antigen (HLA) genes. Because accurate genotype calls and allele frequency estimations are crucial to population genomics analyses, it is important to assess the reliability of NGS data. Here, we evaluate the reliability of genotype calls and allele frequency estimates of the single-nucleotide polymorphisms (SNPs) reported by 1000G (phase I) at five HLA genes (HLA-A, -B, -C, -DRB1, and -DQB1). We take advantage of the availability of HLA Sanger sequencing of 930 of the 1092 1000G samples and use this as a gold standard to benchmark the 1000G data. We document that 18.6% of SNP genotype calls in HLA genes are incorrect and that allele frequencies are estimated with an error greater than ±0.1 at approximately 25% of the SNPs in HLA genes. We found a bias toward overestimation of reference allele frequency for the 1000G data, indicating mapping bias is an important cause of error in frequency estimation in this dataset. We provide a list of sites that have poor allele frequency estimates and discuss the outcomes of including those sites in different kinds of analyses. Because the HLA region is the most polymorphic in the human genome, our results provide insights into the challenges of using of NGS data at other genomic regions of high diversity.

Sex differences in brain plasticity: a new hypothesis for sex ratio bias in autism.

Several observations support the hypothesis that differences in synaptic and regional cerebral plasticity between the sexes account for the high ratio of males to females in autism. First, males are more susceptible than females to perturbations in genes involved in synaptic plasticity. Second, sex-related differences in non-autistic brain structure and function are observed in highly variable regions, namely, the heteromodal associative cortices, and overlap with structural particularities and enhanced activity of perceptual associative regions in autistic individuals. Finally, functional cortical reallocations following brain lesions in non-autistic adults (for example, traumatic brain injury, multiple sclerosis) are sex-dependent. Interactions between genetic sex and hormones may therefore result in higher synaptic and consecutively regional plasticity in perceptual brain areas in males than in females. The onset of autism may largely involve mutations altering synaptic plasticity that create a plastic reaction affecting the most variable and sexually dimorphic brain regions. The sex ratio bias in autism may arise because males have a lower threshold than females for the development of this plastic reaction following a genetic or environmental event.

Vitamin E intake from natural sources and head and neck cancer risk : a pooled analysis in the International Head and Neck Cancer Epidemiology consortium.

BACKGROUND: Evidence for the possible effect of vitamin E on head and neck cancers (HNCs) is limited. METHODS: We used individual-level pooled data from 10 case-control studies (5959 cases and 12 248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium to assess the association between vitamin E intake from natural sources and cancer of the oral cavity/pharynx and larynx. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models applied to quintile categories of nonalcohol energy-adjusted vitamin E intake. RESULTS: Intake of vitamin E was inversely related to oral/pharyngeal cancer (OR for the fifth vs the first quintile category=0.59, 95% CI: 0.49-0.71; P for trend <0.001) and to laryngeal cancer (OR=0.67, 95% CI: 0.54-0.83, P for trend <0.001). There was, however, appreciable heterogeneity of the estimated effect across studies for oral/pharyngeal cancer. Inverse associations were generally observed for the anatomical subsites of oral and pharyngeal cancer and within covariate strata for both sites. CONCLUSION: Our findings suggest that greater vitamin E intake from foods may lower HNC risk, although we were not able to explain the heterogeneity observed across studies or rule out certain sources of bias.

Robust Estimates of the Negative Binomial Model

We consider robust parametric procedures for univariate discrete distributions, focusing on the negative binomial model. The procedures are based on three steps: ?First, a very robust, but possibly inefficient, estimate of the model parameters is computed. ?Second, this initial model is used to identify outliers, which are then removed from the sample. ?Third, a corrected maximum likelihood estimator is computed with the remaining observations. The final estimate inherits the breakdown point (bdp) of the initial one and its efficiency can be significantly higher. Analogous procedures were proposed in [1], [2], [5] for the continuous case. A comparison of the asymptotic bias of various estimates under point contamination points out the minimum Neyman's chi-squared disparity estimate as a good choice for the initial step. Various minimum disparity estimators were explored by Lindsay [4], who showed that the minimum Neyman's chi-squared estimate has a 50% bdp under point contamination; in addition, it is asymptotically fully efficient at the model. However, the finite sample efficiency of this estimate under the uncontaminated negative binomial model is usually much lower than 100% and the bias can be strong. We show that its performance can then be greatly improved using the three step procedure outlined above. In addition, we compare the final estimate with the procedure described in

Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data.

BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). METHODS: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. RESULTS: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). CONCLUSIONS: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.

Comparação entre fatores de calibração em termos de dose absorvida no ar para uma câmara de ionização de placas paralelas

OBJETIVO: O objetivo deste trabalho foi realizar uma comparação entre os fatores de calibração em termos de dose absorvida no ar determinados em feixes gama (60Co) e de elétrons. MATERIAIS E MÉTODOS: Foram utilizados um irradiador de 60Co e um acelerador linear Varian, modelo Clinac 2100C, com feixes de fótons e de elétrons. Foram testadas uma câmara de ionização cilíndrica e três de placas paralelas. RESULTADOS: Os sistemas de medidas foram submetidos aos testes preliminares (estabilidade de resposta e corrente de fuga), com resultados muito bons. Os fatores de calibração em termos de dose absorvida no ar foram determinados utilizando-se quatro sistemas de medidas e dois tipos de objetos simuladores, com a obtenção de resultados dentro das recomendações internacionais. CONCLUSÃO: Os resultados mostraram que os fatores de calibração em termos de dose absorvida no ar obtidos para câmaras de ionização de placas paralelas, determinados em feixes de 60Co, são no máximo 1,2% mais altos que os valores obtidos em feixes de elétrons de altas energias.

Curvas de isodose no ar em uma sala de mamografia

OBJETIVO: O objetivo deste trabalho foi obter a distribuição da dose absorvida no ar numa sala de mamografia durante a simulação de um exame mamográfico, visando a reavaliar a necessidade do uso de barreiras de proteção radiológica nessas salas e a exposição das pacientes. MATERIAIS E MÉTODOS: Os dados da dose absorvida no ar foram coletados mediante simulação de exame mamográfico de um simulador de mama de BR12, em um equipamento Senograph 600T-Senix HF. Para tal, 158 pastilhas de CaSO4 foram distribuídas em malhas retangulares em torno do bucky, em três alturas distintas. RESULTADOS: O valor mais elevado da dose absorvida no ar, registrado no ponto central da superfície do simulador, centralizado no feixe primário, foi de 8,33 mGy, enquanto o menor valor registrado, devido exclusivamente ao espalhamento, foi de 0,008 mGy. CONCLUSÃO: Estes resultados indicam que o uso de blindagem adicional nas salas de mamografia pode não ser necessário na incidência crânio-caudal, desde que as distâncias consideradas neste trabalho sejam observadas. No entanto, eles enfatizam a necessidade de proteção da paciente.

Avaliação do kerma no ar na superfície de entrada e da qualidade da imagem em radiografias de tórax

OBJETIVO: Avaliar os fatores de técnica utilizados durante exames de tórax póstero-anterior em pacientes-padrão e correlacioná-los aos valores de kerma no ar na superfície de entrada e à qualidade das imagens clínicas. MATERIAIS E MÉTODOS: O estudo foi realizado em três hospitais do Rio de Janeiro, num total de cinco salas de raios X, com dez pacientes por sala. As imagens foram avaliadas pelos radiologistas dos serviços segundo o protocolo europeu. O kerma no ar na superfície de entrada foi estimado a partir da curva de rendimento do equipamento de raios X, que foi obtida utilizando câmara de ionização acoplada a um eletrômetro. Análise de variância foi realizada para verificar se a diferença entre os valores de kerma no ar na superfície de entrada é significativa. RESULTADOS: Os valores de kerma no ar na superfície de entrada variaram entre 0,05 e 0,26 mGy, com média 60% inferior ao nível de referência publicado na Portaria 453. Das imagens avaliadas, 98% atenderam acima de 65% dos critérios de qualidade. CONCLUSÃO: Para um padrão de qualidade da imagem, aceitável para o diagnóstico, verificou-se ampla variação do kerma no ar na superfície de entrada para pacientes-padrão. Isto demonstra a falta de padronização dos fatores de técnica e a existência de um potencial de redução do valor do kerma no ar na superfície de entrada.