Impact of phenotype definition on genome-wide association signals: empirical evaluation in human immunodeficiency virus type 1 infection.

Discussion on improving the power of genome-wide association studies to identify candidate variants and genes is generally centered on issues of maximizing sample size; less attention is given to the role of phenotype definition and ascertainment. The authors used genome-wide data from patients infected with human immunodeficiency virus type 1 (HIV-1) to assess whether differences in type of population (622 seroconverters vs. 636 seroprevalent subjects) or the number of measurements available for defining the phenotype resulted in differences in the effect sizes of associations between single nucleotide polymorphisms and the phenotype, HIV-1 viral load at set point. The effect estimate for the top 100 single nucleotide polymorphisms was 0.092 (95% confidence interval: 0.074, 0.110) log(10) viral load (log(10) copies of HIV-1 per mL of blood) greater in seroconverters than in seroprevalent subjects. The difference was even larger when the authors focused on chromosome 6 variants (0.153 log(10) viral load) or on variants that achieved genome-wide significance (0.232 log(10) viral load). The estimates of the genetic effects tended to be slightly larger when more viral load measurements were available, particularly among seroconverters and for variants that achieved genome-wide significance. Differences in phenotype definition and ascertainment may affect the estimated magnitude of genetic effects and should be considered in optimizing power for discovering new associations.

Effect of n-3 fatty acids on markers of brain injury and incidence of sepsis-associated delirium in septic patients.

BACKGROUND: Data regarding immunomodulatory effects of parenteral n-3 fatty acids in sepsis are conflicting. In this study, the effect of administration of parenteral n-3 fatty acids on markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients was investigated. METHODS: Fifty patients with sepsis were randomized to receive either 2 ml/kg/day of a lipid emulsion containing highly refined fish oil (equivalent to n-3 fatty acids 0.12 mg/kg/day) during 7 days after admission to the intensive care unit or standard treatment. Markers of brain injury and inflammatory mediators were measured on days 1, 2, 3 and 7. Assessment for sepsis-associated delirium was performed daily. The primary outcome was the difference in S-100β from baseline to peak level between both the intervention and the control group, compared by t-test. Changes of all markers over time were explored in both groups, fitting a generalized estimating equations model. RESULTS: Mean difference in change of S-100β from baseline to peak level was 0.34 (95% CI: -0.18-0.85) between the intervention and control group, respectively (P = 0.19). We found no difference in plasma levels of S-100β, neuron-specific enolase, interleukin (IL)-6, IL-8, IL-10, and C-reactive protein between groups over time. Incidence of sepsis-associated delirium was 75% in the intervention and 71% in the control groups (risk difference 4%, 95% CI -24-31%, P = 0.796). CONCLUSION: Administration of n-3 fatty acids did not affect markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients.

Seleção de progênies de maracujazeiro-amarelo (Passiflora edulis f. flavicarpa) quanto à qualidade de frutos

Para garantir a sustentabilidade da cultura do maracujazeiro, na Amazônia, é imprescindível realizar pesquisas que busquem o desenvolvimento de cultivares tolerantes às principais doenças e que apresentem frutos com boas características agroindustriais. Este trabalho teve por objetivo avaliar frutos de progênies de maracujazeiro-amarelo, CPATU-casca-fina (CCF), através de características físicas e físico-químicas, buscando obtenção de plantas com características desejáveis para indústria de suco concentrado e fruto in natura. O estudo foi conduzido em 20 progênies de polinização livre oriundas de uma população formada pela mistura de sementes de plantas selecionadas no segundo ciclo de seleção massal. Colheram-se dez frutos por planta para serem analisados, com base nas seguintes características: peso médio dos frutos; comprimento do fruto; espessura de casca; rendimento de suco; número de sementes por fruto; teor de sólidos solúveis totais (SST); acidez total titulável (ATT); pH e relação STT/ATT. Os dados obtidos foram analisados através de estatística simples, envolvendo média, desvio-padrão e coeficiente de variação. As progênies CPATU-casca-fina apresentaram variação para a maioria das características. Os frutos das progênies CCF-001, CCF-074, CCF-212, CCF-395 e CCF-430 apresentam características desejáveis para o mercado in natura, enquanto os das progênies CCF-192, CCF-281, CCF-391 e CCF-505 têm características importantes para a indústria de suco concentrado.

Evolutionary perspective on the interplay between family life, and parent and offspring personality

Consistent inter-individual variation in behaviour over time and across contexts has been reported for a wide variety of animals, a phenomenon commonly referred to as personality. As behavioural patterns develop inside families, rearing conditions could have lasting effects on the expression of adult personality. In species with parental care, conflicts among family members impose selection on parental and offspring behaviour through co-adaptation. Here, we argue that the interplay between the evolution of personality traits (i.e. boldness, exploration, activity, aggressiveness and sociability) expressed outside the family context and the specialized behaviours expressed inside families (i.e. offspring begging behaviour and parental response to offspring solicitations) can have important evolutionary consequences. Personality differences among parents may relate to the typically observed variation in the way they respond to offspring demand, and dependent offspring may already express personality differences which may relate to the way they communicate with their parents and siblings. However, there has been little research on how personality relates to parental and offspring behaviours. Future research should thus focus on how and why personality may be related to the specialized parent and offspring behaviour that evolved as adaptations to family life.

A Potential Contributory Role for Ciliary Dysfunction in the 16p11.2 600 kb BP4-BP5 Pathology.

The 16p11.2 600 kb copy-number variants (CNVs) are associated with mirror phenotypes on BMI, head circumference, and brain volume and represent frequent genetic lesions in autism spectrum disorders (ASDs) and schizophrenia. Here we interrogated the transcriptome of individuals carrying reciprocal 16p11.2 CNVs. Transcript perturbations correlated with clinical endophenotypes and were enriched for genes associated with ASDs, abnormalities of head size, and ciliopathies. Ciliary gene expression was also perturbed in orthologous mouse models, raising the possibility that ciliary dysfunction contributes to 16p11.2 pathologies. In support of this hypothesis, we found structural ciliary defects in the CA1 hippocampal region of 16p11.2 duplication mice. Moreover, by using an established zebrafish model, we show genetic interaction between KCTD13, a key driver of the mirrored neuroanatomical phenotypes of the 16p11.2 CNV, and ciliopathy-associated genes. Overexpression of BBS7 rescues head size and neuroanatomical defects of kctd13 morphants, whereas suppression or overexpression of CEP290 rescues phenotypes induced by KCTD13 under- or overexpression, respectively. Our data suggest that dysregulation of ciliopathy genes contributes to the clinical phenotypes of these CNVs.

Variabilidade genética de cajuzinho-do-cerrado (Anacardium humile St. Hill.) por meio de marcadores rapd

Nativo do Cerrado brasileiro e com alta variabilidade morfológica, o cajuzinho-do-cerrado (Anacardium humile St. Hill.) apresenta frutos de grande aceitação pelas populações locais, os quais atraem por suas características peculiares, como tamanho, sabor único e potencial para uso sustentável por produtores e pela indústria. A produção de sementes limitada, acarretada pela baixa polinização e pela alta predação por animais e insetos, dificulta a propagação da espécie. O conhecimento da variabilidade genética do cajuzinho-do-cerrado é importante para maximizar o uso de seus recursos genéticos para futuros programas de melhoramento e de conservação da espécie. No presente trabalho, a variabilidade genética de 122 acessos de A. humile procedentes de 11 municípios (procedências) do Cerrado de Goiás e Mato Grosso, foi estimada por meio de marcadores RAPD. As similaridades genéticas foram estimadas a partir da matriz binária, tendo sido processadas análises de agrupamento e de dispersão gráfica a partir da matriz de distâncias. Os iniciadores com maior expressão foram OPA11 e 08. Os dez iniciadores utilizados geraram 157 bandas, sendo 156 polimórficas (99 %), com média de 15,6 bandas/ iniciadores. Grande variabilidade dentro de municípios foi detectada, sendo o polimorfismo superior a 90 %, exceto da procedência de Jataí-GO. A distância entre acessos variou de 0,138 a 0,561, com média de 0,370, sendo os menores valores registrados entre os acessos de Mineiros-GO, e Serranópolis-GO. Os acessos de Caiapônia-GO, e Santo Antônio do Descoberto-GO, foram os mais distantes geneticamente. A dissimilaridade total entre acessos variou de 0,103 a 0,796, com médias de 0,390. Os acessos 87 e 114 de Serranópolis-GO, e Santo Antônio do Descoberto-GO, respectivamente, foram os mais distantes geneticamente, demonstrando a importância dessas procedências no enriquecendo do banco de germoplasma da espécie.

Efficacy and safety of once-daily aclidinium in chronic obstructive pulmonary disease

Background: The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Methods: In two double-blind, 52-week studies, ACCLAIM/COPD I (n = 843) and II (n = 804), patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of ≤70% and FEV1 <80% of the predicted value. The primary endpoint was trough FEV1 at 12 and 28 weeks. Secondary endpoints were health status measured by St George"s Respiratory Questionnaire (SGRQ) and time to first moderate or severe COPD exacerbation. Results: At 12 and 28 weeks, aclidinium improved trough FEV1 versus placebo in ACCLAIM/COPD I (by 61 and 67 mL; both p < 0.001) and ACCLAIM/COPD II (by 63 and 59 mL; both p < 0.001). More patients had a SGRQ improvement ≥4 units at 52 weeks with aclidinium versus placebo in ACCLAIM/COPD I (48.1% versus 39.5%; p = 0.025) and ACCLAIM/COPD II (39.0% versus 32.8%; p = 0.074). The time to first exacerbation was significantly delayed by aclidinium in ACCLAIM/COPD II (hazard ratio [HR] 0.7; 95% confidence interval [CI] 0.55 to 0.92; p = 0.01), but not ACCLAIM/COPD I (HR 1.0; 95% CI 0.72 to 1.33; p = 0.9). Adverse events were minor in both studies. Conclusion: Aclidinium is effective and well tolerated in patients with moderate to severe COPD. Trial registration: ClinicalTrials.gov: NCT00363896 ACCLAIM/COPD I) and NCT00358436 (ACCLAIM/COPD II).

The Conceptualisation and Measurement of Issue Ownership

Issue ownership means that some parties are considered by the public at large as being more able to deal with, or more attentive to, certain issues. The theory has been used to explain both party behaviour - parties are expected to focus on owned issues - and voter behaviour - when a voter considers a party to own an issue, this affects the odds of voting for that party. The purpose of this article is, first, to provide a look backward at the existing research through a literature review of the studies that were conducted in the past decade-and-a-half. Secondly, it takes stock of the current conceptualisation and argues that issue ownership is a multidimensional concept. Thereafter the article discusses how this multidimensionality affects both the role of issue ownership in voter and in party behaviour. Finally, the article outlines a number of shortcomings of the extant literature and discusses potential avenues for future research.

Early transjugular intrahepatic portosystemic shunt in cirrhotic patients with acute variceal bleeding: a systematic review and meta-analysis of controlled trials.

INTRODUCTION: There is conflicting evidence on the benefit of early transjugular intrahepatic portosystemic shunt (TIPSS) on the survival of patients with acute variceal bleeding (AVB). AIM: To assess the effect of early TIPSS on patient prognosis. MATERIALS AND METHODS: We carried out a meta-analysis of trials evaluating early TIPSS in cirrhotic patients with AVB. RESULTS: Four studies were included. Early TIPSS was associated with fewer deaths [odds ratio (OR)=0.38, 95% confidence interval (CI)=0.17-0.83, P=0.02], with moderate heterogeneity between studies (P=0.15, I=44%). Early TIPSS was not significantly associated with fewer deaths among Child-Pugh B patients (OR=0.35, 95% CI=0.10-1.17, P=0.087) nor among Child-Pugh C patients (OR=0.34, 95% CI=0.10-1.11, P=0.074). There was no heterogeneity between studies in the Child-Pugh B analysis (P=0.6, I=0%), but there was a high heterogeneity in the Child-Pugh C analysis (P=0.06, I=60%). Early TIPSS was associated with lower rates of bleeding within 1 year (OR=0.08, 95% CI=0.04-0.17, P<0.001) both among Child-Pugh B patients, (OR=0.15, 95% CI=0.05-0.47, P=0.001) and among Child-Pugh C patients (OR=0.05, 95% CI=0.02-0.15, P<0.001), with no heterogeneity between studies. Early TIPSS was not associated with higher rates of encephalopathy (OR=0.84, 95% CI=0.50-1.42, P=0.5). CONCLUSION: Cirrhotic patients with AVB treated with early TIPSS had lower death rates and lower rates of clinically significant bleeding within 1 year compared with patients treated without early TIPSS. Additional studies are required to identify the potential risk factors leading to a poor prognosis after early TIPSS in patients with AVB and to determine the impact of the degree of liver failure on the patient's prognosis.

Febrile Infections in Children with Leukemia with Special Reference to Respiratory Viral Infections

Leukemiaa sairastavien lasten kuumeiset infektiot, erityisesti respiratoriset virusinfektiot Tausta: Hengitysteiden virusinfektiot ovat lasten tavallisimpia sairauksia. Infektiota aiheuttava virus voidaan uusilla menetelmillä löytää lähes kaikissa tapauksissa. Leukemiaa sairastavilla lapsilla on perustaudin ja leukemian hoitojen takia tavallista suurempi infektioalttius, ja kuumeilu on tavallista leukemiahoidon aikana. Suurin osa syöpähoidon aikaisten kuumejaksojen syistä jää kuitenkin selvittämättä. Tavoitteet: Prospektiivisen 5 vuotta kestäneen monikeskustutkimuksen tavoitteena oli etsiä uusimmilla mikrobiologisilla menetelmillä leukemiaa sairastavien lasten kuumeen syy. Tätä varten tutkittiin 16 virusta virusviljelyllä, antigeeniosoituksella ja nukleiinihappo-osoituksella. Näytteitä otettiin nenästä, ulosteesta, virtsasta ja verestä. Lisäksi tutkittiin MxA-proteiinin kykyä osoittaa virusinfektio syöpälapsella. Tulokset: Tutkimuksen aikana analysoitiin 138 kuumejaksoa 51 leukemialapsella. Kokonaisseuranta-aika oli 1.5 vuotta/lapsi. Kuumejaksojen ilmaantuvuus oli 2.1 jaksoa potilasta kohden suhteutettuna vuoden riskiaikaan. Hengistysteiden virusinfektio voitiin osoittaa 82 kuumejaksossa (59%). Kaksi tai useampi virus löydettiin 12 %:ssa kuumejaksoista. Tavallisimmat virukset olivat rhinovirus (22 %), respiratory syncytial virus eli RS-virus (11 %), human herpes virus 6 (7 %), human bocavirus (5 %), sytomegalovirus (5 %), parainfluenssavirukset (5 %) ja influenssa A -virus (4 %). Kahdelle potilaalle kehittyi pneumonia, muilla oireet olivat lievät. Veriviljely oli positiivinen 19 kuumejaksossa (14 %), ja puolessa tapauksista löydettiin samanaikaisesti respiratorinen virus. MxA proteini ilmeni veren lymfosyyteissä useimmilla virusinfektioon sairastuneilla syöpälapsilla. Päätelmät: Kuumeiset respiratoriset virusinfektiot ovat tavallisia leukemiaa sairastavilla lapsilla. Infektion oireet ovat tavallisesti vähäiset, mutta pienelle osalle voi kehittyä veriviljelypositiivinen sepsis tai pneumonia. Kuumeen syy jäi selvittämättä vain harvoissa tapauksissa.

Analyse rétrospective et création d'un modèle prédictif des réadmissions précoces dans le Service de Médecine Interne du CHUV

Le taux de réadmission à 30 jours de la sortie de l'hôpital est un indicateur de la qualité de prise en charge hospitalière pouvant refléter des soins suboptimaux ou une coordination insuffisante avec les intervenants ambulatoires. Il existe un algorithme informatisé validé dénommé SQLape® qui, basé sur des données administratives suisses, les codes diagnostiques et les codes d'interventions, permet d'identifier rétrospectivement les réadmissions potentiellement évitables (REAPE), avec une haute sensibilité (96%) et spécificité (96%). Sont considérées REAPE, les réadmissions précoces (< 30 jours), non planifiées à la sortie du séjour index et dues à un diagnostic déjà actif lors du précédent séjour ou dues à une complication d'un traitement. Le but de notre étude a été d'analyser rétrospectivement tous les séjours des patients admis dans le service de Médecine Interne du CHUV entre le 1 janvier 2009 et le 31 décembre 2011, afin de quantifier la proportion de REAPE, puis d'identifier des facteurs de risques afin d'en dériver un modèle prédictif. Nous avons analysé 11'074 séjours. L'âge moyen était de 72 +/- 16,8 ans et 50,3 % étaient des femmes. Nous avons comptabilisé 8,4 % décès durant les séjours et 14,2 % réadmissions à 30 jours de la sortie, dont la moitié (7,0 %) considérées potentiellement évitables selon SQLape®. Les facteurs de risques de REAPE que nous avons mis en évidence étaient les suivants : au moins une hospitalisation antérieure à l'admission index, un score de comorbidité de Charlson > 1, la présence d'un cancer actif, une hyponatrémie, une durée de séjour > 11 jours ou encore la prescription d'au moins 15 médicaments différents durant le séjour. Ces variables ont été utilisées pour en dériver un modèle prédictif de REAPE de bonne qualité (aire sous la courbe ROC de 0,70), plus performant pour notre population qu'un autre modèle prédictif développé et validé au Canada, dénommé score de LACE. Dans une perspective d'amélioration de la qualité des soins et d'une réduction des coûts, la capacité à identifier précocement les patients à risque élevé de REAPE permettrait d'implémenter rapidement des mesures préventives ciblées (par exemple un plan de sortie détaillé impliquant le patient, son entourage et son médecin traitant) en plus des mesures préventives générales (par exemple la réconciliation médicamenteuse)

Avaliação da reprodutibilidade da tomografia computadorizada no estadiamento da pancreatite aguda

OBJETIVO: Medir a reprodutibilidade da tomografia computadorizada sem e com contraste na avaliação da gravidade da pancreatite aguda. MATERIAIS E MÉTODOS: Cinqüenta e um exames de tomografia computadorizada abdominal sem e com contraste de pacientes com pancreatite aguda foram analisados por dois radiologistas (observadores 1 e 2). Calculamos o índice morfológico pela tomografia computadorizada sem e com contraste, separadamente, e o índice de gravidade da tomografia computadorizada para pancreatite aguda. Medimos a reprodutibilidade intra- e interobservador da tomografia computadorizada através do índice kappa (kapa). RESULTADOS: Para a concordância interobservador obtivemos kapa de 0,666, 0,705, 0,648, 0,547 e 0,631 para índice morfológico sem e com contraste, presença de necrose pancreática, extensão da necrose pancreática e índice de gravidade da tomografia computadorizada, respectivamente. Para a concordância intra-observador dos observadores 1 e 2 obtivemos, respectivamente, kapa de 0,796 e 0,732 para o índice morfológico sem contraste; 0,725 e 0,802 para o índice morfológico com contraste; 0,674 e 0,849 para a presença de necrose pancreática; 0,606 e 0,770 para a extensão da necrose pancreática; e 0,801 e 0,687 para o índice de gravidade da tomografia computadorizada. CONCLUSÃO: O estadiamento da pancreatite aguda pela tomografia computadorizada por meio do índice morfológico e do índice de gravidade da tomografia computadorizada é um método bastante reprodutível. O não-uso do contraste não afeta a reprodutibilidade da tomografia computadorizada para o cálculo do índice morfológico.

Soins à domicile, soins en EMS: de quelles alternatives dispose la personne âgée dépendante de soins?

La dépendance de soins due à l'âge est un phénomène dont l'importance n'a cessé de croître ces dernières années. Différentes alternatives s'offrent aux personnes dépendantes. Les principales sont le recours à des prestations d'aide et de soins à domicile ou le long séjour dans un établissement médico-social (EMS). Au vu des coûts occasionnés par leur dépendance, il est relativement fréquent que les personnes âgées bénéficient d'aides financières ; celles-ci prennent la forme de prestations complémentaires à l'AVS/AI et peuvent être complétées, au besoin, par diverses aides cantonales.

Le projet RDoC : la classification psychiatrique de demain ?

Nous présentons dans cet article l'histoire, les grands principes méthodologiques ainsi que la réception scientifique et médiatique du projet Research domain criteria (RDoC) lancé en 2009 aux États-Unis par le National institute of mental health (NIMH). Le projet RDoC, dévolu à la recherche, s'oppose au Manuel diagnostique et statistique des troubles mentaux (DSM) en mettant l'accent sur les dimensions du fonctionnement normal du cerveau, au croisement des recherches génétiques, des neurosciences cognitives et des sciences comportementales. Ce projet représente un pari sur le futur et son succès est tributaire de l'adhésion des chercheurs américains au nouveau cadre de référence qu'il propose, cadre qui reste encore largement à construire.