Variation in the autism candidate gene GABRB3 modulates tactile sensitivity in typically developing children

Background: Autism spectrum conditions have a strong genetic component. Atypical sensory sensitivities are one of the core but neglected features of autism spectrum conditions. GABRB3 is a well-characterised candidate gene for autism spectrum conditions. In mice, heterozygous Gabrb3 deletion is associated with increased tactile sensitivity. However, no study has examined if tactile sensitivity is associated with GABRB3 genetic variation in humans. To test this, we conducted two pilot genetic association studies in the general population, analysing two phenotypic measures of tactile sensitivity (a parent-report and a behavioural measure) for association with 43 SNPs in GABRB3. Findings: Across both tactile sensitivity measures, three SNPs (rs11636966, rs8023959 and rs2162241) were nominally associated with both phenotypes, providing a measure of internal validation. Parent-report scores were nominally associated with six SNPs (P <0.05). Behaviourally measured tactile sensitivity was nominally associated with 10 SNPs (three after Bonferroni correction). Conclusions: This is the first human study to show an association between GABRB3 variation and tactile sensitivity. This provides support for the evidence from animal models implicating the role of GABRB3 variation in the atypical sensory sensitivity in autism spectrum conditions. Future research is underway to directly test this association in cases of autism spectrum conditions.

Fetal programming effects of testosterone on the reward system and behavioral approach tendencies in humans

BACKGROUND: Sex differences are present in many neuropsychiatric conditions that affect emotion and approach-avoidance behavior. One potential mechanism underlying such observations is testosterone in early development. Although much is known about the effects of testosterone in adolescence and adulthood, little is known in humans about how testosterone in fetal development influences later neural sensitivity to valenced facial cues and approach-avoidance behavioral tendencies. METHODS: With functional magnetic resonance imaging we scanned 25 8-11-year-old children while viewing happy, fear, neutral, or scrambled faces. Fetal testosterone (FT) was measured via amniotic fluid sampled between 13 and 20 weeks gestation. Behavioral approach-avoidance tendencies were measured via parental report on the Sensitivity to Punishment and Sensitivity to Rewards questionnaire. RESULTS: Increasing FT predicted enhanced selectivity for positive compared with negatively valenced facial cues in reward-related regions such as caudate, putamen, and nucleus accumbens but not the amygdala. Statistical mediation analyses showed that increasing FT predicts increased behavioral approach tendencies by biasing caudate, putamen, and nucleus accumbens but not amygdala to be more responsive to positive compared with negatively valenced cues. In contrast, FT was not predictive of behavioral avoidance tendencies, either through direct or neurally mediated paths. CONCLUSIONS: This work suggests that testosterone in humans acts as a fetal programming mechanism on the reward system and influences behavioral approach tendencies later in life. As a mechanism influencing atypical development, FT might be important across a range of neuropsychiatric conditions that asymmetrically affect the sexes, the reward system, emotion processing, and approach behavior.

Possible role of aerosol transmission in a hospital outbreak of influenza.

BACKGROUND: We examined the role of aerosol transmission of influenza in an acute ward setting. METHODS: We investigated a seasonal influenza A outbreak that occurred in our general medical ward (with open bay ward layout) in 2008. Clinical and epidemiological information was collected in real time during the outbreak. Spatiotemporal analysis was performed to estimate the infection risk among patients. Airflow measurements were conducted, and concentrations of hypothetical virus-laden aerosols at different ward locations were estimated using computational fluid dynamics modeling. RESULTS: Nine inpatients were infected with an identical strain of influenza A/H3N2 virus. With reference to the index patient's location, the attack rate was 20.0% and 22.2% in the "same" and "adjacent" bays, respectively, but 0% in the "distant" bay (P = .04). Temporally, the risk of being infected was highest on the day when noninvasive ventilation was used in the index patient; multivariate logistic regression revealed an odds ratio of 14.9 (95% confidence interval, 1.7-131.3; P = .015). A simultaneous, directional indoor airflow blown from the "same" bay toward the "adjacent" bay was found; it was inadvertently created by an unopposed air jet from a separate air purifier placed next to the index patient's bed. Computational fluid dynamics modeling revealed that the dispersal pattern of aerosols originated from the index patient coincided with the bed locations of affected patients. CONCLUSIONS: Our findings suggest a possible role of aerosol transmission of influenza in an acute ward setting. Source and engineering controls, such as avoiding aerosol generation and improving ventilation design, may warrant consideration to prevent nosocomial outbreaks.

Cognition in males and females with autism: similarities and differences

The male bias in autism spectrum conditions (ASC) has led to females with ASC being under-researched. This lack of attention to females could hide variability due to sex that may explain some of the heterogeneity within ASC. In this study we investigate four key cognitive domains (mentalizing and emotion perception, executive function, perceptual attention to detail, and motor function) in ASC, to test for similarities and differences between males and females with and without ASC (n = 128 adults; n = 32 per group). In the mentalizing and facial emotion perception domain, males and females with ASC showed similar deficits compared to neurotypical controls. However, in attention to detail and dexterity involving executive function, although males with ASC showed poorer performance relative to neurotypical males, females with ASC performed comparably to neurotypical females. We conclude that performance in the social-cognitive domain is equally impaired in male and female adults with ASC. However, in specific non-social cognitive domains, performance within ASC depends on sex. This suggests that in specific domains, cognitive profiles in ASC are modulated by sex.

Sex/gender differences and autism: setting the scene for future research

Objective The relationship between sex/gender differences and autism has attracted a variety of research ranging from clinical, neurobiological to etiological, stimulated by the male bias in autism prevalence. Findings are complex and do not always relate to each other in a straightforward manner. Distinct but interlinked questions on the relationship between sex/gender differences and autism remain under addressed. To better understand the implications from existing research and to help design future studies, we propose a four-level conceptual framework to clarify the embedded themes. Method We searched PubMed for publications before September 2014 using search terms “‘sex OR gender OR females’ AND autism.” 1,906 citations were screened for relevance, along with publications identified via additional literature reviews, resulting in 329 reports that were reviewed. Results Level 1 “Nosological and diagnostic challenges” concerns the question “How should autism be defined and diagnosed in males and females?” Level 2 “Sex/gender-independent and sex/gender-dependent characteristics” addresses the question “What are the similarities and differences between males and females with autism?” Level 3 “General models of etiology: liability and threshold” asks the question “How is the liability for developing autism linked to sex/gender?” Level 4 “Specific etiological-developmental mechanisms” focuses on the question “What etiological-developmental mechanisms of autism are implicated by sex/gender and/or sexual/gender differentiation?” Conclusions Using this conceptual framework, findings can be more clearly summarized, and the implications of the links between findings from different levels can become clearer. Based on this four-level framework, we suggest future research directions, methodology, and specific topics in sex/gender differences and autism.

ÅTTA NYANSER AV ROSA? : Riksdagspartiernas anpassning efter Feministiskt initiativ efter Europaparlamentsvalet 2014.

Uppsatsen har som syfte att undersöka förändringen i användningen av begrepp kopplade till partiet Feministiskt initiativ mellan riksdagsvalet år 2010 och år 2014 hos de sittande riksdagspartierna. Utifrån detta syftar uppsatsen även till att undersöka huruvida det går att utläsa mönster i den eventuella förändringen med utgångspunkt i deras placering i det politiska spektrumet. Studiens primärkällor är valmanifest, valaffischer samt almedalstalen från de nuvarande sittande riksdagspartierna. Dessa källor har bearbetats utifrån en kvantitativ deskriptiv innehållsanalys (almedalstal samt valmanifest), deskriptiv kvalitativ innehållsanalys (valaffischerna) samt en kvalitativ innehållsanalys (valmanifesten). Resultaten från dessa analyser har studerats utifrån Bonnie Meguids teori kring etablerade partiers möjlighet att påverka framgången hos nischade partier, samt Anthony Down’s teori som syftar till att förklara varför partier väljer att vara flexibla gentemot åsikts-strömningar, även om åsikten tidigare inte varit en fokusfråga hos partiet. Slutsatserna visar att det finns en påverkan på alla nuvarande sittande riksdagspartier utom Moderaterna, och att det inte går att utläsa något mönster på partiernas anpassning till Feministiskt initiativ utifrån politisk färg. Majoriteten av de undersökta partierna har valt ett följsamt förhållningssätt till Feministiskt initiativ, vilket innebär att de valt att anamma de frågor som Feministiskt initiativ lyfter.

The Nine Circles of Surveillance Hell: An Institutional View of Information Flows and Information Threats in Libraries

In the past few years, libraries have started to design public programs that educate patrons about different tools and techniques to protect personal privacy. But do end user solutions provide adequate safeguards against surveillance by corporate and government actors? What does a comprehensive plan for privacy entail in order that libraries live up to their privacy values? In this paper, the authors discuss the complexity of surveillance architecture that the library institution might confront when seeking to defend the privacy rights of patrons. This architecture consists of three main parts: physical or material aspects, logical characteristics, and social factors of information and communication flows in the library setting. For each category, the authors will present short case studies that are culled from practitioner experience, research, and public discourse. The case studies probe the challenges faced by the library—not only when making hardware and software choices, but also choices related to staffing and program design. The paper shows that privacy choices intersect not only with free speech and chilling effects, but also with questions that concern intellectual property, organizational development, civic engagement, technological innovation, public infrastructure, and more. The paper ends with discussion of what libraries will require in order to sustain and improve efforts to serve as stewards of privacy in the 21st century.

Elementos da cultura que dificultam a entrega de resultados em um órgão público da administração direta

Esta dissertação se insere no campo dos debates que apontam para o impacto da cultura nacional sobre a cultura organizacional, oferecendo, por meio de um estudo de caso, especificidades de um órgão público brasileiro pertencente à administração direta. O trabalho é dedicado à realização de um diagnóstico, buscando compreender como elementos da cultura desse órgão dificultam a sua entrega de resultados. Partindo de um referencial teórico que caracteriza os traços da cultura nacional na maneira brasileira de administrar, assim como da abordagem dos chamados intangíveis na gestão, foi realizado um mergulho na dinâmica organizacional, procurando identificar os passivos intangíveis que dificultam a entrega de seus resultados. Por meio das lentes dos próprios servidores, obtidas a partir de vinte e uma entrevistas em profundidade, foram levantadas as especificidades de cultura e gestão no referido órgão, debatendo temas como: missão, planejamento estratégico, liderança, processos e tecnologia da informação, pessoas, treinamentos e alocação dos recursos. O resultado das análises conduziu para a visão de uma necessidade premente na organização de se tratar o fator humano em uma visão estratégica, criando-se um novo contexto capacitante em busca da excelência organizacional. Foram propostas alternativas para iniciar a pavimentação desse novo caminho, que tem como alicerces principais a integração e o envolvimento de pessoas na busca por resultados.

Gestão de integridade de ativos: aspectos culturais e internacionalização

O presente trabalho de pesquisa, apresentado como dissertação para a conclusão do curso de Mestrado Executivo em Administração de Empresas, teve como objetivo estudar o processo de implantação de um sistema de gestão de integridade de ativos tangíveis na filial brasileira de uma empresa estrangeira com larga experiência no setor de produção de óleo e gás. Embora a empresa matriz esteja presente em inúmeros países, a filial local, chamada neste estudo de Íntegra, é a primeira, fora do país de origem que possui a operação de um campo de petróleo. A análise realizada não foi feita diretamente sobre o processo de implantação do sistema de gestão na prática, mas sim sobre as percepções sobre o tema e os assuntos que este envolve, focando em entender como as partes interessadas entendem a gestão de integridade. O método empregado para o desenvolvimento do trabalho foi o de estudo de caso e a problemática estudada foi a influência dos aspectos culturais e o processo de internacionalização da empresa na implantação dos processos necessários à gestão de integridade de ativos. A fim de reunir material para a elaboração do trabalho, foi realizada pesquisa de campo, onde através de entrevistas com funcionários e prestadores de serviço da Íntegra foram colhidos depoimentos que propiciaram o entendimento da forma como estes viam a condução da implantação de processos na empresa. A confrontação da teoria disponível no meio acadêmico com os dados coletados na pesquisa de campo indicou alguns desafios culturais a serem considerados na implantação do processo de gestão, como os ligados às visões de prazo e aos valores e práticas coletivistas. O trabalho propõe uma discussão especial sobre o papel da liderança para fazer frente a esses desafios.

Estudo comparativo de abordagens de inversão do fator de qualidade Q

Seismic wave dispersion and attenuation studies have become an important tool for lithology and fluid discrimination in hydrocarbon reservoirs. The processes associated to attenuation are complex and are encapsulated in a single quantitative description called quality factor (Q). The present dissertation has the objective of comparing different approaches of Q determination and is divided in two parts. Firstly, we made performance and robustness tests of three different approaches for Q determination in the frequency domain. They are: peak shift, centroid shift and spectral ratio. All these tests were performed in a three-layered model. In the suite of tests performed here, we varied the thickness, Q and inclination of the layers for propagation pulses with central frequency of 30, 40 and 60 Hz. We found that the centroid shift method is produces robust results for the entire suíte of tests. Secondly, we inverted for Q values using the peak and centroid shift methods using an sequential grid search algorithm. In this case, centroid shift method also produced more robust results than the peak shift method, despite being of slower convergence

Validation of the English version of the UNESP-Botucatu multidimensional composite pain scale for assessing postoperative pain in cats

Background: A scale validated in one language is not automatically valid in another language or culture. The purpose of this study was to validate the English version of the UNESP-Botucatu multidimensional composite pain scale (MCPS) to assess postoperative pain in cats. The English version was developed using translation, back-translation, and review by individuals with expertise in feline pain management. In sequence, validity and reliability tests were performed.Results: Of the three domains identified by factor analysis, the internal consistency was excellent for 'pain expression' and 'psychomotor change' (0.86 and 0.87) but not for 'physiological variables' (0.28). Relevant changes in pain scores at clinically distinct time points (e.g., post-surgery, post-analgesic therapy), confirmed the construct validity and responsiveness (Wilcoxon test, p < 0.001). Favorable correlation with the IVAS scores (p < 0.001) and moderate to very good agreement between blinded observers and 'gold standard' evaluations, supported criterion validity. The cut-off point for rescue analgesia was > 7 (range 0-30 points) with 96.5% sensitivity and 99.5% specificity.Conclusions: The English version of the UNESP-Botucatu-MCPS is a valid, reliable and responsive instrument for assessing acute pain in cats undergoing ovariohysterectomy, when used by anesthesiologists or anesthesia technicians. The cut-off point for rescue analgesia provides an additional tool for guiding analgesic therapy. © 2013 Brondani et al.; licensee BioMed Central Ltd.

Breast Milk and Glucose for Pain Relief in Preterm Infants: A Noninferiority Randomized Controlled Trial

OBJECTIVE: The study goal was to compare the efficacy of expressed breast milk (EBM) versus 25% glucose on pain responses of late preterm infants during heel lancing. METHODS: In a noninferiority randomized controlled trial, a total of 113 newborns were randomized to receive EBM (experimental group [EG]) or 25% glucose (control group [CG]) before undergoing heel lancing. The primary outcome was pain intensity (Premature Infant Pain Profile [PIPP]) and a 10% noninferiority margin was established. Secondary outcomes were incidence of cry and percentage of time spent crying and adverse events. Intention-to-treat (ITT) analysis was used. RESULTS: Groups were similar regarding demographics and clinical characteristics, except for birth weight and weight at data collection day. There were lower pain scores in the CG over 3 minutes after lancing (P<.001). A higher number of infants in the CG had PIPP scores indicative of minimal pain or absence of pain (P = .002 and P = .003 on ITT analysis) at 30 seconds after lancing, and the mean difference in PIPP scores was 3 (95% confidence interval: 1.507-4.483). Lower incidence of cry (P = .001) and shorter duration of crying (P = .014) were observed for CG. Adverse events were benign and self-limited, and there was no significant difference between groups (P = .736 and P = .637 on ITT analysis). CONCLUSIONS: Results based on PIPP scores and crying time indicate poorer effects of EBM compared with 25% glucose during heel lancing. Additional studies exploring the vol and administration of EBM and its combination with other strategies such as skin-to-skin contact and sucking are necessary. Pediatrics 2012;129:664-670

Cost-effectiveness and budget impact of saxagliptine as additional therapy to metformin for the treatment of diabetes mellitus type 2 in the Brazilian private health system

Cost-effectiveness and budget impact of saxagliptine as additional therapy to metformin for the treatment of diabetes mellitus type 2 in the Brazilian private health system Objectives: To compare costs and clinical benefits of three additional therapies to metformin (MF) for patients with diabetes mellitus type 2 (DM2). Methods: A discrete event simulation model seas built to estimate the cost-utility ratio (cost per quality-adjusted life years [QALY)) of saxagliptine as an additional therapy to MF when compared to rosiglitazone or pioglitazone. A budget impact model (BIM) was built to simulate the economic impact of saxagliptine use in the context of the Brazilian private health system. Results: The acquiring medication costs for the hypothetical patient group analyzed in a time frame of three years, were R$ 10,850,185, R$ 14,836,265 and R$ 14,679,099 for saxagliptine, pioglitazone and rosiglitazone, respectively. Saxagliptine showed lower costs and greater effectiveness in both comparisons, with projected savings for the first three years of R$ 3,874 and R$ 3,996, respectively. The BIM estimated cumulative savings of R$ 417,958 with the repayment of saxagliptine in three years from the perspective of a health plan with 1,000,000 covered individuals. Conclusion: From the perspective of private paying source, the projection is that adding saxagliptine with MF save costs when compared with the addition of rosiglitazone or pioglitazone in patients with DM2 that have not reached the HbA1c goal with metformin monotherapy. The BIM of including saxagliptine in the reimbursement lists of health plans indicated significant savings on the three-year horizon.

Custo-efetividade e impacto orçamentário da saxagliptina como terapia adicional à metformina para o tratamento do diabetes mellitus tipo 2 no sistema de saúde suplementar do Brasil

OBJETIVOS: Comparar custos e benefícios clínicos de três terapias adicionais à metformina (MF) para pacientes com diabetes mellitus tipo 2 (DMT2). MÉTODOS: Um modelo de simulação de eventos discretos foi construído para estimar a relação custo-utilidade (custo por QALY) da saxagliptina como uma terapia adicional à MF comparada à rosiglitazona ou pioglitazona. Um modelo de impacto orçamentário (BIM - Budget Impact Model) foi construído para simular o impacto econômico da adoção de saxagliptina no contexto do Sistema Suplementar de Saúde brasileiro. RESULTADOS: O custo de aquisição da medicação para o grupo de pacientes hipotéticos analisados, para o horizonte temporal de três anos, foi de R$ 10.850.185,00, R$ 14.836.265,00 e R$ 14.679.099,00 para saxagliptina, pioglitazona e rosiglitazona, respectivamente. Saxagliptina exibiu menores custos e maior efetividade em ambas as comparações, com economias projetadas para os três primeiros anos de -R$ 3.874,00 e -R$ 3.996,00, respectivamente. O BIM estimou uma economia cumulativa de R$ 417.958,00 com o reembolso da saxagliptina em três anos a partir da perspectiva de uma operadora de plano de saúde com 1 milhão de vidas cobertas. CONCLUSÃO: Da perspectiva da fonte pagadora privada, a projeção é de que o acréscimo de saxagliptina à MF poupe custos quando comparado ao acréscimo de rosiglitazona ou pioglitazona em pacientes com DMT2 que não atingiram a meta de hemoglobina glicada (HbA1c) com metformina em monoterapia. O BIM, para a inclusão de saxagliptina nas listas de reembolso das operadoras de planos de saúde, indicou uma economia significativa para o horizonte de 3 anos.