Cell cycle progression or translation control is not essential for vesicular stomatitis virus oncolysis of hepatocellular carcinoma.

The intrinsic oncolytic specificity of vesicular stomatitis virus (VSV) is currently being exploited to develop alternative therapeutic strategies for hepatocellular carcinoma (HCC). Identifying key regulators in diverse transduction pathways that define VSV oncolysis in cancer cells represents a fundamental prerequisite to engineering more effective oncolytic viral vectors and adjusting combination therapies. After having identified defects in the signalling cascade of type I interferon induction, responsible for attenuated antiviral responses in human HCC cell lines, we have now investigated the role of cell proliferation and translation initiation. Cell cycle progression and translation initiation factors eIF4E and eIF2Bepsilon have been recently identified as key regulators of VSV permissiveness in T-lymphocytes and immortalized mouse embryonic fibroblasts, respectively. Here, we show that in HCC, decrease of cell proliferation by cell cycle inhibitors or siRNA-mediated reduction of G(1) cyclin-dependent kinase activities (CDK4) or cyclin D1 protein expression, do not significantly alter viral growth. Additionally, we demonstrate that translation initiation factors eIF4E and eIF2Bepsilon are negligible in sustaining VSV replication in HCC. Taken together, these results indicate that cellular proliferation and the initiation phase of cellular protein synthesis are not essential for successful VSV oncolysis of HCC. Moreover, our observations indicate the importance of cell-type specificity for VSV oncolysis, an important aspect to be considered in virotherapy applications in the future

The role of self-control and cognitive functioning in educational inequalities in adolescent smoking and binge drinking

Abstract Background Large differences in substance use between educational levels originate at a young age, but there is limited evidence explaining these inequalities. The aim of this study was to test whether a) smoking and binge drinking are associated with lower levels of self-control and cognitive functioning, and b) associations between educational track and smoking and binge drinking, respectively, are attenuated after controlling for self-control and cognitive functioning. Methods This study used cross-sectional survey data of 15 to 20-year-olds (N = 191) from low, middle, and high educational tracks. We measured regular binge drinking and regular smoking (more than once a month), cognitive functioning (cognitive ability, reaction time and memory span), and self-control. Logistic regression models were used to assess the associations between educational track and smoking and binge drinking controlled for age, gender and social disadvantage, and for self-control and cognitive functioning. Results According to models that controlled for age, gender and social disadvantage only, respondents in the low educational track were more likely to drink heavily (OR = 3.25, 95% CI = 1.48–7.17) and smoke (OR = 5.74, 95% CI = 2.31–14.29) than adolescents in the high educational track. The association between educational track and binge drinking was hardly reduced after adjustment for self-control and cognitive ability (OR = 2.88, 95% CI = 1.09–7.62). Adjustment for self-control and cognitive functioning, especially cognitive ability, weakened the association between education and smoking (OR = 3.40, 95% CI = 1.11–10.37). However, inequalities in smoking remained significant and substantial. Conclusions In this study population, pre-existing variations between adolescents in terms of self-control and cognitive functioning played a minor role in educational inequalities in smoking, but not in binge drinking

Treating Child Disruptive Behavior in High-Risk Families: A Comparative Effectiveness Trial from a Community-Based Implementation

Parent management training programs have proven the most effective way to treat child behavior problems. This study reports on an effectiveness trial of a community-based implementation of Parent–Child Interaction Therapy (PCIT) in comparison with the Dutch-developed Family Creative Therapy (FCT). Forty-five children (58 % boys) aged between 32 and 102 months (M = 67.7, SD = 15.9) were referred for treatment, and they and their parent(s) were randomly assigned to PCIT or FCT. Treatment effectiveness was measured primarily by the degree of improvement on child behavior problems, using the Eyberg Child Behavior Inventory. Secondary outcomes included parent and teacher report data and independent observations of parenting skills and child behavior. During the trial, randomization was violated by treatment crossovers (from FCT to PCIT). Intention-to-treat analyzes revealed no significant differences in the primary outcome at 6-month follow-up, but interpretation was hampered by the crossovers. Subsequent treatment-received analyzes revealed significant interaction effects between time and treatment condition, with greater improvements in child behavior and parenting skills for PCIT families compared to FCT families. Analyzes on families that fully completed the PCIT protocol also showed higher treatment maintenance at follow-up. The treatment-received analyzes indicated promising results for the effectiveness of PCIT in treating young children’s disruptive behavior problems in a high-risk population. However, caution in generalizing the conclusions is needed in view of the design difficulties in this study. Suggestions are made for enhancing treatment delivery in daily practice, and clinical implications are noted

Mortalidade por câncer nas capitais e no interior do Brasil: uma análise de quatro décadas

OBJECTIVE: to describe the trend of mortality from general cancer and more frequent types among men and women living in the Capitals and other municipalities of the five macro-regions of Brazil between 1978 and 2017. METHODS: Time series study with mortality data corrected by redistribution of ill-defined causes. Proportional cancer mortality was calculated for Brazil and regions. The annual percentage change in rates for total cancer and specific types in each segment and in the selected unit of analysis was calculated by generalized linear regression with Gaussian binding. RESULTS: the proportion of cancer increased progressively for both sexes from 1978 to 2017. Important differences between the Capitals and the interior of the macro-regions were seen with disaggregated data. The greatest declines occurred for stomach cancer, except in the northern and interior regions of the Northeast, and for the cervix cancer, with a generalized fall, with the exception of the interior of the northern region. Lung cancer decreased among men in the Southeast and South regions and had a generalized increase among women. Breast and prostate cancers tended to decrease in the Southeast and South regions and among residents of the Capitals but showing an increase in the interior of the North and Northeast regions. Colorectal cancer had a general tendency to increase; with stability among men in the Capitals of the South region and among women of the Southeast and Midwest regions and, since 2007, a decrease among women in the South region. CONCLUSIONS: Cancer mortality showed great variation among residents of capitals and the interior of the country’s major regions. Clear decrease in mortality was seen for the main types in the Southeast and South regions. The North and Northeast regions have patterns compatible with cancers associated with poverty, while the large increase of the cancers related to sedentary lifestyle stand out.OBJETIVO: Descrever a tendência da mortalidade por câncer geral e tipos mais frequentes entre homens e mulheres residentes nas capitais e demais municípios das cinco macrorregiões do Brasil entre 1978 e 2017. MÉTODOS: Estudo de séries temporais com dados de mortalidade corrigidos por redistribuição das causas maldefinidas. Foi calculada a mortalidade proporcional de câncer para Brasil e regiões. A variação percentual anual das taxas para o total de câncer e tipos específicos em cada segmento e na desagregação selecionada foi calculada por regressão linear generalizada com ligação gaussiana. RESULTADOS: A proporção de câncer aumentou progressivamente para ambos os sexos de 1978 a 2017. Diferenças importantes entre as capitais e o interior das macrorregiões foram vistas com dados desagregados. Os maiores declínios ocorreram para o câncer de estômago, exceto nas regiões Norte e interior da Nordeste, e de colo do útero, com queda generalizada, com exceção do interior da região Norte. O câncer de pulmão teve queda entre homens nas regiões Sudeste e Sul e aumento generalizado entre mulheres. Os cânceres de mama e de próstata tenderam a diminuir nas regiões Sudeste e Sul e entre residentes das capitais, mostrando, porém, aumento no interior das regiões Norte e Nordeste. O câncer colorretal teve tendência geral de aumento; nas capitais houve estabilidade entre homens da região Sul e entre mulheres das regiões Sudeste e Centro-Oeste e queda entre mulheres da região Sul a partir de 2007. CONCLUSÕES: A mortalidade por câncer apresentou grande variação entre os residentes de capitais e do interior das grandes regiões do país. Diminuição clara da mortalidade foi vista para os principais tipos nas regiões Sudeste e Sul. As regiões Norte e Nordeste apresentam padrões compatíveis com cânceres associados à pobreza ao mesmo tempo que se destacam pelo grande aumento daqueles relacionados ao estilo de vida sedentário

Quantum statistical effects in nano-oscillator arrays

We have theoretically predicted the density of states(DOS), the low temperature specific heat, and Brillouin scattering spectra of a large, free standing array of coupled nano-oscillators. We have found significant gaps in the DOS of 2D elastic systems, and predict the average DOS to be nearly independent of frequency over a broad band f < 50GHz. At low temperatures, the measurements probe the quantum statistics obeyed by rigid body modes of the array and, thus, could be used to verify the quantization of the associated energy levels. These states, in turn, involve center-of mass motion of large numbers of atoms, N > 1.e14, and therefore such observations would extend the domain in which quantum mechanics has been experimentally tested. We have found the required measurement capability to carry out this investigation to be within reach of current technology.Comment: 1 tex file, 3 figures, 1 bbl fil

Qualidade do ar e transtornos respiratórios agudos em crianças

OBJETIVO: Avaliar a relação entre poluição do ar e efeitos respiratórios agudos em crianças. MÉTODOS: Foi realizado um estudo ecológico de séries temporais em três unidades públicas de saúde do bairro de Jacarepaguá, município do Rio de Janeiro, entre abril de 2002 e março de 2003. Foram analisados dados diários de PM10, SO2, NO2, CO e O3, e como variáveis de desfecho 45.595 atendimentos pediátricos de emergência por sintomas respiratórios ou específicos por transtornos nas vias aéreas superiores e nas vias aéreas inferiores. Foram incluídas no modelo para controle de confundimento as variáveis referentes à tendência temporal, sazonalidade, temperatura, umidade relativa do ar, precipitação de chuva, infecções respiratórias e os efeitos do calendário (como feriados e finais de semana). Foi empregada a regressão de Poisson via modelos aditivos generalizados para estimar os efeitos dos poluentes e dos fatores de confusão. RESULTADOS: Somente o O3 apresentou resultado positivo e estatisticamente significativo, tanto com todos os atendimentos de emergência por queixas respiratórias como com os atendimentos motivados por sintomas nas vias aéreas inferiores. O efeito foi no mesmo dia da exposição (lag 0). Associação significativa e de sentido inverso ocorreu com o CO e os atendimentos pediátricos por queixas respiratórias. Não se observou resultado significativo com os demais poluentes atmosféricos. CONCLUSÕES: Foram encontradas associações entre indicadores de poluição atmosférica e o número de atendimentos pediátricos de emergência por motivos respiratórios em Jacarepaguá, apesar de os níveis de todos os poluentes monitorados permanecessem abaixo dos limites recomendados durante todo o período de estudos

Qualidade do ar e transtornos respiratórios agudos em crianças

OBJECTIVE: To assess the relationship between air pollution and acute respiratory disorders in children. METHODS: A time series ecological study was carried out in three public health posts in a region of the city of Rio de Janeiro (Southeastern Brazil), between April 2002 and March 2003. Data for PM10, SO2, NO2, CO and O3 were analyzed daily and as closure variables, a total of 45,595 emergency pediatric consultations for respiratory symptoms or specifically for disorders in the upper and lower airways. To control for confounders, other variables were included in the model including those relating to weather, seasonality, temperature, relative air humidity, rain volume, respiratory infections and the calendar effects (such as holidays and weekends). A Poisson regression was applied using generalized counting models to estimate the effects of pollutants and confusing factors. RESULTS: Only O3 had a positive and statistically significant effect, both among emergency consultations for respiratory problems and consultations for symptoms relating to the lower airways. Effect and exposure occurred on the same day (lag 0). A significant negative association was found with CO and pediatric consultations for respiratory complaints. Other air pollutants were not found to have a significant effect. CONCLUSIONS: There were found associations between outdoor air pollution and the number of emergency pediatric consultations for respiratory problems in the studied area, in spite of the fact that the levels of all pollutants monitored during the study period were below recommended levels.OBJETIVO: Avaliar a relação entre poluição do ar e efeitos respiratórios agudos em crianças. MÉTODOS: Foi realizado um estudo ecológico de séries temporais em três unidades públicas de saúde do bairro de Jacarepaguá, município do Rio de Janeiro, entre abril de 2002 e março de 2003. Foram analisados dados diários de PM10, SO2, NO2, CO e O3, e como variáveis de desfecho 45.595 atendimentos pediátricos de emergência por sintomas respiratórios ou específicos por transtornos nas vias aéreas superiores e nas vias aéreas inferiores. Foram incluídas no modelo para controle de confundimento as variáveis referentes à tendência temporal, sazonalidade, temperatura, umidade relativa do ar, precipitação de chuva, infecções respiratórias e os efeitos do calendário (como feriados e finais de semana). Foi empregada a regressão de Poisson via modelos aditivos generalizados para estimar os efeitos dos poluentes e dos fatores de confusão. RESULTADOS: Somente o O3 apresentou resultado positivo e estatisticamente significativo, tanto com todos os atendimentos de emergência por queixas respiratórias como com os atendimentos motivados por sintomas nas vias aéreas inferiores. O efeito foi no mesmo dia da exposição (lag 0). Associação significativa e de sentido inverso ocorreu com o CO e os atendimentos pediátricos por queixas respiratórias. Não se observou resultado significativo com os demais poluentes atmosféricos. CONCLUSÕES: Foram encontradas associações entre indicadores de poluição atmosférica e o número de atendimentos pediátricos de emergência por motivos respiratórios em Jacarepaguá, apesar de os níveis de todos os poluentes monitorados permanecessem abaixo dos limites recomendados durante todo o período de estudos

Women and Illegal Activities: Gender Differences and Women's Willingness to Comply Over Time

In recent years the topics of illegal activities such as corruption or tax evasion have attracted a great deal of attention. However, there is still a lack of substantial empirical evidence about the determinants of compliance. The aim of this paper is to investigate empirically whether women are more willing to be compliant than men and whether we observe (among women and in general) differences in attitudes among similar age groups in different time periods (cohort effect) or changing attitudes of the same cohorts over time (age effect) using data from eight Western European countries from the World Values Survey and the European Values Survey that span the period from 1981 to 1999. The results reveal higher willingness to comply among women and an age rather than a cohort effect. Working Paper 06-5

Young people, crime and school exclusion: a case of some surprises

During the 1990s the number of young people being permanently excluded from schools in England and Wales increased dramatically from 2,910 (1990/91) to a peak of 12,700 (1996/97). Coinciding with this rise was a resurgence of the debate centring on lawless and delinquent youth. With the publication of Young People and Crime (Graham and Bowling 1995) and Misspent Youth (Audit Commission 1996) the 'common sense assumption' that exclusion from school inexorably promoted crime received wide support, with the school excludee portrayed as another latter day 'folk devil'. This article explores the link between school exclusion and juvenile crime, and offers some key findings from a research study undertaken with 56 young people who had experience of being excluded from school. Self-report interview questions reveal that whilst 40 of the young people had offended, 90% (36) reported that the onset of their offending commenced prior to their first exclusion. Moreover, 50 (89.2% of the total number of young people in the sample), stated that they were no more likely to offend subsequent to being excluded and 31 (55.4%) stated that they were less likely to offend during their exclusion period. Often, this was because on being excluded, they were 'grounded' by their parents