Effectiveness and safety of repeat courses of hylan G-F 20 in patients with knee osteoarthritis

Objective: To compare the effectiveness and safety of repeat treatment with hylan G-F 20 based on data from a randomized, controlled trial [Raynauld JP, Torrance GW, Band PA, Goldsmith CH, Tugwell P, Walker V, et al. A prospective, randomized, pragmatic, health outcomes trial evaluating the incorporation of hylan G-F 20 into the treatment paradigm for patients with knee osteoarthritis (Part 1 of 2): clinical results. Osteoarthritis Cartilage 2002;10:506-17]. The hypotheses tested were whether the single-course and repeat-course subgroups would be superior to appropriate care and not different from each other. Method: A total of 255 patients with knee osteoarthritis were randomized to appropriate care with hylan G-F 20 or appropriate care without hylan G-F 20. The hylan G-F 20 group was partitioned into two subgroups: (1) patients who received a single course of hylan G-F 20; and (2) patients who received two or more courses of hylan G-F 20. Results: For the primary effectiveness measure, change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score as a percent of baseline, the single-course subgroup improved by 41%, the repeat-course subgroup by 35%, and the appropriate care group by 14%. Both subgroups improved significantly more than the appropriate care group (P < 0.05), and were not statistically significantly different from each other (70% power to detect a 20% difference). Secondary effectiveness measures showed similar results. In the repeat-course subgroup, no statistically significant differences were found in the number of local adverse events, the number of patients with local adverse events, or arthrocentesis rates between the first and repeat courses of treatment. Conclusions: Although the study was neither designed nor powered to examine repeat treatment, this a posteriori analysis provides support for a favorable effectiveness and safety profile of hylan G-F 20 in repeat course patients. (C) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Protection against group A streptococcal infection by vaccination with self-adjuvanting lipid core M protein peptides

We have investigated the lipid polylysine core peptide (LCP) system as a self-adjuvanting group A streptococcal (GAS) vaccine delivery approach. LCP constructs were synthesised incorporating peptides from the M protein conserved carboxy terminal C-repeat region, the amino terminal type-specific region and from both of these regions. Immunisation with the constructs without adjuvant led to the induction of peptide-specific serum IgG antibody responses, heterologous opsonic antibodies, and complete protection from GAS infection. These data indicate that protective immunity to GAS infection can be evoked using the self-adjuvanting LCP system, and point to the potential application of this system in human mucosal GAS vaccine development. (c) 2005 Elsevier Ltd. All rights reserved.

Double-strand break repair gene polymorphisms and risk of breast or ovarian cancer

Deficiencies in DNA repair have been hypothesized to increase cancer risk and excess cancer incidence is a feature of inherited diseases caused by defects in DNA damage recognition and repair. We investigated, using a case-control design, whether the double-strand break repair gene polymorphisms RAD51 5' untranslated region -135 G > C, XRCC2 R188H G > A, and XRCC3 T241M C > T were associated with risk of breast or ovarian cancer in Australian women. Sample sets included 1,456 breast cancer cases and 793 age-matched controls ages under 60 years of age, 549 incident ovarian cancer cases, and 335 controls of similar age distribution. For the total sample and the subsample of Caucasian women, there were no significant differences in genotype distribution between breast cancer cases and controls or between ovarian cancer cases and combined control groups. The crude odds ratios (OR) and 95% confidence intervals (95% CI) associated with the RAD51 GC/CC genotype frequency was OR, 1.10; 95% CI, 0.80-1.41 for breast cancer and OR, 1.22; 95% CI, 0.92-1.62 for ovarian cancer. Similarly, there were no increased risks associated with the XRCC2 GA/AA genotype (OR, 0.98; 95% CI, 0.76-1.26 for breast cancer and OR, 0.93; 95% CI, 0.69-1.25 for ovarian cancer) or the XRCC3 CT/TT genotype (OR, 0.92; 95% Cl, 0.77-1.10 for breast cancer and OR, 0.87; 95% CI, 0.71-1.08 for ovarian cancer). Results were little changed after adjustment for age and other measured risk factors. Although there was little statistical power to detect modest increases in risk for the homozygote variant genotypes, particularly for the rare RAD51 and XRCC2 variants, the data suggest that none of these variants play a major role in the etiology of breast or ovarian cancer.

Patterns of gene expression in the frontal cortex discriminate alcoholic from non-alcoholic individuals

Alcohol dependence is characterized by tolerance, physical dependence, and craving. The neuroadaptations underlying these effects of chronic alcohol abuse are likely due to altered gene expression. Previous gene expression studies using human post-mortem brain demonstrated that several gene families were altered by alcohol abuse. However, most of these changes in gene expression were small. It is not clear if gene expression profiles have sufficient power to discriminate control from alcoholic individuals and how consistent gene expression changes are when a relatively large sample size is examined. In the present study, microarray analysis (similar to 47 000 elements) was performed on the superior frontal cortex of 27 individual human cases ( 14 well characterized alcoholics and 13 matched controls). A partial least squares statistical procedure was applied to identify genes with altered expression levels in alcoholics. We found that genes involved in myelination, ubiquitination, apoptosis, cell adhesion, neurogenesis, and neural disease showed altered expression levels. Importantly, genes involved in neurodegenerative diseases such as Alzheimer's disease were significantly altered suggesting a link between alcoholism and other neurodegenerative conditions. A total of 27 genes identified in this study were previously shown to be changed by alcohol abuse in previous studies of human post-mortem brain. These results revealed a consistent re-programming of gene expression in alcohol abusers that reliably discriminates alcoholic from non-alcoholic individuals.

Heritability and nineteen-year stability of long and short EPQ-R Neuroticism scales

The heritability and stability over a 19 year period of long (23-item) and short (12-item) versions of Eysenck's Neuroticism scale were compared in a large Australian twin-family sample. Stability over 19 years of the 23-item Neuroticism scale was 0.62 and for the 12-item scale 0.59. Correlations between scores obtained by mailed questionnaire and telephone interview a few weeks apart were 0.87 for the long scale and 0.85 for the short scale; scores obtained by mail were slightly higher, particularly for females. The 12-item scale had slightly reduced power to discriminate both high and low scoring individuals on the full 23-item scale. Mean Neuroticism score for the 12-item scale was atypically low when compared to the distribution of the complete set of scores for all possible combinations (> 1 million) of 12-items drawn from the full 23-item EPQ-R. Mean heritabilities for the lowest and highest 300,000 of these combinations were 43.2% and 42.7%, respectively, somewhat higher than the 41.0% for the actual EPQ-R-S 12-item scale. Heritability for the 23-item scale was 46.5%. We conclude that there is little loss of either stability or heritability in using the short EPQ-R scale, but the choice of which 12-items could have been better. (c) 2005 Elsevier Ltd. All rights reserved.

Visualization of Cerenkov radiation and the fields of a moving charge

For some physics students, the concept of a particle travelling faster than the speed of light holds endless fascination, and. Cerenkov radiation is a visible consequence of a charged particle travelling through a medium at locally superluminal velocities. The Heaviside-Feynman equations for calculating the magnetic and electric fields of a moving charge have been known for many decades, but it is only recently that the computing power to plot the fields of such a particle has become readily available for student use. This paper investigates and illustrates the calculation of Maxwell's D field in homogeneous isotropic media for arbitrary, including superluminal, constant velocity, and uses the results as a basis for discussing energy transfer in the electromagnetic field.

Handedness in twins: Joint analysis of data from 35 samples

Simultaneous analysis of handedness data from 35 samples of twins (with a combined sample size of 21,127 twin pairs) found a small but significant additive genetic effect accounting for 25.47% of the variance (95% confidence interval [CI] 15.69-29.51%). No common environmental influences were detected (C = 0.00; 95% Cl 0.00-7.67%), with the majority of the variance, 74.53%, explained by factors unique to the individual (95% Cl 70.49-78.67%). No significant heterogeneity was observed within studies that used similar methods to assess handedness, or across studies that used different methods. At an individual level the majority of studies had insufficient power to reject a purely unique environmental model due to insufficient power to detect familial aggregation. This lack of power is seldom mentioned within studies, and has contributed to the misconception that twin studies of handedness are not informative.

Bias, precision and heritability of self-reported and clinically measured height in Australian twins

Many studies of quantitative and disease traits in human genetics rely upon self-reported measures. Such measures are based on questionnaires or interviews and are often cheaper and more readily available than alternatives. However, the precision and potential bias cannot usually be assessed. Here we report a detailed quantitative genetic analysis of stature. We characterise the degree of measurement error by utilising a large sample of Australian twin pairs (857 MZ, 815 DZ) with both clinical and self-reported measures of height. Self-report height measurements are shown to be more variable than clinical measures. This has led to lowered estimates of heritability in many previous studies of stature. In our twin sample the heritability estimate for clinical height exceeded 90%. Repeated measures analysis shows that 2-3 times as many self-report measures are required to recover heritability estimates similar to those obtained from clinical measures. Bivariate genetic repeated measures analysis of self-report and clinical height measures showed an additive genetic correlation > 0.98. We show that the accuracy of self-report height is upwardly biased in older individuals and in individuals of short stature. By comparing clinical and self-report measures we also showed that there was a genetic component to females systematically reporting their height incorrectly; this phenomenon appeared to not be present in males. The results from the measurement error analysis were subsequently used to assess the effects of error on the power to detect linkage in a genome scan. Moderate reduction in error (through the use of accurate clinical or multiple self-report measures) increased the effective sample size by 22%; elimination of measurement error led to increases in effective sample size of 41%.

Optimizing Presence–Absence Surveys For Detecting Population Trends

Presence-absence surveys are a commonly used method for monitoring broad-scale changes in wildlife distributions. However, the lack of power of these surveys for detecting population trends is problematic for their application in wildlife management. Options for improving power include increasing the sampling effort or arbitrarily relaxing the type I error rate. We present an alternative, whereby targeted sampling of particular habitats in the landscape using information from a habitat model increases power. The advantage of this approach is that it does not require a trade-off with either cost or the Pr(type I error) to achieve greater power. We use a demographic model of koala (Phascolarctos cinereus) population dynamics and simulations of the monitoring process to estimate the power to detect a trend in occupancy for a range of strategies, thereby demonstrating that targeting particular habitat qualities can improve power substantially. If the objective is to detect a decline in occupancy, the optimal strategy is to sample high-quality habitats. Alternatively, if the objective is to detect an increase in occupancy, the optimal strategy is to sample intermediate-quality habitats. The strategies with the highest power remained the same under a range of parameter assumptions, although observation error had a strong influence on the optimal strategy. Our approach specifically applies to monitoring for detecting long-term trends in occupancy or abundance. This is a common and important monitoring objective for wildlife managers, and we provide guidelines for more effectively achieving it.

TEOLOGIA DA PROSPERIDADE: ADAPTAÇÃO DA RELIGIÃO À LÓGICA DA SOCIEDADE DE CONSUMO.

Esta dissertação analisa a Teologia da Prosperidade, especialmente seu poder de adaptar a religião à lógica da sociedade de consumo. Essa teologia surge nos Estados Unidos na década de 1940, consolidando-se rapidamente no meio evangélico, chegou a influenciar inclusive as igrejas denominadas tradicionais. Sua ênfase está na promessa da prosperidade para seus fiéis. A pesquisa pretende descrever as raízes e o contexto do surgimento desta teologia, sua chegada e propagação no Brasil, seus principais expoentes e sua apropriação pelas igrejas neopentecostais. A suspeita que orienta a pesquisa é a de que o êxito da Teologia da Prosperidade se deve à sua capacidade de adaptar a religião à lógica da sociedade de consumo.

A VONTADE SOB O IMPACTO DA PÓS-MODERNIDADE (A FÉ INTERPELANDO A FRAGMENTAÇÃO DA VONTADE)

Este trabalho investiga uma das formas pelas quais a condição contemporânea, assim chamada pós-moderna, exerce significativo impacto sobre a vontade humana. Numa perspectiva fenomenológica e existencial, apoiada primordialmente no pensamento de Paul Ricoeur e Paul Tillich, esta abordagem busca identificar a relação entre a condição pós-moderna e a crise contemporânea da vontade que, como hipótese de tese, encontra-se vinculada à forma pela qual é estabelecida a relação entre vontade e desejo. A pós-modernidade é analisada a partir de seu desenvolvimento sócio-cultural desde a década de 1930 e em interlocução com os pensamentos de Jean-François Lyotard e Jean Baudrillard de forma a evidenciar o desenvolvimento desta relação. Algumas perspectivas filosófico-teológicas são exploradas a partir da situação de impacto aqui em questão. São tentativas de contribuir para que a vontade redescubra seu caráter integralizador e possa considerá-lo tão imprescindível quanto seu ímpeto expansionista e dissipador, uma vez que ambos os movimentos são partes integrantes da coragem e do poder-de-ser que a fundamentam.(AU)

O Judaísmo Encalacrado: mística e religião em A Hora da Estrela, de Clarice Lispector

O objetivo deste trabalho foi o de demonstrar a importância e pertinência do diálogo entre literatura e religião, concentrando o âmbito de sua pesquisa a partir das relações entre a escritura de Clarice Lispector e as ressonâncias de uma tradição (judaísmo), que embora não tenha sido assumida pela autora, persiste, encalacrada em toda a sua obra. Tendo, como objeto de pesquisa o romance A Hora da Estrela, esta dissertação procurou entender como o drama da narrativa, em seu jogo de tensões e identidades, em sua pluralidade de títulos e referências, sinaliza também um profundo problema com a religião. Focando, de forma especial a personagem Macabéa, este estudo procurou compreender como as referencias da personagem, sua dificuldade com as palavras, seus desencontros do outro (tu) e sua rejeição social, revelam um grave problema de ordem teológica, demonstrando os equívocos de uma sociedade, que fundada sobre o prisma da religião, massacra os mais fracos. O desfecho do livro sinaliza uma possível epifania, mas, desvela-se num fracasso da religião e de seu poder salvífico. O trabalho procurou a partir dos principais temas do romance, perceber suas correspondências com o tema da religião. Pode com isso, a partir das contribuições de Scholem, ver como dilema existencial e subjetivo da personagem possui proximidade com o drama místico cabalístico, além disso, perceber as correlações entre a obra clariceana e textos da tradição judaíca, quer na sua referência explícita (nome da personagem), como também, em seu aspecto de busca, em sua forma de midrash e nas inúmeras exegeses e comentários que propicia. Finaliza seu esforço, levantando uma discussão ética sobre os valores teológicos da sociedade e seus profundos equívocos, ante a vida e morte da pobre Macabéa, uma mulher que viveu a religião nos limites da própria existência.

A PUBLICIDADE RADIOFÔNICA EM BUSCA DE UMA NOVA CONFIGURAÇÃO

Ainda que um conjunto de atributos confira ao rádio um grande potencial para chamar a atenção do ouvinte e envolvê-lo em sua mensagem; ainda que o rádio seja uma das mídias com maior penetração nos domicílios e automóveis do Brasil; ainda que a adaptação do rádio às tecnologias digitais trace perspectivas otimistas para o meio; ainda que a sociedade moderna esteja criando indivíduos extremamente ocupados, que passam mais tempo no trabalho e nos automóveis do que em casa, abrindo espaço para o único meio que permite a execução de outras tarefas enquanto é consumido; comercialmente, o rádio enfrenta grandes dificuldades para atrair investimentos publicitários principal fonte de renda do meio. Nesse sentido, esta pesquisa exploratória pretende identificar e analisar os fatores que influenciam o baixo posicionamento do rádio no ranking dos investimentos publicitários. Para tanto, serão analisadas duas questões consideradas fundamentais: o emprego das possibilidades expressivas e persuasivas da publicidade radiofônica nos anúncios veiculados pelas emissoras e a percepção dos profissionais envolvidos na operacionalização da publicidade radiofônica sobre a atividade publicitária no rádio.

AS PARCERIAS PÚBLICO-PRIVADAS NA EDUCAÇÃO INFANTIL: UM ESTUDO SOBRE A LAICIDADE DO ESTADO E A RELIGIOSIDADE DE INSTITUIÇÕES CONVENIADAS

Uma das políticas mais utilizadas pelo poder publico municipal para garantir o atendimento educacional às crianças de 0 a 3 anos e a ampliação do número de vagas em creches, tem sido a adoção de parcerias por meio de convênios com instituições privadas. Muitas questões emergem desta política pública como, por exemplo, a relação entre a laicidade do Estado e a religiosidade de grande parte destas instituições. Este estudo surgiu da necessidade de se dar maior transparência e ampliar o debate sobre os convênios entre o poder público municipal e entidades assistenciais, principalmente, no que tange o embate entre o público e o privado, entre o laico e o religioso. Este trabalho teve como objetivo investigar as parcerias público-privadas e os possíveis impactos sobre a laicidade do Estado e o direito à Educação. O problema de pesquisa posto foi o que o Parecer CME 12/2011 revela sobre a laicidade do Estado e a religiosidade das instituições conveniadas no atendimento a educação infantil do município de São Bernardo do Campo? Havia a hipótese de que a representação de uma entidade conveniada ao Conselho Municipal de Educação sobre educação espiritual expressasse uma possível projeção de ensino religioso na educação infantil pública. A discussão teórica envolveu autores como FISCHMANN (2009), ARELARO (2008), SARMENTO (2006), ADRIÂO (2009), OLIVEIRA (2005) e ideias que tratavam das deformações dos interesses públicos e privados, da oferta de vagas no seguimento de creche, do ensino religioso em escola pública. A metodologia empregada foi analise bibliográfica e documental. A literatura aponta uma histórica subordinação da educação infantil pública à assistência social privada e as disputas pela implantação do ensino religioso na educação básica pública. Os documentos analisados revelaram que é possível haver certo grau de comprometimento da laicidade do Estado quando se formaliza parcerias com entidades assistenciais de origem religiosa, principalmente, quando se avalia as deficiências e tendências de gestão e supervisão dos convênios realizados pelo poder público. Acredita-se que este estudo abre portas para novas investigações sobre políticas e práticas que enfrentam ou estimulam o ensino religioso em escolas públicas e creches conveniadas.

Data visualization during the early stages of drug discovery

Multidimensional compound optimization is a new paradigm in the drug discovery process, yielding efficiencies during early stages and reducing attrition in the later stages of drug development. The success of this strategy relies heavily on understanding this multidimensional data and extracting useful information from it. This paper demonstrates how principled visualization algorithms can be used to understand and explore a large data set created in the early stages of drug discovery. The experiments presented are performed on a real-world data set comprising biological activity data and some whole-molecular physicochemical properties. Data visualization is a popular way of presenting complex data in a simpler form. We have applied powerful principled visualization methods, such as generative topographic mapping (GTM) and hierarchical GTM (HGTM), to help the domain experts (screening scientists, chemists, biologists, etc.) understand and draw meaningful decisions. We also benchmark these principled methods against relatively better known visualization approaches, principal component analysis (PCA), Sammon's mapping, and self-organizing maps (SOMs), to demonstrate their enhanced power to help the user visualize the large multidimensional data sets one has to deal with during the early stages of the drug discovery process. The results reported clearly show that the GTM and HGTM algorithms allow the user to cluster active compounds for different targets and understand them better than the benchmarks. An interactive software tool supporting these visualization algorithms was provided to the domain experts. The tool facilitates the domain experts by exploration of the projection obtained from the visualization algorithms providing facilities such as parallel coordinate plots, magnification factors, directional curvatures, and integration with industry standard software. © 2006 American Chemical Society.