A coarsened multinomial regression model for perinatal mother to child transmission of HIV

Background: In trials designed to estimate rates of perinatal mother to child transmission of HIV, HIV assays are scheduled at multiple points in time. Still, infection status for some infants at some time points may be unknown, particularly when interim analyses are conducted. Methods: Logistic regression models are commonly used to estimate covariate-adjusted transmission rates, but their methods for handling missing data may be inadequate. Here we propose using coarsened multinomial regression models to estimate cumulative and conditional rates of HIV transmission. Through simulation, we compare the proposed models to standard logistic models in terms of bias, mean squared error, coverage probability, and power. We consider a range of treatment effect and visit process scenarios, while including imperfect sensitivity of the assay and contamination of the endpoint due to early breastfeeding transmission. We illustrate the approach through analysis of data from a clinical trial designed to prevent perinatal transmission. Results: The proposed cumulative and conditional models performed well when compared to their logistic counterparts. Performance of the proposed cumulative model was particularly strong under scenarios where treatment was assumed to increase the risk of in utero transmission but decrease the risk of intrapartum and overall perinatal transmission and under scenarios designed to represent interim analyses. Power to estimate intrapartum and perinatal transmission was consistently higher for the proposed models. Conclusion: Coarsened multinomial regression models are preferred to standard logistic models for estimation of perinatal mother to child transmission of HIV, particularly when assays are missing or occur off-schedule for some infants.U.S. National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and Dept. of Health and Human Services (DHHS)

Structural and biochemical characterization of the exopolysaccharide deacetylase Agd3 required for Aspergillus fumigatus biofilm formation

The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Deletion of a gene encoding a putative deacetylase, Agd3, leads to defects in GAG deacetylation, biofilm formation, and virulence. Here, we show that Agd3 deacetylates GAG in a metal-dependent manner, and is the founding member of carbohydrate esterase family CE18. The active site is formed by four catalytic motifs that are essential for activity. The structure of Agd3 includes an elongated substrate-binding cleft formed by a carbohydrate binding module (CBM) that is the founding member of CBM family 87. Agd3 homologues are encoded in previously unidentified putative bacterial exopolysaccharide biosynthetic operons and in other fungal genomes. The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Here, the authors study an A. fumigatus enzyme that deacetylates GAG in a metal-dependent manner and constitutes a founding member of a new carbohydrate esterase family.Bio-organic Synthesi

Subject specific demands of teaching: Implications for out-of-field teachers

This chapter provides a framework for thinking about the subject-specific nature of teaching in terms of the knowledge, modes of inquiry and discursive practices that delineate one subject from another in the traditional school curriculum. The chapter will explore how these disciplinary traits are translated into teaching as curriculum, knowledge and pedagogy, and how this subject-specificity of teaching is juxtaposed against the more generic aspects of teaching. The chapter explores the idea that if a teacher’s expertise can be situated within a field, then they can also be positioned out-of-field. Implications for teaching out-of-field are discussed in terms of the subject-specific knowledge, processes and skills, and the difficulties associated with teacher practice. English and Australian illustrations of teacher practices from in-field and out-of-field situations are provided, in particular highlighting the demands of moving across subject boundaries. Cross-fertilisation is especially evident when subjects are integrated, therefore, the issues associated with integrated curriculum are discussed where the traditional subject boundaries are being challenged as schools are reorganised to integrate subjects through, for example, STEM teaching, or holistic curriculum designs

Environmental Influences on Mate Preferences as Assessed by a Scenario Manipulation Experiment

Many evolutionary psychology studies have addressed the topic of mate preferences, focusing particularly on gender and cultural differences. However, the extent to which situational and environmental variables might affect mate preferences has been comparatively neglected. We tested 288 participants in order to investigate the perceived relative importance of six traits of an ideal partner (wealth, dominance, intelligence, height, kindness, attractiveness) under four different hypothetical scenarios (status quo/nowadays, violence/post-nuclear, poverty/resource exhaustion, prosperity/global well-being). An equal number of participants (36 women, 36 men) was allotted to each scenario; each was asked to allocate 120 points across the six traits according to their perceived value. Overall, intelligence was the trait to which participants assigned most importance, followed by kindness and attractiveness, and then by wealth, dominance and height. Men appraised attractiveness as more valuable than women. Scenario strongly influenced the relative importance attributed to traits, the main finding being that wealth and dominance were more valued in the poverty and post-nuclear scenarios, respectively, compared to the other scenarios. Scenario manipulation generally had similar effects in both sexes, but women appeared particularly prone to trade off other traits for dominance in the violence scenario, and men particularly prone to trade off other traits for wealth in the poverty scenario. Our results are in line with other correlational studies of situational variables and mate preferences, and represent strong evidence of a causal relationship of environmental factors on specific mate preferences, corroborating the notion of an evolved plasticity to current ecological conditions. A control experiment seems to suggest that our scenarios can be considered as realistic descriptions of the intended ecological conditions

Environmental Influences on Mate Preferences as Assessed by a Scenario Manipulation Experiment

Many evolutionary psychology studies have addressed the topic of mate preferences, focusing particularly on gender and cultural differences. However, the extent to which situational and environmental variables might affect mate preferences has been comparatively neglected. We tested 288 participants in order to investigate the perceived relative importance of six traits of an ideal partner (wealth, dominance, intelligence, height, kindness, attractiveness) under four different hypothetical scenarios (status quo/nowadays, violence/post-nuclear, poverty/resource exhaustion, prosperity/global well-being). An equal number of participants (36 women, 36 men) was allotted to each scenario; each was asked to allocate 120 points across the six traits according to their perceived value. Overall, intelligence was the trait to which participants assigned most importance, followed by kindness and attractiveness, and then by wealth, dominance and height. Men appraised attractiveness as more valuable than women. Scenario strongly influenced the relative importance attributed to traits, the main finding being that wealth and dominance were more valued in the poverty and post-nuclear scenarios, respectively, compared to the other scenarios. Scenario manipulation generally had similar effects in both sexes, but women appeared particularly prone to trade off other traits for dominance in the violence scenario, and men particularly prone to trade off other traits for wealth in the poverty scenario. Our results are in line with other correlational studies of situational variables and mate preferences, and represent strong evidence of a causal relationship of environmental factors on specific mate preferences, corroborating the notion of an evolved plasticity to current ecological conditions. A control experiment seems to suggest that our scenarios can be considered as realistic descriptions of the intended ecological conditions

Eicosapentaenoic acid and docosahexaenoic acid reduce interleukin-1β-mediated cartilage degradation

Introduction: In inflammatory joint disease, such as osteoarthritis (OA), there is an increased level of proinflammatory cytokines, such as interleukin (IL)-1β. These cytokines stimulate the production of matrix metalloproteinases (MMPs), which leads to the degradation of the cartilage extracellular matrix and the loss of key structural components such as sulphated glycosaminoglycan (sGAG) and collagen II. The aim of this study was to examine the therapeutic potential of n-3 polyunsaturated fatty acids (PUFAs) in an in vitro model of cartilage inflammation. Methods: Two specific n-3 compounds were tested, namely, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), each at 0.1, 1 and 10 μM. Full thickness bovine cartilage explants, 5 mm in diameter, were cultured for 5 days with or without IL-1β and in the presence or absence of each n-3 compound. The media were replaced every 24 hours and assayed for sGAG content using the 1,9-dimethylmethylene blue (DMB) method. Chondrocyte viability was determined at the end of the culture period using fluorescence microscopy to visualise cells labelled with calcein AM and ethidium homodimer. Results: Treatment with IL-1β (10 ng.ml-1) produced a large increase in sGAG release compared to untreated controls, but with no effect on cell viability, which was maintained above 80% for all treatments. In the absence of IL-1β, both n-3 compounds induced a mild catabolic response with increased loss of sGAG, particularly at 10 μM. By contrast, in the presence of IL-1β, both EPA and DHA at 0.1 and 1 μM significantly reduced IL-1β-mediated sGAG loss. The efficacy of the EPA treatment was maintained at approximately 75% throughout the 5-day period. However, at the same concentrations, the efficacy of DHA, although initially greater, reduced to approximately half that of EPA after 5 days. For both EPA and DHA, the highest dose of 10 μM was less effective. Conclusions: The results support the hypothesis that n-3 compounds are anti-inflammatory through competitive inhibition of the arachidonic acid oxidation pathway. The efficacy of these compounds is likely to be even greater at more physiological levels of IL-1β. Thus we suggest that n-3 PUFAs, particularly EPA, have exciting therapeutic potential for preventing cartilage degradation associated with chronic inflammatory joint disease

Comparison of generalized estimating equations and quadratic inference functions using data from the National Longitudinal Survey of Children and Youth (NLSCY) database

<p>Abstract</p> <p>Background</p> <p>The generalized estimating equations (GEE) technique is often used in longitudinal data modeling, where investigators are interested in population-averaged effects of covariates on responses of interest. GEE involves specifying a model relating covariates to outcomes and a plausible correlation structure between responses at different time periods. While GEE parameter estimates are consistent irrespective of the true underlying correlation structure, the method has some limitations that include challenges with model selection due to lack of absolute goodness-of-fit tests to aid comparisons among several plausible models. The quadratic inference functions (QIF) method extends the capabilities of GEE, while also addressing some GEE limitations.</p> <p>Methods</p> <p>We conducted a comparative study between GEE and QIF via an illustrative example, using data from the "National Longitudinal Survey of Children and Youth (NLSCY)" database. The NLSCY dataset consists of long-term, population based survey data collected since 1994, and is designed to evaluate the determinants of developmental outcomes in Canadian children. We modeled the relationship between hyperactivity-inattention and gender, age, family functioning, maternal depression symptoms, household income adequacy, maternal immigration status and maternal educational level using GEE and QIF. Basis for comparison include: (1) ease of model selection; (2) sensitivity of results to different working correlation matrices; and (3) efficiency of parameter estimates.</p> <p>Results</p> <p>The sample included 795, 858 respondents (50.3% male; 12% immigrant; 6% from dysfunctional families). QIF analysis reveals that gender (male) (odds ratio [OR] = 1.73; 95% confidence interval [CI] = 1.10 to 2.71), family dysfunctional (OR = 2.84, 95% CI of 1.58 to 5.11), and maternal depression (OR = 2.49, 95% CI of 1.60 to 2.60) are significantly associated with higher odds of hyperactivity-inattention. The results remained robust under GEE modeling. Model selection was facilitated in QIF using a goodness-of-fit statistic. Overall, estimates from QIF were more efficient than those from GEE using AR (1) and Exchangeable working correlation matrices (Relative efficiency = 1.1117; 1.3082 respectively).</p> <p>Conclusion</p> <p>QIF is useful for model selection and provides more efficient parameter estimates than GEE. QIF can help investigators obtain more reliable results when used in conjunction with GEE.</p

Primary care nurses struggle with lifestyle counseling in diabetes care: a qualitative analysis

Contains fulltext : 89605.pdf (publisher's version ) (Open Access)BACKGROUND: Patient outcomes are poorly affected by lifestyle advice in general practice. Promoting lifestyle behavior change require that nurses shift from simple advice giving to a more counseling-based approach. The current study examines which barriers nurses encounter in lifestyle counseling to patients with type 2 diabetes. Based on this information we will develop an implementation strategy to improve lifestyle behavior change in general practice. METHOD: In a qualitative semi-structured study, twelve in-depth interviews took place with nurses in Dutch general practices involved in diabetes care. Specific barriers in counseling patients with type 2 diabetes about diet, physical activity, and smoking cessation were addressed. The nurses were invited to reflect on barriers at the patient and practice levels, but mainly on their own roles as counselors. All interviews were audio-recorded and transcribed. The data were analyzed with the aid of a predetermined framework. RESULTS: Nurses felt most barriers on the level of the patient; patients had limited knowledge of a healthy lifestyle and limited insight into their own behavior, and they lacked the motivation to modify their lifestyles or the discipline to maintain an improved lifestyle. Furthermore, nurses reported lack of counseling skills and insufficient time as barriers in effective lifestyle counseling. CONCLUSIONS: The traditional health education approach is still predominant in primary care of patients with type 2 diabetes. An implementation strategy based on motivational interviewing can help to overcome 'jumping ahead of the patient' and promotes skills in lifestyle behavioral change. We will train our nurses in agenda setting to structure the consultation based on prioritizing the behavior change and will help them to develop social maps that contain information on local exercise programs