Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1.

UNLABELLED: Infants born to HIV-1-infected mothers in resource-limited areas where replacement feeding is unsafe and impractical are repeatedly exposed to HIV-1 throughout breastfeeding. Despite this, the majority of infants do not contract HIV-1 postnatally, even in the absence of maternal antiretroviral therapy. This suggests that immune factors in breast milk of HIV-1-infected mothers help to limit vertical transmission. We compared the HIV-1 envelope-specific breast milk and plasma antibody responses of clade C HIV-1-infected postnatally transmitting and nontransmitting mothers in the control arm of the Malawi-based Breastfeeding Antiretrovirals and Nutrition Study using multivariable logistic regression modeling. We found no association between milk or plasma neutralization activity, antibody-dependent cell-mediated cytotoxicity, or HIV-1 envelope-specific IgG responses and postnatal transmission risk. While the envelope-specific breast milk and plasma IgA responses also did not reach significance in predicting postnatal transmission risk in the primary model after correction for multiple comparisons, subsequent exploratory analysis using two distinct assay methodologies demonstrated that the magnitudes of breast milk total and secretory IgA responses against a consensus HIV-1 envelope gp140 (B.con env03) were associated with reduced postnatal transmission risk. These results suggest a protective role for mucosal HIV-1 envelope-specific IgA responses in the context of postnatal virus transmission. This finding supports further investigations into the mechanisms by which mucosal IgA reduces risk of HIV-1 transmission via breast milk and into immune interventions aimed at enhancing this response. IMPORTANCE: Infants born to HIV-1-infected mothers are repeatedly exposed to the virus in breast milk. Remarkably, the transmission rate is low, suggesting that immune factors in the breast milk of HIV-1-infected mothers help to limit transmission. We compared the antibody responses in plasma and breast milk of HIV-1-transmitting and -nontransmitting mothers to identify responses that correlated with reduced risk of postnatal HIV-1 transmission. We found that neither plasma nor breast milk IgG antibody responses were associated with risk of HIV-1 transmission. In contrast, the magnitudes of the breast milk IgA and secretory IgA responses against HIV-1 envelope proteins were associated with reduced risk of postnatal HIV-1 transmission. The results of this study support further investigations of the mechanisms by which mucosal IgA may reduce the risk of HIV-1 transmission via breastfeeding and the development of strategies to enhance milk envelope-specific IgA responses to reduce mother-to-child HIV transmission and promote an HIV-free generation.

Toxicity profile of bevacizumab in the UK Neurofibromatosis Type 2 cohort

Bevacizumab is considered an established part of the treatment strategies available for schwannomas in patients with Neurofibromatosis Type 2(NF2). In the UK, it is available through NHS National Specialized Commissioning to NF2 patients with a rapidly growing target schwannoma. Regrowth of the tumour on suspension of treatment is often observed resulting in prolonged periods of exposure to bevacizumab to control the disease. Hypertension and proteinuria are common events with bevacizumab use and there are concerns with regards to the long-term risks of prolonged treatment. Dosing, demographic and adverse event(CTCAE 4.03) data from the UK NF2 bevacizumab cohort are reviewed with particular consideration of renal and cardiovascular complications. Eighty patients (48 male:32female), median age 24.5 years (range 11-66years), were followed for a median of 32.7 months (range 12.0–60.2months). The most common adverse events were fatigue, hypertension and infection. A total of 19/80 patients (24%) had either a grade 2 or grade 3 hypertension event and 14/80 patients (17.5%) had proteinuria. Of 36 patients followed for 36 months, 78% were free from hypertension and 86% were free of proteinuria. Logistic regression modeling identified age and induction dosing regime to be predictors of development of hypertension with dose of 7.5mg/kg three weekly and age >30years having higher rates of hypertension. Proteinuria persisted in one of three patients after cessation of bevacizumab. One patient developed congestive heart failure and the details of this case are described. Further work is needed to determine optimal dosing regimes to limit toxicity without impacting on efficacy.

Evaluation of a Quality Improvement (QI) Intervention for Maternal, Newborn, and Child Health (MNCH) in Colombia: The Mil Días Intervention of SINERGIAS in the Department of Bolívar

Thesis (Master's)--University of Washington, 2016-06

An Examination of Parental Engagement During the Middle School Years

The purpose of this quantitative study was to explore the previously unexamined phenomenon of middle school parental engagement in a large urban/suburban/rural school district of 209 schools in the mid-Atlantic region of the United States. Across 22 middle schools serving grades six-eight, this study collected and examined perceptions of the three key adult stakeholder groups – administrators, teachers, and parents – most actively involved in middle school parental engagement as described within the theoretical framework of academic socialization. Their reports of observable parental engagement activities were used to document how district stakeholders operationalize behaviors that represent the five actionable constructs and three themes of academic socialization to determine how the district “fares” in employing academic socialization as a middle school parent engagement strategy. The study also applied quantitative descriptive analysis through a one-way ANOVA to determine the significance of observable variations in actionable constructs between the perspectives of the three stakeholder groups. Finally, the study illuminated, through regression modeling, when confounding factors/independent variables such as race, income, school size, administrator and teacher experience, parents’ educational background, etc., impacted operationalization of academic socialization behaviors for middle school parent and family engagement. Rejecting the null hypothesis, the study found that the three stakeholder groups had statistically significant differences in perceptions of their implementation of activities aligned to academic socialization. This study ultimately illuminated ways in which these adult stakeholder groups share similar and varied perceptions about their engagement actions that support the achievement and maturation of middle school students. Significantly, this study provided key findings that illuminated areas that can be systemically addressed to transform middle school parent engagement practices through applied academic socialization theory into consistent and effective collaborative efforts between the home and school. The process of operationalizing academic socialization was outlined in terms that any school or district can follow to improve programs and practices of middle school parental engagement to serve in the best interests of students during this period of great transition for both child/adolescent growth and development and adult navigation of systems to provide support for students in this unique stage of growth and maturation.

Training civic bridge builders: Outcomes of community leadership development programs

As rural communities experience rapid economic, demographic, and political change, program interventions that focus on the development of community leadership capacity could be valuable. Community leadership development programs have been deployed in rural U.S. communities for the past 30 years by university extension units, chambers of commerce, and other nonprofit foundations. Prior research on program outcomes has largely focused on trainees’ self-reported change in individual leadership knowledge, skills, and attitudes. However, postindustrial leadership theories suggest that leadership in the community relies not on individuals but on social relationships that develop across groups akin to social bridging. The purpose of this study is to extend and strengthen prior evaluative research on community leadership development programs by examining program effects on opportunities to develop bridging social capital using more rigorous methods. Data from a quasi-experimental study of rural community leaders (n = 768) in six states are used to isolate unique program effects on individual changes in both cognitive and behavioral community leadership outcomes. Regression modeling shows that participation in community leadership development programs is associated with increased leadership development in knowledge, skills, attitudes, and behaviors that are a catalyst for social bridging. The community capitals framework is used to show that program participants are significantly more likely to broaden their span of involvement across community capital asset areas over time compared to non-participants. Data on specific program structure elements show that skills training may be important for cognitive outcomes while community development learning and group projects are important for changes in organizational behavior. Suggestions for community leadership program practitioners are presented.

Modelagem univariada e regressão múltipla na análise da oferta e do preço do boi gordo no mercado brasileiro

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Agronomia e Medicina Veterinária, Programa de Pós-Graduação em Agronegócios, 2016.

Integrated soil fertility management in eastern and western Africa: The role of knowledge and innovation systems, its adoption and impact

The rise in population growth, as well as nutrient mining, has contributed to low agricultural productivity in Sub-Saharan Africa (SSA). A plethora of technologies to boost agricultural production have been developed but the dissemination of these agricultural innovations and subsequent uptake by smallholder farmers has remained a challenge. Scientists and philanthropists have adopted the Integrated Soil Fertility Management (ISFM) paradigm as a means to promote sustainable intensification of African farming systems. This comparative study aimed: 1) To assess the efficacy of Agricultural Knowledge and Innovation Systems (AKIS) in East (Kenya) and West (Ghana) Africa in the communication and dissemination of ISFM (Study I); 2) To investigate how specifically soil quality, and more broadly socio-economic status and institutional factors, influence farmer adoption of ISFM (Study II); and 3) To assess the effect of ISFM on maize yield and total household income of smallholder farmers (Study III). To address these aims, a mixed methodology approach was employed for study I. AKIS actors were subjected to social network analysis methods and in-depth interviews. Structured questionnaires were administered to 285 farming households in Tamale and 300 households in Kakamega selected using a stratified random sampling approach. There was a positive relationship between complete ISFM awareness among farmers and weak knowledge ties to both formal and informal actors at both research locations. The Kakamega AKIS revealed a relationship between complete ISFM awareness among farmers and them having strong knowledge ties to formal actors implying that further integration of formal actors with farmers’ local knowledge is crucial for the agricultural development progress. The structured questionnaire was also utilized to answer the query pertaining to study II. Soil samples (0-20 cm depth) were drawn from 322 (Tamale, Ghana) and 459 (Kakamega, Kenya) maize plots and analysed non-destructively for various soil fertility indicators. Ordinal regression modeling was applied to assess the cumulative adoption of ISFM. According to model estimates, soil carbon seemed to preclude farmers from intensifying input use in Tamale, whereas in Kakamega it spurred complete adoption. This varied response by farmers to soil quality conditions is multifaceted. From the Tamale perspective, it is consistent with farmers’ tendency to judiciously allocate scarce resources. Viewed from the Kakamega perspective, it points to a need for farmers here to intensify agricultural production in order to foster food security. In Kakamega, farmers with more acidic soils were more likely to adopt ISFM. Other household and farm-level factors necessary for ISFM adoption included off-farm income, livestock ownership, farmer associations, and market inter-linkages. Finally, in study III a counterfactual model was used to calculate the difference in outcomes (yield and household income) of the treatment (ISFM adoption) in order to estimate causal effects of ISFM adoption. Adoption of ISFM contributed to a yield increase of 16% in both Tamale and Kakamega. The innovation affected total household income only in Tamale, where ISFM adopters had an income gain of 20%. This may be attributable to the different policy contexts under which the two sets of farmers operate. The main recommendations underscored the need to: (1) improve the functioning of AKIS, (2) enhance farmer access to hybrid maize seed and credit, (3) and conduct additional multi-locational studies as farmers operate under varying contexts.

Sparse modeling using orthogonal forward regression with PRESS statistic and regularization

The paper introduces an efficient construction algorithm for obtaining sparse linear-in-the-weights regression models based on an approach of directly optimizing model generalization capability. This is achieved by utilizing the delete-1 cross validation concept and the associated leave-one-out test error also known as the predicted residual sums of squares (PRESS) statistic, without resorting to any other validation data set for model evaluation in the model construction process. Computational efficiency is ensured using an orthogonal forward regression, but the algorithm incrementally minimizes the PRESS statistic instead of the usual sum of the squared training errors. A local regularization method can naturally be incorporated into the model selection procedure to further enforce model sparsity. The proposed algorithm is fully automatic, and the user is not required to specify any criterion to terminate the model construction procedure. Comparisons with some of the existing state-of-art modeling methods are given, and several examples are included to demonstrate the ability of the proposed algorithm to effectively construct sparse models that generalize well.

Particle swarm optimization aided orthogonal forward regression for unified data modeling

We propose a unified data modeling approach that is equally applicable to supervised regression and classification applications, as well as to unsupervised probability density function estimation. A particle swarm optimization (PSO) aided orthogonal forward regression (OFR) algorithm based on leave-one-out (LOO) criteria is developed to construct parsimonious radial basis function (RBF) networks with tunable nodes. Each stage of the construction process determines the center vector and diagonal covariance matrix of one RBF node by minimizing the LOO statistics. For regression applications, the LOO criterion is chosen to be the LOO mean square error, while the LOO misclassification rate is adopted in two-class classification applications. By adopting the Parzen window estimate as the desired response, the unsupervised density estimation problem is transformed into a constrained regression problem. This PSO aided OFR algorithm for tunable-node RBF networks is capable of constructing very parsimonious RBF models that generalize well, and our analysis and experimental results demonstrate that the algorithm is computationally even simpler than the efficient regularization assisted orthogonal least square algorithm based on LOO criteria for selecting fixed-node RBF models. Another significant advantage of the proposed learning procedure is that it does not have learning hyperparameters that have to be tuned using costly cross validation. The effectiveness of the proposed PSO aided OFR construction procedure is illustrated using several examples taken from regression and classification, as well as density estimation applications.

Modeling of average growth curve in Santa Ines sheep using random regression models

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Survival Analysis of Patients with Heart Failure: Implications of Time-Varying Regression Effects in Modeling Mortality

Background: Several models have been designed to predict survival of patients with heart failure. These, while available and widely used for both stratifying and deciding upon different treatment options on the individual level, have several limitations. Specifically, some clinical variables that may influence prognosis may have an influence that change over time. Statistical models that include such characteristic may help in evaluating prognosis. The aim of the present study was to analyze and quantify the impact of modeling heart failure survival allowing for covariates with time-varying effects known to be independent predictors of overall mortality in this clinical setting. Methodology: Survival data from an inception cohort of five hundred patients diagnosed with heart failure functional class III and IV between 2002 and 2004 and followed-up to 2006 were analyzed by using the proportional hazards Cox model and variations of the Cox's model and also of the Aalen's additive model. Principal Findings: One-hundred and eighty eight (188) patients died during follow-up. For patients under study, age, serum sodium, hemoglobin, serum creatinine, and left ventricular ejection fraction were significantly associated with mortality. Evidence of time-varying effect was suggested for the last three. Both high hemoglobin and high LV ejection fraction were associated with a reduced risk of dying with a stronger initial effect. High creatinine, associated with an increased risk of dying, also presented an initial stronger effect. The impact of age and sodium were constant over time. Conclusions: The current study points to the importance of evaluating covariates with time-varying effects in heart failure models. The analysis performed suggests that variations of Cox and Aalen models constitute a valuable tool for identifying these variables. The implementation of covariates with time-varying effects into heart failure prognostication models may reduce bias and increase the specificity of such models.

Semiparametric Latent Variable Regression Models for Spatio-temporal Modeling of Mobile Source Particles in the Greater Boston Area

Traffic particle concentrations show considerable spatial variability within a metropolitan area. We consider latent variable semiparametric regression models for modeling the spatial and temporal variability of black carbon and elemental carbon concentrations in the greater Boston area. Measurements of these pollutants, which are markers of traffic particles, were obtained from several individual exposure studies conducted at specific household locations as well as 15 ambient monitoring sites in the city. The models allow for both flexible, nonlinear effects of covariates and for unexplained spatial and temporal variability in exposure. In addition, the different individual exposure studies recorded different surrogates of traffic particles, with some recording only outdoor concentrations of black or elemental carbon, some recording indoor concentrations of black carbon, and others recording both indoor and outdoor concentrations of black carbon. A joint model for outdoor and indoor exposure that specifies a spatially varying latent variable provides greater spatial coverage in the area of interest. We propose a penalised spline formation of the model that relates to generalised kringing of the latent traffic pollution variable and leads to a natural Bayesian Markov Chain Monte Carlo algorithm for model fitting. We propose methods that allow us to control the degress of freedom of the smoother in a Bayesian framework. Finally, we present results from an analysis that applies the model to data from summer and winter separately

Modeling absolute differences in life expectancy with a censored skew-normal regression approach.

Parameter estimates from commonly used multivariable parametric survival regression models do not directly quantify differences in years of life expectancy. Gaussian linear regression models give results in terms of absolute mean differences, but are not appropriate in modeling life expectancy, because in many situations time to death has a negative skewed distribution. A regression approach using a skew-normal distribution would be an alternative to parametric survival models in the modeling of life expectancy, because parameter estimates can be interpreted in terms of survival time differences while allowing for skewness of the distribution. In this paper we show how to use the skew-normal regression so that censored and left-truncated observations are accounted for. With this we model differences in life expectancy using data from the Swiss National Cohort Study and from official life expectancy estimates and compare the results with those derived from commonly used survival regression models. We conclude that a censored skew-normal survival regression approach for left-truncated observations can be used to model differences in life expectancy across covariates of interest.

Modeling and interpreting interactive hypotheses in regression analysis /

Includes bibliographical references (p. 147-150) and index.

Forecasting Helicoverpa populations in Australia: A comparison of regression based models and a bio-climatic based modeling approach

Long-term forecasts of pest pressure are central to the effective management of many agricultural insect pests. In the eastern cropping regions of Australia, serious infestations of Helicoverpa punctigera (Wallengren) and H. armigera (Hübner)(Lepidoptera: Noctuidae) are experienced annually. Regression analyses of a long series of light-trap catches of adult moths were used to describe the seasonal dynamics of both species. The size of the spring generation in eastern cropping zones could be related to rainfall in putative source areas in inland Australia. Subsequent generations could be related to the abundance of various crops in agricultural areas, rainfall and the magnitude of the spring population peak. As rainfall figured prominently as a predictor variable, and can itself be predicted using the Southern Oscillation Index (SOI), trap catches were also related to this variable. The geographic distribution of each species was modelled in relation to climate and CLIMEX was used to predict temporal variation in abundance at given putative source sites in inland Australia using historical meteorological data. These predictions were then correlated with subsequent pest abundance data in a major cropping region. The regression-based and bioclimatic-based approaches to predicting pest abundance are compared and their utility in predicting and interpreting pest dynamics are discussed.