Assessing effects of behavioral intervention on treatment outcomes among patients initiating HIV care: Rationale and design of iENGAGE intervention trial

During the initial year of HIV diagnosis, while patients are often overwhelmed adjusting to this life changing diagnosis, they must develop self-care behaviors for attending regular medical care visits and antiretroviral therapy (ART) adherence to achieve and sustain viral suppression (VS). Maintaining “HIV adherence” and integrating it into one's daily life is required to sustain VS over time. The HIV care continuum or “treatment cascade,” an epidemiological snapshot of the national epidemic in the United States (US), indicates that a minority of persons living with HIV (PLWH) have achieved VS. Little evidence exists regarding the effects of interventions focusing on PLWH newly initiating outpatient HIV care. An intervention that focuses on both retention in care and ART adherence skills delivered during the pivotal first year of HIV care is lacking. To address this, we developed a theory-based intervention evaluated in the Integrating Engagement and Adherence Goals upon Entry (iENGAGE) study, a National Institute of Allergy and Infectious Diseases (NIAID) funded randomized behavioral intervention trial. Here we present the study objectives, design and rationale, as well as the intervention components, targeting rapid and sustained VS through retention in HIV care and ART adherence during participants' first year of HIV care. The primary outcome of the study is 48-week VS (<200 c/mL). The secondary outcomes are retention in care, including HIV visit adherence and visit constancy, as well as ART adherence

Análise de vida à fadiga sob carregamentos não proporcionais através de modelo de dano contínuo

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Tecnologia, Departamento de Engenharia Mecânica, 2016.Neste trabalho, busca-se utilizar o modelo de dano contínuo de Lemaitre como uma ferramenta de obtenção de vida em fadiga multiaxial para carregamentos proporcionais e não proporcionais. Primeiramente é apresentado o modelo matemático de Lemaitre, em que são formuladas as relações constitutivas necessárias à elaboração do modelo. O modelo de Chaboche foi escolhido para descrever a lei de evolução da tensão de endurecimento cinemático. Em seguida, é desenvolvido o modelo numérico para a solução das equações constitutivas, utilizando a lei de Chaboche com três termos e discretização implícita de Euler. Após, é feita a identificação dos parâmetros constitutivos do modelo para os aços 304 e S460N e para a liga de alumínio 6061-T6. É feita a implementação do modelo em uma rotina em linguagem FORTRAN, a qual é submetida a carregamentos uniaxiais e multiaxiais proporcionais e não proporcionais para cada material. Os dados de vida em fadiga obtidos pelo modelo de Lemaitre são, então, comparados com os dados experimentais disponíveis na literatura. É feita, em seguida, uma análise das amplitudes de tensão obtidas pelo modelo, as quais são comparadas com os dados experimentais. São obtidas, também, curvas de evolução do dano para cada carregamento e material. Os resultados obtidos mostram que o modelo de dano de Lemaitre descreve de maneira adequada o comportamento dos materiais analisados em fadiga de baixo ciclo, quando altas amplitudes de deformação são aplicadas.This project seeks to use Lemaitre’s Continuous Damage Model to obtain fatigue life estimates under multiaxial proportional and non-proportional loadings. Initially, the Lemaitre’s mathematical model is presented, by formulating the necessary constitutive relations. Chaboche’s model was chosen to describe the kinematic hardening law. Then, the numerical model necessary to solve the constitutive relations is developed, utilizing the Chaboche’s law with 3 terms and Euler’s implicit discretization. Then, the material parameters are identified for 304 and S460N steels and 6061-T6 aluminum alloy. The model is implemented in a FORTRAN routine, which is submitted to uniaxial and proportional and non-proportional multiaxial loading histories. The fatigue life data obtained from Lemaitre’s damage model is compared to experimental data. Then, a stress amplitude analysis is conducted and the numerical stresses are compared to experimental data. Damage evolution curves are also obtained for each material and loading. The results show that Lemaitre’s damage model describes adequately the behavior of the analyzed materials under low cycle fatigue, when low strain amplitudes are being applied to the specimen

Evidence for risk stratification when monitoring for toxicities following initiation of combination antiretroviral therapy

Laboratory monitoring is recommended during combination antiretroviral therapy (cART), but the pattern of detected abnormalities and optimal monitoring are unknown. We assessed laboratory abnormalities during initial cART in 2000–2010 across the United States

Physical activity trends and metabolic health outcomes in people living with HIV in the US, 2008–2015

Despite its potential to improve metabolic health outcomes, longitudinal physical activity (PA) patterns and their association with cardiometabolic disease among people living with HIV (PLWH) have not been well characterized. We investigated this relationship among PLWH in the Centers for AIDS Research Network of Integrated Clinical Systems with at least one PA self-report between 2008 and 2015. The 4-item Lipid Research Clinics PA instrument was used to categorize habitual PA levels as: Very Low, Low, Moderate, or High. We analyzed demographic differences in PA patterns. Multivariable generalized estimating equation regression models were fit to assess longitudinal associations of PA with blood pressure, lipid, and glucose levels. Logistic regression modeling was used to assess the odds of being diagnosed with obesity, cardiovascular disease (CVD), cerebrovascular disease, hypertension, diabetes, or multimorbidity. A total of 40,462 unique PA assessments were provided by 11,719 participants. Only 13% of PLWH reported High PA, while 68% reported Very Low/Low PA at baseline and did not increase PA levels during the study period. Compared to those reporting High PA, participants with Very Low PA had almost 2-fold increased risk for CVD. Very Low PA was also associated with several risk factors associated with CVD, most notably elevated triglycerides (odds ratio 25.4), obesity (odds ratio 1.9), hypertension (odds ratio 1.4), and diabetes (odds ratio 2.3; all p < 0.01). Low levels of PA over time among PLWH are associated with increased cardiometabolic disease risk

Hematologic, Hepatic, Renal, and Lipid Laboratory Monitoring After Initiation of Combination Antiretroviral Therapy in the United States, 2000–2010

We assessed laboratory monitoring following combination antiretroviral therapy (cART) initiation among 3,678 patients in a large US multi-site clinical cohort, censoring participants at last clinic visit, cART change, or three years. Median days (interquartile range) to first hematologic, hepatic, renal and lipid tests were 30 (18–53), 31 (19–56), 33 (20–59) and 350 (96–1106), respectively. At one year, approximately 80% received more than two hematologic, hepatic, and renal tests consistent with guidelines. However, only 40% received one or more lipid tests. Monitoring was more frequent in specific subgroups, likely reflecting better clinic attendance or clinician perception of higher susceptibility to toxicities

Impact of Age on Retention in Care and Viral Suppression

Retention in care is important for all HIV-infected persons and is strongly associated with initiation of antiretroviral therapy and viral suppression. However, it is unclear how retention in care and age interact to effect viral suppression. We evaluated whether the association between retention and viral suppression differed by age at entry into care

Transforming growth factor beta signaling: The master sculptor of fingers

Transforming growth factor beta (TGF?) constitutes a large and evolutionarily conserved superfamily of secreted factors that play essential roles in embryonic development, cancer, tissue regeneration, and human degenerative pathology. Studies of this signaling cascade in the regulation of cellular and tissue changes in the three-dimensional context of a developing embryo have notably advanced in the understanding of the action mechanism of these growth factors. In this review, we address the role of TGF? signaling in the developing limb, focusing on its essential function in the morphogenesis of the autopod. As we discuss in this work, modern mouse genetic experiments together with more classical embryological approaches in chick embryos, provided very valuable information concerning the role of TGF? and Activin family members in the morphogenesis of the digits of tetrapods, including the formation of phalanxes, digital tendons, and interphalangeal joints. We emphasize the importance of the Activin and TGF? proteins as digit inducing factors and their critical interaction with the BMP signaling to sculpt the hand and foot morphology

Alternative polyadenylation analysis in animals and plants: newly developed strategies for profiling, processing and validation

Alternative polyadenylation is an essential RNA processing event that contributes significantly to regulation of transcriptome diversity and functional dynamics in both animals and plants. Here we review newly developed next generation sequencing methods for genome-wide profiling of alternative polyadenylation (APA) sites, bioinformatics pipelines for data processing and both wet and dry laboratory approaches for APA validation. The library construction methods LITE-Seq (Low-Input 3'-Terminal sequencing) and PAC-seq (PolyA Click sequencing) tag polyA cDNA, while BAT-seq (BArcoded, three-prime specific sequencing) and PAPERCLIP ( oly( ) binding rotein-mediated mRNA 3' nd etrieval by ross inking mmuno recipitation) enrich polyA RNA. Interestingly, only WTTS-seq (Whole Transcriptome Termini Site sequencing) targets both polyA RNA and polyA cDNA. Varieties of bioinformatics pipelines are well established to pursue read quality control, mapping, clustering, characterization and pathway analysis. The RHAPA (RNase H alternative polyadenylation assay) and 3'RACE-seq (3' rapid amplification of cDNA end sequencing) methods directly validate APA sites, while WTSS-seq (whole transcriptome start site sequencing), RNA-seq (RNA sequencing) and public APA databases can serve as indirect validation methods. We hope that these tools, pipelines and resources trigger huge waves of interest in the research community to investigate APA events underlying physiological, pathological and psychological changes and thus understand the information transfer events from genome to phenome relevant to economically important traits in both animals and plants