In utero and peripartum antiretroviral exposure as predictor of cognition in 6- to 10-year-old HIV-exposed Ugandan children - a prospective cohort study.

OBJECTIVES: To quantify association between in utero/peripartum antiretroviral (IPA) exposure and cognition, i.e. executive function (EF) and socioemotional adjustment (SEA), in school-aged Ugandan children who were perinatally HIV-infected (CPHIV, n = 100) and children who were HIV-exposed but uninfected (CHEU, n = 101). METHODS: Children were enrolled at age 6-10 years and followed for 12 months from March 2017 to December 2018. Caregiver-reported child EF and SEA competencies were assessed using validated questionnaires at baseline, 6 and 12 months. IPA type - combination antiretroviral therapy (cART), intrapartum single-dose nevirapine ± zidovudine (sdNVP ± ZDV), nevirapine + zidovudine + lamivudine (sdNVP + ZDV + 3TC) - or no IPA (reference) was verified via medical records. IPA-related standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) in cognitive competencies were estimated from regression models with adjustment for caregiver sociodemographic and contextual factors. Models were fitted separately for CPHIV and CHEU. RESULTS: Among CPHIV children, cART (SMD = -0.82, 95% CI: -1.37 to -0.28) and sdNVP ± ZDV (SMD = -0.41, 95% CI: -0.81 to -0.00) vs. no IPA predicted lower executive dysfunction over 12 months. Intrapartum sdNVP + ZDV + 3TC vs. no IPA predicted executive dysfunction (SMD = 0.80, 95% CI: 0.30-1.31), SEA problems (SMD = 0.63-0.76, 95% CI: 0.00-1.24) and lower adaptive skills (SMD = -0.36, 95% CI: -0.75-0.02) over 12 months among CHEU. Further adjustment for contextual factors attenuated associations, although most remained of moderate clinical importance (|SMD| > 0.33). CONCLUSIONS: Among CPHIV children, cART and sdNVP ± ZDV IPA exposure predicted, on average, lower executive dysfunction 6-10 years later. However, peripartum sdNVP + ZDV + 3TC predicted executive and SEA dysfunction among CHEU 6-10 years later. These data underscore the need for more research into long-term effects of in utero ART to inform development of appropriate interventions so as to mitigate cognitive sequelae.

Heavy-tailed fractional Pearson diffusions.

We define heavy-tailed fractional reciprocal gamma and Fisher-Snedecor diffusions by a non-Markovian time change in the corresponding Pearson diffusions. Pearson diffusions are governed by the backward Kolmogorov equations with space-varying polynomial coefficients and are widely used in applications. The corresponding fractional reciprocal gamma and Fisher-Snedecor diffusions are governed by the fractional backward Kolmogorov equations and have heavy-tailed marginal distributions in the steady state. We derive the explicit expressions for the transition densities of the fractional reciprocal gamma and Fisher-Snedecor diffusions and strong solutions of the associated Cauchy problems for the fractional backward Kolmogorov equation.

Designing and evaluating Brain Powered Games for cognitive training and rehabilitation in at-risk African children.

BACKGROUND: Valid, reliable, accessible, and cost-effective computer-training approaches can be important components in scaling up educational support across resource-poor settings, such as sub-Saharan Africa. The goal of the current study was to develop a computer-based training platform, the Michigan State University Games for Entertainment and Learning laboratory's Brain Powered Games (BPG) package that would be suitable for use with at-risk children within a rural Ugandan context and then complete an initial field trial of that package. METHODS: After game development was completed with the use of local stimuli and sounds to match the context of the games as closely as possible to the rural Ugandan setting, an initial field study was completed with 33 children (mean age = 8.55 ± 2.29 years, range 6-12 years of age) with HIV in rural Uganda. The Test of Variables of Attention (TOVA), CogState computer battery, and the Non-Verbal Index from the Kaufman Assessment Battery for Children, 2nd edition (KABC-II) were chosen as the outcome measures for pre- and post-intervention testing. The children received approximately 45 min of BPG training several days per week for 2 months (24 sessions). RESULTS: Although some improvements in test scores were evident prior to BPG training, following training, children demonstrated clinically significant changes (significant repeated-measures outcomes with moderate to large effect sizes) on specific TOVA and CogState measures reflecting processing speed, attention, visual-motor coordination, maze learning, and problem solving. CONCLUSIONS: Results provide preliminary support for the acceptability, feasibility, and neurocognitive benefit of BPG and its utility as a model platform for computerized cognitive training in cross-cultural low-resource settings.

Quality of life among advanced breast cancer patients with and without distant metastasis.

This study presents the results of a secondary analysis of data collected during a trial of reflexology that aimed to improve health-related quality of life (HRQOL) among women with advanced breast cancer in treatment. A comparison of HRQOL (functioning, symptoms, spirituality) of those with (n = 298) and without (n = 87) distant metastasis is presented. Following the intake interview, 385 women were randomised to reflexology, lay foot manipulation or conventional care control, and were interviewed again at weeks 5 and 11. Those with distant metastasis were older, had fewer comorbid conditions, and a smaller proportion were employed. Longitudinal analysis of HRQOL at intake, 5 and 11 weeks revealed that those with distant metastasis had lower functioning and more pain; however, no differences were found on fatigue, nausea, shortness of breath, sleep quality, anxiety, depressive symptoms or spirituality. Despite advanced disease, 56% of all women in this study were below the clinical screening cut-off for depressive symptoms. These findings may indicate that patients with advanced breast cancer have adapted emotionally and spiritually; however, the management of physical symptoms remains a priority.

Understanding the role of stimulation in reflexology: development and testing of a robotic device.

Reflexology is a common choice of women with breast cancer as supportive care during treatment. It involves stimulation of specific locations of the feet called reflexes using a specialised walking motion with the thumb of the reflexologist. Reflexology has shown potential for the successful management of cancer and treatment-related symptoms and improvement in physical functioning; however to date, the mechanism of action for these improvements is unknown. One confounder to the study of reflexology is the 'human factor'. To study the effects of the stimulation of the reflexes independent of the 'human factor', there is a need for an alternative method for the delivery of reflexology. The objective of this work was to design and create a robotic reflexology device that would deliver a breast cancer-specific reflexology protocol to the feet of patients. A prototype robotic reflexology device was developed and tested for feasibility, safety and acceptability with breast cancer survivors (n= 13), and preliminary efficacy in symptom management and enhanced functional status with a sample of women undergoing chemotherapy for breast cancer (n= 13). Safety, feasibility and acceptability were established, and significant improvements from pre- to post-device-delivered reflexology were seen in symptom severity among women on chemotherapy.

Quality of life among patients with primary, metastatic and recurrent cancer.

Diagnosis of cancer is an emotionally traumatic event that significantly impacts the quality of life (QoL) of the patients. Progression to metastasis or recurrence of cancer after first diagnosis poses a greater threat to life that further increases this emotional trauma and can worsen the QoL. In this research we sought to explore the differences in QoL (symptom severity and physical functioning) experienced by primary non-metastatic (PNM), primary metastatic (PM) and recurrent (RC) cancer patients. Cancer patients recruited in two cognitive intervention trials formed the sample for this analysis. Data were analysed using longitudinal mixed models, with two interaction terms. Least square means were calculated and compared. Over the period of study RC patients reported the worst symptom severity and physical function followed by PM and PNM patients. Primary non-metastatic patients showed a steady decline in severity whereas PM and RC showed slight gains after the first follow-up. Primary non-metastatic patients displayed best physical functioning followed by PM and RC patients, and remained stable over time. Breast cancer patients displayed most variation in symptom severity among the three progression groups, whereas significant variation in physical function among the three groups was observed within all cancer sites.

Depressive symptoms in mid-pregnancy, lifetime stressors and the 5-HTTLPR genotype.

Few studies of gene-environment interactions for the serotonin transporter promoter polymorphism (5-HTTLPR), life stressors and depression have considered women separately or examined specific types of stressful life events. None have looked at depression during pregnancy. In the Pregnancy Outcomes and Community Health (POUCH) Study, women were queried about history of stressful life events and depressive symptoms at the time of enrollment (15-27 weeks gestation). Stressful life events were grouped a priori into "subconstructs" (e.g. economic, legal, abuse, loss) and evaluated by subconstruct, total subconstruct score and total stressful life event score. The effect of genotype on the association between stressful life events and elevated depressive symptoms was assessed in 568 white non-Hispanic participants. The relationship between exposure to abuse and elevated depressive symptoms was more pronounced in the s/s group (OR = 24.5) than in the s/l group (OR = 3.0) and the l/l group (OR = 7.7), but this significant interaction was detected only after excluding 73 (13%) women with recent use of psychotropic medications. There was no evidence of gene-environment interaction in analytic models with other stressful life events subconstructs, total subconstruct score or total stressful life events score. These data offer modest support to other reports of gene-environment interaction and highlight the importance of considering specific stressful life events.