Comment on "Local accumulation times for source, diffusion, and degradation models in two and three dimensions" [J. Chem. Phys. 138, 104121 (2013)]

In a recent paper, Gordon, Muratov, and Shvartsman studied a partial differential equation (PDE) model describing radially symmetric diffusion and degradation in two and three dimensions. They paid particular attention to the local accumulation time (LAT), also known in the literature as the mean action time, which is a spatially dependent timescale that can be used to provide an estimate of the time required for the transient solution to effectively reach steady state. They presented exact results for three-dimensional applications and gave approximate results for the two-dimensional analogue. Here we make two generalizations of Gordon, Muratov, and Shvartsman’s work: (i) we present an exact expression for the LAT in any dimension and (ii) we present an exact expression for the variance of the distribution. The variance provides useful information regarding the spread about the mean that is not captured by the LAT. We conclude by describing further extensions of the model that were not considered by Gordon,Muratov, and Shvartsman. We have found that exact expressions for the LAT can also be derived for these important extensions..

In vivo clonal expansion and phenotypes of hypocretin-specific CD4(+) T cells in narcolepsy patients and controls

Individuals with narcolepsy suffer from abnormal sleep patterns due to loss of neurons that uniquely supply hypocretin (HCRT). Previous studies found associations of narcolepsy with the human leukocyte antigen (HLA)-DQ6 allele and T-cell receptor alpha (TRA) J24 gene segment and also suggested that in vitro-stimulated T cells can target HCRT. Here, we present evidence of in vivo expansion of DQ6-HCRT tetramer(+)/TRAJ24(+)/CD4(+) T cells in DQ6(+) individuals with and without narcolepsy. We identify related TRAJ24(+) TCRalphabeta clonotypes encoded by identical alpha/beta gene regions from two patients and two controls. TRAJ24-G allele(+) clonotypes only expand in the two patients, whereas a TRAJ24-C allele(+) clonotype expands in a control. A representative tetramer(+)/G-allele(+) TCR shows signaling reactivity to the epitope HCRT87-97. Clonally expanded G-allele(+) T cells exhibit an unconventional effector phenotype. Our analysis of in vivo expansion of HCRT-reactive TRAJ24(+) cells opens an avenue for further investigation of the autoimmune contribution to narcolepsy development

Research priorities in pediatric rheumatology: The Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus

<p>Abstract</p> <p>Background</p> <p>North American pediatric rheumatologists have created an investigator-initiated research network (the Childhood Arthritis and Rheumatology Research Alliance – CARRA) to facilitate multi-centre studies. One of the first projects undertaken by this network was to define, by consensus, research priorities for the group, and if possible a first group-sponsored clinical trial in which all members could participate.</p> <p>Methods</p> <p>We determined consensus using the Delphi approach. This approach has been used extensively in health research to reach consensus in large groups. It uses several successive iterations of surveys eliciting ideas and opinions from specialists in the field. Three surveys were designed based on this method and were distributed to members of CARRA to elicit and rank-order research priorities.</p> <p>Results</p> <p>A response rate of 87.6% was achieved in the final survey. The most highly ranked research suggestion was to study infliximab treatment of uveitis unresponsive to methotrexate. Other highly ranked suggestions were to study i) the treatment of systemic arthritis with anakinra and ii) the treatment of pediatric systemic lupus erythematosus with mycophenolate mofetil.</p> <p>Conclusion</p> <p>The Delphi approach was an effective and practical method to define research priorities in this group. Ongoing discussion and cooperation among pediatric rheumatologists in CARRA and others world-wide will help in developing further research priorities and to facilitate the execution of clinical trials in the future.</p

Enhancing Lay Counselor Capacity to Improve Patient Outcomes with Multimedia Technology

Multimedia technologies offer powerful tools to increase capacity of health workers to deliver standardized, effective, and engaging antiretroviral medication adherence counseling. Masivukeni—is an innovative multimedia-based, computer-driven, lay counselor-delivered intervention designed to help people living with HIV in resource-limited settings achieve optimal adherence. This pilot study examined medication adherence and key psychosocial outcomes among 55 non-adherent South African HIV+ patients, on antiretroviral therapy (ART) for at least 6 months, who were randomized to receive either Masivukeni or standard of care (SOC) counseling for ART non-adherence. At baseline, there were no significant differences between the SOC and Masivukeni groups on any outcome variables. At post-intervention (approximately 5–6 weeks after baseline), -clinic-based pill count adherence data available for 20 participants (10 per intervention arm) showed a 10 % improvement for—participants and a decrease of 8 % for SOC participants. Masivukeni participants reported significantly more positive attitudes towards disclosure and medication social support, less social rejection, and better clinic–patient relationships than did SOC participants. Masivukeni shows promise to promote optimal adherence and provides preliminary evidence that multimedia, computer-based technology can help lay counselors offer better adherence counseling than standard approaches

Individual and Contextual Factors of Sexual Risk Behavior in Youth Perinatally Infected with HIV

Abstract This study prospectively examines the effects of maternal and child HIV infection on youth penetrative and unprotected penetrative sex, as well as the role of internal contextual, external contextual, social and self-regulatory factors in influencing the sexual behaviors of HIV?infected (PHIV+), HIV?affected (uninfected with an HIV+ caregiver), and HIV unaffected (uninfected with an HIV? caregiver) youth over time. Data (N=420) were drawn from two longitudinal studies focused on the effects of pediatric or maternal HIV on youth (51% female; 39% PHIV+) and their caregivers (92% female; 46% HIV+). PHIV+ youth were significantly less likely to engage in penetrative sex than HIV? youth at follow-up, after adjusting for contextual, social, and self-regulatory factors. Other individual- and contextual-level factors such as youth alcohol and marijuana use, residing with a biological parent, caregiver employment, caregiver marijuana use, and youth self-concept were also associated with penetrative sex. Youth who used alcohol were significantly more likely to engage in unprotected penetrative sex. Data suggest that, despite contextual, social, and self-regulatory risk factors, PHIV+ youth are less likely to engage in sexual behavior compared to HIV? youth from similar environments. Further research is required to understand delays in sexual activity in PHIV+ youth and also to understand potential factors that promote resiliency, particularly as they age into older adolescence and young adulthood.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98470/1/apc%2E2012%2E0005.pd

The importance of physical and mental health in explaining health-related academic role impairment among college students

Research consistently documents high rates of mental health problems among college students and strong associations of these problems with academic role impairment. Less is known, though, about prevalence and effects of physical health problems in relation to mental health problems. The current report investigates this by examining associations of summary physical and mental health scores from the widely-used Short-Form 12 (SF-12) Health Survey with self-reported academic role functioning in a self-report survey of 3,855 first-year students from five universities in the northeastern United States (US; mean age 18.5; 53.0% female). The mean SF-12 physical component summary (PCS) score (55.1) was half a standard deviation above the benchmark US adult population mean. The mean SF-12 mental component summary (MCS) score (38.2) was more than a full standard deviation below the US adult population mean. Two-thirds of students (67.1%) reported at least mild and 10.5% severe health-related academic role impairment on a modified version of the Sheehan Disability Scale. Both PCS and MCS scores were significantly and inversely related to these impairment scores, but with nonlinearities and interactions and much stronger associations involving MCS than PCS. Simulation suggests that an intervention that improved the mental health of all students with scores below the MCS median to be at the median would result in a 61.3% reduction in the proportion of students who experienced severe health-related academic role impairment. Although low-cost scalable interventions exist to address student mental health problems, pragmatic trials are needed to evaluate the effectiveness of these interventions in reducing academic role impairment

Masivukeni: Development of a Multimedia Based Antiretroviral Therapy Adherence Intervention for Counselors and Patients in South Africa

Effective medical treatment for HIV/AIDS requires patients’ optimal adherence to antiretroviral therapy (ART). In resource-constrained settings, lack of adequate standardized counseling for patients on ART remains a significant barrier to adherence. Masivukeni (“Let’s Wake Up” in Xhosa) is an innovative multimedia-based intervention designed to help people living with HIV in resource-limited settings achieve and maintain high levels of ART adherence. Adapted from a couples-based intervention tested in the United States (US), Masivukeni was developed through community-based participatory research with US and South African partners and informed by Ewart’s Social Action Theory. Innovative computer-based multimedia strategies were used to translate a labor- and training-intensive intervention into one that could be readily and widely used by lay counselors with relatively little training with low-literacy patients. In this paper, we describe the foundations of this new intervention, the process of its development, and the evidence of its high acceptability and feasibility

Adherence to highly active antiretroviral therapy and its correlates among HIV infected pediatric patients in Ethiopia

BACKGROUND: The introduction of combination antiretroviral therapy (ART) has resulted in striking reductions in HIV-related mortality. Despite increased availability of ART, children remain a neglected population. This may be due to concerns that failure to adhere appears to be related to continued viral replication, treatment failure and the emergence of drug-resistant strains of HIV. This study determines the rates and factors associated with adherence to Antiretroviral (ARV) Drug therapy in HIV-infected children who were receiving Highly Active Antiretroviral Therapy (HAART) in Addis Ababa, Ethiopia in 2008. METHODS: A cross-sectional study was conducted in five hospitals in Addis Ababa from February 18 - April 28, 2008. The study population entailed parents/caretaker and index children who were following ART in the health facilities. A structured questionnaire was used for data collection. RESULTS: A total of 390 children respondents were included in the study with a response rate of 91%. The majority, equaling 205 (52.6%) of the children, were greater than 9 years of age. Fifty five percent of the children were girls. A total of 339 children (86.9%) as reported by caregivers were adherent to antiretroviral drugs for the past 7 days before the interview. Numerous variables were found to be significantly associated with adherence: children whose parents did not pay a fee for treatment [OR = 0.39 (95%CI: 0.16, 0.92)], children who had ever received any nutritional support from the clinic [OR = 0.34 (95%CI: 0.14, 0.79)] were less likely to adhere. Whereas children who took co-trimoxazole medication/syrup besides ARVs [OR = 3.65 (95%CI: 1.24, 10.74)], children who did not know their sero-status [OR = 2.53 (95%CI: 1.24, 5.19)] and children who were not aware of their caregiver's health problem [OR = 2.45 (95%CI: 1.25, 4.81)] were more likely to adhere than their counterparts. CONCLUSION: Adherence to HAART in children in Addis Ababa was higher than other similar set-ups. However, there are still significant numbers of children who are non-adherent to HAART

Improving Antiretroviral Therapy Adherence in Resource-Limited Settings at Scale: a Discussion of Interventions and Recommendations

INTRODUCTION: Successful population-level antiretroviral therapy (ART) adherence will be necessary to realize both the clinical and prevention benefits of antiretroviral scale-up and, ultimately, the end of AIDS. Although many people living with HIV are adhering well, others struggle and most are likely to experience challenges in adherence that may threaten virologic suppression at some point during lifelong therapy. Despite the importance of ART adherence, supportive interventions have generally not been implemented at scale. The objective of this review is to summarize the recommendations of clinical, research, and public health experts for scalable ART adherence interventions in resource-limited settings. METHODS: In July 2015, the Bill and Melinda Gates Foundation convened a meeting to discuss the most promising ART adherence interventions for use at scale in resource-limited settings. This article summarizes that discussion with recent updates. It is not a systematic review, but rather provides practical considerations for programme implementation based on evidence from individual studies, systematic reviews, meta-analyses, and the World Health Organization Consolidated Guidelines for HIV, which include evidence from randomized controlled trials in low- and middle-income countries. Interventions are categorized broadly as education and counselling; information and communication technology-enhanced solutions; healthcare delivery restructuring; and economic incentives and social protection interventions. Each category is discussed, including descriptions of interventions, current evidence for effectiveness, and what appears promising for the near future. Approaches to intervention implementation and impact assessment are then described. RESULTS AND DISCUSSION: The evidence base is promising for currently available, effective, and scalable ART adherence interventions for resource-limited settings. Numerous interventions build on existing health care infrastructure and leverage available resources. Those most widely studied and implemented to date involve peer counselling, adherence clubs, and short message service (SMS). Many additional interventions could have an important impact on ART adherence with further development, including standardized counselling through multi-media technology, electronic dose monitoring, decentralized and differentiated models of care, and livelihood interventions. Optimal targeting and tailoring of interventions will require improved adherence measurement. CONCLUSION: The opportunity exists today to address and resolve many of the challenges to effective ART adherence, so that they do not limit the potential of ART to help bring about the end of AIDS

Factors Associated with HIV/AIDS Diagnostic Disclosure to HIV Infected Children Receiving HAART: A Multi-Center Study in Addis Ababa, Ethiopia

BACKGROUND: Diagnostic disclosure of HIV/AIDS to a child is becoming an increasingly common issue in clinical practice. Nevertheless, some parents and health care professionals are reluctant to inform children about their HIV infection status. The objective of this study was to identify the proportion of children who have knowledge of their serostatus and factors associated with disclosure in HIV-infected children receiving HAART in Addis Ababa, Ethiopia. METHODS: A cross-sectional study was conducted in five hospitals in Addis Ababa from February 18, 2008-April 28, 2008. The study populations were parents/caretakers and children living with HIV/AIDS who were receiving Highly Active Antiretroviral Therapy (HAART) in selected hospitals in Addis Ababa. Univariate and multivariate logistic regression analysis were carried out using SPSS 12.0.1 statistical software. RESULTS: A total of 390 children/caretaker pairs were included in the study. Two hundred forty three children (62.3%) were between 6-9 years of age. HIV/AIDS status was known by 68 (17.4%) children, 93 (29%) caretakers reported knowing the child's serostatus two years prior to our survey, 180 (46.2%) respondents said that the child should be told about his/her HIV/AIDS status when he/she is older than 14 years of age. Children less than 9 years of age and those living with educated caregivers are less likely to know their results than their counterparts. Children referred from hospital's in-patient ward before attending the HIV clinic and private clinic were more likely to know their results than those from community clinic. CONCLUSION: The proportion of disclosure of HIV/AIDS diagnosis to HIV-infected children is low. Strengthening referral linkage and health education tailored to educated caregivers are recommended to increase the rate of disclosure