2010 Scholarship Winners

Kaitlin Lovett, MPH, PhD candidate
The Effects of Antiretroviral Therapy on Resting Memory B Cells in Human Immunodeficiency Virus-Infected Zambian Children.

Zambia has the seventh highest prevalence of human immunodeficiency virus (HIV) infection in Africa and an estimated 95,000 infected children [1]. HIV-infected Zambian children are currently vaccinated with attenuated measles virus around 9 months of age but exhibit rapidly waning protective antibody levels compared to the lifelong immunity observed in healthy individuals [2]. Long-lasting immunity to pathogens such as measles relies on pathogen-specific antibodies and the maintenance of B cell populations that produce them. HIV has been demonstrated to deplete memory B cells and, in adults, the initiation of antiretroviral therapy (ART) suspends this depletion due to a decreased HIV viral load [3, 4]. Protective antibody levels do not return upon successful ART responses, however, and long-term protective immunity is hypothesized to require re-exposure to pathogens to generate new memory B cell populations previously exhausted by HIV. Thus, children without sufficient antibody levels may remain susceptible to infections such as measles. Due to the rapid scale-up and increased access to ART in Zambia, childhood mortality from HIV is expected to decrease but may potentially result in a large pool of children who are susceptible to measles [5].

The proposed research (referred to as the Humoral Immunity Study) will measure and compare levels of memory B cells, antibody-secreting plasma cells and measles virus antibodies in 60 HIV-infected Zambian children before and after ART initiation relative to 60 uninfected Zambian children, all of whom were previously vaccinated against measles virus. The Humoral Immunity Study will be nested within an ongoing prospective, observational cohort study (the Measles Immune Reconstitution Study) assessing the impact of ART initiation on measles virus-specific T cell immunity in Zambian children. The long-term goal of these studies is to determine the effect of HIV and ART on measles population immunity and enhance knowledge about the necessity and timing of measles re-vaccination among HIV-infected children receiving ART.

Aim 1: Measure and compare the proportions of resting memory B cells and antibody-secreting plasma cells among the total B cell population in HIV-infected Zambian children before and after ART initiation relative to age-matched uninfected children.

Hypothesis 1a: HIV infection will be associated with 1) a lower proportion of resting memory B cells and 2) a higher proportion of antibody-secreting plasma cells.

Hypothesis 1b: A decrease in HIV viral load, as induced by ART initiation, will be associated with 1) an increase in the proportion of resting memory B cells and 2) a decrease in the proportion of plasma cells.

Aim 2: Measure changes in the ability of plasmablasts to secrete measles virus-specific antibodies as an assessment of B cell functionality using an enzyme-linked immunospot (ELISpot)-based assay in HIV-infected Zambian children before and after ART initiation relative to age-matched uninfected children.

Hypothesis 2: HIV infection will be associated with a lower concentration of secreted measles virus-specific antibody.

Aim 3: Associate the ability of plasmablasts to secrete measles virus-specific antibodies as measured by an ELISpot-based assay with measles serum antibody levels measured by enzyme-linked immunosorbent assay (EIA) in HIV-infected Zambian children before and after ART initiation.

Hypothesis 3: The concentration of secreted measles virus-specific antibody will be higher in HIV-infected children before ART initiation compared to after ART initiation.

Study Design: Enrollment into the Measles Immune Reconstitution Study occurs during a clinic visit two weeks after an initial evaluation for ART eligibility at the referral clinic. Children who are eligible to receive ART are enrolled at this clinic visit during which a baseline questionnaire is administered and a peripheral blood sample is collected. This visit corresponds with the provision of ART medications and represents the baseline study visit before ART initiation. Children are scheduled to return to the clinic every 3 months for routine clinical follow-up and provision of ART medications, during the first of which the Humoral Immunity Study will use information from the follow-up questionnaire and a portion of the blood sample collected.

Laboratory Assays: Flow cytometry and enzyme-linked immunological assays will be used to quantify B cells and antibody levels. The proportions of resting memory B cells and plasma cells among the total B cell population will be determined using a FACSCalibur™ Flow Cytometer (Becton Dickinson, Franklin Lakes, NJ). Using directly-conjugated monoclonal antibodies, resting memory B lymphocytes will be characterized as CD19⁺CD20⁺CD21^HICD27⁺ and plasma cells will be defined as CD19⁺CD20^-CD21^LOCD27⁺⁺ [6,7]. Memory B cell functionality will be assessed using an ELISpot-based assay as previously described by Crotty et al. [8]. The Enzygnost^® Anti-Measles Virus IgG Combipack enzyme immunoassay (Dade Behring, Liderbach, Germany) will measure measles virus IgG antibody levels in plasma samples collected at the baseline and 3-month follow-up visits according to the manufacturer’s instructions.

Analysis Plan: Random effects models will permit subject-specific and population-level assessments of the change in three outcomes between the baseline and 3-month follow-up visit: 1) the proportion of resting memory B cells, 2) the proportion of plasma cells among the total lymphocyte population, and 3) measles virus antibody levels. Infection with HIV and initiation of ART represent the main effects of interest on the three outcomes after adjustment for determinants of immune reconstitution. Potential determinants of immune reconstitution such as prior illnesses, time since immunizations, perinatal exposure to ART, and ART adherence will be obtained from questionnaires administered to parents or guardians accompanying children to the clinic. Other important determinants such as CD4+ T cell percentage, gender, weight, height, HIV viral load, and ART regimen and dosage will be abstracted from study records.

First, the prospective design of this research will allow us to assess changes in humoral immunity due to ART initiation within a cohort of HIV-infected and uninfected Zambian children. While a few studies have previously assessed changes in humoral immunity due to ART initiation, this work has mainly focused on adults in the United States, Italy, and Sweden, and two studies of the effect of ART in children have been among cohorts in the developed countries of Italy and Germany with poorly characterized control populations. This study will focus on children in sub-Saharan Africa, where the largest burden of HIV resides. Furthermore, this data will contain baseline information regarding B lymphocyte populations in HIV-infected as well as uninfected children, which will be of use to others conducting research on vaccine-preventable diseases and HIV.

Second, this study facilitates an interdisciplinary approach to public health research through the use of advanced laboratory methods combined with epidemiologic principles and analyses. Also, by nesting the Humoral Immunity Study within the Measles Immune Reconstitution Study, relationships between different components of the immune system such as T and B lymphocytes and cytokine levels can be examined.

Finally, the results of the proposed research will have direct implications for the necessity and timing of repeat vaccination, clinical care, and research surrounding HIV in young children. This study specifically addresses infectious disease care and prevention among young children, interventions to prevent re-emerging infectious disease epidemics, and potential measures for containment of global health threats.

Prices are based on the manufacturers’ listed prices adjusted for academic discounts.

This project will be supplemented with funds awarded by the National Institutes of Health to the Measles Immune Reconstitution Study.

Amritha Ramakrishnan, PhD candidate
Heterotypic Immune responses to Seasonal Influenza Vaccination

Influenza is a common respiratory virus that results in over five million annual cases of severe infection world wide. Despite vaccination efforts, the socioeconomic impact of influenza infections is staggering. In the US alone, 200,000 people are hospitalized for influenza-related complications every year and the total economic burden of influenza infections in a single year can be as high as 87 billion US dollars.

Seasonal vaccination remains the most effective method to prevent disease and reduce the impact of influenza infections. Two licensed vaccines are available in the United States: the inactivated vaccine (TIV) and the live, attenuated vaccine (LAIV). While they are effective in preventing influenza infections caused by antigenically similar strains of virus, their efficacy begins to drop off as the antigenicity of the circulating and vaccine strains diverge. With the emergence of the 2009 pandemic H1N1 strain, there has been renewed interest in the field of cross protective immunity and in the development of a broadly cross-reactive “universal” influenza vaccine. One of the primary challenges in the development of such a vaccine is our incomplete understanding of the immune response to influenza infection and vaccinations in humans. The current vaccines are primarily evaluated based on their ability to induce strain specific antibodies with little regard to the development of T cell immunity. T cells, unlike antibodies, target internal proteins that are conserved across influenza strains. In animal models of infection, T cell mediated responses have been shown to play an important role in viral clearance as well as decreased disease severity. This property gives vaccines that induce robust T cell responses the potential to provide protection against a number of antigenically different strains (heterotypic protection). T cell immunity has however, received little attention from the standpoint of vaccine development. This coupled with the fact that these responses are technically more challenging to quantify has resulted in the lack of robust assay systems to measure T cell responses and the corresponding lack of a reliable correlate of protection.

1. Develop a novel high throughput assay system to quantify as well as characterize antigen specific T cells responses to influenza antigens.

2. Use this platform to measure heterotypic T cell responses induced by seasonal influenza vaccination in an adult human cohort.

100 healthy adults aged 18-49 were enrolled during the 2006-2007 and 2007-2008 influenza seasons. All eligible adults provided written informed consent and a pre-vaccination blood sample was collected. Individuals then either received the inactivated (TIV) or the live attenuated (LAIV) seasonal influenza vaccine. Post vaccination blood samples were collected at day 14 and day 28 after vaccination. Serum and PBMCs were isolated from the blood samples and cryopreserved for further analysis.

In order to study antigen specific T cell responses we have developed a multicolor flow cytometry-based assay in collaboration with Becton Dickinson. The assay consists of two parts: First, PBMCs will be stimulated using a “stimulation plate” composed of influenza antigens lyophilized in a 96 well plate format. A whole virus and a peptide based approach will be used for the stimulation of cells. Following stimulation, cells will be transferred to a “staining plate” which is composed of lyophilized antibodies. We have designed a panel of 8 antibodies to quantify and phenotypically characterize influenza specific T cells. Once stained, cells will be acquired on a flow cytometer.

Preliminary experiments testing the feasibility of this approach have been conducted with promising results. We have been able to detect antigen specific T cells after whole virus as well as peptide stimulations of PBMCs. We are now in final stages of virus preparation and inactivation before the viruses and peptides are shipped to Becton Dickinson for lyophilization in a 96-well format.

In the face of the emergence of a pandemic influenza virus and seasonal influenza epidemics, heterotypic immune responses and T cell immunity has become particularly important and relevant. Yet, this aspect of influenza immunobiology is largely under appreciated. Most of the current research on immune response to influenza vaccination is limited to B cell responses and neutralizing antibody titers. However, this basic measure of vaccine efficacy does not account for cell mediated immune responses such as antigen-specific T cell activation and immunologic memory. An important unresolved question remains: is either vaccine formulation better at eliciting cross-protective immune responses to multiple strains of influenza in the event of vaccine mismatch or the emergence of a pandemic influenza strain? Our study aims at answering this important question. Evaluating the current vaccines in terms of their ability to induce such cross reactive responses and characterizing the T cell mediated response can also help identify novel immunologic markers of protection. We also hope to establish a novel assay system to measure such responses which could potentially serve as a, much needed, high throughput method to screen for T cell responses in this and other disease models.

Ideally, we would like to include the live/dead antibody kit (Cat. No.L-34959) to our selected panel of antibodies. This kit is used to distinguish live and dead cells during data acquisition and is available from Invitrogen and hence will not be provided by Becton Dickinson. This kit can help remove background noise that can result from non-specific staining of dead cells. This becomes particularly important when characterizing rare populations of cells such as antigen specific T cells in PBMCs (which can constitute as little as 0.1% of total CD4+T cells in human PBMCs). In the past we have used light scatter as a means of discriminating live and dead cells, however, this kit provides a far more accurate alternative. We have refrained from purchasing this product because of monetary constraints. If awarded the $1000, we will use the money to buy this reagent which we believe could greatly enhance the quality of our data. In designing such high throughout assays, standardization and reliability are very important and we think this kit could help in this regard. The live/dead kit (cost $237) has to be used in conjunction with the corresponding compensation bead kit (Cat. No. A-10346, cost $234). In order to be able to test 100 people, we would need two vials of each. The total cost would, therefore, be in the amount of $942.

Antibodies (with the exception of the live/dead kit) and lyophilization of reagents into a 96 well format will be provided by Becton Dickinson free of cost.

Practice:

Hadley Herbert, MD, Post-doctoral fellow
Exploring the Design, Implementation, and Utilization of Pediatric Trauma Registries: A Case Study of the Red Cross War Memorial Children’s Hospital, South Africa

Injury is a leading cause of childhood death and disability globally. The burden of injury is especially pronounced in low and middle income countries, where 95% of all childhood injury deaths occur. To reduce this burden, public health professionals have sought to identify strategies to improve injury prevention and trauma care. In 2006, the World Health Organization concluded that the lack of data on injury incidence and etiology, particularly in low and middle income countries, served as a significant obstacle in establishing effective prevention strategies.One proposed strategy to address this information disparity is through the implementation of hospital-based trauma registries. Data from trauma registries can be used for injury surveillance, quality assurance, advocacy, education, and research. To explore the role of trauma registries, the Johns Hopkins Bloomberg School of Public Health’s International Injury Research Unit (IIRU), directed by Dr. Adnan Hyder, MD, PhD, MPH, is conducting a study in collaboration with the Red Cross War Memorial Children’s Hospital in Cape Town, South Africa to quantitatively analyze Red Cross’s hospital-based trauma registry. Red Cross’s trauma registry is one of a few hospital-based registries in Africa, and the only African trauma registry specific to pediatric injury. Through its development of a child safety center, a specialized pediatric trauma unit, and a trauma registry, Red Cross has been fundamental in pioneering safety concerns for children in Africa. As such, the trauma registry has a strong potential to become a model for other African countries.

As a surgical resident, pursuing a career in trauma surgery, and a post-doctoral fellow in the Department of International Health, working with Dr. Hyder and the IIRU, I am interested in understanding how systems, such as Red Cross’s trauma registry, are developed to improve global injury prevention. As part of the IIRU’s and Dr. Hyder’s work to understand the burden of injury and develop an affordable means of injury prevention, this study will promote the core values of a health systems approach to injury prevention through strategic research and capacity development.The aim of this study is to learn from the experience of a hospital-based pediatric trauma registry in a developing country as a means to collect accurate data to better understand childhood injury. Through this study, we will estimate the burden of child injury and evaluate trends in the hospital’s incidence of child injury over a ten year period from 1996 to 2005. This will be achieved through a quantitative retrospective epidemiologic study of data available in the Red Cross trauma registry. As a post-doctoral fellow at the Bloomberg School of Public Health, I am applying for funding from the Delta Omega Scholarship to implement this quantitative aspect of the study and conduct the data analysis.

The quantitative data collection and analysis will occur at Red Cross Hospital in Cape Town, South Africa. The Unit’s trauma registry includes primary data on approximately 98,000 injuries between 1996 and 2005. Data will be analyzed with regard to pre-hospital events, outcomes, and severity of injury in the trauma unit. This aspect of the study will outline trends and incidence of childhood injury, in terms of gender, age, outcome, and type of injury that presented to Red Cross between 1996 and 2005. This will be analyzed according to the geographic location where the injury occurred in Cape Town, to further understand the prevalence of injury in certain districts in Cape Town. The data, which is currently in Microsoft Access, will be transferred to SPSS and analyzed in partnership with Red Cross and Johns Hopkins so as to encourage capacity development. To achieve this, we will work jointly with the study’s local PI, Professor Sebastian van As, MD, PhD, the director of the Red Cross Trauma Unit, and Red Cross’s affiliated non-governmental organization, ChildSafe, which is responsible for entering and coding the data. While Red Cross has used data from the trauma registry to publish articles related to specific elements of trauma, such as child abuse, gunshot injuries, and traffic related injuries, it has yet to conduct such an extensive study, examining trends of all injuries over a ten year period. This study has the potential to illustrate quantitatively how Red Cross’s database is a major resource for national and international organizations to understand childhood injuries in South Africa, and how these injuries have changed over a decade. IRB approval has been obtained from the University of Cape Town and an exemption has been obtained from the Johns Hopkins School of Public Health Institutional Review Board Office.

This case study of a South African hospital-based trauma registry is intended to show how trauma registries can be used to collect data to better inform cost-effective and sustainable pediatric trauma care improvements. The results will be disseminated through stakeholder workshops at Red Cross, incorporating ways to enhance the hospital’s pre-existing trauma registry. By working with Red Cross as a hub for pediatric trauma, the long-term aim of this project is to encourage other hospitals to adopt their own trauma registries. Facilitating high-quality data collection throughout South Africa could lead to a better understanding of childhood injury, and thus serve as a call for action at the national level to implement evidence-based protocols. All countries face limitations in their capacity to intervene to prevent injury, provide emergency care, and appropriate rehabilitation services. By highlighting the ways in which a trauma registry can allow for data collection, analysis, and application, it is our hope that this study will help to develop capacity at the hospital level, as well as to facilitate improved health information systems at the district and national levels.

Measurement:

Ava Bittner, PhD Candidate, Graduate Training Program in Clinical Investigation
Yoga Therapy for the Reduction of Intraocular Pressure, Negative Psychosocial Status, And Poor Balance in Visually Impaired Individuals

Introduction

Glaucoma is a leading cause of blindness, affecting 68 million people worldwide. The only treatable risk factor is intraocular pressure (IOP), and while pharmacological treatments and surgical options are available, 45% of patients continue to lose vision despite IOP lowering. Previous research has well-established that both dynamic (involving change in muscle length) and isometric (constant muscle length) exercise can play a role in the short-term, clinically significant, and potentially long-term reduction of IOP. Yoga Therapy (YT) involves both dynamic and isometric exercise, but has not been evaluated as an intervention for glaucoma and IOP reduction.

Retinitis pigmentosa (RP) is a slowly progressive, inexorable retinal degenerative disease, with a prevalence of 1 in 4000. It is hypothesized that sleep disturbances in RP may be related to the extent of photoreceptor loss and narrowing field of view, leading to reductions in retinally mediated light and disruptions in the circadian cycle. Loss of vision is likewise accompanied by poor balance, postural instability, and mobility, significantly reducing independence and quality of life in severely visually impaired patients.

Mind-body practices have been shown to be a viable intervention to improve sleep disturbances, mood disturbances, and balance, in healthy individuals and those with other chronic diseases. Current literature does not directly address the efficacy and efficiency of a YT for the reduction of IOP and secondary symptoms in the visually impaired population. In this proposal, we will implement a regimen specifically tailored to the visually impaired population to attempt to alleviate increased intraocular pressure, sleep disturbances, negative psychosocial factors, and balance.

Methods

Aim 1. To pilot test the feasibility of Yoga Therapy (YT) for the reduction of intraocular pressure in glaucoma patients. Participants will receive YT instruction on a twice weekly basis for 8 weeks. Subjects will be recruited from among patients who present to the JHU Wilmer Low Vision Rehabilitation and Glaucoma Services. Previous research indicates that breath holding, headstand and head down positions will increase IOP, and therefore these positions will be avoided in the YT series for glaucoma. IOP will be measured using standard procedures, with Goldmann applanation tonometry, at three occasions both pre- and post- intervention, as well as once before and after each YT session. Subjects will continue previously prescribed IOP lowering medications.

Aim 2. To pilot test the feasibility of Yoga Therapy (YT) for reducing sleep disturbances and negative psychosocial states in RP patients. Participants will receive weekly YT instruction for 8 weeks. Entry criteria for RP subjects will be defined by increased sleep disturbances, defined according to Buysse: “a PSQI global score >5 indicates that subject is having severe difficulties in at least two areas, or moderate difficulties in more than three areas.” Our preliminary data in 29 legally blind RP subjects indicates that 17 (59%) had a PSQI global score >5. The majority of the RP subjects will be individuals who have participated in previous research at our center. The YT sequence for RP will be Ashtanga-based and will involve some head down positions, as IOP is not a concern in the pathogenesis of RP.

Shared methodology for Aims 1 & 2:

We will enroll 20 subjects who are legally blind due to reduced visual field <20°, 10 glaucoma and 10 RP, as this number is the largest feasible considering the duration and funding for this pilot study, and takes into account that 1 or 2 may be non-compliant or drop-out. Subjects in each ocular disease category will be randomized into equal groups to either start the intervention immediately or to a waitlist control group receiving standard of care during the initial 8-week intervention period. Waitlist control subjects will also receive the YT intervention following the completion of the first group. All procedures will take place at the Johns Hopkins Wilmer Eye Institute’s Lions Vision Center, as we have a dedicated lab for mobility that may be used for the YT sessions.

Two of each of the following vision and psychosocial outcome measures will be collected at both baseline and post-intervention. Vision measures will include ETDRS visual acuity, Goldmann visual fields, and Pelli-Robson contrast sensitivity using standardized, validated measures. The dark-adapted full filed flash test will accommodate subjects with very poor vision (i.e. those with light perception only). Sleep disturbances and daytime sleepiness will be quantified using validated questionnaires (Pittsburgh Sleep Quality Index, and Stanford Sleepiness Scale) and sleep diaries will assess subjective impressions of sleep. Actigraphy using an accelerometer will be used to objectively determine sleep efficiency, sleep latency, wake after sleep onset time, and total sleep time during one-week intervals. Actiwatches are also increasingly being used in sleep research to provide objective estimates of circadian rhythm and sleep continuity. Actigraphy also provides daytime activity levels, which may be relevant to exercise-mediated IOP reduction in glaucoma. Psychosocial factors will be assessed using validated questionnaires: Beck Depression Inventory, Perceived Stress Scale, and Positive and Negative Affect Scales. For outcome measures administered pre- and post-intervention, we plan to use two-sample t-tests or Wilcoxon Rank-Sum tests in the event of non-normal data to look for differences between groups (YT vs. waitlist control). We plan to use General Estimating Equations to handle repeated measures of IOP.

The YT approach includes breathing techniques, yoga postures, and relaxation methods specifically tailored to this population. YT will administered by a JHU post-doctoral fellow with experience as a yoga instructor for the visually impaired. Several studies have successfully used an 8-week period that produced positive outcomes. An orientation session will be conducted prior to the intervention to familiarize subjects with yoga basics that include: alignment, breathing, set up, supplies, journaling, and temperature. Participants will be led through the sequence of postures and the instructor will make adjustments and answer questions. An audio CD created by the investigators will be provided to facilitate the home practice, and help maintain proper duration and compliance to the sequence. Participants will be encouraged to keep a journal either on the computer or with the help of a sighted companion. Intervention sessions will be held in small groups if possible or individually if necessary due to scheduling issues.

Aim 3. To pilot test the efficacy of YT for improving balance in RP and glaucoma patients.
YT has the potential to foster proper alignment, balance and proprioceptive awareness by drawing attention to the breath and movement as an individual performs the postures. Thus, YT may have the added benefit of improving balance in RP and glaucoma patients with visual field loss. Functional balance will be measured at two occasions at both pre- and post- intervention using the Berg Balance Scale. It is a validated and reliable performance-based measure consisting of 14 observable tasks that has been used in several studies measuring balance and additionally meets the requirements of being easy to administer without additional equipment or training. The scale includes tasks such as standing, one-leg standing, tandem stand, sit to stand, etc.

Significance

RP involves an inexorable, slowly progressive photoreceptor loss that manifests as night blindness and gradual visual field loss, and may eventually lead to a loss of functional vision. Glaucoma involves a chronic, progressive optic neuropathy, resulting in loss of retinal ganglion cell function in the periphery. In addition to research that focuses on understanding disease biology and finding effective treatments, studies are needed to understand and mitigate patients’ disease-related symptoms that often result in significant distress, morbidity, and reduced quality of life. Individuals with RP experience secondary symptoms such as stress, depression, and sleep disturbances, as well as impaired balance. RP patients have reported episodes of vision loss or reductions in visual fields that they attributed to stress. Pharmacological treatments or supplements for sleep disturbances and negative mood can be associated with unwanted side effects, drug interactions, tolerance or dependency. Since IOP is the only modifiable risk factor in glaucoma, research should incorporate the broader behavioral factors that may affect glaucoma progression, including exercise. Previous research studies have found an association between open-angle glaucoma and sleep-disturbed breathing and sleep apnea may result in optic nerve vascular dysregulation. YT may help alleviate these symptoms of sleep disturbance.

YT is an integrated system of postures, movement, breath and meditation and is easily implemented regardless of age or level of experience. YT is amenable to study because it is composed of a standardized sequence of postures held for a fixed duration. Studies with normally-sighted individuals practicing yoga have revealed positive results on subjective sleep measures. Evidence that yoga bypasses the diseased retina to affect the regulation of melatonin and possibly target other aspects of sleep makes it a viable intervention to consider for those with severe vision loss. Positive results after yoga have been reported for stress, depression and anxiety that may further alleviate disturbed sleep. Pursuing an integrated approach involving YT may have an immediate and comprehensive impact on secondary symptoms and quality of life. In an on-line survey we conducted, physical and emotional well-being were reported as motivating factors for individuals with RP seeking YT. Of the patients surveyed, 31% tried yoga and of those, 92% reported improved stress, fatigue and anxiety levels. While several studies demonstrating the positive influence of yoga exist, none to our knowledge have rigorously examined the visually impaired population.

The reduced ability to respond to visual cues for individuals with severe vision loss leads to increased barriers to independence and risk of falling due to impaired balance. As the field of view is reduced, proprioceptive cues become more important for localization and navigation. Vestibular (e.g., changes in head position) and somatosensory systems (e.g. proprioception) must work in concert with vision in order to maintain equilibrium. In an eyes-closed condition, elderly subjects trained in yoga were able to retain balance better than a physical exercise group, indicating they were better able to use proprioceptive cues.³ Balance improved substantially in a separate study using a timed, one-legged balance test after yoga training in healthy adults. As vision declines, adopting training strategies that promote the use of other sensory/vestibular information may aid in the development of awareness of the body as it moves in space, potentially reducing injuries and falls.

YT may have the potential to improve several aspects of function and quality of life in the visually impaired. This pilot study will evaluate the feasibility of this approach and provide preliminary data for large scale clinical trials.

Budget

Equipment	Amount	Qty Needed	Total
Yoga Mats	$12	10	$120
Heater for Studio	$80	1	$80

Subjects' honorarium
Participation/Transportation	$40	20	$800

TOTAL			$1,000

Morgan Philbin, PhD Candidate, Health, Behavior & Society
An Ethnographic Inquiry of HIV-positive Urban Adolescents: Challenging the Dominant Paradigm of HIV as a Chronic Illness

Background

The nature of an HIV diagnosis has changed over time as HIV has been transformed from an inevitably fatal disease to a chronic but manageable condition (1, 2). This shift began in the early 1990s with the increased ability to treat common opportunistic infections, and was accelerated in the late 1990s with the introduction of highly active antiretroviral therapy (HAART)(1). With HAART, HIV related morbidity and mortality decreased by 60 percent in the United States (3, 4). An individual diagnosed today at age 20 would be expected to live 49.4 more years, a life span close to that of the general population(5). As life expectancy has been extended and HIV managed as a chronic disease, care for HIV is being integrated into standard medical practice. This is evidenced by the elimination and absorption of many AIDS specific wards into larger hospitals(6) and the Centers for Disease Control and Prevention’s testing recommendations, which state that people 13-64 should be screened as frequently as annually(7).

It is not clear, however, how this transformation of HIV/AIDS is experienced among urban adolescents. Adolescents in this study come from families and neighborhoods where HIV has not been experienced as a chronic but manageable condition. The urban poor tend to be diagnosed late and thus progress more rapidly to AIDS(8), and often lack ready access to medication or care (9). The epidemiology of HIV in urban centers is closely linked to injection drug use, sex work, and illicit activities, increasing levels of stigma surrounding the disease (10). Also, prevalence rates of HIV are higher in urban settings, thus affecting the way HIV is integrated into adolescents’ everyday lives. Along living with HIV, these adolescents must simultaneously negotiate puberty and developmental stages that affect their relationship to health and wellness. This tension of living with a chronic illness while undergoing physical and emotional development that prepares one for adult life is unique to adolescents, and a generally poorly understood phenomenon.

Research Question:

The overall goal of this study is to explore how the transformation of HIV/AIDS from an inevitably fatal disease to a chronic but manageable illness affects how HIV-positive adolescents and providers shape and imagine life for HIV-positive adolescents.

Aim 1: Adolescents:

To explore how adolescents experience and narrate their relationship to HIV as it is now structured as a chronic manageable illness in the post-HAART era, and to examine how an HIV diagnosis is integrated into their concurrent physical and emotional development.

Aim 2: Providers

To examine the role of clinical practice in managing HIV-positive adolescents’ lives and how adolescent medicine’s focus on the development and wellness of the entire individual affects the lived experience of HIV-positive adolescents in the era of HAART.

To explore the type of life-course that providers believe HIV-positive adolescents might expect, and what they imagine for them.

Methods:

This research will be couched within a larger study coordinated by the Johns Hopkins Department of Pediatrics. This study will be conducted through the Adolescent Trials Network (ATN), a coalition of 15 medicine clinics in the United States with over a decade of clinical and research experience.

Aim 1, Adolescent interviews: I will conduct interviews with adolescents at the University of Maryland, Baltimore, one of the 15 ATN sites. Adolescents will be recruited using purposive sampling, a preferred method in qualitative research(11). These adolescents will range in age from 16-24, and will have acquired HIV as adolescents rather than perinatally. Adolescents will be selected based on pre-specified criteria (engagement in clinic, age, length and severity of illness, gender, and race). I will follow 8-10 adolescents over a period of 12 months, and will conduct interviews every two months, for a total of six interviews per adolescent. This is frequent enough that theoretical threads can be continued between interviews, but with enough temporal distance that I will be able to transcribe and reflect on an interview to determine relevant thematic elements to discuss in subsequent sessions. Interviews will begin broadly by asking adolescents to describe their family, work, and social situation. They will then narrow to focus on where HIV is located within daily life, how adolescents narrate their HIV experience, and how it is integrated into their future plans.

Aim 2, Healthcare provider interviews: I will conduct interviews with healthcare providers at all 15-sites in the ATN to allow for broad thematic comparisons to be made across clinic sites and geographic locations. I will use purposeful sampling to conduct in-depth interviews with 3-5 providers (e.g. doctors, nurses, case workers and social workers) at each clinic. Each provider will be interviewed once. Healthcare providers will include those who have had experience in both the pre-HAART and post-HAART era, and who frequently interact with HIV-positive adolescents. The interview guide will focused around the following themes: providers’ experience with HIV, approaches to patient management across time, how HIV is presented to adolescents, clinical services across time, and how adolescents’ future lives are envisioned and imagined by providers.

Data Analysis, Aims 1 and 2: Each interview will last approximately 45-60 minutes, be digitally recorded, and transcribed. These transcripts will be entered into Atlas.ti software. To analyze the resulting data, I will employ specific data reduction and data display techniques that are a preferred method within qualitative research(12). Along with conducting thematic analysis of the transcripts, I will utilize comparative matrices to explore patterns of similarities and differences across adolescents, providers, and ATN sites. These matrices will be organized by themes and research question to facilitate cross-clinical comparison. I will also create 2-page case-summaries of each adolescent and provider to condense the data into a more manageable form.

Significance:

Though therapies and treatments exist, HIV still constitutes a significant health burden in the United States, especially among minorities and youth. An estimated 25% of HIV infections occur in youth ages 13-21(13), and over 100,000 adolescents from 13-24 are currently infected with HIV. Though African American youth make up 15% of the population they constitute two-thirds of newly reported HIV cases; from 2001-2004, 61% of individuals under-25 diagnosed with HIV/AIDS were African American(14).

This proposal takes a novel approach to understanding this unique facet of HIV. It will challenge the dominant public health paradigm of HIV as a chronic, manageable illness by exploring discrepancies between this and how urban adolescents experience HIV. These HIV-positive adolescents are the first generation to live into adulthood, and little research into their condition has thus far been conducted. As a result, the social management of adolescents, and how their future is imagined, is poorly understood. In addition, the infrastructure to diagnose, treat, and manage HIV-positive adolescents is only just beginning to exist. This measurement project will add to the literature through its novel approach to exploring this vulnerable, and only newly studied population. This research will be conducted in an innovative way by applying an anthropological framework and methodology to public health and clinic-based research. As such, this research question provides a unique opportunity to apply an interdisciplinary approach to address an important public health problem.

Achieving an understanding and measurement of urban adolescents’ lived experience, in light of the dominant paradigm depicting HIV as a chronic illness, will provide a critical perspective on how life is navigated, described, and addressed among HIV-positive adolescents and providers. HIV rates among urban adolescents are extremely high, and this population does not have ready access to services or care. HIV diagnoses among adolescents are problematic for a number of reasons, including lower rates of medication adherence and higher rates of loss to follow-up than adults(13). As a result, it is imperative to explore how adolescents are living with HIV, and their interactions with providers and clinics, in order to improve existing programs. An important aspect of this proposal is its ability to directly benefit the community of adolescents. This research will inform interventions to improve the social and medical management of HIV-positive adolescents, with a goal of increasing medication adherence and the clinical experience. As this research is couched within the Adolescent Trials Network, the findings can be immediately disseminated to a large number of clinics and healthcare providers for immediate and expansive impact.

Research Budget

Budget Item	Estimated Cost
Digital Voice Recorder	$140
Transportation Costs (to and from the Baltimore clinic site)	$250
Compensation for Adolescent Interviews	$480 (=$20 per interview8 adolescents6 interviews each)#
Atlas.ti Qualitative Software	$130
Total Projected Expenses	$1000

# = This $480 will cover half of the compensation, the other half will be covered by a $600 fund each PhD student in HBS receives for research related expenses.

Additional Funding: I will have access to the aforementioned $600 fund each HBS PhD student receives to defray research related expenses. I will use this to cover compensation and potential transcription fees.

Alumni

Delta Omega

2010 Delta Omega Scholarship Winners

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