Pairing QuantiFERON gold in-tube with opt-out HIV testing in a tuberculosis contact investigation in the Southeastern United States.

Knowing one's HIV status is particularly important in the setting of recent tuberculosis (TB) exposure. Blood tests for assessment of tuberculosis infection, such as the QuantiFERON Gold in-tube test (QFT; Cellestis Limited, Carnegie, Victoria, Australia), offer the possibility of simultaneous screening for TB and HIV with a single blood draw. We performed a cross-sectional analysis of all contacts to a highly infectious TB case in a large meatpacking factory. Twenty-two percent were foreign-born and 73% were black. Contacts were tested with both tuberculin skin testing (TST) and QFT. HIV testing was offered on an opt-out basis. Persons with TST >or=10 mm, positive QFT, and/or positive HIV test were offered latent TB treatment. Three hundred twenty-six contacts were screened: TST results were available for 266 people and an additional 24 reported a prior positive TST for a total of 290 persons with any TST result (89.0%). Adequate QFT specimens were obtained for 312 (95.7%) of persons. Thirty-two persons had QFT results but did not return for TST reading. Twenty-two percent met the criteria for latent TB infection. Eighty-eight percent accepted HIV testing. Two (0.7%) were HIV seropositive; both individuals were already aware of their HIV status, but one had stopped care a year previously. None of the HIV-seropositive persons had latent TB, but all were offered latent TB treatment per standard guidelines. This demonstrates that opt-out HIV testing combined with QFT in a large TB contact investigation was feasible and useful. HIV testing was also widely accepted. Pairing QFT with opt-out HIV testing should be strongly considered when possible.

Gender differences in the risk of HIV infection among persons reporting abstinence, monogamy, and multiple sexual partners in northern Tanzania.

BACKGROUND: Monogamy, together with abstinence, partner reduction, and condom use, is widely advocated as a key behavioral strategy to prevent HIV infection in sub-Saharan Africa. We examined the association between the number of sexual partners and the risk of HIV seropositivity among men and women presenting for HIV voluntary counseling and testing (VCT) in northern Tanzania. METHODOLOGY/ PRINCIPAL FINDINGS: Clients presenting for HIV VCT at a community-based AIDS service organization in Moshi, Tanzania were surveyed between November 2003 and December 2007. Data on sociodemographic characteristics, reasons for testing, sexual behaviors, and symptoms were collected. Men and women were categorized by number of lifetime sexual partners, and rates of seropositivity were reported by category. Factors associated with HIV seropositivity among monogamous males and females were identified by a multivariate logistic regression model. Of 6,549 clients, 3,607 (55%) were female, and the median age was 30 years (IQR 24-40). 939 (25%) females and 293 (10%) males (p<0.0001) were HIV seropositive. Among 1,244 (34%) monogamous females and 423 (14%) monogamous males, the risk of HIV infection was 19% and 4%, respectively (p<0.0001). The risk increased monotonically with additional partners up to 45% (p<0.001) and 15% (p<0.001) for women and men, respectively with 5 or more partners. In multivariate analysis, HIV seropositivity among monogamous women was most strongly associated with age (p<0.0001), lower education (p<0.004), and reporting a partner with other partners (p = 0.015). Only age was a significant risk factor for monogamous men (p = 0.0004). INTERPRETATION: Among women presenting for VCT, the number of partners is strongly associated with rates of seropositivity; however, even women reporting lifetime monogamy have a high risk for HIV infection. Partner reduction should be coupled with efforts to place tools in the hands of sexually active women to reduce their risk of contracting HIV.

R5 clade C SHIV strains with tier 1 or 2 neutralization sensitivity: tools to dissect env evolution and to develop AIDS vaccines in primate models.

BACKGROUND: HIV-1 clade C (HIV-C) predominates worldwide, and anti-HIV-C vaccines are urgently needed. Neutralizing antibody (nAb) responses are considered important but have proved difficult to elicit. Although some current immunogens elicit antibodies that neutralize highly neutralization-sensitive (tier 1) HIV strains, most circulating HIVs exhibiting a less sensitive (tier 2) phenotype are not neutralized. Thus, both tier 1 and 2 viruses are needed for vaccine discovery in nonhuman primate models. METHODOLOGY/PRINCIPAL FINDINGS: We constructed a tier 1 simian-human immunodeficiency virus, SHIV-1157ipEL, by inserting an "early," recently transmitted HIV-C env into the SHIV-1157ipd3N4 backbone [1] encoding a "late" form of the same env, which had evolved in a SHIV-infected rhesus monkey (RM) with AIDS. SHIV-1157ipEL was rapidly passaged to yield SHIV-1157ipEL-p, which remained exclusively R5-tropic and had a tier 1 phenotype, in contrast to "late" SHIV-1157ipd3N4 (tier 2). After 5 weekly low-dose intrarectal exposures, SHIV-1157ipEL-p systemically infected 16 out of 17 RM with high peak viral RNA loads and depleted gut CD4+ T cells. SHIV-1157ipEL-p and SHIV-1157ipd3N4 env genes diverge mostly in V1/V2. Molecular modeling revealed a possible mechanism for the increased neutralization resistance of SHIV-1157ipd3N4 Env: V2 loops hindering access to the CD4 binding site, shown experimentally with nAb b12. Similar mutations have been linked to decreased neutralization sensitivity in HIV-C strains isolated from humans over time, indicating parallel HIV-C Env evolution in humans and RM. CONCLUSIONS/SIGNIFICANCE: SHIV-1157ipEL-p, the first tier 1 R5 clade C SHIV, and SHIV-1157ipd3N4, its tier 2 counterpart, represent biologically relevant tools for anti-HIV-C vaccine development in primates.

Differences in the cognitive skills of bonobos and chimpanzees.

While bonobos and chimpanzees are both genetically and behaviorally very similar, they also differ in significant ways. Bonobos are more cautious and socially tolerant while chimpanzees are more dependent on extractive foraging, which requires tools. The similarities suggest the two species should be cognitively similar while the behavioral differences predict where the two species should differ cognitively. We compared both species on a wide range of cognitive problems testing their understanding of the physical and social world. Bonobos were more skilled at solving tasks related to theory of mind or an understanding of social causality, while chimpanzees were more skilled at tasks requiring the use of tools and an understanding of physical causality. These species differences support the role of ecological and socio-ecological pressures in shaping cognitive skills over relatively short periods of evolutionary time.

Who tests, who doesn't, and why? Uptake of mobile HIV counseling and testing in the Kilimanjaro Region of Tanzania.

BACKGROUND: Optimally, expanded HIV testing programs should reduce barriers to testing while attracting new and high-risk testers. We assessed barriers to testing and HIV risk among clients participating in mobile voluntary counseling and testing (MVCT) campaigns in four rural villages in the Kilimanjaro Region of Tanzania. METHODS: Between December 2007 and April 2008, 878 MVCT participants and 506 randomly selected community residents who did not access MVCT were surveyed. Gender-specific logistic regression models were used to describe differences in socioeconomic characteristics, HIV exposure risk, testing histories, HIV related stigma, and attitudes toward testing between MVCT participants and community residents who did not access MVCT. Gender-specific logistic regression models were used to describe differences in socioeconomic characteristics, HIV exposure risk, testing histories, HIV related stigma, and attitudes toward testing, between the two groups. RESULTS: MVCT clients reported greater HIV exposure risk (OR 1.20 [1.04 to 1.38] for males; OR 1.11 [1.03 to 1.19] for females). Female MVCT clients were more likely to report low household expenditures (OR 1.47 [1.04 to 2.05]), male clients reported higher rates of unstable income sources (OR 1.99 [1.22 to 3.24]). First-time testers were more likely than non-testers to cite distance to testing sites as a reason for not having previously tested (OR 2.17 [1.05 to 4.48] for males; OR 5.95 [2.85 to 12.45] for females). HIV-related stigma, fears of testing or test disclosure, and not being able to leave work were strongly associated with non-participation in MVCT (ORs from 0.11 to 0.84). CONCLUSIONS: MVCT attracted clients with increased exposure risk and fewer economic resources; HIV related stigma and testing-related fears remained barriers to testing. MVCT did not disproportionately attract either first-time or frequent repeat testers. Educational campaigns to reduce stigma and fears of testing could improve the effectiveness of MVCT in attracting new and high-risk populations.

Perceived acceptability of home-based couples voluntary HIV counseling and testing in Northern Tanzania.

It is estimated that 5.6% of the Tanzanian population ages 15-49 are infected with HIV, but only 30% of adults have ever had an HIV test. Couples' testing has proven to increase testing coverage and introduce HIV prevention, but barriers include access to testing services and unequal gender dynamics in relationships. Innovative approaches are needed to address barriers to couple's testing and increase uptake of HIV testing. Using qualitative data collection methods, a formative study was conducted to assess the acceptability of a home-based couples counseling and testing (HBCCT) approach. Eligible study participants included married men and women, HIV-infected individuals, health care and home-based care providers, voluntary counseling and testing counselors, and community leaders. A total of 91 individuals participated in focus group discussions (FGDs) and in-depth interviews conducted between September 2009 and January 2010 in rural settings in Northern Tanzania. An HBCCT intervention appears to be broadly acceptable among participants. Benefits of HBCCT were identified in terms of access, confidentiality, and strengthening the relationship. Fears of negative consequences from knowing one's HIV status, including stigma, blame, physical abuse, or divorce, remain a concern and a potential barrier to the successful provision of the intervention. Lessons for implementation highlighted the importance of appointments for home visits, building relationships of confidence and trust between counselors and clients, and assessing and responding to a couple's readiness to undergo HIV testing. HBCCT should addresses HIV stigma, emphasize confidentiality, and improve communication skills for disclosure and decision-making among couples.

Correlates of HIV testing among abused women in South Africa.

Gender-based violence increases a woman's risk for HIV but little is known about her decision to get tested. We interviewed 97 women seeking abuse-related services from a nongovernmental organization (NGO) in Johannesburg, South Africa. Forty-six women (47%) had been tested for HIV. Caring for children (odds ratio [OR] = 0.27, 95% confidence interval [CI] = [0.07, 1.00]) and conversing with partner about HIV (OR = 0.13, 95% CI = [0.02, 0.85]) decreased odds of testing. Stronger risk-reduction intentions (OR = 1.27, 95% CI = [1.01, 1.60]) and seeking help from police (OR = 5.51, 95% CI = [1.18, 25.76]) increased odds of testing. Providing safe access to integrated services and testing may increase testing in this population. Infection with HIV is highly prevalent in South Africa where an estimated 16.2% of adults between the ages of 15 and 49 have the virus. The necessary first step to stemming the spread of HIV and receiving life-saving treatment is learning one's HIV serostatus through testing. Many factors may contribute to someone's risk of HIV infection and many barriers may prevent testing. One factor that does both is gender-based violence.

HIV/AIDS-related institutional mistrust among multiethnic men who have sex with men: effects on HIV testing and risk behaviors.

OBJECTIVE: To investigate relationships between institutional mistrust (systematic discrimination, organizational suspicion, and conspiracy beliefs), HIV risk behaviors, and HIV testing in a multiethnic sample of men who have sex with men (MSM), and to test whether perceived susceptibility to HIV mediates these relationships for White and ethnic minority MSM. METHOD: Participants were 394 MSM residing in Central Arizona (M age = 37 years). Three dimensions of mistrust were examined, including organizational suspicion, conspiracy beliefs, and systematic discrimination. Assessments of sexual risk behavior, HIV testing, and perceived susceptibility to HIV were made at study entry (T1) and again 6 months later (T2). RESULTS: There were no main effects of institutional mistrust dimensions or ethnic minority status on T2 risk behavior, but the interaction of systematic discrimination and conspiracy beliefs with minority status was significant such that higher levels of systematic discrimination and more conspiracy beliefs were associated with increased risk only among ethnic minority MSM. Higher levels of systematic discrimination were significantly related to lower likelihood for HIV testing, and the interaction of organizational suspicion with minority status was significant such that greater levels of organizational suspicion were related to less likelihood of having been tested for HIV among ethnic minority MSM. Perceived susceptibility did not mediate these relationships. CONCLUSION: Findings suggest that it is important to look further into the differential effects of institutional mistrust across marginalized groups, including sexual and ethnic minorities. Aspects of mistrust should be addressed in HIV prevention and counseling efforts.

Crafting analytical tools to study institutional change

Most powerful analytical tools used in the social sciences are well suited for studying static situations. Static and mechanistic analysis, however, is not adequate to understand the changing world in which we live. In order to adequately address the most pressing social and environmental challenges looming ahead, we need to develop analytical tools for analyzing dynamic situations -particularly institutional change. In this paper, we develop an analytical tool to study institutional change, more specifically, the evolution of rules and norms. We believe that in order for such an analytical tool to be useful to develop a general theory of institutional change, it needs to enable the analyst to concisely record the processes of change in multiple specific settings so that lessons from such settings can eventually be integrated into a more general predictive theory of change. Copyright © The JOIE Foundation 2010.

Can We Learn in the Sandbox Together?: Interprofessional Case Conferences as Facilitation Tools

Duke Medicine utilized interprofessional case conferences (ICCs) from 2008-2012 with the objective of modeling and facilitating development of teamwork skills among diverse health profession students, including physical therapy, physician assistant, medical doctor and nursing. The purpose of this publication was to describe the operational process used to develop and implement the ICCs and measure the success of the ICCs in order to shape future work. The ICCs were offered to develop skills and attitudes essential for participation in healthcare teams. Students were facilitated by faculty of different professions to conduct a comprehensive historical assessment of a standardized patient (SP), determine pertinent physical and lab assessments to undertake, and develop and share a comprehensive management plan. Cases included patient problems that were authentic and relevant to each professional student in attendance. The main barriers to implementation are outlined and the focus on the process of working together is highlighted. Evaluation showed high satisfaction rates among participants and the outcomes from these experiences are presented. The limitations of these results are discussed and recommendations for future assessment are emphasized. The ICCs demonstrated that students will come together voluntarily to learn in teams, even at a research-focused institution, and express benefit from the collaborative exercise.

Computer vision tools for low-cost and noninvasive measurement of autism-related behaviors in infants.

The early detection of developmental disorders is key to child outcome, allowing interventions to be initiated which promote development and improve prognosis. Research on autism spectrum disorder (ASD) suggests that behavioral signs can be observed late in the first year of life. Many of these studies involve extensive frame-by-frame video observation and analysis of a child's natural behavior. Although nonintrusive, these methods are extremely time-intensive and require a high level of observer training; thus, they are burdensome for clinical and large population research purposes. This work is a first milestone in a long-term project on non-invasive early observation of children in order to aid in risk detection and research of neurodevelopmental disorders. We focus on providing low-cost computer vision tools to measure and identify ASD behavioral signs based on components of the Autism Observation Scale for Infants (AOSI). In particular, we develop algorithms to measure responses to general ASD risk assessment tasks and activities outlined by the AOSI which assess visual attention by tracking facial features. We show results, including comparisons with expert and nonexpert clinicians, which demonstrate that the proposed computer vision tools can capture critical behavioral observations and potentially augment the clinician's behavioral observations obtained from real in-clinic assessments.

Computer vision tools for the non-invasive assessment of autism-related behavioral markers

The early detection of developmental disorders is key to child outcome, allowing interventions to be initiated that promote development and improve prognosis. Research on autism spectrum disorder (ASD) suggests behavioral markers can be observed late in the first year of life. Many of these studies involved extensive frame-by-frame video observation and analysis of a child's natural behavior. Although non-intrusive, these methods are extremely time-intensive and require a high level of observer training; thus, they are impractical for clinical and large population research purposes. Diagnostic measures for ASD are available for infants but are only accurate when used by specialists experienced in early diagnosis. This work is a first milestone in a long-term multidisciplinary project that aims at helping clinicians and general practitioners accomplish this early detection/measurement task automatically. We focus on providing computer vision tools to measure and identify ASD behavioral markers based on components of the Autism Observation Scale for Infants (AOSI). In particular, we develop algorithms to measure three critical AOSI activities that assess visual attention. We augment these AOSI activities with an additional test that analyzes asymmetrical patterns in unsupported gait. The first set of algorithms involves assessing head motion by tracking facial features, while the gait analysis relies on joint foreground segmentation and 2D body pose estimation in video. We show results that provide insightful knowledge to augment the clinician's behavioral observations obtained from real in-clinic assessments.

A COMPARISON OF MARKET CLEARING TOOLS IN ELECTRICITY SYSTEMS

To maintain a strict balance between demand and supply in the US power systems, the Independent System Operators (ISOs) schedule power plants and determine electricity prices using a market clearing model. This model determines for each time period and power plant, the times of startup, shutdown, the amount of power production, and the provisioning of spinning and non-spinning power generation reserves, etc. Such a deterministic optimization model takes as input the characteristics of all the generating units such as their power generation installed capacity, ramp rates, minimum up and down time requirements, and marginal costs for production, as well as the forecast of intermittent energy such as wind and solar, along with the minimum reserve requirement of the whole system. This reserve requirement is determined based on the likelihood of outages on the supply side and on the levels of error forecasts in demand and intermittent generation. With increased installed capacity of intermittent renewable energy, determining the appropriate level of reserve requirements has become harder. Stochastic market clearing models have been proposed as an alternative to deterministic market clearing models. Rather than using a fixed reserve targets as an input, stochastic market clearing models take different scenarios of wind power into consideration and determine reserves schedule as output. Using a scaled version of the power generation system of PJM, a regional transmission organization (RTO) that coordinates the movement of wholesale electricity in all or parts of 13 states and the District of Columbia, and wind scenarios generated from BPA (Bonneville Power Administration) data, this paper explores a comparison of the performance between a stochastic and deterministic model in market clearing. The two models are compared in their ability to contribute to the affordability, reliability and sustainability of the electricity system, measured in terms of total operational costs, load shedding and air emissions. The process of building the models and running for tests indicate that a fair comparison is difficult to obtain due to the multi-dimensional performance metrics considered here, and the difficulty in setting up the parameters of the models in a way that does not advantage or disadvantage one modeling framework. Along these lines, this study explores the effect that model assumptions such as reserve requirements, value of lost load (VOLL) and wind spillage costs have on the comparison of the performance of stochastic vs deterministic market clearing models.

Development and usability testing of a Web-based decision aid for families of patients receiving prolonged mechanical ventilation.

BACKGROUND: Web-based decision aids are increasingly important in medical research and clinical care. However, few have been studied in an intensive care unit setting. The objectives of this study were to develop a Web-based decision aid for family members of patients receiving prolonged mechanical ventilation and to evaluate its usability and acceptability. METHODS: Using an iterative process involving 48 critical illness survivors, family surrogate decision makers, and intensivists, we developed a Web-based decision aid addressing goals of care preferences for surrogate decision makers of patients with prolonged mechanical ventilation that could be either administered by study staff or completed independently by family members (Development Phase). After piloting the decision aid among 13 surrogate decision makers and seven intensivists, we assessed the decision aid's usability in the Evaluation Phase among a cohort of 30 surrogate decision makers using the Systems Usability Scale (SUS). Acceptability was assessed using measures of satisfaction and preference for electronic Collaborative Decision Support (eCODES) versus the original printed decision aid. RESULTS: The final decision aid, termed 'electronic Collaborative Decision Support', provides a framework for shared decision making, elicits relevant values and preferences, incorporates clinical data to personalize prognostic estimates generated from the ProVent prediction model, generates a printable document summarizing the user's interaction with the decision aid, and can digitally archive each user session. Usability was excellent (mean SUS, 80 ± 10) overall, but lower among those 56 years and older (73 ± 7) versus those who were younger (84 ± 9); p = 0.03. A total of 93% of users reported a preference for electronic versus printed versions. CONCLUSIONS: The Web-based decision aid for ICU surrogate decision makers can facilitate highly individualized information sharing with excellent usability and acceptability. Decision aids that employ an electronic format such as eCODES represent a strategy that could enhance patient-clinician collaboration and decision making quality in intensive care.

Patterns of de novo allo B cells and antibody formation in chronic cardiac allograft rejection after alemtuzumab treatment.

Even though the etiology of chronic rejection (CR) is multifactorial, donor specific antibody (DSA) is considered to have a causal effect on CR development. Currently the antibody-mediated mechanisms during CR are poorly understood due to lack of proper animal models and tools. In a clinical setting, we previously demonstrated that induction therapy by lymphocyte depletion, using alemtuzumab (anti-human CD52), is associated with an increased incidence of serum alloantibody, C4d deposition and antibody-mediated rejection in human patients. In this study, the effects of T cell depletion in the development of antibody-mediated rejection were examined using human CD52 transgenic (CD52Tg) mice treated with alemtuzumab. Fully mismatched cardiac allografts were transplanted into alemtuzumab treated CD52Tg mice and showed no acute rejection while untreated recipients acutely rejected their grafts. However, approximately half of long-term recipients showed increased degree of vasculopathy, fibrosis and perivascular C3d depositions at posttransplant day 100. The development of CR correlated with DSA and C3d deposition in the graft. Using novel tracking tools to monitor donor-specific B cells, alloreactive B cells were shown to increase in accordance with DSA detection. The current animal model could provide a means of testing strategies to understand mechanisms and developing therapeutic approaches to prevent chronic rejection.