Evaluation of HIV counseling and testing in ANC settings and adherence to short course antiretroviral prophylaxis for PMTCT in Francistown, Botswana

Worldwide, it is estimated that two million children are infected with HIV (USAID 2005). The vast majority of these infections are the result of mother-to-child transmission (MTCT) of the virus during pregnancy, labor, or breastfeeding. However, there are effective methods for prevention of mother-to-child transmission (PMTCT). Botswana is one of the first countries in the developing world with a national PMTCT program that uses an efficacious and complex regimen to reduce vertical transmission. At the time of this evaluation (August - December 2005), the standard of care for prevention of MTCT of HIV in Botswana included three-drug antiretroviral therapy for HIV-infected women with a CD4 count of 200 (300 mg AZT in the morning and 300 mg AZT in the evening); four weeks of AZT for their infants; single-dose maternal and infant nevirapine (NVP); and 12 months of free infant formula. Botswana's PMTCT program also provided routine HIV testing for all pregnant women during antenatal care (ANC) to identify HIV-positive women for prophylaxis or treatment. While programs often report the number of individuals beginning AZT and receiving nevirapine for PMTCT, effectiveness is dependent on the level of adherence of individuals to these regimens. To describe adherence of pregnant women to the current PMTCT regimen, the Horizons Program of the Population Council, in collaboration with the Centers for Disease Control and Prevention (CDC) and Premiere Personnel in Botswana, conducted an evaluation to describe HIV-related services provided to women during their pregnancies, document the content of post-test counseling sessions for HIV-positive pregnant women, whether HIV-positive women remembered what had been discussed, the extent of AZT adherence based on self-reports, and the operational successes and barriers to adherence to AZT for PMTCT

Is combinatorial chemistry on the right track for drug discovery?

Critical to the effective implementation of high throughput methods of synthesis is the necessity for a significant supporting level of automation. There are a number of critical issues associated with the successful introduction, and supporting role, of automation of small molecule chemical synthesis. Clearly there are needs for automation to increase drug candidate synthesis throughput. Automation of repetitive and laborious tasks associated with the synthesis process can release skilled chemists to apply their talents to the more challenging investigational aspects of developing new synthetic protocols. This provides continuity in the compound supply pipeline and ensures an optimal use of the automated platform for compound production. The very high fidelity of performing repetitive processes that can be managed through automation also removes some of the limitations and errors associated with more fallible human operators. This can include very difficult tasks associated with tracking data, and general information and inventory management. Taken collectively, these attributes associated with automation can lead to greater efficiencies, throughputs and improved allocation of human resources with concomitant reductions in costs associated with current day and future drug discovery. In our library development/synthesis paradigm, we feel that automation support must be invoked early in the process and that this automation support must continue throughout the project

Nonparametric Dark Energy Reconstruction from Supernova Data

Understanding the origin of the accelerated expansion of the Universe poses one of the greatest challenges in physics today. Lacking a compelling fundamental theory to test, observational efforts are targeted at a better characterization of the underlying cause. If a new form of mass-energy, dark energy, is driving the acceleration, the redshift evolution of the equation of state parameter w(z) will hold essential clues as to its origin. To best exploit data from observations it is necessary to develop a robust and accurate reconstruction approach, with controlled errors, for w(z). We introduce a new, nonparametric method for solving the associated statistical inverse problem based on Gaussian Process modeling and Markov chain Monte Carlo sampling. Applying this method to recent supernova measurements, we reconstruct the continuous history of w out to redshift z=1.5.Comment: 4 pages, 2 figures, accepted for publication in Physical Review Letter

Health-state valuations for pertussis: methods for valuing short-term health states

BACKGROUND: The incidence of reported adolescent and adult pertussis continues to rise in the United States. Acellular pertussis vaccines for adolescents and adults have been developed and may be available soon for use in the U.S. Our objectives were: (1) to describe patient valuations of pertussis disease and vaccination; and (2) to compare valuations for short-term and long-term health states associated with pertussis. METHODS: We conducted telephone surveys with 515 adult patients and parents of adolescent patients with pertussis in Massachusetts to determine valuations of pertussis-related health states for disease and vaccination using time trade-off (TTO) and contingent valuation (CV) techniques. Respondents were randomized to complete either a short-term or long-term TTO exercise. Discrimination between health states for each valuation technique was assessed using Tukey's method, and valuations for short-term vs. long-term health states were compared using the Wilcoxon rank-sum test. RESULTS: Three hundred three (59%) and 309 (60%) respondents completed and understood the TTO and CV exercises, respectively. Overall, respondents gave lower valuations (lower TTO and higher CV values) to avoid a given state for adolescent/adult disease compared to vaccine adverse events. Infant complications due to pertussis were considered worse than adolescent/adult disease, regardless of the method of valuation. The short-term TTO resulted in lower mean valuations and larger mean differences between health states than the long-term TTO exercise. CONCLUSION: Pertussis was considered worse than adverse events due to vaccination. Short-term health-state valuation is better able to discriminate among health states, which is useful for cost-utility analysis

Nonparametric Reconstruction of the Dark Energy Equation of State

A basic aim of ongoing and upcoming cosmological surveys is to unravel the mystery of dark energy. In the absence of a compelling theory to test, a natural approach is to better characterize the properties of dark energy in search of clues that can lead to a more fundamental understanding. One way to view this characterization is the improved determination of the redshift-dependence of the dark energy equation of state parameter, w(z). To do this requires a robust and bias-free method for reconstructing w(z) from data that does not rely on restrictive expansion schemes or assumed functional forms for w(z). We present a new nonparametric reconstruction method that solves for w(z) as a statistical inverse problem, based on a Gaussian Process representation. This method reliably captures nontrivial behavior of w(z) and provides controlled error bounds. We demonstrate the power of the method on different sets of simulated supernova data; the approach can be easily extended to include diverse cosmological probes.Comment: 16 pages, 11 figures, accepted for publication in Physical Review

Nonparametric Reconstruction of the Dark Energy Equation of State from Diverse Data Sets

The cause of the accelerated expansion of the Universe poses one of the most fundamental questions in physics today. In the absence of a compelling theory to explain the observations, a first task is to develop a robust phenomenology. If the acceleration is driven by some form of dark energy, then, the phenomenology is determined by the dark energy equation of state w. A major aim of ongoing and upcoming cosmological surveys is to measure w and its time dependence at high accuracy. Since w(z) is not directly accessible to measurement, powerful reconstruction methods are needed to extract it reliably from observations. We have recently introduced a new reconstruction method for w(z) based on Gaussian process modeling. This method can capture nontrivial time-dependences in w(z) and, most importantly, it yields controlled and unbaised error estimates. In this paper we extend the method to include a diverse set of measurements: baryon acoustic oscillations, cosmic microwave background measurements, and supernova data. We analyze currently available data sets and present the resulting constraints on w(z), finding that current observations are in very good agreement with a cosmological constant. In addition we explore how well our method captures nontrivial behavior of w(z) by analyzing simulated data assuming high-quality observations from future surveys. We find that the baryon acoustic oscillation measurements by themselves already lead to remarkably good reconstruction results and that the combination of different high-quality probes allows us to reconstruct w(z) very reliably with small error bounds.Comment: 14 pages, 9 figures, 3 table

Interventions to Promote More Effective Balance-Recovery Reactions in Industrial Settings: New Perspectives on Footwear and Handrails

“Change-in-support” balance-recovery reactions that involve rapid stepping or reaching movements play a critical role in preventing falls. Recent geriatrics studies have led to new interventions to improve ability to execute these reactions effectively. Some of these interventions have the potential to reduce fall risk for younger persons working in industrial settings. In this paper, we review research pertaining to two such interventions: 1) balance-enhancing footwear insoles designed to improve stepping reactions, and 2) proximity-triggered handrail cueing systems designed to improve reach-to-grasp reactions. The insole has a raised ridge around the perimeter that is intended to improve balance control by providing increased stimulation of sensory receptors on the footsole in situations where loss of balance may be imminent. The cueing system uses flashing lights and/or verbal prompts to attract attention to the handrail and ensure that the brain registers its location, thereby facilitating more rapid and accurate grasping of the rail if and when sudden loss of balance occurs. Results to date support the efficacy of both interventions in geriatric populations. There is also some evidence that these interventions may improve balance control in younger persons; however, further research is needed to confirm their efficacy in preventing falls in industrial settings

Responding to Vaccine Safety Signals during Pandemic Influenza: A Modeling Study

Background: Managing emerging vaccine safety signals during an influenza pandemic is challenging. Federal regulators must balance vaccine risks against benefits while maintaining public confidence in the public health system. Methods: We developed a multi-criteria decision analysis model to explore regulatory decision-making in the context of emerging vaccine safety signals during a pandemic. We simulated vaccine safety surveillance system capabilities and used an age-structured compartmental model to develop potential pandemic scenarios. We used an expert-derived multi-attribute utility function to evaluate potential regulatory responses by combining four outcome measures into a single measure of interest: 1) expected vaccination benefit from averted influenza; 2) expected vaccination risk from vaccine-associated febrile seizures; 3) expected vaccination risk from vaccine-associated Guillain-Barre Syndrome; and 4) expected change in vaccine-seeking behavior in future influenza seasons. Results: Over multiple scenarios, risk communication, with or without suspension of vaccination of high-risk persons, were the consistently preferred regulatory responses over no action or general suspension when safety signals were detected during a pandemic influenza. On average, the expert panel valued near-term vaccine-related outcomes relative to long-term projected outcomes by 3∶1. However, when decision-makers had minimal ability to influence near-term outcomes, the response was selected primarily by projected impacts on future vaccine-seeking behavior. Conclusions: The selected regulatory response depends on how quickly a vaccine safety signal is identified relative to the peak of the pandemic and the initiation of vaccination. Our analysis suggested two areas for future investment: efforts to improve the size and timeliness of the surveillance system and behavioral research to understand changes in vaccine-seeking behavior

901-110 Three-Dimensional Ultrasound Can Accurately Reconstruct Intravascular Thrombi: In Vitro Validation

High-frequency ultrasound can potentially display gross morphologic changes during thrombus formation and lysis. Current intravascular ultrasound (IVUS) devices, however, provide only 2-dimensional cross-sectional images with limited overall appreciation of thrombus size and 3-dimensional (3D) configuration. The purpose of this study was to explore the ability of 3D reconstruction of serial ultrasound images to provide a quantitative assessment of intravascular thrombi. We therefore imaged 11 arterial thrombi of varying shape and volume (10 to 116mm3). To avoid thrombus disruption, we used an epivascular approach (also suitable for transvenous imaging) with a 20MHz IVUS catheter withdrawn at 1mm/sec. A 3D voxel image intensity data set was reconstructed, and thrombus volume was semiautomatically extracted based on its intensity. Calculated volume was compared with directly measured values by volume displacement in a miniature cylinder.Results3D reconstruction provided previously unobtainable longitudinal and 3D views that improved spatial appreciation of thrombus size, shape and channel formation. Calculated thrombus volumes agreed well with actual volumes: y=0.92x+2.4, r=0.98, SEE=5mm3, mean error = 1±5mm3(ns vs 0).Conclusion3D reconstruction can improve spatial appreciation of the shape of thrombi and accurately measure their volumes. This approach, suitable for epivascular or transvenous imaging, could potentially be used to study thrombus formation and lysis in research and clinical studies