Good adherence to HAART and improved survival in a community HIV/AIDS treatment and care programme: the experience of The AIDS Support Organization (TASO), Kampala, Uganda.

BACKGROUND: Poor adherence to highly active antiretroviral therapy (HAART) may result in treatment failure and death. Most reports of the effect of adherence to HAART on mortality come from studies where special efforts are made to provide HAART under ideal conditions. However, there are few reports of the impact of non-adherence to HAART on mortality from community HIV/AIDS treatment and care programmes in developing countries. We therefore conducted a study to assess the effect of adherence to HAART on survival in The AIDS Support Organization (TASO) community HAART programme in Kampala, Uganda. METHODS: The study was a retrospective cohort of 897 patients who initiated HAART at TASO clinic, Kampala, between May 2004 and December 2006. A total of 7,856 adherence assessments were performed on the data. Adherence was assessed using a combination of self-report and pill count methods. Patients who took 95%. The crude death rate was 12.2 deaths per 100 patient-years, with a rate of 42.5 deaths per 100 patient-years for non-adherent patients and 6.1 deaths per 100 patient-years for adherent patients. Non-adherence to ART was significantly associated with mortality. Patients with a CD4 count of less than 50 cells/mm3 had a higher mortality (HR = 4.3; 95% CI: 2.22-5.56) compared to patients with a CD4 count equal to or greater than 50 cells/mm3 (HR = 2.4; 95% CI: 1.79-2.38). CONCLUSION: Our study showed that good adherence and improved survival are feasible in community HIV/AIDS programmes such as that of TASO, Uganda. However, there is need to support community HAART programmes to overcome the challenges of funding to provide sustainable supplies particularly of antiretroviral drugs; provision of high quality clinical and laboratory support; and achieving a balance between expansion and quality of services. Measures for the early identification and treatment of HIV infected people including home-based VCT and HAART should be strengthened

Different Lines of Rats Selectively-Bred for High Alcohol-Drinking Demonstrate Disparate Preferences for Nicotine Self-administration

Background. Alcohol and nicotine are commonly co-abused. The search for a common core of neural, behavioral, and genetic factors underlying addiction has been the goal of addiction research. Purpose. Genetic predisposition to high alcohol intake has been studied in rats by selectively breeding rats that have high preference for alcohol. The current experiments were conducted to determine if the level of intravenous nicotine administration for the various lines of alcohol-preferring rats differs from that for nonalcohol-preferring controls. Study design. Adult alcohol-naïve selectively-bred alcohol-preferring male rats from four lines (P, AA, HAD-1, sP) and their control nonalcohol-preferring rats (NP, ANA, LAD-1, sNP) were trained and given access to self-administer nicotine (0.03 mg/kg/infusion). Results. The results show that the P rats self-administered significantly more nicotine than NP rats. In contrast, there were no significant differences in nicotine self-administration between the sP and sNP or the AA and ANA rats. Unexpectedly, high alcohol-drinking HAD-1 rats self-administered significantly less nicotine than low alcohol-drinking LAD-1 rats. Conclusion. This suggests that some genetic factors that underlie high-alcohol intake have more general effects in promoting high nicotine intake tendencies, while other genetic factors are more specific to only heavy drinking

Reliability and Feasibility of the Four Square Step Test for Use in Children with Cerebral Palsy: A Pilot Study

Purpose: The ability to maintain standing balance with a moving base of support and while making rapid postural adjustments is important for independence in various functional activities. Clinical tests and measures have not addressed this ability in children with disability. This pilot study examined the feasibility and reliability of the Four Square Step Test (FSST) as a test of dynamic balance in children with cerebral palsy (CP). Method: Four children with CP (Gross Motor Function Classification Scale levels I-II) were tested on the FSST by 3 assessors on the first occasion (interrater reliability) and repeat-tested by 1 assessor after 2 weeks (test-retest reliability). Six children with typical development (TD) were tested on a separate occasion to explore any between-group difference in performance. Results: The FSST was easy to setup, required no specialized equipment, could be completed in 5 minutes, and might be carried out by clinicians with limited experience in pediatric therapy. It demonstrated excellent interrater reliability (ICC = 0.832) and test-retest reliability (ICC = 0.979) in children with CP. Compared with FSST times for children with TD (mean = 9.12 ± 2.67 seconds), times for children with CP (mean = 18.38 ± 9.02 seconds) were significantly slower (p = 0.019, Mann-Whitney U = -2.345). Conclusions and Recommendations: The pilot study provides initial evidence on the potential usefulness of the FSST as a test of dynamic standing balance in children with CP. This warrants further investigation of the clinimetric properties of the FSST using an adequate sample size

Orbital Payload Reductions Resulting from Booster and Trajectory Modifications for Recovery of a Large Rocket Booster

An analysis was made to determine the reduction in payload for a 300 nautical mile orbit resulting from the addition of inert weight, representing recovery gear, to the first-stage booster of a three-stage rocket vehicle. The values of added inert weight investigated ranged from 0 to 18 percent of gross weight at lift off. The study also included the effects on the payload in orbit and the distance from the launch site at burnout and at impact caused by variation in the vertical rise time before the programmed tilt. The vertical rise times investigated ranged from 16-7 to 100 percent of booster burning time. For a vertical rise of 16.7 percent of booster burning time it was found that a 50-percent increase in the weight of the empty booster resulted in only a 10-percent reduction of the payload in orbit. For no added booster weight, increasing vertical rise time from 16-7 to 100 percent of booster burning time (so that the spent booster would impact in the launch area) reduced the payload by 37 percent. Increasing the vertical rise time from 16-7 to 50 percent of booster burning time resulted in about a 15-percent reduction in the impact distance, and for vertical rise times greater than 50-percent the impact distance decreased rapidly

Liver genomic responses to ciguatoxin: evidence for activation of Phase I and Phase II detoxification pathways following an acute hypothermic response in mice

Ciguatoxins (CTX) are polyether neurotoxins that target voltage-gated sodium channels and are responsible for ciguatera, the most common fish-borne food poisoning in humans. This study characterizes the global transcriptional response of mouse liver to a symptomatic dose (0.26 ng/g) of the highly potent Pacific ciguatoxin-1 (P-CTX-1). At 1 h post-exposure 2.4% of features on a 44K whole genome array were differentially expressed (p ≤ 0.0001), increasing to 5.2% at 4 h and decreasing to 1.4% by 24 h post-CTX exposure. Data were filtered (|fold change| ≥ 1.5 and p ≤ 0.0001 in at least one time point) and a trend set of 1550 genes were used for further analysis. Early gene expression was likely influenced prominently by an acute 4°C decline in core body temperature by 1 h, which resolved by 8 h following exposure. An initial downregulation of 32 different solute carriers, many involved in sodium transport, was observed. Differential gene expression in pathways involving eicosanoid biosynthesis and cholesterol homeostasis was also noted. Cytochrome P450s (Cyps) were of particular interest due to their role in xenobiotic metabolism. Twenty-seven genes, mostly members of Cyp2 and Cyp4 families, showed significant changes in expression. Many Cyps underwent an initial downregulation at 1 h but were quickly and strongly upregulated at 4 and 24 h post-exposure. In addition to Cyps, increases in several glutathione S-transferases were observed, an indication that both phase I and phase II metabolic reactions are involved in the hepatic response to CTX in mice

Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study.

BACKGROUND: In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda. METHODS AND FINDINGS: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045). CONCLUSION: Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART

Lift, Drag, and Pitching Moments of an Arrow Wing Having 80 Degree of Sweepback at Mach Numbers from 2.48 to 3.51 and Reynolds Numbers up to 11.0 Million

Measurements were made of the lift, drag, and pitching moments on an arrow wing (taper ratio of zero) having an aspect ratio of 1.4 and a leading-edge sweepback of 80 (degrees). The wing was designed to have a subsonic leading-edge and a Clark-Y airfoil with a thickness ratio of 12 percent of the chord perpendicular to the wing leading edge. The wing was tested both with and without the wing tips bent upward in an attempt to alleviate possible flow separation in the vicinity of the wing tips. Small jets of air were used to fix transition near the wing leading edge. Force results are presented for Mach numbers of 2.48, 2.75, 3.04, 3.28, and 3.51 at Reynolds numbers of 3.5 and 9.0 million and for a Mach number of 3.04 at a Reynolds number of 11.0 million. The measured aerodynamic characteristics are compared with those estimated by linear theory. The maximum lift-drag ratio measured was much less than that predicted. This difference is attributed to lack of full leading-edge thrust and to the experimental lift-curve slope being about 20 percent below the theoretical value

Brief Embryonic Strychnine Exposure in Zebrafish Causes Long-Term Adult Behavioral Impairment with Indications of Embyronic Synaptic Changes

Zebrafish provide a powerful model of the impacts of embryonic toxicant exposure on neural development that may result in long-term behavioral dysfunction. In this study, zebrafish embryos were treated with 1.5mM strychnine for short embryonic time windows to induce transient changes in inhibitory neural signaling, and were subsequently raised in untreated water until adulthood. PCR analysis showed indications that strychnine exposure altered expression of some genes related to glycinergic, GABAergic and glutamatergic neuronal synapses during embryonic development. In adulthood, treated fish showed significant changes in swimming speed and tank diving behavior compared to controls. Taken together, these data show that a short embryonic exposure to a neurotoxicant can alter development of neural synapses and lead to changes in adult behavior

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

Developmental Exposure of Rats to Chlorpyrifos Leads to Behavioral Alterations in Adulthood, Involving Serotonergic Mechanisms and Resembling Animal Models of Depression

Developmental exposure to chlorpyrifos (CPF) causes persistent changes in serotonergic (5HT) systems. We administered 1 mg/kg/day CPF to rats on postnatal days 1–4, a regimen below the threshold for systemic toxicity. When tested in adulthood, CPF-exposed animals showed abnormalities in behavioral tests that involve 5HT mechanisms. In the elevated plus maze, males treated with CPF spent more time in the open arms, an effect seen with 5HT deficiencies in animal models of depression. Similarly, in an anhedonia test, the CPF-exposed group showed a decreased preference for chocolate milk versus water. Developmental CPF exposure also has lasting effects on cognitive function. We replicated our earlier finding that developmental CPF exposure ablates the normal sex differences in 16-arm radial maze learning and memory: during acquisition training, control male rats typically perform more accurately than do control females, but CPF treatment eliminated this normal sex difference. Females exposed to CPF showed a reduction in working and reference memory errors down to the rate of control males. Conversely, CPF-exposed males exhibited an increase in working and reference memory errors. After radial-arm acquisition training, we assessed the role of 5HT by challenging the animals with the 5HT(2) receptor antagonist ketanserin. Ketanserin did not affect performance in controls but elicited dose-dependent increases in working and reference memory errors in the CPF group, indicating an abnormal dependence on 5HT systems. Our results indicate that neonatal CPF exposures, classically thought to be subtoxic, produce lasting changes in 5HT-related behaviors that resemble animal models of depression