129 research outputs found

    An analysis method for multi-component airfoils in separated flow

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    The multi-component airfoil program (Langley-MCARF) for attached flow is modified to accept the free vortex sheet separation-flow model program (Analytical Methods, Inc.-CLMAX). The viscous effects are incorporated into the calculation by representing the boundary layer displacement thickness with an appropriate source distribution. The separation flow model incorporated into MCARF was applied to single component airfoils. Calculated pressure distributions for angles of attack up to the stall are in close agreement with experimental measurements. Even at higher angles of attack beyond the stall, correct trends of separation, decrease in lift coefficients, and increase in pitching moment coefficients are predicted

    Inviscid analysis of unsteady blade tip flow correlation studies

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    Two computer programs, VSAERO-TS and VSAERO-H, were used for computing the unsteady subsonic aerodynamic characteristics of arbitrarily shaped wings oscillating in pitch. Program VSAERO-TS is a time-stepping analysis capable of treating large amplitude motions while program VSAERO-H uses harmonic wake and small amplitude assumptions. A comparison between the computed (VSAERO-TS and VSAERO-H) and DFVLR test results for chordwise pressure distributions for rectangular, swept, taper and ogee blade tips is presented in this report. A wide range of angles of attack (mean) from 0 to 12 deg and reduced frequencies of 0.1, 0.2 and 0.3 are covered in this report. Also, the comparison includes several spanwise stations

    Airloads on bluff bodies, with application to the rotor-induced downloads on tilt-rotor aircraft

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    The aerodynamic characteristics of airfoils with several flap configurations were studied theoretically and experimentally in environments that simulate a wing immersed in the downwash of a hovering rotor. Special techniques were developed for correcting and validating the wind tunnel data for large blockage effects, and the test results were used to evaluate two modern blockage effects, and the test results were used to evaluate two modern computational aerodynamics codes. The combined computed and measured results show that improved flap and leading-edge configurations can be designed which will achieve large reductions in the downloads of tilt-rotor aircraft, and thereby improve their hover efficiency

    Estimated use of abacavir among adults and children enrolled in public sector antiretroviral therapy programmes in Gauteng Province, South Africa

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    In South Africa, abacavir (ABC) is currently recommended as part of first- and second-line antiretroviral therapy (ART) for HIV-positive paediatric patients. Concerns about overprescribing of the drug, particularly to adults, led to an analysis of ABC use in public sector ART programmes. We investigated current prescription of the drug to adults and children accessing ART in 4 public sector programmes across Gauteng Province, South Africa. ABC was almostexclusively prescribed to children initiating ART and adults requiring regimen changes due to drug toxicities. Patterns of ABC use among HIV-positive paediatric patients followed national ART treatment guidelines on the application of the drug. Although ABC is commonly used in the private sectorfor adults, the current national ART treatment guidelines for adults and adolescents should include ABC as an alternative to standard first- or second-line ART

    Risk factors for discordant immune response among HIV-infected patients initiating antiretroviral therapy: A retrospective cohort study

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    Background. The therapeutic goal of antiretroviral therapy (ART) is sustained immune recovery and viral suppression. However, some patients experience poor CD4 cell count responses despite achieving viral  suppression. Such discordant immune responses have been associated with poor clinical outcomes.Objective. We aimed to determine the prevalence of discordant immune response and explore associated factors in a retrospective cohort of patients attending 2 large public sector clinics, during the 6 months following ART initiation.Methods. Data were analysed from 810 HIV-infected adults initiated on first-line HAART at 2 clinics in Johannesburg, between 1 November 2008 and 31 December 2009. Multivariate logistic regression models were used to estimate adjusted odds ratios (AORs) to determine associations between discordant immune response and clinical and demographic factors.Results. At ART initiation, 65% (n=592) of participants were female, with a mean age of 38.5 years. Median baseline CD4 cell count was 155 cells/mm3, 70% (n=645) of patients had a haemoglobin level >11 g/dl and 88% (n=803) were initiated on stavudine-lamivudine-efavirenz/nevirapine (D4T-3TC-EFV/NVP). Six months after ART initiation, 24% (n=220) of patients had a discordant immune response and 7% (n=67) a discordant virological response. On multivariate analysis, baseline CD cell count .200 cells/mm3 (AOR 3.02; 95% confidence interval (CI) 2.08 - 4.38; p<0.001) and moderate anaemia (8.0 - 9.4 g/dl) atbaseline (AOR 2.30; 95% CI 1.25 - 4.59; p=0.007) were independently associated with the development of discordant immune response, after adjustment for education level, World Health Organization (WHO) clinical stage and ART regimen.Conclusions. Discordant immune response following ART initiation was common and associated with baseline anaemia and CD4 cell count in our cohort. Intensive monitoring of at-risk individuals may improve clinical outcomes

    Effectiveness and safety of 30 mg versus 40 mg stavudine regimens: a cohort study among HIV-infected adults initiating HAART in South Africa

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    <p>Abstract</p> <p>Background</p> <p>As stavudine remains an important and widely prescribed drug in resource-limited settings, the effect of a reduced dose of stavudine (from 40 mg to 30 mg) on outcomes of highly active antiretroviral therapy (HAART) remains an important public health question.</p> <p>Methods</p> <p>We analyzed prospectively collected data from the Themba Lethu Clinic in Johannesburg, South Africa. We assessed the relationship between stavudine dose and six- and/or 12-month outcomes of stavudine substitution, failure to suppress viral load to below 400 copies/ml, development of peripheral neuropathy, lipoatrophy and hyperlactatemia/lactic acidosis. Since individuals with a baseline weight of less than 60 kg were expected to have received the same dose of stavudine throughout the study period, analysis was restricted to individuals who weighed 60 kg or more at baseline. Data were analyzed using logistic regression.</p> <p>Results</p> <p>Between 1 April 2004 and 30 September 2009, 3910 patients were initiated on antiretroviral therapy (ART) with a recorded stavudine dose and were included in the analysis. Of these, 2445 (62.5%) received a 40 mg stavudine dose while 1565 (37.5%) received 30 mg. In multivariate analysis, patients receiving a 40 mg dose were more likely to discontinue stavudine use (adjusted odds ratio, OR 1.71; 95% confidence limits, CI 1.13-2.57) than those receiving 30 mg by 12 months on ART. Additionally, patients receiving 40 mg doses of stavudine were more likely to report peripheral neuropathy (OR 3.12; 95% CI 1.86-5.25), lipoatrophy (OR 11.8; 95% CI 3.2-43.8) and hyperlactatemia/lactic acidosis (OR 8.37; 95% CI 3.83-18.29) in the same time period. Failure to suppress HIV viral load within 12 months of HAART initiation was somewhat more common among those given 40 mg doses (OR 1.62; 95% CI 0.88, 2.97) although this result lacked precision. Sensitivity analyses accounting for death and loss to follow up generally supported these estimates.</p> <p>Conclusions</p> <p>Lower stavudine dosage is associated with fewer reports of several stavudine-associated adverse events and also a lower risk of stavudine discontinuation within the first year on ART.</p

    Lost to follow-up - contributing factors and challenges in South African patients on antiretroviral therapy

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    Background. Patients who do not return for follow-up at clinics providing comprehensive HIV/AIDS care require special attention. This is particularly true where resources are limited and clinic loads are high. Themba Lethu Clinic at Helen Joseph Hospital in Johannesburg is a facility supported by PEPFAR funding through Right to Care (Grant CA-574-A-00-02-00018); more than 800 HIV/AIDS patients are seen there each week. Data on a sample of patients who failed to return for follow-up were analysed to identify the causes and to plan strategies to overcome the problem. Methods. A group of 182 patients who missed follow-up appointments at the clinic were identified. Their files were examined to identify possible contributing factors. The patients were then contacted telephonically and asked their reasons for non-attendance. Results. Results show that the leading cause of failure to follow up was financial (34% of patients). Patients cited transport costs and having to pay to open a file at each visit as the biggest monetary obstacles to obtaining treatment. Fifty-five per cent of patients lost to follow-up showed an improvement in CD4 count on treatment. Death accounted for 27% of the patients lost to follow-up and the mean (± standard deviation (SD)) duration of treatment in this group was only 8 (± 6) weeks. Of the patients in this group who had been seen at 4 months, 60% had failed to respond to treatment. The mean duration of ARV treatment before being lost to follow-up was 21 (± 28) weeks. The mean CD4+ count was 92 (± 74.5) cells/&#956;l and the mean number of visits was 3.33 (± 2.17). Seventy-four per cent of the patients were on regimen 1A, and only 1 cited side-effects of medication as a reason for not returning. Conclusions. This study highlighted financial difficulty as the major obstacle to obtaining treatment. There is evidence in support of providing ARV treatment free of charge to HIVpositive patients who qualify, as occurs in other provinces in South Africa. It is also suggested that providing ARV therapy at more local clinics in the community would make treatment more accessible. Provision of several months\' supply of medicines per visit would help to reduce transport costs and minimise patient expenditure. These interventions may reduce the incidence of patients lost to follow-up in this community. South African Medical Journal Vol. 97 (9) 2007: pp. 853-85

    Structural and functional determination of homologs of the Mycobacterium tuberculosis N-acetylglucosamine-6-phosphate deacetylase (NagA)

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    The (Mtb) pathogen encodes an -acetylglucosamine-6-phosphate deacetylase enzyme, NagA (Rv3332), that belongs to the amidohydrolase superfamily. NagA enzymes catalyze the deacetylation of -acetylglucosamine-6-phosphate (GlcNAc6P) to glucosamine-6-phosphate (GlcN6P). NagA is a potential anti-tubercular drug target because it represents the key enzymatic step in the generation of essential amino-sugar precursors required for cell wall biosynthesis and also influences recycling of cell wall peptidoglycan fragments. Here, we report the structural and functional characterization of NagA from (MSNagA) and (MMNagA), close relatives of Using a combination of X-ray crystallography, site-directed mutagenesis, and biochemical and biophysical assays, we show that these mycobacterial NagA enzymes are selective for GlcNAc6P. Site-directed mutagenesis studies revealed crucial roles of conserved residues in the active site that underpin stereo-selective recognition, binding, and catalysis of substrates. Moreover, we report the crystal structure of MSNagA in both ligand-free form and in complex with the GlcNAc6P substrate at 2.6 Å and 2.0 Å resolutions, respectively. The GlcNAc6P-complex structure disclosed the precise mode of GlcNAc6P binding and the structural framework of the active site, including two divalent metals located in the α/β binuclear site. Furthermore, we observed a cysteine residue located on a flexible loop region that occludes the active site. This cysteine is unique to mycobacteria and may represent a unique subsite for targeting mycobacterial NagA enzymes. Our results provide critical insights into the structural and mechanistic properties of mycobacterial NagA enzymes having an essential role in amino-sugar and nucleotide metabolism in mycobacteria
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