Radio Polarization of the Young High-Magnetic-Field Pulsar PSR J1119-6127

We have investigated the radio polarization properties of PSR J1119-6127, a recently discovered young radio pulsar with a large magnetic field. Using pulsar-gated radio imaging data taken at a center frequency of 2496 MHz with the Australia Telescope Compact Array, we have determined a rotation measure for the pulsar of +842 +/- 23 rad m^-2. These data, combined with archival polarimetry data taken at a center frequency of 1366 MHz with the Parkes telescope, were used to determine the polarization characteristics of PSR J1119-6127 at both frequencies. The pulsar has a fractional linear polarization of ~75% and ~55% at 1366 and 2496 MHz, respectively, and the profile consists of a single, wide component. This pulse morphology and high degree of linear polarization are in agreement with previously noticed trends for young pulsars (e.g., PSR J1513-5908). A rotating-vector (RV) model fit of the position angle (PA) of linear polarization over pulse phase using the Parkes data suggests that the radio emission comes from the leading edge of a conal beam. We discuss PSR J1119-6127 in the context of a recent theoretical model of pulsar spin-down which can in principle be tested with polarization and timing data from this pulsar. Geometric constraints from the RV fit are currently insufficient to test this model with statistical significance, but additional data may allow such a test in the future.Comment: 9 pages, including 6 figures and 1 table. Accepted for publication in Ap

Scaling up of highly active antiretroviral therapy in a rural district of Malawi: an effectiveness assessment.

BACKGROUND: The recording of outcomes from large-scale, simplified HAART (highly active antiretroviral therapy) programmes in sub-Saharan Africa is critical. We aimed to assess the effectiveness of such a programme held by Médecins Sans Frontières (MSF) in the Chiradzulu district, Malawi. METHODS: We scaled up and simplified HAART in this programme since August, 2002. We analysed survival indicators, CD4 count evolution, virological response, and adherence to treatment. We included adults who all started HAART 6 months or more before the analysis. HIV-1 RNA plasma viral load and self-reported adherence were assessed on a subsample of patients, and antiretroviral resistance mutations were analysed in plasma with viral loads greater than 1000 copies per mL. Analysis was by intention to treat. FINDINGS: Of the 1308 patients who were eligible, 827 (64%) were female, the median age was 34.9 years (IQR 29.9-41.0), and 1023 (78%) received d4T/3TC/NVP (stavudine, lamivudine, and nevirapine) as a fixed-dose combination. At baseline, 1266 individuals (97%) were HAART-naive, 357 (27%) were at WHO stage IV, 311 (33%) had a body-mass index of less than 18.5 kg/m2, and 208 (21%) had a CD4 count lower than 50 cells per muL. At follow-up (median 8.3 months, IQR 5.5-13.1), 967 (74%) were still on HAART, 243 (19%) had died, 91 (7%) were lost to follow-up, and seven (0.5%) discontinued treatment. Low body-mass index, WHO stage IV, male sex, and baseline CD4 count lower than 50 cells per muL were independent determinants of death in the first 6 months. At 12 months, the probability of individuals still in care was 0.76 (95% CI 0.73-0.78) and the median CD4 gain was 165 (IQR 67-259) cells per muL. In the cross-sectional survey (n=398), 334 (84%) had a viral load of less than 400 copies per mL. Of several indicators measuring adherence, self-reported poor adherence (<80%) in the past 4 days was the best predictor of detectable viral load (odds ratio 5.4, 95% CI 1.9-15.6). INTERPRETATION: These data show that large numbers of people can rapidly benefit from antiretroviral therapy in rural resource-poor settings and strongly supports the implementation of such large-scale simplified programmes in Africa

Endothelial cells exhibiting angiogenesis in vitro proliferate in response to TGF-beta 1.

Transforming growth factor-beta 1 (TGF-beta 1) has been implicated in the positive regulation of angiogenesis in vivo, whereas it inhibits the proliferation of endothelial cells in vitro. To reconcile these apparently contradictory effects, we have investigated the effect of TGF-beta 1 on bovine aortic endothelial cells that exhibit spontaneous angiogenesis in vitro. We show that concentrations of TGF-beta 1 which stimulate proliferation of cells that form endothelial cords and/or tubes inhibit proliferation of the same cells grown at subconfluent densities. An increase in cell number of 35% over control cultures was achieved with 0.5 ng TGF-beta 1/ml. The proliferative effect was blocked by antibodies against TGF-beta. Immunological detection of BrdU-labeled nuclei revealed an increase greater than 220% in cells treated with TGF-beta 1. Moreover, a population of cells within the cords appeared to be a selective target for this cytokine. The stimulatory effect was not restricted to bovine aortic endothelial cells, as similar results were obtained with endothelial cells derived from rat microvessels. Significant levels of active TGF-beta 1 were detected in cultures containing cords/tubes, whereas only latent TGF-beta 1 was detected in subconfluent cultures. We show further that endothelial cells exhibiting angiogenesis in vitro secrete plasminogen activator, an enzyme that regulates activation of TGF-beta. The major increases in mRNA transcripts for extracellular matrix proteins that are typically associated with TGF-beta 1 were not seen in cells exhibiting angiogenesis in vitro. Since the formation of tubular networks requires both invasion and proliferation, we propose that TGF-beta 1 is a major morphoregulatory factor in angiogenesis that specifically controls endothelial cell proliferation and extracellular matrix turnover