Distribution and Kinematics of O VI in the Galactic Halo

FUSE spectra of 100 extragalactic objects are analyzed to obtain measures of O VI absorption along paths through the Milky Way thick disk/halo. Strong O VI absorption over the approximate velocity range from -100 to 100 km/s reveals a widespread but highly irregular distribution of thick disk O VI, implying the existence of substantial amounts of hot gas with T ~ 3x10^5 K in the Milky Way halo. Large irregularities in the distribution of the absorbing gas are found to be similar over angular scales extending from less than one to 180 degrees, indicating a considerable amount of small and large scale structure in the gas. The overall distribution of Galactic O VI is not well described by a symmetrical plane-parallel layer of patchy O VI absorption. The simplest departure from such a model that provides a reasonable fit to the observations is a plane-parallel patchy absorbing layer with a scale height of 2.3 kpc, and a 0.25 dex excess of O VI in the northern Galactic polar region. The O VI absorption has a Doppler parameter b = 30 to 99 km/s, with an average value of 60 km/s . Thermal broadening alone cannot explain the large observed profile widths. The average O VI absorption velocities toward high latitude objects range from -46 to 82 km/s, with a sample average of 0 km/s and a standard deviation of 21 km/s. O VI associated with the thick disk moves both toward and away from the plane with roughly equal frequency. A combination of models involving the radiative cooling of hot fountain gas, the cooling of supernova bubbles in the halo, and the turbulent mixing of warm and hot halo gases is required to explain the presence of O VI and other highly ionized atoms found in the halo. (abbreviated)Comment: 70 pages, single-spaced, PDF format. Bound copies of this manuscript and two accompanying articles are available upon request. Submitted to ApJ

Structural cerebellar correlates of cognitive functions in spinocerebellar ataxia type 2

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease involving the cerebellum and characterized by a typical motor syndrome. In addition, the presence of cognitive impairment is now widely acknowledged as a feature of SCA2. Given the extensive connections between the cerebellum and associative cerebral areas, it is reasonable to hypothesize that cerebellar neurodegeneration associated with SCA2 may impact on the cerebellar modulation of the cerebral cortex, thus resulting in functional impairment. The aim of the present study was to investigate and quantitatively map the pattern of cerebellar gray matter (GM) atrophy due to SCA2 neurodegeneration and to correlate that with patients' cognitive performances. Cerebellar GM maps were extracted and compared between SCA2 patients (n = 9) and controls (n = 33) by using voxel-based morphometry. Furthermore, the relationship between cerebellar GM atrophy and neuropsychological scores of the patients was assessed. Specific cerebellar GM regions were found to be affected in patients. Additionally, GM loss in cognitive posterior lobules (VI, Crus I, Crus II, VIIB, IX) correlated with visuospatial, verbal memory and executive tasks, while additional correlations with motor anterior (V) and posterior (VIIIA, VIIIB) lobules were found for the tasks engaging motor and planning components. Our results provide evidence that the SCA2 neurodegenerative process affects the cerebellar cortex and that MRI indices of atrophy in different cerebellar subregions may account for the specificity of cognitive symptomatology observed in patients, as result of a cerebello-cerebral dysregulation

Nucleoside analogs plus ritonavir in stable antiretroviral therapy-experienced HIV-infected children - A randomized controlled trial

Context Although protease inhibitors are used routinely in adults with human immunodeficiency virus (HIV) infection, the role of these drugs in the treatment of clinically stable HIV-infected children is not clear. Objective To evaluate the safety, tolerance, and virologic response produced by a change in antiretroviral therapy in HIV-infected children who were clinically and immunologically stable while receiving previous therapy. Design The Pediatric AIDS Clinical Trials Group 338, a multicenter, phase 2, randomized, open-label controlled trial conducted from February 6 to April 30, 1997 (patient entry period); patients were followed up for 48 weeks. Setting Pediatric HIV research clinics in the United States and Puerto Rico. Patients Two hundred ninety-seven antiretroviral-experienced, protease inhibitor-naive, clinically stable HIV-infected children aged 2 to 17 years. Interventions Children were randomized to receive zidovudine, 160 mg/m(2) 3 times per day, plus lamivudine, 4 mg/kg 2 times per day (n = 100); the same regimen plus ritonavir, 350 mg/m(2) 2 times per day (n = 100); or ritonavir, 350 mg/m(2) 2 times per day, and stavudine, 4 mg/kg 2 times per day (n = 97). Main Outcome Measure Plasma HIV-1 RNA levels at study weeks 12 and 48, compared among the 3 treatment groups. Results At study week 12, 12% of patients in the zidovudine-lamivudine group had undetectable plasma HIV RNA levels ( Conclusions In our study, change in antiretroviral therapy to a ritonavir-containing regimen was associated with superior virologic response at study week 12 compared with change to a dual nucleoside analog regimen. More children receiving ritonavir in combination with 2 compared with 1 nucleoside analog had undetectable HIV RNA levels at study week 48

Metabolic Abnormalities and Viral Replication is Associated with Biomarkers of Vascular Dysfunction in HIV-Infected Children

OBJECTIVES: Human immunodeficiency virus (HIV)-infected children may be at risk for premature cardiovascular disease. We compared levels of biomarkers of vascular dysfunction among HIV-infected children with and without hyperlipidemia to HIV-exposed, uninfected children (HEU) enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS), and determined factors associated with these biomarkers. DESIGN: Prospective cohort study METHODS: Biomarkers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP1)); coagulant dysfunction (fibrinogen and P-selectin); endothelial dysfunction (soluble intracellular cell adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM), and E-selectin); and metabolic dysfunction (adiponectin) were measured in 226 HIV-infected and 140 HEU children. Anthropometry, body composition, lipids, glucose, insulin, HIV disease severity, and antiretroviral therapy were recorded. RESULTS: The median ages were 12.3 y (HIV-infected) and 10.1 y (HEU). Body mass index (BMI) Z-scores, waist and hip circumference, and percent body fat were lower among HIV-infected. Total and non-HDL cholesterol and triglycerides were higher in HIV-infected children. HIV-infected children had higher MCP-1, fibrinogen, sICAM, and sVCAM levels. In multivariable analyses in the HIV-infected children alone, BMI z-score was associated with higher CRP and fibrinogen, but lower MCP-1 and sVCAM. Unfavorable lipid profiles were positively associated with IL6, MCP1, fibrinogen, and P- and E-selectin, whereas increased HIV viral load was associated with markers of inflammation (MCP1 and CRP) and endothelial dysfunction (sICAM and sVCAM). CONCLUSIONS: HIV-infected children have higher levels of biomarkers of vascular dysfunction than do HEU children. Risk factors associated with higher biomarkers include unfavorable lipid levels and active HIV replication

Safety and Efficacy of Atorvastatin in Human Immunodeficiency Virus-infected Children, Adolescents and Young Adults With Hyperlipidemia.

BackgroundHuman immunodeficiency virus (HIV)-infected children receiving antiretroviral therapy (ART) have increased prevalence of hyperlipidemia and risk factors for cardiovascular disease. No studies have investigated the efficacy and safety of statins in this population.MethodsHIV-infected youth 10 to <24 years of age on stable ART with low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL for ≥6 months initiated atorvastatin 10 mg once daily. Atorvastatin was increased to 20 mg if LDL-C efficacy criteria (LDL-C < 110 mg/dL or decreased ≥30% from baseline) were not met at week 4. Primary outcomes were safety and efficacy.ResultsTwenty-eight youth initiated atorvastatin; 7 were 10-15 years and 21 were 15-24 years. Mean baseline LDL-C was 161 mg/dL (standard deviation 19 mg/dL). Efficacy criteria were met at week 4 by 17 of 27 (63%) participants. Atorvastatin was increased to 20 mg in 10 participants. Mean LDL-C decreased from baseline by 30% (90% confidence interval: 26%, 35%) at week 4, 28% (90% confidence interval: 23%, 33%) at week 24 and 26% (90% confidence interval: 20%, 33%) at week 48. LDL-C was less than 110 mg/dL in 44% at week 4, 42% at week 12 and 46% at weeks 24 and 48. Total cholesterol, non high-density lipoprotein (non-HDL)-C and apolipoprotein B decreased significantly, but IL-6 and high-sensitivity C-reactive protein did not. Two participants in the younger age group discontinued study for toxicities possibly related to atorvastatin.ConclusionsAtorvastatin lowered total cholesterol, LDL-C, non HDL-C and apolipoprotein B in HIV-infected youth with ART-associated hyperlipidemia. Atorvastatin could be considered for HIV-infected children with hyperlipidemia, but safety monitoring is important particularly in younger children