The Impact of HAART on the Respiratory Complications of HIV Infection: Longitudinal Trends in the MACS and WIHS Cohorts

Objective: To review the incidence of respiratory conditions and their effect on mortality in HIV-infected and uninfected individuals prior to and during the era of highly active antiretroviral therapy (HAART). Design: Two large observational cohorts of HIV-infected and HIV-uninfected men (Multicenter AIDS Cohort Study [MACS]) and women (Women's Interagency HIV Study [WIHS]), followed since 1984 and 1994, respectively. Methods: Adjusted odds or hazards ratios for incident respiratory infections or non-infectious respiratory diagnoses, respectively, in HIV-infected compared to HIV-uninfected individuals in both the pre-HAART (MACS only) and HAART eras; and adjusted Cox proportional hazard ratios for mortality in HIV-infected persons with lung disease during the HAART era. Results: Compared to HIV-uninfected participants, HIV-infected individuals had more incident respiratory infections both pre-HAART (MACS, odds ratio [adjusted-OR], 2.4; 95% confidence interval [CI], 2.2-2.7; p<0.001) and after HAART availability (MACS, adjusted-OR, 1.5; 95%CI 1.3-1.7; p<0.001; WIHS adjusted-OR, 2.2; 95%CI 1.8-2.7; p<0.001). Chronic obstructive pulmonary disease was more common in MACS HIV-infected vs. HIV-uninfected participants pre-HAART (hazard ratio [adjusted-HR] 2.9; 95%CI, 1.02-8.4; p = 0.046). After HAART availability, non-infectious lung diseases were not significantly more common in HIV-infected participants in either MACS or WIHS participants. HIV-infected participants in the HAART era with respiratory infections had an increased risk of death compared to those without infections (MACS adjusted-HR, 1.5; 95%CI, 1.3-1.7; p<0.001; WIHS adjusted-HR, 1.9; 95%CI, 1.5-2.4; p<0.001). Conclusion: HIV infection remained a significant risk for infectious respiratory diseases after the introduction of HAART, and infectious respiratory diseases were associated with an increased risk of mortality. © 2013 Gingo et al

Training for a First-Time Marathon Reverses Age-Related Aortic Stiffening.

BACKGROUND: Aging increases aortic stiffness, contributing to cardiovascular risk even in healthy individuals. Aortic stiffness is reduced through supervised training programs, but these are not easily generalizable. OBJECTIVES: The purpose of this study was to determine whether real-world exercise training for a first-time marathon can reverse age-related aortic stiffening. METHODS: Untrained healthy individuals underwent 6 months of training for the London Marathon. Assessment pre-training and 2 weeks post-marathon included central (aortic) blood pressure and aortic stiffness using cardiovascular magnetic resonance distensibility. Biological "aortic age" was calculated from the baseline chronological age-stiffness relationship. Change in stiffness was assessed at the ascending (Ao-A) and descending aorta at the pulmonary artery bifurcation (Ao-P) and diaphragm (Ao-D). Data are mean changes (95% confidence intervals [CIs]). RESULTS: A total of 138 first-time marathon completers (age 21 to 69 years, 49% male) were assessed, with an estimated training schedule of 6 to 13 miles/week. At baseline, a decade of chronological aging correlated with a decrease in Ao-A, Ao-P, and Ao-D distensibility by 2.3, 1.9, and 3.1 × 10-3 mm Hg-1, respectively (p < 0.05 for all). Training decreased systolic and diastolic central (aortic) blood pressure by 4 mm Hg (95% CI: 2.8 to 5.5 mm Hg) and 3 mm Hg (95% CI: 1.6 to 3.5 mm Hg). Descending aortic distensibility increased (Ao-P: 9%; p = 0.009; Ao-D: 16%; p = 0.002), while remaining unchanged in the Ao-A. These translated to a reduction in "aortic age" by 3.9 years (95% CI: 1.1 to 7.6 years) and 4.0 years (95% CI: 1.7 to 8.0 years) (Ao-P and Ao-D, respectively). Benefit was greater in older, male participants with slower running times (p < 0.05 for all). CONCLUSIONS: Training for and completing a marathon even at relatively low exercise intensity reduces central blood pressure and aortic stiffness-equivalent to a ∼4-year reduction in vascular age. Greater rejuvenation was observed in older, slower individuals

A Non Mouse-Adapted Dengue Virus Strain as a New Model of Severe Dengue Infection in AG129 Mice

The spread of dengue (DEN) worldwide combined with an increased severity of the DEN-associated clinical outcomes have made this mosquito-borne virus of great global public health importance. Progress in understanding DEN pathogenesis and in developing effective treatments has been hampered by the lack of a suitable small animal model. Most of the DEN clinical isolates and cell culture-passaged DEN virus strains reported so far require either host adaptation, inoculation with a high dose and/or intravenous administration to elicit a virulent phenotype in mice which results, at best, in a productive infection with no, few, or irrelevant disease manifestations, and with mice dying within few days at the peak of viremia. Here we describe a non-mouse-adapted DEN2 virus strain (D2Y98P) that is highly infectious in AG129 mice (lacking interferon-α/β and -γ receptors) upon intraperitoneal administration. Infection with a high dose of D2Y98P induced cytokine storm, massive organ damage, and severe vascular leakage, leading to haemorrhage and rapid death of the animals at the peak of viremia. In contrast, very interestingly and uniquely, infection with a low dose of D2Y98P led to asymptomatic viral dissemination and replication in relevant organs, followed by non-paralytic death of the animals few days after virus clearance, similar to the disease kinetic in humans. Spleen damage, liver dysfunction and increased vascular permeability, but no haemorrhage, were observed in moribund animals, suggesting intact vascular integrity, a cardinal feature in DEN shock syndrome. Infection with D2Y98P thus offers the opportunity to further decipher some of the aspects of dengue pathogenesis and provides a new platform for drug and vaccine testing

Measurement of the W+W-gamma Cross Section and Direct Limits on Anomalous Quartic Gauge Boson Couplings at LEP

The process e+e- -> W+W-gamma is analysed using the data collected with the L3 detector at LEP at a centre-of-mass energy of 188.6GeV, corresponding to an integrated luminosity of 176.8pb^-1. Based on a sample of 42 selected W+W- candidates containing an isolated hard photon, the W+W-gamma cross section, defined within phase-space cuts, is measured to be: sigma_WWgamma = 290 +/- 80 +/- 16 fb, consistent with the Standard Model expectation. Including the process e+e- -> nu nu gamma gamma, limits are derived on anomalous contributions to the Standard Model quartic vertices W+W- gamma gamma and W+W-Z gamma at 95% CL: -0.043 GeV^-2 < a_0/Lambda^2 < 0.043 GeV^-2 0.08 GeV^-2 < a_c/Lambda^2 < 0.13 GeV^-2 0.41 GeV^-2 < a_n/Lambda^2 < 0.37 GeV^-2

Production of Single W Bosons at \sqrt{s}=189 GeV and Measurement of WWgamma Gauge Couplings

Single W boson production in electron-positron collisions is studied with the L3 detector at LEP. The data sample collected at a centre-of-mass energy of \sqrt{s} = 188.7GeV corresponds to an integrated luminosity of 176.4pb^-1. Events with a single energetic lepton or two acoplanar hadronic jets are selected. Within phase-space cuts, the total cross-section is measured to be 0.53 +/- 0.12 +/- 0.03 pb, consistent with the Standard Model expectation. Including our single W boson results obtained at lower \sqrt{s}, the WWgamma gauge couplings kappa_gamma and lambda_gamma are determined to be kappa_gamma = 0.93 +/- 0.16 +/- 0.09 and lambda_gamma = -0.31 +0.68 -0.19 +/- 0.13

Search for an invisibly decaying Higgs boson in e^+e^- collisions at \sqrt{s} = 183 - 189 GeV

A search for a Higgs boson decaying into invisible particles is performed using the data collected at LEP by the L3 experiment at centre-of-mass energies of 183 GeV and 189 GeV. The integrated luminosities are respectively 55.3 pb^-1 and 176.4 pb^-1. The observed candidates are consistent with the expectations from Standard Model processes. In the hypothesis that the production cross section of this Higgs boson equals the Standard Model one and the branching ratio into invisible particles is 100%, a lower mass limit of 89.2 GeV is set at 95% confidence level

Search for Neutral Higgs Bosons of the Minimal Supersymmetric Standard Model in e+e- Interactions at \sqrt{s} = 189 GeV

A search for the lightest neutral scalar and neutral pseudoscalar Higgs bosons in the Minimal Supersymmetric Standard Model is performed using 176.4 pb^-1 of integrated luminosity collected by L3 at a center-of-mass energy of 189 GeV. No signal is observed, and the data are consistent with the expected Standard Model background. Lower limits on the masses of the lightest neutral scalar and pseudoscalar Higgs bosons are given as a function of tan(beta). Lower mass limits for tan(beta)>1 are set at the 95% confidence level to be m_h > 77.1 GeV and m_A > 77.1 GeV

Measurement of Bose-Einstein Correlations in e+e- -> W+W- at root(s)=189GeV

We investigate Bose-Einstein correlations (BEC) in W-pair production at root(s)=189GeV using the L3 detector at LEP. We observe BEC between particles from a single W decay in good agreement with those from a light-quark Z decay sample. We investigate their possible existence between particles coming from different W's. No evidence for such inter-W BEC is found

Measurement of the Lifetime of the Tau Lepton

The tau lepton lifetime is measured with the L3 detector at LEP using the complete data taken at centre-of-mass energies around the Z pole resulting in tau_tau = 293.2 +/- 2.0 (stat) +/- 1.5 (syst) fs. The comparison of this result with the muon lifetime supports lepton universality of the weak charged current at the level of six per mille. Assuming lepton universality, the value of the strong coupling constant, alpha_s is found to be alpha_s(m_tau^2) = 0.319 +/- 0.015(exp.) +/- 0.014 (theory)