Long-term effects of intermittent IL-2 in HIV infection: extended follow-up of the INSIGHT STALWART Study

BACKGROUND The Study of Aldesleukin with and without Antiretroviral Therapy (STALWART) was designed to evaluate whether intermittent IL-2 alone or with peri-cycle ART increased CD4+ cell counts (and so delayed initiation of ART) in HIV infected individuals having ≥ 300 CD4+ cells/mm(3) compared to untreated controls. When the results of two large clinical trials, ESPRIT and SILCAAT, showed no clinical benefit from IL-2 therapy, IL-2 administration was halted in STALWART. Because IL-2 recipients in STALWART experienced a greater number of opportunistic disease (OD) or death and adverse events (AEs), participants were asked to consent to an extended follow-up phase in order to assess persistence of IL-2 effects. METHODOLOGY Participants in this study were followed for clinical events and AEs every 4 months for 24 months. Unadjusted Cox proportional hazards models were used to summarize death, death or first OD event, and first grade 3 or 4 AE. PRINCIPAL FINDINGS A total of 267 persons were enrolled in STALWART (176 randomized to the IL-2 arms and 91 to the no therapy arm); 142 individuals in the IL-2 group and 80 controls agreed to enter the extended follow-up study. Initiation of continuous ART was delayed in the IL-2 groups, but once started, resulted in similar CD4+ cell and viral load responses compared to controls. The hazard ratios (95% CI) for IL-2 versus control during the extension phase for death or OD, grade 3 or 4 AE, and grade 4 AE were 1.45 (0.38, 5.45), 0.43 (0.24, 1.63) and 0.20 (0.04, 1.03), respectively. The hazard ratios for the AE outcomes were significantly lower during the extension than during the main study. CONCLUSIONS Adverse events associated with IL-2 cycling did not persist upon discontinuation of IL-2. The use of IL-2 did not impact the subsequent response to initiation of cART

Intelligent Camera Control Using Behavior Trees

Automatic camera systems produce very basic animations for virtual worlds. Users often view environments through two types of cameras: a camera that they control manually, or a very basic automatic camera that follows their character, minimizing occlusions. Real cinematography features much more variety producing more robust stories. Cameras shoot establishing shots, close-ups, tracking shots, and bird’s eye views to enrich a narrative. Camera techniques such as zoom, focus, and depth of field contribute to framing a particular shot. We present an intelligent camera system that automatically positions, pans, tilts, zooms, and tracks events occurring in real-time while obeying traditional standards of cinematography. We design behavior trees that describe how a single intelligent camera might behave from low-level narrative elements assigned by “smart events”. Camera actions are formed by hierarchically arranging behavior sub-trees encapsulating nodes that control specific camera semantics. This approach is more modular and particularly reusable for quickly creating complex camera styles and transitions rather then focusing only on visibility. Additionally, our user interface allows a director to provide further camera instructions, such as prioritizing one event over another, drawing a path for the camera to follow, and adjusting camera settings on the fly.We demonstrate our method by placing multiple intelligent cameras in a complicated world with several events and storylines, and illustrate how to produce a well-shot “documentary” of the events constructed in real-time

T-Lymphocyte Subset Studies to Monitor Patients with AIDS and AIDS-Related Complex

Multiple specimens from 124 patients from our clinic were evaluated for T4/T8 cell ratio over three to 28 months. Twenty-nine of 30 patients with the acquired immunodeficiency syndrome (AIDS), 58 of 71 patients with AIDS-related complex (ARC), and four of 23 patients at risk showed initial T4/T8 cell ratios of less than 0.8. which either remained unchanged or decreased. Seventeen of 23 AIDS patients and two of 20 ARC patients with a consistently low ratio (0.3 or less) died during the follow-up period. This indicated that the severity of disease could be predicted by periodical T4/T8 cell ratio studies. These serial studies appeared to be valuable in monitoring the course of patients with AIDS, ARC, and the human immunodeficiency virus infection and also in evaluating the effects of available drug treatment

Weak anisotropic impurity scattering in unconventional superconductors

The effect of weak anisotropic (momentum-dependent) impurity scattering in unconventional superconductors has been investigated. It is shown that the anisotropic scattering can lead either to a small reduction or a small enhancement of the isotropic pair-breaking effect. The influence of the anisotropy of the scattering potential becomes significant for the order parameters with large Fermi surface average values. In that case an unexpected enhancement (up to 10%) of the critical temperature over the critical temperature in the absence of impurities is predicted for a small impurity concentration.Comment: 12 pages, RevTeX, 3 PostScript figure

The Emerging Role of HTLV-I/II and HIV-1 Among Intravenous Drug Users in Detroit

During 1987-1988, a seroprevalence study of the human immunodeficiency virus (HIV-1) and the human T-cell lymphoma/leukemia virus (HTLV-l/II) was performed among Detroit intravenous drug users unaffiliated with substance abuse programs. Seroprevalence data along with patient demographic information were compared to a similar study performed in 1985-1986. In the earlier study, 12 (12.5%) of 96 individuals tested positive for HIV-1. Of the 74 available negative samples retested in 1987-1988 for retroviruses, 7 (9.5%) tested positive for HTLV-I/II. Thus, the overall retroviral (HIV-1, HTLV-I/II) seropositive rate for 1985-1986 was 22%. In 1987-1988, 11 (15.7%) of 70 individuals tested positive for HIV-1 and 7 (10%) tested positive for HTLV-I/II. Concomitant infection with both viruses was found in 2 (2.9%) of the 70 individuals. Thus, retrovirus seroprevalence in 1987-1988 was 22.9%. In 1987-1988, significant differences between the retroviral-positive group and the retroviral-negative group consisted of intravenous drug use greater than 16 years (P = 0.059) for an odds ratio of 3.80 (Cl 1.12-12.89) and sex with female prostitutes (P = 0.029) for an odds ratio of 5.38 (Cl 1.38-20.95)

Gap Renormalization in Dirty Anisotropic Superconductors: Implications for the Order Parameter of the Cuprates

We contrast the effects of non-magnetic impurities on the properties of superconductors having a \dw\ order parameter, and a highly anisotropic s-wave (ASW) gap with the same nodal structure. The non-vanishing, impurity induced, off-diagonal self-energy in the ASW state is shown to gap out the low energy excitations present in the clean system, leading to a qualitatively different impurity response of the single particle density of states compared to the \dw\ state. We discuss how this behaviour can be employed to distinguish one state from the other by an analysis of high-resolution angle-resolved photoemission spectra.Comment: 12 pages, uuencoded Postscrip

Hematopoietic stem and progenitor cells are a distinct HIV reservoir that contributes to persistent viremia in suppressed patients

Long-lived reservoirs of persistent HIV are a major barrier to a cure. CD4+ hematopoietic stem and progenitor cells (HSPCs) have the capacity for lifelong survival, self-renewal, and the generation of daughter cells. Recent evidence shows that they are also susceptible to HIV infection in vitro and in vivo. Whether HSPCs harbor infectious virus or contribute to plasma virus (PV) is unknown. Here, we provide strong evidence that clusters of identical proviruses from HSPCs and their likely progeny often match residual PV. A higher proportion of these sequences match residual PV than proviral genomes from bone marrow and peripheral blood mononuclear cells that are observed only once. Furthermore, an analysis of near-full-length genomes isolated from HSPCs provides evidence that HSPCs harbor functional HIV proviral genomes that often match residual PV. These results support the conclusion that HIV-infected HSPCs form a distinct and functionally significant reservoir of persistent HIV in infected people

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented