5,035 research outputs found

    Safety and preliminary efficacy of vorinostat with R-EPOCH in high-risk HIV-associated non-Hodgkin\u27s lymphoma (AMC-075)

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    We performed a phase I trial of vorinostat (VOR) given on days 1 to 5 with R-EPOCH (rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride) in patients with aggressive HIV-associated non-Hodgkin lymphoma. VOR was tolerable at 300 mg and seemingly efficacious with chemotherapy with complete response rate of 83% and 1-year event-free survival of 83%. VOR did not significantly alter chemotherapy steady-state concentrations, CD4+ cell counts, or HIV viral loads. Vorinostat (VOR), a histone deacetylase inhibitor, enhances the anti-tumor effects of rituximab (R) and cytotoxic chemotherapy, induces viral lytic expression and cell killing in Epstein-Barr virus-positive (EBV+) or human herpesvirus-8-positive (HHV-8+) tumors, and reactivates latent human immunodeficiency virus (HIV) for possible eradication by combination antiretroviral therapy (cART). We performed a phase I trial of VOR given with R-based infusional EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride) (n = 12) and cART in aggressive HIV-associated B-cell non-Hodgkin lymphoma (NHL) in order to identify safe dosing and schedule. VOR (300 or 400 mg) was given orally on days 1 to 5 with each cycle of R-EPOCH for 10 high-risk patients with diffuse large B-cell lymphoma (1 EBV+), 1 EBV+/HHV-8+ primary effusion lymphoma, and 1 unclassifiable NHL. VOR was escalated from 300 to 400 mg using a standard 3 + 3 design based on dose-limiting toxicity observed in cycle 1 of R-EPOCH. The recommended phase II dose of VOR was 300 mg, with dose-limiting toxicity in 2 of 6 patients at 400 mg (grade 4 thrombocytopenia, grade 4 neutropenia), and 1 of 6 treated at 300 mg (grade 4 sepsis from tooth abscess). Neither VOR, nor cART regimen, significantly altered chemotherapy steady-state concentrations. VOR chemotherapy did not negatively impact CD4+ cell counts or HIV viral loads, which decreased or remained undetectable in most patients during treatment. The response rate in high-risk patients with NHL treated with VOR(R)-EPOCH was 100% (complete 83% and partial 17%) with a 1-year event-free survival of 83% (95% confidence interval, 51.6%-97.9%). VOR combined with R-EPOCH was tolerable and seemingly efficacious in patients with aggressive HIV-NHL

    Spectrometer Scan Mechanism for Encountering Jovian Orbit Trojan Asteroids

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    This paper describes the design, testing, and lessons learned during the development of the Lucy Ralph (L'Ralph) Scan Mirror System (SMS), composed of the Scan Mirror Mechanism (SMM), Differential Position Sensor System (DPSS) and Mechanism Control Electronics (MCE). The L'Ralph SMS evolved from the Advanced Topographic Laser Altimeter System (ATLAS) Beam Steering Mechanism (BSM), so design comparisons will be made. Lucy is scheduled to launch in October 2021, embarking upon a 12-year mission to make close range encounters in 2025 and 2033 with seven Trojan asteroids and one main belt asteroid that are within the Jovian orbit. The L'Ralph instrument is based upon the New Horizons Ralph instrument, which is a panchromatic and color visible imager and infrared spectroscopic mapper that slewed the spacecraft for imaging. The L'Ralph SMM is to provide scanning for imaging to eliminate the need to slew the spacecraft. One purpose of this paper is to gain understanding of the reasoning behind some of the design features as compared with the ATLAS BSM. We will identify similarities and differences between the ATLAS BSM and the L'Ralph SMM that resulted from the latter's unique requirements. Another purpose of this paper is to focus upon "Lessons Learned" that came about during the development of the L'Ralph SMM and its MCE, both mechanism engineering issues and solutions as well as Ground Support Equipment (GSE) issues and solutions that came about during the validation of requirements process. At the time of this writing, the L'Ralph SMM has been flight qualified and delivered to the project

    Doping-Dependent and Orbital-Dependent Band Renormalization in Ba(Fe_1-xCo_x)_2As_2 Superconductors

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    Angle resolved photoemission spectroscopy of Ba(Fe1-xCox)2As2 (x = 0.06, 0.14, and 0.24) shows that the width of the Fe 3d yz/zx hole band depends on the doping level. In contrast, the Fe 3d x^2-y^2 and 3z^2-r^2 bands are rigid and shifted by the Co doping. The Fe 3d yz/zx hole band is flattened at the optimal doping level x = 0.06, indicating that the band renormalization of the Fe 3d yz/zx band correlates with the enhancement of the superconducting transition temperature. The orbital-dependent and doping-dependent band renormalization indicates that the fluctuations responsible for the superconductivity is deeply related to the Fe 3d orbital degeneracy.Comment: 5 pages, 4 figure

    UK Housing Market: Time Series Processes with Independent and Identically Distributed Residuals

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    The paper examines whether a univariate data generating process can be identified which explains the data by having residuals that are independent and identically distributed, as verified by the BDS test. The stationary first differenced natural log quarterly house price index is regressed, initially with a constant variance and then with a conditional variance. The only regression function that produces independent and identically distributed standardised residuals is a mean process based on a pure random walk format with Exponential GARCH in mean for the conditional variance. There is an indication of an asymmetric volatility feedback effect but higher frequency data is required to confirm this. There could be scope for forecasting the index but this is tempered by the reduction in the power of the BDS test if there is a non-linear conditional variance process

    Revealing the electroweak properties of a new scalar resonance

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    One or more new heavy resonances may be discovered in experiments at the CERN Large Hadron Collider. In order to determine if such a resonance is the long-awaited Higgs boson, it is essential to pin down its spin, CP, and electroweak quantum numbers. Here we describe how to determine what role a newly-discovered neutral CP-even scalar plays in electroweak symmetry breaking, by measuring its relative decay rates into pairs of electroweak vector bosons: WW, ZZ, \gamma\gamma, and Z\gamma. With the data-driven assumption that electroweak symmetry breaking respects a remnant custodial symmetry, we perform a general analysis with operators up to dimension five. Remarkably, only three pure cases and one nontrivial mixed case need to be disambiguated, which can always be done if all four decay modes to electroweak vector bosons can be observed or constrained. We exhibit interesting special cases of Higgs look-alikes with nonstandard decay patterns, including a very suppressed branching to WW or very enhanced branchings to \gamma\gamma and Z\gamma. Even if two vector boson branching fractions conform to Standard Model expectations for a Higgs doublet, measurements of the other two decay modes could unmask a Higgs imposter.Comment: 23 pages, two figures; v2: minor revision and version to appear in JHE

    Immunofluorescence Assay for Serologic Diagnosis of SARS

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    We evaluated a virus-infected cell-based indirect immunofluorescence assay for detecting anti–severe acute respiratory syndrome-associated coronavirus (SARS-CoV) immunoglobulin (Ig) G antibody. All confirmed SARS cases demonstrated seroconversion or fourfold rise in IgG antibody titer; no control was positive. Sensitivity and specificity of this assay were both 100%. Immunofluorescence assay can ascertain the status of SARS-CoV infection

    Generalization of the Bound State Model

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    In the bound state approach the heavy baryons are constructed by binding, with any orbital angular momentum, the heavy meson multiplet to the nucleon considered as a soliton in an effective meson theory. We point out that this picture misses an entire family of states, labeled by a different angular momentum quantum number, which are expected to exist according to the geometry of the three-body constituent quark model (for N_C=3). To solve this problem we propose that the bound state model be generalized to include orbitally excited heavy mesons bound to the nucleon. In this approach the missing angular momentum is ``locked-up'' in the excited heavy mesons. In the simplest dynamical realization of the picture we give conditions on a set of coupling constants for the binding of the missing heavy baryons of arbitrary spin. The simplifications made include working in the large M limit, neglecting nucleon recoil corrections, neglecting mass differences among different heavy spin multiplets and also neglecting the effects of light vector mesons.Comment: 35 pages (ReVTeX), 2 PostScript Figure

    Adjusting bone mass for differences in projected bone area and other confounding variables: an allometric perspective.

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    The traditional method of assessing bone mineral density (BMD; given by bone mineral content [BMC] divided by projected bone area [Ap], BMD = BMC/Ap) has come under strong criticism by various authors. Their criticism being that the projected bone "area" (Ap) will systematically underestimate the skeletal bone "volume" of taller subjects. To reduce the confounding effects of bone size, an alternative ratio has been proposed called bone mineral apparent density [BMAD = BMC/(Ap)3/2]. However, bone size is not the only confounding variable associated with BMC. Others include age, sex, body size, and maturation. To assess the dimensional relationship between BMC and projected bone area, independent of other confounding variables, we proposed and fitted a proportional allometric model to the BMC data of the L2-L4 vertebrae from a previously published study. The projected bone area exponents were greater than unity for both boys (1.43) and girls (1.02), but only the boy's fitted exponent was not different from that predicted by geometric similarity (1.5). Based on these exponents, it is not clear whether bone mass acquisition increases in proportion to the projected bone area (Ap) or an estimate of projected bone volume (Ap)3/2. However, by adopting the proposed methods, the analysis will automatically adjust BMC for differences in projected bone size and other confounding variables for the particular population being studied. Hence, the necessity to speculate as to the theoretical value of the exponent of Ap, although interesting, becomes redundant
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