Influence of enrollment sequence effect on observed outcomes in the ADDRESS and PROWESS studies of drotrecogin alfa (activated) in patients with severe sepsis

INTRODUCTION: We performed a study to determine whether an enrollment sequence effect noted in the PROWESS (recombinant human activated Protein C Worldwide Evaluation in Severe Sepsis) trial exists in the ADDRESS (Administration of Drotrecogin Alfa [Activated] [DrotAA] in Early Stage Severe Sepsis) trial. METHODS: We evaluated prospectively defined subgroups from two large phase 3 clinical trials: ADDRESS, which included 516 sites in 34 countries, and PROWESS, which included 164 sites in 11 countries. ADDRESS consisted of patients with severe sepsis at low risk of death not indicated for treatment with DrotAA. PROWESS consisted of patients with severe sepsis with one or more organ dysfunctions. DrotAA (24 microg/kg per hour) or placebo was infused for 96 hours. RESULTS: In ADDRESS and PROWESS, there was a statistically significant interaction between the DrotAA treatment effect and the sequence in which patients were enrolled. In both trials, higher mortality was associated with DrotAA use in the subgroup of patients enrolled first at study sites. Compared with placebo, PROWESS mortality was lower with DrotAA treatment for the second and subsequent patients enrolled, whereas in ADDRESS, mortality remained higher for the second patient enrolled but thereafter was lower for DrotAA-treated patients. Comparison of patients enrolled first with subsequent patients enrolled indicated that the characteristics of patients changed. Subsequently enrolled patients were treated earlier, were less likely to suffer nonserious bleeds (ADDRESS), and experienced fewer protocol violations (PROWESS). CONCLUSIONS: Analyses suggest that an enrollment sequence effect was present in the ADDRESS and PROWESS trials. Analysis of this effect on outcomes suggests that it is most apparent in patients at lower risk of death. In PROWESS, this effect appeared to be associated with a reduction of the DrotAA treatment effect for the first patients enrolled at each site. In ADDRESS, this effect may have contributed to early termination of the study. The finding of an enrollment sequence effect in two separate trials suggests that trial designs, site selection and training, data collection and monitoring, and statistical analysis plans may need to be adjusted for these potentially confounding events. TRIAL REGISTRATION: ADDRESS trial registration number: NCT00568737. PROWESS was completed before trial registration was required

Factors related to tinnitus and hyperacusis handicap in older people.

OBJECTIVE: The aim was to assess factors related to tinnitus and hyperacusis handicap in older people. DESIGN: Retrospective cross-sectional. STUDY SAMPLE: Data were gathered for 184 patients with an average age of 69 years. RESULTS: Tinnitus handicap as measured via the Tinnitus Handicap Inventory (THI) was significantly predicted by tinnitus annoyance as measured via the visual analogue scale (VAS) (regression coefficient, b = 2.9, p < 0.001) and the effect of tinnitus on the patient's life as measured via the VAS (b = 3.9, p < 0.001). Hyperacusis handicap as measured via the Hyperacusis Questionnaire (HQ) was significantly predicted by the score on the depression subscale of the Hospital Anxiety and Depression Scale (HADS) (b = 0.8, p < 0.001) and to a small extent by the THI score (b = 0.07, p = 0.048). Insomnia scores as measured via the Insomnia Severity Index (ISI) were significantly predicted by scores on the depression subscale of the HADS (b = 0.46, p = 0.007). CONCLUSIONS: Since tinnitus annoyance significantly predicts tinnitus handicap, it is important to explore factors associated with annoyance that may be useful in designing appropriate rehabilitative interventions aimed at reducing tinnitus handicap in older people. Future studies should explore whether hyperacusis and insomnia in older people with tinnitus need to be managed in conjunction with treatment for depression

Two-subband electron transport in nonideal quantum wells

Electron transport in nonideal quantum wells (QW) with large-scale variations of energy levels is studied when two subbands are occupied. Although the mean fluctuations of these two levels are screened by the in-plane redistribution of electrons, the energies of both levels remain nonuniform over the plane. The effect of random inhomogeneities on the classical transport is studied within the framework of a local response approach for weak disorder. Both short-range and small-angle scattering mechanisms are considered. Magnetotransport characteristics and the modulation of the effective conductivity by transverse voltage are evaluated for different kinds of confinement potentials (hard wall QW, parabolic QW, and stepped QW).Comment: 10 pages, 6 figure

Formation of Small-Scale Condensations in the Molecular Clouds via Thermal Instability

A systematic study of the linear thermal instability of a self-gravitating magnetic molecular cloud is carried out for the case when the unperturbed background is subject to local expansion or contraction. We consider the ambipolar diffusion, or ion-neutral friction on the perturbed states. In this way, we obtain a non-dimensional characteristic equation that reduces to the prior characteristic equation in the non-gravitating stationary background. By parametric manipulation of this characteristic equation, we conclude that there are, not only oblate condensation forming solutions, but also prolate solutions according to local expansion or contraction of the background. We obtain the conditions for existence of the Field lengths that thermal instability in the molecular clouds can occur. If these conditions establish, small-scale condensations in the form of spherical, oblate, or prolate may be produced via thermal instability.Comment: 16 page, accepted by Ap&S

CDMS, Supersymmetry and Extra Dimensions

The CDMS experiment aims to directly detect massive, cold dark matter particles originating from the Milky Way halo. Charge and lattice excitations are detected after a particle scatters in a Ge or Si crystal kept at ~30 mK, allowing to separate nuclear recoils from the dominating electromagnetic background. The operation of 12 detectors in the Soudan mine for 75 live days in 2004 delivered no evidence for a signal, yielding stringent limits on dark matter candidates from supersymmetry and universal extra dimensions. Thirty Ge and Si detectors are presently installed in the Soudan cryostat, and operating at base temperature. The run scheduled to start in 2006 is expected to yield a one order of magnitude increase in dark matter sensitivity.Comment: To be published in the proceedings of the 7th UCLA symposium on sources and detection of dark matter and dark energy in the universe, Marina del Rey, Feb 22-24, 200

Quantum computing implementations with neutral particles

We review quantum information processing with cold neutral particles, that is, atoms or polar molecules. First, we analyze the best suited degrees of freedom of these particles for storing quantum information, and then we discuss both single- and two-qubit gate implementations. We focus our discussion mainly on collisional quantum gates, which are best suited for atom-chip-like devices, as well as on gate proposals conceived for optical lattices. Additionally, we analyze schemes both for cold atoms confined in optical cavities and hybrid approaches to entanglement generation, and we show how optimal control theory might be a powerful tool to enhance the speed up of the gate operations as well as to achieve high fidelities required for fault tolerant quantum computation.Comment: 19 pages, 12 figures; From the issue entitled "Special Issue on Neutral Particles

Tomato: a crop species amenable to improvement by cellular and molecular methods

Tomato is a crop plant with a relatively small DNA content per haploid genome and a well developed genetics. Plant regeneration from explants and protoplasts is feasable which led to the development of efficient transformation procedures. In view of the current data, the isolation of useful mutants at the cellular level probably will be of limited value in the genetic improvement of tomato. Protoplast fusion may lead to novel combinations of organelle and nuclear DNA (cybrids), whereas this technique also provides a means of introducing genetic information from alien species into tomato. Important developments have come from molecular approaches. Following the construction of an RFLP map, these RFLP markers can be used in tomato to tag quantitative traits bred in from related species. Both RFLP's and transposons are in the process of being used to clone desired genes for which no gene products are known. Cloned genes can be introduced and potentially improve specific properties of tomato especially those controlled by single genes. Recent results suggest that, in principle, phenotypic mutants can be created for cloned and characterized genes and will prove their value in further improving the cultivated tomato.

Magnetic Field Amplification in Galaxy Clusters and its Simulation

We review the present theoretical and numerical understanding of magnetic field amplification in cosmic large-scale structure, on length scales of galaxy clusters and beyond. Structure formation drives compression and turbulence, which amplify tiny magnetic seed fields to the microGauss values that are observed in the intracluster medium. This process is intimately connected to the properties of turbulence and the microphysics of the intra-cluster medium. Additional roles are played by merger induced shocks that sweep through the intra-cluster medium and motions induced by sloshing cool cores. The accurate simulation of magnetic field amplification in clusters still poses a serious challenge for simulations of cosmological structure formation. We review the current literature on cosmological simulations that include magnetic fields and outline theoretical as well as numerical challenges.Comment: 60 pages, 19 Figure

Time-integrated luminosity recorded by the BABAR detector at the PEP-II e+e- collider

This article is the Preprint version of the final published artcile which can be accessed at the link below.We describe a measurement of the time-integrated luminosity of the data collected by the BABAR experiment at the PEP-II asymmetric-energy e+e- collider at the ϒ(4S), ϒ(3S), and ϒ(2S) resonances and in a continuum region below each resonance. We measure the time-integrated luminosity by counting e+e-→e+e- and (for the ϒ(4S) only) e+e-→μ+μ- candidate events, allowing additional photons in the final state. We use data-corrected simulation to determine the cross-sections and reconstruction efficiencies for these processes, as well as the major backgrounds. Due to the large cross-sections of e+e-→e+e- and e+e-→μ+μ-, the statistical uncertainties of the measurement are substantially smaller than the systematic uncertainties. The dominant systematic uncertainties are due to observed differences between data and simulation, as well as uncertainties on the cross-sections. For data collected on the ϒ(3S) and ϒ(2S) resonances, an additional uncertainty arises due to ϒ→e+e-X background. For data collected off the ϒ resonances, we estimate an additional uncertainty due to time dependent efficiency variations, which can affect the short off-resonance runs. The relative uncertainties on the luminosities of the on-resonance (off-resonance) samples are 0.43% (0.43%) for the ϒ(4S), 0.58% (0.72%) for the ϒ(3S), and 0.68% (0.88%) for the ϒ(2S).This work is supported by the US Department of Energy and National Science Foundation, the Natural Sciences and Engineering Research Council (Canada), the Commissariat à l’Energie Atomique and Institut National de Physique Nucléaire et de Physiquedes Particules (France), the Bundesministerium für Bildung und Forschung and Deutsche Forschungsgemeinschaft (Germany), the Istituto Nazionale di Fisica Nucleare (Italy), the Foundation for Fundamental Research on Matter (The Netherlands), the Research Council of Norway, the Ministry of Education and Science of the Russian Federation, Ministerio de Ciencia e Innovación (Spain), and the Science and Technology Facilities Council (United Kingdom). Individuals have received support from the Marie-Curie IEF program (European Union) and the A.P. Sloan Foundation (USA)