The role of the novel D2/β2-agonist, Viozan™ (sibenadet HCl), in the treatment of symptoms of chronic obstructive pulmonary disease: results of a large-scale clinical investigation

AbstractViozan™ (sibenadet HCl, AR-C68397AA) is a novel dual D2 dopamine receptor, β2-adrenoceptor agonist, developed specifically to treat the key symptoms of chronic obstructive pulmonary disease (COPD), breathlessness, cough and sputum. The dual sensory nerve modulation and bronchodilator effects of sibenadet have been demonstrated in initial dose-ranging studies of patients with COPD and large-scale clinical evaluation has now been completed. Sibenadet efficacy was determined by assessing symptomatic changes, as defined by the novel assessment tool, the Breathlessness, Cough and Sputum Scale (BCSS©). The findings of two placebo-controlled studies are reported.These multicentre, double-blind, placebo-controlled studies recruited over 2000 patients with stable COPD, randomized to receive sibenadet (500 μg) or placebo, pressurized metered-dose inhaler (pMDI) (three times daily) for a period of 12 or 26 weeks. Diary cards were completed daily by patients throughout the study to record BCSS scores, peak expiratory flow (PEF), study drug and rescue bronchodilator usage, changes in concomitant medication and adverse events. The primary endpoints were defined as change from baseline to the final 4 weeks of the treatment period in mean BCSS total score, and forced expiratory volume in one second (FEV1) measured 1 hour after administration of the final dose of study drug and expressed as a percentage of the predicted FEV1. In addition, clinic assessments were made to determine changes in pulmonary function, health-related quality of life, perception of treatment efficacy and adverse events.Despite initial improvements in mean daily BCSS total scores in patients receiving sibenadet, the difference in the change from baseline to the final 4 weeks of the treatment period between the two treatment groups was neither statistically significant, nor considered to be of clinical importance. Although marked bronchodilator activity was seen early on with sibenadet treatment, the duration of effect diminished as the studies progressed. Sibenadet use was not associated with any safety concerns.These studies, utilizing the novel BCSS, have clearly illustrated that, despite initial symptomatic improvement with sibenadet therapy, this clinical benefit was not sustained over the course of the study

On the exciton binding energy in a quantum well

We consider a model describing the one-dimensional confinement of an exciton in a symmetrical, rectangular quantum-well structure and derive upper and lower bounds for the binding energy $E_b$ of the exciton. Based on these bounds, we study the dependence of $E_b$ on the width of the confining potential with a higher accuracy than previous reports. For an infinitely deep potential the binding energy varies as expected from $1 Ry$ at large widths to $4 Ry$ at small widths. For a finite potential, but without consideration of a mass mismatch or a dielectric mismatch, we substantiate earlier results that the binding energy approaches the value $1 Ry$ for both small and large widths, having a characteristic peak for some intermediate size of the slab. Taking the mismatch into account, this result will in general no longer be true. For the specific case of a $Ga_{1-x}Al_{x}As/GaAs/Ga_{1-x}Al_{x}As$ quantum-well structure, however, and in contrast to previous findings, the peak structure is shown to survive.Comment: 32 pages, ReVTeX, including 9 figure

Temporal shifts in prokaryotic metabolism in response to organic carbon dynamics in the mesopelagic ocean during an export event in the Southern ocean

As the major term in downward organic carbon flux attenuation, determining prokaryotic metabolism over depth in the mesopelagic ocean is crucial for constraining the efficiency of the gravitational biological carbon pump (BCP). We hypothesize that the enhancement of particulate organic carbon (POC) concentrations in the mesopelagic twilight zone during export events leads to a temporally dynamic prokaryotic metabolic response, which likely has consequences for the efficiency of the BCP. We tested this hypothesis by making repeated measurements of leucine assimilation and leucine respiration at in situ concentrations over six depths throughout the upper 500 m of the water column during the collapse of a large-scale Southern Ocean spring diatom bloom. Rates of prokaryotic leucine assimilation were used to indicate levels of prokaryotic heterotrophic production, and leucine assimilation efficiency (LAE; the proportion of leucine used for growth versus respiration) was taken as an indicator of prokaryotic growth efficiency. Thus, relative shifts in LAE are indicative of shifts in rates of prokaryotic production relative to respiration. The flux of POC through the oceans’ interior led to a dynamic prokaryotic response, characterized by a temporary elevation in mesopelagic prokaryote leucine assimilation rates, LAE and prokaryotic abundance. By the final measurement these changes had already begun to revert, despite POC concentrations still being enriched. As hypothesized, our data revealed distinctions in the phases of the mesopelagic system, likely due to an evolution in bulk prokaryotic metabolic status and the amount and composition of organic matter available. This indicates that estimating ocean carbon sequestration during export events necessitates a time course of measurements throughout the period of POC downward flux. Our findings also revealed distinctions in the ecophysiological prokaryotic responses to substrate regimes between the surface mixed layer and the mesopelagic. Specifically, in the latter in situ leucine concentrations appeared more significant in controlling prokaryote metabolism than POC concentration, and were more closely related to per cell leucine assimilation, than respiration. Whereas, in the mixed layer, the concentration of in situ leucine did not seem to drive rates of its assimilation, rather POC concentration was a strong negative driver of cell specific leucine respiration. These findings are suggestive of stronger levels of energy limitation in the deeper ocean. We surmised that ocean regions with sporadic substrate supply to the mesopelagic are likely to experience stronger energy limitation which favors prokaryotic respiration over production

The Fueling and Evolution of AGN: Internal and External Triggers

In this chapter, I review the fueling and evolution of active galactic nuclei (AGN) under the influence of internal and external triggers, namely intrinsic properties of host galaxies (morphological or Hubble type, color, presence of bars and other non-axisymmetric features, etc) and external factors such as environment and interactions. The most daunting challenge in fueling AGN is arguably the angular momentum problem as even matter located at a radius of a few hundred pc must lose more than 99.99 % of its specific angular momentum before it is fit for consumption by a BH. I review mass accretion rates, angular momentum requirements, the effectiveness of different fueling mechanisms, and the growth and mass density of black BHs at different epochs. I discuss connections between the nuclear and larger-scale properties of AGN, both locally and at intermediate redshifts, outlining some recent results from the GEMS and GOODS HST surveys.Comment: Invited Review Chapter to appear in LNP Volume on "AGN Physics on All Scales", Chapter 6, in press. 40 pages, 12 figures. Typo in Eq 5 correcte

The sensorium at work: the sensory phenomenology of the working body

The sociology of the body and the sociology of work and occupations have both neglected to some extent the study of the ‘working body’ in paid employment, particularly with regard to empirical research into the sensory aspects of working practices. This gap is perhaps surprising given how strongly the sensory dimension features in much of working life. This article is very much a first step in calling for a more phenomenological, embodied and ‘fleshy’ perspective on the body in employment, and examines some of the theoretical and conceptual resources available to researchers wishing to focus on the lived working-body experiences of the sensorium. We also consider some possible representational forms for a more evocative, phenomenologically-inspired portrayal of sensory, lived-working-body experiences, and offer suggestions for future avenues of research

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

The performance of the jet trigger for the ATLAS detector during 2011 data taking

The performance of the jet trigger for the ATLAS detector at the LHC during the 2011 data taking period is described. During 2011 the LHC provided proton–proton collisions with a centre-of-mass energy of 7 TeV and heavy ion collisions with a 2.76 TeV per nucleon–nucleon collision energy. The ATLAS trigger is a three level system designed to reduce the rate of events from the 40 MHz nominal maximum bunch crossing rate to the approximate 400 Hz which can be written to offline storage. The ATLAS jet trigger is the primary means for the online selection of events containing jets. Events are accepted by the trigger if they contain one or more jets above some transverse energy threshold. During 2011 data taking the jet trigger was fully efficient for jets with transverse energy above 25 GeV for triggers seeded randomly at Level 1. For triggers which require a jet to be identified at each of the three trigger levels, full efficiency is reached for offline jets with transverse energy above 60 GeV. Jets reconstructed in the final trigger level and corresponding to offline jets with transverse energy greater than 60 GeV, are reconstructed with a resolution in transverse energy with respect to offline jets, of better than 4 % in the central region and better than 2.5 % in the forward direction

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM