Collaborative working within UK NHS secondary care and across sectors for COPD and the impact of peer review: qualitative findings from the UK National COPD Resources and Outcomes Project

The main NCROP study was funded by the Health Foundation’s Engaging with Quality Initiative (EwQI). The researchers are grateful to GlaxoSmithKline UK Ltd, Boehringer Ingelheim and AstraZeneca UK Ltd for a combined Educational Grant that has funded this research evaluation

Hospitalized poisonings after renal transplantation in the United States

BACKGROUND: The national incidence of and risk factors for hospitalized poisonings in renal transplant recipients has not been reported. METHODS: Historical cohort study of 39,628 renal transplant recipients in the United States Renal Data System between 1 July 1994 and 30 June 1998. Associations with time to hospitalizations for a primary diagnosis of poisonings (ICD-9 codes 960.x-989.x) within three years after renal transplant were assessed by Cox Regression. RESULTS: The incidence of hospitalized poisonings was 2.3 patients per 1000 person years. The most frequent causes of poisonings were immunosuppressive agents (25.3%), analgesics/antipyretics (14.1%), psychotropic agents (10.0%), and insulin/antidiabetic agents (7.1%). In Cox Regression analysis, low body mass index (BMI, <21.6 vs. >28.3 kg/m(2), adjusted hazard ratio (AHR), 3.02, 95% CI, 1.45–6.28, and allograft rejection, AHR 1.83, 95% CI, 1.15–2.89, were the only factors independently associated with hospitalized poisonings. Hospitalized poisonings were independently associated with increased mortality (AHR, 1.54, 95% CI 1.22–1.92, p = 0.002). CONCLUSIONS: Hospitalized poisonings were associated with increased mortality after renal transplantation. However, almost all reported poisonings in renal transplant recipients were due to the use of prescribed medications. Allograft rejection and low BMI were the only independent risk factors for poisonings identified in this population

Gravitational Wave Detection by Interferometry (Ground and Space)

Significant progress has been made in recent years on the development of gravitational wave detectors. Sources such as coalescing compact binary systems, neutron stars in low-mass X-ray binaries, stellar collapses and pulsars are all possible candidates for detection. The most promising design of gravitational wave detector uses test masses a long distance apart and freely suspended as pendulums on Earth or in drag-free craft in space. The main theme of this review is a discussion of the mechanical and optical principles used in the various long baseline systems in operation around the world - LIGO (USA), Virgo (Italy/France), TAMA300 and LCGT (Japan), and GEO600 (Germany/U.K.) - and in LISA, a proposed space-borne interferometer. A review of recent science runs from the current generation of ground-based detectors will be discussed, in addition to highlighting the astrophysical results gained thus far. Looking to the future, the major upgrades to LIGO (Advanced LIGO), Virgo (Advanced Virgo), LCGT and GEO600 (GEO-HF) will be completed over the coming years, which will create a network of detectors with significantly improved sensitivity required to detect gravitational waves. Beyond this, the concept and design of possible future "third generation" gravitational wave detectors, such as the Einstein Telescope (ET), will be discussed.Comment: Published in Living Reviews in Relativit

Strong and Tunable Nonlinear Optomechanical Coupling in a Low-Loss System

A major goal in optomechanics is to observe and control quantum behavior in a system consisting of a mechanical resonator coupled to an optical cavity. Work towards this goal has focused on increasing the strength of the coupling between the mechanical and optical degrees of freedom; however, the form of this coupling is crucial in determining which phenomena can be observed in such a system. Here we demonstrate that avoided crossings in the spectrum of an optical cavity containing a flexible dielectric membrane allow us to realize several different forms of the optomechanical coupling. These include cavity detunings that are (to lowest order) linear, quadratic, or quartic in the membrane's displacement, and a cavity finesse that is linear in (or independent of) the membrane's displacement. All these couplings are realized in a single device with extremely low optical loss and can be tuned over a wide range in situ; in particular, we find that the quadratic coupling can be increased three orders of magnitude beyond previous devices. As a result of these advances, the device presented here should be capable of demonstrating the quantization of the membrane's mechanical energy.Comment: 12 pages, 4 figures, 1 tabl

Radiation-pressure cooling and optomechanical instability of a micro-mirror

Recent experimental progress in table-top experiments or gravitational-wave interferometers has enlightened the unique displacement sensitivity offered by optical interferometry. As the mirrors move in response to radiation pressure, higher power operation, though crucial for further sensitivity enhancement, will however increase quantum effects of radiation pressure, or even jeopardize the stable operation of the detuned cavities proposed for next-generation interferometers. The appearance of such optomechanical instabilities is the result of the nonlinear interplay between the motion of the mirrors and the optical field dynamics. In a detuned cavity indeed, the displacements of the mirror are coupled to intensity fluctuations, which modifies the effective dynamics of the mirror. Such "optical spring" effects have already been demonstrated on the mechanical damping of an electromagnetic waveguide with a moving wall, on the resonance frequency of a specially designed flexure oscillator, and through the optomechanical instability of a silica micro-toroidal resonator. We present here an experiment where a micro-mechanical resonator is used as a mirror in a very high-finesse optical cavity and its displacements monitored with an unprecedented sensitivity. By detuning the cavity, we have observed a drastic cooling of the micro-resonator by intracavity radiation pressure, down to an effective temperature of 10 K. We have also obtained an efficient heating for an opposite detuning, up to the observation of a radiation-pressure induced instability of the resonator. Further experimental progress and cryogenic operation may lead to the experimental observation of the quantum ground state of a mechanical resonator, either by passive or active cooling techniques

Physics, Astrophysics and Cosmology with Gravitational Waves

Gravitational wave detectors are already operating at interesting sensitivity levels, and they have an upgrade path that should result in secure detections by 2014. We review the physics of gravitational waves, how they interact with detectors (bars and interferometers), and how these detectors operate. We study the most likely sources of gravitational waves and review the data analysis methods that are used to extract their signals from detector noise. Then we consider the consequences of gravitational wave detections and observations for physics, astrophysics, and cosmology.Comment: 137 pages, 16 figures, Published version <http://www.livingreviews.org/lrr-2009-2

Cooling a nanomechanical resonator with quantum back-action

Quantum mechanics demands that the act of measurement must affect the measured object. When a linear amplifier is used to continuously monitor the position of an object, the Heisenberg uncertainty relationship requires that the object be driven by force impulses, called back-action. Here we measure the back-action of a superconducting single-electron transistor (SSET) on a radiofrequency nanomechanical resonator. The conductance of the SSET, which is capacitively coupled to the resonator, provides a sensitive probe of the latter's position;back-action effects manifest themselves as an effective thermal bath, the properties of which depend sensitively on SSET bias conditions. Surprisingly, when the SSET is biased near a transport resonance, we observe cooling of the nanomechanical mode from 550mK to 300mK-- an effect that is analogous to laser cooling in atomic physics. Our measurements have implications for nanomechanical readout of quantum information devices and the limits of ultrasensitive force microscopy (such as single-nuclear-spin magnetic resonance force microscopy). Furthermore, we anticipate the use of these backaction effects to prepare ultracold and quantum states of mechanical structures, which would not be accessible with existing technology.Comment: 28 pages, 7 figures; accepted for publication in Natur

Generation and physiological roles of linear ubiquitin chains

Ubiquitination now ranks with phosphorylation as one of the best-studied post-translational modifications of proteins with broad regulatory roles across all of biology. Ubiquitination usually involves the addition of ubiquitin chains to target protein molecules, and these may be of eight different types, seven of which involve the linkage of one of the seven internal lysine (K) residues in one ubiquitin molecule to the carboxy-terminal diglycine of the next. In the eighth, the so-called linear ubiquitin chains, the linkage is between the amino-terminal amino group of methionine on a ubiquitin that is conjugated with a target protein and the carboxy-terminal carboxy group of the incoming ubiquitin. Physiological roles are well established for K48-linked chains, which are essential for signaling proteasomal degradation of proteins, and for K63-linked chains, which play a part in recruitment of DNA repair enzymes, cell signaling and endocytosis. We focus here on linear ubiquitin chains, how they are assembled, and how three different avenues of research have indicated physiological roles for linear ubiquitination in innate and adaptive immunity and suppression of inflammation

Nanomechanical motion measured with precision beyond the standard quantum limit

Nanomechanical oscillators are at the heart of ultrasensitive detectors of force, mass and motion. As these detectors progress to even better sensitivity, they will encounter measurement limits imposed by the laws of quantum mechanics. For example, if the imprecision of a measurement of an oscillator's position is pushed below the standard quantum limit (SQL), quantum mechanics demands that the motion of the oscillator be perturbed by an amount larger than the SQL. Minimizing this quantum backaction noise and nonfundamental, or technical, noise requires an information efficient measurement. Here we integrate a microwave cavity optomechanical system and a nearly noiseless amplifier into an interferometer to achieve an imprecision below the SQL. As the microwave interferometer is naturally operated at cryogenic temperatures, the thermal motion of the oscillator is minimized, yielding an excellent force detector with a sensitivity of 0.51 aN/rt(Hz). In addition, the demonstrated efficient measurement is a critical step towards entangling mechanical oscillators with other quantum systems.Comment: 5 pages, 4 figure