In this trial, two new programs for delivering implantable cardioverter–defibrillator therapy resulted in fewer inappropriate interventions (shocks or antitachycardia pacing) and an unexpected ...reduction in mortality. Improved programming could benefit patients with ICDs.
The implantable cardioverter–defibrillator (ICD), either alone or in conjunction with cardiac-resynchronization therapy (CRT), is highly effective in reducing the rate of death due to ventricular tachyarrhythmia among high-risk cardiac patients.
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However, inappropriate ICD activations, which are typically caused by supraventricular tachyarrhythmias, are frequent, despite sophisticated device-related detection algorithms that are designed to differentiate supraventricular from ventricular tachyarrhythmias; such activations have potentially life-threatening side effects.
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Inappropriate device-delivered therapy, defined as therapy delivered for nonventricular tachyarrhythmias, affects 8 to 40% of patients with ICDs.
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The best method for programming ICD devices to reduce inappropriate therapy is unknown.
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We conducted a . . .
Three-dimensional flows around a full-scale cyclist mannequin were investigated experimentally to explain the large variations in aerodynamic drag that are measured as the legs are positioned around ...the
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crank cycle. It is found that the dominant mechanism affecting drag is not the small variation in frontal surface area over the pedal stroke but rather due to large changes in the flow structure over the crank cycle. This is clearly shown by a series of detailed velocity field wake surveys and skin friction flow visualizations. Two characteristic flow regimes are identified, corresponding to symmetrical low-drag and asymmetrical high-drag regimes, in which the primary feature of the wake is shown to be a large trailing streamwise vortex pair, orientated asymmetrically in the centre plane of the mannequin. These primary flow structures in the wake are the dominant mechanism driving the variation in drag throughout the pedal stroke. Topological critical points have been identified on the suction surfaces of the mannequin’s back and are discussed with velocity field measurements to elucidate the time-average flow topologies, showing the primary flow structures of the low- and high-drag flow regimes. The proposed flow topologies are then related to the measured surface pressures acting on the suction surface of the mannequin’s back. These measurements show that most of the variation in drag is due to changes in the pressure distribution acting on the lower back, where the large-scale flow structures having the greatest impact on drag develop.
Positron Emission Tomography (PET) is a widely-used imaging modality for medical research and clinical diagnosis. Imaging of the radiotracer is obtained from the detected hit positions of the two ...positron annihilation photons in a detector array. The image is degraded by backgrounds from random coincidences and in-patient scatter events which require correction. In addition to the geometric information, the two annihilation photons are predicted to be produced in a quantum-entangled state, resulting in enhanced correlations between their subsequent interaction processes. To explore this, the predicted entanglement in linear polarisation for the two photons was incorporated into a simulation and tested by comparison with experimental data from a cadmium zinc telluride (CZT) PET demonstrator apparatus. Adapted apparati also enabled correlation measurements where one of the photons had undergone a prior scatter process. We show that the entangled simulation describes the measured correlations and, through simulation of a larger preclinical PET scanner, illustrate a simple method to quantify and remove the unwanted backgrounds in PET using the quantum entanglement information alone.
In patients with reduced ejection fraction, mild heart failure, and prolonged QRS duration, CRT with a defibrillator improved survival, as compared with defibrillator therapy alone. The survival ...benefit was limited to patients with left bundle-branch block.
The Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) showed the safety and effectiveness of cardiac-resynchronization therapy (CRT) with a defibrillator (CRT-D) in patients with asymptomatic or mildly symptomatic heart failure, a reduced ejection fraction, and a prolonged QRS duration.
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The study showed that treatment with CRT-D was associated with a 34% relative reduction in the risk of nonfatal heart-failure events or death from any cause, as compared with implantable cardioverter–defibrillator (ICD) therapy alone over a median follow-up period of 2.4 years. The benefit of CRT-D in the trial was primarily driven by a significant relative reduction of . . .
A new version of the ERICA Tool (version 1.2) was released in November 2014; this constitutes the first major update of the Tool since release in 2007. The key features of the update are presented in ...this article. Of particular note are new transfer databases extracted from an international compilation of concentration ratios (CRwo-media) and the modification of ‘extrapolation’ approaches used to select transfer data in cases where information is not available. Bayesian updating approaches have been used in some cases to draw on relevant information that would otherwise have been excluded in the process of deriving CRwo-media statistics. All of these efforts have in turn led to the requirement to update Environmental Media Concentration Limits (EMCLs) used in Tier 1 assessments. Some of the significant changes with regard to EMCLs are highlighted.
•The ERICA Tool for performing environmental risk assessment has been updated.•The new version is underpinned by an internationally supported transfer database.•The Tool provides coverage for many organism groups and radioisotopes.•New calculations were required to derive environmental media concentration limits.•Modified approaches to deriving missing transfer parameters are elaborated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Climate change is altering the productivity of natural resources with far-reaching implications for those who depend on them. Resource-dependent industries and communities need the capacity to adapt ...to a range of climate risks if they are to remain viable. In some instances, the scale and nature of the likely impacts means that transformations of function or structure will be required. Transformations represent a switch to a distinct new system where a different suite of factors become important in the design and implementation of response strategies. There is a critical gap in knowledge on understanding transformational capacity and its influences. On the basis of current knowledge on adaptive capacity we propose four foundations for measuring transformational capacity: (1) how risks and uncertainty are managed, (2) the extent of skills in planning, learning and reorganizing, (3) the level of financial and psychological flexibility to undertake change and (4) the willingness to undertake change. We test the influence of place attachment and occupational identity on transformational capacity using the Australian peanut industry, which is presently assessing significant structural change in response to predicted climatic changes. Survey data from 88% of peanut farmers in Queensland show a strong negative correlation between transformational capacity and both place attachment and occupational attachment, suggesting that whilst these factors may be important positive influences on the capacity to adapt to incremental change, they act as barriers to transformational change.
The Laser Interferometer Gravitational Wave Observatory (LIGO) has been directly detecting gravitational waves from compact binary mergers since 2015. We report on the first use of squeezed vacuum ...states in the direct measurement of gravitational waves with the Advanced LIGO H1 and L1 detectors. This achievement is the culmination of decades of research to implement squeezed states in gravitational-wave detectors. During the ongoing O3 observation run, squeezed states are improving the sensitivity of the LIGO interferometers to signals above 50 Hz by up to 3 dB, thereby increasing the expected detection rate by 40% (H1) and 50% (L1).
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
We present an improved analysis of the final data set from the QUaD experiment. Using an improved technique to remove ground contamination, we double the effective sky area and hence increase the ...precision of our cosmic microwave background (CMB) power spectrum measurements by ~30% versus that previously reported. In addition, we have improved our modeling of the instrument beams and have reduced our absolute calibration uncertainty from 5% to 3.5% in temperature. The robustness of our results is confirmed through extensive jackknife tests, and by way of the agreement that we find between our two fully independent analysis pipelines. For the standard six-parameter Delta *LCDM model, the addition of QUaD data marginally improves the constraints on a number of cosmological parameters over those obtained from the WMAP experiment alone. The impact of QUaD data is significantly greater for a model extended to include either a running in the scalar spectral index, or a possible tensor component, or both. Adding both the QUaD data and the results from the Arcminute Cosmology Bolometer Array Receiver experiment, the uncertainty in the spectral index running is reduced by ~25% compared to WMAP alone, while the upper limit on the tensor-to-scalar ratio is reduced from r < 0.48 to r < 0.33 (95% c.l.). This is the strongest limit on tensors to date from the CMB alone. We also use our polarization measurements to place constraints on parity-violating interactions to the surface of last scattering, constraining the energy scale of Lorentz violating interactions to <1.5 X 10-43 GeV (68% c.l.). Finally, we place a robust upper limit on the strength of the lensing B-mode signal. Assuming a single flat band power between = 200 and = 2000, we constrain the amplitude of B-modes to be <0.57 Delta *mK2 (95% c.l.).
Akt activation supports survival of cardiomyocytes against ischemia/reperfusion, which induces cell death through opening of the mitochondrial permeability transition pore (PT-pore). Mitochondrial ...depolarization induced by treatment of cardiomyocytes with H(2)O(2) is prevented by activation of Akt with leukemia inhibitory factor (LIF). This protective effect is observed even when cardiomyocytes treated with LIF are permeabilized and mitochondrial depolarization is elicited by elevating Ca(2+). Cell fractionation studies demonstrate that LIF treatment increases both total and phosphorylated Akt in the mitochondrial fraction. Furthermore, the association of Akt with HK-II is increased by LIF. HK-II contains consensus sequences for phosphorylation by Akt and LIF treatment induces PI3K- and Akt-dependent HK-II phosphorylation. Addition of recombinant kinase-active Akt to isolated adult mouse heart mitochondria stimulates phosphorylation of HK-II and concomitantly inhibits the ability of Ca(2+) to induce cytochrome c release. This protection is prevented when HK-II is dissociated from mitochondria by incubation with glucose 6-phosphate or HK-II-dissociating peptide. Finally LIF increases HK-II association with mitochondria and dissociation of HK-II from mitochondria attenuates the protective effect of LIF on H(2)O(2)-induced mitochondrial depolarization in cardiomyocytes. We conclude that Akt has a direct effect at the level of the mitochondrion, which is mediated via phosphorylation of HK-II and results in protection of mitochondria against oxidant or Ca(2+)-stimulated PT-pore opening.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The Ultraviolet/Optical Telescope (UVOT) is one of three instruments onboard the Swift observatory. The photometric calibration has been published, and this paper follows up with details on other ...aspects of the calibration including a measurement of the point spread function with an assessment of the orbital variation and the effect on photometry. A correction for large-scale variations in sensitivity over the field of view is described, as well as a model of the coincidence loss which is used to assess the coincidence correction in extended regions. We have provided a correction for the detector distortion and measured the resulting internal astrometric accuracy of the UVOT, also giving the absolute accuracy with respect to the International Celestial Reference System. We have compiled statistics on the background count rates, and discuss the sources of the background, including instrumental scattered light. In each case, we describe any impact on UVOT measurements, whether any correction is applied in the standard pipeline data processing or whether further steps are recommended.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
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