2,516 research outputs found
Experimental test of magnetic photons
A "magnetic" photon hypothesis associated with magnetic monopoles is tested
experimentally. These photons are predicted to easily penetrate metal.
Experimentally the optical transmittance T of a metal foil was less than 2 x
10^-17. The hypothesis is not supported since it predicts T = 2 x 10^-12
Time to review the role of surrogate endpoints in health policy: state of the art and the way forward
The efficacy of medicines, medical devices, and other health technologies should be proved in trials that assess final patient-relevant outcomes such as survival or morbidity. However, market access and coverage decisions are often based on surrogate endpoints, biomarkers, or intermediate endpoints, which aim to substitute and predict patient-relevant outcomes that are unavailable due to methodological, financial, or practical constraints. We provide a summary of the current use of surrogate endpoints in healthcare policy, discussing the case for and against their adoption and reviewing validation methods. We introduce a three-step framework for policy makers to handle surrogates, which involves establishing the level of evidence, assessing the strength of the association, and quantifying relations between surrogates and final outcomes. Although use of surrogates can be problematic, they can, when selected and validated appropriately, offer important opportunities for more efficient clinical trials and faster access to new health technologies that benefit patients and healthcare systems
An idealized numerical study of tropical cyclogenesis and evolution at the Equator
Tropical cyclone formation and evolution at, or near, the Equator is explored using idealized threeâdimensional model simulations, starting from a prescribed, initial, weak counterclockwise rotating vortex in an otherwise quiescent, nonrotating environment. Three simulations are carried out in which the maximum tangential wind speed (5âmâsurn:x-wiley:qj:media:qj3701:qj3701-math-0001) is specified at an initial radius of 50, 100, or 150âkm. After a period of gestation lasting between 30 and 60âhr, the vortices intensify rapidly, the evolution being similar to that for vortices away from the Equator. In particular, the larger the initial vortex size, the longer the gestation period, the larger the maximum intensity attained, and the longer the vortex lifetime. Beyond a few days, the vortices decay as the cyclonic vorticity source provided by the initial vortex is depleted and negative vorticity surrounding the vortex core is drawn inwards by the convectively driven overturning circulation. In these negative vorticity regions, the flow is inertially/centrifugally unstable. The vortex evolution during the mature and decay phases differs from that in simulations away from the Equator, where inertially unstable regions are much more limited in area. Vortex decay in the simulations appears to be related intimately to the development of inertial instability, which is accompanied by an outwardâpropagating band of deep convection. The degree to which this band of deep convection is realistic is unknown
Evaluation of the relative contribution of meteorological and oceanic forces to the drift of ice islands offshore Newfoundland
On 29 April 2015, four beacons were deployed onto an ice island in the Strait of Belle Isle to record positional data. The ice island later broke up into many fragments, four of which were tracked by the beacons. The relative influences of wind drag, current drag, Coriolis force, sea surface height gradient and sea-ice force on the drift of the tracked ice island fragments were analyzed. Using atmospheric and oceanic model outputs, the sea-ice force was calculated as the residual of the fragments' net forces and the sum of all other forces. This was compared against the force obtained through ice concentration-dependent relationships when sea ice was present. The sea-ice forces calculated from the residual approach and concentration-dependent relationships were significant only when sea ice was present at medium-high concentrations in the vicinity of the ice island fragments. The forces from ocean currents and sea surface tilt contributed the most to the drift of the
Diffusion in supersonic, turbulent, compressible flows
We investigate diffusion in supersonic, turbulent, compressible flows.
Supersonic turbulence can be characterized as network of interacting shocks. We
consider flows with different rms Mach numbers and where energy necessary to
maintain dynamical equilibrium is inserted at different spatial scales. We find
that turbulent transport exhibits super-diffusive behavior due to induced bulk
motions. In a comoving reference frame, however, diffusion behaves normal and
can be described by mixing length theory extended into the supersonic regime.Comment: 11 pages, incl. 5 figures, accepted for publication in Physical
Review E (a high-resolution version is available at
http://www.aip.de./~ralf/Publications/p21.abstract.html
Non--decoupling, triviality and the parameter
The dependence of the parameter on the mass of the Higgs scalar and
the top quark is computed non--perturbatively using the expansion in
the standard model. We find an explicit expression for the parameter
that requires the presence of a physical cutoff. This should come as no
surprise since the theory is presumably trivial. By taking this cutoff into
account, we find that the parameter can take values only within a
limited range and has finite ambiguities that are suppressed by inverse powers
of the cutoff scale, the so called ``scaling--violations". We find that large
deviations from the perturbative results are possible, but only when the cutoff
effects are also large.Comment: 16pp, Figures NOT included, harvmac, minor modifications incl.
wording, refs., UCLA/92/TEP/23,OHSTPY-HEP-T-92-00
Home-based exercise rehabilitation in addition to specialist heart failure nurse care: design, rationale and recruitment to the Birmingham Rehabilitation Uptake Maximisation study for patients with congestive heart failure (BRUM-CHF): a randomised controlled trial.
Background
Exercise has been shown to be beneficial for selected patients with heart failure, but questions remain over its effectiveness, cost-effectiveness and uptake in a real world setting. This paper describes the design, rationale and recruitment for a randomised controlled trial that will explore the effectiveness and uptake of a predominantly home-based exercise rehabilitation programme, as well as its cost-effectiveness and patient acceptability.
Methods/design
Randomised controlled trial comparing specialist heart failure nurse care plus a nurse-led predominantly home-based exercise intervention against specialist heart failure nurse care alone in a multiethnic city population, served by two NHS Trusts and one primary care setting, in the United Kingdom.
169 English speaking patients with stable heart failure, defined as systolic impairment (ejection fraction †40%). with one or more hospital admissions with clinical heart failure or New York Heart Association (NYHA) II/III within previous 24-months were recruited.
Main outcome measures at 1 year: Minnesota Living with Heart Failure Questionnaire, incremental shuttle walk test, death or admission with heart failure or myocardial infarction, health care utilisation and costs. Interviews with purposive samples of patients to gain qualitative information about acceptability and adherence to exercise, views about their treatment, self-management of their heart failure and reasons why some patients declined to participate.
The records of 1639 patients managed by specialist heart failure services were screened, of which 997 (61%) were ineligible, due to ejection fraction>40%, current NYHA IV, no admission or NYHA II or more within the previous 2 years, or serious co-morbidities preventing physical activity. 642 patients were contacted: 289 (45%) declined to participate, 183 (39%) had an exclusion criterion and 169 (26%) agreed to randomisation.
Discussion
Due to safety considerations for home-exercise less than half of patients treated by specialist heart failure services were eligible for the study. Many patients had co-morbidities preventing exercise and others had concerns about undertaking an exercise programme
Aprotinin inhibits proinflammatory activation of endothelial cells by thrombin through the protease-activated receptor 1
ObjectiveThrombin is generated in significant quantities during cardiopulmonary bypass and mediates adverse events, such as platelet aggregation and proinflammatory responses, through activation of the high-affinity thrombin receptor protease-activated receptor 1, which is expressed on platelets and endothelium. Thus antagonism of protease-activated receptor 1 might have broad therapeutic significance. Aprotinin, used clinically to reduce transfusion requirements and the inflammatory response to bypass, has been shown to inhibit protease-activated receptor 1 on platelets in vitro and in vivo. Here we have examined whether aprotinin inhibits endothelial protease-activated receptor 1 activation and resulting proinflammatory responses induced by thrombin.MethodsProtease-activated receptor 1 expression and function were examined in cultured human umbilical vein endothelial cells after treatment with α-thrombin at 0.02 to 0.15 U/mL in the presence or absence of aprotinin (200-1600 kallikrein inhibitory units/mL). Protease-activated receptor 1 activation was assessed by using an antibody, SPAN-12, which detects only the unactivated receptor, and thrombin-mediated calcium fluxes. Other thrombin-dependent inflammatory pathways investigated were phosphorylation of the p42/44 mitogen-activated protein kinase, upregulation of the early growth response 1 transcription factor, and production of the proinflammatory cytokine interleukin 6.ResultsPretreatment of cultured endothelial cells with aprotinin significantly spared protease-activated receptor 1 receptor cleavage (P < .0001) and abrogated calcium fluxes caused by thrombin. Aprotinin inhibited intracellular signaling through p42/44 mitogen-activated protein kinase (P < .05) and early growth response 1 transcription factor (P < .05), as well as interleukin 6 secretion caused by thrombin (P < .005).ConclusionsThis study demonstrates that endothelial cell activation by thrombin and downstream inflammatory responses can be inhibited by aprotinin in vitro through blockade of protease-activated receptor 1. Our results provide a new molecular basis to help explain the anti-inflammatory properties of aprotinin reported clinically
Discriminating among Earth composition models using geo-antineutrinos
It has been estimated that the entire Earth generates heat corresponding to
about 40 TW (equivalent to 10,000 nuclear power plants) which is considered to
originate mainly from the radioactive decay of elements like U, Th and K,
deposited in the crust and mantle of the Earth. Radioactivity of these elements
produce not only heat but also antineutrinos (called geo-antineutrinos) which
can be observed by terrestrial detectors. We investigate the possibility of
discriminating among Earth composition models predicting different total
radiogenic heat generation, by observing such geo-antineutrinos at Kamioka and
Gran Sasso, assuming KamLAND and Borexino (type) detectors, respectively, at
these places. By simulating the future geo-antineutrino data as well as reactor
antineutrino background contributions, we try to establish to which extent we
can discriminate among Earth composition models for given exposures (in units
of kt yr) at these two sites on our planet. We use also information on
neutrino mixing parameters coming from solar neutrino data as well as KamLAND
reactor antineutrino data, in order to estimate the number of geo-antineutrino
induced events.Comment: 24 pages, 10 figures, final version to appear in JHE
Cosmological parameter estimation using Very Small Array data out to â= 1500
We estimate cosmological parameters using data obtained by the Very Small Array (VSA) in its extended configuration, in conjunction with a variety of other cosmic microwave background (CMB) data and external priors. Within the flat Î cold dark matter (ÎCDM) model, we find that the inclusion of high-resolution data from the VSA modifies the limits on the cosmological parameters as compared to those suggested by the Wilkinson Microwave Anisotropy Probe (WMAP) alone, while still remaining compatible with their estimates. We find that Ωbh2= 0.0234+0.0012â0.0014, Ωdmh2= 0.111+0.014â0.016, h= 0.73+0.09â0.05, nS= 0.97+0.06â0.03, 1010AS= 23+7â3 and Ï= 0.14+0.14â0.07 for WMAP and VSA when no external prior is included. On extending the model to include a running spectral index of density fluctuations, we find that the inclusion of VSA data leads to a negative running at a level of more than 95 per cent confidence ( nrun=â0.069 ± 0.032 ), something that is not significantly changed by the inclusion of a stringent prior on the Hubble constant. Inclusion of prior information from the 2dF galaxy redshift survey reduces the significance of the result by constraining the value of Ωm. We discuss the veracity of this result in the context of various systematic effects and also a broken spectral index model. We also constrain the fraction of neutrinos and find that fÎœ < 0.087 at 95 per cent confidence, which corresponds to mÎœ < 0.32 eV when all neutrino masses are equal. Finally, we consider the global best fit within a general cosmological model with 12 parameters and find consistency with other analyses available in the literature. The evidence for nrun < 0 is only marginal within this model
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