Critical appraisal and issues regarding generalisability of comparative effectiveness studies of NOACs in atrial fibrillation and their relation to clinical trial data: a systematic review

Objective To critically appraise the published comparative effectiveness studies on non-vitamin K antagonist oral anticoagulants (NOACs) in non-valvular atrial fibrillation (NVAF). Results were compared with expectations formulated on the basis of trial results with specific attention to the patient years in each study. Methods All studies that compared the effectiveness or safety between at least two NOACs in patients with NVAF were eligible. We performed a systematic literature review in Medline and EMbase to investigate the way comparisons between NOACs were made, search date 23 April 2019. Critical appraisal of the studies was done using among others ISPOR Good Research Practices for comparative effectiveness research. Results We included 39 studies in which direct comparison between at least two NOACs were made. Almost all studies concerned patient registries, pharmacy or prescription databases and/or health insurance database studies using a cohort design. Corrections for differences in patient characteristics was applied in all but two studies. Eighteen studies matched using propensity scores (PS), 8 studies weighted patients based on the inverse probability of treatment, 1 study used PS stratification and 10 studies applied a proportional hazards model. These studies have some important limitations regarding unmeasured confounders and channelling bias, even though the larger part of the studies were well conducted technically. On the basis of trial results, expected differences are small and a naïve analysis suggests trials with between 7200 and 56 500 patients are needed to confirm the observed differences in bleedings and between 51 800 and 7 994 300 to confirm differences in efficacy. Discussion Comparisons regarding effectiveness and safety between NOACs on the basis of observational data, even after correction for baseline characteristics, may not be reliable due to unmeasured confounders, channelling bias and insufficient sample size. These limitations should be kept in mind when results of these studies are used to decide on ranking NOAC treatment options

Proposed RF Breakdown Studies at the AWA

A study of breakdown mechanism has been initiated at the Argonne Wakefield Accelerator (AWA). Breakdown may include several factors such as local field enhancement, explosive electron emission, Ohmic heating, tensile stress produced by electric field, and others. The AWA is building a dedicated facility to test various models for breakdown mechanisms and to determine the roles of different factors in the breakdown. We plan to trigger breakdown events with a high-powered laser at various wavelengths (IR to UV) to determine the role of explosive electron emission in the breakdown process. Another experimental idea follows from the recent work on a Schottky-enabled photoemission in an RF photoinjector [1] that allows us to determine in situ the field enhancement factor on a cathode surface. Monitoring the field enhancement factor before and after the breakdown can shed some light on a number of observations such as the crater formation process

The design of a liquid lithium lens for a muon collider

The last stage of ionization cooling for the muon collider requires a multistage liquid lithium lens. This system uses a large ({approximately}0.5 MA) pulsed current through liquid lithium to focus the beam while energy loss in the lithium removes momentum which is replaced by linacs. The beam optics are designed to maximize the 6 dimensional transmission from one lens to the next while minimizing emittance growth. The mechanical design of the lithium vessel is constrained by a pressure pulse due to the sudden ohmic heating, and the stress on the Be window. The authors describe beam optics, the liquid lithium pressure vessel, pumping, power supplies, as well as the overall optimization of the system

A High Statistics Search for Electron-Neutrino --> Tau-Neutrino Oscillations

We present new limits on nu_e to nu_tau and nu_e to nu_sterile oscillations by searching for electron neutrino dissappearance in the high-energy wide-band CCFR neutrino beam. Sensitivity to nu_tau appearance comes from tau decay modes in which a large fraction of the energy deposited is electromagnetic. The beam is composed primarily of muon neutrinos but this analysis uses the 2.3% electron neutrino component of the beam. Electron neutrino energies range from 30 to 600 GeV and flight lengths vary from 0.9 to 1.4 km. This limit improves the sensitivity of existing limits and obtains a lowest 90% confidence upper limit in sin**2(2*alpha) of 9.9 x 10**(-2) at delta-m**2 of 125 eV**2.Comment: submitted to Phys. Rev. D. Rapid Com

New Measurements of Nucleon Structure Functions from CCFR/NuTeV

We report on the extraction of the structure functions F_2 and Delta xF_3 = xF_3nu-xF_3nub from CCFR neutrino-Fe and antineutrino-Fe differential cross sections. The extraction is performed in a physics model independent (PMI) way. This first measurement for Delta xF_3, which is useful in testing models of heavy charm production, is higher than current theoretical predictions. Within 5% the F_2 (PMI) values measured in neutrino and muon scattering are in agreement with the predictions of Next-to-Leading-Order PDFs (using massive charm production schemes), thus resolving the long-standing discrepancy between the two measurements.Comment: 3 pages, Presented by Arie Bodek at DPF2000 Conference, Columbus, Ohio, Aug. 200

A Precise Determination of Electroweak Parameters in Neutrino-Nucleon Scattering

The NuTeV collaboration has extracted sin^2theta_W from the ratios of neutral current to charged current neutrino and anti-neutrino cross-sections. Our value, sin^2theta_W(on-shell)=0.2277+/-0.0013(stat)+/-0.0009(syst), is three standard deviations above the standard model prediction. We also present a model independent analysis of the same data.Comment: ReVTeX, 5 pp, 1fig; v2. revised SM prediction; v3. more sig. digits in Eqns 6-7, fix error in Eqn