Self-controlled case series studies: just how rare does a rare non-recurrent outcome need to be?

The self-controlled case series method assumes that adverse outcomes arise according to a non-homogeneous Poisson process. This implies that it is applicable to independent recurrent outcomes. However, the self-controlled case series method may also be applied to unique, non-recurrent outcomes or first outcomes only, in the limit where these become rare. We investigate this rare outcome assumption when the self-controlled case series method is applied to non-recurrent outcomes. We study this requirement analytically and by simulation, and quantify what is meant by ‘rare’ in this context. In simulations we also apply the self-controlled risk interval design, a special case of the self-controlled case series design. To illustrate, we extract data on the incidence rate of some recurrent and non-recurrent outcomes within a defined study population to check whether outcomes are sufficiently rare for the rare outcome assumption to hold when applying the self-controlled case series method to first or unique outcomes. The main findings are that the relative bias should be no more than 5% when the cumulative incidence over total time observed is less than 0.1 per individual. Inclusion of age (or calendar time) effects will further reduce bias. Designs that begin observation with exposure maximise bias, whereas little or no bias will be apparent when there is no time trend in the distribution of exposures, or when exposure is central within time observed

Sertraline Versus Placebo in Patients with Major Depressive Disorder Undergoing Hemodialysis : A Randomized, Controlled Feasibility Trial

This document is the Accepted Manuscript version of the following article: Karin Friedli, et al, ‘Sertraline Versus Placebo in Patients with Major Depressive Disorder Undergoing Hemodialysis: A Randomized, Controlled Feasibility Trial’, Clinical Journal of the American Society of Nephrology, Vol. 12 (2): 280-286, February 2017. The final, published version is available online at DOI: https://doi.org/10.2215/​CJN.02120216.BACKGROUND AND OBJECTIVES: Depression is common in patients on hemodialysis, but data on the benefits and risks of antidepressants in this setting are limited. We conducted a multicenter, randomized, double-blind, placebo-controlled trial of sertraline over 6 months in patients on hemodialysis with depression to determine study feasibility, safety, and effectiveness. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients on hemodialysis at five United Kingdom renal centers completed the Beck Depression Inventory II. Those scoring ≥16 and not already on treatment for depression were invited to undergo diagnostic interview to confirm major depressive disorder. Eligible patients with major depressive disorder were randomized to receive the study medication-either sertraline or placebo. Outcomes included recruitment and dropout rates, change in the Montgomery-Asberg Depression Rating Scale and Beck Depression Inventory II, and qualitative information to guide design of a large-scale trial. RESULTS: In total, 709 patients were screened and enrolled between April of 2013 and October of 2014; 231 (32.6%) had Beck Depression Inventory II scores ≥16, and 68 (29%) of these were already receiving treatment for depression. Sixty-three underwent diagnostic interview, 37 were diagnosed with major depressive disorder, and 30 were randomized; 21 completed the trial: eight of 15 on sertraline and 13 of 15 on placebo (P=0.05). Dropouts due to adverse and serious adverse events were greater in the sertraline group. All occurred in the first 3 months. Over 6 months, depression scores improved in both groups. Beck Depression Inventory II score fell from 29.1±8.4 to 17.3±12.4 (P<0.001), and Montgomery-Asberg Depression Rating Scale score fell from 24.5±4.1 to 10.3±5.8 (P<0.001). There were no differences between sertraline and placebo groups. CONCLUSIONS: Although small, this is the largest randomized trial to date of antidepressant medication in patients on hemodialysis. Our results highlight recruitment issues. No benefit was observed, but trial size and the substantial dropout render consideration of benefit inconclusive. A definitive trial could use shorter follow-up and include depressed patients already taking antidepressants.Peer reviewedFinal Accepted Versio

Data processing model for the CDF experiment

The data processing model for the CDF experiment is described. Data processing reconstructs events from parallel data streams taken with different combinations of physics event triggers and further splits the events into datasets of specialized physics datasets. The design of the processing control system faces strict requirements on bookkeeping records, which trace the status of data files and event contents during processing and storage. The computing architecture was updated to meet the mass data flow of the Run II data collection, recently upgraded to a maximum rate of 40 MByte/sec. The data processing facility consists of a large cluster of Linux computers with data movement managed by the CDF data handling system to a multi-petaByte Enstore tape library. The latest processing cycle has achieved a stable speed of 35 MByte/sec (3 TByte/day). It can be readily scaled by increasing CPU and data-handling capacity as required.Comment: 12 pages, 10 figures, submitted to IEEE-TN

The Orbits and Dynamical Masses of the Castor System

Castor is a system of six stars in which the two brighter objects, Castor A and B, revolve around each other every $\sim$450 yr and are both short-period spectroscopic binaries. They are attended by the more distant Castor C, which is also a binary. Here we report interferometric observations with the CHARA array that spatially resolve the companions in Castor A and B for the first time. We complement these observations with new radial velocity measurements of A and B spanning 30 yr, with the Hipparcos intermediate data, and with existing astrometric observations of the visual AB pair obtained over the past three centuries. We perform a joint orbital solution to solve simultaneously for the three-dimensional orbits of Castor A and B as well as the AB orbit. We find that they are far from being coplanar: the orbit of A is nearly at right angles (92 degrees) relative to the wide orbit, and that of B is inclined about 59 degrees compared to AB. We determine the dynamical masses of the four stars in Castor A and B to a precision better than 1%. We also determine the radii of the primary stars of both subsystems from their angular diameters measured with CHARA, and use them together with stellar evolution models to infer an age for the system of 290 Myr. The new knowledge of the orbits enables us to measure the slow motion of Castor C as well, which may assist future studies of the dynamical evolution of this remarkable sextuple system.Comment: 17 pages in emulateapj format, including figures and tables. Accepted for publication in The Astrophysical Journa

CDF II production farm project

We describe the architecture and discuss our operational experience in running the off-line reconstruction farm of the CDFII experiment. The Linux PC-based farm performs a wide set of tasks,ranging from producing calibrations and primary event reconstruction to large scale ntuple production.The farm control software uses a standard Condor toolkit and the data handling part is based on SAM (Sequential Access via Metadata)software.During its lifetime,the CDFII experiment will integrate a large amount of data (several petabytes)and the data processing chain is one of the key components of the successful physics program of the experiment

Engineering coherent interactions in molecular nanomagnet dimers

Proposals for systems embodying condensed matter spin qubits cover a very wide range of length scales, from atomic defects in semiconductors all the way to micron-sized lithographically defined structures. Intermediate scale molecular components exhibit advantages of both limits: like atomic defects, large numbers of identical components can be fabricated; as for lithographically defined structures, each component can be tailored to optimise properties such as quantum coherence. Here we demonstrate what is perhaps the most potent advantage of molecular spin qubits, the scalability of quantum information processing structures using bottom-up chemical self-assembly. Using Cr7Ni spin qubit building blocks, we have constructed several families of two-qubit molecular structures with a range of linking strategies. For each family, long coherence times are preserved, and we demonstrate control over the inter-qubit quantum interactions that can be used to mediate two-qubit quantum gates