Evaluation of person-level heterogeneity of treatment effects in published multiperson N-of-1 studies: systematic review and reanalysis.

OBJECTIVE:Individual patients with the same condition may respond differently to similar treatments. Our aim is to summarise the reporting of person-level heterogeneity of treatment effects (HTE) in multiperson N-of-1 studies and to examine the evidence for person-level HTE through reanalysis. STUDY DESIGN:Systematic review and reanalysis of multiperson N-of-1 studies. DATA SOURCES:Medline, Cochrane Controlled Trials, EMBASE, Web of Science and review of references through August 2017 for N-of-1 studies published in English. STUDY SELECTION:N-of-1 studies of pharmacological interventions with at least two subjects. DATA SYNTHESIS:Citation screening and data extractions were performed in duplicate. We performed statistical reanalysis testing for person-level HTE on all studies presenting person-level data. RESULTS:We identified 62 multiperson N-of-1 studies with at least two subjects. Statistical tests examining HTE were described in only 13 (21%), of which only two (3%) tested person-level HTE. Only 25 studies (40%) provided person-level data sufficient to reanalyse person-level HTE. Reanalysis using a fixed effect linear model identified statistically significant person-level HTE in 8 of the 13 studies (62%) reporting person-level treatment effects and in 8 of the 14 studies (57%) reporting person-level outcomes. CONCLUSIONS:Our analysis suggests that person-level HTE is common and often substantial. Reviewed studies had incomplete information on person-level treatment effects and their variation. Improved assessment and reporting of person-level treatment effects in multiperson N-of-1 studies are needed

First measurement of discrimination between helium and electron recoils in liquid xenon for low-mass dark matter searches

We report the first measurement of discrimination between low-energy helium recoils and electron recoils in liquid xenon. This result is relevant to proposed low-mass dark matter searches which seek to dissolve light target nuclei in the active volume of liquid-xenon time projection chambers. Low-energy helium recoils were produced by degrading $\alpha$ particles from $^{210}$Po with a gold foil situated on the cathode of a liquid xenon time-projection chamber. The resulting population of helium recoil events is well separated from electron recoils and is also offset from the expected position of xenon nuclear recoil events.Comment: 4 pages, 3 figure

The Effect of Patients’ Met Expectations on Consultation Outcomes. A Study with Family Medicine Residents

OBJECTIVES: To know the patients’ expectations and the fulfillment of these at family medicine consultations by resident doctors and to assess their effect on some consultation outcomes. DESIGN: A prospective cohort study. PARTICIPANTS: Patients attending family medicine consultations held by 38 resident doctors: 1,301 eligible patients, 702 filled in all questionnaires. MEASUREMENTS: Before each visit, the patients’ expectations about that particular consultation were registered. Right after the visit was over, their perception of several aspects of the communicative interaction with the doctor was measured. Later, patients were interviewed on the phone to know how their expectations had been fulfilled, how satisfied they were about the consultation, how they had followed the doctor’s suggestions, if they were going to seek further care for the same cause later, and the evolution of their clinical problem. Logistic regression was the main analysis used. RESULTS: The most common expectations were the doctor showing interest and listening (30.5%), getting some information about the diagnosis (16.3%), and sharing problems and doubts (11.1%). The rate of main expectations that were met was 76.5%. Satisfaction with the encounter was associated with the clinical evolution [odds ratio (OR) 2.23; confidence interval (CI): 1.32–3.75], and the fulfilling of the patients’ main or two main expectations was significantly related to all the measured outcomes (satisfaction OR 3.51, CI: 1.73–7.8; adherence OR 1.80, CI: 1.11–2.92; clinical evolution OR 1.54, CI: 1.01–2.35; and seeking further care later OR 0.54, CI:0.36–0.81) CONCLUSIONS: Patients prioritize expectations of a more general sort when they attend primary care consultations and residents fulfill these acceptably. The fulfillment of expectations seems to affect the studied outcomes more than other factors

Observation of activity prior to dielectric breakdown in liquid xenon with the XeBrA experiment

Maintaining the electric fields necessary for the current generation of noble liquid time projection chambers (TPCs), with drift lengths exceeding one meter, requires a large negative voltage applied to their cathode. Delivering such high voltage is associated with an elevated risk of electrostatic discharge and electroluminescence, which would be detrimental to the performance of the TPC. The Xenon Breakdown Apparatus (XeBrA) is a five-liter high-voltage test chamber built to investigate the factors contributing to high voltage breakdown in noble liquids. Area scaling and surface finish were observed to be the dominant factors affecting breakdown. In addition, small electrical activity was frequently observed during high voltage ramps prior to electrostatic discharge. The position of breakdowns was reconstructed with a system of high-speed cameras and good agreement with electric field simulations was found. Based on the results presented in this work, we recommend that the next generation of TPCs should not withstand fields larger than 20 kV/cm on the electrode surfaces.Comment: 29 pages, 13 figures; typo in the author list correcte

Psychometric precision in phenotype definition is a useful step in molecular genetic investigation of psychiatric disorders

Affective disorders are highly heritable, but few genetic risk variants have been consistently replicated in molecular genetic association studies. The common method of defining psychiatric phenotypes in molecular genetic research is either a summation of symptom scores or binary threshold score representing the risk of diagnosis. Psychometric latent variable methods can improve the precision of psychiatric phenotypes, especially when the data structure is not straightforward. Using data from the British 1946 birth cohort, we compared summary scores with psychometric modeling based on the General Health Questionnaire (GHQ-28) scale for affective symptoms in an association analysis of 27 candidate genes (249 single-nucleotide polymorphisms (SNPs)). The psychometric method utilized a bi-factor model that partitioned the phenotype variances into five orthogonal latent variable factors, in accordance with the multidimensional data structure of the GHQ-28 involving somatic, social, anxiety and depression domains. Results showed that, compared with the summation approach, the affective symptoms defined by the bi-factor psychometric model had a higher number of associated SNPs of larger effect sizes. These results suggest that psychometrically defined mental health phenotypes can reflect the dimensions of complex phenotypes better than summation scores, and therefore offer a useful approach in genetic association investigations

Search for nucleon decays with EXO-200

A search for instability of nucleons bound in $^{136}$Xe nuclei is reported with 223 kg$\cdot$yr exposure of $^{136}$Xe in the EXO-200 experiment. Lifetime limits of 3.3$\times 10^{23}$ and 1.9$\times 10^{23}$ yrs are established for nucleon decay to $^{133}$Sb and $^{133}$Te, respectively. These are the most stringent to date, exceeding the prior decay limits by a factor of 9 and 7, respectively

Deep Neural Networks for Energy and Position Reconstruction in EXO-200

We apply deep neural networks (DNN) to data from the EXO-200 experiment. In the studied cases, the DNN is able to reconstruct the relevant parameters - total energy and position - directly from raw digitized waveforms, with minimal exceptions. For the first time, the developed algorithms are evaluated on real detector calibration data. The accuracy of reconstruction either reaches or exceeds what was achieved by the conventional approaches developed by EXO-200 over the course of the experiment. Most existing DNN approaches to event reconstruction and classification in particle physics are trained on Monte Carlo simulated events. Such algorithms are inherently limited by the accuracy of the simulation. We describe a unique approach that, in an experiment such as EXO-200, allows to successfully perform certain reconstruction and analysis tasks by training the network on waveforms from experimental data, either reducing or eliminating the reliance on the Monte Carlo.Comment: Accepted version. 33 pages, 28 figure