Patient-Reported Satisfaction and Study Drug Discontinuation: Post-Hoc Analysis of Findings from ROCKET AF.

IntroductionPatient-reported outcomes (PROs) and satisfaction endpoints are increasingly important in clinical trials and may be associated with treatment adherence. In this post hoc substudy from ROCKET AF, we examined whether patient-reported satisfaction was associated with study drug discontinuation.MethodsROCKET AF (n = 14,264) compared rivaroxaban with warfarin for prevention of stroke and systemic embolism in patients with atrial fibrillation. We analyzed treatment satisfaction scores: the Anti-Clot Treatment Scale (ACTS) and Treatment Satisfaction Questionnaire for Medication version II (TSQM II). We compared satisfaction with study drug between the two treatment arms, and examined the association between satisfaction and patient-driven study drug discontinuation (stopping study drug due to withdrawal of consent, noncompliance, or loss to follow-up).ResultsA total of 1577 (11%) patients participated in the Patient Satisfaction substudy; 1181 (8.3%) completed both the ACTS and TSQM II 4 weeks after starting study drug. Patients receiving rivaroxaban did not experience significant differences in satisfaction compared with those receiving warfarin. During a median follow-up of 1.6 years, 448 premature study drug discontinuations occurred (213 rivaroxaban group; 235 warfarin group), of which 116 (26%) were patient-driven (52 [24%] rivaroxaban group; 64 [27%] warfarin group). No significant differences were observed between satisfaction level and rates of patient-driven study drug discontinuation.ConclusionsStudy drug satisfaction did not predict rate of study drug discontinuation. No significant difference was observed between satisfaction with warfarin and rivaroxaban, as expected given the double-blind trial design. Although these results are negative, the importance of PRO data will only increase, and these analyses may inform future studies that explore the relationship between drug-satisfaction PROs, adherence, and clinical outcomes. CLINICALTRIALS.GOV: NCT00403767.FundingThe ROCKET AF trial was funded by Johnson & Johnson and Bayer

Strength can be controlled by edge dislocations in refractory high-entropy alloys

Energy efficiency is motivating the search for new high-temperature (high-T) metals. Some new body-centered-cubic (BCC) random multicomponent “high-entropy alloys (HEAs)” based on refractory elements (Cr-Mo-Nb-Ta-V-W-Hf-Ti-Zr) possess exceptional strengths at high temperatures but the physical origins of this outstanding behavior are not known. Here we show, using integrated in-situ neutron-diffraction (ND), high-resolution transmission electron microscopy (HRTEM), and recent theory, that the high strength and strength retention of a NbTaTiV alloy and a high-strength/low-density CrMoNbV alloy are attributable to edge dislocations. This finding is surprising because plastic flows in BCC elemental metals and dilute alloys are generally controlled by screw dislocations. We use the insight and theory to perform a computationally-guided search over 10(7) BCC HEAs and identify over 10(6) possible ultra-strong high-T alloy compositions for future exploration

Tactile Presentation of Network Data: Text, Matrix or Diagram?

Visualisations are commonly used to understand social, biological and other kinds of networks. Currently, we do not know how to effectively present network data to people who are blind or have low-vision (BLV). We ran a controlled study with 8 BLV participants comparing four tactile representations: organic node-link diagram, grid node-link diagram, adjacency matrix and braille list. We found that the node-link representations were preferred and more effective for path following and cluster identification while the matrix and list were better for adjacency tasks. This is broadly in line with findings for the corresponding visual representations.Comment: To appear in the ACM CHI Conference on Human Factors in Computing Systems (CHI 2020

Linguistic analysis of empathy in medical school admission essays.

Objectives: This study aimed to determine whether words used in medical school admissions essays can predict physician empathy. Methods: A computational form of linguistic analysis was used for the content analysis of medical school admissions essays. Words in medical school admissions essays were computationally grouped into 20 \u27topics\u27 which were then correlated with scores on the Jefferson Scale of Empathy. The study sample included 1,805 matriculants (between 2008-2015) at a single medical college in the North East of the United States who wrote an admissions essay and completed the Jefferson Scale of Empathy at matriculation. Results: After correcting for multiple comparisons and controlling for gender, the Jefferson Scale of Empathy scores significantly correlated with a linguistic topic (r = .074, p \u3c .05). This topic was comprised of specific words used in essays such as understanding, compassion, empathy, feeling, and trust. These words are related to themes emphasized in both theoretical writing and empirical studies on physician empathy. Conclusions: This study demonstrates that physician empathy can be predicted from medical school admission essays. The implications of this methodological capability, i.e. to quantitatively associate linguistic features or words with psychometric outcomes, bears on the future of medical education research and admissions. In particular, these findings suggest that those responsible for medical school admissions could identify more empathetic applicants based on the language of their application essays

Epithelial-to-mesenchymal transition drives a pro-metastatic Golgi compaction process through scaffolding protein PAQR11

Tumor cells gain metastatic capacity through a Golgi phosphoprotein 3-dependent (GOLPH3-dependent) Golgi membrane dispersal process that drives the budding and transport of secretory vesicles. Whether Golgi dispersal underlies the prometastatic vesicular trafficking that is associated with epithelial-to-mesenchymal transition (EMT) remains unclear. Here, we have shown that, rather than causing Golgi dispersal, EMT led to the formation of compact Golgi organelles with improved ribbon linking and cisternal stacking. Ectopic expression of the EMT-activating transcription factor ZEB1 stimulated Golgi compaction and relieved microRNA-mediated repression of the Golgi scaffolding protein PAQR11. Depletion of PAQR11 dispersed Golgi organelles and impaired anterograde vesicle transport to the plasma membrane as well as retrograde vesicle tethering to the Golgi. The N-terminal scaffolding domain of PAQR11 was associated with key regulators of Golgi compaction and vesicle transport in pull-down assays and was required to reconstitute Golgi compaction in PAQR11-deficient tumor cells. Finally, high PAQR11 levels were correlated with EMT and shorter survival in human cancers, and PAQR11 was found to be essential for tumor cell migration and metastasis in EMT-driven lung adenocarcinoma models. We conclude that EMT initiates a PAQR11-mediated Golgi compaction process that drives metastasis

X-ray transfocators: focusing devices based on compound refractive lenses

A tunable X-ray focusing and/or monochromating device, called a transfocator, is described. Examples of its implementation on ID11 at the ESRF are given