Infobuttons for Genomic Medicine: Requirements and Barriers

Objectives  The study aimed to understand potential barriers to the adoption of health information technology projects that are released as free and open source software (FOSS). Methods  We conducted a survey of research consortia participants engaged in genomic medicine implementation to assess perceived institutional barriers to the adoption of three systems: ClinGen electronic health record (EHR) Toolkit, DocUBuild, and MyResults.org. The survey included eight barriers from the Consolidated Framework for Implementation Research (CFIR), with additional barriers identified from a qualitative analysis of open-ended responses. Results  We analyzed responses from 24 research consortia participants from 18 institutions. In total, 14 categories of perceived barriers were evaluated, which were consistent with other observed barriers to FOSS adoption. The most frequent perceived barriers included lack of adaptability of the system, lack of institutional priority to implement, lack of trialability, lack of advantage of alternative systems, and complexity. Conclusion  In addition to understanding potential barriers, we recommend some strategies to address them (where possible), including considerations for genomic medicine. Overall, FOSS developers need to ensure systems are easy to trial and implement and need to clearly articulate benefits of their systems, especially when alternatives exist. Institutional champions will remain a critical component to prioritizing genomic medicine projects.     

In Vivo Evaluation and Dosimetry Estimate for a High Affinity Affibody PET Tracer Targeting PD-L1

Molecular Imaging and Biology - In vivo imaging of programmed death ligand 1 (PD-L1) during immunotherapy could potentially monitor changing PD-L1 expression and PD-L1 expression heterogeneity...     

Comparison of bleeding risk scores in patients with atrial fibrillation: insights from the RE‐LY trial

Background

Oral anticoagulation is the mainstay of stroke prevention in atrial fibrillation (AF), but must be balanced against the associated bleeding risk. Several risk scores have been proposed for prediction of bleeding events in patients with AF.

Objectives

To compare the performance of contemporary clinical bleeding risk scores in 18 113 patients with AF randomized to dabigatran 110 mg, 150 mg or warfarin in the RE‐LY trial.

Methods

HAS‐BLED, ORBIT, ATRIA and HEMORR₂HAGES bleeding risk scores were calculated based on clinical information at baseline. All major bleeding events were centrally adjudicated.

Results

There were 1182 (6.5%) major bleeding events during a median follow‐up of 2.0 years. For all the four schemes, high‐risk subgroups had higher risk of major bleeding (all P  < 0.001). The ORBIT score showed the best discrimination with c‐indices of 0.66, 0.66 and 0.62, respectively, for major, life‐threatening and intracranial bleeding, which were significantly better than for the HAS‐BLED score (difference in c‐indices: 0.050, 0.053 and 0.048, respectively, all P  < 0.05). The ORBIT score also showed the best calibration compared with previous data. Significant treatment interactions between the bleeding scores and the risk of major bleeding with dabigatran 150 mg BD versus warfarin were found for the ORBIT (P  = 0.0019), ATRIA (P  < 0.001) and HEMORR₂HAGES (P  < 0.001) scores. HAS‐BLED score showed a nonsignificant trend for interaction (P  = 0.0607).

Conclusions

Amongst the current clinical bleeding risk scores, the ORBIT score demonstrated the best discrimination and calibration. All the scores demonstrated, to a variable extent, an interaction with bleeding risk associated with dabigatran or warfarin.

     

Genetic recombination in Escherichia coli: Holliday junctions made by RecA protein are resolved by fractionated cell-free extracts.

Escherichia coli RecA protein catalyzes reciprocal strand-exchange reactions between duplex DNA molecules, provided that one contains a single-stranded gap or tail, to form recombination intermediates containing Holliday junctions. Recombination reactions are thought to occur within helical RecA-nucleoprotein filaments in which DNA molecules are interwound. Structures generated in vitro by RecA protein have been used to detect an activity from fractionated E. coli extracts that resolves the intermediates into heteroduplex recombinant products. Resolution occurs by specific endonucleolytic cleavage at the Holliday junction. The products of cleavage are characteristic of patch and splice recombinants.     

Precipitin reactions between insulin,proinsulin, insulin chains and insulin antibody

Summary Insulin antibody was produced in guinea pigs and the precipitins tested by double diffusion in agarose gel. Pork, beef and monocomponent insulin produced precipitin lines. Proinsulin also produced a precipitin line with these antisera but no lines appeared with either the A-chain or the B-chain of insulin. There was good correlation between the precipitin titre and the radioimmunoassay titre.     

Progression of Device-Detected Subclinical Atrial Fibrillation and the Risk of Heart Failure

Background

Long-term continuous monitoring detects short-lasting, subclinical atrial fibrillation (SCAF) in approximately one-third of older individuals with cardiovascular conditions. The relationship between SCAF, its progression, and the development of heart failure (HF) is unclear.