Safety of guidewire-based measurement of fractional flow reserve and the index of microvascular resistance using intravenous adenosine in patients with acute or recent myocardial infarction

Aims: Coronary guidewire-based diagnostic assessments with hyperemia may cause iatrogenic complications. We assessed the safety of guidewire-based measurement of coronary physiology, using intravenous adenosine, in patients with an acute coronary syndrome. Methods: We prospectively enrolled invasively managed STEMI and NSTEMI patients in two simultaneously conducted studies in 6 centers (NCT01764334; NCT02072850). All of the participants underwent a diagnostic coronary guidewire study using intravenous adenosine (140 μg/kg/min) infusion for 1–2 min. The patients were prospectively assessed for the occurrence of serious adverse events (SAEs) and symptoms and invasively measured hemodynamics were also recorded. Results: 648 patients (n = 298 STEMI patients in 1 hospital; mean time to reperfusion 253 min; n = 350 NSTEMI in 6 hospitals; median time to angiography from index chest pain episode 3 (2, 5) days) were included between March 2011 and May 2013. Two NSTEMI patients (0.03% overall) experienced a coronary dissection related to the guidewire. No guidewire dissections occurred in the STEMI patients. Chest symptoms were reported in the majority (86%) of patient's symptoms during the adenosine infusion. No serious adverse events occurred during infusion of adenosine and all of the symptoms resolved after the infusion ceased. Conclusions: In this multicenter analysis, guidewire-based measurement of FFR and IMR using intravenous adenosine was safe in patients following STEMI or NSTEMI. Self-limiting symptoms were common but not associated with serious adverse events. Finally, coronary dissection in STEMI and NSTEMI patients was noted to be a rare phenomenon

Deep forecasting of translational impact in medical research

The value of biomedical research--a $1.7 trillion annual investment--is ultimately determined by its downstream, real-world impact. Current objective predictors of impact rest on proxy, reductive metrics of dissemination, such as paper citation rates, whose relation to real-world translation remains unquantified. Here we sought to determine the comparative predictability of future real-world translation--as indexed by inclusion in patents, guidelines or policy documents--from complex models of the abstract-level content of biomedical publications versus citations and publication meta-data alone. We develop a suite of representational and discriminative mathematical models of multi-scale publication data, quantifying predictive performance out-of-sample, ahead-of-time, across major biomedical domains, using the entire corpus of biomedical research captured by Microsoft Academic Graph from 1990 to 2019, encompassing 43.3 million papers across all domains. We show that citations are only moderately predictive of translational impact as judged by inclusion in patents, guidelines, or policy documents. By contrast, high-dimensional models of publication titles, abstracts and metadata exhibit high fidelity (AUROC > 0.9), generalise across time and thematic domain, and transfer to the task of recognising papers of Nobel Laureates. The translational impact of a paper indexed by inclusion in patents, guidelines, or policy documents can be predicted--out-of-sample and ahead-of-time--with substantially higher fidelity from complex models of its abstract-level content than from models of publication meta-data or citation metrics. We argue that content-based models of impact are superior in performance to conventional, citation-based measures, and sustain a stronger evidence-based claim to the objective measurement of translational potential

FracPaQ: A MATLAB™ toolbox for the quantification of fracture patterns

The patterns of fractures in deformed rocks are rarely uniform or random. Fracture orientations, sizes, and spatial distributions often exhibit some kind of order. In detail, relationships may exist among the different fracture attributes, e.g. small fractures dominated by one orientation, larger fractures by another. These relationships are important because the mechanical (e.g. strength, anisotropy) and transport (e.g. fluids, heat) properties of rock depend on these fracture attributes and patterns. This paper describes FracPaQ, a new open source, cross-platform toolbox to quantify fracture patterns, including distributions in fracture attributes and their spatial variation. Software has been developed to quantify fracture patterns from 2-D digital images, such as thin section micrographs, geological maps, outcrop or aerial photographs or satellite images. The toolbox comprises a suite of MATLAB™ scripts based on previously published quantitative methods for the analysis of fracture attributes: orientations, lengths, intensity, density and connectivity.An estimate of permeability in 2-D is made using a parallel plate model. The software provides an objective and consistent methodology for quantifying fracture patterns and their variations in 2-D across a wide range of length scales, rock types and tectonic settings. The implemented methods presented are inherently scale independent, and a key task where applicable is analysing and integrating quantitative fracture pattern data from micro-to macro-scales. The toolbox was developed in MATLAB™ and the source code is publicly available on GitHub™ and the Mathworks™ FileExchange. The code runs on any computer with MATLAB installed, including PCs with Microsoft Windows, Apple Macs with Mac OS X, and machines running different flavours of Linux. The application, source code and sample input files are available in open repositories in the hope that other developers and researchers will optimise and extend the functionality for the benefit of the wider community

PULSE-I - Is rePetitive Upper Limb SEnsory stimulation early after stroke feasible and acceptable? A stratified single-blinded randomised controlled feasibility study

Background Reduction in sensorimotor function of the upper limb is a common and persistent impairment after stroke, and less than half of stroke survivors recover even basic function of the upper limb after a year. Previous work in stroke has shown that repetitive sensory stimulation (RSS) of the upper limb may benefit motor function. As yet, there have been no investigations of RSS in the early-acute period despite this being the time window during which the neuroplastic processes underpinning sensorimotor recovery are likely to occur. Methods A single-blinded stratified randomised controlled feasibility study was undertaken at 2 NHS acute trusts to determine the recruitment rate, intervention adherence, and safety and acceptability of an RSS intervention in the early after stroke. Participants were recruited within two weeks of index stroke. Stratified on arm function, they were randomised to receive either 45 minutes of daily RSS and usual care or usual care alone (UC) for two weeks. Changes from baseline on the primary outcome of the Action Research Arm Test (ARAT) to measurements taken by a blinded assessor were examined after completion of the intervention (2 weeks) and at 3 months from randomisation. Results Forty patients were recruited and randomised (RSS: n=23; UC: n=17) with a recruitment rate of 9.5% (40/417) of patients admitted with a stroke of which 52 (12.5%) were potentially eligible, with 10 declining to participate for various reasons. Participants found the RSS intervention acceptable and 20 adherence was good. The intervention was safe and there were no serious adverse events. Conclusions This study indicates that recruitment to a trial of RSS in the acute period after stroke is feasible. The intervention was well tolerated and appeared to provide additional benefit to usual care. In addition to a definitive trial of efficacy, further work is warranted to examine the effects of varying doses of RSS upon arm function and the mechanism by which RSS induces sensorimotor recovery in the acute period after stroke

Identification of a Cardiac Specific Protein Transduction Domain by In Vivo Biopanning Using a M13 Phage Peptide Display Library in Mice

Background: A peptide able to transduce cardiac tissue specifically, delivering cargoes to the heart, would be of significant therapeutic potential for delivery of small molecules, proteins and nucleic acids. In order to identify peptide(s) able to transduce heart tissue, biopanning was performed in cell culture and in vivo with a M13 phage peptide display library. Methods and Results: A cardiomyoblast cell line, H9C2, was incubated with a M13 phage 12 amino acid peptide display library. Internalized phage was recovered, amplified and then subjected to a total of three rounds of in vivo biopanning where infectious phage was isolated from cardiac tissue following intravenous injection. After the third round, 60% of sequenced plaques carried the peptide sequence APWHLSSQYSRT, termed cardiac targeting peptide (CTP). We demonstrate that CTP was able to transduce cardiomyocytes functionally in culture in a concentration and cell-type dependent manner. Mice injected with CTP showed significant transduction of heart tissue with minimal uptake by lung and kidney capillaries, and no uptake in liver, skeletal muscle, spleen or brain. The level of heart transduction by CTP also was greater than with a cationic transduction domain. Conclusions: Biopanning using a peptide phage display library identified a peptide able to transduce heart tissue in vivo efficiently and specifically. CTP could be used to deliver therapeutic peptides, proteins and nucleic acid specifically to the heart. © 2010 Zahid et al

Seroprevalence of SARS-CoV-2 among Blood Donors and Changes after Introduction of Public Health and Social Measures, London, UK.

We describe results of testing blood donors in London, UK, for severe acute respiratory disease coronavirus 2 (SARS-CoV-2) IgG before and after lockdown measures. Anonymized samples from donors 17-69 years of age were tested using 3 assays: Euroimmun IgG, Abbott IgG, and an immunoglobulin receptor-binding domain assay developed by Public Health England. Seroprevalence increased from 3.0% prelockdown (week 13, beginning March 23, 2020) to 10.4% during lockdown (weeks 15-16) and 12.3% postlockdown (week 18) by the Abbott assay. Estimates were 2.9% prelockdown, 9.9% during lockdown, and 13.0% postlockdown by the Euroimmun assay and 3.5% prelockdown, 11.8% during lockdown, and 14.1% postlockdown by the receptor-binding domain assay. By early May 2020, nearly 1 in 7 donors had evidence of past SARS-CoV-2 infection. Combining results from the Abbott and Euroimmun assays increased seroprevalence by 1.6%, 2.3%, and 0.6% at the 3 timepoints compared with Euroimmun alone, demonstrating the value of using multiple assays