Stunning and Right Ventricular Dysfunction Is Induced by Coronary Balloon Occlusion and Rapid Pacing in Humans: Insights From Right Ventricular Conductance Catheter Studies

BACKGROUND: We sought to determine whether right ventricular stunning could be detected after supply (during coronary balloon occlusion [BO]) and supply/demand ischemia (induced by rapid pacing [RP] during transcatheter aortic valve replacement) in humans. METHODS AND RESULTS: Ten subjects with single-vessel right coronary artery disease undergoing percutaneous coronary intervention with normal ventricular function were studied in the BO group. Ten subjects undergoing transfemoral transcatheter aortic valve replacement were studied in the RP group. In both, a conductance catheter was placed into the right ventricle, and pressure volume loops were recorded at baseline and for intervals over 15 minutes after a low-pressure BO for 1 minute or a cumulative duration of RP for up to 1 minute. Ischemia-induced diastolic dysfunction was seen 1 minute after RP (end-diastolic pressure [mm Hg]: 8.1±4.2 versus 12.1±4.1, P<0.001) and BO (end-diastolic pressure [mm Hg]: 8.1±4.0 versus 8.7±4.0, P=0.03). Impairment of systolic and diastolic function after BO remained at 15-minutes recovery (ejection fraction [%]: 55.7±9.0 versus 47.8±6.3, P<0.01; end-diastolic pressure [mm Hg]: 8.1±4.0 versus 9.2±3.9, P<0.01). Persistent diastolic dysfunction was also evident in the RP group at 15-minutes recovery (end-diastolic pressure [mm Hg]: 8.1±4.1 versus 9.9±4.4, P=0.03) and there was also sustained impairment of load-independent indices of systolic function at 15 minutes after RP (end-systolic elastance and ventriculo-arterial coupling [mm Hg/mL]: 1.25±0.31 versus 0.85±0.43, P<0.01). CONCLUSIONS: RP and right coronary artery balloon occlusion both cause ischemic right ventricular dysfunction with stunning observed later during the procedure. This may have intraoperative implications in patients without right ventricular functional reserve

Effectiveness and persistence of acitretin, ciclosporin, fumaric acid esters and methotrexate for patients with moderate-to-severe psoriasis: a cohort study from BADBIR

Background Real-world data evaluating effectiveness and persistence of systemic therapies for patients with psoriasis are limited. Objectives To determine the effectiveness and persistence of acitretin, ciclosporin, fumaric acid esters (FAEs) and methotrexate in patients with moderate-to-severe psoriasis. Methods Data from The British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), a prospective, multi-centre pharmacovigilance register of patients with moderate-to-severe psoriasis receiving biologic and/or conventional systemic therapies, were analysed. Eligible patients were ≥16 years of age receiving a first course of acitretin, ciclosporin, FAEs or methotrexate between 2007 and 2021 with ≥6 months’ follow-up. Effectiveness was defined as achieving absolute Psoriasis Area and Severity Index (aPASI) ≤ 2 reported ≥4 weeks after treatment start date until stop date. To identify baseline clinical variables associated with treatment effectiveness, we used multivariable logistic regression models estimating the adjusted odds ratio (aOR) of achieving aPASI ≤2. To describe drug persistence associated with ineffectiveness, occurrence of adverse events or other reasons of discontinuation, survival estimates with 95% confidence interval (CI) were obtained using a flexible parametric model. Results were obtained using multiple imputed data. Results In total, 5430 patients were included in the analysis: 1023 (19%) on acitretin, 1401 (26%) ciclosporin, 347 (6%) FAEs and 2659 (49%) methotrexate at registration. The proportion of patients who achieved aPASI ≤ 2 was lower with acitretin 118 (21%) compared with those on ciclosporin 233 (34%), FAEs 43 (30%) and methotrexate 372 (32%). Factors associated with ineffectiveness included prior experience to previous non-biologic systemic therapies (acitretin) [(aOR, (95% CI) 0.64 (0.42, 0.96)], male sex (methotrexate) 0.58 (0.46, 0.74), co-morbidities 0.70 (0.51, 0.97) and alcohol consumption (≤14 units per week) (ciclosporin) 0.70 (0.50, 0.98). Persistence associated with all reasons of discontinuation showed better survival for methotrexate compared with acitretin, ciclosporin and FAEs cohorts at 12 months [(Survival estimate (95% CI), 46.1 (44.0, 48.3), 31.9 (29.4, 34.7), 30.0 (27.5, 32.4) and 35.0 (29.9, 40.9)], respectively. Conclusions The real-world effectiveness and persistence of acitretin, ciclosporin, FAEs and methotrexate were generally low. Previous non-biologic systemic therapies, male sex, comorbidities and alcohol consumption were risk factors associated with treatment ineffectiveness

Critical design review: Speedfest Orange Team

A task was given to create a small, hand launchable, jet propelled hotliner to compete in the 30N class. The aircraft must not only demonstrate specific speed and efficiency characteristics, but it also must be easy and fast to assemble, reliable and desirable for purchase. The Oklahoma Sate Orange team developed such an aircraft that is marketed to be an attractive and stylish hotliner, and is able to travel at high speeds and turn fast. The Tempest, which was envisioned, designed, and built by the team is a forward swept aircraft that has a bottom mounted engine, and a inverted Y tail. The aircraft can be launched by hand or cart, and goes upwards of 200 mph. The task to fly for 4 minutes and fly pylons was completed on Speedfest day

The use of interim data and Data Monitoring Committee recommendations in randomized controlled trial reports: frequency, implications and potential sources of bias

Background: Interim analysis of accumulating trial data is important to protect participant safety during randomized controlled trials (RCTs). Data Monitoring Committees (DMCs) often undertake such analyses, but their widening role may lead to extended use of interim analysis or recommendations that could potentially bias trial results.Methods: Systematic search of eight major publications: Annals of Internal Medicine, BMJ, Circulation, CID, JAMA, JCO, Lancet and NEJM, including all randomised controlled trials ( RCTs) between June 2000 and May 2005 to identify RCTs that reported use of interim analysis, with or without DMC involvement. Recommendations made by the DMC or based on interim analysis were identified and potential sources of bias assessed. Independent double data extraction was performed on all included trials.Results: We identified 1772 RCTs, of which 470 (27%; 470/1772) reported the use of a DMC and a further 116 (7%; 116/1772) trials reported some form of interim analysis without explicit mention of a DMC. There were 28 trials ( 24 with a formal DMC), randomizing a total of 79396 participants, identified as recommending changes to the trial that may have lead to biased results. In most of these, some form of sample size re-estimation was recommended with four trials also reporting changes to trial endpoints. The review relied on information reported in the primary publications and methods papers relating to the trials, higher rates of use may have occurred but not been reported.Conclusion: The reported use of interim analysis and DMCs in clinical trials has been increasing in recent years. It is reassuring that in most cases recommendations were made in the interest of participant safety. However, in practice, recommendations that may lead to potentially biased trial results are being made

A Widespread Chromosomal Inversion Polymorphism Contributes to a Major Life-History Transition, Local Adaptation, and Reproductive Isolation

A set of experiments demonstrates the involvement of a chromosomal inversion in the adaptive transition between annual and perennial ecotypes of the yellow monkeyflower, Mimulus guttatu

Recognition justice and the evaluation of low carbon innovation projects

Evaluations of energy system innovation projects serve multiple purposes. They inform funders and stakeholders of project performance against key indicators and targets; assess value for money; document lessons learned; and provide insights for future innovation initiatives. Against the backdrop of the climate emergency, issues of equity and inclusion are being increasingly incorporated into living laboratory projects, reflecting a broader shift in energy discourse and governance towards concern for a just transition. Evaluators are key actors in assessing the justice implications of energy innovations, representing those voices and perspectives with less influence in innovation discourse and governance. However, their success in doing so depends on a range of internal and external factors. Internal factors include those frames of reference, motivations and methodological practices which vary amongst different kinds of evaluators, while external factors include the availability of data, access to users and participants, and the prioritisation of justice and inclusivity by project partners and funders. This paper draws on evidence from three energy system innovation projects in the United Kingdom to analyse the practice of evaluation as a key determinant of recognition justice. The projects, of strategic national importance, involve trials of innovative technologies and practices, including on-street electric vehicle charging, heat-pumps with load-control, and neighbourhood-scale flexibility. Each has explicit aims to address issues of energy justice, including tackling energy poverty and demonstrating the potential for demand-side practices to contribute towards grid balancing. We discuss examples of how the motivations, methods and expertise of particular evaluators influences the ways in which users are represented and issues of justice addressed, as well as practical barriers such as gathering quantitative data on electricity usage and vehicle charging data. Given the changing nature of evaluation for energy innovation, we highlight the need for critical reflexivity amongst evaluators, relating to their positionality, motivations, capabilities and limitations. Evaluation is an essential, but under-acknowledged, component of energy innovation and effective policy making. This article highlights its potential to address issues of energy justice and calls for further research and policy attention

Essentialism, word use, and concepts

The essentialist approach to word meaning has been used to undermine the fundamental assumptions of the cognitive psychology of concepts. Essentialism assumes that a word refers to a natural kind category in virtue of category members possessing essential properties. In support of this thesis, Kripke and Putnam deploy various intuitions concerning word use under circumstances in which discoveries about natural kinds are made. Although some studies employing counterfactual discoveries and related transformations appear to vindicate essentialism, we argue that the intuitions have not been investigated exhaustively. In particular, we argue that discoveries concerning the essential properties of whole categories (rather than simply of particular category members) are critical to the essentialist intuitions. The studies reported here examine such discovery contexts, and demonstrate that words and concepts are not used in accordance with essentialism. The results are, however, consistent with “representational change” views of concepts, which are broadly Fregean in their motivation. We conclude that since essentialism is not vindicated by ordinary word use, it fails to undermine the cognitive psychology of concepts

The medical history as a diagnostic technology

The medical history is a powerful diagnostic technology. However, in seeking to establish an appropriate balance between the history and the other diagnostic modalities more explicit consideration must be given to the performance characteristics of the medical history. Building on recent work undertaken in the UK and elsewhere in Europe it is now feasible to develop a library of setting-specific likelihood ratios and κ statistics for key elements of the medical history. Of particular importance to those working in primary care, statistically adjusted combinations of information from the medical history can be generated; furnishing clinicians with likelihood ratios of significant magnitudes. It is suggested that developing a more rational approach to the use of the medical history could lead to improvements in diagnostic efficiency and effectiveness, with benefits for individual patient care in addition to the overall NHS budget. When diagnosis is viewed as a processing pathway founded on a robust medical history, it becomes clear than in some situations investigations may become unnecessary and, in other circumstances, their impact will be enhanced