The COVID-19 pandemic began in early 2020 with major health consequences. While a need to disseminate information to the medical community and general public was paramount, concerns have been raised ...regarding the scientific rigor in published reports. We performed a systematic review to evaluate the methodological quality of currently available COVID-19 studies compared to historical controls. A total of 9895 titles and abstracts were screened and 686 COVID-19 articles were included in the final analysis. Comparative analysis of COVID-19 to historical articles reveals a shorter time to acceptance (13.0IQR, 5.0-25.0 days vs. 110.0IQR, 71.0-156.0 days in COVID-19 and control articles, respectively; p < 0.0001). Furthermore, methodological quality scores are lower in COVID-19 articles across all study designs. COVID-19 clinical studies have a shorter time to publication and have lower methodological quality scores than control studies in the same journal. These studies should be revisited with the emergence of stronger evidence.
Despite advances in our understanding of the pathophysiology and the management of pulmonary arterial hypertension (PAH), significant therapeutic gaps remain for this devastating disease. Yet, few ...innovative therapies beyond the traditional pathways of endothelial dysfunction have reached clinical trial phases in PAH. Although there are inherent limitations of the currently available models of PAH, the leaky pipeline of innovative therapies relates, in part, to flawed preclinical research methodology, including lack of rigour in trial design, incomplete invasive hemodynamic assessment, and lack of careful translational studies that replicate randomized controlled trials in humans with attention to adverse effects and benefits. Rigorous methodology should include the use of prespecified eligibility criteria, sample sizes that permit valid statistical analysis, randomization, blinded assessment of standardized outcomes, and transparent reporting of results. Better design and implementation of preclinical studies can minimize inherent flaws in the models of PAH, reduce the risk of bias, and enhance external validity and our ability to distinguish truly promising therapies form many false-positive or overstated leads. Ideally, preclinical studies should use advanced imaging, study several preclinical pulmonary hypertension models, or correlate rodent and human findings and consider the fate of the right ventricle, which is the major determinant of prognosis in human PAH. Although these principles are widely endorsed, empirical evidence suggests that such rigor is often lacking in pulmonary hypertension preclinical research. The present article discusses the pitfalls in the design of preclinical pulmonary hypertension trials and discusses opportunities to create preclinical trials with improved predictive value in guiding early-phase drug development in patients with PAH, which will need support not only from researchers, peer reviewers, and editors but also from academic institutions, funding agencies, and animal ethics authorities.
In this paper, we develop algorithms to independently draw from a family of conjugate posterior distributions over the structural parameterization when sign and zero restrictions are used to identify ...structural vector autoregressions (SVARs). We call this family of conjugate posteriors normal-generalized-normal. Our algorithms draw from a conjugate uniform-normal-inverse-Wishart posterior over the orthogonal reduced-form parameterization and transform the draws into the structural parameterization; this transformation induces a normal-generalized-normal posterior over the structural parameterization. The uniform-normal-inverse-Wishart posterior over the orthogonal reduced-form parameterization has been prominent after the work of Uhlig (2005). We use Beaudry, Nam, and Wang's (2011) work on the relevance of optimism shocks to show the dangers of using alternative approaches to implementing sign and zero restrictions to identify SVARs like the penalty function approach. In particular, we analytically show that the penalty function approach adds restrictions to the ones described in the identification scheme.
Existing approaches to solving combinatorial optimization problems on graphs suffer from the need to engineer each problem algorithmically, with practical problems recurring in many instances. The ...practical side of theoretical computer science, such as computational complexity, then needs to be addressed. Relevant developments in machine learning research on graphs are surveyed for this purpose. We organize and compare the structures involved with learning to solve combinatorial optimization problems, with a special eye on the telecommunications domain and its continuous development of live and research networks.
Structural vector autoregressions (SVARs) are widely used for policy analysis and to provide stylized facts for dynamic stochastic general equilibrium (DSGE) models; yet no workable rank conditions ...to ascertain whether an SVAR is globally identified have been established. Moreover, when nonlinear identifying restrictions are used, no efficient algorithms exist for small-sample estimation and inference. This paper makes four contributions towards filling these important gaps in the literature. First, we establish general rank conditions for global identification of both identified and exactly identified models. These rank conditions are sufficient for general identification and are necessary and sufficient for exact identification. Second, we show that these conditions can be easily implemented and that they apply to a wide class of identifying restrictions, including linear and certain nonlinear restrictions. Third, we show that the rank condition for exactly identified models amounts to a straightforward counting exercise. Fourth, we develop efficient algorithms for small-sample estimation and inference, especially for SVARs with nonlinear restrictions.
Atrial fibrillation is the most common sustained cardiac arrhythmia and is associated with considerable morbidity and mortality. Electrically isolating the pulmonary veins from the left atrium by ...catheter ablation is superior to antiarrhythmic drug therapy for maintaining sinus rhythm, but its success varies depending on multiple factors, including arrhythmic burden. Although procedural outcomes have improved over the years, further gains are limited by a seemingly zero-sum relationship between effectiveness and safety, which is largely a product of the available technologies. Current energies used to create contiguous, transmural, and durable atrial lesions can result in serious complications if they reach the esophagus or phrenic nerve, for instance—structures that can be adjacent to the atrial myocardium, often within millimeters of the energy source. Consequently, high rates of pulmonary vein-left atrium reconnections are consistently seen in clinical studies and in clinical practice as operators appropriately forgo ablation effectiveness to protect patients from harm. However, as ablative technologies evolve to circumvent this stalemate, safer, and more effective pulmonary vein isolation seems increasingly realistic. Furthermore, the innovative nature of these technologies raises the prospect of markedly improved procedural efficiency, which could increase patient comfort, reduce operator occupational injuries, and enhance the use of health resources—all of which are increasingly important considerations particularly as the demand for catheter ablation for atrial fibrillation continues to rise. We herein review 3 promising candidate ablation technologies with the potential to revolutionize the management of patients with atrial fibrillationelectroporation (pulsed-field ablation), expandable lattice-tip radiofrequency ablation/electroporation, and ultra-low temperature cryoablation.
Introduction
Human atria comprise distinct layers. One layer can bypass another, and lead to a downstream centrifugal propagation at their interface. We sought to characterize anatomical substrates, ...electrophysiological properties, and ablation outcomes of "pseudo‐focal" atrial tachycardias (ATs), defined as macroreentrant ATs mimicking focal ATs.
Methods and Results
We retrospectively analyzed left atrial ATs showing centrifugal propagation with postpacing intervals (PPIs) after entrainment pacing suggestive of a macroreentrant mechanism. A total of 22 patients had pseudo‐focal ATs consisting of 15 perimitral and 7 roof‐dependent flutters. A low‐voltage area was consistently found at the collision site and colocalized with distinct anatomical structures like the: (1) coronary sinus‐great cardiac vein bundle (27%), (2) vein of Marshall bundle (18%), (3) Bachmann bundle (27%), (4) septopulmonary bundle (18%), and (5) fossa ovalis (9%). The mean missing tachycardia cycle length (TCL) was 65 ± 31 ms (22%) on the endocardial activation map. PPI was 0 0–15 ms and 0 0–21 ms longer than TCL at the breakthrough site and the opposite site, respectively. While feasible in 21 pseudo‐focal ATs (95%), termination was better achieved by blocking the anatomical isthmus than ablating the breakthrough site 20/21 (95%) vs. 1/5 (20%); p < .001.
Conclusion
Perimitral and roof‐dependent flutters with centrifugal propagation are favored by a low‐voltage area located at well‐identified anatomical structures. Comprehensive entrainment pacing maneuvers are crucial to distinguish pseudo‐focal ATs from true focal ATs. Blocking the anatomical isthmus is a better therapeutic option than ablating the breakthrough site.
Snow cover and its melt dominate regional climate and water resources in many of the world's mountainous regions. Snowmelt timing and magnitude in mountains are controlled predominantly by absorption ...of solar radiation and the distribution of snow water equivalent (SWE), and yet both of these are very poorly known even in the best-instrumented mountain regions of the globe. Here we describe and present results from the Airborne Snow Observatory (ASO), a coupled imaging spectrometer and scanning lidar, combined with distributed snow modeling, developed for the measurement of snow spectral albedo/broadband albedo and snow depth/SWE. Snow density is simulated over the domain to convert snow depth to SWE. The result presented in this paper is the first operational application of remotely sensed snow albedo and depth/SWE to quantify the volume of water stored in the seasonal snow cover. The weekly values of SWE volume provided by the ASO program represent a critical increase in the information available to hydrologic scientists and resource managers in mountain regions.
•ASO developed to map snow spectral albedo/snow water equivalent for full watersheds.•ASO provides first mountain-basin SWE distributions at weekly to monthly repeats•ASO data are transformative for hydrologic sciences and water resource management
Within the span of a few years, watches have functionally morphed from objects that tell time to wearable minicomputers that allow real-time recording of electrocardiograms (ECGs). Considerable ...information can be deduced from these single lead tracings, and it is now not uncommon to see patients in whom diagnostic tracings of clinically relevant but elusive arrhythmias are captured using a smartwatch. Empowering individuals to record their own ECG tracings in scenarios such as palpitations, syncope, and for risk stratification of sudden death intuitively has considerable potential, but its value remains to be robustly demonstrated. The main objective of this review is to describe the information that can be obtained from smartwatch-based single-lead ECG recordings beyond simply differentiating between sinus rhythm and atrial fibrillation. We also review the strengths and limitations of using these devices in clinical settings and offer potential solutions to address the latter.
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