Adaptive Platform Trials in Stroke.

Clinical trials of treatments for stroke have generally utilized 2-arm, randomized designs to evaluate a single intervention against a control. Running separate clinical trials, with each addressing a single therapeutic question, is resource intensive and slows evidence generation, especially in a field with rapidly expanding treatment options and evolving practices. Platform trials-randomized clinical trials designed to evaluate multiple interventions that may enter and exit the ongoing platform based on a master protocol-accelerate the investigation of multiple therapeutic options within a single infrastructure.

The Simons Observatory: Production-Level Fabrication of the Mid- and Ultra-High-Frequency Wafers.

The Simons Observatory (SO) is a cosmic microwave background instrumentation suite in the Atacama Desert of Chile. More than 65,000 polarization-sensitive transition-edge sensor (TES) bolometers will be fielded in the frequency range spanning 27 to 280 GHz, with three separate dichroic designs. The mid-frequency 90/150 GHz and ultra-high-frequency 220/280 GHz detector arrays, fabricated at NIST, account for 39 of 49 total detector modules and implement the feedhorn-fed orthomode transducer-coupled TES bolometer architecture.

Design considerations for Factorial Adaptive Multi-Arm Multi-Stage (FAST) clinical trials.

Background: Multi-Arm, Multi-Stage (MAMS) clinical trial designs allow for multiple therapies to be compared across a spectrum of clinical trial phases. MAMS designs fall under several overarching design groups, including adaptive designs (AD) and multi-arm (MA) designs. Factorial clinical trials designs represent a combination of factorial and MAMS trial designs and can provide increased efficiency relative to fixed, traditional designs.

Machine Learning Guided AQFEP: A Fast and Efficient Absolute Free Energy Perturbation Solution for Virtual Screening.

Structure-based methods in drug discovery have become an integral part of the modern drug discovery process. The power of virtual screening lies in its ability to rapidly and cost-effectively explore enormous chemical spaces to select promising ligands for further experimental investigation. Relative free energy perturbation (RFEP) and similar methods are the gold standard for binding affinity prediction in drug discovery hit-to-lead and lead optimization phases, but have high computational cost and the requirement of a structural analog with a known activity.

Evaluating the strength and quality of evidence in American heart association/American stroke association's guidelines for aneurysmal subarachnoid hemorrhage and spontaneous intracerebral hemorrhage.

Background: Clinical practice recommendations guide healthcare decisions. This study aims to evaluate the strength and quality of evidence supporting the American Heart Association (AHA)/American Stroke Association (ASA) guidelines for aneurysmal subarachnoid hemorrhage (aSAH) and spontaneous intracerebral hemorrhage (ICH).

Methods: We reviewed the current AHA/ASA guidelines for aSAH and spontaneous ICH and compared with previous guidelines.

Improved mortality analysis in early-phase dose-ranging clinical trials for emergency medical diseases using Bayesian time-to-event models with active comparators.

Emergency medical diseases (EMDs) are the leading cause of death worldwide. A time-to-death analysis is needed to accurately identify the risks and describe the pattern of an EMD because the mortality rate can peak early and then decline. Dose-ranging Phase II clinical trials are essential for developing new therapies for EMDs.

Bayesian hierarchical profile regression for binary covariates.

Dysphagia, a common result of other medical conditions, is caused by malfunctions in swallowing physiology resulting in difficulty eating and drinking. The Modified Barium Swallow Study (MBSS), the most commonly used diagnostic tool for evaluating dysphagia, can be assessed using the Modified Barium Swallow Impairment Profile (MBSImP™). The MBSImP assessment tool consists of a hierarchical grouped data structure with multiple domains, a set of components within each domain which characterize specific swallowing physiologies, and a set of tasks scored on a discrete scale within each component.

CRISPR-Cas tools for simultaneous transcription & translation control in bacteria.

Robust control over gene translation at arbitrary mRNA targets is an outstanding challenge in microbial synthetic biology. The development of tools that can regulate translation will greatly expand our ability to precisely control genes across the genome. In Escherichia coli, most genes are contained in multi-gene operons, which are subject to polar effects where targeting one gene for repression leads to silencing of other genes in the same operon.

Subarachnoid Hemorrhage Trials: Cutting, Sliding, or Keeping mRS Scores and WFNS Grades.

Rigorous evidence generation with randomized controlled trials has lagged for aneurysmal subarachnoid hemorrhage (SAH) compared with other forms of acute stroke. Besides its lower incidence compared with other stroke subtypes, the presentation and outcome of patients with SAH also differ. This must be considered and adjusted for in designing pivotal randomized controlled trials of patients with SAH.

Usage of mineralocorticoids and isotonic crystalloids in subarachnoid hemorrhage patients in the United States.

Background: The usage rates of mineralocorticoids (fludrocortisone) to treat hyponatremia and isotonic crystalloids (saline and balanced crystalloids) to maintain intravascular volume in patients with aneurysmal subarachnoid hemorrhage (aSAH) patients across the United States are unknown.

Methods: We surveyed National Institute of Neurologic Disorders and Stroke (NINDS) StrokeNet sites in 2023, which are mostly large, tertiary, academic centers, and analyzed subarachnoid hemorrhage encounters from 2010 to 2020 in the Premier Healthcare Database that is representative of all types of hospitals and captures about 20 % of all acute inpatient care in the United States.

Results: Although mineralocorticoids are used by 70 % of the NINDS StrokeNet sites, it is used in less than 20 % of the aSAH encounters in the Premier Database.

Normal Variations in Upper Esophageal Sphincter Function During Deglutition: A Secondary Analysis of Videofluoroscopic Data.

Objective: Cricopharyngeal dysfunction is a common potential cause of pharyngoesophageal dysphagia. Contextual factors (i.e.

Subarachnoid Hemorrhage Trials: Cutting, Sliding, or Keeping mRS Scores and WFNS Grades.

Rigorous evidence generation with randomized controlled trials (RCTs) has lagged for aneurysmal subarachnoid hemorrhage (SAH) compared to other forms of acute stroke. Besides its lower incidence compared to other stroke subtypes, the presentation and outcome of SAH patients also differ. This must be considered and adjusted for in designing pivotal RCTs of SAH patients.

Usage of Mineralocorticoids and Isotonic Crystalloids in Subarachnoid Hemorrhage Patients in the United States.

Background: The usage rates of mineralocorticoids (fludrocortisone) to treat hyponatremia and isotonic crystalloids (saline and balanced crystalloids) to maintain intravascular volume in patients with aneurysmal subarachnoid hemorrhage (aSAH) patients across the United States are unknown.

Methods: We surveyed National Institute of Neurologic Disorders and Stroke (NINDS) StrokeNet sites, which are mostly large, tertiary, academic centers, and analyzed subarachnoid hemorrhage encounters in the Premier Healthcare Database that is representative of all types of hospitals and captures about 20% of all acute inpatient care in the United States.

Results: Although mineralocorticoids are used by 70% of the NINDS StrokeNet sites in aSAH patients, it is used in less than 25% of the aSAH encounters in the Premier Database.

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Purpose: Our study aims were (a) to examine laryngeal vestibular closure (LVC) temporal measures in healthy adults across tasks used in the Modified Barium Swallow Impairment Profile (MBSImP) protocol to establish normative reference values and (b) to examine influences of age, gender, and swallow task on LVC temporal measures.

Method: A retrospective analysis of 195 healthy adults (85 men, 110 women; age range: 21-89 years) who participated in a videofluoroscopic swallowing study was completed. Seven swallow tasks of standardized viscosities and volumes, as per the MBSImP protocol, were analyzed to measure time-to-LVC and LVC duration (LVCd).

Experimental characterization of a planar phase-engineered metamaterial lenslet for millimeter astronomy.

To unveil presently inscrutable details of the origins of our universe imprinted in the cosmic microwave background, future experiments in the millimeter and submillimeter range are focusing on the detection of fine features, which necessitate large and sensitive detector arrays to enable multichroic mapping of the sky. Currently, various approaches for coupling light to such detectors are under investigation, namely, coherently summed hierarchical arrays, platelet horns, and antenna-coupled planar lenslets. The last option offers increased bandwidth and a simpler fabrication while maintaining the desired optical performance.

Beta-Blockers in the Prevention and Treatment of Ischemic Heart Disease: Evidence and Clinical Practice.

Coronary artery disease (CAD) is the most prevalent cardiovascular disease characterized by atherosclerotic plaque buildup that can lead to partial or full obstruction of blood flow in the coronary arteries. Treatment for CAD involves a combination of lifestyle changes, pharmacologic therapy, and modern revascularization procedures. Beta-adrenoceptor antagonists (or beta-blockers) have been widely used for decades as a key therapy for CAD.

101 30-Day Outcomes of Resolute Onyx Stent for Symptomatic Intracranial Stenosis: A Multicenter Propensity-Score Matched Comparison With SAMMPRIS Trial.

Introduction: Symptomatic intracranial atherosclerotic disease (sICAD) is estimated to cause over 10% of strokes annually in the US alone. Previous investigations employing stenting, most notably SAMMPRIS trial, have produced unfavorable results in regards to both periprocedural complications and risk of recurrent stroke. However, newer generation balloon-mounted drug-eluting stents (BM-DES) have been hypothesized to harbor several technical advantages that may confer improvements in these critical metrics.

Examining the Effects of In Vitro Co-Culture of Equine Adipose-Derived Mesenchymal Stem Cells With Tendon Proper and Peritenon Cells.

Tendinopathies remain the leading contributor to career-ending injuries in horses because of the complexity of tendon repair. As such, cell-based therapies like injections of adipose-derived mesenchymal stem cells (ADMSCs, or MSCs) into injured tendons are becoming increasingly popular though their long-term efficacy on a molecular and wholistic level remains contentious. Thus, we co-cultured equine MSCs with intrinsic (tendon proper) and extrinsic (peritenon) tendon cell populations to examine interactions between these cells.

Association Between Birth Weight Z-Scores and Early Outcomes Following Truncus Arteriosus Repair.

In infants undergoing truncus arteriosus (TA) repair, we sought to determine associations between fetal growth restrictions as measured by birth weight Z-score and early outcomes. We utilized the Pediatric Health Information System (PHIS) database to identify infants < 90 days old who underwent TA repair from 2004 to 2019. The primary exposure variable was birth weight Z-score, calculated based on gestational age at birth, gender, and birth weight.

Staged vs Complete Repair in Tetralogy of Fallot With Pulmonary Atresia.

Background: We sought to compare outcomes for infants with tetralogy of Fallot with pulmonary atresia (TOF/PA) and confluent pulmonary arteries who underwent staged or primary complete surgical repair.

Methods: This retrospective study included infants undergoing initial surgical intervention between 0 and 60 days of age with TOF/PA without aortopulmonary collaterals from 2009 to 2018 at 20 centers. The primary outcome was days alive and out of the hospital in the first year of life (DAOH365).

Thirty-Day Outcomes of Resolute Onyx Stent for Symptomatic Intracranial Stenosis: A Multicenter Propensity Score-Matched Comparison With Stenting Versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis Trial.

Background: Symptomatic intracranial atherosclerotic disease (sICAD) is estimated to cause 10% of strokes annually in the United States. However, treatment remains a challenge with several different stenting options studied in the past with unfavorable results.

Objective: To report the 30-day stroke and/or death rate associated with intracranial stent placement for sICAD using Resolute Onyx Zotarolimus-Eluting Stent (RO-ZES) and provide a comparison with the results of Stenting Versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial.