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The effects of gamma irradiation on the dielectric and piezoelectric responses of Pb[Zr0.52Ti0.48]O3 (PZT) thin film stacks were investigated for structures with conductive oxide (IrO2) and metallic (Pt) top electrodes. The samples showed, generally, degradation of various key dielectric, ferroelectric, and electromechanical responses when exposed to 2.5 Mrad (Si) 60Co gamma radiation. However, the low-field, relative dielectric permittivity, εT, remained largely unaffected by irradiation in samples with both types of electrodes. Samples with Pt top electrodes showed substantial degradation of the remanent polarization and overall piezoelectric response, as well as pinching of the polarization hysteresis curves and creation of multiple peaks in the permittivityelectric field curves post irradiation. The samples with oxide electrodes, however, were largely impervious to the same radiation dose, with less than 5% change in any of the functional characteristics. The results suggest a radiation-induced change in the defect population or defect energy in PZT with metallic top electrodes, which substantially affects motion of internal interfaces such as domain walls. Additionally, the differences observed for stacks with different electrode materials implicate the ferroelectric-electrode interface as either the predominant source of radiationinduced effects (Pt electrodes) or the site of healing for radiation-induced defects (IrO2 electrodes). [ABSTRACT FROM AUTHOR]

The Nursing Home Reform Act (NHRA) of 1987 established nursing home requirements and dually emphasized quality of care and quality of life outcomes. We researched elders' perceptions of quality of life in nursing homes using focus groups. Analysis revealed four major themes important to residents: generativity, spiritual well-being, homelike environment, and privacy. Themes were used to analyze the disparity between NHRA's goal of dual emphasis and the dominance of quality of care in the treatment of frail elders living in nursing homes. Policies and procedures must be developed that promote decisional control in everyday matters of an older person's life. [ABSTRACT FROM AUTHOR]

This gruop's improved availability has contributed to increases in patient satisfaction, new patients and productivity. [ABSTRACT FROM AUTHOR]

Loop fusion is a reordering transformation that merges multiple loops into a single loop. It can increase data locality and the granularity of parallel loops, thus improving program performance. Previous approaches to this problem have looked at these two benefits in isolation. In this work, we propose a new model which considers data locality, parallelism and register pressure together. We build a weighted directed acyclic graph in which the nodes represent program loops along with their register pressure, and the edges represent the amount of locality and parallelism present. The direction of an edge represents an execution order constraint. We then partition the graph into components such that the sum of the weights on the edges cut is minimized, subject to the constraint that the nodes in the same partition can be safely fused together, and the register pressure of the combined loop does not exceed the number of available registers. Previous work demonstrates that the general problem of finding optimal partitions is NP-hard. In restricted cases, we show that it is possible to arrive at the optimal solution. We give an algorithm for the restricted case and a heuristic for the general case. We demonstrate the effectiveness of fusion and our approach with experimental results. [ABSTRACT FROM AUTHOR]

The article reviews the web site Pew Global Attitudes Project from the Pew Charitable Trusts, available at http://pewglobal.org/.

This paper describes the evolution of the Jikes™ Research Virtual Machine project from an IBM internal research project, called Jalapeño, into an open-source project. After summarizing the original goals of the project, we discuss the motivation for releasing it as an open-source project and the activities performed to ensure the success of the project. Throughout, we highlight the unique challenges of developing and maintaining an open-source project designed specifically to support a research community. [ABSTRACT FROM AUTHOR]

Polythioesters are attracting increasing interest in applications requiring degradability or recyclability. However, few general methods exist for the synthesis of these polymers. This report presents a fast and versatile method for synthesizing polythioesters from readily available lactone feedstocks. The two-step process begins with the thionation of lactones to thionolactones, followed by the ring-opening polymerization of the thionolactones to polythioesters. Unlike previous methods that rely on harsh reagents to accomplish this transformation, we demonstrate that the mild tetrabutylammonium thioacetate is a competent initiator for polymerization. This method exhibits broad applicability, as demonstrated by the successful polymerizations of an unstrained 17-membered macrocycle and an N-substituted cyclic thionocarbamate. Furthermore, the generality of this scheme enables the synthesis of polythioesters with highly tunable properties, as demonstrated here by the synthesis of a set of polymers with glass transition temperatures spanning 180 °C. Finally, the polythioesters are efficiently depolymerized into the corresponding thiolactones.

A cyclic thioenone system capable of controlled ring-opening polymerization (ROP) is presented that leverages a reversible Michael addition-elimination (MAE) mechanism. The cyclic thioenone monomers are easy to access and modify and for the first time incorporate the dynamic reversibility of MAE with chain-growth polymerization. This strategy features mild polymerization conditions, tunable functionalities, controlled molecular weights ( M n ), and narrow dispersities. The obtained polythioenones exhibit excellent optical transparency and good mechanical properties and can be depolymerized to recover the original monomers. Density functional theory (DFT) calculations of model reactions offer insights into the role of monomer conformation in the polymerization process, as well as explaining divergent reactivity observed in seven-membered thiepane ( TP ) and eight-membered thiocane ( TC ) ring systems. Collectively, these findings demonstrate the feasibility of MAE mechanisms in ring-opening polymerization and provide important guidelines toward future monomer designs.

Gregarines are symbiotic protists that are found in a broad spectrum of invertebrates, including insects, crustaceans, and annelids. Among these the globally distributed amphipod Gammarus pulex is one of the earliest recognized hosts for aquatic gregarines and is prevalent among macroinvertebrates in freshwater environments. In this study, samples of G. pulex were collected in the Water of Leith river, Scotland, UK. Gregarines were identified using light and scanning electron microscopy as well as standard molecular techniques. We identified three septate eugregarine symbionts-Heliospora longissima, Cephaloidophora gammari, and the here newly characterized Cephaloidophora conus n. sp. (formerly Cephaloidophora sp.) associated with Gammarus pulex in the Water of Leith. Prevalences for identified gregarine species were calculated and seasonal dynamics of gregarine infections/colonization were analyzed. Prevalences were highest in autumn and spring reaching almost 50 %. While the two Cephaloidophora species showed similar colonization patterns, the prevalence of Heliospora showed an opposite trend. Identifying gregarine infection/colonization patterns is one step towards better understanding the gregarine-host relationship, as well as possible impacts of the gregarines on their hosts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Acanthamoeba keratitis (AK) is a severe infection of the cornea. Prevention and treatment are difficult due to the inefficacy of currently available compounds. The impact of many commonly used compounds for routine examinations of Acanthamoeba is unexplored but might offer insight useful in combatting AK. In this study, we demonstrate that sodium metabisulfite, a common preservation constituent of eye care solutions, was found to be active against Acanthamoeba trophozoites at concentrations lower than that commonly found in eye drops (IC 50 0.03 mg/mL). We demonstrate that sodium metabisulfite depletes thiamine from growth medium and that Acanthamoeba is a thiamine auxotroph, requiring thiamine salvage for growth. The inhibitory effects of sodium metabisulfite can be overcome by thiamine supplementation. These results are consistent with the lack of key enzymes for thiamine biosynthesis in the genome of Acanthamoeba , an area which might prove exploitable using new or existing compounds. Indeed, this study highlights sodium metabisulfite as a useful inhibitor of Acanthamoeba castellanii trophozoites in vitro and that it acts, at least in part, by limiting available thiamine.

Given recent trends in National Resident Matching Program (NRMP) data, there exists a looming deficit of practicing pathologists. As such, the Pathology Outreach Program (POP) was established in 2018 in the United States, and in 2022 in Canada, to educate high school students about pathology and laboratory medicine to help curb this projected shortage. We present survey data gathered from several educational sessions hosted at high schools in the United States (U.S.) and Canada over a 5-year period comparing participants' perceptions and awareness of pathology both before and after each session. Using this data, we wish to highlight the positive impact of POP on increasing students' awareness and appreciation for careers in pathology or laboratory medicine. This data will also highlight the additional work that must be done to further boost public knowledge of laboratory medicine's contributions to patient care. We hope this project will lay the foundation for further improvements to laboratory visibility and inspire additional outreach efforts to mitigate a future workforce shortage., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objectives: Boarding admitted patients in the emergency department is an important cause of throughput delays and safety risks in adults, though has been less studied in children. We assessed changes in boarding in a pediatric ED (PED) from 2018 to 2022 and modeled associations between boarding and select quality metrics., Methods: We performed a retrospective analysis of PED patients admitted to non-psychiatric services, broken into four periods: pre-COVID-19 (Period I, 01/2018-02/2020), early pandemic (II, 03/2020-06/2021), COVID-19 variants (III, 07/2021-06/2022), and non-COVID respiratory viruses (IV, 07/2022-12/2022). Patients were classified as critical (intensive care units (ICU)) or acute care (non-ICU inpatient services) based on their initial bed request. We compared median boarding times with Kruskal-Wallis tests. We assessed the relationship between boarding time and hospital length-of-stay (LOS) through hazard regression models, and the association between boarding time and PED return visit, readmission, and patient safety events through adjusted logistic regressions., Results: Median PED boarding time significantly increased from Period I (acute: 2.4 h; critical: 3.0 h) to Period II (acute: 3.0 h, critical: 4.0 h) to Period III (acute: 4.4 h, critical: 6.6 h) to Period IV (acute: 6.2 h; critical: 9.5 h). On survival analysis, as boarding time increased, hospital LOS increased for acute admissions and decreased for critical admissions. Increased acute care boarding time was associated with higher odds of a filed safety report., Conclusions: Since July 2021, PED boarding time increased for admitted children across acute and critical admissions. The relationship between acute care boarding and longer hospital LOS suggests a resource-inefficient, self-perpetuating cycle that demands multi-disciplinary solutions., Competing Interests: Declaration of Competing Interest The other authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: We set out to describe academic machine learning (ML) researchers' ethical considerations regarding the development of ML tools intended for use in clinical care., Materials and Methods: We conducted in-depth, semistructured interviews with a sample of ML researchers in medicine (N = 10) as part of a larger study investigating stakeholders' ethical considerations in the translation of ML tools in medicine. We used a qualitative descriptive design, applying conventional qualitative content analysis in order to allow participant perspectives to emerge directly from the data., Results: Every participant viewed their algorithm development work as holding ethical significance. While participants shared positive attitudes toward continued ML innovation, they described concerns related to data sampling and labeling (eg, limitations to mitigating bias; ensuring the validity and integrity of data), and algorithm training and testing (eg, selecting quantitative targets; assessing reproducibility). Participants perceived a need to increase interdisciplinary training across stakeholders and to envision more coordinated and embedded approaches to addressing ethics issues., Discussion and Conclusion: Participants described key areas where increased support for ethics may be needed; technical challenges affecting clinical acceptability; and standards related to scientific integrity, beneficence, and justice that may be higher in medicine compared to other industries engaged in ML innovation. Our results help shed light on the perspectives of ML researchers in medicine regarding the range of ethical issues they encounter or anticipate in their work, including areas where more attention may be needed to support the successful development and integration of medical ML tools., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: High return visit rates after hospitalization for people with sickle cell disease (SCD) have been previously established. Due to a lack of multicenter emergency department (ED) return visit rate data, the return visit rate following ED discharge for pediatric SCD pain treatment is currently unknown., Procedure: A seven-site retrospective cohort study of discharged ED visits for pain by children with SCD was conducted using the Pediatric Emergency Care Applied Research Network Registry. Visits between January 2017 and November 2021 were identified using previously validated criteria. The primary outcome was the 14-day return visit rate, with 3- and 7-day rates also calculated. Modified Poisson regression was used to analyze associations for age, sex, initial hospitalization rate, and a visit during the COVID-19 pandemic with return visit rates., Results: Of 2548 eligible ED visits, approximately 52% were patients less than 12 years old, 50% were female, and over 95% were non-Hispanic Black. The overall 14-day return visit rate was 29.1% (95% confidence interval [CI]: 27.4%-30.9%; site range 22.7%-31.7%); the 7- and 3-day return visit rates were 23.0% (95% CI: 21.3%-24.6%) and 16.7% (95% CI: 15.3%-18.2%), respectively. Younger children had slightly lower 14-day return visit rates (27.3% vs. 31.1%); there were no associations for site hospitalization rate, sex, and a visit occurring during the pandemic with 14-day returns., Conclusion: Nearly 30% of ED discharged visits after SCD pain treatment had a return visit within 14 days. Increased efforts are needed to identify causes for high ED return visit rates and ensure optimal ED and post-ED care., (© 2023 Wiley Periodicals LLC.)

Background: Among persons presenting to the emergency department with suspected acute myocardial infarction (MI), cardiac troponin (cTn) testing is commonly used to detect acute myocardial injury. Accelerated diagnostic protocols (ADPs) guide clinicians to integrate cTn results with other clinical information to decide whether to order further diagnostic testing., Objective: To determine the change in the rate and yield of stress test or coronary CT angiogram following cTn measurement in patients with chest pain presenting to the emergency department pre- and post-transition to a high-sensitivity (hs-cTn) assay in an updated ADP., Methods: Using electronic health records, we examined visits for chest pain at five emergency departments affiliated with an integrated academic health system 1-year pre- and post-hs-cTn assay transition. Outcomes included stress test or coronary imaging frequency, ADP compliance among those with additional testing, and diagnostic yield (ratio of positive tests to total tests)., Results: There were 7564 patient-visits for chest pain, including 3665 in the pre- and 3899 in the post-period. Following the updated ADP using hs-cTn, 862 (23.5 per 100 patient visits) visits led to subsequent testing versus 1085 (27.8 per 100 patient visits) in the pre-hs-cTn period, (P < 0.001). Among those who were tested, the protocol-compliant rate fell from 80.9% to 46.5% (P < 0.001), but the yield of those tests rose from 24.5% to 29.2% (P = 0.07). Among tests that were noncompliant with ADP guidance, yield was similar pre- and post-updated hs-cTn ADP implementation (pre 13.0%, post 15.4% (P = 0.43)., Conclusion: Implementation of hs-cTn supported by an updated ADP was associated with a lower rate of stress testing and coronary CT angiogram., Competing Interests: Declaration of Competing Interest C.W.B. is a paid speaker for Roche Diagnostics and has previously participated in a Roche Advisory Board and is an advisor to Lucia Health Guidelines. I.G. reports consulting fees from F-Prime Capital. B.M.S. reports research grants via Brigham and Women's Hospital from AstraZeneca, Eisai, Novartis, and Merck and consulting fees from AstraZeneca, Biogen Idec, Boehringer Ingelheim, Covance, Dr. Reddy's Laboratory, Eisai, Elsevier Practice Update Cardiology, GlaxoSmithKline, Lexicon, Merck, NovoNordisk, Sanofi, St. Jude's Medical, and equity in Health [at] Scale. J.L.J. is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals and a Director at Jana Care; has received research support from Abbott, Applied Therapeutics, Innolife, Novartis Pharmaceuticals, and Roche Diagnostics; has received consulting income from Abbott, Beckman, Bristol Myers, Boehringer-Ingelheim, Janssen, Novartis, Pfizer, Merck, Roche Diagnostics and Siemens; and participates in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Bayer, CVRx, Intercept, Janssen, and Takeda. D.A.M. reports research grants to Brigham and Women's Hospital from Abbott Laboratories, Amgen, AstraZeneca/MedImmune, Daiichi Sankyo, Eisai, GlaxoSmithKline, Medicines Company, Merck, Novartis, Roche Diagnostics, and Takeda. He has received consulting fees from Abbott Laboratories, Aralez, AstraZeneca, Bayer, InCarda, Merck, Peloton, Roche Diagnostics, and Verseon. J.T.N.'s institution has received research funding on his behalf to perform research for Alere/Biosite/Quidel, Roche/IMARC, and Thermo-Fisher., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Left without being seen (LWBS) rates are an important quality metric for pediatric emergency departments (EDs), with high-acuity LWBS children representing a patient safety risk. Since July 2021, our ED experienced a surge in LWBS after the most stringent COVID-19 quarantine restrictions ended., Objective: We assessed changes in LWBS rates and examined associations of system factors and patient characteristics with LWBS., Methods: We performed a retrospective study in a large, urban pediatric ED for all arriving patients, comparing the following three time-periods: before COVID-19 (PRE, January 2018-February 2020), during early COVID-19 (COVID, March 2020-June 2021), and after the emergence of COVID-19 variants and re-emergence of seasonal viruses (POST, July 2021-December 2021). We compared descriptive statistics of daily LWBS rates, patient demographic characteristics, and system characteristics. Negative binomial (system factors) and logistic regression (patient characteristics) models were developed to evaluate the associations between system factors and LWBS, and patient characteristics and LWBS, respectively., Results: Mean daily LWBS rates changed from 1.8% PRE to 1.4% COVID to 10.7% during POST. Rates increased across every patient demographic and triage level during POST, despite a decrease in daily ED volume compared with PRE. LWBS rates were significantly associated with patients with an Emergency Severity Index score of 2, mean ED census, and staff productivity within multiple periods. Patient characteristics associated with LWBS included lower assigned triage levels and arrival between 8 pm and 4 am., Conclusions: LWBS rates have shown a large and sustained increase since July 2021, even for high-acuity patients. We identified system factors that may provide opportunities to reduce LWBS. Further work should develop strategies to prevent LWBS in at-risk patients., Competing Interests: Declaration of Competing Interest The other authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Diagnostic tools that can rapidly identify and characterize microbes growing in blood cultures are important components of clinical microbiology practice because they help to provide timely information that can be used to optimize patient management. This publication describes the bioMérieux BIOFIRE Blood Culture Identification 2 (BCID2) Panel clinical study that was submitted to the U.S. Food & Drug Administration. Results obtained with the BIOFIRE BCID2 Panel were compared to standard-of-care (SoC) results, sequencing results, PCR results, and reference laboratory antimicrobial susceptibility testing results to evaluate the accuracy of its performance. Results for 1,093 retrospectively and prospectively collected positive blood culture samples were initially enrolled, and 1,074 samples met the study criteria and were included in the final analyses. The BIOFIRE BCID2 Panel demonstrated an overall sensitivity of 98.9% (1,712/1,731) and an overall specificity of 99.6% (33,592/33,711) for Gram-positive bacteria, Gram-negative bacteria and yeast targets which the panel is designed to detect. One hundred eighteen off-panel organisms, which the BIOFIRE BCID2 Panel is not designed to detect, were identified by SoC in 10.6% (114/1,074) of samples. The BIOFIRE BCID2 Panel also demonstrated an overall positive percent agreement (PPA) of 97.9% (325/332) and an overall negative percent agreement (NPA) of 99.9% (2,465/2,767) for antimicrobial resistance determinants which the panel is designed to detect. The presence or absence of resistance markers in Enterobacterales correlated closely with phenotypic susceptibility and resistance. We conclude that the BIOFIRE BCID2 Panel produced accurate results in this clinical trial., Competing Interests: The authors declare a conflict of interest. This info is included in the body of the manuscript: Authors received research funds paid to their institutions from BIOFIRE Diagnostics, LLC, which is now known as bioMérieux, Inc. K.H., B.K., and D.Y.L. are employed by the study sponsor. D.D.R. was employed by University Hospitals Cleveland Medical Center during this study. D.D.R. has received research support from Altona, BD, bioMérieux, Bio-Rad, Cepheid, Cleveland Diagnostics, Luminex, HelixBind, Hologic, Qiagen, Q-Linea, Specific Diagnostics, Thermo Fisher, and Vela; and D.D.R. has or has had advisory relationships with Luminex, Next Gen Diagnostics, Renascent Diagnostics, Roche, and Seegene. A.L. has received research funding from BIOFIRE, Cepheid, and Luminex. J.-M.B.-L. has served as a consultant for bioMérieux and also participated in other BIOFIRE clinical studies. A.H. has received industry sponsored grant funding from bioMérieux (BIOFIRE), and Beckman Coulter, and she has consulted for Bio-Rad. G.J.B. has given educational seminars sponsored by BIOFIRE and has also served on a BIOFIRE advisory panel. R.S. has received honoraria from bioMérieux for speaking engagements.

Background: Evidence should guide decisions in aphasia practice across the continuum of stroke care; however, evidence-practice gaps persist. This is particularly pertinent in the acute setting where 30% of people with stroke will have aphasia, and speech pathologists experience many challenges implementing evidence-based practice. This has important consequences for people with aphasia and their close others, as well as speech pathologists working in acute settings., Aims: This study protocol details how we will target practice change using a behavioural approach, with the aim of promoting the uptake of synthesized evidence in aphasia management post-stroke in the acute hospital setting., Methods & Procedures: We will conduct a mixed-methods before-and-after study following the Knowledge-to-Action (KTA) framework. Researchers, speech pathologists and people with lived experience of aphasia will collaborate to identify and prioritize practice gaps, and develop and implement changes to clinical practice based on the Theoretical Domains Framework and Behaviour Change Wheel., Discussion: This study may provide a template for acute stroke services in how to use an implementation science approach to promote the application of synthesized evidence into routine clinical practice to ensure people with aphasia receive high-quality services. Collaboration among researchers, healthcare providers, people with aphasia and their close others ensures that the identification and targeting of practice gaps are driven by theory, lived experience and the local context., What This Paper Adds: What is already known on this subject Synthesized evidence, such as clinical guidelines and consensus statements, provides the highest level of evidence to inform clinical practice, yet discrepancies between delivered care and evidence remain. This discrepancy is of note in the acute setting where clinicians report many challenges implementing the best available evidence, combined with a high proportion of people with stroke who will have aphasia (30%). There are many reasons why evidence is not put into practice, and efforts to change clinical practice need to consider these barriers when developing interventions. What this paper adds to existing knowledge This study protocol details an implementation science approach to affect clinical practice change, informed by a collaboration of key stakeholders (researchers, speech pathologists, and people with aphasia and their close others). Protocol papers that focus on bridging the gap between evidence and practice are uncommon in communication disorders; moreover, explicit prioritization of practice gaps is a critical but often overlooked aspect of promoting evidence-based practice. What are the potential or actual clinical implications of this work? This protocol provides insights into how one study site identified and prioritized evidence-practice gaps using a participatory approach. We provide insights into how clinical practice change may occur by describing how we plan to identify priority evidence-practice gaps and develop an intervention to improve the use of aphasia evidence in routine practice. This protocol aims to share an implementation science approach to service improvement that may be replicated across other services., (© 2022 Royal College of Speech and Language Therapists.)

Background: Vaso-occlusive pain crisis (VOC) is the most frequent cause for Emergency Department (ED) visits and hospital admissions for patients with sickle cell disease (SCD). Nitric oxide plays a critical role in the pathogenesis of vaso-occlusion. The amino acid, citrulline, is the main endothelial nitric oxide booster that offers the potential to ameliorate vaso-occlusion and decrease the risk of hospitalization., Objective: In this two-part study, the goal of the first part is to determine the pharmacokinetic profile of intravenous (IV) l-citrulline and optimal dose for the second part of the study, which is to determine the efficacy and tolerability of the intervention in patients with SCD., Design: A phase I/IIA open-label dose-finding study with subsequent double-blind, placebo-controlled, randomized Study of l-citrulline in children and adolescents with SCD presenting to the ED in VOC., Methods: Part 1: Subjects experiencing VOC are enrolled in an open-label, ascending dose of IV l-citrulline to identify the optimum dose with endpoints of pharmacokinetic parameters, pain scores, reduction of opioid use, quality of life, proportion admitted to the hospital for treatment of pain, readmission rates, and assessment of adverse events. Part 2 of the trial is a double-blind, placebo-controlled adaptive "pick-the-winner" design to evaluate the efficacy and tolerability of IV l-citrulline in patients with SCD while receiving standard of care therapy for VOC., Summary: This ED based sickle cell adaptive trial will determine the optimal dose for IV citrulline and whether the intervention improves outcome as a potential novel therapy for VOC in SCD., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SM and MS are co-patent holders for the indication of intravenous citrulline for sickle cell pain crisis. GK is an employee of Asklepion Pharmaceuticals., (© 2023 Published by Elsevier Inc.)

Background: Systematic evidence maps (SEMs) are gaining visibility in environmental health for their utility to serve as problem formulation tools and assist in decision-making, especially for priority setting. SEMs are now routinely prepared as part of the assessment development process for the US Environmental Protection Agency (EPA) Integrated Risk Information System (IRIS) and Provisional Peer Reviewed Toxicity Value (PPRTV) assessments. SEMs can also be prepared to explore the available literature for an individual chemical or groups of chemicals of emerging interest., Objectives: This document describes the typical methods used to produce SEMs for the IRIS and PPRTV Programs, as well as "fit for purpose" applications using a variety of examples drawn from existing analyses. It is intended to serve as an example base template that can be adapted as needed for the specific SEM. The presented methods include workflows intended to facilitate rapid production. The Populations, Exposures, Comparators and Outcomes (PECO) criteria are typically kept broad to identify mammalian animal bioassay and epidemiological studies that could be informative for human hazard identification. In addition, a variety of supplemental content is tracked, e.g., studies presenting information on in vitro model systems, non-mammalian model systems, exposure-level-only studies in humans, pharmacokinetic models, and absorption, distribution, metabolism, and excretion (ADME). The availability of New Approach Methods (NAMs) evidence is also tracked (e.g., high throughput, transcriptomic, in silico, etc.). Genotoxicity studies may be considered as PECO relevant or supplemental material, depending on the topic and context of the review. Standard systematic review practices (e.g., two independent reviewers per record) and specialized software applications are used to search and screen the literature and may include the use of machine learning software. Mammalian bioassay and epidemiological studies that meet the PECO criteria after full-text review are briefly summarized using structured web-based extraction forms with respect to study design and health system(s) assessed. Extracted data is available in interactive visual formats and can be downloaded in open access formats. Methods for conducting study evaluation are also presented which is conducted on a case-by-case basis, depending on the usage of the SEM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Nitric oxide depletion secondary to arginase induced arginine deficiency has been shown to be important in the pathophysiology of vaso-occlusion in sickle cell pain crisis. Our objective of this study was to perform a comprehensive amino acid evaluation during sickle cell pain crisis. In a total of 58 subjects (29 in steady-state sickle cell disease and 29 with sickle cell pain crisis), the amino acids related to nitric oxide pathway was significantly decreased during sickle cell pain crisis compared to steady-state sickle cell disease: arginine (p = 0.001), citrulline (p = 0.012), and ornithine (p = 0.03). In addition, the amino acids related to energy metabolism was significantly decreased during a pain crisis: asparagine (p < 0.001), serine (p = 0.002), histidine (p = 0.017), alanine (p = 0.004), tyrosine (p = 0.012), methionine (p = 0.007), cystine (p = 0.016), isoleucine (p = 0.016) and lysine (p = 0.006). The amino acid related to oxidative stress were significantly higher during a sickle cell pain crisis (glutamic acid (p < 0.001). Furthermore, multivariate analysis with partial least squares-discriminant analysis (PLS-DA) showed that deficiencies of the amino acids arginine, asparagine, citrulline, methionine and alanine were the most important related to sickle cell pain crisis., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

As the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) begins to overlap with the traditional respiratory season in the Northern Hemisphere, simultaneous testing for SARS-CoV-2 and the other common causes of respiratory infections is imperative. This has led to the development of multiplex respiratory assays that include SARS-CoV-2 as a target. One such assay is the BioFire respiratory panel 2.1 (RP2.1), which is an expansion of the original BioFire FilmArray respiratory panel 2 (RP2) to include SARS-CoV-2. In this multicenter evaluation, we assessed the performance characteristics of the BioFire RP2.1 for the detection of SARS-CoV-2. One or more targets on the panel were detected in 19.3% (101/524) of specimens tested, with SARS-CoV-2 detected in 12.6% (66/524) of specimens. Human rhinovirus/enterovirus was also detected in 32.7% (33/101) and adenovirus in 3.0% (3/101) of positive specimens, with one dual positive for both SARS-CoV-2 and adenovirus being detected. A further breakdown of pathogens by age revealed a 4-fold predominance of human rhinovirus/enterovirus in subjects 0 to 18 years of age, whereas in all other age groups, SARS-CoV-2 was clearly the predominant pathogen. Overall, SARS-CoV-2 results obtained from the BioFire RP2.1 were highly concordant with the composite result, exhibiting 98.4% (61/62) positive percent agreement (95% confidence interval [CI], 91.4 to 99.7%) and 98.9% (457/462) negative percent agreement (95% CI, 97.5 to 99.5%) with further analysis of discordant results suggesting that the concentration of SARS-CoV-2 in the specimens was near the limit of detection (LoD) for both the BioFire RP2.1 and the comparator assays. Overall, the BioFire RP2.1 exhibited excellent performance in the detection of SARS-CoV-2.

The unusual reactivity of twisted amides has long been associated with the degree of amide distortion, though classical bridged bicyclic amides offer limited methods to further modify these parameters. Here, we report that the geometry and reactivity of a single twisted amide scaffold can be significantly modulated through remote substituent effects. Guided by calculated ground state geometries, a library of twisted amide derivatives was efficiently prepared through a divergent synthetic strategy. Kinetic and mechanistic investigations of these amides in the alkylation/halide-rebound ring-opening reaction with alkyl halides show a strong positive correlation between the electron donating ability of the substituent and distortion of the amide bond, leading to rates of nucleophilic substitution spanning nearly 2 orders of magnitude. The rate limiting step of the cascade sequence is found to be dependent on the nature of the substituent, and additional studies highlight the role of solvent polarity and halide ion on reaction pathway and efficiency.

Introduction: Ketamine is a phencyclidine derivative first used in clinical practice in the 1970's. Specifically within the emergency department (ED), ketamine is utilized for a wide variety of indications including but not limited to procedural sedation, rapid sequence intubation, agitation, and pain. As providers continue to utilize ketamine more frequently and for additional indications, additional data describing its safety and efficacy in the ED setting is warranted., Objectives: To describe current trends in ketamine usage within a large tertiary-care Emergency Department., Methods: All patients receiving intravenous (IV) or intramuscular (IM) ketamine within the Emergency Department between January 1, 2019 and December 31, 2019 were eligible for study inclusion. Patients were excluded from the study if they were less than 18 years of age, pregnant, or incarcerated. Data was collected using a report of ketamine removal from the ED automatic dispensing cabinets, with administration confirmed by electronic medical record review., Results: During the study period, 170 patients received 195 doses of ketamine for the indications of agitation, procedural sedation, rapid sequence intubation, pain, sedation, seizure, status asthmaticus, and unknown. Patients were mostly male (74%) with a mean age of 45 years (range 20-97 years). The most common indications for ketamine administration were agitation and procedural sedation. For agitation, ketamine was utilized as first line therapy in 45% of patients. Seventy-seven percent of these patients did not require an additional sedative agent up to 60 min after ketamine administration. Procedural sedations were most commonly orthopedic reductions, and ketamine was given more frequently in combination with propofol than as monotherapy. Five percent of patients had an adverse event documented in the electronic medical record, with a single incidence of ketamine induced laryngospasm requiring intubation., Conclusion: This descriptive review supports the versatility, safety, and efficacy of ketamine use within a large, tertiary-care, academic emergency department. Larger, prospective studies are warranted to draw further conclusions regarding ideal ketamine utilization within the emergency department., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Refractory and super-refractory status epilepticus (RSE and SRSE) are life-threatening conditions requiring prompt initiation of appropriate treatment to avoid permanent neurological damage and reduce morbidity and mortality. RSE is defined as status epilepticus that persists despite administering at least two appropriately dosed parenteral medications, including a benzodiazepine. SRSE is status epilepticus that persists at least 24 h after adding at least one appropriately dosed continuous anesthetic (i.e., midazolam, propofol, pentobarbital, and ketamine). Other therapeutic interventions include immunotherapy, neuromodulation, ketogenic diet, or even surgical intervention in certain cases. Continuous electroencephalogram is an essential monitoring tool for diagnosis and treatment. In this review, we focus on the diagnosis and treatment of RSE and SRSE.

Objectives: Hospitals accredited by The Joint Commission (TJC) are now required to use a validated screening tool and a standardized method for assessment of suicide risk in all behavioral health patients. Our aims for this study were (1) to implement a TJC-compliant process of suicide risk screening and assessment in the pediatric emergency department (ED) and outpatient behavioral health clinic in a large tertiary care children's hospital, (2) to describe characteristics of this population related to suicide risk, and (3) to report the impact of this new process on ED length of stay (LOS)., Methods: A workflow using the Columbia Suicide Severity Rating Scale was developed and implemented. Monthly reviews of compliance with screening and assessment were conducted. Descriptive statistics were used to define the study population, and multivariable regression was used to model factors associated with high suicide risk and discharge from the ED. ED LOS of behavioral health patients was compared before and after implementation., Results: Average compliance rates for screening was 83% in the ED and 65% in the outpatient clinics. Compliance with standardized assessments in the ED went from 0% before implementation to 88% after implementation. The analysis revealed that 72% of behavioral health patients in the ED and 18% of patients in behavioral health outpatient clinics had a positive suicide risk. ED LOS did not increase. The majority of patients screening at risk was discharged from the hospital after assessment., Conclusions: A TJC-compliant process for suicide risk screening and assessment was implemented in the ED and outpatient behavioral health clinic for behavioral health patients without increasing ED LOS., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Psychiatric researchers grapple with concerns that individuals with mental illness may be less likely to appreciate risks of research participation, particularly compared to people not suffering from mental illness. Therefore, empirical studies that directly compare the perspectives of such individuals are needed. In addition, it is important to evaluate perspectives regarding varied types of research protocols, particularly as innovative psychiatric research protocols emerge. In this pilot study, respondents with a mood disorder (n = 25) as well as respondents without a mood disorder (n = 55) were recruited using Amazon's Mechanical Turk (MTurk) platform. These respondents were surveyed regarding four psychiatric research projects (i.e., experimental medication [pill form]; non-invasive magnetic brain stimulation; experimental medication [intravenous infusion]; and implantation of a device in the brain). Regardless of health status, respondents rated the four research protocols as somewhat to highly risky. The brain-device implant protocol was seen as the most risky, while the magnetic brain stimulation project was viewed as "somewhat risky". Respondents, on average and regardless of health status, rated their willingness at or below "somewhat willing." Respondents were least willing to participate in the brain-device implant protocol, whereas they were "somewhat willing" to participate in the magnetic brain stimulation protocol. Trust in medical research was negatively associated with perceived risk of research protocols. Perceived risk was negatively associated with willingness to participate, even when adjusting for potential confounders, suggesting that attunement to risk crosses diagnostic, gender, and ethnic categories, and is more salient to research decision-making than trust in medical research and dispositional optimism. The findings of this study may offer reassurance about the underlying decision-making processes of individuals considering participation in innovative neuroscience studies., Competing Interests: Declaration of competing interest Dr. Roberts reports grants from the National Institute of Mental Health, the National Institute on Aging, and the National Human Genome Research Institute. Dr. Roberts serves as Editor-In-Chief (select) of the journal Academic Medicine. All other authors declare no conflict of interest., (Copyright © 2019. Published by Elsevier Ltd.)

Purpose : To apply a human rights lens to measuring patient experience. Specifically, to determine if the perspectives of communicatively vulnerable people have been included in the patient experience research used to inform the development of the Australian Hospital Patient Experience Question Set (AHPEQS). Method : Thirty-nine qualitative studies on patient experience that informed the development of AHPEQS were critically appraised in terms of reporting on: population of interest, eligibility criteria, communicative demands of the research and communicative supports provided. Result : Eleven of 39 studies included sufficient information about the population to determine that communicatively vulnerable people would have been approached to participate. Three of these studies explicitly excluded people who were communicatively vulnerable, and four did not report on the provision of any communication supports to enable communicatively vulnerable people to participate. Conclusion : Intentional exclusion and/or a lack of communication supports restrict the rights of people who are communicatively vulnerable to express their opinions about what matters to them in hospital. Inadequate reporting of qualitative research on patient experience also makes it difficult to determine if the perspectives of people who are communicatively vulnerable have informed the development of the AHPEQS.