On March 11, 2020, the World Health Organization declared COVID-19 a global pandemic, and organizational life around the world changed dramatically overnight. In response, there has been a flurry of ...management research that seeks to understand the wide-ranging implications of this crisis. In this article, we summarize a scoping review of 69 articles that focused on management issues during the pandemic to understand how it affected individuals, teams, leaders, organizations, and society at large. We also identify and discuss the theoretical perspectives that were prominent in these investigations. We conclude by identifying directions for future inquiry with a mind toward research questions that are likely to be relevant in a postpandemic workplace and note some implications for management scholarship as well.
"Molecular histology" of the breast may be conceptualized as encompassing the normative ranges of histologic structure and marker expression in normal breast tissues in relation to a woman's age and ...life experiences. Studies of molecular histology can aid our understanding of early events in breast carcinogenesis and provide data for comparison with diseased breast tissues. Until recently, lack of epidemiologically annotated, optimally prepared normal breast tissues obtained from healthy women presented a barrier to breast cancer research. The Komen Tissue Bank at Indiana University (Indianapolis, IN) is a unique biorepository that was developed to overcome this limitation. The Bank enrolls healthy donors who provide questionnaire data, blood, and up to four breast biopsies, which are prepared as both formalin-fixed, paraffin-embedded and frozen tissues. The resource is accessible to researchers worldwide through a proposal submission, review, and approval process. As of November 2010, the Bank had collected specimens and information from 1,174 donors. In this review, we discuss the importance of studying normal breast tissues, assess the strengths and limitations of studying normal tissues obtained from different sources, and summarize the features of the Komen Tissue Bank. As research projects are completed, results will be posted on the Bank's website.
Objectives
To determine the diagnostic accuracy of a rapid host‐protein test for differentiating bacterial from viral infections in patients who presented to the emergency department (ED) or urgent ...care center (UCC).
Methods
This was a prospective multicenter, blinded study. MeMed BV (MMBV), a test based on tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL), interferon gamma‐inducible protein‐10 (IP‐10), and C‐reactive protein (CRP), was measured using a rapid measurement platform. Patients were enrolled from 9 EDs and 3 UCCs in the United States and Israel. Patients >3 months of age presenting with fever and clinical suspicion of acute infection were considered eligible. MMBV results were not provided to the treating clinician. MMBV results (bacterial/viral/equivocal) were compared against a reference standard method for classification of infection etiology determined by expert panel adjudication. Experts were blinded to MMBV results. They were provided with comprehensive patient data, including laboratory, microbiological, radiological and follow‐up.
Results
Of 563 adults and children enrolled, 476 comprised the study population (314 adults, 162 children). The predominant clinical syndrome was respiratory tract infection (60.5% upper, 11.3% lower). MMBV demonstrated sensitivity of 90.0% (95% confidence interval CI: 80.3–99.7), specificity of 92.8% (90.0%–95.5%), and negative predictive value of 98.8% (96.8%–99.6%) for bacterial infections. Only 7.2% of cases yielded equivocal MMBV scores. Area under the curve for MMBV was 0.95 (0.90–0.99).
Conclusions
MMBV had a high sensitivity and specificity relative to reference standard for differentiating bacterial from viral infections. Future implementation of MMBV for patients with suspected acute infections could potentially aid with appropriate antibiotic decision‐making.
Sepsis‐induced metabolic dysfunction contributes to organ failure and death. L‐carnitine has shown promise for septic shock, but a recent phase II study of patients with vasopressor‐dependent septic ...shock demonstrated a non‐significant reduction in mortality. We undertook a pharmacometabolomics study of these patients (n = 250) to identify metabolic profiles predictive of a 90‐day mortality benefit from L‐carnitine. The independent predictive value of each pretreatment metabolite concentration, adjusted for L‐carnitine dose, on 90‐day mortality was determined by logistic regression. A grid‐search analysis maximizing the Z‐statistic from a binomial proportion test identified specific metabolite threshold levels that discriminated L‐carnitine responsive patients. Threshold concentrations were further assessed by hazard ratio and Kaplan‐Meier estimate. Accounting for L‐carnitine treatment and dose, 11 1H‐NMR metabolites and 12 acylcarnitines were independent predictors of 90‐day mortality. Based on the grid‐search analysis numerous acylcarnitines and valine were identified as candidate metabolites of drug response. Acetylcarnitine emerged as highly viable for the prediction of an L‐carnitine mortality benefit due to its abundance and biological relevance. Using its most statistically significant threshold concentration, patients with pretreatment acetylcarnitine greater than or equal to 35 µM were less likely to die at 90 days if treated with L‐carnitine (18 g) versus placebo (p = 0.01 by log rank test). Metabolomics also identified independent predictors of 90‐day sepsis mortality. Our proof‐of‐concept approach shows how pharmacometabolomics could be useful for tackling the heterogeneity of sepsis and informing clinical trial design. In addition, metabolomics can help understand mechanisms of sepsis heterogeneity and variable drug response, because sepsis induces alterations in numerous metabolite concentrations.
Non-invasive tests (NITs) offer a practical solution for advanced fibrosis identification in non-alcoholic fatty liver disease (NAFLD). Despite increasing implementation, their use is not ...standardised, which can lead to inconsistent interpretation and risk stratification. We aimed to assess the types of NITs and the corresponding cut-offs used in a range of healthcare settings.
A survey was distributed to a convenience sample of liver health experts who participated in a global NAFLD consensus statement. Respondents provided information on the NITs used in their clinic with the corresponding cut-offs and those used in established care pathways in their areas.
There were 35 respondents from 24 countries, 89% of whom practised in tertiary level settings. A total of 14 different NITs were used, and each respondent reported using at least one (median = 3). Of the respondents, 80% reported using FIB-4 and liver stiffness by vibration-controlled transient elastography (Fibroscan®), followed by the NAFLD fibrosis score (49%). For FIB-4, 71% of respondents used a low cut-off of <1.3 (range <1.0 to <1.45) and 21% reported using age-specific cut-offs. For Fibroscan®, 21% of respondents used a single liver stiffness cut-off: 8 kPa in 50%, while the rest used 7.2 kPa, 7.8 kPa and 8.7 kPa. Among the 63% of respondents who used lower and upper liver stiffness cut-offs, there were variations in both values (<5 to <10 kPa and >7.5 to >20 kPa, respectively).
The cut-offs used for the same NITs for NAFLD risk stratification vary between clinicians. As cut-offs impact test performance, these findings underscore the heterogeneity in risk-assessment and support the importance of establishing consistent guidelines on the standardised use of NITs in NAFLD management.
Owing to the high prevalence of non-alcoholic fatty liver disease (NAFLD) in the general population it is important to identify those who have more advanced stages of liver fibrosis, so that they can be properly treated. Non-invasive tests (NITs) provide a practical way to assess fibrosis risk in patients. However, we found that the cut-offs used for the same NITs vary between clinicians. As cut-offs impact test performance, these findings highlight the importance of establishing consistent guidelines on the standardised use of NITs to optimise clinical management of NAFLD.
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•NITs are a valuable tool to identify patients with NAFLD and fibrosis who require specialist care.•Lower and upper cut-offs have important implications for test performance and clinical decision making.•Among 35 survey respondents, 14 different NITs were used, of which FIB-4 and transient elastography were the most common.•This study is the first to describe the considerable heterogeneity in the NIT cut-offs used by clinicians in different settings.•Guidelines to standardise NIT cut-offs are needed to improve consistency in risk-stratification in NAFLD.
Abstract Purpose As the role of extracorporeal life support (ECLS) continues to evolve in the adult and pediatric populations, smaller studies and case reports have described successful use of ECLS ...in specific groups of pediatric trauma patients. To further define the role of ECLS in pediatric trauma, we examined indications and outcomes for use of ECLS in injured children using a large national database. Methods All trauma patients ≤ 18 years old were identified from the 2007 to 2011 National Trauma Data Bank. We collected patient demographics, mechanism of injury, injury severity, use of ECLS, and survival to discharge. Children undergoing ECLS were compared to those who did not undergo ECLS, using a 3:1 propensity matched analysis to compare outcomes between ECLS and non-ECLS patients with similar injury patterns. Results Of 589,895 pediatric trauma patients identified, 36 patients underwent ECLS. Within the ECLS cohort, 21/36 (58%) survived, and 10/36 (28%) were discharged directly home. Most ECLS patients were between 15 and 18 years 20/36 (56%). Mechanisms of injury (MOI) resulting in ECLS use included: motor vehicle collision (MVC) 16/36 (44%), gunshot wound (GSW) 6/36 (17%), burns 6/36 (17%), and drowning/suffocation (D/S) 5/36 (14%). Among the ECLS cohort, survival varied by MOI from 75% in D/S to 56% in MVC and 33% in GSW and was 55% in patients with significant head injuries. Using propensity analysis for matched injury patterns, survival for ECLS and non-ECLS patients was similar (58% vs. 65%, p = 0.61). Conclusions In the largest study to date of ECLS support in pediatric trauma patients, we found encouraging survival rates to discharge, comparable to patients not undergoing ECLS with similar injuries. These results support further use and focused research of ECLS in pediatric trauma, including drowning, burn, and MVC victims and those with significant head injuries. Level of evidence Level III; treatment study.
Determining the spatial organization and morphological characteristics of molecularly defined cell types is a major bottleneck for characterizing the architecture underpinning brain function. We ...developed Expansion-Assisted Iterative Fluorescence In Situ Hybridization (EASI-FISH) to survey gene expression in brain tissue, as well as a turnkey computational pipeline to rapidly process large EASI-FISH image datasets. EASI-FISH was optimized for thick brain sections (300 μm) to facilitate reconstruction of spatio-molecular domains that generalize across brains. Using the EASI-FISH pipeline, we investigated the spatial distribution of dozens of molecularly defined cell types in the lateral hypothalamic area (LHA), a brain region with poorly defined anatomical organization. Mapping cell types in the LHA revealed nine spatially and molecularly defined subregions. EASI-FISH also facilitates iterative reanalysis of scRNA-seq datasets to determine marker-genes that further dissociated spatial and morphological heterogeneity. The EASI-FISH pipeline democratizes mapping molecularly defined cell types, enabling discoveries about brain organization.
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•EASI-FISH enables robust gene expression profiling in thick brain slices•A turnkey analysis pipeline for facile analysis of large EASI-FISH image datasets•EASI-FISH reveals molecularly defined subregions of the lateral hypothalamus•Cell type subdivisions corresponding to morphology, functional tuning, and location
Multiplexed FISH in thick tissue sections with deep-learning based 3D segmentation enables facile characterization of spatial organization for different cell types in defined brain regions.
Wetland hydrologic connections to downstream waters influence stream water quality. However, no systematic approach for characterizing this connectivity exists. Here using physical principles, we ...categorized conterminous US freshwater wetlands into four hydrologic connectivity classes based on stream contact and flowpath depth to the nearest stream: riparian, non-riparian shallow, non-riparian mid-depth and non-riparian deep. These classes were heterogeneously distributed over the conterminous United States; for example, riparian dominated the south-eastern and Gulf coasts, while non-riparian deep dominated the Upper Midwest and High Plains. Analysis of a national stream dataset indicated acidification and organic matter brownification increased with connectivity. Eutrophication and sedimentation decreased with wetland area but did not respond to connectivity. This classification advances our mechanistic understanding of wetland influences on water quality nationally and could be applied globally.
Following the adoption of new nomenclature for steatotic liver disease, we aimed to build consensus on the use of International Classification of Diseases codes and recommendations for future ...research and advocacy.
Through a two-stage Delphi process, a core group (n = 20) reviewed draft statements and recommendations (n = 6), indicating levels of agreement. Following revisions, this process was repeated with a large expert panel (n = 243) from 73 countries.
Consensus ranged from 88.8% to 96.9% (mean = 92.3%).
This global consensus statement provides guidance on harmonizing the International Classification of Diseases coding for steatotic liver disease and future directions to advance the field.
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