Preparing the occupational safety and health workforce for future disruptions.

BACKGROUND: Despite some emerging lessons learned from the COVID-19 pandemic, evidence suggests the world remains largely underprepared for-and vulnerable to-similar threats in the future. METHODS: In 2022, researchers at the US National Institute for Occupational Safety and Health (NIOSH) led a team of volunteers to explore how future disruptions, such as pandemics, might impact work and the practice of occupational safety and health (OSH). This qualitative inquiry was framed as a strategic foresight project and included a series of activities designed to help better understand, prepare for, and influence the future. RESULTS: Findings from a thorough search for indicators of change were synthesized into nine critical uncertainties and four plausible future scenarios. Analysis of these outputs elucidated three key challenges that may impact OSH research, policy, and practice during future disruptions: (1) data access, (2) direct-to-worker communications, and (3) mis- and dis-information management. CONCLUSIONS: A robust strategic response is offered to address these challenges, and next steps are proposed to enhance OSH preparedness and institutionalize strategic foresight across the OSH community.

Disrupted endosomal trafficking of the Vangl-Celsr polarity complex underlies congenital anomalies in trachea-esophageal morphogenesis.

Disruptions in foregut morphogenesis can result in life-threatening conditions where the trachea and esophagus fail to separate properly, such as esophageal atresia (EA) and tracheoesophageal fistulas (TEF). The developmental basis of these congenital anomalies is poorly understood, but recent genome sequencing reveals that de novo variants in intracellular trafficking genes are enriched in EA/TEF patients. Here we show that mutation of orthologous genes in Xenopus disrupts trachea-esophageal separation similar to EA/TEF patients. We show that the Rab11a recycling endosome pathway is required to localize Vangl-Celsr polarity complexes at the cell surface where opposite sides of the common foregut tube fuse. Partial loss of endosome trafficking or the Vangl/Celsr complex disrupts epithelial polarity and cell division orientation. Mutant cells accumulate at the fusion point, fail to downregulate cadherin, and do not separate into distinct trachea and esophagus. These data provide new insights into the mechanisms of congenital anomalies and general paradigms of tissue fusion during organogenesis.

Directly reprogrammed fragile X syndrome dorsal forebrain precursor cells generate cortical neurons exhibiting impaired neuronal maturation.

Introduction: The neurodevelopmental disorder fragile X syndrome (FXS) is the most common monogenic cause of intellectual disability associated with autism spectrum disorder. Inaccessibility to developing human brain cells is a major barrier to studying FXS. Direct-to-neural precursor reprogramming provides a unique platform to investigate the developmental profile of FXS-associated phenotypes throughout neural precursor and neuron generation, at a temporal resolution not afforded by post-mortem tissue and in a patient-specific context not represented in rodent models. Direct reprogramming also circumvents the protracted culture times and low efficiency of current induced pluripotent stem cell strategies. Methods: We have developed a chemically modified mRNA (cmRNA) -based direct reprogramming protocol to generate dorsal forebrain precursors (hiDFPs) from FXS patient-derived fibroblasts, with subsequent differentiation to glutamatergic cortical neurons and astrocytes. Results: We observed differential expression of mature neuronal markers suggesting impaired neuronal development and maturation in FXS- hiDFP-derived neurons compared to controls. FXS- hiDFP-derived cortical neurons exhibited dendritic growth and arborization deficits characterized by reduced neurite length and branching consistent with impaired neuronal maturation. Furthermore, FXS- hiDFP-derived neurons exhibited a significant decrease in the density of pre- and post- synaptic proteins and reduced glutamate-induced calcium activity, suggesting impaired excitatory synapse development and functional maturation. We also observed a reduced yield of FXS- hiDFP-derived neurons with a significant increase in FXS-affected astrocytes. Discussion: This study represents the first reported derivation of FXS-affected cortical neurons following direct reprogramming of patient fibroblasts to dorsal forebrain precursors and subsequently neurons that recapitulate the key molecular hallmarks of FXS as it occurs in human tissue. We propose that direct to hiDFP reprogramming provides a unique platform for further study into the pathogenesis of FXS as well as the identification and screening of new drug targets for the treatment of FXS.

From cup to dish: how to make and use endometrial organoid and stromal cultures derived from menstrual fluid.

Diseases impacting the female reproductive tract pose a critical health concern. The establishment of in vitro models to study primary endometrial cells is crucial to understanding the mechanisms that contribute to normal endometrial function and the origins of diseases. Established protocols for endometrial stromal cell culture have been in use for decades but recent advances in endometrial organoid culture have paved the way to allowing study of the roles of both epithelial and stromal endometrial cells in vitro. Due to inter-individual variability, primary cell cultures must be established from numerous persons. Generally, endometrial epithelial and stromal cells can be isolated from an endometrial biopsy, however, this is collected in a clinical setting by an invasive transcervical procedure. Our goal was to develop a non-invasive method for the isolation of paired endometrial epithelial organoids and stromal cells from menstrual fluid collected from individual women, based on recent reports describing the isolation of endometrial epithelial organoids or endometrial stromal cells from menstrual fluid. Participants recruited by the NIEHS Clinical Research Unit were provided with a menstrual cup and instructed to collect on the heaviest day of their menstrual period. Endometrial tissue fragments in the menstrual fluid samples were washed to remove blood, minced, and digested with proteinases. Following digestion, the solution was strained to separate epithelial fragments from stromal cells. Epithelial fragments were washed, resuspended in Matrigel, and plated for organoid formation. Stromal cells were separated from residual red blood cells using a Ficoll gradient and then plated in a flask. Once established, estrogen responsiveness of endometrial epithelial organoids was assessed and the decidual response of stromal cells was evaluated. Following treatments, qPCR was performed on organoids for genes induced by estradiol and on stromal cells for genes induced by decidualization. In this manner, the relative responsiveness of paired organoid and stroma cell cultures isolated from each woman could be assessed. In conclusion, we can isolate both epithelial and stromal cells from a single menstrual fluid sample, allowing us to establish organoids and cells in a paired manner. This protocol can greatly enhance our knowledge of the role of epithelial and stromal cells alone and in coordination.

The park physical activity questionnaire (Park-PAQ): A reliable measurement tool for park-based and total physical activity.

BACKGROUND: Few studies have explicitly quantified the proportion of park-based physical activity to park users' overall physical activity levels. Population studies need new context-specific physical activity measurement tools to achieve this. The objective of this study was to develop a reliable measure of self-reported park use and physical activity undertaken within and outside of parks to determine the contribution that park-based physical activity makes to overall physical activity levels. METHODS: A test-retest reliability study (n = 104) was conducted using the Park Physical Activity Questionnaire (Park-PAQ), an instrument based on the Active Australia Survey. Park-PAQ items captured the frequency and duration of walking for recreation or exercise, walking for transport, moderate and vigorous physical activity and strength, conditioning and balance activities done in parks and elsewhere. RESULTS: Recall of doing any walking for recreation (kappa = 0.649, p < 0.001) and any vigorous physical activity (kappa = 0.772, p < 0.001) was 'substantial', recall of doing any moderate physical activity (kappa = 0.553, p < 0.001) was 'moderate/acceptable', and recall of any walking for transport (kappa = 0.840, p < 0.001) 'near perfect'. Recall of the time spent walking for recreation in parks (ICC = 0.928, p < 0.001) was 'near perfect', whilst recall of time spent doing moderate activity in parks (ICC = 0.925, p < 0.001) and vigorous activity in parks (ICC = 0.962, p < 0.001) was 'near perfect'. Time spent walking for transport in a park (ICC = 0.200, p = 0.056) showed 'poor' agreement. Repeatability of the usual level of park use was 'substantial' (kappa = 0.744). CONCLUSIONS: The Park-PAQ reliably measures six domains of physical activity and quantifies the proportion of physical activity done in parks as a proportion of total physical activity. The Park-PAQ, used alone or embedded into park or physical activity surveys, will reliably capture context-specific activities that will optimise population level physical activity interventions, park programming and park management and design.

The architecture of mental health: identifying the combination of apartment building design requirements for positive mental health outcomes.

Background: Housing quality is a crucial determinant of mental health. While the construction of high-rise buildings is a popular policy strategy for accommodating population growth in cities, there is considerable debate about the health consequences of living in poorly designed apartments. Drawing on three Australian state government apartment design policies introduced to improve apartment design quality, this study aimed to identify the combination of design requirements that were optimally supportive of positive mental health. Methods: K-means cluster analyses identified groups of buildings (n = 172) that were homogenous in their implementation of a mix of n = 80 measured design requirements. Positive mental health was measured using the Warwick-Edinburgh Mental Well-being Scale (WEMWBS). Linear mixed-effects models controlling for demographic characteristics, self-selection factors and clustering of participants within buildings compared residents in the different clusters. Findings: Residents in the "high policy performance buildings", characterised by having a greater implementation of n = 29 design requirements across nine design elements, had significantly higher (+1.96 points) WEMWBS scores compared with residents in the "low policy performance buildings". Interpretation: This study is the first to empirically identify a mix of policy-specific architecture design requirements that are associated with positive mental health in apartment residents. These findings provide vital empirical evidence to inform national and international apartment and high-rise housing policies, and design instruments and practices to protect people's health in apartment dwellings. Funding: The High Life project is funded by a Healthway Research Intervention Project grant (#31986) and an Australian Research Council (ARC), Discovery Early Career Researcher Award (DECRA) (DE160100140). NE is supported by an Australian Research Council (ARC) Linkage Project (LP190100558). SF is supported by an Australian Research Council (ARC) Future Fellowship (FT210100899).

Deletion of p66Shc Dysregulates ERK and STAT3 Activity in Mouse Embryonic Stem Cells, Enhancing Their Naive-Like Self-Renewal in the Presence of Leukemia Inhibitory Factor.

The ShcA adapter protein is necessary for early embryonic development. The role of ShcA in development is primarily attributed to its 52 and 46 kDa isoforms that transduce receptor tyrosine kinase signaling through the extracellular signal regulated kinase (ERK). During embryogenesis, ERK acts as the primary signaling effector, driving fate acquisition and germ layer specification. P66Shc, the largest of the ShcA isoforms, has been observed to antagonize ERK in several contexts; however, its role during embryonic development remains poorly understood. We hypothesized that p66Shc could act as a negative regulator of ERK activity during embryonic development, antagonizing early lineage commitment. To explore the role of p66Shc in stem cell self-renewal and differentiation, we created a p66Shc knockout murine embryonic stem cell (mESC) line. Deletion of p66Shc enhanced basal ERK activity, but surprisingly, instead of inducing mESC differentiation, loss of p66Shc enhanced the expression of core and naive pluripotency markers. Using pharmacologic inhibitors to interrogate potential signaling mechanisms, we discovered that p66Shc deletion permits the self-renewal of naive mESCs in the absence of conventional growth factors, by increasing their responsiveness to leukemia inhibitory factor (LIF). We discovered that loss of p66Shc enhanced not only increased ERK phosphorylation but also increased phosphorylation of Signal transducer and activator of transcription in mESCs, which may be acting to stabilize their naive-like identity, desensitizing them to ERK-mediated differentiation cues. These findings identify p66Shc as a regulator of both LIF-mediated ESC pluripotency and of signaling cascades that initiate postimplantation embryonic development and ESC commitment.

Four Futures for Occupational Safety and Health.

Rapid changes to the nature of work have challenged the capacity of existing occupational safety and health (OSH) systems to ensure safe and productive workplaces. An effective response will require an expanded focus that includes new tools for anticipating and preparing for an uncertain future. Researchers at the U.S. National Institute for Occupational Safety and Health (NIOSH) have adopted the practice of strategic foresight to structure inquiry into how the future will impact OSH. Rooted in futures studies and strategic management, foresight creates well-researched and informed future scenarios that help organizations better prepare for potential challenges and take advantage of new opportunities. This paper summarizes the inaugural NIOSH strategic foresight project, which sought to promote institutional capacity in applied foresight while exploring the future of OSH research and practice activities. With multidisciplinary teams of subject matter experts at NIOSH, we undertook extensive exploration and information synthesis to inform the development of four alternative future scenarios for OSH. We describe the methods we developed to craft these futures and discuss their implications for OSH, including strategic responses that can serve as the basis for an action-oriented roadmap toward a preferred future.

Formation and characterization of BMP2/GDF5 and BMP4/GDF5 heterodimers.

BACKGROUND: Proteins of the TGFß family, which are largely studied as homodimers, are also known to form heterodimers with biological activity distinct from their component homodimers. For instance, heterodimers of bone morphogenetic proteins, including BMP2/BMP7, BMP2/BMP6, and BMP9/BMP10, among others, have illustrated the importance of these heterodimeric proteins within the context of TGFß signaling. RESULTS: In this study, we have determined that mature GDF5 can be combined with mature BMP2 or BMP4 to form BMP2/GDF5 and BMP4/GDF5 heterodimer. Intriguingly, this combination of a BMP2 or BMP4 monomer, which exhibit high affinity to heparan sulfate characteristic to the BMP class, with a GDF5 monomer with low heparan sulfate affinity produces a heterodimer with an intermediate affinity. Using heparin affinity chromatography to purify the heterodimeric proteins, we then determined that both the BMP2/GDF5 and BMP4/GDF5 heterodimers consistently signaled potently across an array of cellular and in vivo systems, while the activities of their homodimeric counterparts were more context dependent. These differences were likely driven by an increase in the combined affinities for the type 1 receptors, Alk3 and Alk6. Furthermore, the X-ray crystal structure of BMP2/GDF5 heterodimer was determined, highlighting the formation of two asymmetric type 1 receptor binding sites that are both unique relative to the homodimers. CONCLUSIONS: Ultimately, this method of heterodimer production yielded a signaling molecule with unique properties relative to the homodimeric ligands, including high affinity to multiple type 1 and moderate heparan binding affinity.

Reprogramming of adult human dermal fibroblasts to induced dorsal forebrain precursor cells maintains aging signatures.

Introduction: With the increase in aging populations around the world, the development of in vitro human cell models to study neurodegenerative disease is crucial. A major limitation in using induced pluripotent stem cell (hiPSC) technology to model diseases of aging is that reprogramming fibroblasts to a pluripotent stem cell state erases age-associated features. The resulting cells show behaviors of an embryonic stage exhibiting longer telomeres, reduced oxidative stress, and mitochondrial rejuvenation, as well as epigenetic modifications, loss of abnormal nuclear morphologies, and age-associated features. Methods: We have developed a protocol utilizing stable, non-immunogenic chemically modified mRNA (cmRNA) to convert adult human dermal fibroblasts (HDFs) to human induced dorsal forebrain precursor (hiDFP) cells, which can subsequently be differentiated into cortical neurons. Analyzing an array of aging biomarkers, we demonstrate for the first time the effect of direct-to-hiDFP reprogramming on cellular age. Results: We confirm direct-to-hiDFP reprogramming does not affect telomere length or the expression of key aging markers. However, while direct-to-hiDFP reprogramming does not affect senescence-associated ß-galactosidase activity, it enhances the level of mitochondrial reactive oxygen species and the amount of DNA methylation compared to HDFs. Interestingly, following neuronal differentiation of hiDFPs we observed an increase in cell soma size as well as neurite number, length, and branching with increasing donor age suggesting that neuronal morphology is altered with age. Discussion: We propose direct-to-hiDFP reprogramming provides a strategy for modeling age-associated neurodegenerative diseases allowing the persistence of age-associated signatures not seen in hiPSC-derived cultures, thereby facilitating our understanding of neurodegenerative disease and identification of therapeutic targets.

"Do the Best You Can with Resources You Have to Offer": Community stakeholder views on supporting immigrant families.

First and second-generation immigrant families of young children in the United States face potential challenges that may be mitigated with stakeholder support in their communities. We examined self-reported views and behaviors among professionals (n = 76) working with families in a mid-Atlantic urban community, and whether these views correlated with demographic factors. Over half of respondents were not able/willing to report the number of immigrant families served and over half believed immigrant parents are less likely to advocate for themselves or their child. Participants were fairly split in seeking advice from others and comfort in talking with immigrant families about their culture/needs. It is essential to assess stakeholders' views on perceived roles, roadblocks, and desired supports. This analysis informs efforts to work more collaboratively with community partners to improve outreach to immigrant families during those formative years in a child's development. Implications for research, practice, and policy are discussed.

Community-Level Alcohol Availability and Child Maltreatment: A Statewide Panel Analysis Over 13 Years.

OBJECTIVE: Parental or caregiver alcohol use, particularly heavy regular or episodic use, can increase the risk of child maltreatment within individual families. At the national level, higher per capita alcohol consumption has been associated with increased child injury mortality in Australia. This study aimed to investigate whether an association exists between substantiated child maltreatment cases, numbers of licensed outlets, and average alcohol sales volumes at the community level (local government area [LGA]) over a 13-year period across Western Australia (WA). METHOD: Annual panel data were obtained for 132 WA LGAs over the period 2001-2013. Bayesian conditional autoregressive Poisson regression was applied to test associations between numbers of substantiated child maltreatment cases and per-population densities and mean sales volumes of off-trade and on-trade alcohol outlets. Associations were adjusted for the presence of local alcohol restrictions and mandatory reporting; density of on-trade outlets; and their sales, demographic, and socioeconomic variables. RESULTS: Comprehensive area-level alcohol bans and policies restricting alcohol sales reduced child maltreatment by 9.6% and 38.5%, whereas mandatory reporting of child maltreatment increased substantiations by 15.3%. Counterintuitively, for each additional 1,000 L of ethanol sold per off-premise outlet, there was a 3.7% decline in child maltreatment. CONCLUSIONS: Local government alcohol restrictions predicted reduced child abuse and neglect. Findings that increases in off-trade outlets predicted a decreased risk of child maltreatment at a local level are seemingly at odds with these findings, but outlet density may be acting as a measure of less disorganization. Alcohol policy that affects alcohol availability can reduce child maltreatment in at-risk areas. Local area alcohol bans and interventions reducing hours of sale should be further evaluated to confirm these findings.

Single-cell mapping of regenerative and fibrotic healing responses after musculoskeletal injury.

After injury, a cascade of events repairs the damaged tissue, including expansion and differentiation of the progenitor pool and redeposition of matrix. To guide future wound regeneration strategies, we compared single-cell sequencing of regenerative (third phalangeal element [P3]) and fibrotic (second phalangeal element [P2]) digit tip amputation (DTA) models as well as traumatic heterotopic ossification (HO; aberrant). Analyses point to a common initial response to injury, including expansion of progenitors, redeposition of matrix, and activation of transforming growth factor ß (TGF-ß) and WNT pathways. Surprisingly, fibrotic P2 DTA showed greater transcriptional similarity to HO than to regenerative P3 DTA, suggesting that gene expression more strongly correlates with healing outcome than with injury type or cell origin. Differential analysis and immunostaining revealed altered activation of inflammatory pathways, such as the complement pathway, in the progenitor cells. These data suggests that common pathways are activated in response to damage but are fine tuned within each injury. Modulating these pathways may shift the balance toward regenerative outcomes.

Measuring the high life: A method for assessing apartment design policy implementation.

This paper introduces a comprehensive method to measure the implementation of residential apartment design policies in Australia. It describes a protocol for extracting and measuring potentially health-enhancing policy-specific design requirements derived from three current residential apartment design policies in Sydney, Melbourne and Perth. These requirements focus on ten key design elements: (1) solar access, (2) natural ventilation, (3) private open space, (4) communal open space, (5) circulation spaces, (6) acoustic privacy, (7) outlook and (8) visual privacy, (9) bicycle and car parking and (10) apartment mix. This paper also describes the computation of scores to quantify the levels of on-ground implementation of the design requirements and compliance with the policies. The method will allow researchers to objectively quantify, benchmark and assess the uptake of apartment policy in apartment design and construction to inform future policy development. • Measurements were developed to systematically assess apartment buildings for their implementation of specific design requirements stipulated by State Government design policies. • Policy implementation was defined as the degree to which the apartment buildings adhered to the requirements outlined by the apartment design policies. A scoring system was developed to quantify policy implementation at both the apartment and building levels. • This method can be replicated to allow researchers to objectively quantify, benchmark and assess the uptake of apartment policy in apartment design and construction to inform future policy development.

Erratum: Identification and validation of candidate risk genes in endocytic vesicular trafficking associated with esophageal atresia and tracheoesophageal fistulas.

[This corrects the article DOI: 10.1016/j.xhgg.2022.100107.].

Identification and validation of candidate risk genes in endocytic vesicular trafficking associated with esophageal atresia and tracheoesophageal fistulas.

Esophageal atresias/tracheoesophageal fistulas (EA/TEF) are rare congenital anomalies caused by aberrant development of the foregut. Previous studies indicate that rare or de novo genetic variants significantly contribute to EA/TEF risk, and most individuals with EA/TEF do not have pathogenic genetic variants in established risk genes. To identify the genetic contributions to EA/TEF, we performed whole genome sequencing of 185 trios (probands and parents) with EA/TEF, including 59 isolated and 126 complex cases with additional congenital anomalies and/or neurodevelopmental disorders. There was a significant burden of protein-altering de novo coding variants in complex cases (p = 3.3 × 10-4), especially in genes that are intolerant of loss-of-function variants in the population. We performed simulation analysis of pathway enrichment based on background mutation rate and identified a number of pathways related to endocytosis and intracellular trafficking that as a group have a significant burden of protein-altering de novo variants. We assessed 18 variants for disease causality using CRISPR-Cas9 mutagenesis in Xenopus and confirmed 13 with tracheoesophageal phenotypes. Our results implicate disruption of endosome-mediated epithelial remodeling as a potential mechanism of foregut developmental defects. Our results suggest significant genetic heterogeneity of EA/TEF and may have implications for the mechanisms of other rare congenital anomalies.

Small Molecules Enhance Reprogramming of Adult Human Dermal Fibroblasts to Dorsal Forebrain Precursor Cells.

The development of human cell-based platforms for disease modeling, drug discovery, and regenerative therapy relies on robust and practical methods to derive high yields of relevant neuronal subtypes. Direct reprogramming strategies have sought to provide a means of deriving human neurons that mitigate the low conversion efficiencies, and protracted timing of human embryonic stem cell and induced pluripotent stem cell-derived neuron specification in vitro. However, few studies have demonstrated the direct conversion of adult human fibroblasts into multipotent neural precursors with the capacity to differentiate into cortical neurons with high efficiency. In this study, we demonstrate a reprogramming strategy using chemically modified mRNA encoding the proneural genes SOX2 and PAX6 coupled with small molecule supplementation to enhance the derivation of human-induced dorsal forebrain precursors directly from adult human dermal fibroblasts (aHDFs). Through transcriptional and phenotypic analysis of lineage-specific precursor and cortical neuron markers, we have demonstrated that this combined strategy significantly enhances the direct derivation of dorsal forebrain precursors from aHDFs, which, after timely exposure to defined differentiation media, gives rise to high yields of functional glutamatergic neurons. We propose that this combined strategy provides a highly tractable and efficient human cell-based platform for disease modeling and drug discovery.

All causes of death among veterinarians in the United States during 1979 through 2015.

OBJECTIVE: To assess proportionate mortality from all causes for male and female US veterinarians during 1979 through 2015. SAMPLE: Death records for 11,620 veterinarians. PROCEDURES: For this proportionate mortality ratio (PMR) study, information for veterinarians who died during 1979 through 2015 was obtained from AVMA obituary and life insurance databases and submitted to a centralized database of US death records to obtain underlying causes of death. Decedent data that met records-matching criteria were imported into a software program for calculation of PMRs for all causes stratified by sex and indirectly standardized for age, race, and 5-year calendar period with 95% CIs. RESULTS: 11,620 decedents consisted of 11,049 (95%) males and 571 (5%) females with a median age at death of 77 years. Proportionate mortality for all veterinarian decedents was higher than expected for melanoma (PMRs, 2.1 and 2.2 for males and females, respectively), suicide (PMRs, 2.1 and 3.5 for males and females, respectively), and transportation injuries (PMRs, 1.7 and 1.6 for males and females, respectively). Proportionate mortality for all decedents was lower than expected for respiratory cancers (PMRs, 0.6 and 0.5 for males and females, respectively), diabetes mellitus (PMRs, 0.7 and 0.4 for males and females, respectively), heart disease (PMRs, 0.9 and 0.6 for males and females, respectively), and respiratory disorders (PMRs, 0.7 and 0.6 for males and females, respectively). CLINICAL RELEVANCE: Results indicated proportionate mortality from malignant melanoma, transportation injuries, and suicide for male and female veterinarians was higher than the general population. These data may help stakeholders improve veterinarian workplace safety and health guidelines.

Towards Ethical International Research Partnerships in Gender-Based Violence Research: Insights From Research Partners in Kenya.

Research with survivors of gender-based violence in low- and middle-income countries is important to improve understanding of experiences of violence and the policies that can help combat it. But this research also implies risks for survivors, such as re-traumatization, safety concerns, and feelings of exploitation. These risks are magnified if research is undertaken by researchers from high-income countries, whose positionality produces power inequalities affecting both participants and research partners. This article describes the ethical challenges of international gender-based violence research from the perspective of Kenyan researchers and organizations and identifies recommendations about how to prevent them.

Simulation-based User-centered Design: An Approach to Device Development during COVID-19.

INTRODUCTION: Since the onset of COVID-19, intubations have become very high risk for clinical teams. Barrier devices during endotracheal intubation protect clinicians from the aerosols generated. Simulation-based user-centered design (UCD) was an iterative design process used to develop a pediatric intubation aerosol containment system (IACS). Simulation was anchored in human factor engineering and UCD to better understand clinicians' complex interaction with the IACS device, elicit user wants and needs, identify design inefficiencies, and unveil safety concerns. METHODS: This study was a prospective observational study of a simulation-based investigation used to design a pediatric IACS rapidly. Debriefing and Failure Mode and Effect Analysis identified latent conditions related to 5 device prototypes. Design iterations made were based on feedback provided to the engineering team after each simulation. RESULTS: Simulation identified 32 latent conditions, resulting in 5 iterations of the IACS prototype. The prototypes included an (1) intubation box; (2) IACS shield; (3) IACS frame with PVC pipes; (4) IACS plexiglass frame, and finally, (5) IACS frame without a plexiglass top. CONCLUSIONS: Integration of simulation with human factor ergonomics and UCD, in partnership with mechanical engineers, facilitated a novel context to design and redesign a pediatric IACS to meet user needs and address safety concerns.