Endocrine persistence in ER+ breast cancer is accompanied by metabolic vulnerability in oxidative phosphorylation.

Despite adjuvant treatment with endocrine therapies, estrogen receptor-positive (ER+) breast cancers recur in a significant proportion of patients. Recurrences are attributable to clinically undetectable endocrine-tolerant persister cancer cells that retain tumor-forming potential. Therefore, strategies targeting such persister cells may prevent recurrent disease. Using CRISPR-Cas9 genome-wide knockout screening in ER+ breast cancer cells, we identified a survival mechanism involving metabolic reprogramming with reliance upon mitochondrial respiration in endocrine-tolerant persister cells. Quantitative proteomic profiling showed reduced levels of glycolytic proteins in persisters. Metabolic tracing of glucose revealed an energy-depleted state in persisters where oxidative phosphorylation was required to generate ATP. A phase II clinical trial was conducted to evaluate changes in mitochondrial markers in primary ER+/HER2-breast tumors induced by neoadjuvant endocrine therapy ( NCT04568616 ). In an analysis of tumor specimens from 32 patients, tumors exhibiting residual cell proliferation after aromatase inhibitor-induced estrogen deprivation with letrozole showed increased mitochondrial content. Genetic profiling and barcode lineage tracing showed that endocrine-tolerant persistence occurred stochastically without genetic predisposition. Mice bearing cell line- and patient-derived xenografts were used to measure the anti-tumor effects of mitochondrial complex I inhibition in the context of endocrine therapy. Pharmacological inhibition of complex I suppressed the tumor-forming potential of persisters and synergized with the anti-estrogen fulvestrant to induce regression of patient-derived xenografts. These findings indicate that mitochondrial metabolism is essential in endocrine-tolerant persister ER+ breast cancer cells and warrant the development of treatment strategies to leverage this vulnerability in the context of endocrine-sensitive disease. Statement of Significance: Endocrine-tolerant persister cancer cells that survive endocrine therapy can cause recurrent disease. Persister cells exhibit increased energetic dependence upon mitochondria for survival and tumor re-growth potential.

Reproducible research practices: A tool for effective and efficient leadership in collaborative statistics.

With data and code sharing policies more common and version control more widely used in statistics, standards for reproducible research are higher than ever. Reproducible research practices must keep up with the fast pace of research. To do so, we propose combining modern practices of leadership with best practices for reproducible research in collaborative statistics as an effective tool for ensuring quality and accuracy while developing stewardship and autonomy in the people we lead. First, we establish a framework for expectations of reproducible statistical research. Then, we introduce Stephen M.R. Covey's theory of trusting and inspiring leadership. These two are combined as we show how stewardship agreements can be used to make reproducible coding a team norm. We provide an illustrative code example and highlight how this method creates a more collaborative rather than evaluative culture where team members hold themselves accountable. The goal of this manuscript is for statisticians to find this application of leadership theory useful and to inspire them to intentionally develop their personal approach to leadership.

Sleep Disturbance and Subsequent Suicidal Behaviors in Preadolescence.

Importance: Suicide is a leading cause of death among adolescents, who demonstrate high rates of sleep disturbance. Poor sleep appears to confer risk for suicide, but longitudinal investigation of suicidal behaviors remains rare, particularly in the transition from childhood to early adolescence. Objective: To evaluate sleep disturbances in preadolescent children (aged 9 and 10 years) in association with longitudinal risk for suicidal ideation and suicide attempts at the 2-year follow-up. Design, Setting, and Participants: This cohort study used data from the Adolescent Brain Cognitive Development Study between June 2016 and January 2021. This dataset included children aged 9 or 10 years at baseline and their parents or caregivers who were recruited at 21 sites across the US. Data were analyzed July 2023 to June 2024. Exposures: The Sleep Disturbance Scale for Children, a 26-item parent-reported inventory, was administered at baseline, generating a total score and 6 subscales. Central covariates included the Child Behavior Checklist Anxiety and Depression subscale and demographic variables. Main Outcomes and Measures: The computerized Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-COMP) assessed parent- and youth-reported suicidal behaviors and outcomes (none; passive, active nonspecific, and active specific suicidal ideation; and suicide attempt) at the 2-year follow-up. Sleep disturbance was further grouped by symptom severity (minimal, moderate, elevated, high, and severe). Results: Of the 10 136 youths who reported no baseline suicidal ideation or behavior, 8807 youths (mean [SD] age, 9.9 [0.6] years; 4507 males [51.2%]; 197 Asian individuals [2.2%], 1273 Black individuals [14.5%], and 5775 White individuals [65.6%]) completed the K-SADS-COMP assessment at the 2-year follow-up and were included in the analysis. At the follow-up, 8044 participants (91.3%) had no suicidal behavior, 317 (3.6%) had passive suicidal ideation, 258 (2.9%) had active nonspecific suicidal ideation, 130 (1.5%) had active specific suicidal ideation, and 58 (0.7%) had a first-time suicide attempt. Baseline sleep disturbance was associated with increased incidence risk for suicidal behavior at age 12 years (odds ratio, 2.68; 95% CI, 1.44-4.98; P = .002), adjusting for covariates. Individual subscales or items demonstrating associations with risk included disorders of excessive somnolence and frequency of nightmares. Conclusions and Relevance: Results of this longitudinal cohort study revealed that disturbed sleep at age 10 years was associated with risk for suicidal thoughts and behaviors in the next 2 years. The findings highlight the potential importance of sleep as a visible risk factor and intervention target in the prevention of youth suicide.

Potential Health Hazards of Cryptocurrency Mining: Protecting Health in a "Digital Oil Boom".

This Viewpoint discusses the need for research on and mitigation strategies for the potential community and population health effects of cryptocurrency mining, an energy-intensive and noise-producing industry.

The association between socio-economic deprivation and receipt of long-acting reversible contraception at a single clinic visit.

OBJECTIVES: To determine the relationship between area deprivation index (ADI) and obtaining single-visit long-acting reversible contraception (LARC). STUDY DESIGN: We utilized Poisson regression to determine the association between area deprivation and single-visit LARC insertion within a state-wide healthcare system between 2019-2021. RESULTS: Among our cohort (N = 4417), 68.60% of patients desiring LARC obtained single-visit LARC. Participants living in high deprivation areas were less likely to receive single-visit LARC (aRR 0.72, 95% CI 0.65-0.80). CONCLUSIONS: Living in areas of high deprivation is independently negatively associated with obtaining a single-visit LARC. IMPLICATIONS: While access to single-visit LARC should be universally improved, reducing barriers for patientswith a higher ADI may help limit inequities in reproductive healthcare.

Modeling Lewy body disease with SNCA triplication iPSC-derived cortical organoids and identifying therapeutic drugs.

Aggregated α-synuclein (α-SYN) proteins, encoded by the SNCA gene, are hallmarks of Lewy body disease (LBD), affecting multiple brain regions. However, the specific mechanisms underlying α-SYN pathology in cortical neurons, crucial for LBD-associated dementia, remain unclear. Here, we recapitulated α-SYN pathologies in human induced pluripotent stem cells (iPSCs)-derived cortical organoids generated from patients with LBD with SNCA gene triplication. Single-cell RNA sequencing, combined with functional and molecular validation, identified synaptic and mitochondrial dysfunction in excitatory neurons exhibiting high expression of the SNCA gene, aligning with observations in the cortex of autopsy-confirmed LBD human brains. Furthermore, we screened 1280 Food and Drug Administration-approved drugs and identified four candidates (entacapone, tolcapone, phenazopyridine hydrochloride, and zalcitabine) that inhibited α-SYN seeding activity in real-time quaking-induced conversion assays with human brains, reduced α-SYN aggregation, and alleviated mitochondrial dysfunction in SNCA triplication organoids and excitatory neurons. Our findings establish human cortical LBD models and suggest potential therapeutic drugs targeting α-SYN aggregation for LBD.

Stress increases sperm respiration and motility in mice and men.

Semen quality and fertility has declined over the last 50 years, corresponding to ever-increasing environmental stressors. However, the cellular mechanisms involved and their impact on sperm functions remain unknown. In a repeated sampling human cohort study, we identify a significant effect of prior perceived stress to increase sperm motility 2-3 months following stress, timing that expands upon our previous studies revealing significant stress-associated changes in sperm RNA important for fertility. We mechanistically examine this post-stress timing in mice using an in vitro stress model in the epididymal epithelial cells responsible for sperm maturation and find 7282 differentially H3K27me3 bound DNA regions involving genes critical for mitochondrial and metabolic pathways. Further, prior stress exposure significantly changes the composition and size of epithelial cell-secreted extracellular vesicles that when incubated with mouse sperm, increase mitochondrial respiration and sperm motility, adding to our prior work showing impacts on embryo development. Together, these studies identify a time-dependent, translational signaling pathway that communicates stress experience to sperm, ultimately affecting reproductive functions.

Balance Impairment in the Burn Population: A Burn Model System National Database Study.

Balance is an important component of daily function and impairments can lead to injury and quality-of-life limitations. Balance is not well studied in the burn population. This study examines the frequency of long-term balance impairments and associated factors after a burn injury. The Burn Model System National Database was analyzed. Trouble with balance was self-reported at discharge, 6, 12, 24, and 60 months after injury. Regression analyses examined the associations between demographic and clinical characteristics and balance impairments at 12 months. Of 572 participants, balance impairments were most reported at discharge (40.3%), continuing over 60 months (26.8-36.0%). Those reporting balance impairments (n = 153) were more likely to be older, unemployed, have Medicaid or Medicare, receive inpatient rehabilitation, receive outpatient physical or occupational therapy, have vision problems, have leg or feet burns and swelling, and have foot numbness compared to those without (p ≤ 0.001). Regression analysis demonstrated a 4% increased odds of balance impairment for every increase in year of age (p < 0.001), 71% lower odds if employed at time of injury (p < 0.001), and 140% higher odds if receiving outpatient physical or occupational therapy at 12 months (p = 0.008). Common reports of balance impairments highlight the need for routine screenings to identify burn survivors that may benefit from targeted interventions.

Treating new-onset cognitive complaints after risk-reducing salpingo-oophorectomy: A randomized controlled crossover trial of lisdexamfetamine.

OBJECTIVE: To determine whether the psychostimulant lisdexamfetamine improves subjective and objective measures of cognitive functioning among women genetically at-risk for cancer who have undergone risk-reducing salpingo-oophorectomy and report new-onset executive functioning difficulties. METHODS: 69 participants were assigned to a randomized controlled crossover trial with 6-week trials of active medication (lisdexamfetamine) and placebo, separated by a minimum 2-week washout in an intent-to-treat framework (clinical trial registration number: NCT03187353). At trial baseline, midpoint, and endpoint, participants completed a self-report measure of executive functioning (Brown Attention Deficit Disorder Scale). At study baseline and trial endpoint, participants completed sustained attention, attention/working memory, and verbal learning/memory cognitive tasks. Side effects were assessed at 2, 3, 4, and 6 weeks for each trial. RESULTS: From trial baseline to trial endpoint, lisdexamfetamine - relative to placebo - significantly improved total scores on the self-report Brown Attention Deficit Disorder Scale (and scores on four of five subdomains) as well as attention and working memory performance. Significantly more participants endorsed side effects across the lisdexamfetamine trial versus placebo; however, trial completion rates were similar, indicating that lisdexamfetamine was nonetheless well-tolerated. CONCLUSIONS: Lisdexamfetamine improved both subjective and objective measures of attention and working memory and could offer women experiencing cognitive difficulties post-risk-reducing salpingo-oophorectomy an alternative therapeutic option.

Improving spatial exposure data for everyone - lifecourse social context and ascertaining residential history.

Measuring age-specific, contextual exposures is crucial for lifecourse epidemiology research. Longitudinal residential data offers a "golden ticket" to cumulative exposure metrics and can enhance our understanding of health disparities. Residential history can be linked to myriad spatiotemporal databases to characterize environmental, socioeconomic, and policy contexts that a person experienced throughout life. However, obtaining accurate residential history is challenging in the United States due to the limitations of administrative registries and self-reports. Xu et al. (Am J Epidemiol. 2024; 193(2):348-359) detail an approach to linking residential history sourced from LexisNexis ® Accurint ® to a Wisconsin-based research cohort, offering insights into challenges with residential history collection. Researchers must analyze the magnitude of selection and misclassification biases inherent to ascertaining residential history from cohort data. A lifecourse framework can provide insights into why the frequency and distance of moves is patterned by age, birth cohort, racial/ethnic identity, socioeconomic status, and urbanicity. Historic and contemporary migration patterns of marginalized people seeking economic and political opportunities must guide interpretations of residential history data. We outline methodologic priorities for use of residential history in health disparities research, including contextualizing residential history data with determinants of residential moves, triangulating spatial exposure assessment methods, and transparently quantifying measurement error.

A comparison of population-level exposure and equity tradeoffs across strategies to reduce fine particulate matter emissions from transportation sources in the northeastern US.

BACKGROUND: Many climate mitigation policies to reduce transportation emissions have public health benefits related to ambient air pollution. However, few health analyses consider the equity implications of alternative policies. Equity can be conceptualized in many different ways that may be relevant to communities, decision-makers, and other stakeholders. OBJECTIVES: To evaluate alternative transportation emissions reduction scenarios across the northeastern United States considering population exposure reductions and multiple equity constructs. METHODS: We developed four quantitative indicators reflecting equity constructs that aligned with stakeholder perspectives, including racial/ethnic exposure inequities, proportion of benefits in environmental justice communities, distribution of benefits among participating states, and rural/urban share of benefits. We analyzed numerous transportation emissions reduction scenarios for directly emitted fine particulate matter (primary PM2.5) covering 12 Northeast states and the District of Columbia. We used the Community Multiscale Air Quality model with the decoupled direct method to estimate the reduction in population-weighted primary PM2.5 exposure and the impact on equity for each scenario. RESULTS: Scenarios that yielded greater reductions in population-weighted primary PM2.5 exposure generally emphasized emissions reductions in urban areas or states with large urban centers, with a more than threefold difference in benefits across scenarios. The higher exposure-benefit scenarios typically also had greater reductions in racial/ethnic exposure inequities but led to higher between-state or rural/urban inequality. Scenarios that targeted uniform percentage emission reductions from light or heavy-duty trucks best addressed rural/urban inequalities but led to the smallest reductions in racial/ethnic inequity. CONCLUSION: There are intrinsic tradeoffs among equity constructs, where focusing resources on distributing benefits across states or between urban and rural populations could come at the expense of less reduction in racial/ethnic exposure inequities or in environmental justice communities. Future health benefits analyses should incorporate multiple equity indicators that reflect different stakeholder perspectives and articulate the underlying constructs and tradeoffs.

Longitudinal Exposure to Neighborhood Concentrated Poverty Contributes to Differences in Adiposity in Midlife Women.

Background: Neighborhood poverty is associated with adiposity in women, though longitudinal designs, annually collected residential histories, objectively collected anthropometric measures, and geographically diverse samples of midlife women remain limited. Objective: To investigate whether longitudinal exposure to neighborhood concentrated poverty is associated with differences in body mass index (BMI) and waist circumference (WC) among 2,328 midlife women (age 42-52 years at baseline) from 6 U.S. cities enrolled in the Study of Women's Health Across the Nation (SWAN) from 1996 to 2007. Methods: Residential addresses and adiposity measures were collected at approximately annual intervals from the baseline visit through a 10-year follow-up. We used census poverty data and local spatial statistics to identify hot-spots of high concentrated poverty areas and cold-spots of low concentrated poverty located within each SWAN site region, and used linear mixed-effect models to estimate percentage differences (95% confidence interval [CI]) in average BMI and WC levels between neighborhood concentrated poverty categories. Results: After adjusting for individual-level sociodemographics, health-related factors, and residential mobility, compared to residents of moderate concentrated poverty communities, women living in site-specific hot-spots of high concentrated poverty had 1.5% higher (95% CI: 0.6, 2.3) BMI and 1.3% higher (95% CI: 0.5, 2.0) WC levels, whereas women living in cold-spots of low concentrated poverty had 0.7% lower (95% CI: -1.2, -0.1) BMI and 0.3% lower (95% CI: -0.8, 0.2) WC. Site-stratified results remained in largely similar directions to overall estimates, despite wide CIs and small sample sizes. Conclusions: Longitudinal exposure to neighborhood concentrated poverty is associated with slightly higher BMI and WC among women across midlife.

Residential Proximity to Oil and Gas Development and Mental Health in a North American Preconception Cohort Study: 2013-2023.

Objectives. To evaluate associations between oil and gas development (OGD) and mental health using cross-sectional data from a preconception cohort study, Pregnancy Study Online. Methods. We analyzed baseline data from a prospective cohort of US and Canadian women aged 21 to 45 years who were attempting conception without fertility treatment (2013-2023). We developed residential proximity measures for active OGD during preconception, including distance from nearest site. At baseline, participants completed validated scales for perceived stress (10-item Perceived Stress Scale, PSS) and depressive symptoms (Major Depression Inventory, MDI) and reported psychotropic medication use. We used log-binomial regression and restricted cubic splines to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs). Results. Among 5725 participants across 37 states and provinces, residence at 2 km versus 20 to 50 km of active OGD was associated with moderate to high perceived stress (PSS ≥ 20 vs < 20: PR = 1.08; 95% CI = 0.98, 1.18), moderate to severe depressive symptoms (MDI ≥ 20 vs < 20: PR = 1.27; 95% CI = 1.11, 1.45), and psychotropic medication use (PR = 1.11; 95% CI = 0.97, 1.28). Conclusions. Among North American pregnancy planners, closer proximity to OGD was associated with adverse preconception mental health symptomatology. (Am J Public Health. 2024;114(9):923-934. https://doi.org/10.2105/AJPH.2024.307730).

Wildfires increasingly threaten oil and gas wells in the western United States with disproportionate impacts on marginalized populations.

The western United States is home to most of the nation's oil and gas production and, increasingly, wildfires. We examined historical threats of wildfires for oil and gas wells, the extent to which wildfires are projected to threaten wells as climate change progresses, and exposure of human populations to these wells. From 1984-2019, we found that cumulatively 102,882 wells were located in wildfire burn areas, and 348,853 people were exposed (resided ≤ 1 km). During this period, we observed a five-fold increase in the number of wells in wildfire burn areas and a doubling of the population within 1 km of these wells. These trends are projected to increase by late century, likely threatening human health. Approximately 2.9 million people reside within 1 km of wells in areas with high wildfire risk, and Asian, Black, Hispanic, and Native American people have disproportionately high exposure to wildfire-threatened wells.

EXPOSURE TO AMBIENT HEAT AND RISK OF SPONTANEOUS ABORTION: A CASE-CROSSOVER STUDY.

BACKGROUND: Few epidemiologic studies have examined the association of ambient heat with spontaneous abortion, a common and devastating pregnancy outcome. METHODS: We conducted a case-crossover study nested within Pregnancy Study Online, a preconception cohort study (2013-2022). We included all participants reporting spontaneous abortion (n=1,524). We defined the case window as the 7 days preceding the event and used time-stratified referent selection to select control windows matched on calendar month and day of week. Within each 7-day case and control window, we measured mean, maximum, and minimum of daily maximum outdoor air temperatures. We fit splines to examine non-linear relationships across the entire year and conditional logistic regression to estimate odds ratios (OR) and 95% CI of spontaneous abortion with increases in temperature during the warm season (May-September) and decreases during the cool season (November-March). RESULTS: We found evidence of a U-shaped association between outdoor air temperature and spontaneous abortion risk based on year-round data. When restricting to warm season events (n=657), the OR for a 10-percentile increase in the mean of lag 0-6 daily maximum temperatures was 1.1 (95% CI: 0.96, 1.2) and, for the maximum, 1.1 (95% CI: 0.99, 1.2). The OR associated with any extreme heat days (>95th county-specific percentile) in the preceding week was 1.2 (95% CI: 0.95, 1.5). Among cool season events (n=615), there was no appreciable association between lower temperatures and spontaneous abortion risk. CONCLUSION: Our study provides evidence of an association between high outdoor temperatures and incidence of spontaneous abortion.

Intersectional Care for Asian American and Pacific Islander Youth With Sexual or Gender Minority Identities in the Acute Psychiatric Care Setting.

Youth who hold both Asian American and Pacific Islander (AAPI) and sexual or gender minority (SGM) identities are frequently overlooked and underserved, and experience intersecting forms of discrimination, interpersonal stressors, and structural barriers.1 Amid heightened anti-AAPI and anti-SGM violence, these populations are particularly vulnerable to poor mental health outcomes. In 2023, over half of AAPI SGM reported experiences of depression, anxiety, and gender-based discrimination, and nearly half reported racial abuse.2 Despite growing need, there are few established best practices for supporting the mental health needs of AAPI SGM youth. Guidelines tailoring psychiatric care to this population's needs in outpatient settings1 have recently been complemented with considerations for SGM youth in the inpatient psychiatric setting.3 Building on this work, we identify 5 considerations that we believe to be key to the provision of high-quality mental health care to AAPI SGM youth and their families in both the acute emergency department (ED) and inpatient settings.

Ectodermal dysplasia and cholesteatoma: A cross-sectional analysis of otologic issues.

OBJECTIVES: Previous studies have also associated cleft palate with increased cholesteatoma risk. Despite this close relation, the incidence of cholesteatoma and associated otologic issues in patients with ectodermal dysplasia types highly associated with cleft palate (EDT-ACPs) has not been formally analyzed. This study provides insight to guide clinicians caring for patients with ED types associated with cleft palate. METHODS: Individuals with TP63 disorders and Goltz syndrome/Focal Dermal Hypoplasia in the National Foundation for Ectodermal Dysplasia database were contacted for participation in an online REDCap survey from Sept-Dec '22. Descriptive statistics were generated using SAS JMP Pro 17 statistical software. RESULTS: 65 individuals participated in the survey (response rate approx. 18 %). The median [IQR] age was 22 [14, 43], 41 (63 %) were female, and Ectrodactyly-Ectodermal Dysplasia-Cleft Lip/Palate Syndrome (EEC) was most common (n = 26, 40 %). We found that, among our respondents with a history of cleft palate, the incidence of cholesteatoma was 39 %. Among respondents without a history of cleft palate, the incidence of cholesteatoma was 13 % CONCLUSIONS: Otologic issues, such as cholesteatoma, can have permanent implications including hearing loss that can be minimized by early identification and treatment. The estimated incidence of cholesteatoma among our participants is far above the estimated incidence of cholesteatoma in the general population with and without a history of cleft palate, suggesting an independent contribution of EDT-ACPs to the risk of cholesteatoma.

Exposure to residential greenness, perceived stress, and depressive symptoms in a North American preconception cohort.

BACKGROUND: Studies suggest that greater exposure to natural vegetation (i.e., greenness) is associated with better mental health. However, there is limited research on greenness and mental health in the preconception period, a critical window of exposure in the life course. We investigated the associations of residential greenness with perceived stress and depressive symptoms using cross-sectional data from a cohort of pregnancy planners. METHODS: From 2013 to 2019, we enrolled female-identified participants aged 21-45 years who were trying to conceive without the use of fertility treatment into a North American preconception cohort study (Pregnancy Study Online [PRESTO]). On the baseline questionnaire, participants completed the 10-item Perceived Stress Scale (PSS) and the Major Depression Inventory (MDI). Using geocoded addresses, we estimated residential greenness exposure via satellite imagery (Normalized Difference Vegetation Index [NDVI]) in a 100m buffer. We estimated mean differences and 95% confidence intervals for the association of greenness with perceived stress and depression scores using linear regression models, adjusting for individual and neighborhood sociodemographic characteristics. We also evaluated the extent to which associations were modified by urbanicity and neighborhood socioeconomic status (SES). RESULTS: Among 9718 participants, mean age was 29.9 years, 81.5% identified as non-Hispanic White, 25% had household incomes <$50,000, and mean neighborhood income was $61,932. In adjusted models, higher greenness was associated with lower stress and depression scores (mean difference per interquartile range in greenness: -0.20, 95% CI: -0.39, -0.01; and -0.19, 95% CI: -0.48, 0.10, respectively). The association was stronger among residents of lower SES neighborhoods in urban areas (PSS: -0.57, 95% CI: -1.00, -0.15; MDI: -0.72, 95% CI: -1.40, -0.04). CONCLUSIONS: Higher greenness exposure was associated with lower stress and depressive symptoms among pregnancy planners, particularly in lower-SES neighborhoods.

Measuring the Social Impact of Burn injuries in Australia: An Adaptation of the Life Impact Burn Recovery Evaluation - The Aus-LIBRE Profile.

Burn survivors can experience social participation challenges throughout their recovery. The aim of this study was to develop a novel Australian English translation of the Life Impact Burn Recovery Evaluation (LIBRE) Profile, the Aus-LIBRE Profile. This study consisted of three stages: 1) translation of the LIBRE Profile from American to Australian English by Australian researchers/burns clinicians; 2) piloting and cognitive evaluation of the Aus-LIBRE Profile with burn survivors to assess the clarity and consistency of the interpretation of each individual item, and 3) review of the Aus-LIBRE Profile by colleagues who identify as Aboriginal Australians for cross-cultural validation. In stage 2, investigators administered the translated questionnaire to 20 Australian patients with burn injuries in the outpatient clinic (10 patients from xx and 10 patients from yy). Face validity of the Aus-LIBRE Profile was tested in 20 burns survivors (11 females) ranging from 21 to 74 years (median age 43 years). The total body surface area (TBSA) burned ranged from 1% to 50% (median 10%). Twelve language changes were made based on the feedback from the burn clinicians/researchers, study participants and colleagues who identify as Aboriginal Australians. Using a formal translation process, the Aus-LIBRE Profile was adapted for use in the Australian burn population. The Aus-LIBRE Profile will require psychometric validation and testing in the Australian burn patient population before broader application of the scale.