Evolution and lineage dynamics of a transmissible cancer in Tasmanian devils.

Devil facial tumour 1 (DFT1) is a transmissible cancer clone endangering the Tasmanian devil. The expansion of DFT1 across Tasmania has been documented, but little is known of its evolutionary history. We analysed genomes of 648 DFT1 tumours collected throughout the disease range between 2003 and 2018. DFT1 diverged early into five clades, three spreading widely and two failing to persist. One clade has replaced others at several sites, and rates of DFT1 coinfection are high. DFT1 gradually accumulates copy number variants (CNVs), and its telomere lengths are short but constant. Recurrent CNVs reveal genes under positive selection, sites of genome instability, and repeated loss of a small derived chromosome. Cultured DFT1 cell lines have increased CNV frequency and undergo highly reproducible convergent evolution. Overall, DFT1 is a remarkably stable lineage whose genome illustrates how cancer cells adapt to diverse environments and persist in a parasitic niche.

How Much Data Is Enough? A Reliable Methodology to Examine Long-Term Wearable Data Acquisition in Gait and Postural Sway.

Wearable sensors facilitate the evaluation of gait and balance impairment in the free-living environment, often with observation periods spanning weeks, months, and even years. Data supporting the minimal duration of sensor wear, which is necessary to capture representative variability in impairment measures, are needed to balance patient burden, data quality, and study cost. Prior investigations have examined the duration required for resolving a variety of movement variables (e.g., gait speed, sit-to-stand tests), but these studies use differing methodologies and have only examined a small subset of potential measures of gait and balance impairment. Notably, postural sway measures have not yet been considered in these analyses. Here, we propose a three-level framework for examining this problem. Difference testing and intra-class correlations (ICC) are used to examine the agreement in features computed from potential wear durations (levels one and two). The association between features and established patient reported outcomes at each wear duration is also considered (level three) for determining the necessary wear duration. Utilizing wearable accelerometer data continuously collected from 22 persons with multiple sclerosis (PwMS) for 6 weeks, this framework suggests that 2 to 3 days of monitoring may be sufficient to capture most of the variability in gait and sway; however, longer periods (e.g., 3 to 6 days) may be needed to establish strong correlations to patient-reported clinical measures. Regression analysis indicates that the required wear duration depends on both the observation frequency and variability of the measure being considered. This approach provides a framework for evaluating wear duration as one aspect of the comprehensive assessment, which is necessary to ensure that wearable sensor-based methods for capturing gait and balance impairment in the free-living environment are fit for purpose.

Spatiotemporal coordination of cell division and growth during organ morphogenesis.

A developing plant organ exhibits complex spatiotemporal patterns of growth, cell division, cell size, cell shape, and organ shape. Explaining these patterns presents a challenge because of their dynamics and cross-correlations, which can make it difficult to disentangle causes from effects. To address these problems, we used live imaging to determine the spatiotemporal patterns of leaf growth and division in different genetic and tissue contexts. In the simplifying background of the speechless (spch) mutant, which lacks stomatal lineages, the epidermal cell layer exhibits defined patterns of division, cell size, cell shape, and growth along the proximodistal and mediolateral axes. The patterns and correlations are distinctive from those observed in the connected subepidermal layer and also different from the epidermal layer of wild type. Through computational modelling we show that the results can be accounted for by a dual control model in which spatiotemporal control operates on both growth and cell division, with cross-connections between them. The interactions between resulting growth and division patterns lead to a dynamic distributions of cell sizes and shapes within a deforming leaf. By modulating parameters of the model, we illustrate how phenotypes with correlated changes in cell size, cell number, and organ size may be generated. The model thus provides an integrated view of growth and division that can act as a framework for further experimental study.

A second transmissible cancer in Tasmanian devils.

Clonally transmissible cancers are somatic cell lineages that are spread between individuals via the transfer of living cancer cells. There are only three known naturally occurring transmissible cancers, and these affect dogs, soft-shell clams, and Tasmanian devils, respectively. The Tasmanian devil transmissible facial cancer was first observed in 1996, and is threatening its host species with extinction. Until now, this disease has been consistently associated with a single aneuploid cancer cell lineage that we refer to as DFT1. Here we describe a second transmissible cancer, DFT2, in five devils located in southern Tasmania in 2014 and 2015. DFT2 causes facial tumors that are grossly indistinguishable but histologically distinct from those caused by DFT1. DFT2 bears no detectable cytogenetic similarity to DFT1 and carries a Y chromosome, which contrasts with the female origin of DFT1. DFT2 shows different alleles to both its hosts and DFT1 at microsatellite, structural variant, and major histocompatibility complex (MHC) loci, confirming that it is a second cancer that can be transmitted between devils as an allogeneic, MHC-discordant graft. These findings indicate that Tasmanian devils have spawned at least two distinct transmissible cancer lineages and suggest that transmissible cancers may arise more frequently in nature than previously considered. The discovery of DFT2 presents important challenges for the conservation of Tasmanian devils and raises the possibility that this species is particularly prone to the emergence of transmissible cancers. More generally, our findings highlight the potential for cancer cells to depart from their hosts and become dangerous transmissible pathogens.

Large-effect loci affect survival in Tasmanian devils (Sarcophilus harrisii) infected with a transmissible cancer.

Identifying the genetic architecture of complex phenotypes is a central goal of modern biology, particularly for disease-related traits. Genome-wide association methods are a classical approach for identifying the genomic basis of variation in disease phenotypes, but such analyses are particularly challenging in natural populations due to sample size difficulties. Extensive mark-recapture data, strong linkage disequilibrium and a lethal transmissible cancer make the Tasmanian devil (Sarcophilus harrisii) an ideal model for such an association study. We used a RAD-capture approach to genotype 624 devils at ~16,000 loci and then used association analyses to assess the heritability of three cancer-related phenotypes: infection case-control (where cases were infected devils and controls were devils that were never infected), age of first infection and survival following infection. The SNP array explained much of the phenotypic variance for female survival (>80%) and female case-control (>61%). We found that a few large-effect SNPs explained much of the variance for female survival (~5 SNPs explained >61% of the total variance), whereas more SNPs (~56) of smaller effect explained less of the variance for female case-control (~23% of the total variance). By contrast, these same SNPs did not account for a significant proportion of phenotypic variance in males, suggesting that the genetic bases of these traits and/or selection differ across sexes. Loci involved with cell adhesion and cell-cycle regulation underlay trait variation, suggesting that the devil immune system is rapidly evolving to recognize and potentially suppress cancer growth through these pathways. Overall, our study provided necessary data for genomics-based conservation and management in Tasmanian devils.

A novel role for STOMATAL CARPENTER 1 in stomata patterning.

BACKGROUND: Guard cells (GCs) are specialised cells within the plant epidermis which form stomatal pores, through which gas exchange can occur. The GCs derive through a specialised lineage of cell divisions which is specified by the transcription factor SPEECHLESS (SPCH), the expression of which can be detected in undifferentiated epidermal cells prior to asymmetric division. Other transcription factors may act before GC specification and be required for correct GC patterning. Previously, the DOF transcription factor STOMATAL CARPENTER 1 (SCAP1) was shown to be involved in GC function, by activating a set of GC-specific genes required for GC maturation and activity. It is thus far unknown whether SCAP1 can also affect stomatal development. RESULTS: Here we show that SCAP1 expression can also be observed in young leaf primordia, before any GC differentiation occurs. The study of transgenic plants carrying a proSCAP1:GUS-GFP transcriptional fusion, coupled with qPCR analyses, indicate that SCAP1 expression peaks in a temporal window which is coincident with expression of stomatal patterning genes. Independent scap1 loss-of-function mutants have a reduced number of GCs whilst SCAP1 over expression lines have an increased number of GCs, in addition to altered GC distribution and spacing patterns. The study of early markers for stomatal cell lineage in a background carrying gain-of-function alleles of SCAP1 revealed that, compared to the wild type, an increased number of protodermal cells are recruited in the GC lineage, which is reflected in an increased number of meristemoids. CONCLUSIONS: Our results suggest an early role for SCAP1 in GC differentiation. We propose that a function of SCAP1 is to integrate different aspects of GC biology including specification, spacing, maturation and function.

Standards for plant synthetic biology: a common syntax for exchange of DNA parts.

Inventors in the field of mechanical and electronic engineering can access multitudes of components and, thanks to standardization, parts from different manufacturers can be used in combination with each other. The introduction of BioBrick standards for the assembly of characterized DNA sequences was a landmark in microbial engineering, shaping the field of synthetic biology. Here, we describe a standard for Type IIS restriction endonuclease-mediated assembly, defining a common syntax of 12 fusion sites to enable the facile assembly of eukaryotic transcriptional units. This standard has been developed and agreed by representatives and leaders of the international plant science and synthetic biology communities, including inventors, developers and adopters of Type IIS cloning methods. Our vision is of an extensive catalogue of standardized, characterized DNA parts that will accelerate plant bioengineering.

Cortical microtubule arrays undergo rotary movements in Arabidopsis hypocotyl epidermal cells.

Plant-cell expansion is controlled by cellulose microfibrils in the wall with microtubules providing tracks for cellulose synthesizing enzymes. Microtubules can be reoriented experimentally and are hypothesized to reorient cyclically in aerial organs, but the mechanism is unclear. Here, Arabidopsis hypocotyl microtubules were labelled with AtEB1a-GFP (Arabidopsis microtubule end-binding protein 1a) or GFP-TUA6 (Arabidopsis alpha-tubulin 6) to record long cycles of reorientation. This revealed microtubules undergoing previously unseen clockwise or counter-clockwise rotations. Existing models emphasize selective shrinkage and regrowth or the outcome of individual microtubule encounters to explain realignment. Our higher-order view emphasizes microtubule group behaviour over time. Successive microtubules move in the same direction along self-sustaining tracks. Significantly, the tracks themselves migrate, always in the direction of the individual fast-growing ends, but twentyfold slower. Spontaneous sorting of tracks into groups with common polarities generates a mosaic of domains. Domains slowly migrate around the cell in skewed paths, generating rotations whose progressive nature is interrupted when one domain is displaced by collision with another. Rotary movements could explain how the angle of cellulose microfibrils can change from layer to layer in the polylamellate cell wall.

Mapping human resources for eye health in 21 countries of sub-Saharan Africa: current progress towards VISION 2020.

BACKGROUND: Development of human resources for eye health (HReH) is a major focus of the Global Action Plan 2014 to 2019 to reduce the prevalence of avoidable visual impairment by 25% by the year 2019. The eye health workforce is thought to be much smaller in sub-Saharan Africa than in other regions of the world but data to support this for policy-making is scarce. We collected HReH and cataract surgeries data from 21 countries in sub-Sahara to estimate progress towards key suggested population-based VISION 2020 HReH indicators and cataract surgery rates (CSR) in 2011. METHODS: Routinely collected data on practitioner and surgery numbers in 2011 was requested from national eye care coordinators via electronic questionnaires. Telephone and e-mail discussions were used to determine data collection strategies that fit the national context and to verify reported data quality. Information was collected on six practitioner cadres: ophthalmologists, cataract surgeons, ophthalmic clinical officers, ophthalmic nurses, optometrists and 'mid-level refractionists' and combined with publicly available population data to calculate practitioner to population ratios and CSRs. Associations with development characteristics were conducted using Wilcoxon rank sum tests and Spearman rank correlations. RESULTS: HReH data was not easily available. A minority of countries had achieved the suggested VISION 2020 targets in 2011; five countries for ophthalmologists/cataract surgeons, four for ophthalmic nurses/clinical officers and two for CSR. All countries were below target for optometrists, even when other cadres who perform refractions as a primary duty were considered. The regional (sample) ratio for surgeons (ophthalmologists and cataract surgeons) was 2.9 per million population, 5.5 for ophthalmic clinical officers and nurses, 3.7 for optometrists and other refractionists, and 515 for CSR. A positive correlation between GDP and CSR as well as many practitioner ratios was observed (CSR P = 0.0042, ophthalmologists P = 0.0034, cataract surgeons, ophthalmic nurses and optometrists 0.1 > P > 0.05). CONCLUSIONS: With only a minority of countries in our sample having reached suggested ophthalmic cadre targets and none having reached targets for refractionists in 2011, substantially more targeted investment in HReH may be needed for VISION 2020 aims to be achieved in sub-Saharan Africa.

Trends and implications for achieving VISION 2020 human resources for eye health targets in 16 countries of sub-Saharan Africa by the year 2020.

BACKGROUND: Development of human resources for eye health (HReH) is a major global eye health strategy to reduce the prevalence of avoidable visual impairment by the year 2020. Building on our previous analysis of current progress towards key HReH indicators and cataract surgery rates (CSRs), we predicted future indicator achievement among 16 countries of sub-Saharan Africa by 2020. METHODS: Surgical and HReH data were collected from national eye care programme coordinators on six practitioner cadres: ophthalmologists, cataract surgeons, ophthalmic clinical officers, ophthalmic nurses, optometrists and 'mid-level refractionists' and combined them with publicly available population data to calculate practitioner-to-population ratios and CSRs. Data on workforce entry and exit (2008 to 2010) was used to project practitioner population and CSR growth between 2011 and 2020 in relation to projected growth in the general population. Associations between indicator progress and the presence of a non-physician cataract surgeon cadre were also explored using Wilcoxon rank sum tests and Spearman rank correlations. RESULTS: In our 16-country sample, practitioner per million population ratios are predicted to increase slightly for surgeons (ophthalmologists/cataract surgeons, from 3.1 in 2011 to 3.4 in 2020) and ophthalmic nurses/clinical officers (5.8 to 6.8) but remain low for refractionists (including optometrists, at 3.6 in 2011 and 2020). Among countries that have not already achieved target indicators, however, practitioner growth will be insufficient for any additional countries to reach the surgeon and refractionist targets by year 2020. Without further strategy change and investment, even after 2020, surgeon growth is only expected to sufficiently outpace general population growth to reach the target in one country. For nurses, two additional countries will achieve the target while one will fall below it. In 2011, high surgeon practitioner ratios were associated with high CSR, regardless of the type of surgeon employed. The cataract surgeon workforce is growing proportionately faster than the ophthalmologist. CONCLUSIONS: The HReH workforce is not growing fast enough to achieve global eye health targets in most of the sub-Saharan countries we surveyed by 2020. Countries seeking to make rapid progress to improve CSR could prioritise investment in training new cataract surgeons over ophthalmologists and improving surgical output efficiency.

Characterising the Tasmanian devil (Sarcophilus harrisii) pouch microbiome in lactating and non-lactating females.

Wildlife harbour a diverse range of microorganisms that affect their health and development. Marsupials are born immunologically naïve and physiologically underdeveloped, with primary development occurring inside a pouch. Secretion of immunological compounds and antimicrobial peptides in the epithelial lining of the female's pouch, pouch young skin, and through the milk, are thought to boost the neonate's immune system and potentially alter the pouch skin microbiome. Here, using 16S rRNA amplicon sequencing, we characterised the Tasmanian devil pouch skin microbiome from 25 lactating and 30 non-lactating wild females to describe and compare across these reproductive stages. We found that the lactating pouch skin microbiome had significantly lower amplicon sequence variant richness and diversity than non-lactating pouches, however there was no overall dissimilarity in community structure between lactating and non-lactating pouches. The top five phyla were found to be consistent between both reproductive stages, with over 85% of the microbiome being comprised of Firmicutes, Proteobacteria, Fusobacteriota, Actinobacteriota, and Bacteroidota. The most abundant taxa remained consistent across all taxonomic ranks between lactating and non-lactating pouch types. This suggests that any potential immunological compounds or antimicrobial peptide secretions did not significantly influence the main community members. Of the more than 16,000 total identified amplicon sequence variants, 25 were recognised as differentially abundant between lactating and non-lactating pouches. It is proposed that the secretion of antimicrobial peptides in the pouch act to modulate these microbial communities. This study identifies candidate bacterial clades on which to test the activity of Tasmanian devil antimicrobial peptides and their role in pouch young protection, which in turn may lead to future therapeutic development for human diseases.

Obstetric fistula in Southern Sudan: situational analysis and Key Informant Method to estimate prevalence.

BACKGROUND: Obstetric fistula is a severe condition which can have devastating consequences for a woman's life. Despite a considerable literature, very little is known about its prevalence. This project was conducted to carry out a situational analysis of fistula services in South Sudan and to pilot test the Key Informant Method (KIM) to estimate the prevalence of fistula in a region of South Sudan. METHODS: Key stakeholder interviews, document reviews and fistula surgery record reviews were undertaken. A KIM survey was conducted in a district of Western Bahr-el-Ghazal in January 2012. One hundred sixty-six community-based distributors, traditional birth attendants and village midwives were trained as key informants to identify women with fistula in the community. Women identified were subsequently examined by an obstetrician and nurse to verify whether they had a fistula. RESULTS: There were limited fistula repair services in South Sudan. Approximately 50-80 women per year attend periodic campaigns, with around half having a fistula and receiving a repair. On average a further 5 women a year received fistula repair from hospital services. Ten women with potential fistula were identified via KIM; all confirmed by the obstetrician. Of these, three were from the survey area, which had 8,865 women of reproductive age (15-49 years). This gives a minimal estimated prevalence of at least 30 fistulas per 100,000 women of reproductive age (95% CI 10-100). CONCLUSIONS: Routine fistula repair services available do not meet the population's needs. The pilot study suggests that KIM can be used to identify women with fistula in the community. Data on fistula are generally poor; the KIM methodology we used in South Sudan yielded a lower fistula prevalence than estimates reported previously in the region.

Chest-Based Wearables and Individualized Distributions for Assessing Postural Sway in Persons With Multiple Sclerosis.

Typical assessments of balance impairment are subjective or require data from cumbersome and expensive force platforms. Researchers have utilized lower back (sacrum) accelerometers to enable more accessible, objective measurement of postural sway for use in balance assessment. However, new sensor patches are broadly being deployed on the chest for cardiac monitoring, opening a need to determine if measurements from these devices can similarly inform balance assessment. Our aim in this work is to validate postural sway measurements from a chest accelerometer. To establish concurrent validity, we considered data from 16 persons with multiple sclerosis (PwMS) asked to stand on a force platform while also wearing sensor patches on the sacrum and chest. We found five of 15 postural sway features derived from the chest and sacrum were significantly correlated with force platform-derived features, which is in line with prior sacrum-derived findings. Clinical significance was established using a sample of 39 PwMS who performed eyes-open, eyes-closed, and tandem standing tasks. This cohort was stratified by fall status and completed several patient-reported measures (PRM) of balance and mobility impairment. We also compared sway features derived from a single 30-second period to those derived from a one-minute period with a sliding window to create individualized distributions of each postural sway feature (ID method). We find traditional computation of sway features from the chest is sensitive to changes in PRMs and task differences. Distribution characteristics from the ID method establish additional relationships with PRMs, detect differences in more tasks, and distinguish between fall status groups. Overall, the chest was found to be a valid location to monitor postural sway and we recommend utilizing the ID method over single-observation analyses.

ADMANI: Annotated Digital Mammograms and Associated Non-Image Datasets.

Supplemental material is available for this article. Keywords: Mammography, Screening, Convolutional Neural Network (CNN) Published under a CC BY 4.0 license. See also the commentary by Cadrin-Chênevert in this issue.

The evolution of two transmissible cancers in Tasmanian devils.

Tasmanian devils have spawned two transmissible cancer lineages, named devil facial tumor 1 (DFT1) and devil facial tumor 2 (DFT2). We investigated the genetic diversity and evolution of these clones by analyzing 78 DFT1 and 41 DFT2 genomes relative to a newly assembled, chromosome-level reference. Time-resolved phylogenetic trees reveal that DFT1 first emerged in 1986 (1982 to 1989) and DFT2 in 2011 (2009 to 2012). Subclone analysis documents transmission of heterogeneous cell populations. DFT2 has faster mutation rates than DFT1 across all variant classes, including substitutions, indels, rearrangements, transposable element insertions, and copy number alterations, and we identify a hypermutated DFT1 lineage with defective DNA mismatch repair. Several loci show plausible evidence of positive selection in DFT1 or DFT2, including loss of chromosome Y and inactivation of MGA, but none are common to both cancers. This study reveals the parallel long-term evolution of two transmissible cancers inhabiting a common niche in Tasmanian devils.

The experience of being an 'extracorporeal membrane oxygenation' relative within the CESAR trial.

AIMS AND OBJECTIVES: This article reports a study exploring experiences of the relatives of adult patients receiving extracorporeal membrane oxygenation (ECMO) within the CESAR trial. BACKGROUND: Relatives of ECMO patients have undergone unique experiences which have not previously been addressed in the literature and thus may have different needs which may not be met by present practice. DESIGN AND METHODS: A grounded theory approach was adopted. In-depth unstructured interviews were conducted with family members of 10 surviving adult patients who had been randomized and received ECMO within the CESAR trial. RESULTS: Relatives have a range of needs specific to the ECMO experience, these include the depth and positivity of information. Particular areas for support were concerning a perceived self-inflicted nature of illness, personal guilt, distance from home, receiving 'the call', weaning from sedation and transfer/discharge from the ECMO unit. CONCLUSIONS: Relatives would benefit from the opportunity to talk about their 'ECMO experiences' following the patient's recovery to enable them and their families to 'move on'. RELEVANCE TO CLINICAL PRACTICE: Interventions need to be in place to follow-up relatives and patients to provide ongoing support to the family unit.

The Sit-to-Stand Transition as a Biomarker for Impairment: Comparison of Instrumented 30-Second Chair Stand Test and Daily Life Transitions in Multiple Sclerosis.

Falls and mobility deficits are common in people with multiple sclerosis (PwMS) across all levels of clinical disability. However, functional mobility observed in supervised settings may not reflect daily life which may impact assessments of fall risk and impairment in the clinic. To investigate this further, we compared the utility of sensor-based performance metrics from sit-stand transitions during daily life and a structured task to inform fall risk and impairment in PwMS. Thirty-seven PwMS instrumented with wearable sensors (thigh and chest) completed supervised 30-second chair stand tests (30CST) and underwent two days of instrumented daily life monitoring. Performance metrics were computed for sit-stand transitions during daily life and 30CSTs. EDSS sub scores and fall history were used to dichotomize participants into groups: pyramidal/no pyramidal impairment, sensory/no sensory impairment and high/low fall risk. The ability of performance metrics to discriminate between groups was assessed using the area under the curve (AUC). The feature that best discriminated between high and low fall risk was a chest acceleration measurement from the supervised instrumented 30CST (AUC = 0.89). Only chest features indicated sensory impairment, however the task was different between supervised and daily life. The metric that best discriminated pyramidal impairment was a chest-derived feature (AUC = 0.89) from supervised 30CSTs. The highest AUC from daily life was observed in faller classification with the average sit-stand time (0.81). While characterizing sit-stand performance during daily life may yield insights into fall risk and may be performed without a clinic visit, there remains value to conducting supervised functional assessments to provide the best classification performance between the investigated impairments in this sample.

Restoring faith in conservation action: Maintaining wild genetic diversity through the Tasmanian devil insurance program.

Conservation breeding programs aim to maintain 90% wild genetic diversity, but rarely assess functional diversity. Here, we compare both genome-wide and functional diversity (in over 500 genes) of Tasmanian devils (Sarcophilus harrisii) within the insurance metapopulation and across the species' range (64,519 km2). Populations have declined by 80% since 1996 due to a contagious cancer, devil facial tumor disease (DFTD). However, predicted local extinctions have not occurred. Recent suggestions of selection for "resistance" alleles in the wild precipitated concerns that insurance population devils may be unsuitable for translocations. Using 830 wild samples collected at 31 locations between 2012 and 2021, and 553 insurance metapopulation devils, we show that the insurance metapopulation is representative of current wild genetic diversity. Allele frequencies at DFTD-associated loci were not substantially different between captive and wild devils. Methods presented here are valuable for others investigating evolutionary potential in threatened species, particularly ones under significant selective pressures.

Quality of life and functional status of patients treated with venovenous extracorporeal membrane oxygenation at 6 months.

PURPOSE: Quality of life (QoL) outcomes of patients treated with extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) have been conflicting. This study reports on QoL outcomes for a broad group of ARDS patients managed with up-to-date treatment modalities. METHODS: We prospectively recruited patients at a quaternary hospital in the United Kingdom from 2013 to 2015 who were treated with ECMO for ARDS. We evaluated their pulmonary function and QoL at 6-months after admission using three QoL instruments: EuroQoL 5D (EQ-5), HADS, and PTSS-14. RESULTS: Forty-three patients included in the analysis had near-normal pulmonary function at 6 months. HADS showed moderate-to-severe anxiety and depression in 32% and 11% of patients, respectively. PTSS-14 showed 29% had signs of post-traumatic stress disorder. EQ-5D showed that 67% of patients had difficulty returning to usual activities, 74% suffered some pain, none reported severe problems and 77% were able to return to work. No clinical or demographic variables were associated with poor 6-month QoL. CONCLUSIONS: Patients with ARDS treated with ECMO generally had good QoL outcomes, similar to outcomes reported for patients managed without ECMO. With respect to QoL, VV-EMCO represents a valid treatment modality for patients with refractory ARDS.