Characterizing intracellular mechanics via optical tweezers-based microrheology.

Intracellular organization is a highly regulated homeostatic state maintained to ensure eukaryotic cells' correct and efficient functioning. Thanks to decades of research, vast knowledge of the proteins involved in intracellular transport and organization has been acquired. However, how these influence and potentially regulate the intracellular mechanical properties of the cell is largely unknown. There is a deep knowledge gap between the understanding of cortical mechanics, which is accessible by a series of experimental tools, and the intracellular situation that has been largely neglected due to the difficulty of performing intracellular mechanics measurements. Recently, tools required for such quantitative and localized analysis of intracellular mechanics have been introduced. Here, we review how these approaches and the resulting viscoelastic models lead the way to a full mechanical description of the cytoplasm, which is instrumental for a quantitative characterization of the intracellular life of cells.

Fungal traits help to understand the decomposition of simple and complex plant litter.

Litter decomposition is a key ecosystem process, relevant for the release and storage of nutrients and carbon in soil. Soil fungi are one of the dominant drivers of organic matter decomposition, but fungal taxa differ substantially in their functional ability to decompose plant litter. Knowledge is mostly based on observational data and subsequent molecular analyses and in vitro studies have been limited to forest ecosystems. In order to better understand functional traits of saprotrophic soil fungi in grassland ecosystems, we isolated 31 fungi from a natural grassland and performed several in vitro studies testing for i) leaf and wood litter decomposition, ii) the ability to use carbon sources of differing complexity, iii) the enzyme repertoire. Decomposition strongly varied among phyla and isolates, with Ascomycota decomposing the most and Mucoromycota decomposing the least. The phylogeny of the fungi and their ability to use complex carbon were the most important predictors for decomposition. Our findings show that it is crucial to understand the role of individual members and functional groups within the microbial community. This is an important way forward to understand the role of microbial community composition for the prediction of litter decomposition and subsequent potential carbon storage in grassland soils.

Trapped tidal currents generate freely propagating internal waves at the Arctic continental slope.

Energetic tidal currents in the Arctic play an important role in local mixing processes, but they are primarily confined to the shelves and continental slopes due to topographic trapping north of their critical latitude. Recent studies employing idealized models have suggested that the emergence of higher harmonic tidal waves along these slopes could serve as a conduit for tidal energy transmission into the Arctic Basin. Here we provide observational support from an analysis of yearlong observations from three densely-instrumented oceanographic moorings spanning 30 km across the continental slope north of Svalbard ([Formula: see text]81.3[Formula: see text]N). Full-depth current records show strong barotropic diurnal tidal currents, dominated by the K[Formula: see text] constituent. These sub-inertial currents vary sub-seasonally and are strongest at the 700-m isobath due to the topographic trapping. Coinciding with the diurnal tide peak in summer 2019, we observe strong baroclinic semidiurnal currents exceeding 10 cm s[Formula: see text] between 500 m and 1000 m depth about 10 km further offshore at the outer mooring. In this semidiurnal band, we identify super-inertial K[Formula: see text] waves, and present evidence that their frequency, timing, polarization, propagation direction and depths are consistent with the generation as higher harmonics of the topographically trapped K[Formula: see text] tide at the continental slope.

Descemet Membrane Endothelial Keratoplasty and Triple Descemet Membrane Endothelial Keratoplasty in Eyes With Macular Comorbidity.

PURPOSE: The aim of this study was to evaluate results after Descemet membrane endothelial keratoplasty (DMEK) and DMEK with cataract surgery (triple DMEK) in eyes with endothelial dysfunction and concomitant macular pathology. METHODS: A monocentric, prospective clinical observational study of patients who underwent DMEK or triple DMEK surgery at the Department of Ophthalmology, University Hospital Düsseldorf, Germany, from June 2013 to February 2016 was conducted. Sex, age, best-corrected visual acuity (BCVA), central corneal thickness, endothelial cell density, and central retinal thickness in the 1 millimeter zone were analyzed. RESULTS: A total of 209 eyes were included in the study. Forty-two eyes (20.1%) had vision-limiting concomitant maculopathies. These were age-related macular degeneration (n = 17, 8.1%), epiretinal gliosis (n = 13, 6.2%), chronic macular edema (n = 7, 3.3%), macular holes (n = 3, 1.4%), and macular scarring (n = 2, 1.0%). BCVA significantly increased in patients without maculopathy from 0.6 ± 0.33 logMAR to 0.1 ± 0.15 logMAR ( P < 0.001) and also in patients with maculopathy from 0.9 ± 0.38 logMAR to 0.27 ± 0.23 logMAR 12 months postoperatively ( P < 0.001). There was a significant central retinal thickness increase of 34.1 µm 6 weeks after triple DMEK in the central 1-mm zone ( P = 0.011). This increase was insignificant after DMEK. Postoperative macular edema occurred in 5.9% of cases after DMEK and 8.1% after triple DMEK, which was not significantly different. CONCLUSIONS: DMEK and triple DMEK significantly increase BCVA in eyes with concomitant maculopathy. Postoperative macular edema is a common disorder after lamellar keratoplasty; therefore, prophylactic treatment with nonsteroidal antiinflammatory drugs should be considered. Maculopathies did not predispose the development of postoperative macular edema.

Cerebellar transcranial current stimulation - An intraindividual comparison of different techniques.

Transcranial current stimulation (tCS) techniques have been shown to induce cortical plasticity. As an important relay in the motor system, the cerebellum is an interesting target for plasticity induction using tCS, aiming to modulate its excitability and connectivity. However, until now it remains unclear, which is the most effective tCS method for inducing plasticity in the cerebellum. Thus, in this study, the effects of anodal transcranial direct current stimulation (tDCS), 50 Hz transcranial alternating current stimulation (50 Hz tACS), and high frequency transcranial random noise stimulation (tRNS) were compared with sham stimulation in 20 healthy subjects in a within-subject design. tCS was applied targeting the cerebellar lobe VIIIA using neuronavigation. We measured corticospinal excitability, short-interval intracortical inhibition (SICI), short-latency afferent inhibition (SAI), and cerebellar brain inhibition (CBI) and performed a sensor-based movement analysis at baseline and three times after the intervention (post1 = 15 min; post2 = 55 min; post3 = 95 min). Corticospinal excitability increased following cerebellar tACS and tRNS compared to sham stimulation. This effect was most pronounced directly after stimulation but lasted for at least 55 min after tACS. Cortico-cortical and cerebello-cortical conditioning protocols, as well as sensor-based movement analyses, did not change. Our findings suggest that cerebellar 50 Hz tACS is the most effective protocol to change corticospinal excitability.

A novel gradient echo data based vein segmentation algorithm and its application for the detection of regional cerebral differences in venous susceptibility.

Accurate segmentation of cerebral venous vasculature from gradient echo data is of central importance in several areas of neuroimaging such as for the susceptibility-based assessment of brain oxygenation or planning of electrode placement in deep brain stimulation. In this study, a vein segmentation algorithm for single- and multi-echo gradient echo data is proposed. First, susceptibility maps, true susceptibility-weighted images, and, in the multi-echo case, R2* maps were generated from the gradient echo data. These maps were filtered with an inverted Hamming filter to suppress background contrast as well as artifacts from field inhomogeneities at the brain boundaries. A shearlet-based scale-wise representation was generated to calculate a vesselness function and to generate segmentations based on local thresholding. The accuracy of the proposed algorithm was evaluated for different echo times and image resolutions using a manually generated reference segmentation and two vein segmentation algorithms (Frangi vesselness-based, recursive vesselness filter) as a reference with the Dice and Cohen's coefficients as well as the modified Hausdorff distance. The Frangi-based and recursive vesselness filter methods were significantly outperformed with regard to all error metrics. Applying the algorithm, susceptibility differences likely related to differences in blood oxygenation between superficial and deep venous territories could be demonstrated.

Pediatric multicellular tumor spheroid models illustrate a therapeutic potential by combining BH3 mimetics with Natural Killer (NK) cell-based immunotherapy.

The induction of apoptosis is a direct way to eliminate tumor cells and improve cancer therapy. Apoptosis is tightly controlled by the balance of pro- and antiapoptotic Bcl-2 proteins. BH3 mimetics neutralize the antiapoptotic function of Bcl-2 proteins and are highly promising compounds inducing apoptosis in several cancer entities including pediatric malignancies. However, the clinical application of BH3 mimetics in solid tumors is impeded by the frequent resistance to single BH3 mimetics and the anticipated toxicity of high concentrations or combination treatments. One potential avenue to increase the potency of BH3 mimetics is the development of immune cell-based therapies to counteract the intrinsic apoptosis resistance of tumor cells and sensitize them to immune attack. Here, we describe spheroid cultures of pediatric cancer cells that can serve as models for drug testing. In these 3D models, we were able to demonstrate that activated allogeneic Natural Killer (NK) cells migrated into tumor spheroids and displayed cytotoxicity against a wide range of pediatric cancer spheroids, highlighting their potential as anti-tumor effector cells. Next, we investigated whether treatment of tumor spheroids with subtoxic concentrations of BH3 mimetics can increase the cytotoxicity of NK cells. Notably, the cytotoxic effects of NK cells were enhanced by the addition of BH3 mimetics. Treatment with either the Bcl-XL inhibitor A1331852 or the Mcl-1 inhibitor S63845 increased the cytotoxicity of NK cells and reduced spheroid size, while the Bcl-2 inhibitor ABT-199 had no effect on NK cell-mediated killing. Taken together, this is the first study to describe the combination of BH3 mimetics targeting Bcl-XL or Mcl-1 with NK cell-based immunotherapy, highlighting the potential of BH3 mimetics in immunotherapy.

Using Probabilistic Movement Primitives in Analyzing Human Motion Differences Under Transcranial Current Stimulation.

In medical tasks such as human motion analysis, computer-aided auxiliary systems have become the preferred choice for human experts for their high efficiency. However, conventional approaches are typically based on user-defined features such as movement onset times, peak velocities, motion vectors, or frequency domain analyses. Such approaches entail careful data post-processing or specific domain knowledge to achieve a meaningful feature extraction. Besides, they are prone to noise and the manual-defined features could hardly be re-used for other analyses. In this paper, we proposed probabilistic movement primitives (ProMPs), a widely-used approach in robot skill learning, to model human motions. The benefit of ProMPs is that the features are directly learned from the data and ProMPs can capture important features describing the trajectory shape, which can easily be extended to other tasks. Distinct from previous research, where classification tasks are mostly investigated, we applied ProMPs together with a variant of Kullback-Leibler (KL) divergence to quantify the effect of different transcranial current stimulation methods on human motions. We presented an initial result with 10 participants. The results validate ProMPs as a robust and effective feature extractor for human motions.

Multiparametric MRI for Characterization of the Basal Ganglia and the Midbrain.

Objectives To characterize subcortical nuclei by multi-parametric quantitative magnetic resonance imaging. Materials and Methods: The following quantitative multiparametric MR data of five healthy volunteers were acquired on a 7T MRI system: 3D gradient echo (GRE) data for the calculation of quantitative susceptibility maps (QSM), GRE sequences with and without off-resonant magnetic transfer pulse for magnetization transfer ratio (MTR) calculation, a magnetization-prepared 2 rapid acquisition gradient echo sequence for T1 mapping, and (after a coil change) a density-adapted 3D radial pulse sequence for 23Na imaging. First, all data were co-registered to the GRE data, volumes of interest (VOIs) for 21 subcortical structures were drawn manually for each volunteer, and a combined voxel-wise analysis of the four MR contrasts (QSM, MTR, T1, 23Na) in each structure was conducted to assess the quantitative, MR value-based differentiability of structures. Second, a machine learning algorithm based on random forests was trained to automatically classify the groups of multi-parametric voxel values from each VOI according to their association to one of the 21 subcortical structures. Results The analysis of the integrated multimodal visualization of quantitative MR values in each structure yielded a successful classification among nuclei of the ascending reticular activation system (ARAS), the limbic system and the extrapyramidal system, while classification among (epi-)thalamic nuclei was less successful. The machine learning-based approach facilitated quantitative MR value-based structure classification especially in the group of extrapyramidal nuclei and reached an overall accuracy of 85% regarding all selected nuclei. Conclusion Multimodal quantitative MR enabled excellent differentiation of a wide spectrum of subcortical nuclei with reasonable accuracy and may thus enable sensitive detection of disease and nucleus-specific MR-based contrast alterations in the future.

Intraoperative indocyanine green-visualization in a difficult to localize central cholangiocarcinoma - A case report.

INTRODUCTION AND IMPORTANCE: Near infrared fluorescence imaging with indocyanine green (ICG) can facilitate the intraoperative tumour localization and therefore a complete resection. Cholangiocarcinoma is an aggressive tumour and complete resection improves the outcome. Therefore, it is necessary to localize the tumour exactly but the translation of the preoperative imaging into the intraoperative setting can be difficult based only on sonography, computed tomography or magnetic resonance imaging. CASE PRESENTATION/CLINICAL FINDINGS AND INVESTIGATIONS/INTERVENTIONS AND OUTCOME: In this case a hepatic lesion suspicious for cholangiocarcinoma was discovered accidentally. Further diagnostics were unable to prove the diagnosis, therefore right hepatectomy was recommended and performed. Preoperatively ICG was administered and near infrared imaging was used intraoperatively clearly localizing the tumour, thus facilitating the resection. The intra- and postoperative course was uneventful. RELEVANCE AND IMPACT: This case report supports the very promising intraoperative use of fluorescence imaging for the localization of superficial hepatic tumours. Timing and correct administration of ICG is important.

Multi-oscillation microrheology via acoustic force spectroscopy enables frequency-dependent measurements on endothelial cells at high-throughput.

Active microrheology is one of the main methods to determine the mechanical properties of cells and tissue, and the modelling of these viscoelastic properties is under heavy debate with many competing approaches. Most experimental methods of active microrheology such as optical tweezers or atomic force microscopy based approaches rely on single cell measurements, and thus suffer from a low throughput. Here, we present a novel method for frequency-dependent microrheology on cells using acoustic forces which allows multiplexed measurements of several cells in parallel. Acoustic force spectroscopy (AFS) is used to generate multi-oscillatory forces in the range of pN-nN on particles attached to primary human umbilical vein endothelial cells (HUVEC) cultivated inside a microfluidic chip. While the AFS was introduced as a single-molecule technique to measure mechanochemical properties of biomolecules, we exploit the AFS to measure the dynamic viscoelastic properties of cells exposed to different conditions, such as flow shear stresses or drug injections. By controlling the force and measuring the position of the particle, the complex shear modulus G*(ω) can be measured continuously over several hours. The resulting power-law shear moduli are consistent with fractional viscoelastic models. In our experiments we confirm a decrease in shear modulus after perturbing the actin cytoskeleton via cytochalasin B. This effect was reversible after washing out the drug. Additionally, we include critical information for the usage of the new method AFS as a measurement tool showing its capabilities and limitations and we find that for performing viscoelastic measurements with the AFS, a thorough calibration and careful data analysis is crucial, for which we provide protocols and guidelines.

Measuring capabilities in health and physical activity promotion: a systematic review.

BACKGROUND: The capability approach by Amartya Sen and Martha Nussbaum has gained increasing attention in the field of public health. As it combines individual, social and structural factors and shifts the focus of attention from the actual behavior towards available options for health behaviors that people can actually choose from, it may help advance our understanding of complex health issues. OBJECTIVES: The aim of this article is to identify and describe tools available to measure capabilities within the context of health, with a specific focus on capabilities for health-enhancing physical activity. METHOD: We conducted a systematic literature review using 11 databases covering scientific journal articles published in English or German between the years 2000 and 2020 with a focus on capabilities for health or physical activity. RESULTS: We found a total of 51 articles meeting our inclusion criteria. Four articles measured capabilities using qualitative methods, one combined qualitative and quantitative methods, while the rest used quantitative methods. We identified a total 11 different capability questionnaires, all showing moderate to good validity/reliability. Only one questionnaire and one interview-based tool specifically dealt with capabilities for health enhancing physical activity. CONCLUSION: Although we were able to identify measurement tools for capabilities in health, this review has shown that there is no generic tool available for the measurement across all population- and age-groups, and tools focusing on physical activity are scarce. However, our results can be used as guide for future projects that aim at measuring capabilities.

Arctic tidal current atlas.

Tidal and wind-driven near-inertial currents play a vital role in the changing Arctic climate and the marine ecosystems. We compiled 429 available moored current observations taken over the last two decades throughout the Arctic to assemble a pan-Arctic atlas of tidal band currents. The atlas contains different tidal current products designed for the analysis of tidal parameters from monthly to inter-annual time scales. On shorter time scales, wind-driven inertial currents cannot be analytically separated from semidiurnal tidal constituents. Thus, we include 10-30 h band-pass filtered currents, which include all semidiurnal and diurnal tidal constituents as well as wind-driven inertial currents for the analysis of high-frequency variability of ocean dynamics. This allows for a wide range of possible uses, including local case studies of baroclinic tidal currents, assessment of long-term trends in tidal band kinetic energy and Arctic-wide validation of ocean circulation models. This atlas may also be a valuable tool for resource management and industrial applications such as fisheries, navigation and offshore construction.

Susceptibility-Based Characterization of Cerebral Arteriovenous Malformations.

OBJECTIVES: The aim of this study was to explore blood deoxygenation across cerebral arteriovenous malformations (AVMs) for functional characterization of AVM vasculature. MATERIALS AND METHODS: Fifteen patients with cerebral arteriovenous vascular malformation were prospectively studied by digital subtraction angiography and using a 3 T magnetic resonance imaging system, with which three-dimensional (3D) gradient echo data for the calculation of quantitative susceptibility maps, velocity-encoded 3D gradient echo data for 3D flow assessment, and contrast-enhanced 3D time-of-flight data were acquired.The nidus, major supplying artery, and major draining veins were identified on digital subtraction angiography, and volumes of interest of the AVM nidus, AVM-related inflow and outflow vessels, and non-AVM-related normal veins were drawn on coregistered contrast-enhanced 3D time-of-flight data. The resulting volumes of interest were applied to quantitative susceptibility mapping and flow data. RESULTS: All patients showed a significant stepwise increase in susceptibility between feeding artery and nidus as well as between nidus and draining vein (Padjusted = 0.035, Padjusted= 0.007, respectively). Results revealed between 9.3% and 50.9% of the normal transcapillary blood deoxygenation-related susceptibility change between the feeding artery and the draining vein of the AVMs. When normalized by nidal blood flow velocity, this change was correlated with the presence of perinidal blood products. The mean susceptibility change across cerebral AVMs normalized with nidal volume inversely correlated with mean nidal flow velocity. CONCLUSIONS: Susceptibility changes indicating blood deoxygenation across cerebral AVMs were shown for the first time in this study and were associated with the presence of perinidal blood products. Deoxygenation measures may serve as functional characterization of AVM vasculature and may offer the potential for individual treatment assessment and possible risk stratification.

Assessment of Melanin Content and its Influence on Susceptibility Contrast in Melanoma Metastases.

PURPOSE: To quantify the influence of melanin content on magnetic susceptibility of cerebral melanoma metastases. METHODS: Patients with non-hemorrhagic metastases were included based on the absence of susceptibility blooming artifacts. Susceptibility maps were calculated from 3D gradient echo data, using Laplacian-based phase unwrapping, sophisticated harmonic artefact reduction for phase data (V-SHARP) with varying spherical kernel sizes for background field removal and the iLSQR algorithm for the inversion of phase data. Susceptibility maps were referenced to cerebrospinal fluid. Non-hemorrhagic metastases were identified on contrast-enhanced T1-weighted images and susceptibility weighted images. Metastases masks were drawn on T1-weighted post-contrast images and used to compute mean susceptibility values of each metastasis. RESULTS: A total of 33 non-hemorrhagic melanoma brain metastases in 20 patients were quantitatively evaluated. Metastases without and with hyperintense signal on T1-weighted images, which corresponds to the melanin content, showed median susceptibility values of -0.028 ppm and -0.020 ppm, respectively. The susceptibility differences between metastases without and with T1-weighted hyperintense signal was not statistically significant (p ≥ 0.05). CONCLUSION: Non-hemorrhagic cerebral melanoma metastases showed weak diamagnetic susceptibility values and susceptibility did not significantly correlate to T1-weighted signals. Therefore, melanin does not seem to be a major contributor to susceptibility in cerebral melanoma metastases.

Quantitative susceptibility mapping and 23 Na imaging-based in vitro characterization of blood clotting kinetics.

Blood clotting is a fundamental biochemical process in post-hemorrhagic hemostasis. Although the varying appearance of coagulating blood in T1 - and T2 -weighted images is widely used to qualitatively determine bleeding age, the technique permits only a rough discrimination of coagulation stages, and it remains difficult to distinguish acute and chronic hemorrhagic stages because of low T1 - and T2 -weighted signal intensities in both instances. To investigate new biomedical parameters for magnetic resonance imaging-based characterization of blood clotting kinetics, sodium imaging and quantitative susceptibility mapping (QSM) were compared with conventional T1 - and T2 -weighted imaging, as well as with biochemical hemolysis parameters. For this purpose, a blood-filled spherical agar phantom was investigated daily for 14 days, as well as after 24 days at 7 T after initial preparation with fresh blood. T1 - and T2 -weighted sequences, a three-dimensional (3D) gradient echo sequence and a density-adapted 3D radial projection reconstruction pulse sequence for 23 Na imaging were applied. For hemolysis estimations, free hemoglobin and free potassium concentrations were measured photometrically and with the direct ion-selective electrode method, respectively, in separate heparinized whole-blood samples along the same timeline. Initial mean susceptibility was low (0.154 ± 0.020 ppm) and increased steadily during the course of coagulation to reach up to 0.570 ± 0.165 ppm. The highest total sodium (NaT) values (1.02 ± 0.06 arbitrary units) in the clot were observed initially, dropped to 0.69 ± 0.13 arbitrary units after one day and increased again to initial values. Compartmentalized sodium (NaS) showed a similar signal evolution, and the NaS/NaT ratio steadily increased over clot evolution. QSM depicts clot evolution in vitro as a process associated with hemoglobin accumulation and transformation, and enables the differentiation of the acute and chronic coagulation stages. Sodium imaging visualizes clotting independent of susceptibility and seems to correspond to clot integrity. A combination of QSM and sodium imaging may enhance the characterization of hemorrhage.

Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression.

Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.

Return to work and lost earnings after acute respiratory distress syndrome: a 5-year prospective, longitudinal study of long-term survivors.

BACKGROUND: Delayed return to work is common after acute respiratory distress syndrome (ARDS), but has undergone little detailed evaluation. We examined factors associated with the timing of return to work after ARDS, along with lost earnings and shifts in healthcare coverage. METHODS: Five-year, multisite prospective, longitudinal cohort study of 138 2-year ARDS survivors hospitalised between 2004 and 2007. Employment and healthcare coverage were collected via structured interview. Predictors of time to return to work were evaluated using Fine and Grey regression analysis. Lost earnings were estimated using Bureau of Labor Statistics data. RESULTS: Sixty-seven (49%) of the 138 2-year survivors were employed prior to ARDS. Among 64 5-year survivors, 20 (31%) never returned to work across 5-year follow-up. Predictors of delayed return to work (HR (95% CI)) included baseline Charlson Comorbidity Index (0.77 (0.59 to 0.99) per point; p=0.04), mechanical ventilation duration (0.67 (0.55 to 0.82) per day up to 5 days; p<0.001) and discharge to a healthcare facility (0.49 (0.26 to 0.93); p=0.03). Forty-nine of 64 (77%) 5-year survivors incurred lost earnings, with average (SD) losses ranging from US$38 354 (21,533) to US$43 510 (25,753) per person per year. Jobless, non-retired survivors experienced a 33% decrease in private health insurance and concomitant 37% rise in government-funded coverage. CONCLUSIONS: Across 5-year follow-up, nearly one-third of previously employed ARDS survivors never returned to work. Delayed return to work was associated with patient-related and intensive care unit/hospital-related factors, substantial lost earnings and a marked rise in government-funded healthcare coverage. These important consequences emphasise the need to design and evaluate vocation-based interventions to assist ARDS survivors return to work.