Development of a ground-based sensorimotor disorientation analog to replicate astronaut postflight experience.

The perceptual and motor coordination problems experienced following return from spaceflight reflect the sensory adaptation to altered gravity. The purpose of this study was to develop a ground-based analog that replicates similar sensorimotor impairment using a standard measures test battery and subjective feedback from experienced crewmembers. This Sensorimotor Disorientation Analog (SDA) included varying levels of sensorimotor disorientation through combined vestibular, visual, and proprioceptive disruptions. The SDA was evaluated on five previously flown astronauts to compare with their postflight experience and functional motor performance immediately (Return (R)+0 days) and +24 h (R+1) after landing. The SDA consisted of galvanic vestibular stimulation (GVS), visual disruption goggles, and a weighted suit to alter proprioceptive feedback and replicate perceived heaviness postflight. Astronauts reported that GVS alone replicated ∼50-90% of their postflight performance with the weighted suit fine-tuning the experience to replicate an additional 10%-40% of their experience. Astronauts did not report feeling that the disruption goggles represented either the visual disruptions or illusory sensations that they experienced, nor did they impact motor performance in postflight tasks similarly. Based on these results, we recommend an SDA including the GVS and the weighted suit. These results provide a more realistic and portable SDA framework to provide transient spaceflight-relevant sensorimotor disruptions for use in countermeasure testing and as a pre-flight training tool.

Dynamic changes in perivascular space morphology predict signs of spaceflight-associated neuro-ocular syndrome in bed rest.

During long-duration spaceflight, astronauts experience headward fluid shifts and expansion of the cerebral perivascular spaces (PVS). A major limitation to our understanding of the changes in brain structure and physiology induced by spaceflight stems from the logistical difficulties of studying astronauts. The current study aimed to determine whether PVS changes also occur on Earth with the spaceflight analog head-down tilt bed rest (HDBR). We examined how the number and morphology of magnetic resonance imaging-visible PVS (MV-PVS) are affected by HDBR with and without elevated carbon dioxide (CO2). These environments mimic the headward fluid shifts, body unloading, and elevated CO2 observed aboard the International Space Station. Additionally, we sought to understand how changes in MV-PVS are associated with signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), ocular structural alterations that can occur with spaceflight. Participants were separated into two bed rest campaigns: HDBR (60 days) and HDBR + CO2 (30 days with elevated ambient CO2). Both groups completed multiple magnetic resonance image acquisitions before, during, and post-bed rest. We found that at the group level, neither spaceflight analog affected MV-PVS quantity or morphology. However, when taking into account SANS status, persons exhibiting signs of SANS showed little or no MV-PVS changes, whereas their No-SANS counterparts showed MV-PVS morphological changes during the HDBR + CO2 campaign. These findings highlight spaceflight analogs as models for inducing changes in MV-PVS and implicate MV-PVS dynamic compliance as a mechanism underlying SANS. These findings may lead to countermeasures to mitigate health risks associated with human spaceflight.

Evaluation of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) Samples from Advanced Non-Small Cell Lung Cancer for Whole Genome, Whole Exome and Comprehensive Panel Sequencing.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is often the only source of tumor tissue from patients with advanced, inoperable lung cancer. EBUS-TBNA aspirates are used for the diagnosis, staging, and genomic testing to inform therapy options. Here we extracted DNA and RNA from 220 EBUS-TBNA aspirates to evaluate their suitability for whole genome (WGS), whole exome (WES), and comprehensive panel sequencing. For a subset of 40 cases, the same nucleic acid extraction was sequenced using WGS, WES, and the TruSight Oncology 500 assay. Genomic features were compared between sequencing platforms and compared with those reported by clinical testing. A total of 204 aspirates (92.7%) had sufficient DNA (100 ng) for comprehensive panel sequencing, and 109 aspirates (49.5%) had sufficient material for WGS. Comprehensive sequencing platforms detected all seven clinically reported tier 1 actionable mutations, an additional three (7%) tier 1 mutations, six (15%) tier 2-3 mutations, and biomarkers of potential immunotherapy benefit (tumor mutation burden and microsatellite instability). As expected, WGS was more suited for the detection and discovery of emerging novel biomarkers of treatment response. WGS could be performed in half of all EBUS-TBNA aspirates, which points to the enormous potential of EBUS-TBNA as source material for large, well-curated discovery-based studies for novel and more effective predictors of treatment response. Comprehensive panel sequencing is possible in the vast majority of fresh EBUS-TBNA aspirates and enhances the detection of actionable mutations over current clinical testing.

Back to the future-revisiting Skylab data on ocular counter-rolling and motion sickness.

In the early 1970s, nine astronauts participated in missions to the Skylab space station. During two preflight testing sessions at the Naval Aerospace Medical Research Laboratory in Pensacola, the amplitudes of their ocular counter-rolling (OCR) during body tilts were assessed to determine if their vestibular functions were within normal ranges. We recently re-evaluated this data to determine asymmetry of each astronaut's OCR response and their OCR slope from sigmoid fits during static leftward and rightward body tilts, which we then compared with their Coriolis sickness susceptibility index (CSSI) on the ground, their motion sickness symptom scores during 0 g maneuvers in parabolic flight, and the severity of the symptoms of space motion sickness (SMS) they reported during their spaceflights. We arranged the astronauts in rank order for SMS severity based on the SMS symptoms they reported during spaceflight and the amount of anti-motion sickness medication they used. As previously reported, the OCR amplitudes of these astronauts were within the normal range. We determined that the OCR amplitudes were not correlated with SMS severity ranking, CSSI, or motion sickness symptoms experienced during parabolic flight. Indices of asymmetry in the OCR reflex were generally small and poorly correlated with SMS scores; however, the only subject with a high index of asymmetry also ranked highly for SMS. Although OCR slope, CSSI, and motion sickness symptoms induced during parabolic flight were each only moderately correlated with SMS severity ranking (rho = 0.41-0.44), a combined index that included all three parameters with equal weighting was significantly correlated with SMS severity ranking (rho = 0.71, p = 0.015). These results demonstrate the challenge of predicting an individual's susceptibility to SMS by measuring a single test parameter in a terrestrial environment and from a limited sample size.

Cognitive and balance functions of astronauts after spaceflight are comparable to those of individuals with bilateral vestibulopathy.

Introduction: This study compares the balance control and cognitive responses of subjects with bilateral vestibulopathy (BVP) to those of astronauts immediately after they return from long-duration spaceflight on board the International Space Station. Methods: Twenty-eight astronauts and thirty subjects with BVP performed five tests using the same procedures: sit-to-stand, walk-and-turn, tandem walk, duration judgment, and reaction time. Results: Compared to the astronauts' preflight responses, the BVP subjects' responses were impaired in all five tests. However, the BVP subjects' performance during the walk-and-turn and the tandem walk tests were comparable to the astronauts' performance on the day they returned from space. Moreover, the BVP subjects' time perception and reaction time were comparable to those of the astronauts during spaceflight. The BVP subjects performed the sit-to-stand test at a level that fell between the astronauts' performance on the day of landing and 1 day later. Discussion: These results indicate that the alterations in dynamic balance control, time perception, and reaction time that astronauts experience after spaceflight are likely driven by central vestibular adaptations. Vestibular and somatosensory training in orbit and vestibular rehabilitation after spaceflight could be effective countermeasures for mitigating these post-flight performance decrements.

The oesophageal adenocarcinoma tumour immune microenvironment dictates outcomes with different modalities of neoadjuvant therapy - results from the AGITG DOCTOR trial and the cancer evolution biobank.

A plateau in treatment effect can be seen for the current 'one-size-fits-all' approach to oesophageal adenocarcinoma (OAC) management using neoadjuvant chemoradiotherapy (nCRT) or chemotherapy (nCT). In OAC, the tumour microenvironment (TME) is largely immunosuppressed, however a subgroup of patients with an immune-inflamed TME exist and show improved outcomes. We aimed to understand the overall immune-based mechanisms underlying treatment responses and patient outcomes in OAC, and in relation to neoadjuvant therapy modality. This study included 107 patients; 68 patients were enrolled in the Australian Gastro-Intestinal Trials Group sponsored DOCTOR Trial, and 38 patients were included from the Cancer Evolution Biobank. Matched pre-treatment and post-treatment tumour biopsies were used to perform multi-modality analysis of the OAC TME including NanoString mRNA expression analysis, multiplex and single colour immunohistochemistry (IHC), and peripheral blood mononuclear cell analysis of tumour-antigen specific T cell responses. Patients with the best clinicopathological outcomes and survival had an immune-inflamed TME enriched with anti-tumour immune cells and pathways. Those with the worst survival showed a myeloid T regulatory cell enriched TME, with decreased CD8+ cell infiltration and increased pro-tumour immune cells. Multiplex IHC analysis identified that high intra-tumoural infiltration of CD8+ cells, and low infiltration with CD163+ cells was associated with improved survival. High tumour core CD8+ T cell infiltration, and a low tumour margin infiltration of CD163+ cells was also associated with improved survival. nCRT showed improved survival compared with nCT for patients with low CD8+, or high CD163+ cell infiltration. Poly-functional T cell responses were seen with tumour-antigen specific T cells. Overall, our study supports the development of personalised therapeutic approaches based on the immune microenvironment in OAC. Patients with an immune-inflamed TME show favourable outcomes regardless of treatment modality. However, in those with an immunosuppressed TME with CD163+ cell infiltration, treatment with nCRT can improve outcomes. Our findings support previous studies into the TME of OAC and with more research, immune based biomarker selection of treatment modality may lead in improved outcomes in this deadly disease.

The clinical utility and costs of whole-genome sequencing to detect cancer susceptibility variants-a multi-site prospective cohort study.

BACKGROUND: Many families and individuals do not meet criteria for a known hereditary cancer syndrome but display unusual clusters of cancers. These families may carry pathogenic variants in cancer predisposition genes and be at higher risk for developing cancer. METHODS: This multi-centre prospective study recruited 195 cancer-affected participants suspected to have a hereditary cancer syndrome for whom previous clinical targeted genetic testing was either not informative or not available. To identify pathogenic disease-causing variants explaining participant presentation, germline whole-genome sequencing (WGS) and a comprehensive cancer virtual gene panel analysis were undertaken. RESULTS: Pathogenic variants consistent with the presenting cancer(s) were identified in 5.1% (10/195) of participants and pathogenic variants considered secondary findings with potential risk management implications were identified in another 9.7% (19/195) of participants. Health economic analysis estimated the marginal cost per case with an actionable variant was significantly lower for upfront WGS with virtual panel ($8744AUD) compared to standard testing followed by WGS ($24,894AUD). Financial analysis suggests that national adoption of diagnostic WGS testing would require a ninefold increase in government annual expenditure compared to conventional testing. CONCLUSIONS: These findings make a case for replacing conventional testing with WGS to deliver clinically important benefits for cancer patients and families. The uptake of such an approach will depend on the perspectives of different payers on affordability.

Performance of tumour microenvironment deconvolution methods in breast cancer using single-cell simulated bulk mixtures.

Cells within the tumour microenvironment (TME) can impact tumour development and influence treatment response. Computational approaches have been developed to deconvolve the TME from bulk RNA-seq. Using scRNA-seq profiling from breast tumours we simulate thousands of bulk mixtures, representing tumour purities and cell lineages, to compare the performance of nine TME deconvolution methods (BayesPrism, Scaden, CIBERSORTx, MuSiC, DWLS, hspe, CPM, Bisque, and EPIC). Some methods are more robust in deconvolving mixtures with high tumour purity levels. Most methods tend to mis-predict normal epithelial for cancer epithelial as tumour purity increases, a finding that is validated in two independent datasets. The breast cancer molecular subtype influences this mis-prediction. BayesPrism and DWLS have the lowest combined numbers of false positives and false negatives, and have the best performance when deconvolving granular immune lineages. Our findings highlight the need for more single-cell characterisation of rarer cell types, and suggest that tumour cell compositions should be considered when deconvolving the TME.

Circulating Tumor DNA: A Promising Biomarker for Predicting Recurrence in Patients with BRAF-Negative Melanoma.

For patients with BRAF wild-type stage III and IV melanoma, there is an urgent clinical need to identify prognostic biomarkers and biomarkers predictive of treatment response. Circulating tumor DNA (ctDNA) is emerging as a blood-based biomarker and has shown promising results for many cancers, including melanoma. The purpose of this study was to identify targetable, tumor-derived mutations in patient blood that may lead to treatment alternatives and improved outcomes for patients with BRAF-negative melanoma. Using a CAncer Personalized Profiling by deep Sequencing (CAPP-seq) pan-cancer gene panel, ctDNA from 150 plasma samples (n = 106 patients) was assessed, including serial blood collections for a subset of patients (n = 16). ctDNA variants were detected in 85% of patients, all in targetable pathways, such as vascular endothelial growth factor receptor, epidermal growth factor receptor, phosphatidylinositol 3-kinase/AKT, Bcl2/mammalian target of rapamycin (mTOR), ALK/MET, and cyclin-dependent kinase 4/6. Patients with stage IV melanoma with low ctDNA concentrations, <10 ng/mL, had significantly better disease-specific survival and progression-free survival. Patients with both a high concentration of ctDNA and any detectable ctDNA variants had the worst prognosis. In addition, these results indicated that longitudinal changes in ctDNA correlated with treatment response and disease progression determined by radiology. This study confirms that ctDNA may be used as a noninvasive liquid biopsy to identify recurrent disease and detect targetable variants in patients with late-stage melanoma.

Daily Artificial Gravity Partially Mitigates Vestibular Processing Changes Associated with Head-down Tilt Bedrest.

Microgravity alters vestibular signaling and reduces body loading, driving sensory reweighting and adaptation. The unloading effects can be modelled using head down tilt bedrest (HDT). Artificial gravity (AG) has been hypothesized to serve as an integrated countermeasure for the physiological declines associated with HDT and spaceflight. Here, we examined the efficacy of 30 minutes of daily AG to counteract brain and behavior changes that arise from 60 days of HDT. One group of participants received 30 minutes of AG daily (AG; n = 16) while in HDT, and another group served as controls, spending 60 days in HDT bedrest with no AG (CTRL; n = 8). We examined how HDT and AG affect vestibular processing by collecting fMRI scans from participants as they received vestibular stimulation. We collected these data prior to, during (2x), and post HDT. We assessed brain activation initially in 10 regions of interest (ROIs) and then conducted an exploratory whole brain analysis. The AG group showed no changes in brain activation during vestibular stimulation in a cerebellar ROI, whereas the CTRL group showed decreased cerebellar activation specific to the HDT phase. Additionally, those that received AG and showed little pre- to post-bed rest changes in left OP2 activation during HDT had better post-HDT balance performance. Exploratory whole brain analyses identified increased pre- to during-HDT activation in the CTRL group in the right precentral gyrus and the right inferior frontal gyrus specific to HDT, where the AG group maintained pre-HDT activation levels. Together, these results indicate that AG could mitigate brain activation changes in vestibular processing in a manner that is associated with better balance performance after HDT.

Artificial gravity during a spaceflight analog alters brain sensory connectivity.

Spaceflight has numerous untoward effects on human physiology. Various countermeasures are under investigation including artificial gravity (AG). Here, we investigated whether AG alters resting-state brain functional connectivity changes during head-down tilt bed rest (HDBR), a spaceflight analog. Participants underwent 60 days of HDBR. Two groups received daily AG administered either continuously (cAG) or intermittently (iAG). A control group received no AG. We assessed resting-state functional connectivity before, during, and after HDBR. We also measured balance and mobility changes from pre- to post-HDBR. We examined how functional connectivity changes throughout HDBR and whether AG is associated with differential effects. We found differential connectivity changes by group between posterior parietal cortex and multiple somatosensory regions. The control group exhibited increased functional connectivity between these regions throughout HDBR whereas the cAG group showed decreased functional connectivity. This finding suggests that AG alters somatosensory reweighting during HDBR. We also observed brain-behavioral correlations that differed significantly by group. Control group participants who showed increased connectivity between the putamen and somatosensory cortex exhibited greater mobility declines post-HDBR. For the cAG group, increased connectivity between these regions was associated with little to no mobility declines post-HDBR. This suggests that when somatosensory stimulation is provided via AG, functional connectivity increases between the putamen and somatosensory cortex are compensatory in nature, resulting in reduced mobility declines. Given these findings, AG may be an effective countermeasure for the reduced somatosensory stimulation that occurs in both microgravity and HDBR.

Impacts of spaceflight experience on human brain structure.

Spaceflight induces widespread changes in human brain morphology. It is unclear if these brain changes differ with varying mission duration or spaceflight experience history (i.e., novice or experienced, number of prior missions, time between missions). Here we addressed this issue by quantifying regional voxelwise changes in brain gray matter volume, white matter microstructure, extracellular free water (FW) distribution, and ventricular volume from pre- to post-flight in a sample of 30 astronauts. We found that longer missions were associated with greater expansion of the right lateral and third ventricles, with the majority of expansion occurring during the first 6 months in space then appearing to taper off for longer missions. Longer inter-mission intervals were associated with greater expansion of the ventricles following flight; crew with less than 3 years of time to recover between successive flights showed little to no enlargement of the lateral and third ventricles. These findings demonstrate that ventricle expansion continues with spaceflight with increasing mission duration, and inter-mission intervals less than 3 years may not allow sufficient time for the ventricles to fully recover their compensatory capacity. These findings illustrate some potential plateaus in and boundaries of human brain changes with spaceflight.

Generalising uncertainty improves accuracy and safety of deep learning analytics applied to oncology.

Uncertainty estimation is crucial for understanding the reliability of deep learning (DL) predictions, and critical for deploying DL in the clinic. Differences between training and production datasets can lead to incorrect predictions with underestimated uncertainty. To investigate this pitfall, we benchmarked one pointwise and three approximate Bayesian DL models for predicting cancer of unknown primary, using three RNA-seq datasets with 10,968 samples across 57 cancer types. Our results highlight that simple and scalable Bayesian DL significantly improves the generalisation of uncertainty estimation. Moreover, we designed a prototypical metric-the area between development and production curve (ADP), which evaluates the accuracy loss when deploying models from development to production. Using ADP, we demonstrate that Bayesian DL improves accuracy under data distributional shifts when utilising 'uncertainty thresholding'. In summary, Bayesian DL is a promising approach for generalising uncertainty, improving performance, transparency, and safety of DL models for deployment in the real world.

Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy.

Oesophageal adenocarcinoma is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigate whole genome, transcriptomic and methylation data from 115 oesophageal adenocarcinoma patients mostly from the DOCTOR phase II clinical trial (Australian New Zealand Clinical Trials Registry-ACTRN12609000665235), with exploratory analysis pre-specified in the study protocol of the trial. We report genomic features associated with poorer overall survival, such as the APOBEC mutational and RS3-like rearrangement signatures. We also show that positron emission tomography non-responders have more sub-clonal genomic copy number alterations. Transcriptomic analysis categorises patients into four immune clusters correlated with survival. The immune suppressed cluster is associated with worse survival, enriched with myeloid-derived cells, and an epithelial-mesenchymal transition signature. The immune hot cluster is associated with better survival, enriched with lymphocytes, myeloid-derived cells, and an immune signature including CCL5, CD8A, and NKG7. The immune clusters highlight patients who may respond to immunotherapy and thus may guide future clinical trials.

Daily artificial gravity is associated with greater neural efficiency during sensorimotor adaptation.

Altered vestibular signaling and body unloading in microgravity results in sensory reweighting and adaptation. Microgravity effects are well-replicated in head-down tilt bed rest (HDBR). Artificial gravity (AG) is a potential countermeasure to mitigate the effects of microgravity on human physiology and performance. We examined the effectiveness of daily AG for mitigating brain and/or behavioral changes in 60 days of HDBR. One group received AG for 30 minutes daily (AG; n = 16) and a control group spent the same time in HDBR but received no AG (CTRL; n = 8). All participants performed a sensorimotor adaptation task five times during fMRI scanning: twice prior to HDBR, twice during HDBR, and once following HDBR. The AG group showed similar behavioral adaptation effects compared with the CTRLs. We identified decreased brain activation in the AG group from pre to late HDBR in the cerebellum for the task baseline portion and in the thalamus, calcarine, cuneus, premotor cortices, and superior frontal gyrus in the AG group during the early adaptation phase. The two groups also exhibited differential brain-behavior correlations. Together, these results suggest that AG may result in a reduced recruitment of brain activity for basic motor processes and sensorimotor adaptation. These effects may stem from the somatosensory and vestibular stimulation that occur with AG.

Comparison of Asymmetry between Perceptual, Ocular, and Postural Vestibular Screening Tests.

BACKGROUND: A better understanding of how vestibular asymmetry manifests across tests is important due to its potential implications for balance dysfunction, motion sickness susceptibility, and adaptation to new environments. OBJECTIVE: We report the results of multiple tests for vestibular asymmetry in 32 healthy participants. METHODS: Asymmetry was measured using perceptual reports during unilateral centrifugation, oculomotor responses during visual alignment tasks, vestibulo-ocular reflex gain during head impulse tests, and body rotation during stepping tests. RESULTS: A significant correlation was observed between asymmetries of subjective visual vertical and verbal report during unilateral centrifugation. Another significant correlation was observed between the asymmetries of ocular alignment, vestibulo-ocular reflex gain, and body rotation. CONCLUSIONS: These data suggest that there are underlying vestibular asymmetries in healthy individuals that are consistent across various vestibular challenges. In addition, these findings have value in guiding test selection during experimental design for assessing vestibular asymmetry in healthy adults.

Efficient detection and monitoring of pediatric brain malignancies with liquid biopsy based on patient-specific somatic mutation screening.

BACKGROUND: Brain cancer is the leading cause of cancer-related death in children. Early detection and serial monitoring are essential for better therapeutic outcomes. Liquid biopsy has recently emerged as a promising approach for detecting these tumors by screening body fluids for the presence of circulating tumor DNA (ctDNA). Here we tested the limits of liquid biopsy using patient-specific somatic mutations to detect and monitor primary and metastatic pediatric brain cancer. METHODS: Somatic mutations were identified in 3 ependymoma, 1 embryonal tumor with multilayered rosettes, 1 central nervous system neuroblastoma, and 7 medulloblastoma patients. The mutations were used as liquid biomarkers for serial assessment of cerebrospinal fluid (CSF) samples using a droplet digital PCR (ddPCR) system. The findings were correlated to the imaging data and clinical assessment to evaluate the utility of the approach for clinical translation. RESULTS: We developed personalized somatic mutation ddPCR assays which we show are highly specific, sensitive, and efficient in detection and monitoring of ctDNA, with a positive correlation between presence of ctDNA, disease course, and clinical outcomes in the majority of patients. CONCLUSIONS: We demonstrate the feasibility and clinical utility of personalized mutation-based liquid biopsy for the surveillance of brain cancer in children. However, even with this specific and sensitive approach, we identified some potential false negative analyses. Overall, our results indicate that changes in ctDNA profiles over time demonstrate the great potential of our specific approach for predicting tumor progression, burden, and response to treatment.

Changes in working memory brain activity and task-based connectivity after long-duration spaceflight.

We studied the longitudinal effects of approximately 6 months of spaceflight on brain activity and task-based connectivity during a spatial working memory (SWM) task. We further investigated whether any brain changes correlated with changes in SWM performance from pre- to post-flight. Brain activity was measured using functional magnetic resonance imaging while astronauts (n = 15) performed a SWM task. Data were collected twice pre-flight and 4 times post-flight. No significant effects on SWM performance or brain activity were found due to spaceflight; however, significant pre- to post-flight changes in brain connectivity were evident. Superior occipital gyrus showed pre- to post-flight reductions in task-based connectivity with the rest of the brain. There was also decreased connectivity between the left middle occipital gyrus and the left parahippocampal gyrus, left cerebellum, and left lateral occipital cortex during SWM performance. These results may reflect increased visual network modularity with spaceflight. Further, increased visual and visuomotor connectivity were correlated with improved SWM performance from pre- to post-flight, while decreased visual and visual-frontal cortical connectivity were associated with poorer performance post-flight. These results suggest that while SWM performance remains consistent from pre- to post-flight, underlying changes in connectivity among supporting networks suggest both disruptive and compensatory alterations due to spaceflight.

Mission-critical tasks for assessing risks from vestibular and sensorimotor adaptation during space exploration.

To properly assess the risk induced by vestibular and sensorimotor adaptation during exploration missions, we examined how long-duration stays on the International Space Station affect functional performance after gravity transitions. Mission-critical tasks that challenge the balance and the locomotion control systems were assessed: i.e., sit-to-stand, recovery-from-fall, tandem-walk, and walk-and-turn. We assessed 19 astronauts, including 7 first-time flyers and 12 experienced flyers, before their flight, a few hours after landing, and then 1 day and 6-11 days later. Results show that adaptation to long-term weightlessness causes deficits in functional performance immediately after landing that can last for up to 1 week. No differences were observed between first-time and experienced astronaut groups. These data suggest that additional sensorimotor-based countermeasures may be necessary to maintain functional performance at preflight levels when landing on planetary surfaces after a long period in weightlessness.

Multiple field tests on landing day: Early mobility may improve postural recovery following spaceflight.

Adaptation to microgravity causes astronauts to experience sensorimotor disturbances during return to Earth leading to functional difficulties. Recently, the Field Test (FT) study involving an incrementally demanding sensorimotor functional test battery has allowed for an unprecedented view into early decrements and recovery from multiple tests conducted on the landing day following 6-months International Space Station missions. Although the protocol was challenging and temporarily increased motion sickness symptoms, there were anecdotal reports that performing these tasks within the first few hours of landing accelerated their recovery. Therefore, results from computerized dynamic posturography (CDP) following return to Houston were used to compare recovery between crewmembers that participated in FT (n = 18) with those that did not (controls, n = 11). While there were significant decrements in postural performance for both groups, some FT participants tended to perform closer to their preflight baseline in the most challenging condition of the CDP sensitive to vestibular function-eyes closed, unstable support and head movements. However, the distribution of difference scores appeared bimodal with other FT participants in the lower range of performance. We attribute these observations to the manner in which the field tests were implemented-some benefitted by encouraging early movement to drive adaptation when performed in a constrained incremental fashion; however, movements above aversive thresholds may have impaired adaptation in others. Challenging the sensorimotor system with increasingly provocative movements performed as close to landing as possible, as long as within individual thresholds, could be a useful intervention to accelerate astronaut's sensorimotor readaptation that deserves further study.