Asymmetrical representation of body orientation

The perceived orientation of objects, gravity, and the body are biased to the left. Whether this leftward bias is attributable to biases in sensing or processing vestibular, visual, and body sense cues has never been assessed directly. The orientation in which characters are most easily recognized-the perceived upright (PU)-can be well predicted from a weighted vector sum of these sensory cues. A simple form of this model assumes that the directions of the contributing inputs are coded accurately and as a consequence participants tilted leftor right-side-down relative to gravity should exhibit mirror symmetric patterns of responses. If a left/right asymmetry were present then varying these sensory cues could be used to assess in which sensory modality or modalities a PU bias may have arisen. Participants completed the Oriented Character Recognition Test (OCHART) while manipulating body posture and visual orientation cues relative to gravity. The response patterns showed systematic differences depending on which side they were tilted. An asymmetry of the PU was found to be best modeled by adding a leftward bias of 5.68 to the perceived orientation of the body relative to its actual orientation relative to the head. The asymmetry in the effect of body orientation is reminiscent of the body-defined left-leaning asymmetry in the perceived direction of light coming from above and reports that people tend to adopt a right-leaning posture

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Neutral buoyancy and the static perception of upright

The perceptual upright results from the multisensory integration of the directions indicated by vision and gravity as well as a prior assumption that upright is towards the head. The direction of gravity is signalled by multiple cues, the predominant of which are the otoliths of the vestibular system and somatosensory information from contact with the support surface. Here, we used neutral buoyancy to remove somatosensory information while retaining vestibular cues, thus "splitting the gravity vector" leaving only the vestibular component. In this way, neutral buoyancy can be used as a microgravity analogue. We assessed spatial orientation using the oriented character recognition test (OChaRT, which yields the perceptual upright, PU) under both neutrally buoyant and terrestrial conditions. The effect of visual cues to upright (the visual effect) was reduced under neutral buoyancy compared to on land but the influence of gravity was unaffected. We found no significant change in the relative weighting of vision, gravity, or body cues, in contrast to results found both in long-duration microgravity and during head-down bed rest. These results indicate a relatively minor role for somatosensation in determining the perceptual upright in the presence of vestibular cues. Short-duration neutral buoyancy is a weak analogue for microgravity exposure in terms of its perceptual consequences compared to long-duration head-down bed rest

The effect of long-term exposure to microgravity on the perception of upright

AbstractGoing into space is a disorienting experience. Many studies have looked at sensory functioning in space but the multisensory basis of orientation has not been systematically investigated. Here, we assess how prolonged exposure to microgravity affects the relative weighting of visual, gravity, and idiotropic cues to perceived orientation. We separated visual, body, and gravity (when present) cues to perceived orientation before, during, and after long-term exposure to microgravity during the missions of seven astronauts on the International Space Station (mean duration 168 days) and measuring perceived vertical using the subjective visual vertical and the perceptual upright. The relative influence of each cue and the variance of their judgments were measured. Fourteen ground-based control participants performed comparable measurements over a similar period. The variance of astronauts’ subjective visual vertical judgments in the absence of visual cues was significantly larger immediately upon return to earth than before flight. Astronauts’ perceptual upright demonstrated a reduced reliance on visual cues upon arrival on orbit that re-appeared long after returning to earth. For earth-bound controls, the contributions of body, gravity, and vision remained constant throughout the year-long testing period. This is the first multisensory study of orientation behavior in space and the first demonstration of long-term perceptual changes that persist after returning to earth. Astronauts showed a plasticity in the weighting of perceptual cues to orientation that could form the basis for future countermeasures.</jats:p

The unassisted visual system on earth and in space

Chuck Oman has been a guide and mentor for research in human perception and performance during space exploration for over 25 years. His research has provided a solid foundation for our understanding of how humans cope with the challenges and ambiguities of sensation and perception in space. In many of the environments associated with work in space the human visual system must operate with unusual combinations of visual and other perceptual cues. On Earth physical acceleration cues are normally available to assist the visual system in interpreting static and dynamic visual features. Here we consider two cases where the visual system is not assisted by such cues. Our first experiment examines perceptual stability when the normally available physical cues to linear acceleration are absent. Our second experiment examines perceived orientation when there is no assistance from the physically sensed direction of gravity. In both cases the effectiveness of vision is paradoxically reduced in the absence of physical acceleration cues. The reluctance to rely heavily on vision represents an important human factors challenge to efficient performance in the space environment.</jats:p