A novel simplified biomechanical assessment of the heel pad during foot plantarflexion

International audienc

T Cells from Programmed Death-1 Deficient Mice Respond Poorly to Mycobacterium tuberculosis Infection

Programmed Death-1 (PD-1; CD279) receptor molecule is widely believed to be a negative regulator predominantly expressed by exhausted/activated mouse T cells. Upon interaction with its ligands, PD-L1 and PD-L2, PD-1 inhibits activation of T cells and cytokine production, which has been documented in various viral and fungal infections as well as in vitro studies. Therefore, inhibition of T cell responses by PD-1 resulted in disease resistance in a variety of mouse infection models studied heretofore.Here, we report that PD-1 deficient (PD-1(-/-)) mice infected with Mycobacterium tuberculosis (M. tb) H37Rv by the aerosol route have increased susceptibility as compared with their wild type littermates. Surprisingly, M. tb antigen-specific T cell proliferation was dramatically reduced in PD-1 deficient animals compared with wild-type littermates, and this was due to increased numbers of regulatory T cells (Tregs) and recruitment of mesenchymal stem cells. Furthermore, PD-1(-/-) mice exhibited decreases in the autophagy-induced LC3-B marker protein in macrophages.Our findings suggest that PD-1 does not play an inhibitory role during M. tb infection and instead promotes mycobacterial clearance in mice

Data Assimilation Enhancements to Air Force Weathers Land Information System

The United States Air Force (USAF) has a proud and storied tradition of enabling significant advancements in the area of characterizing and modeling land state information. 557th Weather Wing (557 WW; DoDs Executive Agent for Land Information) provides routine geospatial intelligence information to warfighters, planners, and decision makers at all echelons and services of the U.S. military, government and intelligence community. 557 WW and its predecessors have been home to the DoDs only operational regional and global land data analysis systems since January 1958. As a trusted partner since 2005, Air Force Weather (AFW) has relied on the Hydrological Sciences Laboratory at NASA/GSFC to lead the interagency scientific collaboration known as the Land Information System (LIS). LIS is an advanced software framework for high performance land surface modeling and data assimilation of geospatial intelligence (GEOINT) information

The University of Salford Sound of Laughter project

What follows is a report of the University of Salford’s Sound of Laughter Project (2018). This pilot study was set up as an initial attempt to ascertain whether it is possible to discern any meaning from the different laughter sounds that audiences might make during a stand-up comedy show. The experiment also aimed to discover whether comedians can recognise variations in the properties of laughter responses made during the act of public joking. Further, the study aimed to establish whether performers can discern these different audience laughter sounds in real time and use them as identifiable ‘cues’ to check the efficacy (or otherwise) of their comic communication. This combined report on the pilot study has been prepared by a group of researchers at the University of Salford, all of which were involved in different stages of the experiment and whose initials are appended to each relevant section of the report. Keywords: Audience laughter; stand-up comedy; joking; psychoacoustics, audience respons

Lessons learned from shallow subglacial bedrock drilling campaigns in Antarctica

We review successes and challenges from five recent subglacial bedrock drilling campaigns intended to find evidence for Antarctic Ice Sheet retreat during warm periods in the geologic past. Insights into times when the polar ice sheets were smaller than present serve as guiding information for modeling efforts that aim to predict the rate and magnitude of future sea level rise that would accompany major retreat of the Antarctic Ice Sheet. One method to provide direct evidence for the timing of deglaciations and minimum extent of prior ice sheets is to extract subglacial bedrock cores for cosmogenic nuclide analysis from beneath the modern ice sheet surface. Here we summarize the lessons learned from five field seasons tasked with obtaining bedrock cores from shallow depths (<120 m beneath ice surface) across West Antarctica since 2016. We focus our findings on drilling efforts and technology and geophysical surveys with ground-penetrating radar. Shallow subglacial drilling provides a high risk, high reward means to test for past instabilities of the Antarctic Ice Sheet, and we highlight key challenges and solutions to increase the likelihood of success for future subglacial drilling efforts in polar regions

Historical volcanism and the state of stress in the East African Rift System

Crustal extension at the East African Rift System (EARS) should, as a tectonic ideal, involve a stress field in which the direction of minimum horizontal stress is perpendicular to the rift. A volcano in such a setting should produce dykes and fissures parallel to the rift. How closely do the volcanoes of the EARS follow this? We answer this question by studying the 21 volcanoes that have erupted historically (since about 1800) and find that 7 match the (approximate) geometrical ideal. At the other 14 volcanoes the orientation of the eruptive fissures/dykes and/or the axes of the host rift segments are oblique to the ideal values. To explain the eruptions at these volcanoes we invoke local (non-plate tectonic) variations of the stress field caused by: crustal heterogeneities and anisotropies (dominated by NW structures in the Protoerozoic basement), transfer zone tectonics at the ends of offset rift segments, gravitational loading by the volcanic edifice (typically those with 1-2 km relief) and magmatic pressure in central reservoirs. We find that the more oblique volcanoes tend to have large edifices, large eruptive volumes and evolved and mixed magmas capable of explosive behaviour. Nine of the volcanoes have calderas of varying ellipticity, 6 of which are large, reservoir-collapse types mainly elongated across rift (e.g. Kone) and 3 are smaller, elongated parallel to the rift and contain active lava lakes (e.g. Erta Ale), suggesting different mechanisms of formation and stress fields. Nyamuragira is the only EARS volcano with enough sufficiently well-documented eruptions to infer its long-term dynamic behaviour. Eruptions within 7 km of the volcano are of relatively short duration (<100 days), but eruptions with more distal fissures tend to have lesser obliquity and longer durations, indicating a changing stress field away from the volcano. There were major changes in long-term magma extrusion rates in 1977 (and perhaps in 2002) due to major along-rift dyking events that effectively changed the Nyamuragira stress field and the intrusion/extrusion ratios of eruptions

Review article: Existing and potential evidence for Holocene grounding line retreat and readvance in Antarctica

Widespread existing geological records from above the modern ice sheet surface and outboard of the current ice margin show that the Antarctic Ice Sheet (AIS) was much more extensive at the Last Glacial Maximum (∼ 20 ka) than at present. However, whether it was ever smaller than present during the last few millennia, and (if so) by how much, is known only for a few locations because direct evidence lies within or beneath the ice sheet, which is challenging to access. Here, we describe how retreat and readvance (henceforth “readvance”) of AIS grounding lines during the Holocene could be detected and quantified using subglacial bedrock, subglacial sediments, marine sediment cores, relative sea-level (RSL) records, geodetic observations, radar data, and ice cores. Of these, only subglacial bedrock and subglacial sediments can provide direct evidence for readvance. Marine archives are of limited utility because readvance commonly covers evidence of earlier retreat. Nevertheless, stratigraphic transitions documenting change in environment may provide support for direct evidence from subglacial records, as can the presence of transgressions in RSL records, and isostatic subsidence. With independent age control, ice structure revealed by radar can be used to infer past changes in ice flow and geometry, and therefore potential readvance. Since ice cores capture changes in surface mass balance, elevation, and atmospheric and oceanic circulation that are known to drive grounding line migration, they also have potential for identifying readvance. A multidisciplinary approach is likely to provide the strongest evidence for or against a smaller-than-present AIS in the Holocene

Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK:a prospective multicentre cohort study

BACKGROUND: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. METHODS: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2-7 months after hospital discharge and a later time point 10-14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4-6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5-8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (-19%; 95% CI -20 to -16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18-39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27-41% of this effect. INTERPRETATION: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. FUNDING: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council

Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study

BACKGROUND: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. METHODS: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2-7 months after hospital discharge and a later time point 10-14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4-6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5-8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (-19%; 95% CI -20 to -16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18-39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27-41% of this effect. INTERPRETATION: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. FUNDING: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council