Tetraspanin CD53 promotes lymphocyte recirculation by stablising L-selectin surface expression

Tetraspanins regulate key processes in immune cells; however, the function of the leukocyterestricted tetraspanin, CD53 has remained unknown. Here we show that CD53 is essential for lymphocyte recirculation. Lymph nodes of Cd53-/- mice were smaller than wild-type mice due to a marked reduction in B cells and a 50% decrease in T cells. This reduced cellularity reflected an inability of Cd53-/- B and T cells to efficiently home to lymph nodes, due to the near absence of L-selectin from Cd53-/- B cells and reduced stability of L-selectin on Cd53-/- T cells. Further analyses, including on human lymphocytes, showed that CD53 inhibits L-selectin shedding via both ADAM17-dependent and -independent mechanisms. The disruption in lymphocyte recirculation in Cd53-/- mice led to impaired immune responses dependent on antigen delivery to lymph nodes. Together these findings demonstrate a previously unrecognized essential role for CD53 in lymphocyte trafficking and immune responses

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License

Self-awareness of falls risk in older adults

Falls and fall-related injuries are a significant clinical issue in the older population. Reduced awareness of falls risk has been identified as a barrier to undertaking fall prevention advice and may be associated with risk-taking behaviour. However, previous research has not comprehensively investigated self-awareness of falls risk in older adults and little is known about the prevalence, factors and outcomes associated with reduced awareness of falls risk. This may be attributed to a lack of validated measures available to assess this construct. The aim of this thesis, therefore, was to expand current understanding in this area by developing and validating a measure of falls risk self-awareness; providing initial data regarding the proportion of older adults that underestimate falls risk; and exploring some associated factors and outcomes. Participants comprised 91 older adults aged over 60 undergoing inpatient rehabilitation. Treating physiotherapists and occupational therapists also participated in the studies. The first study described the development and psychometric evaluation of the three part (intellectual, emergent and anticipatory) Self-Awareness of Falls Risk Measure (SAFRM) to be used in the older population undergoing inpatient rehabilitation. The SAFRM demonstrated a three factor structure corresponding to the theoretically developed subsections and good internal consistency, clinician inter-rater reliability, convergent validity and ecological validity. The second study utilised the SAFRM to provide initial data regarding the proportion of older adult rehabilitation inpatients that underestimate and overestimate falls risk, and explored some factors associated with reduced self-awareness. The results indicated that reduced self-awareness of falls risk is not uncommon in the older population with eight to 28 percent of patients demonstrating moderately to severely reduced self-awareness of falls risk. Moderate to severe overestimation of falls risk was relatively uncommon (1-3%). Male gender, higher educational attainment and neurological history were independent predictors of overall self-awareness. The third study investigated the relationship between self-awareness of falls risk and rehabilitation engagement, motivation for rehabilitation, and falls three months post hospital discharge. The results indicated that different types of awareness (i.e. intellectual, emergent, anticipatory, overall) may be important for engagement in specific aspects of therapy (i.e. physiotherapy, occupational therapy). Regression analyses indicated that overall self-awareness provided a unique contribution to occupational-therapist rated rehabilitation engagement when controlling for age, gender, cognition, and functional ability. However, no such relationship was found for physiotherapist-rated engagement or patient-reported motivation. Falls were reported by 29.85% of participants; however, self-awareness did not differ between fallers and non-fallers. Overall, the present thesis provided a psychometrically validated measure for the assessment of self-awareness of falls risk in older adults. It is acknowledged that further evaluation of its reliability and validity is required. Preliminary data presented highlights that underestimation of risk is not uncommon in older adults. Some key variables associated with reduced self-awareness were identified and negative outcomes such as lower rehabilitation engagement and motivation were demonstrated. Current results provide directions for future research in this area, which could examine the biopsychosocial factors and other outcomes associated with reduced awareness of falls risk in older adults

Spatially resolved spectroscopy of detached recombining plasmas in the University of Manchester Linear System divertor simulator

The University of Manchester Linear System (ULS) [M. G. Rusbridge et al., Plasma Phys. Controlled Fusion 42, 588 (2000)] is an experiment in which a steady-state plasma stream is confined along a longitudinal magnetic field. The plasma passes through a tapered orifice into a separate gas target chamber (GTC) where it interacts with neutral gas at pressures of up to 15 mTorr. The upstream plasma beam is 6–14 mm in diameter with electron temperatures between 2 and 15 eV, and densities in the range of 1017–1019 m−3. The primary aim of this study is to investigate physical processes relevant to gas target divertors in tokamaks. Upstream parameters, in terms of electron temperature and density, can be varied in the ULS enabling the investigation of electron-ion recombination (EIR) or molecular-activated recombination (MAR) processes. Detached recombining plasmas have been studied in the GTC using an axially scanning spectroscopic system with a spatial resolution of less than 5 mm. We have investigated two distinct plasma regimes having the same electron temperature upstream, but upstream densities that differ by an order of magnitude. Vibrationally excited molecules, which are a necessary prerequisite for MAR, have been detected in both these cases. In the higher density case, which ultimately detaches via EIR processes, these excited molecules are present upstream of the EIR region

Studies of detached plasmas on the ULS divertor simulator

We report on studies of detached plasma operation in the UMIST linear system (ULS). The ULS, designed to study a range of edge physics issues relevant to tokamak divertors, is capable of producing plasmas with electron densities and temperatures in the range 1017–1019 m−3 and 2–15 eV, respectively. Previous studies of the interaction between the hydrogen plasma and low-pressure hydrogen gas have identified a regime where molecular activated recombination (MAR) processes dominate plasma losses. Here we report on studies in which the upstream plasma parameters are varied such that three-body and radiative electron–ion recombination (EIR) dominates. Initial modelling of the recombination region is undertaken using a simplified version of the one-dimensional electron energy and continuity equations. We determine the factors that govern the threshold between MAR and EIR dominated detached regimes in terms of upstream plasma parameters and compare this with predictions based on the competing effects of electron cooling and recombination

Spatial structure of detached plasmas in the ULS divertor simulator

The UMIST Linear system (ULS) is a linear plasma device designed to study plasma and atomic physics issues relevant to tokamak divertors. The ULS produces a steady state plasma beam which interacts with neutral gas in a target chamber. Dependent on the upstream conditions, either electron-ion recombination (EIR) or molecular activated recombination (MAR) may dominate. Here we report on detailed studies of the plasma spatial structure in both regimes. A specially designed optical spectroscopy probe is used to measure the visible emission, with spatial resolution less than 5 mm. Atomic and molecular lines are identified, and the results are interpreted using a collisional-radiative model, enabling the MAR rate to be calculated. One dimensional plasma modelling also demonstrates a transition between EIR and MAR dominated regimes, as the upstream conditions are varied

A sequence of flux transfer events potentially generated by different generation mechanisms

Flux transfer events (FTEs) are magnetic structures generated by time-varying reconnection at the dayside magnetopause. Understanding their generation mechanism is important, because it is necessary in order to understand the global contribution of FTEs to the convection process. We present observations of several FTEs sequentially observed by Cluster at the subsolar magnetopause. Cluster detected also several reconnection jets, which seem to be systematically associated with the trailing edge of the FTEs. This association is expected only in the FTEs formed by single X line reconnection but could be compatible also with the multiple X line model, when reconnection at one X line is dominant. Instead, it does not seem compatible with original mechanism proposed by Russell and Elphic (1978). For a large FTE, not associated with any reconnection jet, the Grad-Shafranov reconstruction obtained from Cluster 1 data recovers a flux rope, indicative of multiple X line reconnection. This same FTE was detected also by Cluster 3, which observed an asymmetric signature in the magnetic field component normal to the magnetopause. We show that this asymmetric signature was caused by an outward motion of the magnetopause. The orientation of the other FTEs, obtained from a Grad-Shafranov optimization, shows considerable spread, despite the relatively steady conditions. Our interpretation is that a combination of single and multiple X line reconnection generated these FTEs. The FTEs in the first part of the crossing, associated with reconnection jets, are generated by the single X line model and may therefore not satisfy the Grad-Shafranov assumptions so well. Instead, the last FTE, slower, bigger, and well separated from the previous ones, may be formed by multiple X line reconnection

Poststroke cognitive impairment negatively impacts activity and participation outcomes : A systematic review and meta-analysis

This systematic review and meta-analysis aimed to investigate whether cognition is associated with activity and participation outcomes in adult stroke survivors. Five databases were systematically searched for studies investigating the relationship between general- and domain-specific cognition and longer-term (>3 months) basic activities of daily living (ADL), instrumental ADLs, and participation outcomes. Eligibility for inclusion, data extraction, and study quality was evaluated by 2 reviewers using a standardized protocol. Effect sizes (r) were estimated using a random-effects model. Sixty-two publications were retained for review, comprising 7817 stroke survivors (median age 63.57 years, range:18–96 years). Median length of follow-up was 12 months (range: 3 months–11 years). Cognition (all domains combined) demonstrated a significant medium association with all 3 functional outcomes combined, r=0.37 (95% CI, 0.33–0.41), P<0.001. Moderator analyses revealed these effects persisted regardless of study quality, order in which outcomes were collected (sequential versus concurrent), age, sample size, or follow-up period. Small to medium associations were also identified between each individual cognitive domain and the separate ADL, instrumental ADL, and participation outcomes. In conclusion, poststroke cognitive impairment is associated with early and enduring activity limitations and participation restrictions, and the association is robust to study design factors, such as sample size, participant age, follow-up period, or study quality. Cognitive assessment early poststroke is recommended to facilitate early detection of disability, prediction of functional outcomes, and to inform tailored rehabilitation therapies

Comparing memory group training and computerized cognitive training for improving memory function following stroke: A phase II randomized controlled trial

Objectives: Memory deficits are common after stroke, yet remain a high unmet need within the community. The aim of this phase II randomized controlled trial was to determine whether group compensatory or computerized cognitive training approaches were effective in rehabilitating memory following stroke. Methods: A parallel, 3-group, single-blind, randomized controlled trial was used to compare the effectiveness of a compensatory memory skills group with restorative computerized training on functional goal attainment. Secondary outcomes explored change in neuropsychological measures of memory, subjective ratings of prospective and everyday memory failures and ratings of internal and external strategy use. Results: A total of 65 community dwelling survivors of stroke were randomized (24: memory group, 22: computerized cognitive training, and 19: wait-list control). Participants allocated to the memory group reported significantly greater attainment of memory goals and internal strategy use at 6-week follow-up relative to participants in computerized training and wait-list control conditions. However, groups did not differ significantly on any subjective or objective secondary outcomes. Conclusion: Preliminary evidence shows that memory skills groups, but not computerized training, may facilitate achievement of functional memory goals for community dwelling survivors of stroke. These findings require further replication, given the modest sample size, subjective nature of the outcomes and the absence of objective eligibility for inclusion