The West Antarctic Ice Sheet may not be vulnerable to marine ice cliff instability during the 21st century.

The collapse of ice shelves could expose tall ice cliffs at ice sheet margins. The marine ice cliff instability (MICI) is a hypothesis that predicts that, if these cliffs are tall enough, ice may fail structurally leading to self-sustained retreat. To date, projections that include MICI have been performed with a single model based on a simple parameterization. Here, we implement a physically motivated parameterization in three ice sheet models and simulate the response of the Amundsen Sea Embayment after a hypothetical collapse of floating ice. All models show that Thwaites Glacier would not retreat further in the 21st century. In another set of simulations, we force the grounding line to retreat into Thwaites' deeper basin to expose a taller cliff. In these simulations, rapid thinning and velocity increase reduce the calving rate, stabilizing the cliff. These experiments show that Thwaites may be less vulnerable to MICI than previously thought, and model projections that include this process should be re-evaluated.

Long-term Outcomes of Multiligament Knee Injuries in American Football Players.

BACKGROUND: Long-term outcomes for isolated anterior cruciate ligament (ACL) reconstructions in competitive American football athletes are well reported in the literature, but little data currently exist regarding multiligament knee injury (MLKI) reconstruction outcomes. PURPOSE: To examine patient-reported and return-to-sport outcomes of competitive American football athletes who underwent primary, single-staged, multiligament knee reconstruction. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: We identified patients from our institution's prospectively collected data repository between 2001 and 2020 who underwent single-staged surgical reconstruction of an MLKI sustained during competitive participation in American football. We assessed patient-reported outcomes at a minimum of 2 years after surgery using the International Knee Documentation Committee (IKDC) Subjective Knee Form and questions regarding surgical satisfaction and return to sport. Successful return to sport was defined as a return to preinjury level of competition. We summarized all outcome data and compared outcomes between 2-ligament and >2-ligament groups and between ACL-only MLKI injury and bicruciate MLKI injury groups using independent t test for IKDC scores and chi-square test for return to sport. Additionally, we evaluated predictors of postoperative IKDC scores using linear regression and predictors of return to sport using logistic regression. RESULTS: Outcome data were successfully collected for 53 of 73 total eligible patients (73%; mean follow-up time, 7.7 ± 4.0 years; all male; mean age at surgery, 18.1 ± 2.7 years). The mean postoperative IKDC score was 84 ± 16. The most common level of preinjury competition was high school (n = 36; 68%), followed by college (n = 10; 19%). Seven patients did not return to sport competition at any level due to limitations from their knee surgery, and 82% of patients that attempted to return to preinjury level of sport were able to do so. A total of 50 patients (94%) were satisfied or very satisfied with their surgical outcome. The 2-ligament (n = 39) and >2-ligament (n = 14) groups did not significantly differ in IKDC scores (P = .96) or proportions with successful return to sport (P = .77). Similarly, the ACL-MLKI injury (n = 39) and bicruciate MLKI injury (n = 14) groups did not significantly differ in IKDC scores (P = .89) or proportions with successful return to sport (P = .77). Age and body mass index were not significantly associated with IKDC scores or successful return to sport at follow-up (all P > .05). CONCLUSION: This study may represent the largest cohort of competitive American football athletes evaluated for longitudinal outcomes after multiligament knee reconstruction. Despite the severity of these injuries, we found good knee-related function and that the large majority of athletes who attempted to return to sport were successful. The majority of athletes (94%) were satisfied with their operative treatment.

Hemispheric asymmetries in hippocampal volume related to memory in left and right temporal variants of frontotemporal degeneration.

In addition to Alzheimer's disease (AD), the hippocampus is now known to be affected in variants of frontotemporal degeneration (FTD). In semantic variant primary progressive aphasia (svPPA), characterized by language impairments, hippocampal atrophy is greater in the left hemisphere. Nonverbal impairments (e.g., visual object recognition) are prominent in the right temporal variant of FTD (rtvFTD), and hippocampal atrophy may be greater in the right hemisphere. In this study we examined the hypothesis that leftward hippocampal asymmetry (predicted in svPPA) would be associated with selective verbal memory impairments (with relative preservation of visual memory), while rightward asymmetry (predicted in rtvFTD) would be associated with the opposite pattern (greater visual memory impairment). In contrast, we predicted that controls and individuals in the amnestic mild cognitive impairment stage of AD (aMCI), both of whom were expected to show symmetrical hippocampal volumes, would show roughly equivalent scores in verbal and visual memory. Participants completed delayed recall tests with words and geometric shapes, and hippocampal volumes were assessed with MRI. The aMCI sample showed symmetrical hippocampal atrophy, and similar degree of verbal and visual memory impairment. The svPPA sample showed greater left hippocampal atrophy and verbal memory impairment, while rtvFTD showed greater right hippocampal atrophy and visual memory impairment. Greater asymmetry in hippocampal volumes was associated with larger differences between verbal and visual memory in the FTD samples. Unlike AD, asymmetry is a core feature of brain-memory relationships in temporal variants of FTD.

Impact of the geriatric emergency medicine specialist intervention on final emergency department disposition.

BACKGROUND: The Geriatric Emergency Medicine Specialist (GEMS) pilot program is an innovative approach that utilizes geriatric-trained advanced practice providers to facilitate geriatric assessments and care planning for older adults in the emergency department (ED). The objective of this study was to explore the effect of GEMS on the use of observation status and final ED disposition. METHODS: This was a retrospective study under a target trial emulation framework. Geriatric patients (65+ years old) who presented to two ED sites within a large regional healthcare system between December 2020 and December 2022 were included. The primary outcome was final ED disposition (discharge, hospital inpatient admission, or hospital observation admission). Secondary outcomes included ED observation and ED length of stay. Non-GEMS patients were propensity score matched 5:1 to GEMS patients. Doubly robust regression was used to estimate the odds ratios and 95% confidence intervals of inpatient admission, discharge, hospital observation admission, ED observation admission, and estimate the mean ED length of stay. RESULTS: A total of 427 of 43,064 total patients (1.0%) received a GEMS intervention during the study period. Our analysis included 2,302 geriatric ED patients (410 GEMS, 1,892 non-GEMS) after propensity score matching. Hospital admission rates were 34.1% for GEMS compared to 56.4% for conventional treatment. GEMS patients had decreased odds of inpatient admission (OR: 0.41, 95 CI: 0.34-0.51, p < 0.001), increased odds of discharge (OR: 1.19 95 CI: 1.00-1.42, p = 0.047), hospital observation admission (OR: 2.97, 95 CI: 2.35-3.75, p < 0.001), ED observation admission (OR: 4.84 95 CI: 3.67-6.38, p < 0.001), and had a longer average ED length of stay (170 min, 95 CI: 84.6-256, p < 0.001) compared to non-GEMS patients. CONCLUSIONS: Patients seen by GEMS during their ED visit were associated with higher rates of hospital discharge and lower rates of hospital admissions.

Risk of severe COVID-19 outcomes after autumn 2022 COVID-19 booster vaccinations: a pooled analysis of national prospective cohort studies involving 7.4 million adults in England, Northern Ireland, Scotland and Wales.

Background: UK COVID-19 vaccination policy has evolved to offering COVID-19 booster doses to individuals at increased risk of severe Illness from COVID-19. Building on our analyses of vaccine effectiveness of first, second and initial booster doses, we aimed to identify individuals at increased risk of severe outcomes (i.e., COVID-19 related hospitalisation or death) post the autumn 2022 booster dose. Methods: We undertook a national population-based cohort analysis across all four UK nations through linked primary care, vaccination, hospitalisation and mortality data. We included individuals who received autumn 2022 booster doses of BNT162b2 (Comirnaty) or mRNA-1273 (Spikevax) during the period September 1, 2022 to December 31, 2022 to investigate the risk of severe COVID-19 outcomes. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) for the association between demographic and clinical factors and severe COVID-19 outcomes after the autumn booster dose. Analyses were adjusted for age, sex, body mass index (BMI), deprivation, urban/rural areas and comorbidities. Stratified analyses were conducted by vaccine type. We then conducted a fixed-effect meta-analysis to combine results across the four UK nations. Findings: Between September 1, 2022 and December 31, 2022, 7,451,890 individuals ≥18 years received an autumn booster dose. 3500 had severe COVID-19 outcomes (2.9 events per 1000 person-years). Being male (male vs female, aHR 1.41 (1.32-1.51)), older adults (≥80 years vs 18-49 years; 10.43 (8.06-13.50)), underweight (BMI <18.5 vs BMI 25.0-29.9; 2.94 (2.51-3.44)), those with comorbidities (≥5 comorbidities vs none; 9.45 (8.15-10.96)) had a higher risk of COVID-19 hospitalisation or death after the autumn booster dose. Those with a larger household size (≥11 people within household vs 2 people; 1.56 (1.23-1.98)) and from more deprived areas (most deprived vs least deprived quintile; 1.35 (1.21-1.51)) had modestly higher risks. We also observed at least a two-fold increase in risk for those with various chronic neurological conditions, including Down's syndrome, immunodeficiency, chronic kidney disease, cancer, chronic respiratory disease, or cardiovascular disease. Interpretation: Males, older individuals, underweight individuals, those with an increasing number of comorbidities, from a larger household or more deprived areas, and those with specific underlying health conditions remained at increased risk of COVID-19 hospitalisation and death after the autumn 2022 vaccine booster dose. There is now a need to focus on these risk groups for investigating immunogenicity and efficacy of further booster doses or therapeutics. Funding: National Core Studies-Immunity, UK Research and Innovation (Medical Research Council and Economic and Social Research Council), Health Data Research UK, the Scottish Government, and the University of Edinburgh.

Decreased Glycocalyx Shedding on Presentation in Hemorrhaging Geriatric Trauma Patients.

INTRODUCTION: Plasma levels of syndecan-1 (Sdc-1), a biomarker of endothelial glycocalyx (EG) damage, correlate with worse outcomes in trauma patients. However, EG injury is not well characterized in injured older adults (OA). The aims of this study were to characterize Sdc-1 shedding in OA trauma patients relative to younger adults (YA) and determine associations with putative regulators of EG sheddases. METHODS: We performed a secondary analysis of data from the Pragmatic, Randomized Optimal Platelet, and Plasma Ratios (PROPPR) trial, stratifying bluntly injured subjects into OA and YA groups based on upper age quartile (57 y). Plasma Sdc-1 levels were compared in OA and YA at hospital arrival through postinjury day 3, and the independent association between age and Sdc-1 level at arrival was determined after adjusting for differences in gender, shock index (SI), and pre-existing comorbidities. In a follow-up analysis, case-control matching was used to create populations of OA and YA with equivalent SI and injury severity score. Levels of Sdc-1 were compared between these matched groups, and the relationships with candidate regulators of EG shedding were assessed. RESULTS: Of 680 subjects in the Pragmatic, Randomized Optimal Platelet, and Plasma Ratios trial, 350 (51%) had blunt injuries, and 92 (26.3%) of these were OA. Plasma Sdc-1 levels at arrival, 2 h, and 6 h were significantly lower in OA compared to YA (all P < 0.05). After adjusting for sex, pre-existing morbidities and SI, age was associated with decreased Sdc-1 levels at arrival. In the matched analyses, Sdc-1, high-mobility group box 1 and tissue inhibitor of metalloproteinase-2 levels were lower in OA compared to YA. Both high-mobility group box-1 and tissue inhibitor of metalloproteinase-2 significantly correlated with arrival Sdc-1 and were inversely associated with age. CONCLUSIONS: This study indicates that increased age is independently associated with decreased Sdc-1 levels among patients with blunt injuries. Suppressed plasma levels of sheddases in relation to diminished Sdc-1 shedding suggest that mechanisms regulating EG cleavage may be impaired in injured older adults. These findings provide novel insight into the age-dependent impact of injury on the vascular endothelium, which could have important implications for the clinical management of older adults following trauma.

Dementia risk analysis using temporal event modeling on a large real-world dataset.

The objective of the study is to identify healthcare events leading to a diagnosis of dementia from a large real-world dataset. This study uses a data-driven approach to identify temporally ordered pairs and trajectories of healthcare codes in the electronic health record (EHR). This allows for discovery of novel temporal risk factors leading to an outcome of interest that may otherwise be unobvious. We identified several known (Down syndrome RR = 116.1, thiamine deficiency RR = 76.1, and Parkinson's disease RR = 41.1) and unknown (Brief psychotic disorder RR = 68.6, Toxic effect of metals RR = 40.4, and Schizoaffective disorders RR = 40.0) factors for a specific dementia diagnosis. The associations with the greatest risk for any dementia diagnosis were found to be primarily related to mental health (Brief psychotic disorder RR = 266.5, Dissociative and conversion disorders RR = 169.8), or neurologic conditions or procedures (Dystonia RR = 121.9, Lumbar Puncture RR = 119.0). Trajectory and clustering analysis identified factors related to cerebrovascular disorders, as well as diagnoses which increase the risk of toxic imbalances. The results of this study have the ability to provide valuable insights into potential patient progression towards dementia and improve recognition of patients at risk for developing dementia.