Alpine plants are on the move: Quantifying distribution shifts of Australian alpine plants through time

Aim Alpine plant species’ distributions are thought to have been shifting to higher elevations in response to climate change. By moving upslope, species can occupy cooler and more suitable environments as climate change warms their current ranges. Despite evidence of upslope migration in the northern hemisphere, there is limited evidence for elevational shifts in southern hemisphere plants. Our study aimed to determine if alpine plants in Australia have migrated upslope in the last 2 to 6 decades. Location Kosciuszko National Park, NSW, Australia. Methods We collated historic occurrence data for 36 Australian alpine plant species from herbarium specimens and historic field observations and combined these historic data with modern occurrence data collected in the field. Results Eleven of the thirty-six species had shifted upslope in mean elevation and four species showed downslope elevational shifts. The rate of change for upslope shifts varied between 4 and 10 m per year and the rate of change for most downslope shifts was between 4 and 8 m per year, with one species shifting downslope at a high rate of 18 m per year. Additionally, some species showed shifts upward in their upper range edge and/or upward or downward shifts in their lower range edge. Five species also showed range contractions in the difference between their lower and upper range edges over time, while two showed range expansions. We found no significant differences in elevational shifts through time among herbaceous dicotyledons, herbaceous monocotyledons and shrubs. Main Conclusions Plant elevational shifts are occurring rapidly in the Australian alpine zone. This may allow species to persist under climate change. However, if current warming trends continue, several species within the Australian alpine zone will likely run out of suitable habitat within a century

Are people who participate in cultural activities more satisfied with life?

The influence of various aspects of life on wellbeing has been extensively researched. However, despite little empirical evidence, participation in leisure activities has been assumed to increase subjective wellbeing. Leisure is important because it is more under personal control than other sources of life satisfaction. This study asked whether people who participate in cultural leisure activities have higher life satisfaction than people who do not, if different types of leisure have the same influence on life satisfaction and if satisfaction is dependent on the frequency of participation or the number of activities undertaken. It used data from UKHLS Survey to establish associations between type, number and frequency of participation in leisure activities and life satisfaction. Results showed an independent and positive association of participation in sport, heritage and active-creative leisure activities and life satisfaction but not for participation in popular entertainment, theatre hobbies and museum/galleries. The association of reading hobbies and sedentary-creative activities and life satisfaction was negative. High life satisfaction was associated with engaging in a number of different activities rather than the frequency of participation in each of them. The results have implications for policy makers and leisure services providers, in particular those associated with heritage recreation. Subjective wellbeing measures, such as life satisfaction, and not economic measures alone should be considered in the evaluation of services. The promotion of leisure activities which are active and promote social interaction should be considered in programmes aimed at improving the quality of life

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Mortality in Hip Fracture Patients During the COVID-19 Pandemic: A Retrospective Analysis in a District General Hospital in the United Kingdom

Introduction Hip fracture is commonly seen in elderly patients because of low-energy trauma. It carries significant morbidity and mortality. Scoring systems such as the Nottingham hip fracture score (NHFS) have shown a good correlation with increased mortality as the value of these scores increases. In our study, we aim to ascertain the hip fracture mortality in our population, compare the mortality in hip fractures compared to previously reported figures in literature and nationally reported figures during the first year of the COVID-19 pandemic, and also ascertain the usefulness of NHFS in predicting mortality in hip fractures. Methods We gathered mortality data on hip fracture patients admitted to our unit from January 1, 2020 to December 31, 2020.&nbsp;NHFS was calculated for all patients and the 30-day mortality rate was compared to previously reported hip fracture mortality rates using the standard mortality ratio (SMR). One-year mortality was stratified by placing patients in high and low NHFS groups. The log-rank test was used to compare hip fracture survival at one month and at one year in the high NHFS (NHFS &gt;4) group and low NHFS group (NHFS value 4 or below). Additionally, a log-rank test was used to compare one-month and one-year survival in hip fractures managed with hemiarthroplasty, dynamic hip screw and intramedullary nail. Results In 2020, 388 patients were admitted with hip fractures to our unit. The crude mortality rate was 3.9% at 30 days and 20.88% at one year. Compared to the National Hip Fracture Database report for 2020, the incidence risk ratio for mortality was 0.46 (p-value&lt;0.05). The SMR at 30 days was 0.34 (CI=0.17-0.51) and the SMR at one year was 0.63 (CI=0.49-0.77). The survival rate was higher at 30 days and one year in the low NHFS group compared to the high NHFS group (p-value&lt;0.01). The survival rate at one month and one year were similar in groups managed with hemiarthroplasty, dynamic hip screws, and intramedullary nails (p-value&gt;0.05). Conclusions Hip fracture mortality has been decreasing steadily and we noted a lower rate of hip fracture mortality compared to figures reported previously as per NHFS studies even though the study was conducted during the COVID-19 pandemic period. We also noted lower 30-day mortality in our hospital as compared to the national 30-day mortality rate for hip fracture patients in 2020. &nbsp;</p

Impact of COVID-19 Pandemic on the Length of Hospital Stay in Hip Fracture Patients: A Single Centre Study

Background Hip fracture is a debilitating injury, especially in older individuals, which is associated with significant morbidity and mortality. In recent decades, there has been a great focus on early rehabilitation and discharge after hip fractures. The aim of such efforts is to minimize the financial and clinical burden of this condition. We conducted our study during the COVID-19 pandemic and compared the length of hospital stay (LOS) in 2020 to the LOS in 2019. Additionally, we studied the factors which may impact the LOS, such as premorbid status according to established scoring systems, the type of fracture, an operation performed, and time to surgery. &nbsp; Methods We collected the data regarding the length of stay (in days) for all hip fracture patients admitted to our unit from 1st January 2019 until 31st December 2020. We then compared the mean LOS for both years using the t-test. We calculated the Nottingham Hip Fracture Score (NHFS) and American Society of Anaesthesiologists (ASA) scores for patients admitted in 2020 and calculated the correlation between increasing values of these scores and the LOS. We also compared the mean LOS for patients admitted in 2020 based on the type of fracture and type of management. We studied the correlation between the time to surgery and the LOS for patients admitted in 2020. &nbsp; Results Three hundred and eighty-eight patients were admitted with hip fractures in 2020, and 452 were admitted in 2019. LOS in 2020 was significantly lower (23.39 days) compared to 2019 (31.36 days) with p&lt;0.01. While evaluating data from 2019, it was noted that there was a small positive correlation between LOS and NHFS (r=0.231, p&lt;0.001) and LOS and ASA (r=0.18, p&lt;0.001). The mean LOS for intracapsular fractures was noted to be lower than that of extracapsular fractures, but this was not statistically significant (p=0.17). An ANOVA test showed that the mean LOS for patients undergoing hemiarthroplasty, dynamic hip screws (DHS), and intramedullary nails (IMN) was significantly longer than for patients managed with total hip replacement or patients managed non-operatively (F=3.551, p&lt;0.01). &nbsp; Conclusion Hip fracture patients admitted to our department were discharged quicker during the first year of the COVID-19 pandemic. The LOS for hip fractures increases with an increase in their NHFS or ASA scores. Extracapsular and intracapsular fractures lead to roughly the same periods of inpatient stay. Patients undergoing hemiarthroplasty, DHS, or IMN stay longer in the hospital compared to other treatment modalities.</p

Oligosaccharyltransferase Inhibition Induces Senescence in RTK-Driven Tumor Cells

Asparagine (N)-linked glycosylation is a protein modification critical for glycoprotein folding, stability, and cellular localization. To identify small molecules that inhibit new targets in this biosynthetic pathway, we initiated a cell-based high throughput screen and lead compound optimization campaign that delivered a cell permeable inhibitor (NGI-1). NGI-1 targets the oligosaccharyltransferase (OST), a hetero-oligomeric enzyme that exists in multiple isoforms and transfers oligosaccharides to recipient proteins. In non-small cell lung cancer cells NGI-1 blocks cell surface localization and signaling of the EGFR glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or FGFR) for survival. In these cell lines OST inhibition causes cell cycle arrest accompanied by induction of p21, autofluorescence, and changes in cell morphology; all hallmarks of senescence. These results identify OST inhibition as a potential therapeutic approach for treating receptor tyrosine kinase-dependent tumors and provides a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types