Re United Food Processors Union, Local 483 and Canada Starch Co (McKay)

Employee grievances, pursuant to the Collective Agreement between the parties effective May 28, 1967, alleging improper assignment of work to a probationary employee and requesting payment of overtime. It was agreed by the parties that the result in the McKay grievance would be accepted as governing the two McLaughlin grievances

Living at home after emergency hospital admission:prospective cohort study in older adults with and without cognitive spectrum disorder

Background: Cognitive spectrum disorders (CSDs) are common in hospitalised older adults and associated with adverse outcomes. Their association with the maintenance of independent living has not been established. The aim was to establish the role of CSDs on the likelihood of living at home 30 days after discharge or being newly admitted to a care home. Methods: A prospective cohort study with routine data linkage was conducted based on admissions data from the acute medical unit of a district general hospital in Scotland. 5570 people aged ≥ 65 years admitted from a private residence who survived to discharge and received the Older Persons Routine Acute Assessment (OPRAA) during an incident emergency medical admission were included. The outcome measures were living at home, defined as a private residential address, 30 days after discharge and new care home admission at hospital discharge. Outcomes were ascertained through linkage to routine data sources. Results: Of the 5570 individuals admitted from a private residence who survived to discharge, those without a CSD were more likely to be living at home at 30 days than those with a CSD (93.4% versus 81.7%; difference 11.7%, 95%CI 9.7–13.8%). New discharge to a care home affected 236 (4.2%) of the cohort, 181 (76.7%) of whom had a CSD. Logistic regression modelling identified that all four CSD categories were associated with a reduced likelihood of living at home and an increased likelihood of discharge to a care home. Those with delirium superimposed on dementia were the least likely to be living at home (OR 0.25), followed by those with dementia (OR 0.43), then unspecified cognitive impairment (OR 0.55) and finally delirium (OR 0.57). Conclusions: Individuals with a CSD are at significantly increased risk of not returning home after hospitalisation, and those with CSDs account for the majority of new admissions to care homes on discharge. Individuals with delirium superimposed on dementia are the most affected. We need to understand how to configure and deliver healthcare services to enable older people to remain as independent as possible for as long as possible and to ensure transitions of care are managed supportively

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

Deprescribing interventions and their impact on medication adherence in community-dwelling older adults with polypharmacy: a systematic review

Background: Polypharmacy, and the associated adverse drug events such as non-adherence to prescriptions, is a common problem for elderly people living with multiple comorbidities. Deprescribing, i.e. the gradual withdrawal from medications with supervision by a healthcare professional, is regarded as a means of reducing adverse effects of multiple medications including non-adherence. This systematic review examines the evidence of deprescribing as an effective strategy for improving medication adherence amongst older, community dwelling adults. Methods: A mixed methods review was undertaken. Eight bibliographic database and two clinical trials registers were searched between May and December 2017. Results were double screened in accordance with pre-defined inclusion/exclusion criteria related to polypharmacy, deprescribing and adherence in older, community dwelling populations. The Mixed Methods Appraisal Tool (MMAT) was used for quality appraisal and an a priori data collection instrument was used. For the quantitative studies, a narrative synthesis approach was taken. The qualitative data was analysed using framework analysis. Findings were integrated using a mixed methods technique. The review was performed in accordance with the PRISMA reporting statement. Results: A total of 22 original studies were included, of which 12 were RCTs. Deprescribing with adherence as an outcome measure was identified in randomised controlled trials (RCTs), observational and cohort studies from 13 countries between 1996 and 2017. There were 17 pharmacy-led interventions; others were led by General Practitioners (GP) and nurses. Four studies demonstrated an overall reduction in medications of which all studies corresponded with improved adherence. A total of thirteen studies reported improved adherence of which 5 were RCTs. Adherence was reported as a secondary outcome in all but one study. Conclusions: There is insufficient evidence to show that deprescribing improves medication adherence. Only 13 studies (of 22) reported adherence of which only 5 were randomised controlled trials. Older people are particularly susceptible to non-adherence due to multi-morbidity associated with polypharmacy. Bio-psycho-social factors including health literacy and multi-disciplinary team interventions influence adherence. The authors recommend further study into the efficacy and outcomes of medicines management interventions. A consensus on priority outcome measurements for prescribed medications is indicated

Topological cell clustering in the ATLAS calorimeters and its performance in LHC Run 1

The reconstruction of the signal from hadrons and jets emerging from the proton–proton collisions at the Large Hadron Collider (LHC) and entering the ATLAS calorimeters is based on a three-dimensional topological clustering of individual calorimeter cell signals. The cluster formation follows cell signal-significance patterns generated by electromagnetic and hadronic showers. In this, the clustering algorithm implicitly performs a topological noise suppression by removing cells with insignificant signals which are not in close proximity to cells with significant signals. The resulting topological cell clusters have shape and location information, which is exploited to apply a local energy calibration and corrections depending on the nature of the cluster. Topological cell clustering is established as a well-performing calorimeter signal definition for jet and missing transverse momentum reconstruction in ATLAS

A Subset of Replication Proteins Enhances Origin Recognition and Lytic Replication by the Epstein-Barr Virus ZEBRA Protein

ZEBRA is a site-specific DNA binding protein that functions as a transcriptional activator and as an origin binding protein. Both activities require that ZEBRA recognizes DNA motifs that are scattered along the viral genome. The mechanism by which ZEBRA discriminates between the origin of lytic replication and promoters of EBV early genes is not well understood. We explored the hypothesis that activation of replication requires stronger association between ZEBRA and DNA than does transcription. A ZEBRA mutant, Z(S173A), at a phosphorylation site and three point mutants in the DNA recognition domain of ZEBRA, namely Z(Y180E), Z(R187K) and Z(K188A), were similarly deficient at activating lytic DNA replication and expression of late gene expression but were competent to activate transcription of viral early lytic genes. These mutants all exhibited reduced capacity to interact with DNA as assessed by EMSA, ChIP and an in vivo biotinylated DNA pull-down assay. Over-expression of three virally encoded replication proteins, namely the primase (BSLF1), the single-stranded DNA-binding protein (BALF2) and the DNA polymerase processivity factor (BMRF1), partially rescued the replication defect in these mutants and enhanced ZEBRA's interaction with oriLyt. The findings demonstrate a functional role of replication proteins in stabilizing the association of ZEBRA with viral DNA. Enhanced binding of ZEBRA to oriLyt is crucial for lytic viral DNA replication

Age, anticoagulants, hypertension and cardiovascular genetic traits predict cranial ischaemic complications in patients with giant cell arteritis

\ua9 Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.Objectives: This project aimed to determine whether cranial ischaemic complications at the presentation of giant cell arteritis (GCA) were associated with pre-existing cardiovascular (CV) risk factors, CV disease or genetic risk of CV-related traits. Methods: 1946 GCA patients with clinicodemographic data at GCA presentation were included. Associations between pre-existing CV-related traits (including Polygenic Risk Scores (PRS) for CV traits) and cranial ischaemic complications were tested. A model for cranial ischaemic complications was optimised using an elastic net approach. Positional gene mapping of associated PRS was performed to improve biological understanding. Results: In a sample of 1946 GCA patients (median age=71, 68.7% female), 17% had cranial ischaemic complications at presentation. In univariable analyses, 10 variables were associated with complications (likelihood-ratio test p≤0.05). In multivariable analysis, the two variables with the strongest effects, with or without PRS in the model, were anticoagulant therapy (adjusted OR (95% CI)=0.21 (0.05 to 0.62), p=4.95 710-3) and age (adjusted OR (95% CI)=1.60 (0.73 to 3.66), p=2.52 710-3, for ≥80 years versus <60 years). In sensitivity analyses omitting anticoagulant therapy from multivariable analysis, age and hypertension were associated with cranial ischaemic complications at presentation (hypertension: adjusted OR (95% CI)=1.35 (1.03 to 1.75), p=0.03). Positional gene mapping of an associated transient ischaemic attack PRS identified TEK, CD96 and MROH9 loci. Conclusion: Age and hypertension were risk factors for cranial ischaemic complications at GCA presentation, but in this dataset, anticoagulation appeared protective. Positional gene mapping suggested a role for immune and coagulation-related pathways in the pathogenesis of complications. Further studies are needed before implementation in clinical practice

Risk loci involved in giant cell arteritis susceptibility: a genome-wide association study

Background: Giant cell arteritis is an age-related vasculitis that mainly affects the aorta and its branches in individuals aged 50 years and older. Current options for diagnosis and treatment are scarce, highlighting the need to better understand its underlying pathogenesis. Genome-wide association studies (GWAS) have emerged as a powerful tool for unravelling the pathogenic mechanisms involved in complex diseases. We aimed to characterise the genetic basis of giant cell arteritis by performing the largest GWAS of this vasculitis to date and to assess the functional consequences and clinical implications of identified risk loci. Methods: We collected and meta-analysed genomic data from patients with giant cell arteritis and healthy controls of European ancestry from ten cohorts across Europe and North America. Eligible patients required confirmation of giant cell arteritis diagnosis by positive temporal artery biopsy, positive temporal artery doppler ultrasonography, or imaging techniques confirming large-vessel vasculitis. We assessed the functional consequences of loci associated with giant cell arteritis using cell enrichment analysis, fine-mapping, and causal gene prioritisation. We also performed a drug repurposing analysis and developed a polygenic risk score to explore the clinical implications of our findings. Findings: We included a total of 3498 patients with giant cell arteritis and 15 550 controls. We identified three novel loci associated with risk of giant cell arteritis. Two loci, MFGE8 (rs8029053; p=4·96 × 10–8; OR 1·19 [95% CI 1·12–1·26]) and VTN (rs704; p=2·75 × 10–9; OR 0·84 [0·79–0·89]), were related to angiogenesis pathways and the third locus, CCDC25 (rs11782624; p=1·28 × 10–8; OR 1·18 [1·12–1·25]), was related to neutrophil extracellular traps (NETs). We also found an association between this vasculitis and HLA region and PLG. Variants associated with giant cell arteritis seemed to fulfil a specific regulatory role in crucial immune cell types. Furthermore, we identified several drugs that could represent promising candidates for treatment of this disease. The polygenic risk score model was able to identify individuals at increased risk of developing giant cell arteritis (90th percentile OR 2·87 [95% CI 2·15–3·82]; p=1·73 × 10–13). Interpretation: We have found several additional loci associated with giant cell arteritis, highlighting the crucial role of angiogenesis in disease susceptibility. Our study represents a step forward in the translation of genomic findings to clinical practice in giant cell arteritis, proposing new treatments and a method to measure genetic predisposition to this vasculitis. Funding: Institute of Health Carlos III, Spanish Ministry of Science and Innovation, UK Medical Research Council, and National Institute for Health and Care Researc