Elizabeth Webber Correspondence

Entries include brief biographical information, a handwritten postcard sent in 1940 with Webber\u27s date and place of birth, a letter typed to Miss Margaret Fallin Eicks, whose cookbook review had been noticed by the Maine State Library, requesting information concerning Webber, a letter typed on Boston Evening Transcript, Editorial Rooms, stationery from woman\u27s page editor Eicks, providing Webber\u27s Cambridge, Massachusetts, street address, a typed introductory letter from the Maine State Library to Webber about the Maine Author Collection, a typed letter of reply from Webber on Dinner Is Served ---- Your Room is Ready, A Pocket Guide to Smart Tea Rooms, Hotels and Inns, stationery inked in blue with a Quimper design, concerning the forthcoming publication of a spiral-bound book of recipes sent by east coast managers, of foods relished by guests -- an enlargement of her annual June pocket guide, with news of the opening of the Buttercup Hill Tea Room, and some information concerning her years at the Patten Free Library in Bath, Maine, a typed letter from the Maine State Library thanking Webber for the Dinner Is Served Cook Book for the Maine Author Collection, and a prepublication, biographical, book review newspaper clipping

Securing a sustainable and fit-for-purpose UK health and care workforce

Approximately 13% of the total UK workforce is employed in the health and care sector. Despite substantial workforce planning efforts, the effectiveness of this planning has been criticised. Education, training, and workforce plans have typically considered each health-care profession in isolation and have not adequately responded to changing health and care needs. The results are persistent vacancies, poor morale, and low retention. Areas of particular concern highlighted in this Health Policy paper include primary care, mental health, nursing, clinical and non-clinical support, and social care. Responses to workforce shortfalls have included a high reliance on foreign and temporary staff, small-scale changes in skill mix, and enhanced recruitment drives. Impending challenges for the UK health and care workforce include growing multimorbidity, an increasing shortfall in the supply of unpaid carers, and the relative decline of the attractiveness of the National Health Service (NHS) as an employer internationally. We argue that to secure a sustainable and fit-for-purpose health and care workforce, integrated workforce approaches need to be developed alongside reforms to education and training that reflect changes in roles and skill mix, as well as the trend towards multidisciplinary working. Enhancing career development opportunities, promoting staff wellbeing, and tackling discrimination in the NHS are all needed to improve recruitment, retention, and morale of staff. An urgent priority is to offer sufficient aftercare and support to staff who have been exposed to high-risk situations and traumatic experiences during the COVID-19 pandemic. In response to growing calls to recognise and reward health and care staff, growth in pay must at least keep pace with projected rises in average earnings, which in turn will require linking future NHS funding allocations to rises in pay. Through illustrative projections, we show that, to sustain annual growth in the workforce at approximately 2·4%, increases in NHS expenditure of 4% annually in real terms will be required. Above all, a radical long-term strategic vision is needed to ensure that the future NHS workforce is fit for purpose

Council tax valuation bands, socio-economic status and health outcome: a cross-sectional analysis from the Caerphilly Health and Social Needs Study

Council tax valuation bands (CTVBs) are a categorisation of household property value in Great Britain. The aim of the study was to assess the CTVB as a measure of socio-economic status by comparing the strength of the associations between selected health and lifestyle outcomes and CTVBs with two measures of socio-economic status: the National Statistics Socio-Economic Classification (NS-SEC) and the 2001 UK census-based Townsend deprivation index. METHODS: Cross-sectional analysis of data on 12,092 respondents (adjusted response 62.7%) to the Caerphilly Health and Social Needs Study, a postal questionnaire survey undertaken in Caerphilly county borough, south-east Wales, UK. The CTVB was assigned to each individual by matching the sampling frame to the local authority council tax register. Crude and age-gender adjusted odds ratios for each category of CTVB, NS-SEC and fifth of the ward distribution of Townsend scores were estimated for smoking, poor diet, obesity, and limiting long-term illness using logistic regression. Mean mental (MCS) and physical (PCS) component summary scores of the Short-Form SF-36 health status questionnaire were estimated in general linear models. RESULTS: There were significant trends in odds ratios across the CTVB categories for all outcomes, most marked for smoking and mental and physical health status. The adjusted odds ratio for being a smoker in the lowest versus highest CTVB category was 3.80 (95% CI: 3.06, 4.71), compared to 3.00 (95% CI: 2.30, 3.90) for the NS-SEC 'never worked and long-term unemployed' versus 'higher managerial and professional' categories, and 1.61 (95% CI: 1.42, 1.83) for the most deprived versus the least deprived Townsend fifth. The difference in adjusted mean MCS scores was 5.9 points on the scale for CTVB, 9.2 for NS-SEC and 3.2 for the Townsend score. The values for the adjusted mean PCS scores were 6.3 points for CTVB, 11.3 for NS-SEC, and 2.5 for the Townsend score. CONCLUSION: CTVBs assigned to individuals were strongly associated with the health and lifestyle outcomes modelled in this study. CTVBs are readily available for all residential properties and deserve further consideration as a proxy for socio-economic status in epidemiological studies in Great Britain

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

Longitudinal analysis of vertebral fracture and BMD in a Canadian cohort of adult cystic fibrosis patients

<p>Abstract</p> <p>Background</p> <p>Vertebral fractures in patients with cystic fibrosis (CF) may contribute to an accelerated decline in lung function and can be a contraindication to lung transplantation. In this study, we examined longitudinal change in bone mineral density (BMD) and the prevalence of vertebral fractures in adult CF patients, without lung-transplant, attending a Canadian specialty clinic.</p> <p>Methods</p> <p>Retrospective chart review of all patients attending an Adult Cystic Fibrosis Clinic at Hamilton Health Sciences in Hamilton, Canada. Forty-nine of 56 adults met inclusion criteria. Chest radiographs were graded by consensus approach using Genant's semi-quantitative method to identify and grade fractured vertebrae. Dual x-ray absorptiometry (DXA) scans were also reviewed.</p> <p>Results</p> <p>The mean age of the cohort was 25.2 years (SD 9.4), 43% were male. The mean body mass index (BMI) was 19.8 (2.8) for males and 21.7 (5.1) for females. At baseline, the rate of at least one vertebral fracture was 16.3%; rising to 21.3% (prevalent and incident) after a 3-year follow-up. The mean BMD T-or Z-scores at baseline were -0.80 (SD 1.1) at the lumbar spine, -0.57 (SD 0.97) at the proximal femur, and -0.71 (SD 1.1) at the whole body. Over approximately 4-years, the mean percent change in BMD was -1.93% at the proximal femur and -0.73% at the lumbar spine.</p> <p>Conclusion</p> <p>Approximately one in five CF patients demonstrated at least one or more vertebral fractures. Moderate declines in BMD were observed. Given the high rate of vertebral fractures noted in this cohort of adult CF patients, and the negative impact they have on compromised lung functioning, regular screening for vertebral fractures should be considered on routine chest radiographs.</p

Minimum joint space width and tibial cartilage morphology in the knees of healthy individuals: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The clinical use of minimum joint space width (mJSW) and cartilage volume and thickness has been limited to the longitudinal measurement of disease progression (i.e. change over time) rather than the diagnosis of OA in which values are compared to a standard. This is primarily due to lack of establishment of normative values of joint space width and cartilage morphometry as has been done with bone density values in diagnosing osteoporosis. Thus, the purpose of this pilot study is to estimate reference values of medial joint space width and cartilage morphometry in healthy individuals of all ages using standard radiography and peripheral magnetic resonance imaging.</p> <p>Design</p> <p>For this cross-sectional study, healthy volunteers underwent a fixed-flexion knee X-ray and a peripheral MR (pMR) scan of the same knee using a 1T machine (ONI OrthOne™, Wilmington, MA). Radiographs were digitized and analyzed for medial mJSW using an automated algorithm. Only knees scoring ≤1 on the Kellgren-Lawrence scale (no radiographic evidence of knee OA) were included in the analyses. All 3D SPGRE fat-sat sagittal pMR scans were analyzed for medial tibial cartilage morphometry using a proprietary software program (Chondrometrics GmbH).</p> <p>Results</p> <p>Of 119 healthy participants, 73 were female and 47 were male; mean (SD) age 38.2 (13.2) years, mean BMI 25.0 (4.4) kg/m². Minimum JSW values were calculated for each sex and decade of life. Analyses revealed mJSW did not significantly decrease with increasing decade (p > 0.05) in either sex. Females had a mean (SD) medial mJSW of 4.8 (0.7) mm compared to males with corresponding larger value of 5.7 (0.8) mm. Cartilage morphometry results showed similar trends with mean (SD) tibial cartilage volume and thickness in females of 1.50 (0.19) μL/mm²and 1.45 (0.19) mm, respectively, and 1.77 (0.24) μL/mm²and 1.71 (0.24) mm, respectively, in males.</p> <p>Conclusion</p> <p>These data suggest that medial mJSW values do not decrease with aging in healthy individuals but remain fairly constant throughout the lifespan with "healthy" values of 4.8 mm for females and 5.7 mm for males. Similar trends were seen for cartilage morphology. Results suggest there may be no need to differentiate a t-score and a z-score in OA diagnosis because cartilage thickness and JSW remain constant throughout life in the absence of OA.</p

Cerebral small vessel disease genomics and its implications across the lifespan

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.Peer reviewe

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

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