Tackling barriers to COVID-19 vaccine uptake in London: a mixed-methods evaluation.

BACKGROUND: In response to the COVID-19 pandemic, the first vaccine was administered in December 2020 in England. However, vaccination uptake has historically been lower in London than in other English regions. METHODS: Mixed-methods: This comprised an analysis of cumulative percentage uptake across London between 8 December 2020 and 6 June 2021 by vaccine priority cohorts and ethnicity. We also undertook thematic analyses of uptake barriers, interventions to tackle these and key learning from a qualitative survey of 27 London local authority representatives, vaccine plans from London's five Integrated Care Systems and interviews with 38 London system representatives. RESULTS: Vaccine uptake was lower in Black ethnic (57-65% uptake) compared with the White British group (90% uptake). Trust was a critical issue, including mistrust in the vaccine itself and in authorities administering or promoting it. The balance between putative costs and benefits of vaccination created uptake barriers for zero-hour and shift workers. Intensive, targeted and 'hyper-local' initiatives, which sustained community relationships and were not constrained by administrative boundaries, helped tackle these barriers. CONCLUSIONS: The success of the national vaccination programme depended on conceding local autonomy, investing in responsive and long-term partnerships to engender trust through in-depth understanding of communities' beliefs.

Paradox of meritocracy in surgical selection, and of variation in the attractiveness of individual specialties: to what extent are women still disadvantaged?

BACKGROUND: Evidence from outside surgery suggests that meritocracy-based processes around selection tend to reduce, rather than increase, diversity. In recent years, the surgical training boards have gone to considerable effort to achieve greater transparency and fairness in their selection processes, and to identify those attributes that are believed to best predict future success as a surgeon. This is consistent with the Royal Australasian College of Surgeons Diversity and Inclusion Plan, which places emphasis on gender equity and has goals that include increasing the attractiveness of surgery as a vocation for women, removing impediments to them applying to the surgical training programmes and removing any biases that might disadvantage them during the selection process. METHODS: This study uses the Female Opportunity Index and rate ratio metrics to measure the level of female disadvantage in surgical selection, whether it be by the perception of its attractiveness to women which influences their application rates, or by the likelihood of successful selection for those who have applied, compared with their male counterparts. RESULTS: There are marked differences between the nine surgical specialties and 13 specialty training boards in both the proportion of women who apply, and the proportion who are successful in gaining entry onto the Surgical Education and Training programmes. The Female Opportunity Index ranged from 0.21 to 0.87, which represents a wide variation between surgical specialties. CONCLUSION: These data raise the question as to whether unconscious bias is occurring in an apparently meritocracy-based selection process in some specialties. The data also suggest that some specialties are relatively unattractive to women, for which the reasons are likely to be complex.

Identification of Novel Loci Associated With Hip Shape: A Meta-Analysis of Genomewide Association Studies.

We aimed to report the first genomewide association study (GWAS) meta-analysis of dual-energy X-ray absorptiometry (DXA)-derived hip shape, which is thought to be related to the risk of both hip osteoarthritis and hip fracture. Ten hip shape modes (HSMs) were derived by statistical shape modeling using SHAPE software, from hip DXA scans in the Avon Longitudinal Study of Parents and Children (ALSPAC; adult females), TwinsUK (mixed sex), Framingham Osteoporosis Study (FOS; mixed), Osteoporotic Fractures in Men study (MrOS), and Study of Osteoporotic Fractures (SOF; females) (total N = 15,934). Associations were adjusted for age, sex, and ancestry. Five genomewide significant (p < 5 × 10-9 , adjusted for 10 independent outcomes) single-nucleotide polymorphisms (SNPs) were associated with HSM1, and three SNPs with HSM2. One SNP, in high linkage disequilibrium with rs2158915 associated with HSM1, was associated with HSM5 at genomewide significance. In a look-up of previous GWASs, three of the identified SNPs were associated with hip osteoarthritis, one with hip fracture, and five with height. Seven SNPs were within 200 kb of genes involved in endochondral bone formation, namely SOX9, PTHrP, RUNX1, NKX3-2, FGFR4, DICER1, and HHIP. The SNP adjacent to DICER1 also showed osteoblast cis-regulatory activity of GSC, in which mutations have previously been reported to cause hip dysplasia. For three of the lead SNPs, SNPs in high LD (r2 > 0.5) were identified, which intersected with open chromatin sites as detected by ATAC-seq performed on embryonic mouse proximal femora. In conclusion, we identified eight SNPs independently associated with hip shape, most of which were associated with height and/or mapped close to endochondral bone formation genes, consistent with a contribution of processes involved in limb growth to hip shape and pathological sequelae. These findings raise the possibility that genetic studies of hip shape might help in understanding potential pathways involved in hip osteoarthritis and hip fracture. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

Using Research Findings to Design an Evidence-Based Practice Curriculum.

Evidence from a system-wide research study highlighted strengths and weaknesses in evidence-based practice (EBP) implementation, beliefs, and organizational readiness. To address this evidence, a curriculum was developed within the context of the shared governance and EBP models for nursing practice. The curriculum, Evidence-Based Practice: Clinical Applications in Professional Nursing Practice, consists of five modules that provide the knowledge, skills, and abilities relative to each step of EBP. The learning approach incorporates classroom- and unit-based education, facilitated by EBP curriculum mentors. Each module is rolled out quarterly for a 15-month curriculum cycle. Outcome data include pre- and post-learning assessments, in addition to EBP projects. This seamless approach to nursing education, based on research findings and established shared governance and EBP models, can be undertaken by community hospital systems. J Contin Nurs Educ. 2017;48(4):184-189.

Loss of connectivity among island-dwelling Peary caribou following sea ice decline.

Global warming threatens to reduce population connectivity for terrestrial wildlife through significant and rapid changes to sea ice. Using genetic fingerprinting, we contrasted extant connectivity in island-dwelling Peary caribou in northern Canada with continental-migratory caribou. We next examined if sea-ice contractions in the last decades modulated population connectivity and explored the possible impact of future climate change on long-term connectivity among island caribou. We found a strong correlation between genetic and geodesic distances for both continental and Peary caribou, even after accounting for the possible effect of sea surface. Sea ice has thus been an effective corridor for Peary caribou, promoting inter-island connectivity and population mixing. Using a time series of remote sensing sea-ice data, we show that landscape resistance in the Canadian Arctic Archipelago has increased by approximately 15% since 1979 and may further increase by 20-77% by 2086 under a high-emission scenario (RCP8.5). Under the persistent increase in greenhouse gas concentrations, reduced connectivity may isolate island-dwelling caribou with potentially significant consequences for population viability.

Loss of MHC and neutral variation in Peary caribou: genetic drift is not mitigated by balancing selection or exacerbated by MHC allele distributions.

Theory and empirical results suggest that the rate of loss of variation at Mhc and neutral microsatellite loci may differ because selection influences Mhc genes, and because a high proportion of rare alleles at Mhc loci may result in high rates of loss via drift. Most published studies compare Mhc and microsatellite variation in various contemporary populations to infer the effects of population size on genetic variation, even though different populations are likely to have different demographic histories that may also affect contemporary genetic variation. We directly compared loss of variation at Mhc and microsatellite loci in Peary caribou by comparing historical and contemporary samples. We observed that similar proportions of genetic variation were lost over time at each type of marker despite strong evidence for selection at Mhc genes. These results suggest that microsatellites can be used to estimate genome-wide levels of variation, but also that adaptive potential is likely to be lost following population bottlenecks. However, gene conversion and recombination at Mhc loci may act to increase variation following bottlenecks.

Population size and major valleys explain microsatellite variation better than taxonomic units for caribou in western Canada.

Identifying conservation units below the species level is becoming increasingly important, particularly when limited resources necessitate prioritization for conservation among such units. This problem is exemplified with caribou, a mammal with a circum-Arctic distribution that is exposed to a broad spectrum of ecological conditions, but is also declining in many parts of its range. We used microsatellite markers to evaluate the suitability of existing intra-specific taxonomic designations to act as population units for conservation and contrasted this with landscape features that were independent of taxonomy. We also quantified the relationship between genetic differentiation and subpopulation size, a factor that has been under-represented in landscape genetic research. Our data set included three subspecies and three ecotypes of caribou that varied in population size by five orders of magnitude. Our results indicated that genetic structure did not correspond to existing taxonomic designation, particularly at the level of ecotype. Instead, we found that major valleys and population size were the strongest factors associated with substructure. There was a negative exponential relationship between population size and F(ST) between pairs of adjacent subpopulations, suggesting that genetic drift was the mechanism causing the structure among the smallest subpopulations. A genetic assignment test revealed that movement among subpopulations was a fraction of the level needed to stabilize smaller subpopulations, indicating little chance for demographic rescue. Such results may be broadly applicable to landscape genetic studies, because population size and corresponding rates of drift have the potential to confound interpretations of landscape effects on population structure.

Absence of Akt1 reduces vascular smooth muscle cell migration and survival and induces features of plaque vulnerability and cardiac dysfunction during atherosclerosis.

OBJECTIVE: Deletion of Akt1 leads to severe atherosclerosis and occlusive coronary artery disease. Vascular smooth muscle cells (VSMCs) are an important component of atherosclerotic plaques, responsible for promoting plaque stability in advanced lesions. Fibrous caps of unstable plaques contain less collagen and ECM components and fewer VSMCs than caps from stable lesions. Here, we investigated the role of Akt1 in VSMC proliferation, migration, and oxidative stress-induced apoptosis. In addition, we also characterized the atherosclerotic plaque morphology and cardiac function in an atherosclerosis-prone mouse model deficient in Akt1. METHODS AND RESULTS: Absence of Akt1 reduces VSMC proliferation and migration. Mechanistically, the proliferation and migratory phenotype found in Akt1-null VSMCs was linked to reduced Rac-1 activity and MMP-2 secretion. Serum starvation and stress-induced apoptosis was enhanced in Akt1 null VSMCs as determined by flow cytometry using Annexin V/PI staining. Immunohistochemical analysis of atherosclerotic plaques from Akt1(-/-ApoE-/-) mice showed a dramatic increase in plaque vulnerability characteristics such as enlarged necrotic core and reduced fibrous cap and collagen content. Finally, we show evidence of myocardial infarcts and cardiac dysfunction in Akt1(-/-ApoE-/-) mice analyzed by immunohistochemistry and echocardiography, respectively. CONCLUSIONS: Akt1 is essential for VSMC proliferation, migration, and protection against oxidative stress-induced apoptosis. Absence of Akt1 induces features of plaque vulnerability and cardiac dysfunction in a mouse model of atherosclerosis.

Socially informed random walks: incorporating group dynamics into models of population spread and growth.

Simple correlated random walk (CRW) models are rarely sufficient to describe movement of animals over more than the shortest time scales. However, CRW approaches can be used to model more complex animal movement trajectories by assuming individuals move in one of several different behavioural or movement states, each characterized by a different CRW. The spatial and social context an individual experiences may influence the proportion of time spent in different movement states, with subsequent effects on its spatial distribution, survival and fecundity. While methods to study habitat influences on animal movement have been previously developed, social influences have been largely neglected. Here, we fit a 'socially informed' movement model to data from a population of over 100 elk (Cervus canadensis) reintroduced into a new environment, radio-collared and subsequently tracked over a 4-year period. The analysis shows how elk move further when they are solitary than when they are grouped and incur a higher rate of mortality the further they move away from the release area. We use the model to show how the spatial distribution and growth rate of the population depend on the balance of fission and fusion processes governing the group structure of the population. The results are briefly discussed with respect to the design of species reintroduction programmes.