HR strategies for researchers: a review of the HR Excellence in Research Award implementation activities across Europe

This report explores how research institutions and funders across Europe are approaching the researcher HRM, particularly in response to the European Commission’s initiative to provide the HR Excellence in Research Award for organisations demonstrating their practical commitment to the principles set out in the Charter and Code.Vita

Understanding the recruitment and selection of postgraduate researchers by English higher education institutions.

HEFC

Locations, Networks and Cycles: Studying the Everyday Life of Richard Stonley (1520-1600)

This project explores everyday life in the early modern period and utilises an extended case study examining the diaries of Richard Stonley, in order to develop new methodological strategies for the analysis and interpretation of archival sources. Taking an interdisciplinary approach, the thesis draws on theoretical frameworks from fields including anthropology and material culture studies, and combines qualitative and quantitative modes of analysis. The conclusions of this study draw out effective methods with which to approach highly personal and idiosyncratic, or seemingly mundane archival sources. These methods enable a nuanced understanding of early modern individuals who may fall between established categories, such as 'elite' and 'middling' or 'urban' and 'rural'. The three surviving volumes of Richard Stonley's unpublished diary, dating from 1581 to 1597, contain large amounts of information about daily life at his homes in London and Essex, and in the Fleet prison where he resided in the final years of his life following a serious debt problem. As a Teller of the Exchequer, Richard Stonley also spent much of his time working at the Receipt at Westminster. These four locations would have been inhabited by Stonley on a regular or daily basis, and they were the sites for numerous routine activities recorded in the diary entries and in other archival sources, including inventories and accounts. Social interactions were also recorded in the diary, allowing for an analysis of his quotidian social network, alongside behaviours connected to both routine activities and special occasions. This thesis demonstrates that rather than viewing everyday life merely as a category of activities or objects centered around a domestic setting, this theme can be utilised as a lens through which to examine challenging or dense historical sources. This methodological approach includes exploring a wide range of archival evidence in detail, generating a deeper understanding of the working practices and daily tasks undertaken by historic individuals in the navigation of their quotidian lives and the creation of their social and cultural identities

Inuit Traditional Ecological Knowledge of Anadromous Arctic Char, iqalukpik (Salvelinus alpinus) Under Changing Climatic Conditions in the Amundsen Gulf, Western Canadian Arctic

Inuit in the western Canadian Arctic have observed climate change impacts in marine and freshwater environments that have resulted in changes in the abundance, movement ecology, and health of Arctic char, iqalukpik (Salvelinus alpinus), with implications for their fisheries. This research was co-designed with Inuit to investigate reported changes in anadromous Arctic char in waters near Ulukhaktok, Northwest Territories, Canada. An analysis of semi-structured interviews with 26 Inuit fishers not only documented changes in Arctic char population abundance, spatial movement, appearance, and taste but also changes in access to the fishery. Over the past several decades and becoming pronounced in recent years, fewer fish and specifically fewer medium-sized fish that are preferred by fishers, have been caught using nets near the settlement, with some showing poor body condition, and others appearing to originate from lakes outside of the expected spatial range, earlier in an extended summer coastal fishing season. Inuit have observed changes in individual fish with broader environmental changes that are also disrupting fishing activities: the increasing prevalence of Pacific salmon, warmer air and marine sea surface temperatures, inconsistent sea and lake ice conditions, stronger and more frequent wind and wave activity, fluctuating water levels in rivers, and a seasonal tunicate bloom. Inuit have responded to these changes by altering personal subsistence fishing practices and temporarily halting a small-scale community-based commercial fishery because of observations in stock declines and in order to prioritize the subsistence fishery

Life-course neighbourhood deprivation and brain structure in older adults: the Lothian Birth Cohort 1936

Neighbourhood disadvantage may be associated with brain health but the importance of exposure at different stages of the life course is poorly understood. Utilising the Lothian Birth Cohort 1936, we explored the relationship between residential neighbourhood deprivation from birth to late adulthood, and global and local neuroimaging measures at age 73. A total of 689 participants had at least one valid brain measures (53% male); to maximise the sample size structural equation models with full information maximum likelihood were conducted. Residing in disadvantaged neighbourhoods in mid- to late adulthood was associated with smaller total brain (β = −0.06; SE = 0.02; sample size[N] = 658; number of pairwise complete observations[n]=390), grey matter (β = −0.11; SE = 0.03; N = 658; n = 390), and normal-appearing white matter volumes (β = −0.07; SE = 0.03; N = 658; n = 390), thinner cortex (β = −0.14; SE = 0.06; N = 636; n = 379), and lower general white matter fractional anisotropy (β = −0.19; SE = 0.06; N = 665; n = 388). We also found some evidence on the accumulating impact of neighbourhood deprivation from birth to late adulthood on age 73 total brain (β = −0.06; SE = 0.02; N = 658; n = 276) and grey matter volumes (β = −0.10; SE = 0.04; N = 658; n = 276). Local analysis identified affected focal cortical areas and specific white matter tracts. Among individuals belonging to lower social classes, the brain-neighbourhood associations were particularly strong, with the impact of neighbourhood deprivation on total brain and grey matter volumes, and general white matter fractional anisotropy accumulating across the life course. Our findings suggest that living in deprived neighbourhoods across the life course, but especially in mid- to late adulthood, is associated with adverse brain morphologies, with lower social class amplifying the vulnerability

Early-Onset Progressive Retinal Atrophy Associated with an IQCB1 Variant in African Black-Footed Cats (Felis nigripes)

African black-footed cats (Felis nigripes) are endangered wild felids. One male and full-sibling female African black-footed cat developed vision deficits and mydriasis as early as 3 months of age. The diagnosis of early-onset progressive retinal atrophy (PRA) was supported by reduced direct and consensual pupillary light reflexes, phenotypic presence of retinal degeneration, and a non-recordable electroretinogram with negligible amplitudes in both eyes. Whole genome sequencing, conducted on two unaffected parents and one affected offspring was compared to a variant database from 51 domestic cats and a Pallas cat, revealed 50 candidate variants that segregated concordantly with the PRA phenotype. Testing in additional affected cats confirmed that cats homozygous for a 2 base pair (bp) deletion within IQ calmodulin-binding motif-containing protein-1 (IQCB1), the gene that encodes for nephrocystin-5 (NPHP5), had vision loss. The variant segregated concordantly in other related individuals within the pedigree supporting the identification of a recessively inherited early-onset feline PRA. Analysis of the black-footed cat studbook suggests additional captive cats are at risk. Genetic testing for IQCB1 and avoidance of matings between carriers should be added to the species survival plan for captive management

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Non-canonical Hedgehog signaling mediates profibrotic hematopoiesis-stroma crosstalk in myeloproliferative neoplasms

The role of hematopoietic Hedgehog signaling in myeloproliferative neoplasms (MPNs) remains incompletely understood despite data suggesting that Hedgehog (Hh) pathway inhibitors have therapeutic activity in patients. We aim to systematically interrogate the role of canonical vs. non-canonical Hh signaling in MPNs. We show that Gli1 protein levels in patient peripheral blood mononuclear cells (PBMCs) mark fibrotic progression and that, in murine MPN models, absence of hematopoietic Gli1, but not Gli2 or Smo, significantly reduces MPN phenotype and fibrosis, indicating that GLI1 in the MPN clone can be activated in a non-canonical fashion. Additionally, we establish that hematopoietic Gli1 has a significant effect on stromal cells, mediated through a druggable MIF-CD74 axis. These data highlight the complex interplay between alterations in the MPN clone and activation of stromal cells and indicate that Gli1 represents a promising therapeutic target in MPNs, particularly that Hh signaling is dispensable for normal hematopoiesis.</p

Non-canonical Hedgehog Signaling Mediates Profibrotic Hematopoiesis-Stroma Crosstalk in Myeloproliferative Neoplasms

The role of hematopoietic Hedgehog signaling in myeloproliferative neoplasms (MPNs) remains incompletely understood despite data suggesting that Hedgehog (Hh) pathway inhibitors have therapeutic activity in patients. We aim to systematically interrogate the role of canonical vs. non-canonical Hh signaling in MPNs. We show that Gli1 protein levels in patient peripheral blood mononuclear cells (PBMCs) mark fibrotic progression and that, in murine MPN models, absence of hematopoietic Gli1, but not Gli2 or Smo, significantly reduces MPN phenotype and fibrosis, indicating that GLI1 in the MPN clone can be activated in a non-canonical fashion. Additionally, we establish that hematopoietic Gli1 has a significant effect on stromal cells, mediated through a druggable MIF-CD74 axis. These data highlight the complex interplay between alterations in the MPN clone and activation of stromal cells and indicate that Gli1 represents a promising therapeutic target in MPNs, particularly that Hh signaling is dispensable for normal hematopoiesis