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The history of the British Isles and Ireland is characterized by multiple periods of major cultural change, including the influential transformation after the end of Roman rule, which precipitated shifts in language, settlement patterns and material culture 1 . The extent to which migration from continental Europe mediated these transitions is a matter of long-standing debate 2-4 . Here we study genome-wide ancient DNA from 460 medieval northwestern Europeans-including 278 individuals from England-alongside archaeological data, to infer contemporary population dynamics. We identify a substantial increase of continental northern European ancestry in early medieval England, which is closely related to the early medieval and present-day inhabitants of Germany and Denmark, implying large-scale substantial migration across the North Sea into Britain during the Early Middle Ages. As a result, the individuals who we analysed from eastern England derived up to 76% of their ancestry from the continental North Sea zone, albeit with substantial regional variation and heterogeneity within sites. We show that women with immigrant ancestry were more often furnished with grave goods than women with local ancestry, whereas men with weapons were as likely not to be of immigrant ancestry. A comparison with present-day Britain indicates that subsequent demographic events reduced the fraction of continental northern European ancestry while introducing further ancestry components into the English gene pool, including substantial southwestern European ancestry most closely related to that seen in Iron Age France 5,6 ., (© 2022. The Author(s).)

Orkney was a major cultural center during the Neolithic, 3800 to 2500 BC. Farming flourished, permanent stone settlements and chambered tombs were constructed, and long-range contacts were sustained. From ∼3200 BC, the number, density, and extravagance of settlements increased, and new ceremonial monuments and ceramic styles, possibly originating in Orkney, spread across Britain and Ireland. By ∼2800 BC, this phenomenon was waning, although Neolithic traditions persisted to at least 2500 BC. Unlike elsewhere in Britain, there is little material evidence to suggest a Beaker presence, suggesting that Orkney may have developed along an insular trajectory during the second millennium BC. We tested this by comparing new genomic evidence from 22 Bronze Age and 3 Iron Age burials in northwest Orkney with Neolithic burials from across the archipelago. We identified signals of inward migration on a scale unsuspected from the archaeological record: As elsewhere in Bronze Age Britain, much of the population displayed significant genome-wide ancestry deriving ultimately from the Pontic-Caspian Steppe. However, uniquely in northern and central Europe, most of the male lineages were inherited from the local Neolithic. This suggests that some male descendants of Neolithic Orkney may have remained distinct well into the Bronze Age, although there are signs that this had dwindled by the Iron Age. Furthermore, although the majority of mitochondrial DNA lineages evidently arrived afresh with the Bronze Age, we also find evidence for continuity in the female line of descent from Mesolithic Britain into the Bronze Age and even to the present day., Competing Interests: The authors declare no competing interest., (Copyright © 2022 the Author(s). Published by PNAS.)

Objective: To estimate the lifetime risk of knee and hip replacement following a diagnosis of RA., Methods: The analysis was undertaken using routinely collected data from the English NHS. Diagnosis of RA was identified using primary care records, with knee and hip replacement observed in linked hospital records. Parametric survival models were fitted for up to 15 years of follow-up, with age, sex, Charlson comorbidity score, socioeconomic status, BMI and smoking status included as explanatory variables. A decision model was used to combine and extrapolate survival models to estimate lifetime risk., Results: The number of individuals with a diagnosis of RA and included in the study was 13 961. Lifetime risk of knee replacement and hip replacement was estimated to be 22% (95% CI: 16, 29%) and 17% (95% CI: 11, 26%) following a diagnosis of RA for the average patient profile (non-smoking women aged 64 with no other comorbidities, BMI of 27 and in the top socioeconomic quintile). Risks were higher for younger patients., Conclusion: The lifetime risk of knee and hip replacement for individuals with a diagnosis of RA is approximately double that of the general population. These findings allow for a better understanding of long-term prognosis and healthcare resource use, and highlight the importance of timely diagnosis and effective treatment., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Domestication of the now-extinct wild aurochs, Bos primigenius, gave rise to the two major domestic extant cattle taxa, B. taurus and B. indicus. While previous genetic studies have shed some light on the evolutionary relationships between European aurochs and modern cattle, important questions remain unanswered, including the phylogenetic status of aurochs, whether gene flow from aurochs into early domestic populations occurred, and which genomic regions were subject to selection processes during and after domestication. Here, we address these questions using whole-genome sequencing data generated from an approximately 6,750-year-old British aurochs bone and genome sequence data from 81 additional cattle plus genome-wide single nucleotide polymorphism data from a diverse panel of 1,225 modern animals., Results: Phylogenomic analyses place the aurochs as a distinct outgroup to the domestic B. taurus lineage, supporting the predominant Near Eastern origin of European cattle. Conversely, traditional British and Irish breeds share more genetic variants with this aurochs specimen than other European populations, supporting localized gene flow from aurochs into the ancestors of modern British and Irish cattle, perhaps through purposeful restocking by early herders in Britain. Finally, the functions of genes showing evidence for positive selection in B. taurus are enriched for neurobiology, growth, metabolism and immunobiology, suggesting that these biological processes have been important in the domestication of cattle., Conclusions: This work provides important new information regarding the origins and functional evolution of modern cattle, revealing that the interface between early European domestic populations and wild aurochs was significantly more complex than previously thought.

Objective: Interstitial lung disease (ILD) is an important feature of idiopathic inflammatory myositis (IIM). Factors associated with its development and progression remain incompletely understood. The authors report ethnicity differences and lung function trends that characterize the predilection for and natural history of ILD in a group of British patients with IIM., Methods: A 10-year retrospective analysis of patients with IIM at two hospitals was conducted. Demographic, clinico-radiological and laboratory features of cases with and without ILD were compared. Serial pulmonary function tests, including measurements of forced vital capacity, volume and diffusing capacity for carbon monoxide, were used to identify longitudinal patterns of lung disease., Results: A total of 107 patients with IIM were identified. ILD was present in 37.4%, with non-specific interstitial pneumonia being the most common radiological pattern (75%). ILD was more common in IIM patients of Black ethnicity (OR 3.42), and in cases where ANA (OR 3.06) and anti-histidyl-tRNA synthetase (OR 3.2) antibodies were detected. In the ILD cohort, 50% deteriorated, defined as a drop in diffusing capacity of the lung for carbon monoxide by <15% or forced vital capacity <10% during the study period, occurring in all within a year of onset of ILD and significantly more frequently in those with a synchronous onset of IIM and ILD. Black ethnicity was not associated with poor lung function outcome., Conclusion: In IIM, the risk of developing ILD is significantly higher in patients of Black ethnicity. Progressive lung damage occurs in an appreciable subgroup of patients with IIM-ILD, heralded by functional lung decline at 1 year despite systemic immunomodulatory treatment.