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Sökning: WFRF:(Lord J) > (2020-2024)

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1.
  • Tabiri, S, et al. (författare)
  • 2021
  • swepub:Mat__t
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2.
  • Bravo, L, et al. (författare)
  • 2021
  • swepub:Mat__t
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3.
  • Khatri, C, et al. (författare)
  • Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
  • 2021
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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4.
  • Vogel, Jacob W., et al. (författare)
  • Four distinct trajectories of tau deposition identified in Alzheimer’s disease
  • 2021
  • Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
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5.
  • Falster, Daniel, et al. (författare)
  • AusTraits, a curated plant trait database for the Australian flora
  • 2021
  • Ingår i: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge.
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7.
  • Hewitt, Graeme, et al. (författare)
  • Defective ALC1 nucleosome remodeling confers PARPi sensitization and synthetic lethality with HRD
  • 2021
  • Ingår i: Molecular Cell. - : Cell Press. - 1097-2765 .- 1097-4164. ; 81:4, s. 767-783.e11
  • Tidskriftsartikel (refereegranskat)abstract
    • Chromatin is a barrier to efficient DNA repair, as it hinders access and processing of certain DNA lesions. ALC1/CHD1L is a nucleosome-remodeling enzyme that responds to DNA damage, but its precise function in DNA repair remains unknown. Here we report that loss of ALC1 confers sensitivity to PARP inhibitors, methyl-methanesulfonate, and uracil misincorporation, which reflects the need to remodel nucleosomes following base excision by DNA glycosylases but prior to handover to APEX1. Using CRISPR screens, we establish that ALC1 loss is synthetic lethal with homologous recombination deficiency (HRD), which we attribute to chromosome instability caused by unrepaired DNA gaps at replication forks. In the absence of ALC1 or APEX1, incomplete processing of BER intermediates results in post-replicative DNA gaps and a critical dependence on HR for repair. Hence, targeting ALC1 alone or as a PARP inhibitor sensitizer could be employed to augment existing therapeutic strategies for HRD cancers.
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8.
  • Lord, Edna, et al. (författare)
  • Ancient DNA of Guinea Pigs (Cavia spp.) Indicates a Probable New Center of Domestication and Pathways of Global Distribution
  • 2020
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Guinea pigs (Cavia spp.) have a long association with humans. From as early as 10,000 years ago they were a wild food source. Later, domesticated Cavia porcellus were dispersed well beyond their native range through pre-Columbian exchange networks and, more recently, widely across the globe. Here we present 46 complete mitogenomes of archaeological guinea pigs from sites in Peru, Bolivia, Colombia, the Caribbean, Belgium and the United States to elucidate their evolutionary history, origins and paths of dispersal. Our results indicate an independent centre of domestication of Cavia in the eastern Colombian Highlands. We identify a Peruvian origin for the initial introduction of domesticated guinea pigs (Cavia porcellus) beyond South America into the Caribbean. We also demonstrate that Peru was the probable source of the earliest known guinea pigs transported, as part of the exotic pet trade, to both Europe and the southeastern United States. Finally, we identify a modern reintroduction of guinea pigs to Puerto Rico, where local inhabitants use them for food. This research demonstrates that the natural and cultural history of guinea pigs is more complex than previously known and has implications for other studies regarding regional to global-scale studies of mammal domestication, translocation, and distribution.
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10.
  • Patterson, Nick, et al. (författare)
  • Large-scale migration into Britain during the Middle to Late Bronze Age
  • 2022
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
  • Tidskriftsartikel (refereegranskat)abstract
    • Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
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