| 1. |
- Alves, Isabel, et al.
(författare)
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Human genetic structure in Northwest France provides new insights into West European historical demography
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- The demographical history of France remains largely understudied despite its central role toward understanding modern population structure across Western Europe. Here, by exploring publicly available Europe-wide genotype datasets together with the genomes of 3234 present-day and six newly sequenced medieval individuals from Northern France, we found extensive fine-scale population structure across Brittany and the downstream Loire basin and increased population differentiation between the northern and southern sides of the river Loire, associated with higher proportions of steppe vs. Neolithic-related ancestry. We also found increased allele sharing between individuals from Western Brittany and those associated with the Bell Beaker complex. Our results emphasise the need for investigating local populations to better understand the distribution of rare (putatively deleterious) variants across space and the importance of common genetic legacy in understanding the sharing of disease-related alleles between Brittany and people from western Britain and Ireland.
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| 2. |
- Menon, Nandakumar, et al.
(författare)
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Task-sharing spinal anaesthesia care in three rural Indian hospitals: a non-inferiority randomised controlled clinical trial
- 2024
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Ingår i: BMJ GLOBAL HEALTH. - 2059-7908. ; 9:8, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Background Task-sharing of spinal anaesthesia care by non-specialist graduate physicians, termed medical officers (MOs), is commonly practised in rural Indian healthcare facilities to mitigate workforce constraints. We sought to assess whether spinal anaesthesia failure rates of MOs were non-inferior to those of consultant anaesthesiologists (CA) following a standardised educational curriculum.Methods We performed a randomised, non-inferiority trial in three rural hospitals in Tamil Nadu and Chhattisgarh, India. Patients aged over 18 years with low perioperative risk (ASA I & II) were randomised to receive MO or CA care. Prior to the trial, MOs underwent task-based anaesthesia training, inclusive of remotely accessed lectures, simulation-based training and directly observed anaesthetic procedures and intraoperative care. The primary outcome measure was spinal anaesthesia failure with a non-inferiority margin of 5%. Secondary outcome measures consisted of incidence of perioperative and postoperative complications.Findings Between 12 July 2019 and 8 June 2020, a total of 422 patients undergoing surgical procedures amenable to spinal anaesthesia care were randomised to receive either MO (231, 54.7%) or CA care (191, 45.2%). Spinal anaesthesia failure rate for MOs (7, 3.0%) was non-inferior to those of CA (5, 2.6%); difference in success rate of 0.4% (95% CI=0.36-0.43%; p=0.80). Additionally, there were no statistically significant differences observed between the two groups for intraoperative or postoperative complications, or patients' experience of pain during the procedure.Interpretation This study demonstrates that failure rates of spinal anaesthesia care provided by trained MOs are non-inferior to care provided by CAs in low-risk surgical patients. This may support policy measures that use task-sharing as a means of expanding anaesthesia care capacity in rural Indian hospitals.Trial registration number NCT04438811.
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| 3. |
- Rydholm, Emma, 1994, et al.
(författare)
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Expanding the chemical space using a chemical reaction knowledge graph
- 2024
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Ingår i: Digital Discovery. - 2635-098X. ; 3:7, s. 1378-1388
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we present a new molecular de novo design approach which utilizes a knowledge graph encoding chemical reactions, extracted from the publicly available USPTO (United States Patent and Trademark Office) dataset. Our proposed method can be used to expand the chemical space by performing forward synthesis prediction by finding new combinations of reactants in the knowledge graph and can in this way generate libraries of de novo compounds along with a valid synthetic route. The forward synthesis prediction of novel compounds involves two steps. In the first step, a graph neural network-based link prediction model is used to suggest pairs of existing reactant nodes in the graph that are likely to react. In the second step, product prediction is performed using a molecular transformer model to obtain the potential products for the suggested reactant pairs. We achieve a ROC-AUC score of 0.861 for link prediction in the knowledge graph and for the product prediction, a top-1 accuracy of 0.924. The method's utility is demonstrated by generating a set of de novo compounds by predicting high probability reactions in the USPTO. The generated compounds are diverse in nature and many exhibit drug-like properties. A brief comparison with a template-based library design is provided. Furthermore, evaluation of the potential activity using a quantitative structure-activity relationship (QSAR) model suggested the presence of potential dopamine receptor D2 (DRD2) modulators among the proposed compounds. In summary, our results suggest that the proposed method can expand the easily accessible chemical space, by combining known compounds, and identify novel drug-like compounds for a specific target.
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| 4. |
- Seersholm, Frederik Valeur, et al.
(författare)
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Repeated plague infections across six generations of Neolithic Farmers
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 632:8023, s. 114-121
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Tidskriftsartikel (refereegranskat)abstract
- In the period between 5,300 and 4,900 calibratedyears before present (cal. bp), populations across large parts of Europe underwent a period of demographic decline1,2. However, the cause of this so-called Neolithic decline is still debated. Some argue for an agricultural crisis resulting in the decline3, others for the spread of an early form of plague4. Here we use population-scale ancient genomics to infer ancestry, social structure and pathogen infection in 108 Scandinavian Neolithic individuals from eight megalithic graves and a stone cist. We find that the Neolithic plague was widespread, detected in at least 17% of the sampled population and across large geographical distances. We demonstrate that the disease spread within the Neolithic community in three distinct infection events within a period of around 120 years. Variant graph-based pan-genomics shows that the Neolithic plague genomes retained ancestral genomic variation present in Yersinia pseudotuberculosis, including virulence factors associated with disease outcomes. In addition, we reconstruct four multigeneration pedigrees, the largest of which consists of 38 individuals spanning six generations, showing a patrilineal social organization. Lastly, we document direct genomic evidence for Neolithic female exogamy in a woman buried in a different megalithic tomb than her brothers. Taken together, our findings provide a detailed reconstruction of plague spread within a large patrilineal kinship group and identify multiple plague infections in a population dated to the beginning of the Neolithic decline.
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| 5. |
- Andersdotter Svensson, Emma, et al.
(författare)
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Natural almost Hermitian structures on conformally foliated 4-dimensional Lie groups with minimal leaves
- 2023
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Ingår i: Rendiconti del Circolo Matematico di Palermo. - : Springer Science and Business Media LLC. - 0009-725X .- 1973-4409. ; 72, s. 2265-2286
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Tidskriftsartikel (refereegranskat)abstract
- Let (G, g) be a 4-dimensional Riemannian Lie group with a 2-dimensional left-invariant, conformal foliation F with minimal leaves. Let J be an almost Hermitian structure on G adapted to the foliation F . We classify such structures J which are almost Kähler (AK), integrable (I) or Kähler (K). Hereby we construct several new multi-dimensional examples in each class.
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| 6. |
- Blasi, Maria, et al.
(författare)
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Historical and citizen-reported data show shifts in bumblebee phenology over the last century in Sweden
- 2023
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Ingår i: Biodiversity and Conservation. - : Springer Science and Business Media LLC. - 0960-3115 .- 1572-9710. ; 32:5, s. 1523-1547
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Tidskriftsartikel (refereegranskat)abstract
- Bumblebees are a key taxon contributing to the provision of crop pollination and ecosystem functioning. However, land use and climate change are two of the main factors causing bee decline across the world. In this study, we investigated how the flight period of bumblebee spring queens has shifted over the last century in Sweden, and to what extent such shifts depended on climate change, landscape context, latitude, and the phenology of bumblebee species. We studied ten species of bumblebees and used observations from museum specimens covering 117 years from the southernmost region in Sweden (Scania), combined with citizen-reported observations during the past 20 years across Sweden. We found that the flight period of bumblebees has advanced by 5 days on average during the last 20 years across Sweden. In the agriculture-dominated region of Scania, we found that in the late 2010s bumblebee spring queen activity in simplified landscapes had advanced by on average 14 days, compared to 100 years ago. In addition, in simplified landscapes the flight period of early species was significantly earlier compared to in complex landscapes. Our results provide knowledge on the intraspecific variation of phenological traits, indicating that early species (often common species) exhibit a higher plastic response to the environment, which may facilitate adaptation to both climate and landscape changes, compared to the late species of which many are declining.
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| 7. |
- Bläckberg, Anna, et al.
(författare)
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A Population-Based Study of Unfavorable Prognostic Factors Associated With Pyogenic Liver Abscess
- 2023
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Ingår i: Open Forum Infectious Diseases. - 2328-8957. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPyogenic liver abscess (PLA) is a rare entity that is associated with substantial mortality and morbidity. Our objective was to investigate variables associated with mortality and subsequent PLA in patients diagnosed with PLA in southern Sweden.MethodsWe conducted a population-based observational study comprising all episodes of PLA that occurred between 2011 and 2020 in the county of Skåne, southern Sweden. The primary outcome was defined as all-cause 90-day mortality and the secondary outcome was defined as the occurrence of a subsequent PLA.ResultsA total of 452 episodes of PLA occurred in 360 patients during the study period. The 90-day mortality rate was 16% (n = 58) and the subsequent PLA rate was 20% (n = 92). In a multivariable logistic regression model, female sex (odds ratio [OR], 2.0 [95% confidence interval {CI}, 1.1–3.9]), malignancy (OR, 3.7 [95% CI, 1.9–7.1]), liver failure (OR, 6.3 [95% CI, 2.7–14.5]), and polymicrobial findings (OR, 3.8 [95% CI, 2.2–6.9]) were associated with death within 90 days (P < .05). Male sex (OR, 2.1 [95% CI, 1.2–3.6]), malignancy (OR, 2.1 [95% CI, 1.3–3.6]), age (64–74 years: OR, 2.5 [95% CI, 1.3–4.8]), and chronic liver disease (OR, 3.0 [95% CI, 1.4–6.5]) were associated with the risk of subsequent PLA (P ≤ .01).ConclusionsIdentifying different clinical variables associated with an unfavorable outcome may improve the management and treatment of patients with PLA and thus prevent the risk of death and subsequent PLA.
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| 8. |
- Mattila, Tiina M., et al.
(författare)
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Genetic continuity, isolation, and gene flow in Stone Age Central and Eastern Europe
- 2023
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Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- The genomic landscape of Stone Age Europe was shaped by multiple migratory waves and population replacements, but different regions do not all show similar patterns. To refine our understanding of the population dynamics before and after the dawn of the Neolithic, we generated and analyzed genomic sequence data from human remains of 56 individuals from the Mesolithic, Neolithic, and Eneolithic across Central and Eastern Europe. We found that Mesolithic European populations formed a geographically widespread isolation-by-distance zone ranging from Central Europe to Siberia, which was already established 10,000 years ago. We found contrasting patterns of population continuity during the Neolithic transition: people around the lower Dnipro Valley region, Ukraine, showed continuity over 4000 years, from the Mesolithic to the end of the Neolithic, in contrast to almost all other parts of Europe where population turnover drove this cultural change, including vast areas of Central Europe and around the Danube River. Genome-wide sequencing of 56 ancient hunter-gatherer and early farmer individuals from Stone Age Central and Eastern Europe reveals striking population continuity in the east in contrast to central Europe that displays extensive admixture.
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| 9. |
- Simões, Luciana G., 1986-
(författare)
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Uncovering the Past through ancient DNA : The Fate and Legacy of the last hunter-gatherers in Western Europe and Northwestern Africa
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The genetic analysis of ancient human remains has revolutionized the study of human history, opening a direct window onto the demographic and evolutionary events that shaped our species' past. I use state-of-the-art ancient DNA methodologies, from sample collection and DNA extraction to data analysis, to study the ancient past of the western Mediterranean region, where climate does not favour DNA preservation. After the Last Glacial Maximum, amenable climatic conditions enabled the development of agriculture in the Levant, initiating the Neolithic period. In Europe, the transition from foraging to farming was driven by the migration of people from Anatolia, but in North Africa, evidence indicates a cultural diffusion, instead of population replacement. In this thesis, I show that this transition was in fact ignited by the migration of early farmers from Iberia. Moreover, a different migration wave, originating in the Levant and expanding within Africa, was associated with pastoralism in that region during the Neolithic. While the Neolithic transition is one of the most studied periods of pre-history, earlier periods are comparatively under-studied. Using whole genome sequencing data for 36 hunter-gatherers from Iberia and France, I observed that genetic lineages rooted in the Palaeolithic, survived throught the Mesolithic. Mesolithic hunter-gatherer populations formed social units that were not based on familial bonds; exchanges between groups avoided consanguinity. Coexistence with the first farming communities resulted in unidirectional admixture patterns, as we do not find gene flow from farmers to the last hunter-gatherers. Finally, using a multidisciplinary approach to study an exceptional individual of African descent buried in a Mesolithic shell midden, we find that the burial of this man during the transatlantic slave trade period could be an example of the maintenance of African cultural practices by African people displaced to Europe. My thesis highlights the power of ancient DNA analysis to uncover events and patterns of the human evolutionary history, but also that integrative approaches, where different lines of evidence are combined, can lead to exciting findings.
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| 10. |
- Svensson, Emma, et al.
(författare)
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Increasing incidence of pyogenic liver abscess in Southern Sweden : a population-based study from 2011 to 2020
- 2023
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 55:6, s. 375-383
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pyogenic liver abscess (PLA) is a rare but potentially life-threatening disease, and estimates suggest a gradual increase in the incidence during the last decades. The primary aim of this study was to report the incidence, trend and aetiology of PLA during a decade in Southern Sweden.METHODS: This was a population-based observational cohort study between 2011 and 2020 in Skåne, Southern Sweden. Data were retrieved from the Swedish National Board of Health and Welfare for all individuals diagnosed with liver abscess (K750) according to ICD-10 (International Statistical Classification of Diseases, 10th revision).RESULTS: A total of 456 episodes of PLA occurred in 364 patients during the study period. The median age of the first PLA episode was 71 years (range 3-97) and 57% (n = 206) were men. The mean incidence of all patients was 3.4/100,000 person-years (range 1.8-5.2). The incidence increased almost three times, from 1.8/100,000 person-years in 2011 to 5.2/100,000 person-years in 2020. Streptococcus species, Escherichia coli and Klebsiella species accounted for the vast majority of both mono- and polymicrobial findings in both blood and local abscess cultures. 16s rDNA added information about aetiology in 37% of episodes.CONCLUSION: The incidence of PLA increased during the study period, and Streptococcus spp., Klebsiella spp. and E. coli dominated both blood and local cultures. Despite antimicrobial therapy, pathogens could be found in local abscess cultures several weeks into treatment. Increased use of 16s rDNA in the management of PLA could be beneficial.
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