| 1. |
- Surendran, Praveen, et al.
(författare)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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| 2. |
- Evangelou, Evangelos, et al.
(författare)
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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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| 3. |
- Pennells, Lisa, et al.
(författare)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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| 4. |
- Johansson, Viktor, 1979-
(författare)
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Dissonant Voices : Philosophy, Children's Literature, and Perfectionist Education
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Dissonant Voices has a twofold aspiration. First, it is a philosophical treatment of everyday pedagogical interactions between children and their elders, between teachers and pupils. More specifically it is an exploration of the possibilities to go on with dissonant voices that interrupt established practices – our attunement – in behaviour, practice and thinking. Voices that are incomprehensible or expressions that are unacceptable, morally or otherwise. The text works on a tension between two inclinations: an inclination to wave off, discourage, or change an expression that is unacceptable or unintelligible; and an inclination to be tolerant and accept the dissonant expression as doing something worthwhile, but different.The second aspiration is a philosophical engagement with children’s literature. Reading children’s literature becomes a form of philosophising, a way to explore the complexity of a range of philosophical issues. This turn to literature marks a dissatisfaction with what philosophy can accomplish through argumentation and what philosophy can do with a particular and limited set of concepts for a subject, such as ethics. It is a way to go beyond philosophising as the founding of theories that justify particular responses. The philosophy of dissonance and children’s literature becomes a way to destabilise justifications of our established practices and ways of interacting.The philosophical investigations of dissonance are meant to make manifest the possibilities and risks of engaging in interactions beyond established agreement or attunements. Thinking of the dissonant voice as an expression beyond established practices calls for improvisation. Such improvisations become a perfectionist education where both the child and the elder, the teacher and the student, search for as yet unattained forms of interaction and take responsibility for every word and action of the interaction.The investigation goes through a number of picture books and novels for children such as Harry Potter, Garmann’s Summer, and books by Shaun Tan, Astrid Lindgren and Dr. Seuss as well narratives by J.R.R. Tolkien, Henrik Ibsen, Jane Austen and Henry David Thoreau. These works of fiction are read in conversation with philosophical works of, and inspired by, Ludwig Wittgenstein and Stanley Cavell, their moral perfectionism and ordinary language philosophy.
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| 5. |
- Larsen, Simon Rosenqvist, 1993-
(författare)
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Strategies for finding new magnetic materials
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Magnetic materials are indispensable in modern day society. The vast majority of energy generation and conversion involves some kind of magnetic material, and several other applications such as data storage also use them. Despite this there are relatively few types of magnetic materials in use today, which is due to the difficulty of finding new materials that have the necessary properties. In this thesis synthesis of new magnetic materials is performed using a variety oftechniques in an attempt to identify a structured approach to finding crystal structures suited for further development.Three approaches for developing new magnetic materials were used. Targeted substitutions of Mn was done in AlCoCrFeMnxNi and Mn3Co20B6, where Mn provided significant contributions to the magnetic moment, at the cost of stability of the ferromagnetic structures. A new system was identified using theoretical screening, Mn2Co3Ge, which was successfully synthesised. Application of the substitution method revealed properties in the system favourable for magnetic refrigeration. New systems were also discovered in synthesis attempts of Mn2Co3Ge and Ce-based magnets, but these materials were ferrimagnetic, or canted anti-ferromagnetic, resulting in low magnetisation.Varying degrees of success were seen in creating magnetic materials with these approaches. Theoretical screening is likely to become an incredibly powerful tool in the future as more understanding of systems is gained. Complementing the theoretical screening method with the newly discovered structures could be a promising avenue for developing new applicable materials. Substitution of elements will remain an extremely powerful tool for tuning properties and by combining it with theoretical screening will likely be key to discovering new applicable magnet systems in the future.
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| 6. |
- Diarbakerli, Elias, et al.
(författare)
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Swedish musculoskeletal researchers view on a collaborative network and future research priorities in Swedish healthcare
- 2024
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Ingår i: Musculoskeletal Care. - : John Wiley & Sons. - 1478-2189 .- 1557-0681. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Musculoskeletal disorders (MSK) are a global burden causing significant suffering and economic impact. Systematic identification and targeting of research questions of highest interest for stakeholders can aid in improving MSK disorder knowledge and management.Objective: To obtain Swedish MSK researchers' opinions and views on a collaborative Swedish MSK network (SweMSK) and identify future research areas of importance for Swedish MSK research.Methods: A web-based survey was conducted July to September 2021 to collect data from 354 Swedish MSK researchers. The survey focused on the need, objectives, and structure of a SweMSK network and identified prioritised areas for future MSK research.Results: The study included 141 respondents, of which 82 were associate professors or professors. The majority (68%) supported the creation of a new musculoskeletal network. The most supported element was increased collaboration regarding nationwide and multicenter studies. Respondents recommended the creation of a homepage and the establishment of national work groups with different specific interests as the primary elements of a new network.Conclusion: The results demonstrated a need and desire for increased national research collaboration and the creation of a new musculoskeletal network. The high academic experience and active research participation of the respondents suggest the need for MSK disorder knowledge and management improvement in Sweden. Therefore, the SweMSK network may help facilitate effective collaboration and research efforts that can contribute to the advancement of MSK disorder management and care. This study may provide valuable insights for policymakers, clinicians, and researchers to improve MSK disorder care and management in Sweden.
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| 7. |
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| 8. |
- Alström, Per, Professor, et al.
(författare)
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Systematics of the avian family Alaudidae using multilocus and genomic data
- 2023
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Ingår i: Avian Research. - : Elsevier BV. - 2053-7166. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- The family Alaudidae, larks, comprises 93–100 species (depending on taxonomy) that are widely distributed across Africa and Eurasia, with single species extending their ranges to North and northernmost South America and Australia. A decade-old molecular phylogeny, comprising ∼80% of the species, revealed multiple cases of parallel evolution and large variation in rates of morphological evolution, which had misled taxonomists into creating many non-monophyletic genera. Here, we reconstruct the phylogeny of the larks, using a dataset covering one mitochondrial and 16 nuclear loci and comprising all except one of the currently recognised species as well as several recently proposed new species (in total 133 taxa; not all loci available for all species). We provide additional support using genome-wide markers to infer a genus-level phylogeny based on near-complete generic sampling (in total 51 samples of 44 taxa across 40 species). Our results confirm the previous findings of rampant morphological convergence and divergence, and reveal new cases of paraphyletic genera. We propose a new subfamily classification, and also that the genus Mirafra is divided into four genera to produce a more balanced generic classification of the Alaudidae. Our study supports recently proposed species splits as well as some recent lumps, while also questioning some of the latter. This comprehensive phylogeny will form an important basis for future studies, such as comparative studies of lark natural history, ecology, evolution and conservation.
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| 9. |
- de Jong, R. S., et al.
(författare)
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4MOST : Project overview and information for the First Call for Proposals
- 2019
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Ingår i: The Messenger. - : European Southern Observatory. - 0722-6691. ; 175, s. 3-11
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We introduce the 4-metre Multi-Object Spectroscopic Telescope (4MOST), a new high-multiplex, wide-field spectroscopic survey facility under development for the four-metre-class Visible and Infrared Survey Telescope for Astronomy (VISTA) at Paranal. Its key specifications are: a large field of view (FoV) of 4.2 square degrees and a high multiplex capability, with 1624 fibres feeding two low-resolution spectrographs (R = λ/Δλ ~ 6500), and 812 fibres transferring light to the high-resolution spectrograph (R ~ 20 000). After a description of the instrument and its expected performance, a short overview is given of its operational scheme and planned 4MOST Consortium science; these aspects are covered in more detail in other articles in this edition of The Messenger. Finally, the processes, schedules, and policies concerning the selection of ESO Community Surveys are presented, commencing with a singular opportunity to submit Letters of Intent for Public Surveys during the first five years of 4MOST operations.
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| 10. |
- Dranichnikov, Paul, MD, PhD Candidate, 1980-
(författare)
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HIPECology : Aspects of Postoperative Morbidity Following the HIPEC Procedure
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Peritoneal surface malignancy (PM), regardless of the dissemination site, was once considered a terminal condition. However, the introduction of a surgical approach with cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) with or without early intraperitoneal chemotherapy (EPIC) shifted the attitude from managing the symptoms of PM to disease treatment with curative intent. The magnitude of this combined therapy leaves the patients at risk for a diverse range of postoperative morbidities. Moreover, some small cohort studies argued that combining HIPEC with EPIC is associated with a higher risk of postoperative complications compared to HIPEC alone. The overall aim of the thesis was to investigate postoperative morbidity following the management of PM with CRS and HIPEC ± EPIC.We investigated readmission morbidity within 6 months after CRS and HIPEC, using a national population-based register. The results of this study showed that morbidity causing HIPEC-related readmission was higher than expected, with almost half of the interventions occurring outside the HIPEC centre. Gastric resection and advanced age are independent predictors of morbidity and readmission. We analyzed postoperative coagulopathy and the risk for venous thromboembolic events (VTE) in a prospective study. Results revealed that significant postoperative changes in coagulation biomarkers occur with dynamic changes over 10 days postoperatively. The incidence of symptomatic VTE was low. Residual tumor at completion of surgery, and elevated D-dimer on day 2, were independent risk factors for postoperative VTE. Postoperative morbidity following HIPEC + EPIC was compared to morbidity following HIPEC alone in our propensity score matched study. Results showed that HIPEC + EPIC is associated with a prolonged hospital stay (LOS), but there was no statistically significant relevant increase in postoperative morbidity, reoperation rate or incidence of readmission. Finally, we also analyzed the impact of different strategies of intraoperative fluid management during CRS and HIPEC on postoperative outcomes. Goal-directed therapy (GDT) is associated with significantly improved LOS despite an increase in morbidity in some patients. GDT management does not affect the postoperative risk for hemorrhage, although the choice of an oxaliplatin-based HIPEC does. Personalized GDT based on patients’ characteristics and surgery should be utilized during the management of CRS and HIPEC patients.
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