| 1. |
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| 2. |
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| 3. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 6. |
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| 7. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 8. |
- Clement, E., et al.
(författare)
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Conceptual design of the AGATA 1 π array at GANIL
- 2017
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 855, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- The Advanced GAmma Tracking Array (AGATA) has been installed at the GANIL facility, Caen-France. This setup exploits the stable and radioactive heavy-ions beams delivered by the cyclotron accelerator complex of GANIL. Additionally, it benefits from a large palette of ancillary detectors and spectrometers to address in-beam γ-ray spectroscopy of exotic nuclei. The set-up has been designed to couple AGATA with a magnetic spectrometer, charged-particle and neutron detectors, scintillators for the detection of high-energy γ rays and other devices such as a plunger to measure nuclear lifetimes. In this paper, the design and the mechanical characteristics of the set-up are described. Based on simulations, expected performances of the AGATA l π array are presented.
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| 9. |
- Lango Allen, Hana, et al.
(författare)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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| 10. |
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| 11. |
- Jones, G., et al.
(författare)
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Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n=48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1p=4x10(-17)), arthritis (GDF5p=4x10(-13)), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing. Muscle weakness has been associated with morbidity and mortality in older people. Here, the authors have investigated this trait further by performing a genome-wide meta-analysis of grip strength and Mendelian randomization to discover causal relationships between muscle weakness and other diseases.
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| 12. |
- Divaris, K., et al.
(författare)
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Phenotype Harmonization in the GLIDE2 Oral Health Genomics Consortium
- 2022
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Ingår i: Journal of Dental Research. - : Sage Publications. - 0022-0345 .- 1544-0591. ; 101:11, s. 1408-1416
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Tidskriftsartikel (refereegranskat)abstract
- Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and “precision,” data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface–level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.
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| 13. |
- Ardern, Clare, et al.
(författare)
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2018 International Olympic Committee consensus statement on prevention, diagnosis and management of paediatric anterior cruciate ligament (ACL) injuries
- 2018
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 26:4, s. 989-1010
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Tidskriftsartikel (refereegranskat)abstract
- In October 2017, the International Olympic Committee hosted an international expert group of physiotherapists and orthopaedic surgeons who specialise in treating and researching paediatric anterior cruciate ligament (ACL) injuries. Representatives from the American Orthopaedic Society for Sports Medicine, European Paediatric Orthopaedic Society, European Society for Sports Traumatology, Knee Surgery and Arthroscopy, International Society of Arthroscopy Knee Surgery and Orthopaedic Sports Medicine, Pediatric Orthopaedic Society of North America, and Sociedad Latinoamericana de Artroscopia, Rodilla y Deporte attended. Physiotherapists and orthopaedic surgeons with clinical and research experience in the field, and an ethics expert with substantial experience in the area of sports injuries also participated. Injury management is challenging in the current landscape of clinical uncertainty and limited scientific knowledge. Injury management decisions also occur against the backdrop of the complexity of shared decision-making with children and the potential long-term ramifications of the injury. This consensus statement addresses six fundamental clinical questions regarding the prevention, diagnosis, and management of paediatric ACL injuries. The aim of this consensus statement is to provide a comprehensive, evidence-informed summary to support the clinician, and help children with ACL injury and their parents/guardians make the best possible decisions.
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| 14. |
- Ardern, Clare, et al.
(författare)
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2018 International Olympic Committee consensus statement on prevention, diagnosis and management of paediatric anterior cruciate ligament (ACL) injuries
- 2018
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Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 52:7, s. 422-438
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Tidskriftsartikel (refereegranskat)abstract
- In October 2017, the International Olympic Committee hosted an international expert group of physiotherapists and orthopaedic surgeons who specialise in treating and researching paediatric ACL injuries. Representatives from the American Orthopaedic Society for Sports Medicine, European Paediatric Orthopaedic Society, European Society for Sports Traumatology, Knee Surgery & Arthroscopy, International Society of Arthroscopy Knee Surgery and Orthopaedic Sports Medicine, Pediatric Orthopaedic Society of North America and Sociedad Latinoamericana de Artroscopia, Rodilla y Deporte attended. Physiotherapists and orthopaedic surgeons with clinical and research experience in the field, and an ethics expert with substantial experience in the area of sports injuries also participated. Injury management is challenging in the current landscape of clinical uncertainty and limited scientific knowledge. Injury management decisions also occur against the backdrop of the complexity of shared decision-making with children and the potential long-term ramifications of the injury. This consensus statement addresses six fundamental clinical questions regarding the prevention, diagnosis and management of paediatric ACL injuries. The aim of this consensus statement is to provide a comprehensive, evidence-informed summary to support the clinician, and help children with ACL injury and their parents/guardians make the best possible decisions.
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| 15. |
- Ardern, C. L., et al.
(författare)
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2018 International Olympic Committee consensus statement
- 2019
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Ingår i: Journal of Orthopaedic and Sports Physical Therapy. - : Elsevier BV. - 0190-6011. ; 35:2, s. 98-122
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Tidskriftsartikel (refereegranskat)abstract
- - In October 2017, the International Olympic Committee hosted an international expert group of physiotherapists and orthopaedic surgeons who specialise in treating and researching paediatric ACL injuries. Representatives from the American Orthopaedic Society for Sports Medicine, European Paediatric Orthopaedic Society, European Society for Sports Traumatology, Knee Surgery & Arthroscopy, International Society of Arthroscopy Knee Surgery and Orthopaedic Sports Medicine, Pediatric Orthopaedic Society of North America and Sociedad Latinoamericana de Artroscopia, Rodilla y Deporte attended. Physiotherapists and orthopaedic surgeons with clinical and research experience in the field, and an ethics expert with substantial experience in the area of sports injuries also participated. Injury management is challenging in the current landscape of clinical uncertainty and limited scientific knowledge. Injury management decisions also occur against the backdrop of the complexity of shared decision-making with children and the potential long-term ramifications of the injury. This consensus statement addresses six fundamental clinical questions regarding the prevention, diagnosis and management of paediatric ACL injuries. The aim of this consensus statement is to provide a comprehensive, evidence-informed summary to support the clinician, and help children with ACL injury and their parents/guardians make the best possible decisions. © 2019
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| 16. |
- Ardern, C. L., et al.
(författare)
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2018 International Olympic Committee Consensus Statement on Prevention, Diagnosis, and Management of Pediatric Anterior Cruciate Ligament Injuries
- 2018
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Ingår i: Orthopaedic Journal of Sports Medicine. - : SAGE Publications. - 2325-9671. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- In October 2017, the International Olympic Committee hosted an international expert group of physical therapists and orthopaedic surgeons who specialize in treating and researching pediatric anterior cruciate ligament (ACL) injuries. The purpose of this meeting was to provide a comprehensive, evidence-informed summary to support the clinician and help children with ACL injury and their parents/guardians make the best possible decisions. Representatives from the following societies attended: American Orthopaedic Society for Sports Medicine; European Paediatric Orthopaedic Society; European Society for Sports Traumatology, Knee Surgery, and Arthroscopy; International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine; Pediatric Orthopaedic Society of North America; and Sociedad Latinoamericana de Artroscopia, Rodilla, y Deporte. Physical therapists and orthopaedic surgeons with clinical and research experience in the field and an ethics expert with substantial experience in the area of sports injuries also participated. This consensus statement addresses 6 fundamental clinical questions regarding the prevention, diagnosis, and management of pediatric ACL injuries. Injury management is challenging in the current landscape of clinical uncertainty and limited scientific knowledge. Injury management decisions also occur against the backdrop of the complexity of shared decision making with children and the potential long-term ramifications of the injury.
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| 17. |
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| 18. |
- Brawand, David, et al.
(författare)
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The genomic substrate for adaptive radiation in African cichlid fish
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 513:7518, s. 375-381
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Tidskriftsartikel (refereegranskat)abstract
- Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand themolecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.
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| 19. |
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| 20. |
- Rioux, John D., et al.
(författare)
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Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease
- 2001
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 29:2, s. 223-228
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Tidskriftsartikel (refereegranskat)abstract
- Linkage disequilibrium (LD) mapping provides a powerful method for fine-structure localization of rare disease genes, but has not yet been widely applied to common disease1. We sought to design a systematic approach for LD mapping and apply it to the localization of a gene (IBD5) conferring susceptibility to Crohn disease. The key issues are: (i) to detect a significant LD signal (ii) to rigorously bound the critical region and (iii) to identify the causal genetic variant within this region. We previously mapped the IBD5 locus to a large region spanning 18 cM of chromosome 5q31 (P<10−4). Using dense genetic maps of microsatellite markers and single-nucleotide polymorphisms (SNPs) across the entire region, we found strong evidence of LD. We bound the region to a common haplotype spanning 250 kb that shows strong association with the disease (P<2×10−7) and contains the cytokine gene cluster. This finding provides overwhelming evidence that a specific common haplotype of the cytokine region in 5q31 confers susceptibility to Crohn disease. However, genetic evidence alone is not sufficient to identify the causal mutation within this region, as strong LD across the region results in multiple SNPs having equivalent genetic evidence—each consistent with the expected properties of the IBD5 locus. These results have important implications for Crohn disease in particular and LD mapping in general.
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| 21. |
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| 22. |
- Nibali, L, et al.
(författare)
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Periodontal Furcation Lesions : A Survey of Diagnosis and Management by General Dental Practitioners.
- 2021
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Ingår i: Journal of Clinical Periodontology. - : John Wiley & Sons. - 0303-6979 .- 1600-051X. ; 48:11, s. 1441-1448
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The aim of this study was to explore general dental practitioners' (GDP) attitude to periodontal furcation involvement (FI).MATERIALS AND METHODS: An online survey focused on diagnosis and management of periodontal FI was circulated to general dental practitioners in 7 different countries.RESULTS: A total of 400 responses were collected. Nearly a fifth of participants reported rarely or never taking 6-point pocket charts. 65.8% of participants had access to a Nabers probe in their practice. When shown clinical pictures and radiographs of FI-involved molars, the majority of participants correctly diagnosed it. Although 47.1% of participants were very/extremely confident in detecting FI, only 8.9% felt very-extremely confident at treating it. Differences in responses were detected according to country and year of qualification, with a trend towards less interest in periodontal diagnosis and treatment in younger generations. Lack of knowledge of management/referral pathways (reported by 22.8%) and lack of correct equipment were considered the biggest barriers to FI management. Most participants (80.9%) were interested in learning more about FI, ideally face-to-face, followed by online tutorials.CONCLUSIONS: Plans should be put in place to improve general dentists' knowledge and ability to manage FI, as this can have a significant public health impact.
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| 23. |
- Engel, Philipp, et al.
(författare)
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The Bee Microbiome: Impact on Bee Health and Model for Evolution and Ecology of Host-Microbe Interactions
- 2016
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Ingår i: mBio. - : American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 7:2
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Forskningsöversikt (refereegranskat)abstract
- As pollinators, bees are cornerstones for terrestrial ecosystem stability and key components in agricultural productivity. All animals, including bees, are associated with a diverse community of microbes, commonly referred to as the micro biome. The bee micro biome is likely to be a crucial factor affecting host health. However, with the exception of a few pathogens, the impacts of most members of the bee microbiome on host health are poorly understood. Further, the evolutionary and ecological forces that shape and change the microbiome are unclear. Here, we discuss recent progress in our understanding of the bee microbiome, and we present challenges associated with its investigation. We conclude that global coordination of research efforts is needed to fully understand the complex and highly dynamic nature of the interplay between the bee micro biome, its host, and the environment. High-throughput sequencing technologies are ideal for exploring complex biological systems, including host-microbe interactions. To maximize their value and to improve assessment of the factors affecting bee health, sequence data should be archived, curated, and analyzed in ways that promote the synthesis of different studies. To this end, the BeeBiome consortium aims to develop an online database which would provide reference sequences, archive metadata, and host analytical resources. The goal would be to support applied and fundamental research on bees and their associated microbes and to provide a collaborative framework for sharing primary data from different research programs, thus furthering our understanding of the bee microbiome and its impact on pollinator health.
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| 24. |
- Grimm, S., et al.
(författare)
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Sharing or gambling? On risk attitudes in social contexts
- 2021
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Ingår i: Experimental Economics. - : Springer Science and Business Media LLC. - 1386-4157 .- 1573-6938. ; 24, s. 1075-1104
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Tidskriftsartikel (refereegranskat)abstract
- Decisions under risk are often embedded in a social context that we usually abstract from when studying decision-making in the laboratory. In contrast to that practice, our experiment investigates whether risk-taking is affected by social comparisons. In particular, we focus on situations where some amount of money has to be allocated to two parties: either the amount can be shared, or a random device allocates the entire amount to one of the parties. We find that the social context of the decision matters strongly: When participants are in a disadvantageous initial position compared to the other party, they select the risky option much more often than in a purely individual decision, identical in all other respects. Overall, we find that individuals are relatively more risk-seeking in the socially unfavorable domain than in isolation, in contrast to the favorable one, where we find no or little change in elicited risk attitudes in comparison to an isolated decision.
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| 25. |
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| 26. |
- Kocher, Martin G., et al.
(författare)
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Ambiguity aversion is not universal
- 2018
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Ingår i: European Economic Review. - : Elsevier BV. - 0014-2921 .- 1873-572X. ; 101, s. 268-283
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Tidskriftsartikel (refereegranskat)abstract
- Assuming universal ambiguity aversion, an extensive theoretical literature studies how ambiguity can account for market anomalies from the perspective of expected utility-based theories. We provide a systematic experimental assessment of ambiguity attitudes in different likelihood ranges, and in the gain domain, the loss domain and with mixed outcomes. We draw on a unified framework to elicit preferences across these domains. We replicate the usual finding of ambiguity aversion for moderate likelihood gains. However, when introducing losses or lower likelihoods, we observe predominantly ambiguity neutrality or seeking, rejecting universal ambiguity aversion. (C) 2017 Elsevier B.V. All rights reserved.
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| 27. |
- Shungin, Dmitry, et al.
(författare)
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Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Dental caries and periodontitis account for a vast burden of morbidity and healthcare spending, yet their genetic basis remains largely uncharacterized. Here, we identify self-reported dental disease proxies which have similar underlying genetic contributions to clinical disease measures and then combine these in a genome-wide association study meta-analysis, identifying 47 novel and conditionally-independent risk loci for dental caries. We show that the heritability of dental caries is enriched for conserved genomic regions and partially overlapping with a range of complex traits including smoking, education, personality traits and metabolic measures. Using cardio-metabolic traits as an example in Mendelian randomization analysis, we estimate causal relationships and provide evidence suggesting that the processes contributing to dental caries may have undesirable downstream effects on health.
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| 28. |
- Sutter, Matthias, 1968, et al.
(författare)
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Impatience and uncertainty: Experimental decisions predict adolescents' field behavior
- 2013
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Ingår i: The American Economic Review. - 0002-8282. ; 103:1, s. 510-531
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Tidskriftsartikel (refereegranskat)abstract
- We study risk attitudes, ambiguity attitudes, and time preferences of 661 children and adolescents, aged ten to eighteen years, in an incentivized experiment and relate experimental choices to field behavior. Experimental measures of impatience are found to be significant predictors of health-related field behavior, saving decisions, and conduct at school. In particular, more impatient children and adolescents are more likely to spend money on alcohol and cigarettes, have a higher body mass index, are less likely to save money, and show worse conduct at school. Experimental measures for risk and ambiguity attitudes are only weak predictors of field behavior.
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