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- Sodergren, Erica, et al.
(författare)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Tidskriftsartikel (refereegranskat)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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| 3. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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- Frazier-Wood, Alexis C., et al.
(författare)
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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
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Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
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Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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- Blom, A. W., et al.
(författare)
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Clinical and cost effectiveness of single stage compared with two stage revision for hip prosthetic joint infection (INFORM): pragmatic, parallel group, open label, randomised controlled trial
- 2022
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 0959-535X. ; 379
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVESTo determine whether patient reported outcomes improve after single stage versus two stage revision surgery for prosthetic joint infection of the hip, and to determine the cost effectiveness of these procedures.DESIGNPragmatic, parallel group, open label, randomised controlled trial.SETTINGHigh volume tertiary referral centres or orthopaedic units in the UK (n=12) and in Sweden (n=3), recruiting from 1 March 2015 to 19 December 2018.PARTICIPANTS 140 adults (aged a18 years) with a prosthetic joint infection of the hip who required revision (65 randomly assigned to single stage and 75 to two stage revision).INTERVENTIONS A computer generated 1:1 randomisation list stratified by hospital was used to allocate participants with prosthetic joint infection of the hip to a single stage or a two stage revision procedure.MAIN OUTCOME MEASURES The primary intention-to-treat outcome was pain, stiffness, and functional limitations 18 months after randomisation, measured by the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) score. Secondary outcomes included surgical complications and joint infection. The economic evaluation (only assessed in UK participants) compared quality adjusted life years and costs between the randomised groups.RESULTS The mean age of participants was 71 years (standard deviation 9) and 51 (36%) were women. WOMAC scores did not differ between groups at 18 months (mean difference 0.13 (95% confidence interval-8.20 to 8.46), P=0.98); however, the single stage procedure was better at three months (11.53 (3.89 to 19.17), P=0.003), but not from six months onwards. Intraoperative events occurred in five (8%) participants in the single stage group and 20 (27%) in the two stage group (P=0.01). At 18 months, nine (14%) participants in the single stage group and eight (11%) in the two stage group had at least one marker of possible ongoing infection (P=0.62). From the perspective of healthcare providers and personal social services, single stage revision was cost effective with an incremental net monetary benefit of (sic)11 167 (95% confidence interval (sic)638 to (sic)21 696) at a (sic)20 000 per quality adjusted life years threshold ((sic)1.0; $1.1; (sic) 1.4).CONCLUSIONS At 18 months, single stage revision compared with two stage revision for prosthetic joint infection of the hip showed no superiority by patient reported outcome. Single stage revision had a better outcome at three months, fewer intraoperative complications, and was cost effective. Patients prefer early restoration of function, therefore, when deciding treatment, surgeons should consider patient preferences and the cost effectiveness of single stage surgery.
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- Blom, A. W., et al.
(författare)
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Infection after total joint replacement of the hip and knee: research programme including the INFORM RCT
- 2022
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Ingår i: Programme Grants for Applied Research. - 2050-4322. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: People with severe osteoarthritis, other joint conditions or injury may have joint replacement to reduce pain and disability. In the UK in 2019, over 200,000 hip and knee replacements were performed. About 1 in 100 replacements becomes infected, and most people with infected replacements require further surgery. Objectives: To investigate why some patients are predisposed to joint infections and how this affects patients and the NHS, and to evaluate treatments. Design: Systematic reviews, joint registry analyses, qualitative interviews, a randomised controlled trial, health economic analyses and a discrete choice questionnaire. Setting: Our studies are relevant to the NHS, to the Swedish health system and internationally. Participants: People with prosthetic joint infection after hip or knee replacement and surgeons. Interventions: Revision of hip prosthetic joint infection with a single-or two-stage procedure. Main outcome measures: Long-term patient-reported outcomes and reinfection. Cost-effectiveness of revision strategies over 18 months from two perspectives: health-care provider and Personal Social Services, and societal. Data sources: National Joint Registry; literature databases; published cohort studies; interviews with 67 patients and 35 surgeons; a patient discrete choice questionnaire; and the INFORM (INFection ORthopaedic Management) randomised trial. Review methods: Systematic reviews of studies reporting risk factors, diagnosis, treatment outcomes and cost comparisons. Individual patient data meta-analysis. Results: In registry analyses, about 0.62% and 0.75% of patients with hip and knee replacement, respectively, had joint infection requiring surgery. Rates were four times greater after aseptic revision. The costs of inpatient and day-case admissions in people with hip prosthetic joint infection were about five times higher than those in people with no infection, an additional cost of > £30,000. People described devastating effects of hip and knee prosthetic joint infection and treatment. In the treatment of hip prosthetic joint infection, a two-stage procedure with or without a cement spacer had a greater negative impact on patient well-being than a single-or two-stage procedure with a custom-made articulating spacer. Surgeons described the significant emotional impact of hip and knee prosthetic joint infection and the importance of a supportive multidisciplinary team. In systematic reviews and registry analyses, the risk factors for hip and knee prosthetic joint infection included male sex, diagnoses other than osteoarthritis, high body mass index, poor physical status, diabetes, dementia and liver disease. Evidence linking health-care setting and surgeon experience with prosthetic joint infection was inconsistent. Uncemented fixation, posterior approach and ceramic bearings were associated with lower infection risk after hip replacement. In our systematic review, synovial fluid alpha-defensin and leucocyte esterase showed high diagnostic accuracy for prosthetic joint infection. Systematic reviews and individual patient data meta-analysis showed similar reinfection outcomes in patients with hip or knee prosthetic joint infection treated with single-and two-stage revision. In registry analysis, there was a higher rate of early rerevision after single-stage revision for hip prosthetic joint infection, but, overall, 40% fewer operations are required as part of a single-stage procedure than as part of a two-stage procedure. The treatment of hip or knee prosthetic joint infection with early debridement and implant retention may be effective in > 60% of cases. In the INFORM randomised controlled trial, 140 patients with hip prosthetic joint infection were randomised to single-or two-stage revision. Eighteen months after randomisation, pain, function and stiffness were similar between the randomised groups (p = 0.98), and there were no differences in reinfection rates. Patient outcomes improved earlier in the single-stage than in the two-stage group. Participants randomised to a single-stag procedure had lower costs (mean difference –£10,055, 95% confidence interval –£19,568 to –£542) and higher quality-adjusted life-years (mean difference 0.06, 95% confidence interval –0.07 to 0.18) than those randomised to a two-stage procedure. Single-stage was the more cost-effective option, with an incremental net monetary benefit at a threshold of £20,000 per quality-adjusted life-year of £11,167 (95% confidence interval £638 to £21,696). In a discrete choice questionnaire completed by 57 patients 18 months after surgery to treat hip prosthetic joint infection, the most valued characteristics in decisions about revision were the ability to engage in valued activities and a quick return to normal activity. Limitations: Some research was specific to people with hip prosthetic joint infection. Study populations in meta-analyses and registry analyses may have been selected for joint replacement and specific treatments. The INFORM trial was not powered to study reinfection and was limited to 18 months’ follow-up. The qualitative study subgroups were small. Conclusions: We identified risk factors, diagnostic biomarkers, effective treatments and patient preferences for the treatment of hip and knee prosthetic joint infection. The risk factors include male sex, diagnoses other than osteoarthritis, specific comorbidities and surgical factors. Synovial fluid alpha-defensin and leucocyte esterase showed high diagnostic accuracy. Infection is devastating for patients and surgeons, both of whom describe the need for support during treatment. Debridement and implant retention is effective, particularly if performed early. For infected hip replacements, single-and two-stage revision appear equally efficacious, but single-stage has better early results, is cost-effective at 18-month follow-up and is increasingly used. Patients prefer treatments that allow full functional return within 3–9 months.
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