| 1. |
- Shungin, Dmitry, et al.
(author)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Journal article (peer-reviewed)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 2. |
- Angelin, Marcus, et al.
(author)
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Crystallization Driven Asymmetric Synthesis of Pyridine β-Nitroalcoholsvia Discovery-Oriented Self-Resolution of a Dynamic System
- 2010
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In: European Journal of Organic Chemistry. - : Wiley. - 1434-193X .- 1099-0690. ; 33, s. 6315-6318
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Journal article (peer-reviewed)abstract
- The study of dynamic nitroaldol systems aided the discovery of a diastereoselective crystallization process through amplification of 2-nitro-1-(pyridine-4-yl)propan-1-ol. The phenomenon was further developed into an effective procedure for asymmetic synthesis of pyridine-nitroalcohols and several substrates were screened to this end. These results demonstrate how work with larger dynamic systems facilitates and increases the likelihood of serendipitous discoveries.
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| 3. |
- Angelin, Marcus, et al.
(author)
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Crystallization-induced secondary selection from a tandem driven dynamic combinatorial resolution process
- 2008
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In: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 73:9, s. 3593-3595
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Journal article (peer-reviewed)abstract
- Crystallization-induced secondary selection from a tandem driven dynamic combinatorial library is presented. In a one-pot experiment, an initial nitroaldol equilibrium was kinetically driven by a tandem reaction resulting in a subsequent dynamic library of diastereoisomers. This library was then further driven by a phase change, resulting in amplification and isolation of a highly diastereomerically enriched and synthetically interesting isoindolinone.
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| 4. |
- Angelin, Marcus, et al.
(author)
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Diastereoselective One-Pot Tandem Synthesis of 3-Substituted Isoindolinones : A Mechanistic Investigation
- 2010
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In: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 75:17, s. 5882-5887
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Journal article (peer-reviewed)abstract
- The mechanism of a base-catalyzed one-pot reaction of 2-cyanobenzaldehyde and primary nitroalkanes, to produce 3-substituted isoindolinones, has been investigated. A route starting with a nitroaldol (Henry) reaction, followed by a subsequent cyclization and rearrangement, was supported by intermediate analogue synthesis and DFT calculations. Direct diastereoselective crystallization from the reaction mixture was also achieved and studied for a number of substrates. Furthermore, the 3-substituted isoindolinones are an interesting group of compounds, both present important natural products, as well as being precursors to other valuable building blocks.
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| 5. |
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| 6. |
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| 7. |
- Assimes, Themistocles L., et al.
(author)
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Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies
- 2010
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 56:19, s. 1552-1563
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Journal article (peer-reviewed)abstract
- Objectives We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD). Background Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers. Methods The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports. Results A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of >= 2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups. Conclusions The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study. (J Am Coll Cardiol 2010;56:1552-63) (C) 2010 by the American College of Cardiology Foundation
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| 8. |
- Berndt, Sonja I., et al.
(author)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Journal article (peer-reviewed)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 9. |
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| 10. |
- Bjorling, Patrik, et al.
(author)
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Ten Year Follow-up After Total Wrist Arthroplasty
- 2017
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Conference paper (peer-reviewed)abstract
- Hypothesis Total wrist arthroplasty (TWA) is an option in the management of wrist arthritis. The aim of the study was to evaluate the long-term results of TWA.Methods In this cohort study, we followed 56 cases that underwent TWA (Avanta, Biax, Universal 2 and Maestro) between 2005 and 2006 at a single-center. Data was collected preoperatively and 10 years postoperatively. Patient-related outcome measures, grip strength, range of motion (ROM), VAS pain scores were analyzed.Results VAS pain scores and patient-related measures were significantly improved at the 10-year follow-up. Jamar grip strength was also significantly improved. ROM remained largely unchanged, except for extension which improved significantly at the 10-year follow-up. Five of 56 TWAs were revised. Five patients died of unrelated causes and 10 were lost to follow-up.Summary Points This study shows good long-term results after TWA with a high level of patient satisfaction. The revision rate was acceptable.
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| 11. |
- Cortes, Diana S., et al.
(author)
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Mixed support for a causal link between single dose intranasal oxytocin and spiritual experiences: opposing effects depending on individual proclivities for absorption
- 2018
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In: Social Cognitive and Affective Neuroscience. - : Oxford University Press (OUP). - 1749-5016 .- 1749-5024. ; 13:9, s. 921-932
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Journal article (peer-reviewed)abstract
- Intranasal oxytocin (OT) has previously been found to increase spirituality, an effect moderated by OT-related genotypes. This pre-registered study sought to conceptually replicate and extend those findings. Using a single dose of intranasal OT vs placebo (PL), we investigated experimental treatment effects, and moderation by OT-related genotypes on spirituality, mystical experiences, and the sensed presence of a sentient being. A more exploratory aim was to test for interactions between treatment and the personality disposition absorption on these spirituality-related outcomes. A priming plus sensory deprivation procedure that has facilitated spiritual experiences in previous studies was used. The sample (N = 116) contained both sexes and was drawn from a relatively secular context. Results failed to conceptually replicate both the main effects of treatment and the treatment by genotype interactions on spirituality. Similarly, there were no such effects on mystical experiences or sensed presence. However, the data suggested an interaction between treatment and absorption. Relative to PL, OT seemed to enhance spiritual experiences in participants scoring low in absorption and dampen spirituality in participants scoring high in absorption.
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| 12. |
- Do, Ron, et al.
(author)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Journal article (peer-reviewed)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 13. |
- Erdmann, Jeanette, et al.
(author)
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New susceptibility locus for coronary artery disease on chromosome 3q22.3
- 2009
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:3, s. 280-282
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Journal article (peer-reviewed)abstract
- We present a three-stage analysis of genome-wide SNP data in 1,222 German individuals with myocardial infarction and 1,298 controls, in silico replication in three additional genome-wide datasets of coronary artery disease (CAD) and subsequent replication in similar to 25,000 subjects. We identified one new CAD risk locus on 3q22.3 in MRAS (P = 7.44 x 10(-13); OR = 1.15, 95% CI = 1.11-1.19), and suggestive association with a locus on 12q24.31 near HNF1A-C12orf43 (P = 4.81 x 10(-7); OR = 1.08, 95% CI = 1.05-1.11).
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| 14. |
- Fischer, Per, 1981-
(author)
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Hemi and total wrist arthroplasty
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Aim: To study implant survival and implant loosening following primary total wrist arthroplasty (TWA) using four different implants. To report outcome following wrist revision arthroplasty. To evaluate a new radial wrist hemi arthroplasty (RWHA) design clinically and biomechanically.Method: The studies included 136 primary TWAs and 16 revision TWAs, both studies with prospectively collected data. Six fresh frozen cadaveric wrist specimen were used for biomechanical analysis. The RHWA was evaluated clinically in a pilot series of 20 cases.Results: Total implant survival was 92% but with high frequency of implant loosening of surviving Re-Motion implants. None of the surviving Maestro implants were considered radiographically loose. Implant survival following revision arthroplasty was 75%, considerably lower than following primary TWAs. However, none of the patients with surviving revision implants had pain at rest and little or no pain in activity. The surgical procedure and placement of the RHWA was feasible. Overall, the kinematic and functional changes appeared acceptable compared to the native wrist. None of the patients underwent revision following RHWA but reoperation was performed in 7 patients on the indication of persistent pain. However, patients reported relief of pain and improvement of patient-reported outcome measures.Conclusion: High long-term implant survival and no signs of radiographic loosening was found for the Maestro implant. However, the Maestro implant is no longer available on the market and we believe there is a need for new TWA designs. Revision arthroplasty is a valid option in the management of failed TWA. However, implant survival is lower than for primary TWAs and as many as 25% require additional surgery. Promising results were found using the new RHWA design but the implant needs modification before further testing.
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| 15. |
- Fischer, Per, 1981-, et al.
(author)
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Revision Arthroplasty of the Wrist in Patients With Rheumatoid Arthritis, Mean Follow-Up 6.6 Years
- 2018
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In: Journal of Hand Surgery-American Volume. - : Elsevier. - 0363-5023 .- 1531-6564. ; 43:5, s. 489.e1-489.e7
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Journal article (peer-reviewed)abstract
- PURPOSE: Management of failed total wrist arthroplasty (TWA) can be challenging; surgical treatment options include salvage arthrodesis, revision arthroplasty, and resection arthroplasty. There are few studies regarding salvage arthrodesis, and revision arthroplasty has been infrequently investigated. The aim of the study was to report the outcome after revision arthroplasty of the wrist.METHODS: A retrospective cohort of 16 revision TWAs was evaluated between 2003 and 2016. Data were collected before surgery and 1 and 5 years after surgery. The indication for revision arthroplasty was failed TWA. The primary end point was implant survival. Secondary outcome measures included visual analog scale (VAS) pain scores, range of motion, handgrip strength, and functional scoring with the Canadian Occupational Performance Measure (COPM), Patient-Rated Wrist Evaluation (PRWE), and Disabilities of the Arm, Shoulder, and Hand (DASH).RESULTS: Mean follow-up was 6.6 years. Synthetic bone graft was used in 9 cases, allograft corticocancellous bone graft in 1 case, and cement in 6 cases. Of the 16 revision TWAs, 4 were re-revised, 1 because of infection, and 3 cases underwent total wrist arthrodesis. In the non-re-revised cases, range of motion and grip strength was preserved compared with preoperative results. The VAS pain score in activity improved, but not significantly, at 1 (median, 1; range, 0-4.5) and 5 years after surgery (median, 0) compared with before surgery (median, 5). The COPM performance and satisfaction as well as PRWE scores improved significantly at 1 year (median COPM performance, 4.8; COPM satisfaction, 5.6; and PRWE, 24) and improved, but not significantly, at the 5-year follow (median COPM performance, 4.8; COPM satisfaction, 5.0; and PRWE, 37) in the non-re-revised cases.CONCLUSIONS: Revision arthroplasty of the wrist is a valid motion-preserving option to wrist arthrodesis in the management of failed TWA. However, the outcome is uncertain and as many as 25% require additional surgery.TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
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| 16. |
- Fischer, Per, 1981-, et al.
(author)
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Total Wrist Arthroplasty : A 10-Year Follow-Up
- 2020
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In: Journal of Hand Surgery-American Volume. - : Elsevier. - 0363-5023 .- 1531-6564. ; 45:8, s. 780.e1-780.e10
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Journal article (peer-reviewed)abstract
- Purpose: To assess long-term implant survival in total wrist arthroplasty (TWA), comparing 4 different implants.Methods: In a prospective cohort of 124 patients, 136 TWAs were evaluated 5 years and 10 years after surgery. The TWAs were implanted between 2005 and 2009. The primary outcome was implant survival. Survival analysis was performed with revision and radiographic loosening as the final end point. Revision was defined as exchange of whole or parts of the prosthesis. Implant loosening was assessed using radiographic examination at the 5-year and 10-year follow-up. Secondary outcome measures included wrist range of motion, hand grip strength, visual analog scale (VAS) pain scores, and patient-related outcome measures, including Disabilities of the Arm, Shoulder, and Hand (DASH), Patient-Rated Wrist Evaluation (PRWE), and Canadian Occupational Performance Measure (COPM).Results: Total cumulative implant survival was 92% with revision as the primary end point. When including a nonrevised radiographic loose implant as a failure, total implant survival was 75%. Radiographic loosening differed significantly between the implants with a range in frequency from 0% to 37.5%. At the 10-year follow-up, assessing the nonrevised TWAs, range of motion was preserved compared with preoperative values. Significant improvement was recorded for hand grip strength, VAS pain scores, and patient-related outcome measures at the 10-year follow-up compared with preovperative values.Conclusions: High 10-year implant survival was found when defining the primary end point as revision of any cause. When including radiographic loosening of the implant in the survival analysis, implant survival was considerably lower. However, radiographic loosening does not seem to correlate with changes in secondary outcome measures, questioning the need for revision surgery in these cases.
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| 17. |
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| 18. |
- Ganesh, Santhi K., et al.
(author)
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Loci influencing blood pressure identified using a cardiovascular gene-centric array
- 2013
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 22:8, s. 1663-1678
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Journal article (peer-reviewed)abstract
- Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped 50 000 single-nucleotide polymorphisms (SNPs) that capture variation in 2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P 2.4 10(6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Kelsen, Jesper, et al.
(author)
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Copenhagen Head Injury Ciclosporin Study : A Phase IIa Safety, Pharmacokinetics, and Biomarker Study of Ciclosporin in Severe Traumatic Brain Injury Patients
- 2019
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In: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 36:23, s. 3253-3263
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Journal article (peer-reviewed)abstract
- Traumatic brain injury (TBI) contributes to almost one third of all trauma-related deaths, and those that survive often suffer from long-term physical and cognitive deficits. Ciclosporin (cyclosporine, cyclosporin A) has shown promising neuroprotective properties in pre-clinical TBI models. The Copenhagen Head Injury Ciclosporin (CHIC) study was initiated to establish the safety profile and pharmacokinetics of ciclosporin in patients with severe TBI, using a novel parenteral lipid emulsion formulation. Exploratory pharmacodynamic study measures included microdialysis in brain parenchyma and protein biomarkers of brain injury in the cerebrospinal fluid (CSF). Sixteen adult patients with severe TBI (Glasgow Coma Scale 4-8) were included, and all patients received an initial loading dose of 2.5 mg/kg followed by a continuous infusion for 5 days. The first 10 patients received an infusion dosage of 5 mg/kg/day whereas the subsequent 6 patients received 10 mg/kg/day. No mortality was registered within the study duration, and the distribution of adverse events was similar between the two treatment groups. Pharmacokinetic analysis of CSF confirmed dose-dependent brain exposure. Between- and within-patient variability in blood concentrations was limited, whereas CSF concentrations were more variable. The four biomarkers, glial fibrillary acidic protein, neurofilament light, tau, and ubiquitin carboxy-terminal hydrolase L1, showed consistent trends to decrease during the 5-day treatment period, whereas the samples taken on the days after the treatment period showed higher values in the majority of patients. In conclusion, ciclosporin, as administered in this study, is safe and well tolerated. The study confirmed that ciclosporin is able to pass the blood-brain barrier in a TBI population and provided an initial biomarker-based signal of efficacy.
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| 23. |
- Locke, Adam E, et al.
(author)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Journal article (peer-reviewed)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 24. |
- Lundqvist, Eva, 1985-
(author)
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Distal radius fractures AO type C : A clinical and radiographic investigation
- 2022
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Doctoral thesis (other academic/artistic)abstract
- The function of the hand is of substantial importance, and injuries have an impact on daily life. Distal radius fracture (DRF) is the most common fracture among adults. The annual incidence is 26 per 10,000 inhabitants, and the incidence is increasing because of an aging population. There has been a shift from conservative and other operative treatments, toward volar plate fixation to restore the anatomy and improve results. Operative treatment is often considered for displaced and unstable fractures. The optimal choice of treatment and fixation is still debated. The aim of this thesis was to study results after internal fixation of DRF AO type C.Study I (retrospective study, n=74) assessed outcomes after combined plating (CP) of DRFs AO type C, with 1-year follow-up. CP restored the anatomy and achieved a good functional outcome. The radiographic outcome did not correspond to the clinical or functional outcome.Study II (prospective study, n=97) assessed the prevalence of post-traumatic arthritis (PA) following CP of DRFs AO type C. CP yielded a good clinical outcome 7 years postoperatively and the prevalence of PA was low (29%). The presence of PA did not correlate with fracture group, radio-graphic, clinical, or functional outcome. Study III (randomized controlled trial, n=147) assessed the radiographic and clinical outcome following surgical treatment of DRFs AO type C, comparing volar plating (VP) with CP. Fixation with VP yieldedthe same radiographic and functional results as CP, but with a lower frequency of complications in the VP group.Study IV (prospective pilot study, n=10) assessed fragment migration with CTMA (CT-based micromotion analysis) after osteosynthesis with VP after DRF AO type C. The CTMA technique indicated that variable angle volar locking plate fixation can yield and maintain a stable reduction of the fracture fragments. CT volume registration could be a valuable tool in the detailed assessment of fracture fragment migration following VP fixation of DRFs.
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| 25. |
- Lundqvist, Eva, 1985-, et al.
(author)
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Posttraumatic Arthritis After Combined Plating of Distal Radius Fractures AO Type C : A 7-Year Follow-up of 97 Cases
- 2022
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In: Hand (New York, N.Y.). - : Sage Publications. - 1558-9447 .- 1558-9455. ; :Sup. 1, s. 50S-59S
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Journal article (peer-reviewed)abstract
- BACKGROUND: Volar locking plate fixation is the most common method of operative fixation of distal radius fractures (DRFs). For more complex cases, combined plating is an option for stabilizing intra-articular fragments. The prevalence of posttraumatic arthritis (PA) after an intra-articular DRF, and its relation to patient-reported outcome measures (PROMs), remains unclear. The purpose of this study was to study the prevalence of PA and its correlation to clinical outcome measures.METHODS: We evaluated 97 consecutive patients with intra-articular DRF, operated with combined plating, 7 years postoperatively. The primary outcome measure was the prevalence of radiographic PA. Secondary outcome measures included visual analog scale (VAS) pain score, hand grip strength, wrist range of motion (ROM), Patient-Rated Wrist Evaluation (PRWE) score, and Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score. Radiographic examination was performed between 1 and 7 years postoperatively.RESULTS: The prevalence of PA was 29% at the 7-year follow-up. No correlation was found between PA and ROM, hand grip strength, PRWE, QuickDASH, VAS pain scores, or radiographic reduction. Median wrist ROM and grip strength were significantly inferior compared with the uninjured side. Hardware removal was performed in 51.5% of cases. There were 2 cases of tendon ruptures.CONCLUSIONS: Combined plating can yield a good clinical outcome 7 years postoperatively and a low prevalence of PA. The presence of PA did not correlate to clinical outcome measures or to the accuracy of anatomical reduction 1 year postoperatively. The frequency of tendon ruptures was acceptable, but the high frequency of hardware removal is a concern.
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| 26. |
- Lundqvist, Eva, 1985-, et al.
(author)
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Volar Locking Plate Compared With Combined Plating of AO Type C Distal Radius Fractures : A Randomized Controlled Study of 150 Cases
- 2022
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In: Journal of Hand Surgery-American Volume. - : Elsevier. - 0363-5023 .- 1531-6564. ; 47:9, s. 813-822
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Journal article (peer-reviewed)abstract
- PURPOSE: The optimal way to stabilize intra-articular distal radius fractures is unclear despite recent advances in surgical management. Volar plating is the most common treatment but may not be sufficient for more complex intra-articular AO type C fractures. The purpose of this randomized controlled study was to evaluate the radiographic and clinical outcomes following surgical treatment of AO type C distal radius fractures, comparing volar with combined plating.METHODS: In this study, 150 patients were randomized to volar locking plate (n = 75) or combined plating (n = 75) following a distal radius fracture AO type C. The 1-year follow-up included radiographic outcome (Batra score), visual analog scale pain score, hand grip strength, wrist range of motion, Patient-Rated Wrist Evaluation score, and Quick Disabilities of the Arm, Shoulder, and Hand score.RESULTS: Overall, 147 patients (median age 61 years) completed the 1-year follow-up (73 patients with volar plate and 74 with combined plating). No difference was found in radiographic outcome between the treatment groups. The volar plate group had significantly better Patient-Rated Wrist Evaluation scores, Quick Disabilities of the Arm, Shoulder, and Hand scores, hand grip strength, visual analog scale scores during activity, and flexion, extension, ulnar and radial deviation than the combined plate group. Hardware removal was performed in 10% in the volar plate group and in 31% in the combined plate group. There was no postoperative infection in the volar plate group but 3 cases in the combined plate group.CONCLUSIONS: In patients with complex AO type C intra-articular fractures, volar and combined plating yielded the same radiographic result. The differences in Patient-Rated Wrist Evaluation and Quick Disabilities of the Arm, Shoulder, and Hand scores between the groups did not reach the thresholds for minimal clinically important differences, suggesting similar clinical outcome. The combined plating group had a considerably higher frequency of hardware removal and postoperative infections.TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.
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| 27. |
- Maergner, Paul, et al.
(author)
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Combining graph edit distance and triplet networks for offline signature verification
- 2019
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In: Pattern Recognition Letters. - : Elsevier. - 0167-8655 .- 1872-7344. ; 125, s. 527-533
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Journal article (peer-reviewed)abstract
- Offline signature verification is a challenging pattern recognition task where a writer model is inferred using only a small number of genuine signatures. A combination of complementary writer models can make it more difficult for an attacker to deceive the verification system. In this work, we propose to combine a recent structural approach based on graph edit distance with a statistical approach based on deep triplet networks. The combination of the structural and statistical models achieve significant improvements in performance on four publicly available benchmark datasets, highlighting their complementary perspectives.
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| 28. |
- Maurer, D, et al.
(author)
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Peripheral blood dendritic cells express Fc epsilon RI as a complex composed of Fc epsilon RI alpha- and Fc epsilon RI gamma-chains and can use this receptor for IgE-mediated allergen presentation
- 1996
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In: Journal of Immunology. - : American association of immunologists. - 0022-1767 .- 1550-6606. ; 157:2, s. 607-616
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Journal article (peer-reviewed)abstract
- Originally limited to basophils and mast cells, the spectrum of high affinity IgE receptor (Fc epsilon RI-bearing cells has expanded recently to include Langerhans cells, dermal dendritic cells (DC), monocytes, and eosinophils. As a result of studies on the distribution, structure, and function of Fc epsilon RI on APCs, we discovered a minor nonbasophil, nonmonocyte PBMC population that can bind IgE via Fc epsilon RI. This receptor occurs on the surface of these cells as a multimeric structure containing Fc epsilon RI alpha- and Fc epsilon RI gamma-chains but, unlike its counterpart on basophils, lacking Fc epsilon RI beta. Further experiments revealed that these Fc epsilon RI alpha gamma-expressing cells closely resemble peripheral blood DC by immunophenotype (HLA-DRhigh, HLA-DQhhigh; CD4+, CD11a+, CD32+, CD33+, B7/2 (CD86)+; CD11blow, CD14low, CD40low, CD54low, CD64low) and cell morphology. These features allowed us to isolate Fc epsilon RI-expressing DC from the peripheral blood and to investigate their immunostimulatory properties. We found Fc epsilon RI-positive DC to be efficient stimulators of both primary (allogeneic MLR) and Fc epsilon RI/IgE-dependent, secondary T cell responses at low cell numbers. Thus, Fc epsilon RI-expressing DC may not only amplify established type I allergic immune reactions but, unlike Fc epsilon RI-positive semiprofessional APCs, may be able to prime naive T cells to common and/or cryptic epitopes of IgE-reactive Ags.
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| 29. |
- Misra, Deepankar, et al.
(author)
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Two-Center Double-Capture Interference in Fast He2++H2 Collisions
- 2009
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:15, s. 153201-
-
Journal article (peer-reviewed)abstract
- We report the first observation of Young-type interference effects in a two-electron transfer process. These effects change strongly as the projectile velocity changes in fast (1.2 and 2.0 MeV) He^{2+}-H_2 collisions as manifested in strong variations of the double-electron capture rates with the H_2 orientation. This is consistent with fully quantum mechanical calculations, which ignore sequential electron transfer, and a simple projectile de Broglie wave picture assuming that two-electron transfer probabilities are higher in collisions where the projectile passes close to either one of the H_2 nuclei.
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| 30. |
- Mulvaney, Robert, et al.
(author)
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The ST22 chronology for the Skytrain Ice Rise ice core - Part 2 : An age model to the last interglacial and disturbed deep stratigraphy
- 2023
-
In: Climate of the Past. - 1814-9324. ; 19:4, s. 851-864
-
Journal article (peer-reviewed)abstract
- We present an age model for the 651g€¯m deep ice core from Skytrain Ice Rise, situated inland of the Ronne Ice Shelf, Antarctica. The top 2000 years have previously been dated using age markers interpolated through annual layer counting. Below this, we align the Skytrain core to the AICC2012 age model using tie points in the ice and air phase, and we apply the Paleochrono program to obtain the best fit to the tie points and glaciological constraints. In the gas phase, ties are made using methane and, in critical sections, δ18Oair; in the ice phase ties are through 10Be across the Laschamps event and through ice chemistry related to long-range dust transport and deposition. This strategy provides a good outcome to about 108g€¯ka (g1/4g€¯605g€¯m). Beyond that there are signs of flow disturbance, with a section of ice probably repeated. Nonetheless values of CH4 and δ18Oair confirm that part of the last interglacial (LIG), from about 117-126g€¯ka (617-627g€¯m), is present and in chronological order. Below this there are clear signs of stratigraphic disturbance, with rapid oscillation of values in both the ice and gas phase at the base of the LIG section, below 628g€¯m. Based on methane values, the warmest part of the LIG and the coldest part of the penultimate glacial are missing from our record. Ice below 631g€¯m appears to be of ageg€¯>g€¯150g€¯ka.
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| 31. |
- Patterson, Nick, et al.
(author)
-
Large-scale migration into Britain during the Middle to Late Bronze Age
- 2022
-
In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
-
Journal article (peer-reviewed)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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| 32. |
- Rask-Andersen, Helge, et al.
(author)
-
Supernumerary human hair cells-signs of regeneration or impaired development? : A field emission scanning electron microscopy study
- 2017
-
In: Upsala Journal of Medical Sciences. - : TAYLOR & FRANCIS LTD. - 0300-9734 .- 2000-1967. ; 122:1, s. 11-19
-
Journal article (peer-reviewed)abstract
- Background: Current attempts to regenerate cochlear sensorineural structures motivate further inspection of the human organ of hearing. Here, we analyzed the supernumerary inner hair cell (sIHC), a possible sign of regeneration and cell replacement. Methods: Human cochleae were studied using field emission scanning electron microscopy (FESEM; maximum resolution 2 nm) obtained from individuals aged 44, 48, and 58 years with normal sensorineural pure-tone average (PTA) thresholds (PTA < 20 dB). The wasted tissue was harvested during trans-cochlear approaches and immediately fixed for ultrastructural analysis. Results: All specimens exhibited sIHCs at all turns except at the extreme lower basal turn. In one specimen, it was possible to image and count the inner hair cells (IHCs) along the cochlea representing the 0.2 kHz-8 kHz region according to the Greenwood place/frequency scale. In a region with 2,321 IHCs, there were 120 scattered one-cell losses or 'gaps' (5%). Forty-two sIHCs were present facing the modiolus. Thirty-eight percent of the sIHCs were located near a 'gap' in the IHC row (+/- 6 IHCs). Conclusions: The prevalence of ectopic inner hair cells was higher than expected. The morphology and placement could reflect a certain ongoing regeneration. Further molecular studies are needed to verify if the regenerative capacity of the human auditory periphery might have been underestimated.
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| 33. |
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| 34. |
- Reiser, Daniel, 1972-, et al.
(author)
-
Clinical, Radiographic, and Patient-Perceived Outcome After Radial Hemi-Wrist Arthroplasty With a New Implant : 20 Cases With 5-Year Follow-up
- 2023
-
In: Hand (New York, N.Y.). - : Sage Publications. - 1558-9447 .- 1558-9455.
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Distal component loosening is a common mode of failure in total wrist arthroplasty (TWA). A radial hemi-wrist arthroplasty (RHWA) has the potential to avoid problems related to the distal component in TWA. The aim of this study is to investigate clinical outcomes following surgical treatment with a new RHWA design.METHODS: In this pilot study of 20 consecutive RHWAs, patients were assessed preoperatively and postoperatively for range of motion, grip strength, Visual Analog Scale (VAS) pain scores, and functional scoring using Patient-Rated Wrist Evaluation (PRWE), Disabilities of the Arm, Shoulder, and Hand (DASH), and Canadian Occupational Performance Measure. Radiographs were analyzed at 12 months and 5 years (mean, 5.1 years) postoperatively.RESULTS: A total of 46 secondary surgeries were undertaken in 16 wrists, including 7 revisions. Another 6 patients are waiting for revision to radiocarpal arthrodesis. In non-revised patients, the DASH and PRWE scores improved, and wrist range of motion remained largely unchanged except for wrist flexion, which decreased. The VAS pain score during activity was reduced, and hand grip strength remained largely unchanged.CONCLUSIONS: The new implant resulted in improved functional scoring and improved VAS pain scores in non-revised patients, but many cases needed secondary surgery due to persistent pain. The high revision rate is a major concern, and further use of the implant in its current form cannot be recommended.
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| 35. |
- Reiser, Daniel, et al.
(author)
-
Total Wrist Arthroplasty With a New Design, 20 Cases With 8-Year Follow-Up
- 2023
-
In: Journal of Hand Surgery-American Volume. - : Elsevier. - 0363-5023 .- 1531-6564.
-
Journal article (peer-reviewed)abstract
- PURPOSE: Total wrist arthroplasty (TWA) is an established motion-preserving alternative to arthrodesis in the treatment of wrist arthritis, but post-TWA complications requiring additional surgery remain an issue. A new TWA design has been proposed. The purpose of this study was to report the outcome of a cohort study of 20 patients who underwent surgery using the new TWA design.METHODS: Patients were assessed before surgery and at 1, 2, and 8 years after surgery for visual analog scale (VAS) pain scores, wrist range of motion, hand grip strength, and patient-reported outcome measures (PROMs). Radiographic examination was conducted for evidence of prosthetic loosening. Reasons for revision were analyzed.RESULTS: In total, 24 reoperations were performed, including 12 revisions in 6 patients. Patient-reported outcome measures improved significantly at the 2-year follow-up compared with preoperative values. Hand grip strength, wrist extension, and VAS pain scores improved significantly at the 2-year follow-up. No radiographic loosening of the components was observed, but backing out of the carpal screws was noted in 16 of the 20 cases.CONCLUSIONS: The new TWA resulted in improved VAS pain scores, PROMs, wrist extension, and hand grip strength. The high frequency of reoperation is a concern, and modification of the implant is needed.TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
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| 36. |
- Ried, Janina S., et al.
(author)
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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
- 2016
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Journal article (peer-reviewed)abstract
- Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
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| 37. |
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| 38. |
- Rundqvist, Helene, et al.
(author)
-
Activation of the erythropoietin receptor in human skeletal muscle
- 2009
-
In: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 161:3, s. 427-434
-
Journal article (peer-reviewed)abstract
- Objective: Erythropoietin receptor (EPOR) expression in non-hematological tissues has been shown to be activated by locally produced and/or systemically delivered EPO. Improved oxygen homeostasis, a well-established consequence of EPOR activation, is very important for human skeletal muscle performance. In the present study we investigate whether human skeletal muscle fibers and satellite cells express EPOR and if it is activated by exercise. Design and methods: Ten healthy males performed 65 min of cycle exercise. Biopsies were obtained from the vastus lateralis muscle and femoral arterio-venous differences in EPO concentrations were estimated. Results: The EPOR proteinwas localized in areas corresponding to the sarcolemma and capillaries. Laser dissection identified EPOR mRNA expression in muscle fibers. Also, EPOR mRNA and protein were both detected in human skeletal muscle satellite cells. In the initial part of the exercise bout there was a release of EPO from the exercising leg to the circulation, possibly corresponding to an increased bioavailability of EPO. After exercise, EPOR mRNA and EPOR-associated JAK2 phosphorylation were increased. Conclusions: Interaction with JAK2 is required for EPOR signaling and the increase found in phosphorylation is therefore closely linked to the activation of EPOR. The receptor activation by acute exercise suggests that signaling through EPOR is involved in exercise-induced skeletal muscle adaptation, thus extending the biological role of EPO into the skeletal muscle.
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| 39. |
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| 40. |
- Schunkert, Heribert, et al.
(author)
-
Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
- 2011
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:4, s. 153-333
-
Journal article (peer-reviewed)abstract
- We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 x 10(-8) and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
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| 41. |
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| 42. |
- Studer, Linda, et al.
(author)
-
A Comprehensive Study of ImageNet Pre-Training for Historical Document Image Analysis
- 2019
-
In: The 15th IAPR International Conference on Document Analysis and Recognition. - : IEEE. ; , s. 720-725
-
Conference paper (other academic/artistic)abstract
- Automatic analysis of scanned historical documents comprises a wide range of image analysis tasks, which are often challenging for machine learning due to a lack of human-annotated learning samples. With the advent of deep neural networks, a promising way to cope with the lack of training data is to pre-train models on images from a different domain and then fine-tune them on historical documents. In the current research, a typical example of such cross-domain transfer learning is the use of neural networks that have been pre-trained on the ImageNet database for object recognition. It remains a mostly open question whether or not this pre-training helps to analyse historical documents, which have fundamentally different image properties when compared with ImageNet. In this paper, we present a comprehensive empirical survey on the effect of ImageNet pre-training for diverse historical document analysis tasks, including character recognition, style classification, manuscript dating, semantic segmentation, and content-based retrieval. While we obtain mixed results for semantic segmentation at pixel-level, we observe a clear trend across different network architectures that ImageNet pre-training has a positive effect on classification as well as content-based retrieval.
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| 43. |
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| 44. |
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| 45. |
- Tragante, Vinicius, et al.
(author)
-
Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci.
- 2014
-
In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:3, s. 349-360
-
Journal article (peer-reviewed)abstract
- Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.
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| 46. |
- van der Harst, Pim, et al.
(author)
-
Seventy-five genetic loci influencing the human red blood cell
- 2012
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
-
Journal article (peer-reviewed)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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| 47. |
- van Zuydam, Natalie R., et al.
(author)
-
Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus
- 2020
-
In: Circulation. - : Lippincott Williams & Wilkins. - 2574-8300. ; 13:6, s. 640-648
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D).METHODS: To test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D).RESULTS: None of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background.CONCLUSIONS: This study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.
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| 48. |
- Voight, Benjamin F, et al.
(author)
-
Plasma HDL cholesterol and risk of myocardial infarction : a mendelian randomisation study
- 2012
-
In: The Lancet. - 0140-6736 .- 1474-547X. ; 380:9841, s. 572-580
-
Journal article (peer-reviewed)abstract
- BACKGROUND: High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal.METHODS: We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20,913 myocardial infarction cases, 95,407 controls). Second, we used as an instrument a genetic score consisting of 14 common SNPs that exclusively associate with HDL cholesterol and tested this score in up to 12,482 cases of myocardial infarction and 41,331 controls. As a positive control, we also tested a genetic score of 13 common SNPs exclusively associated with LDL cholesterol.FINDINGS: Carriers of the LIPG 396Ser allele (2·6% frequency) had higher HDL cholesterol (0·14 mmol/L higher, p=8×10(-13)) but similar levels of other lipid and non-lipid risk factors for myocardial infarction compared with non-carriers. This difference in HDL cholesterol is expected to decrease risk of myocardial infarction by 13% (odds ratio [OR] 0·87, 95% CI 0·84-0·91). However, we noted that the 396Ser allele was not associated with risk of myocardial infarction (OR 0·99, 95% CI 0·88-1·11, p=0·85). From observational epidemiology, an increase of 1 SD in HDL cholesterol was associated with reduced risk of myocardial infarction (OR 0·62, 95% CI 0·58-0·66). However, a 1 SD increase in HDL cholesterol due to genetic score was not associated with risk of myocardial infarction (OR 0·93, 95% CI 0·68-1·26, p=0·63). For LDL cholesterol, the estimate from observational epidemiology (a 1 SD increase in LDL cholesterol associated with OR 1·54, 95% CI 1·45-1·63) was concordant with that from genetic score (OR 2·13, 95% CI 1·69-2·69, p=2×10(-10)).INTERPRETATION: Some genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of myocardial infarction. These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction.
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| 49. |
- Wei, Hao, et al.
(author)
-
Selecting Autoencoder Features for Layout Analysis of Historical Documents
- 2015
-
In: Third International Workshop on Historical Document Imaging and Processing. - New York, NY, USA : ACM. ; , s. 55-62
-
Conference paper (peer-reviewed)abstract
- Automatic layout analysis of historical documents has to cope with a large number of different scripts, writing sup- ports, and digitalization qualities. Under these conditions, the design of robust features for machine learning is a highly challenging task. We use convolutional autoencoders to learn features from the images. In order to increase the classifica- tion accuracy and to reduce the feature dimension, in this paper we propose a novel feature selection method. The method cascades adapted versions of two conventionalmeth- ods. Compared to three conventional methods and our pre- vious work, the proposed method achieves a higher classifi- cation accuracy in most cases, while maintaining low feature dimension. In addition, we find that a significant number of autoencoder features are redundant or irrelevant for the clas- sification, and we give our explanations. To the best of our knowledge, this paper is one of the first investigations in the field of image processing on the detection of redundancy and irrelevance of autoencoder features using feature selection.
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| 50. |
- Willer, Cristen J., et al.
(author)
-
Discovery and refinement of loci associated with lipid levels
- 2013
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
-
Journal article (peer-reviewed)abstract
- Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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