| 1. |
- De Rosa, G., et al.
(författare)
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Velocity-resolved Reverberation Mapping of Five Bright Seyfert 1 Galaxies
- 2018
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 866:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the first results from a reverberation-mapping campaign undertaken during the first half of 2012, with additional data on one active galactic nucleus (AGN) (NGC 3227) from a 2014 campaign. Our main goals are (1) to determine the black hole masses from continuum-H beta reverberation signatures, and (2) to look for velocity-dependent time delays that might be indicators of the gross kinematics of the broad-line region. We successfully measure H beta time delays and black hole masses for five AGNs, four of which have previous reverberation mass measurements. The values measured here are in agreement with earlier estimates, though there is some intrinsic scatter beyond the formal measurement errors. We observe velocity-dependent H beta lags in each case, and find that the patterns have changed in the intervening five years for three AGNs that were also observed in 2007.
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| 2. |
- Flannick, Jason, et al.
(författare)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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| 3. |
- Fuchsberger, Christian, et al.
(författare)
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The genetic architecture of type 2 diabetes
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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| 4. |
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| 5. |
- Nicholas, M. K., et al.
(författare)
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Implementation of Early Intervention Protocol in Australia for 'High Risk' Injured Workers is Associated with Fewer Lost Work Days Over 2 Years Than Usual (Stepped) Care
- 2020
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Ingår i: Journal of occupational rehabilitation. - : Springer. - 1053-0487 .- 1573-3688. ; 30:1, s. 93-104
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate whether a protocol for early intervention addressing the psychosocial risk factors for delayed return to work in workers with soft tissue injuries would achieve better long-term outcomes than usual (stepped) care.Methods: The study used a controlled, non-randomised prospective design to compare two case management approaches. For the intervention condition, workers screened within 1-3 weeks of injury as being at high risk of delayed returned to work by the Örebro Musculoskeletal Pain Screening Questionnaire-short version (ÖMPSQ-SF) were offered psychological assessment and a comprehensive protocol to address the identified obstacles for return to work. Similarly identified injured workers in the control condition were managed under usual (stepped) care arrangements.Results: At 2-year follow-up, the mean lost work days for the Intervention group was less than half that of the usual care group, their claim costs were 30% lower, as was the growth trajectory of their costs after 11 months.Conclusions: The findings supported the hypothesis that brief psychological risk factor screening, combined with a protocol for active collaboration between key stakeholders to address identified psychological and workplace factors for delayed return to work, can achieve better return on investment than usual (stepped) care.
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| 6. |
- Nicholas, M. K., et al.
(författare)
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Predicting Return to Work in a Heterogeneous Sample of Recently Injured Workers Using the Brief ÖMPSQ-SF
- 2019
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Ingår i: Journal of occupational rehabilitation. - : Springer. - 1053-0487 .- 1573-3688. ; 29:2, s. 295-302
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: (1) to examine the ability of the Örebro Musculoskeletal Pain Screening Questionnaire-short version (ÖMPSQ-SF) to predict time to return to pre-injury work duties (PID) following a work-related soft tissue injury (regardless of body location); and (2) to examine the appropriateness of 50/100 as a suitable cut-off score for case identification.Methods: Injured workers (IW) from six public hospitals in Sydney, Australia, who had taken medically-sanctioned time off work due to their injury, were recruited by insurance case managers within 5-15 days of their injury. Eligible participants (N = 213 in total) were administered the ÖMPSQ-SF over the telephone by the case manager. For objective (1) Cox proportional hazards regression analysis was used to predict days to return to PID using the ÖMPSQ-SF. For objective (2) receiver operator characteristic (ROC) analysis was used to determine the ÖMPSQ-SF total score that optimises sensitivity and specificity in detecting whether or not participants had returned to PID within 2-7 weeks.Results: The total ÖMPSQ-SF score significantly predicted number of days to return to PID, such that for every 1-point increase in the total ÖMPSQ-SF score the predicted chance of returning to work reduced by 4% (i.e., hazard ratio = 0.96), p < 0.001. Sensitivity and specificity for the ROC analysis comparing ÖMPSQ-SF total score to return to PID within 2-7 weeks suggested 48 as the optimal cut off (sensitivity = 0.65, specificity = 0.79).Conclusion: The results provide strong support for the use of the ÖMPSQ-SF in an applied setting for identifying those IW likely to have delayed RTW when administered within 15 days of the injury. While a score of 48/100 was the optimal cut point for sensitivity and specificity, pragmatically, 50/100 should be acceptable as a cut-off in future studies of this type.
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| 7. |
- Ong, Jue-Sheng, et al.
(författare)
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Assessment of moderate coffee consumption and risk of epithelial ovarian cancer : a Mendelian randomization study
- 2018
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 1464-3685 .- 0300-5771. ; 47:2, s. 450-459
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Tidskriftsartikel (refereegranskat)abstract
- Background: Coffee consumption has been shown to be associated with various health outcomes in observational studies. However, evidence for its association with epithelial ovarian cancer (EOC) is inconsistent and it is unclear whether these associations are causal.Methods: We used single nucleotide polymorphisms associated with (i) coffee and (ii) caffeine consumption to perform Mendelian randomization (MR) on EOC risk. We conducted a two-sample MR using genetic data on 44 062 individuals of European ancestry from the Ovarian Cancer Association Consortium (OCAC), and combined instrumental variable estimates using a Wald-type ratio estimator.Results: For all EOC cases, the causal odds ratio (COR) for genetically predicted consumption of one additional cup of coffee per day was 0.92 [95% confidence interval (CI): 0.79, 1.06]. The COR was 0.90 (95% CI: 0.73, 1.10) for high-grade serous EOC. The COR for genetically predicted consumption of an additional 80 mg caffeine was 1.01 (95% CI: 0.92, 1.11) for all EOC cases and 0.90 (95% CI: 0.73, 1.10) for high-grade serous cases.Conclusions: We found no evidence indicative of a strong association between EOC risk and genetically predicted coffee or caffeine levels. However, our estimates were not statistically inconsistent with earlier observational studies and we were unable to rule out small protective associations.
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| 9. |
- Stolk, Lisette, et al.
(författare)
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Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:3, s. 260-268
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Tidskriftsartikel (refereegranskat)abstract
- To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.
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| 10. |
- Tritos, Nicholas A, et al.
(författare)
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Effects of long-term growth hormone replacement in adults with growth hormone deficiency following cure of acromegaly : a KIMS analysis.
- 2014
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 99:6, s. 2018-2029
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: GH deficiency (GHD) may occur in adults with cured acromegaly (acroGHD).OBJECTIVE: Our objective was to examine the effectiveness and safety of GH replacement in acroGHD.DESIGN: This study was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database).SETTING: Data were extracted from a pharmaco-epidemiological survey of >16 000 GHD adults from 31 countries.PATIENTS: The effectiveness population included 115 adults with acroGHD and 142 age-, gender-, and body mass index-matched GHD adults with nonfunctioning pituitary adenoma (NFPA) followed up to 5 years on GH. The safety population included 164 adults with acroGHD and 2469 with NFPA, all GH-replaced. Both acroGHD and NFPA were compared with several cohorts from the general population (including the World Health Organization Global Burden of Disease).OUTCOME MEASURES: Outcome measures included quality of life (QoL-AGHDA), lipids, serious adverse events, and additional safety endpoints.RESULTS: Median GH dose was 0.3 mg/d in acroGHD and NFPA at 5 years. There were comparable improvements in QoL-AGHDA and total and low-density lipoprotein cholesterol in acroGHD and NFPA. High-density lipoprotein cholesterol increased only in acroGHD. Cardiovascular mortality was increased in acroGHD vs NFPA (standardized mortality ratio = 3.03, P = .02). All-cause mortality was similar in acroGHD (ratio between observed/expected cases [95% confidence interval] = 1.32 [0.70-2.25]) and lower in NFPA [observed/expected = 0.58 [0.48-0.70]) in comparison with the general population. There was no difference in incidence of all cancers, benign or malignant brain tumors, or diabetes mellitus between acroGHD and NFPA.CONCLUSIONS: GH replacement has comparable effects on quality of life and lipids in acroGHD and NFPA. Further investigation is needed to examine whether the increased cardiovascular mortality may be attributed to the history of previous GH excess in acroGHD.
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| 11. |
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