| 1. |
- Patel, Riyaz S., et al.
(författare)
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Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
- 2019
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Ingår i: Circulation. - 2574-8300. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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| 2. |
- Triplett, Laura D., et al.
(författare)
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Changes in amorphous silica sequestration with eutrophication of riverine impoundments
- 2012
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Ingår i: Biogeochemistry. - : Springer Science and Business Media LLC. - 1573-515X .- 0168-2563. ; 108:1-3, s. 413-427
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Tidskriftsartikel (refereegranskat)abstract
- The effect of eutrophication on particulate amorphous silica (ASi) sequestration was isolated and quantified in Lake St. Croix and Lake Pepin, two natural, human-impacted impoundments of the upper Mississippi River. In contrast to impoundments behind engineered dams, where silica (Si) fluxes may be changed by various aspects of dam construction, these two riverine lakes have long (9,000+ years) sedimentary sequences that record the entire span of cultural eutrophication and the resulting silica sequestration. The concentrations of dissolved silicate (DSi) and ASi in the lake inflows were measured for 1 year to obtain the total flux of bioavailable silica (TSib = DSi + ASi) to each impoundment. Historical rates of Si sequestration in each lake were determined using ASi burial in multiple sediment cores and modeled estimates of historical TSib fluxes. The Si trapping efficiency of each lake was found to have increased exponentially with cultural eutrophication (estimated two- to fivefold increase in Lake St. Croix and 9- to 16-fold increase in Lake Pepin over the last 100 years), indicating the degree to which eutrophication of impoundments can reduce silica export to downstream coastal and marine ecosystems. Because these two lakes presently exhibit different degrees of eutrophication, together they depict a relationship between phosphorus concentration and Si trapping efficiency that may be applied to other impoundments, including human-made reservoirs.
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| 3. |
- Arlien-Soborg, Mai C., et al.
(författare)
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Acromegaly management in the Nordic countries: A Delphi consensus survey
- 2024
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Ingår i: Clinical Endocrinology. - : WILEY. - 0300-0664 .- 1365-2265.
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveAcromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.MethodsA Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as >= 80% of panelists rating their agreement as >= 5 or <= 3 on the Likert-type scale.ResultsConsensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.ConclusionThis consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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| 4. |
- Arlien-Soborg, Mai C., et al.
(författare)
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Acromegaly management in the Nordic countries: A Delphi consensus survey
- 2024
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Ingår i: CLINICAL ENDOCRINOLOGY. - : WILEY. - 0300-0664 .- 1365-2265.
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveAcromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.MethodsA Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as >= 80% of panelists rating their agreement as >= 5 or <= 3 on the Likert-type scale.ResultsConsensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.ConclusionThis consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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| 5. |
- Arlien-Søborg, Mai C., et al.
(författare)
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Acromegaly management in the nordic countries : a Delphi consensus survey
- 2024
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Ingår i: Clinical Endocrinology. - : John Wiley & Sons. - 0300-0664 .- 1365-2265.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.Methods: A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1−7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale.Results: Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.Conclusion: This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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| 6. |
- Di Angelantonio, Emanuele, et al.
(författare)
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Association of Cardiometabolic Multimorbidity With Mortality : The Emerging Risk Factors Collaboration
- 2015
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 314:1, s. 52-60
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing.OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity.DESIGN, SETTING, AND PARTICIPANTS Age-and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689 300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128 843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499 808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI).MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy.RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy.CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
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| 7. |
- Kallesoe, Christian, et al.
(författare)
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Integration, gap formation, and sharpening of III-V heterostructure nanowires by selective etching
- 2010
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Ingår i: Journal of Vacuum Science and Technology B. - : American Vacuum Society. - 1520-8567. ; 28:1, s. 21-26
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Tidskriftsartikel (refereegranskat)abstract
- Epitaxial growth of heterostructure nanowires allows for the definition of narrow sections with specific semiconductor composition. The authors demonstrate how postgrowth engineering of III-V heterostructure nanowires using selective etching can form gaps, sharpening of tips, and thin sections simultaneously on multiple nanowires. They investigate the potential of combining nanostencil deposition of catalyst, epitaxial III-V heterostructure nanowire growth, and selective etching, as a road toward wafer scale integration and engineering of nanowires with existing silicon technology. Nanostencil lithography is used for deposition of catalyst particles on trench sidewalls and the lateral growth of III-V nanowires is achieved from such catalysts. The selectivity of a bromine-based etch on gallium arsenide segments in gallium phosphide nanowires is examined, using a hydrochloride etch to remove the III-V native oxides. Depending on the etching conditions, a variety of gap topologies and tiplike structures are observed, offering postgrowth engineering of material composition and morphology.
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| 8. |
- Kroepelin, S, et al.
(författare)
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Climate-driven ecosystem succession in the Sahara: The past 6000 years
- 2008
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 320:5877, s. 765-768
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Tidskriftsartikel (refereegranskat)abstract
- Desiccation of the Sahara since the middle Holocene has eradicated all but a few natural archives recording its transition from a "green Sahara" to the present hyperarid desert. Our continuous 6000- year paleoenvironmental reconstruction from northern Chad shows progressive drying of the regional terrestrial ecosystem in response to weakening insolation forcing of the African monsoon and abrupt hydrological change in the local aquatic ecosystem controlled by site- specific thresholds. Strong reductions in tropical trees and then Sahelian grassland cover allowed large- scale dust mobilization from 4300 calendar years before the present ( cal yr B. P.). Today's desert ecosystem and regional wind regime were established around 2700 cal yr B. P. This gradual rather than abrupt termination of the African Humid Period in the eastern Sahara suggests a relatively weak biogeophysical feedback on climate.
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| 9. |
- Triplett, L D, et al.
(författare)
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Silica fluxes and trapping in two contrasting natural impoundments of the upper Mississippi River
- 2008
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Ingår i: Biogeochemistry. - : Springer Science and Business Media LLC. - 1573-515X .- 0168-2563. ; 87:3, s. 217-230
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Tidskriftsartikel (refereegranskat)abstract
- Human activities have altered riverine silica cycling and diminished the supply of silica to the oceans, but few rivers have been intensively monitored to evaluate the magnitude of these changes. In this study we measured dissolved silica (DSi) and amorphous silica (ASi) fluxes into and out of two large, culturally-impacted natural impoundments of the upper Mississippi River, Lakes St. Croix and Pepin, USA. ASi sedimentation rates and sediment-water fluxes of DSi were calculated for each lake, and a mass-balance approach was used to determine in-lake ASi production. ASi from terrestrial phytoliths in the lake sediments was determined to be only partially available to biotic recycling, and in-lake ASi dissolution was small relative to the total silica budgets. The river reaches upstream of the two lakes were found to have abundant DSi, and riverine diatom production was found to contribute significant amounts of ASi to each lake. The average total phosphorus concentration in Lake Pepin is four times that in Lake St. Croix but ASi production in Lake Pepin is only 2.3 times higher than in Lake St. Croix, indicating that diatom growth in Pepin is limited by factors such as turbidity. Lake St. Croix currently traps about 10% of the inflowing total bioavailable silica (TSib = DSi + ASi) while Lake Pepin traps closer to 20% of its inflowing TSib, clearly demonstrating the importance of silica retention in lakes and reservoirs along the land-ocean continuum.
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| 10. |
- Tuominen, Rainer, et al.
(författare)
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The Role of Germline Alterations in the DNA Damage Response Genes BRIP1 and BRCA2 in Melanoma Susceptibility
- 2016
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley-Blackwell. - 1045-2257 .- 1098-2264. ; 55:7, s. 601-611
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Tidskriftsartikel (refereegranskat)abstract
- We applied a targeted sequencing approach to identify germline mutations conferring a moderately to highly increased risk of cutaneous and uveal melanoma. Ninety-two high-risk melanoma patients were screened for inherited variation in 120 melanoma candidate genes. Observed gene variants were filtered based on frequency in reference populations, cosegregation with melanoma in families and predicted functional effect. Several novel or rare genetic variants in genes involved in DNA damage response, cell-cycle regulation and transcriptional control were identified in melanoma patients. Among identified genetic alterations was an extremely rare variant (minor allele frequency of 0.00008) in the BRIP1 gene that was found to cosegregate with the melanoma phenotype. We also found a rare nonsense variant in the BRCA2 gene (rs11571833), previously associated with cancer susceptibility but not with melanoma, which showed weak association with melanoma susceptibility in the Swedish population. Our results add to the growing knowledge about genetic factors associated with melanoma susceptibility and also emphasize the role of DNA damage response as an important factor in melanoma etiology.
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