| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Haycock, Philip C., et al.
(författare)
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Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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| 3. |
- Voight, Benjamin F, et al.
(författare)
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Plasma HDL cholesterol and risk of myocardial infarction : a mendelian randomisation study
- 2012
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 380:9841, s. 572-580
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Tidskriftsartikel (refereegranskat)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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| 4. |
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| 5. |
- Sohler, D, et al.
(författare)
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Maximally Aligned States in the Proton Drip Line Nucleus 106Sb
- 2005
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Ingår i: Nuclear Physics, Section A. - : Elsevier BV. - 0375-9474 .- 1873-1554. ; 753:3-4, s. 251-262
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Tidskriftsartikel (refereegranskat)abstract
- High-spin states in Sb-106 have been investigated in the Fe-54(Ni-58, 1α 1p1n) reaction by in-beam γ-spectroscopic methods using the EUROBALL detector array equipped with charged particle and neutron detectors. On the basis of measured γγ-coincidence relations, angular distributions, and linear polarization ratios a significantly extended level scheme has been constructed up to spin and parity I-π = (19(-)) and E-x ∼ 6.5 MeV. The experimental results are interpreted within the framework of the gdsh shell model using a realistic effective nucleon-nucleon interaction. Candidates for states with fully aligned angular momenta in the π(d(5/2), g(7/2))(1) v (d(5/2), g(7/2))(5) valence space are identified at 4338 and 5203 keV, as well as in the π(d(5/2), g(7/2))(1) V(d(5/2), g(7/2))(4)h(11/2)(1) space at 6087, 6573 and 6783 keV.
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| 6. |
- Callesen, Michael Thude, et al.
(författare)
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Phthalate metabolites in urine and asthma, allergic rhinoconjunctivitis and atopic dermatitis in preschool children
- 2014
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Ingår i: International journal of hygiene and environmental health. - : Elsevier BV. - 1438-4639 .- 1618-131X. ; 217:6, s. 645-652
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Tidskriftsartikel (refereegranskat)abstract
- Phthalate esters are among the most ubiquitous of indoor pollutants and have been associated with various adverse health effects. In the present study we assessed the cross-sectional association between eight different phthalate metabolites in urine and allergic disease in young children. As part of the Danish Indoor Environment and Children's Health study, urine samples were collected from 440 children aged 3-5 years, of whom 222 were healthy controls, 68 were clinically diagnosed with asthma, 76 with rhinoconjunctivitis and 81 with atopic dermatitis (disease subgroups are not mutually exclusive; some children had more than one disease). There were no statistically significant differences in the urine concentrations of phthalate metabolites between cases and healthy controls with the exception of MnBP and MECPP, which were higher in healthy controls compared with the asthma case group. In the crude analysis MnBP and MiBP were negatively associated with asthma. In the analysis adjusted for multiple factors, only a weak positive association between MEP in urine and atopic dermatitis was found; there were no positive associations between any phthalate metabolites in urine and either asthma or rhinoconjunctivitis. These findings appear to contradict earlier studies. Differences may be due to higher exposures to certain phthalates (e.g., BBzP) via non-dietary pathways in earlier studies, phthalates serving as surrogates for an agent associated with asthma (e.g., PVC flooring) in previous studies but not the present study or altered cleaning habits and the use of "allergy friendly" products by parents of children with allergic disease in the current study in contrast to studies conducted earlier.
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| 7. |
- Otero, Jaime, et al.
(författare)
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Basin-scale phenology and effects of climate variability on global timing of initial seaward migration of Atlantic salmon (Salmo salar)
- 2014
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 20:1, s. 61-75
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Tidskriftsartikel (refereegranskat)abstract
- Migrations between different habitats are key events in the lives of many organisms. Such movements involve annually recurring travel over long distances usually triggered by seasonal changes in the environment. Often, the migration is associated with travel to or from reproduction areas to regions of growth. Young anadromous Atlantic salmon (Salmo salar) emigrate from freshwater nursery areas during spring and early summer to feed and grow in the North Atlantic Ocean. The transition from the freshwater ('parr') stage to the migratory stage where they descend streams and enter salt water ('smolt') is characterized by morphological, physiological and behavioural changes where the timing of this parr-smolt transition is cued by photoperiod and water temperature. Environmental conditions in the freshwater habitat control the downstream migration and contribute to within- and among-river variation in migratory timing. Moreover, the timing of the freshwater emigration has likely evolved to meet environmental conditions in the ocean as these affect growth and survival of the post-smolts. Using generalized additive mixed-effects modelling, we analysed spatio-temporal variations in the dates of downstream smolt migration in 67 rivers throughout the North Atlantic during the last five decades and found that migrations were earlier in populations in the east than the west. After accounting for this spatial effect, the initiation of the downstream migration among rivers was positively associated with freshwater temperatures, up to about 10 °C and levelling off at higher values, and with sea-surface temperatures. Earlier migration occurred when river discharge levels were low but increasing. On average, the initiation of the smolt seaward migration has occurred 2.5 days earlier per decade throughout the basin of the North Atlantic. This shift in phenology matches changes in air, river, and ocean temperatures, suggesting that Atlantic salmon emigration is responding to the current global climate changes.
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| 8. |
- Schiffman, E, et al.
(författare)
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Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for Clinical and Research Applications : recommendations of the International RDC/TMD Consortium Network* and Orofacial Pain Special Interest Group
- 2014
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Ingår i: Journal of oral & facial pain and headache. - : Quintessence. - 2333-0384 .- 2333-0376. ; 28:1, s. 6-27
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The original Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis I diagnostic algorithms have been demonstrated to be reliable. However, the Validation Project determined that the RDC/TMD Axis I validity was below the target sensitivity of ≥ 0.70 and specificity of ≥ 0.95. Consequently, these empirical results supported the development of revised RDC/TMD Axis I diagnostic algorithms that were subsequently demonstrated to be valid for the most common pain-related TMD and for one temporomandibular joint (TMJ) intra-articular disorder. The original RDC/TMD Axis II instruments were shown to be both reliable and valid. Working from these findings and revisions, two international consensus workshops were convened, from which recommendations were obtained for the finalization of new Axis I diagnostic algorithms and new Axis II instruments. METHODS: Through a series of workshops and symposia, a panel of clinical and basic science pain experts modified the revised RDC/TMD Axis I algorithms by using comprehensive searches of published TMD diagnostic literature followed by review and consensus via a formal structured process. The panel's recommendations for further revision of the Axis I diagnostic algorithms were assessed for validity by using the Validation Project's data set, and for reliability by using newly collected data from the ongoing TMJ Impact Project-the follow-up study to the Validation Project. New Axis II instruments were identified through a comprehensive search of the literature providing valid instruments that, relative to the RDC/TMD, are shorter in length, are available in the public domain, and currently are being used in medical settings. RESULTS: The newly recommended Diagnostic Criteria for TMD (DC/TMD) Axis I protocol includes both a valid screener for detecting any pain-related TMD as well as valid diagnostic criteria for differentiating the most common pain-related TMD (sensitivity ≥ 0.86, specificity ≥ 0.98) and for one intra-articular disorder (sensitivity of 0.80 and specificity of 0.97). Diagnostic criteria for other common intra-articular disorders lack adequate validity for clinical diagnoses but can be used for screening purposes. Inter-examiner reliability for the clinical assessment associated with the validated DC/TMD criteria for pain-related TMD is excellent (kappa ≥ 0.85). Finally, a comprehensive classification system that includes both the common and less common TMD is also presented. The Axis II protocol retains selected original RDC/TMD screening instruments augmented with new instruments to assess jaw function as well as behavioral and additional psychosocial factors. The Axis II protocol is divided into screening and comprehensive self report instrument sets. The screening instruments' 41 questions assess pain intensity, pain-related disability, psychological distress, jaw functional limitations, and parafunctional behaviors, and a pain drawing is used to assess locations of pain. The comprehensive instruments, composed of 81 questions, assess in further detail jaw functional limitations and psychological distress as well as additional constructs of anxiety and presence of comorbid pain conditions. CONCLUSION: The recommended evidence-based new DC/TMD protocol is appropriate for use in both clinical and research settings. More comprehensive instruments augment short and simple screening instruments for Axis I and Axis II. These validated instruments allow for identification of patients with a range of simple to complex TMD presentations
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| 9. |
- Brautigam, Lars, et al.
(författare)
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Glutaredoxin regulates vascular development by reversible glutathionylation of sirtuin 1
- 2013
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:50, s. 20057-20062
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Tidskriftsartikel (refereegranskat)abstract
- Embryonic development depends on complex and precisely orchestrated signaling pathways including specific reduction/oxidation cascades. Oxidoreductases of the thioredoxin family are key players conveying redox signals through reversible posttranslational modifications of protein thiols. The importance of this protein family during embryogenesis has recently been exemplified for glutaredoxin 2, a vertebrate-specific glutathione-disulfide oxidoreductase with a critical role for embryonic brain development. Here, we discovered an essential function of glutaredoxin 2 during vascular development. Confocal microscopy and time-lapse studies based on two-photon microscopy revealed that morpholino-based knockdown of glutaredoxin 2 in zebrafish, a model organism to study vertebrate embryogenesis, resulted in a delayed and disordered blood vessel network. We were able to show that formation of a functional vascular system requires glutaredoxin 2-dependent reversible S-glutathionylation of the NAD(+)-dependent protein deacetylase sirtuin 1. Using mass spectrometry, we identified a cysteine residue in the conserved catalytic region of sirtuin 1 as target for glutaredoxin 2-specific deglutathionylation. Thereby, glutaredoxin 2-mediated redox regulation controls enzymatic activity of sirtuin 1, a mechanism we found to be conserved between zebrafish and humans. These results link S-glutathionylation to vertebrate development and successful embryonic angiogenesis.
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| 10. |
- Finstad, Anders G., et al.
(författare)
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Competitive exclusion along climate gradients : energy efficiency influences the distribution of two salmonid fishes
- 2011
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 17:4, s. 1703-1711
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Tidskriftsartikel (refereegranskat)abstract
- We tested the importance of thermal adaptations and energy efficiency in relation to the geographical distribution of two competing freshwater salmonid fish species. Presence–absence data for Arctic char and brown trout were obtained from 1502 Norwegian lakes embracing both temperature and productivity gradients. The distributions were contrasted with laboratory-derived temperature scaling models for food consumption, growth and energy efficiency. Thermal performances of the two species were almost identical. However, Arctic char exhibited double the growth efficiency (per unit of food) and appear to have out-competed brown trout from cold, low-productivity lakes, perhaps by scramble competition. Brown trout, for which previous reports have shown to be aggressive and dominant, have likely excluded the more energy-efficient Arctic char from relatively warm, productive lakes, perhaps by contest competition. Competitive interaction changing in outcome with lake productivity, rather than thermal performance, is likely a major determinant of the range distribution of the two species. Our study highlights the need for more focus on choice of relevant ecophysiological traits in ecological climate impact studies and species distribution modelling.
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