| 1. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 2. |
- Lind, Lars, et al.
(författare)
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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
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Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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| 3. |
- Armbrecht, Gabriele, et al.
(författare)
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Degenerative inter-vertebral disc disease osteochondrosis intervertebralis in Europe : Prevalence, geographic variation and radiological correlates in men and women aged 50 and over
- 2017
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 56:7, s. 1189-1199
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To assess the prevalences across Europe of radiological indices of degenerative inter-vertebral disc disease (DDD); and to quantify their associations with, age, sex, physical anthropometry, areal BMD (aBMD) and change in aBMD with time. Methods. In the population-based European Prospective Osteoporosis Study, 27 age-stratified samples of men and women from across the continent aged 50+ years had standardized lateral radiographs of the lumbar and thoracic spine to evaluate the severity of DDD, using the Kellgren-Lawrence (KL) scale. Measurements of anterior, mid-body and posterior vertebral heights on all assessed vertebrae from T4 to L4 were used to generate indices of end-plate curvature. Results. Images from 10 132 participants (56% female, mean age 63.9 years) passed quality checks. Overall, 47% of men and women had DDD grade 3 or more in the lumbar spine and 36% in both thoracic and lumbar spine. Risk ratios for DDD grades 3 and 4, adjusted for age and anthropometric determinants, varied across a three-fold range between centres, yet prevalences were highly correlated in men and women. DDD was associated with flattened, non-ovoid inter-vertebral disc spaces. KL grade 4 and loss of inter-vertebral disc space were associated with higher spine aBMD. Conclusion. KL grades 3 and 4 are often used clinically to categorize radiological DDD. Highly variable European prevalences of radiologically defined DDD grades 3+ along with the large effects of age may have growing and geographically unequal health and economic impacts as the population ages. These data encourage further studies of potential genetic and environmental causes.
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| 4. |
- Armbrecht, G., et al.
(författare)
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Vertebral Scheuermann's disease in Europe: prevalence, geographic variation and radiological correlates in men and women aged 50 and over
- 2015
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 26:10, s. 2509-2519
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Tidskriftsartikel (refereegranskat)abstract
- The Summary In 27 centres across Europe, the prevalence of deforming spinal Scheuermann's disease in age-stratified population-based samples of over 10,000 men and women aged 50+ averaged 8 % in each sex, but was highly variable between centres. Low DXA BMD was un-associated with Scheuermann's, helping the differential diagnosis from osteoporosis. Introduction This study aims to assess the prevalence of Scheuermann's disease of the spine across Europe in men and women over 50 years of age, to quantitate its association with bone mineral density (BMD) and to assess its role as a confounder for the radiographic diagnosis of osteoporotic fracture. Methods In 27 centres participating in the population-based European Vertebral Osteoporosis Study (EVOS), standardised lateral radiographs of the lumbar and of the thoracic spine from T4 to L4 were assessed in all those of adequate quality. The presence of Scheuermann's disease, a confounder for prevalent fracture in later life, was defined by the presence of at least one Schmorl's node or irregular endplate together with kyphosis (sagittal Cobb angle > 40A degrees between T4 and T12) or a wedged-shaped vertebral body. Alternatively, the (rare) Edgren-Vaino sign was taken as diagnostic. The 6-point-per-vertebral-body (13 vertebrae) method was used to assess osteoporotic vertebral shape and fracture caseness. DXA BMD of the L2-L4 and femoral neck regions was measured in subsets. We also assessed the presence of Scheuermann's by alternative published algorithms when these used the radiographic signs we assessed. Results Vertebral radiographic images from 4486 men and 5655 women passed all quality checks. Prevalence of Scheuermann's varied considerably between centres, and based on random effect modelling, the overall European prevalence using our method was 8 % with no significant difference between sexes. The highest prevalences were seen in Germany, Sweden, the UK and France and low prevalences were seen in Hungary, Poland and Slovakia. Centre-level prevalences in men and women were highly correlated. Scheuermann's was not associated with BMD of the spine or hip. Conclusions Since most of the variation in population impact of Scheuermann's was unaccounted for by the radiological and anthropometric data, the search for new genetic and environmental determinants of this disease is encouraged.
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| 5. |
- Bixby, H., et al.
(författare)
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Rising rural body-mass index is the main driver of the global obesity epidemic in adults
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
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Tidskriftsartikel (refereegranskat)abstract
- Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
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| 6. |
- Brennan, S. J., et al.
(författare)
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Photometric and spectroscopic evolution of the interacting transient AT 2016jbu(Gaia16cfr)
- 2022
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 513:4, s. 5642-5665
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Tidskriftsartikel (refereegranskat)abstract
- We present the results from a high-cadence, multiwavelength observation campaign of AT 2016jbu (aka Gaia16cfr), an interacting transient. This data set complements the current literature by adding higher cadence as well as extended coverage of the light-curve evolution and late-time spectroscopic evolution. Photometric coverage reveals that AT 2016jbu underwent significant photometric variability followed by two luminous events, the latter of which reached an absolute magnitude of MV ∼ −18.5 mag. This is similar to the transient SN 2009ip whose nature is still debated. Spectra are dominated by narrow emission lines and show a blue continuum during the peak of the second event. AT 2016jbu shows signatures of a complex, non-homogeneous circumstellar material (CSM). We see slowly evolving asymmetric hydrogen line profiles, with velocities of 500 km s−1 seen in narrow emission features from a slow-moving CSM, and up to 10 000 km s−1 seen in broad absorption from some high-velocity material. Late-time spectra (∼+1 yr) show a lack of forbidden emission lines expected from a core-collapse supernova and are dominated by strong emission from H, He I, and Ca II. Strong asymmetric emission features, a bumpy light curve, and continually evolving spectra suggest an inhibit nebular phase. We compare the evolution of H α among SN 2009ip-like transients and find possible evidence for orientation angle effects. The light-curve evolution of AT 2016jbu suggests similar, but not identical, circumstellar environments to other SN 2009ip-like transients.
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| 7. |
- Brennan, S. J., et al.
(författare)
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Progenitor, environment, and modelling of the interacting transient AT 2016jbu (Gaia16cfr)
- 2022
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 513:4, s. 5666-5685
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Tidskriftsartikel (refereegranskat)abstract
- We present the bolometric light curve, identification and analysis of the progenitor candidate, and preliminary modelling of AT 2016jbu (Gaia16cfr). We find a progenitor consistent with a ∼ 22–25 M⊙ yellow hypergiant surrounded by a dusty circumstellar shell, in agreement with what has been previously reported. We see evidence for significant photometric variability in the progenitor, as well as strong Hα emission consistent with pre-existing circumstellar material. The age of the environment, as well as the resolved stellar population surrounding AT 2016jbu, supports a progenitor age of >10 Myr, consistent with a progenitor mass of ∼22 M⊙. A joint analysis of the velocity evolution of AT 2016jbu and the photospheric radius inferred from the bolometric light curve shows the transient is consistent with two successive outbursts/explosions. The first outburst ejected material with velocity ∼650 km s−1, while the second, more energetic event ejected material at ∼4500 km s−1. Whether the latter is the core collapse of the progenitor remains uncertain. We place a limit on the ejected 56Ni mass of <0.016 M⊙. Using the Binary Population And Spectral Synthesis (BPASS) code, we explore a wide range of possible progenitor systems and find that the majority of these are in binaries, some of which are undergoing mass transfer or common-envelope evolution immediately prior to explosion. Finally, we use the SuperNova Explosion Code (SNEC) to demonstrate that the low-energy explosions within some of these binary systems, together with sufficient circumstellar material, can reproduce the overall morphology of the light curve of AT 2016jbu.
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| 8. |
- Camacho, E. M., et al.
(författare)
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Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study
- 2013
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 168:3, s. 445-455
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Health and lifestyle factors are associated with variations in serum testosterone levels in ageing men. However, it remains unclear how age-related changes in testosterone may be attenuated by lifestyle modifications. The objective was to investigate the longitudinal relationships between changes in health and lifestyle factors with changes in hormones of the reproductive endocrine axis in ageing men. Design: A longitudinal survey of 2736 community-dwelling men aged 40-79 years at baseline recruited from eight centres across Europe. Follow-up assessment occurred mean (+/- S.D.) 4.4 +/- 0.3 years later. Results: Paired testosterone results were available for 2395 men. Mean (+/- S.D.) annualised hormone changes were as follows: testosterone -0.1 +/- 0.95 nmol/l; free testosterone (FT) -3.83 +/- 16.8 pmol/l; sex hormone-binding globulin (SHBG) 0.56 +/- 2.5 nmol/l and LH 0.08 +/- 0.57 U/l. Weight loss was associated with a proportional increase, and weight gain a proportional decrease, in testosterone and SHBG. FT showed a curvilinear relationship to weight change; only those who gained or lost >= 15% of weight showed a significant change (in the same direction as testosterone). Smoking cessation was associated with a greater decline in testosterone than being a non-smoker, which was unrelated to weight change. Changes in number of comorbid conditions or physical activity were not associated with significant alterations in hypothalamic-pituitary-testicular (HPT) axis function. Conclusions: Body weight and lifestyle factors influence HPT axis function in ageing. Weight loss was associated with a rise, and weight gain a fall, in testosterone, FT and SHBG. Weight management appears to be important in maintaining circulating testosterone in ageing men, and obesity-associated changes in HPT axis hormones are reversible following weight reduction. European Journal of Endocrinology 168 445-455
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| 9. |
- Condurache, C. I., et al.
(författare)
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Screening for high hip fracture risk does not impact on falls risk: a post hoc analysis from the SCOOP study
- 2020
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 31:3, s. 457-464
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Tidskriftsartikel (refereegranskat)abstract
- A reduction in hip fracture incidence following population screening might reflect the effectiveness of anti-osteoporosis therapy, behaviour change to reduce falls, or both. This post hoc analysis demonstrates that identifying high hip fracture risk by FRAX was not associated with any alteration in falls risk. Introduction To investigate whether effectiveness of an osteoporosis screening programme to reduce hip fractures was mediated by modification of falls risk in the screening arm. Methods The SCOOP study recruited 12,483 women aged 70-85 years, individually randomised to a control (n = 6250) or screening (n = 6233) arm; in the latter, osteoporosis treatment was recommended to women at high risk of hip fracture, while the control arm received usual care. Falls were captured by self-reported questionnaire. We determined the influence of baseline risk factors on future falls, and then examined for differences in falls risk between the randomisation groups, particularly in those at high fracture risk. Results Women sustaining one or more falls were slightly older at baseline than those remaining falls free during follow-up (mean difference 0.70 years, 95%CI 0.55-0.85, p < 0.001). A higher FRAX 10-year probability of hip fracture was associated with increased likelihood of falling, with fall risk increasing by 1-2% for every 1% increase in hip fracture probability. However, falls risk factors were well balanced between the study arms and, importantly, there was no evidence of a difference in falls occurrence. In particular, there was no evidence of interaction (p = 0.18) between baseline FRAX hip fracture probabilities and falls risk in the two arms, consistent with no impact of screening on falls in women informed to be at high risk of hip fracture. Conclusion Effectiveness of screening for high FRAX hip fracture probability to reduce hip fracture risk was not mediated by a reduction in falls.
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| 10. |
- Corona, G, et al.
(författare)
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Thyroid hormones and male sexual function.
- 2012
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Ingår i: International Journal of Andrology. - : Wiley. - 1365-2605 .- 0105-6263. ; 35:5, s. 668-679
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Tidskriftsartikel (refereegranskat)abstract
- The role of thyroid hormones in the control of erectile functioning has been only superficially investigated. The aim of the present study was to investigate the association between thyroid and erectile function in two different cohorts of subjects. The first one derives from the European Male Ageing Study (EMAS study), a multicentre survey performed on a sample of 3369 community-dwelling men aged 40-79 years (mean 60 ± 11 years). The second cohort is a consecutive series of 3203 heterosexual male patients (mean age 51.8 ± 13.0 years) attending our Andrology and Sexual Medicine Outpatient Clinic for sexual dysfunction at the University of Florence (UNIFI study). In the EMAS study all subjects were tested for thyroid-stimulating hormone (TSH) and free thyroxine (FT4). Similarly, TSH levels were checked in all patients in the UNIFI study, while FT4 only when TSH resulted outside the reference range. Overt primary hyperthyroidism (reduced TSH and elevated FT4, according to the reference range) was found in 0.3 and 0.2% of EMAS and UNIFI study respectively. In both study cohorts, suppressed TSH levels were associated with erectile dysfunction (ED). Overt hyperthyroidism was associated with an increased risk of severe erectile dysfunction (ED, hazard ratio = 14 and 16 in the EMAS and UNIFI study, respectively; both p < 0.05), after adjusting for confounding factors. These associations were confirmed in nested case-control analyses, comparing subjects with overt hyperthyroidism to age, BMI, smoking status and testosterone-matched controls. Conversely, no association between primary hypothyroidism and ED was observed. In conclusion, erectile function should be evaluated in all individuals with hyperthyroidism. Conversely, assessment of thyroid function cannot be recommended as routine practice in all ED patients.
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