| 21. |
- Sandblom, Gabriel, et al.
(author)
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Prostate Cancer Registration in Four Swedish Regions 1996 : Differences in Incidence, Age Structure and Management
- 1999
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In: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 33:5, s. 306-311
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Journal article (peer-reviewed)abstract
- Introduction: In 1996 registration of prostate cancer in four of the six Swedish regions was started to facilitate evaluation of geographical variations in incidence and treatment.Material and methods: For all cases of prostate cancer, personal identification number, tumour stage, tumour grade and primary treatment were registered.Results: In the four regions covered by the register, 3541 cases of prostate cancer were registered. Altogether there were 5795 cases of prostate cancer diagnosed in Sweden the same year. The age-standardized incidence varied from 89/100 000 to 169/100 000 among counties. The proportion of localized tumours correlated positively to the incidence (p < 0.05) and negatively to mean age at diagnosis (p < 0.01). There was also a significant positive correlation between the proportion of localized tumours and the percentage of patients given curative treatment. All registered variables showed large geographical variations, especially concerning percentage of T1c tumours, treatment of localized tumours and choice of palliative treatment.Conclusion: Diagnostic activity varied considerably among counties, resulting in large variation in age-standardized incidence. High incidence is associated with a larger proportion of localized tumours, which, in turn, is associated with early age at diagnosis. In counties where a policy of detecting tumours early is practised, curative treatment is also given more often. Treatment of localized tumours and preference for palliative treatment seem to depend on local traditions. The lack of cytological and histopathological standards makes geographical comparisons based on tumour grade impossible.
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| 22. |
- Sonderby, Ida E., et al.
(author)
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Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
- 2020
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In: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
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Journal article (peer-reviewed)abstract
- Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
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| 23. |
- Speliotes, Elizabeth K., et al.
(author)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Journal article (peer-reviewed)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 24. |
- Stattin, Pär, et al.
(author)
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Outcomes in localized prostate cancer: National Prostate Cancer Register of Sweden follow-up study.
- 2010
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 102:13, s. 950-8
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Journal article (peer-reviewed)abstract
- Treatment for localized prostate cancer remains controversial. To our knowledge, there are no outcome studies from contemporary population-based cohorts that include data on stage, Gleason score, and serum levels of prostate-specific antigen (PSA).
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| 25. |
- Stattin, Pär, et al.
(author)
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Surveillance and deferred treatment for localized prostate cancer : Population based study in the National Prostate Cancer Register of Sweden
- 2008
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In: Journal of Urology. - Baltimore : Williams and Wilkins. - 0022-5347 .- 1527-3792. ; 180:6, s. 2423-2430
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Journal article (peer-reviewed)abstract
- PURPOSE: To what extent active surveillance and deferred treatment for localized risk prostate cancer are used is unclear. We assessed the use of surveillance and of deferred treatment in a population based, nationwide cohort in Sweden.MATERIALS AND METHODS: In the National Prostate Cancer Register of Sweden, with a 98% coverage vs the compulsory Swedish Cancer Registry, we identified 8,304 incident cases of prostate cancer in 1997 to 2002 with age younger than 70 years, clinical local stage T1 or 2, N0 or Nx, M0 or Mx and serum prostate specific antigen less than 20 ng/ml. Data were extracted from medical charts for 7,782 of these men (94%) at a median of 4 years after diagnosis.RESULTS: Primary treatment was surveillance for 2,065 men (26%), radical prostatectomy for 3,722 (48%), radiotherapy for 1,632 (21%) and hormonal treatment for 363 (5%). Men on surveillance had lower local tumor stage, grade and prostate specific antigen, and were older than those who received active primary treatment (p <0.001). After a median surveillance of 4 years 711 men (34%) on surveillance had received deferred treatment, which was radical prostatectomy for 279 (39%), radiotherapy for 212 (30%) and hormonal treatment for 220 (30%).CONCLUSIONS: Surveillance was a common treatment for patients younger than 70 years with localized prostate cancer in Sweden in 1997 to 2002, 26% of men with localized prostate cancer started surveillance and after a median followup of 4 years, 66% of these men remained on surveillance.
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| 26. |
- Sønderby, Ida E., et al.
(author)
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1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
- 2021
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In: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 11:1
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Journal article (peer-reviewed)abstract
- Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
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| 27. |
- van der Meer, Dennis, et al.
(author)
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Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition
- 2020
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In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 77:4, s. 420-430
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Journal article (peer-reviewed)abstract
- Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
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| 28. |
- Anderbro, Therese, et al.
(author)
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Fear of hypoglycemia : relationship to hypoglycemic risk and psychological factors
- 2014
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In: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233.
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The major aims of this study were to examine (1) the association between fear of hypoglycemia (FOH) in adults with type 1 diabetes with demographic, psychological (anxiety and depression), and disease-specific clinical factors (hypoglycemia history and unawareness, A1c), including severe hypoglycemia (SH), and (2) differences in patient subgroups categorized by level of FOH and risk of SH.RESEARCH DESIGN AND METHODS: Questionnaires were mailed to 764 patients with type 1 diabetes including the Swedish translation of the Hypoglycemia Fear Survey (HFS) and other psychological measures including the Perceived Stress Scale, Hospital Anxiety and Depression Scale, Anxiety Sensitivity Index, Social Phobia Scale, and Fear of Complications Scale. A questionnaire to assess hypoglycemia history was also included and A1c measures were obtained from medical records. Statistical analyses included univariate approaches, multiple stepwise linear regressions, Chi-square t tests, and ANOVAs.RESULTS: Regressions showed that several clinical factors (SH history, frequency of nocturnal hypoglycemia, self-monitoring) were significantly associated with FOH but R (2) increased from 16.25 to 39.2 % when anxiety measures were added to the model. When patients were categorized by level of FOH (low, high) and SH risk (low, high), subgroups showed significant differences in non-diabetes-related anxiety, hypoglycemia history, self-monitoring, and glycemic control.CONCLUSION: There is a strong link between FOH and non-diabetes-related anxiety, as well as hypoglycemia history. Comparison of patient subgroups categorized according to level of FOH and SH risk demonstrated the complexity of FOH and identified important differences in psychological and clinical variables, which have implications for clinical interventions.
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| 29. |
- Bill-Axelson, Anna, et al.
(author)
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Long-term Distress After Radical Prostatectomy Versus Watchful Waiting in Prostate Cancer : A Longitudinal Study from the Scandinavian Prostate Cancer Group-4 Randomized Clinical Trial
- 2013
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In: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 64:6, s. 920-928
-
Journal article (peer-reviewed)abstract
- BACKGROUND:Studies enumerating the dynamics of physical and emotional symptoms following prostate cancer (PCa) treatment are needed to guide therapeutic strategy. Yet, overcoming patient selection forces is a formidable challenge for observational studies comparing treatment groups.OBJECTIVE:To compare patterns of symptom burden and distress in men with localized PCa randomized to radical prostatectomy (RP) or watchful waiting (WW) and followed up longitudinally.DESIGN, SETTING, AND PARTICIPANTS:The three largest, Swedish, randomization centers for the Scandinavian Prostate Cancer Group-4 trial conducted a longitudinal study to assess symptoms and distress from several psychological and physical domains by mailed questionnaire every 6 mo for 2 yr and then yearly through 8 yr of follow-up.INTERVENTION:RP compared with WW.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:A questionnaire was mailed at baseline and then repeatedly during follow-up with questions concerning physical and mental symptoms. Each analysis of quality of life was based on a dichotomization of the outcome (yes vs no) studied in a binomial response, generalized linear mixed model.RESULTS AND LIMITATIONS:Of 347 randomized men, 272 completed at least five questionnaires during an 8-yr follow-up period. Almost all men reported that PCa negatively influenced daily activities and relationships. Health-related distress, worry, feeling low, and insomnia were consistently reported by approximately 30-40% in both groups. Men in the RP group consistently reported more leakage, impaired erection and libido, and fewer obstructive voiding symptoms. For men in the WW group, distress related to erectile symptoms increased gradually over time. Symptom burden and distress at baseline was predictive of long-term outlook.CONCLUSIONS:Cancer negatively influenced daily activities among almost all men in both treatment groups; health-related distress was common. Trade-offs exist between physiologic symptoms, highlighting the importance of tailored treatment decision-making. Men who are likely to experience profound long-term distress can be identified early in disease management.
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| 30. |
- Bohgard, Mats, et al.
(author)
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Nu krävs satsning på forskning för ett hållbart arbetsliv
- 2021
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In: Dagens Medicin. - 1104-7488.
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Journal article (pop. science, debate, etc.)abstract
- Debatt: Vi vill att forskningsråden skapar tvärvetenskapliga regionala forskningscentrum för arbetslivsforskning, som är internationellt konkurrenskraftiga och ger nationellt och regionalt kunskapsstöd. Dessa centrum ska ge kunskaper för både befintliga och framtida utmaningar. Stora vinster kan fås om forskning om folkhälsa och yttre miljö samordnas i centrumen. Arbetslivet är grunden för hälsa, välstånd och ett välfungerande samhälle. För att säkra att framtidens arbetsliv bidrar till hälsa och välstånd behövs både kunskap om hur det ska utformas och en uthållig infrastruktur för forskning. Tyvärr saknas detta. Gammal kunskap faller i glömska.
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