1. |
- Sampson, Joshua N., et al.
(author)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Journal article (peer-reviewed)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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2. |
- Emaus, Marleen J., et al.
(author)
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Weight change in middle adulthood and breast cancer risk in the EPIC-PANACEA study
- 2014
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:12, s. 2887-2899
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Journal article (peer-reviewed)abstract
- Long-term weight gain (i.e., weight gain since age 20) has been related to higher risk of postmenopausal breast cancer, but a lower risk of premenopausal breast cancer. The effect of weight change in middle adulthood is unclear. We investigated the association between weight change in middle adulthood (i.e., women aged 40-50 years) and the risk of breast cancer before and after the age of 50. We included female participants of the European Prospective Investigation into Cancer and Nutrition cohort, with information on anthropometric measures at recruitment and after a median follow-up of 4.3 years. Annual weight change was categorized using quintiles taking quintile 2 and 3 as the reference category (-0.44 to 0.36 kg/year). Multivariable Cox proportional hazards regression analysis was used to examine the association. 205,723 women were included and 4,663 incident breast cancer cases were diagnosed during a median follow-up of 7.5 years (from second weight assessment onward). High weight gain (Q5: 0.83-4.98 kg/year) was related to a slightly, but significantly higher breast cancer risk (HRQ5_versus_Q2/3: 1.09, 95% CI: 1.01-1.18). The association was more pronounced for breast cancer diagnosed before or at age 50 (HRQ5_versus_Q2/3: 1.37, 95% CI: 1.02-1.85). Weight loss was not associated with breast cancer risk. There was no evidence for heterogeneity by hormone receptor status. In conclusion, high weight gain in middle adulthood increases the risk of breast cancer. The association seems to be more pronounced for breast cancer diagnosed before or at age 50. Our results illustrate the importance of avoiding weight gain in middle adulthood.
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3. |
- McKenzie, Fiona, et al.
(author)
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Healthy lifestyle and risk of breast cancer among postmenopausal women in the European Prospective Investigation into Cancer and Nutrition cohort study
- 2015
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:11, s. 2640-2648
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Journal article (peer-reviewed)abstract
- Breast cancer is the most common cancer among women and prevention strategies are needed to reduce incidence worldwide. A healthy lifestyle index score (HLIS) was generated to investigate the joint effect of modifiable lifestyle factors on postmenopausal breast cancer risk. The study included 242,918 postmenopausal women from the multinational European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, with detailed information on diet and lifestyle assessed at baseline. The HLIS was constructed from five factors (diet, physical activity, smoking, alcohol consumption and anthropometry) by assigning scores of 0-4 to categories of each component, for which higher values indicate healthier behaviours. Hazard ratios (HR) were estimated by Cox proportional regression models. During 10.9 years of median follow-up, 7,756 incident breast cancer cases were identified. There was a 3% lower risk of breast cancer per point increase of the HLIS. Breast cancer risk was inversely associated with a high HLIS when fourth versus second (reference) categories were compared [adjusted HR=0.74; 95% confidence interval (CI): 0.66-0.83]. The fourth versus the second category of the HLIS was associated with a lower risk for hormone receptor double positive (adjusted HR=0.81, 95% CI: 0.67-0.98) and hormone receptor double negative breast cancer (adjusted HR=0.60, 95% CI: 0.40-0.90). Findings suggest having a high score on an index of combined healthy behaviours reduces the risk of developing breast cancer among postmenopausal women. Programmes which engage women in long term health behaviours should be supported. What's new? How much does behavior really affect cancer risk? These authors set out to measure just that. First, they created a Healthy Lifestyle Index, which quantified five modifiable behaviors, such as smoking and physical activity. Then, using data from the European Prospective Investigation into Cancer and Nutrition (EPIC), they assigned each participant a score between 0 and 4 on each of the behaviors. It turned out that with each point added to a person's Healthy Lifestyle Index score, breast cancer risk fell by 3%, suggesting that public programs to help women maintain these behaviors could be worthwhile for cancer prevention.
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4. |
- Steindorf, Karen, et al.
(author)
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Physical activity and risk of breast cancer overall and by hormone receptor status : The European prospective investigation into cancer and nutrition
- 2013
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 132:7, s. 1667-1678
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Journal article (peer-reviewed)abstract
- Physical activity is associated with reduced risks of invasive breast cancer. However, whether this holds true for breast cancer subtypes defined by the estrogen receptor (ER) and the progesterone receptor (PR) status is controversial. The study included 257,805 women from the multinational EPIC-cohort study with detailed information on occupational, recreational and household physical activity and important cofactors assessed at baseline. During 11.6 years of median follow-up, 8,034 incident invasive breast cancer cases were identified. Data on ER, PR and combined ER/PR expression were available for 6,007 (67.6%), 4,814 (54.2%) and 4,798 (53.9%) cases, respectively. Adjusted hazard ratios (HR) were estimated by proportional hazards models. Breast cancer risk was inversely associated with moderate and high levels of total physical activity (HR = 0.92, 95% confidence interval (CI): 0.860.99, HR = 0.87, 95%-CI: 0.790.97, respectively; p-trend = 0.002), compared to the lowest quartile. Among women diagnosed with breast cancer after age 50, the largest risk reduction was found with highest activity (HR = 0.86, 95%-CI: 0.770.97), whereas for cancers diagnosed before age 50 strongest associations were found for moderate total physical activity (HR = 0.78, 95%-CI: 0.640.94). Analyses by hormone receptor status suggested differential associations for total physical activity (p-heterogeneity = 0.04), with a somewhat stronger inverse relationship for ER+/PR+ breast tumors, primarily driven by PR+ tumors (p-heterogeneity < 0.01). Household physical activity was inversely associated with ER/PR tumors. The results of this largest prospective study on the protective effects of physical activity indicate that moderate and high physical activity are associated with modest decreased breast cancer risk. Heterogeneities by receptor status indicate hormone-related mechanisms.
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5. |
- Allione, Alessandra, et al.
(author)
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Blood cell DNA methylation biomarkers in preclinical malignant pleural mesothelioma : the EPIC prospective cohort
- 2023
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In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 152:4, s. 725-737
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Journal article (peer-reviewed)abstract
- Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer mainly caused by asbestos exposure. Specific and sensitive noninvasive biomarkers may facilitate and enhance screening programs for the early detection of cancer. We investigated DNA methylation (DNAm) profiles in MPM prediagnostic blood samples in a case-control study nested in the European Prospective Investigation into Cancer and nutrition (EPIC) cohort, aiming to characterise DNAm biomarkers associated with MPM. From the EPIC cohort, we included samples from 135 participants who developed MPM during 20 years of follow-up and from 135 matched, cancer-free, controls. For the discovery phase we selected EPIC participants who developed MPM within 5 years from enrolment (n = 36) with matched controls. We identified nine differentially methylated CpGs, selected by 10-fold cross-validation and correlation analyses: cg25755428 (MRI1), cg20389709 (KLF11), cg23870316, cg13862711 (LHX6), cg06417478 (HOOK2), cg00667948, cg01879420 (AMD1), cg25317025 (RPL17) and cg06205333 (RAP1A). Receiver operating characteristic (ROC) analysis showed that the model including baseline characteristics (age, sex and PC1wbc) along with the nine MPM-related CpGs has a better predictive value for MPM occurrence than the baseline model alone, maintaining some performance also at more than 5 years before diagnosis (area under the curve [AUC] < 5 years = 0.89; AUC 5-10 years = 0.80; AUC >10 years = 0.75; baseline AUC range = 0.63-0.67). DNAm changes as noninvasive biomarkers in prediagnostic blood samples of MPM cases were investigated for the first time. Their application can improve the identification of asbestos-exposed individuals at higher MPM risk to possibly adopt more intensive monitoring for early disease identification.
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6. |
- Andersson, Anders-Petter, et al.
(author)
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What do we create in a responsible workshop in 2030?
- 2023
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In: Proceedings of the international conference on engineering and product design education, E&PD 2023. - : The Design Society. - 9781912254194 ; , s. 559-564
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Conference paper (peer-reviewed)abstract
- What should design students learn, not to lose hope, but be able to design in the current dire climate, energy and health situation? What can we design and still stay on track with the Sustainable Development Goals (SDG) in 2030? What can we design in the long run, not worsening critical human and non-human systems? In the paper we question "good intentions" and business-as-usual approaches, to challenges facing many of our most existential systems. We suggest changes to the Design field's understanding of the SDG's. Further, we suggest focusing on several solutions at the same time, in local communities, with collaboration with others and design educations. The paper argues that a holistic and systemic view is required that rather focuses on root-problems, than the symptoms these problems cause. Based on a multidisciplinary selection of scientific literature, the paper shows how acclaimed systemic approaches often harm the health of both human and non-human systems. In addition, the paper argues that these acclaimed systemic approaches tend to suggest "solutions" that stand in the way of more realistic solutions emerging from supportive and social environments. One of the insights from the literature, is how individuals by reconnecting to community- and practice-based activities strengthen hope of better futures. In the paper we argue how designers and design educations, can act multidisciplinary, with others, to become agents towards the kind of holistically, community-based, and radical changes required to heal all broken systems. We suggest how designers can situate themselves in the responsible workshop of 2030.
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7. |
- Andersson, Christer, 1982, et al.
(author)
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A SiC Varactor With Large Effective Tuning Range for Microwave Power Applications
- 2011
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In: IEEE Electron Device Letters. - : Institute of Electrical and Electronics Engineers (IEEE). - 0741-3106 .- 1558-0563. ; 32:6, s. 788-790
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Journal article (peer-reviewed)abstract
- SiC Schottky diode varactors have been fabricated for use in microwave power applications, specifically the dynamic load modulation of power amplifiers. A custom doping profile has been employed to spread the C(V) over a large bias voltage range, thereby increasing the effective tuning range under large voltage swing conditions. The small-signal tuning range is approximately six, and punch through is reached at a bias voltage of -60 V, while the breakdown voltage is on the order of -160 V. An interdigitated layout is utilized together with a self-aligned Schottky anode etch process to improve the Q-factor at 2 GHz, which is 20 at zero bias and approximately 160 at punch through.
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8. |
- Andersson, Christer M, et al.
(author)
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A SiC Varactor With Large Effective Tuning Range for Microwave Power Applications
- 2011
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In: IEEE ELECTRON DEVICE LETTERS. - : IEEE Institute of Electrical and Electronics. - 0741-3106. ; 32:6, s. 788-790
-
Journal article (peer-reviewed)abstract
- SiC Schottky diode varactors have been fabricated for use in microwave power applications, specifically the dynamic load modulation of power amplifiers. A custom doping profile has been employed to spread the C(V) over a large bias voltage range, thereby increasing the effective tuning range under large voltage swing conditions. The small-signal tuning range is approximately six, and punch through is reached at a bias voltage of -60 V, while the breakdown voltage is on the order of -160 V. An interdigitated layout is utilized together with a self-aligned Schottky anode etch process to improve the Q-factor at 2 GHz, which is 20 at zero bias and approximately 160 at punch through.
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9. |
- Berman, Anne H, et al.
(author)
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Teaching digital mental health treatment in theory and practice : a proof-of-concept pilot and feasibility study
- 2023
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In: International Journal of Behavioral Medicine. ; , s. 66-66, s. 6-7
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Conference paper (peer-reviewed)abstract
- Objective: The labor market for mental health professionals increasingly requires competency in digital mental health treatment (DMHT). This presentation targets DMHT practitioners as course developers and teachers, describing proof-of-concept findings based on a) development of a remotely delivered DMHT course; and b) results from a qualitative evaluation of students’ experiences from the first course round.Methods: The course syllabus was developed through two structured workshops, attended by 11 stakeholders with DMHT experience. For the qualitative evaluation, interviews with seven women participants in the first course round were analyzed according to an inductive, phenomenographic approach.Results: The course development process established a 12-week syllabus covering historical development and evidence for DMHT and an 8-week DMHT clinical practicum treating students with common mental health problems. Examination was formulated as individual case reports encompassing reflections on a) the therapist and client roles; b) ethical aspects of DMHT; and c) future innovations for DMHT. The course is offered via a standard learning management system, with the practicum completed on a separate DMHT platform. The qualitative analysis of the first pilot course round, where students role-played therapists and clients, yielded six themes: overall course experience, treatment program and platform, therapist role, client role, supervision and the alliance.Conclusions: This proof-of-concept procedure led to course establishment in two formats: as an ordinary elective course for advanced clinical psychology students, and as a stand-alone national course for health professionals with basic psychotherapy training. Following local adaptation, the course could be replicated at additional universities globally.
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10. |
- Berman, Anne H., et al.
(author)
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Teaching digital mental health treatment in theory and practice : A proof-of-concept pilot and feasibility study
- 2023
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In: International Journal of Behavioral Medicine. - : Springer. - 1070-5503 .- 1532-7558. ; 30, s. S67-S67
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Journal article (other academic/artistic)abstract
- Background: Improving relationship dynamics positively impacts both partners’ health among couples. However, few studies have investigated sexual and gender minority (SGM) couples’ relationship goals and their experiences toward achieving them.Purpose: The present study investigated SGM couples’ experiences that centered on them working toward or maintaining their relationship goals over time.Method: From a cohort study with SGM couples, a purposive sample of 40 couples was selected and interviewed over Zoom. Interviews were individual-level, semi-structured, and recorded. Thematic analysis was used to analyze the transcripts.Results: Approximately half of the 40 couples identified as gay male couples, a third as lesbian couples, and about one-fifth as queer or gender minority couples. Top three reported relationship goals were 1) improving communication, 2) working on finances, and 3) enhancing intimacy. Feeling emotionally connected, career-related decisions, and improving sexual satisfaction were other commonly reported goals. Overall, most partners felt they made progress toward at least 1 of their 3 relationship goals within the prior 6 months. However, perceived relationship goal progress varied extensively between partners across couple groups. Facilitator-related themes about relationship goal progress included dyadic efforts, having a support system including professional help, and planning. Barrier-related themes included nonexistent or minimal effort, different communication styles, employment and economical struggles, and competing life and health priorities.Conclusion(s): Dyadic efforts and support systems were key toward someone working toward or maintaining their relationships goals. Findings suggest key relationship functioning areas to target in a future multiple health behavior change intervention for SGM couples.
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11. |
- Berman, Anne H., Professor, et al.
(author)
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Transdiagnostic and tailored internet intervention to improve mental health among university students : Research protocol for a randomized controlled trial
- 2024
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In: Trials. - : Springer Nature. - 1745-6215. ; 25:1
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Journal article (peer-reviewed)abstract
- Background: Emerging adulthood is often associated with mental health problems. About one in three university students report symptoms of depression and anxiety that can negatively affect their developmental trajectory concerning work, intimate relationships, and health. This can interfere with academic performance, as mood and anxiety disorders are key predictors of dropout from higher education. A treatment gap exists, where a considerable proportion of students do not seek help for mood and anxiety symptoms. Offering internet interventions to students with mental health problems could reduce the treatment gap, increase mental health, and improve academic performance. A meta-analysis on internet interventions for university students showed small effects for depression and none for anxiety. Larger trials are recommended to further explore effects of guidance, transdiagnostic approaches, and individual treatment components.Methods: This study will offer 1200 university students in Sweden participation in a three-armed randomized controlled trial (RCT) evaluating a guided or unguided transdiagnostic internet intervention for mild to moderate depression and anxiety, where the waitlist control group accesses the intervention at 6-month follow-up. Students reporting suicidal ideation/behaviors will be excluded and referred to treatment within the existing healthcare system. An embedded study within the trial (SWAT) will assess at week 3 of 8 whether participants in the guided and unguided groups are at higher risk of failing to benefit from treatment. Those at risk will be randomized to an adaptive treatment strategy, or to continue the treatment as originally randomized. Primary outcomes are symptoms of depression and anxiety. Follow-ups will occur at post-treatment and at 6-, 12-, and 24-month post-randomization. Between-group outcome analyses will be reported, and qualitative interviews about treatment experiences are planned.Discussion: This study investigates the effects of a transdiagnostic internet intervention among university students in Sweden, with an adaptive treatment strategy employed during the course of treatment to minimize the risk of treatment failure. The study will contribute knowledge about longitudinal trajectories of mental health and well-being following treatment, taking into account possible gender differences in responsiveness to treatment. With time, effective internet interventions could make treatment for mental health issues more widely accessible to the student group.
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12. |
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14. |
- Clendenen, Tess V., et al.
(author)
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Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer : a nested case-control study
- 2015
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In: PLOS ONE. - : PLOS one. - 1932-6203. ; 10:10
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Journal article (peer-reviewed)abstract
- Genetic polymorphisms in vitamin D metabolism and signaling genes have been inconsistently associated with risk of breast cancer, though few studies have examined SNPs in vitamin D-related genes other than the vitamin D receptor (VDR) gene and particularly have not examined the association with the retinoid X receptor alpha (RXRA) gene which may be a key vitamin D pathway gene. We conducted a nested case-control study of 734 cases and 1435 individually matched controls from a population-based prospective cohort study, the Northern Sweden Mammary Screening Cohort. Tag and functional SNPs were genotyped for the VDR, cytochrome p450 24A1 (CYP24A1), and RXRA genes. We also genotyped specific SNPs in four other genes related to vitamin D metabolism and signaling (GC/VDBP, CYP2R1, DHCR7, and CYP27B1). SNPs in the CYP2R1, DHCR7, and VDBP gene regions that were associated with circulating 25(OH) D concentration in GWAS were also associated with plasma 25(OH) D in our study (p-trend < 0.005). After taking into account the false discovery rate, these SNPs were not significantly associated with breast cancer risk, nor were any of the other SNPs or haplotypes in VDR, RXRA, and CYP24A1. We observed no statistically significant associations between polymorphisms or haplotypes in key vitamin D-related genes and risk of breast cancer. These results, combined with the observation in this cohort and most other prospective studies of no association of circulating 25(OH) D with breast cancer risk, do not support an association between vitamin D and breast cancer risk.
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15. |
- Fazey, Ioan, et al.
(author)
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Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
- 2020
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In: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
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Journal article (peer-reviewed)abstract
- Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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16. |
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17. |
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18. |
- Hughes, David J., et al.
(author)
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Prediagnostic selenium status, selenoprotein gene variants and association with breast cancer risk in a European cohort study
- 2023
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In: Free Radical Biology & Medicine. - : Elsevier. - 0891-5849 .- 1873-4596. ; 209, s. 381-393
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Journal article (peer-reviewed)abstract
- Selenium (Se) may help prevent breast cancer (BC) development. Owing to limited observational evidence, we investigated whether prediagnostic Se status and/or variants in the selenoprotein genes are associated with BC risk in a large European cohort. Se status was assessed by plasma measures of Se and its major circulating proteins, selenoprotein P (SELENOP) and glutathione peroxidase 3 (GPX3), in matched BC case-control pairs (2208 for SELENOP; 1785 for GPX3 and Se) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Single nucleotide polymorphisms (SNPs, n = 452) in 55 selenoprotein and Se metabolic pathway genes and an additional 18 variants previously associated with Se concentrations were extracted from existing genotyping data within EPIC for 1564 case-control pairs. Multivariable-adjusted logistic regression models were used to calculate the odds ratios (ORs) and 95 % confidence intervals (CIs) of the association between Se status markers, SNP variants and BC risk. Overall, there was no statistically significant association of Se status with BC risk. However, higher GPX3 activity was associated with lower risk of premenopausal BC (4th versus 1st quartile, OR = 0.54, 95 % CI: 0.30–0.98, Ptrend = 0.013). While none of the genetic variant associations (P ≤ 0.05) retained significance after multiple testing correction, rs1004243 in the SELENOM selenoprotein gene and two SNPs in the related antioxidant TXN2 gene (rs4821494 and rs5750261) were associated with respective lower and higher risks of BC at a significance threshold of P ≤ 0.01. Fourteen SNPs in twelve Se pathway genes (P ≤ 0.01) in interaction with Se status were also associated with BC risk. Higher Se status does not appear to be associated with BC risk, although activity of the selenoenzyme GPX3 may be inversely associated with premenopausal BC risk, and SNPs in the Se pathway alone or in combination with suboptimal Se status may influence BC risk.
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19. |
- Jacobs, Kevin B, et al.
(author)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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In: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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Journal article (peer-reviewed)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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20. |
- Jonsson, Ulf, et al.
(author)
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Psychological Treatment of Depression in People Aged 65 Years and Over : A Systematic Review of Efficacy, Safety, and Cost-Effectiveness.
- 2016
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 11:8
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Depression in elderly people is a major public health concern. As response to antidepressants is often unsatisfactory in this age group, there is a need for evidence-based non-pharmacological treatment options. Our objectives were twofold: firstly, to synthesize published trials evaluating efficacy, safety and cost-effectiveness of psychological treatment of depression in the elderly and secondly, to assess the quality of evidence.METHOD: The electronic databases PubMed, EMBASE, Cochrane Library, CINAL, Scopus, and PsycINFO were searched up to 23 May 2016 for randomized controlled trials (RCTs) of psychological treatment for depressive disorders or depressive symptoms in people aged 65 years and over. Two reviewers independently assessed relevant studies for risk of bias. Where appropriate, the results were synthesized in meta-analyses. The quality of the evidence was graded according to GRADE (Grading of Recommendations Assessment, Development and Evaluation).RESULTS: Twenty-two relevant RCTs were identified, eight of which were excluded from the synthesis due to a high risk of bias. Of the remaining trials, six evaluated problem-solving therapy (PST), five evaluated other forms of cognitive behavioural therapy (CBT), and three evaluated life review/reminiscence therapy. In frail elderly with depressive symptoms, the evidence supported the efficacy of PST, with large but heterogeneous effect sizes compared with treatment as usual. The results for life-review/reminiscence therapy and CBT were also promising, but because of the limited number of trials the quality of evidence was rated as very low. Safety data were not reported in any included trial. The only identified cost-effectiveness study estimated an incremental cost per additional point reduction in Beck Depression Inventory II score for CBT compared with talking control and treatment as usual.CONCLUSION: Psychological treatment is a feasible option for frail elderly with depressive symptoms. However, important questions about efficacy, generalizability, safety and cost-effectiveness remain.
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21. |
- Kaaks, Rudolf, et al.
(author)
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Insulin-like growth factor I and risk of breast cancer by age and hormone receptor status : A prospective study within the EPIC cohort
- 2014
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 134:11, s. 2683-2690
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Journal article (peer-reviewed)abstract
- Experimental evidence shows cross-talk in mammary cells between estrogen, insulin-like growth factor I (IGF-I) and their respective receptors and possible synergistic effects of estrogen receptor (ER) activation and increased IGF-I signaling with regard to breast tumor development, and epidemiological evidence suggests that circulating IGF-I levels may be related more to the risk of ER-positive than ER-negative breast cancer. Using a case–control study nested within the prospective European EPIC cohort (938 breast cancer cases and 1,394 matched control subjects), we analyzed the relationships of prediagnostic serum IGF-I levels with the risk of estrogen and progesterone receptor-positive and -negative breast tumors. IGF-I levels were positively associated with the risk of ER+ breast tumors overall (pre- and postmenopausal women combined, odds ratio (OR)Q4-Q1 = 1.41 [95% confidence interval (CI) 1.01–1.98] for the highest vs. lowest quartile; OR = 1.17 [95% CI 1.04–1.33] per 1-standard deviation (SD) increase in IGF-I, ptrend = 0.01) and among women who were diagnosed with breast cancer at 50 years or older (ORQ3-Q1 = 1.38 [95% CI 1.01–1.89]; OR = 1.19 [95% CI 1.04–1.36] per 1-SD increase in IGF-I, ptrend = 0.01) but not with receptor-positive disease diagnosed at an earlier age. No statistically significant associations were observed for ER− breast tumors overall and by age at diagnosis. Tests for heterogeneity by receptor status of the tumor were not statistically significant, except for women diagnosed with breast cancer at 50 years or older (phet = 0.03 for ER+/PR+ vs. ER−/PR− disease). Our data add to a global body of evidence indicating that higher circulating IGF-I levels may increase risk specifically of receptor-positive, but not receptor-negative, breast cancer diagnosed at 50 years or older.
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22. |
- Kaaks, Rudolf, et al.
(author)
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Premenopausal serum sex hormone levels in relation to breast cancer risk, overall and by hormone receptor status-Results from the EPIC cohort
- 2014
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 134:8, s. 1947-1957
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Journal article (peer-reviewed)abstract
- Results from prospective studies on premenopausal serum hormone levels in relation to breast cancer risk have been inconclusive, especially with regard to tumor subtypes. Using a case-control study nested within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (801 breast cancer cases and 1,132 matched control subjects), we analyzed the relationships of prediagnostic serum estradiol, free estradiol, progesterone, testosterone, free testosterone and sex hormone-binding globulin (SHBG) levels with the risk of breast cancer by estrogen and progesterone receptor-positive and -negative breast tumors and by age at diagnoses. Higher prediagnostic serum levels of testosterone and free testosterone were associated with an increased overall risk of breast cancer [ORQ4-Q1=1.56 (95% CI 1.15-2.13), p(trend)=0.02 for testosterone and ORQ4-Q1=1.33 (95% CI 0.99-1.79), p(trend)=0.04 for free testosterone], but no significant risk association was observed for estradiol, free estradiol, progesterone and SHBG. Tests for heterogeneity between receptor-positive and -negative tumors were not significant. When analysis were stratified by age at tumor diagnosis, the odds ratios observed for estradiol were stronger and borderline significant for breast cancer diagnosed at age less than 50 [ORQ4-Q1=1.32 (95% CI 0.87-2.01), p(trend)=0.05] compared to breast cancer diagnosed at age 50 or above [ORQ4-Q1=0.94 (95% CI 0.60-1.47), p(trend)=0.34, p(het)=0.04]. In conclusion, our data indicate that higher premenopausal circulating testosterone levels are associated with an increased risk of developing breast cancer, but do not show a significant association of estradiol or progesterone with breast cancer risk, overall, by menstrual cycle phase or by tumor receptor status, although a possible risk increase with higher estradiol levels for tumors diagnosed before age 50 was seen.
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23. |
- Kagwesage, Anne Marie
(author)
-
Coping with Learning through a Foreign Language in Higher Education in Rwanda
- 2013
-
Doctoral thesis (other academic/artistic)abstract
- The overarching aims of this thesis are to investigate how students in higher education in Rwanda experience learning through the medium of a foreign language, mainly English, and the strategies they employ in order to successfully complete their university studies during a period of both language and educational change. Taking a sociocultural perspective, the thesis subscribes to a qualitative research design. Interviews were used in order to gain in-depth understanding of how higher education students reflect on, handle and cope with learning through a foreign language. Video and audio recorded interactions of students’ formal and informal group discussions were used to capture some of the seen but unnoticed linguistic and communicative details that might be of interest in shedding light on aspects related to learning in a foreign language. Four empirical studies show that students face different challenges in using the newly adopted language of learning and teaching. They are, however, aware of the fact that the globalisation process and dissolution of national boundaries may create new opportunities and are therefore willing to upgrade their English in order to cope with the new academic situation. Findings show that active use of multiple languages, although time consuming, has great potential to facilitate learning, thus emphasizing the complementarities rather than the exclusion of languages used in Rwanda. Also, teacher and student initiated group discussions have the potential to promote knowledge construction in content subjects as students afford a context for confident participation. Although the mother tongue is not officially recognised as language of instruction in higher education, it plays a mediating role for the negotiation of meaning of domain specific content through responsible code switching and translanguaging.
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24. |
- Key, Timothy J., et al.
(author)
-
Consumption of Meat, Fish, Dairy Products, Eggs and Risk of Ischemic Heart Disease : A Prospective Study of 7198 Incident Cases Among 409,885 Participants in the Pan-European EPIC Cohort
- 2019
-
In: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 139:25, s. 2835-2845
-
Journal article (peer-reviewed)abstract
- BACKGROUND: There is uncertainty about the relevance of animal foods to the etiology of ischemic heart disease (IHD). We examined meat, fish, dairy products and eggs and risk for IHD in the pan-European EPIC cohort.METHODS: A prospective study of 409,885 men and women in nine European countries. Diet was assessed using validated questionnaires, calibrated using 24-hour recalls. Lipids and blood pressure were measured in a subsample. During 12.6 years mean follow up, 7198 participants had a myocardial infarction or died from IHD. The relationships of animal foods with risk were examined using Cox regression with adjustment for other animal foods and relevant covariates.RESULTS: The hazard ratio (HR) for IHD was 1.19 (95% CI 1.06-1.33) for a 100 g/d increment in intake of red and processed meat, and this remained significant after excluding the first 4 years of follow-up (HR 1.25 [1.09-1.42]). Risk was inversely associated with intakes of yogurt (HR 0.93 [0.89-0.98] per 100 g/d increment), cheese (HR 0.92 [0.86-0.98] per 30 g/d increment) and eggs (HR 0.93 [0.88-0.99] per 20 g/d increment); the associations with yogurt and eggs were attenuated and non-significant after excluding the first 4 years of follow-up. Risk was not significantly associated with intakes of poultry, fish or milk. In analyses modelling dietary substitutions, replacement of 100 kcal/d from red and processed meat with 100 kcal/d from fatty fish, yogurt, cheese or eggs was associated with approximately 20% lower risk of IHD. Consumption of red and processed meat was positively associated with serum non-HDL cholesterol concentration and systolic blood pressure, and consumption of cheese was inversely associated with serum non-HDL cholesterol.CONCLUSIONS: Risk for IHD was positively associated with consumption of red and processed meat, and inversely associated with consumption of yogurt, cheese and eggs, although the associations with yogurt and eggs may be influenced by reverse causation bias. It is not clear whether the associations with red and processed meat and cheese reflect causality, but they were consistent with the associations of these foods with plasma non-HDL cholesterol, and for red and processed meat with systolic blood pressure, which could mediate such effects.
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25. |
- Kühn, Tilman, et al.
(author)
-
Plasma 25-hydroxyvitamin D and the risk of breast cancer in the European prospective investigation into cancer and nutrition : A nested case-control study
- 2013
-
In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 133:7, s. 1689-1700
-
Journal article (peer-reviewed)abstract
- Experimental evidence suggests that vitamin D might play a role in the development of breast cancer. Although the results of case-control studies indicate that circulating 25-hydroxyvitamin D [25(OH)D] is inversely associated with the risk of breast cancer, the results of prospective studies are inconsistent. A case-control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) was carried out comprising 1,391 incident breast cancer cases and 1,391 controls. Multivariable conditional logistic regression models did not reveal a significant overall association between season-standardized 25(OH)D levels and the risk of breast cancer (ORQ4-Q1 [95% CI]: 1.07 [0.85-1.36], ptrend = 0.67). Moreover, 25(OH)D levels were not related to the risks of estrogen receptor positive tumors (ORQ4-Q1 [95% CI]: 0.97 [0.67-1.38], ptrend = 0.90) and estrogen receptor negative tumors (ORQ4-Q1 [95% CI]: 0.97 [0.66-1.42], ptrend = 0.98). In hormone replacement therapy (HRT) users, 25(OH)D was significantly inversely associated with incident breast cancer (ORlog2 [95% CI]: 0.62 [0.42-0.90], p = 0.01), whereas no significant association was found in HRT nonusers (ORlog2 [95% CI]: 1.14 [0.80-1.62], p = 0.48). Further, a nonsignificant inverse association was found in women with body mass indices (BMI) < 25 kg/m(2) (ORlog2 [95% CI]: 0.83 [0.67-1.03], p = 0.09), as opposed to a borderline significant positive association in women with BMI ≥ 25 kg/m(2) (ORlog2 [95% CI]: 1.30 [1.0-1.69], p = 0.05). Overall, prediagnostic levels of circulating 25(OH)D were not related to the risk of breast cancer in the EPIC study. This result is in line with findings in the majority of prospective studies and does not support a role of vitamin D in the development of breast cancer.
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26. |
- Olsson, Mia, et al.
(author)
-
A Novel Unstable Duplication Upstream of HAS2 Predisposes to a Breed-Defining Skin Phenotype and a Periodic Fever Syndrome in Chinese Shar-Pei Dogs
- 2011
-
In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:3, s. e1001332-
-
Journal article (peer-reviewed)abstract
- Hereditary periodic fever syndromes are characterized by recurrent episodes of fever and inflammation with no known pathogenic or autoimmune cause. In humans, several genes have been implicated in this group of diseases, but the majority of cases remain unexplained. A similar periodic fever syndrome is relatively frequent in the Chinese Shar-Pei breed of dogs. In the western world, Shar-Pei have been strongly selected for a distinctive thick and heavily folded skin. In this study, a mutation affecting both these traits was identified. Using genome-wide SNP analysis of Shar-Pei and other breeds, the strongest signal of a breed-specific selective sweep was located on chromosome 13. The same region also harbored the strongest genome-wide association (GWA) signal for susceptibility to the periodic fever syndrome (p(raw) = 2.3 x 10(-6), p(genome) = 0.01). Dense targeted resequencing revealed two partially overlapping duplications, 14.3 Kb and 16.1 Kb in size, unique to Shar-Pei and upstream of the Hyaluronic Acid Synthase 2 (HAS2) gene. HAS2 encodes the rate-limiting enzyme synthesizing hyaluronan (HA), a major component of the skin. HA is up-regulated and accumulates in the thickened skin of Shar-Pei. A high copy number of the 16.1 Kb duplication was associated with an increased expression of HAS2 as well as the periodic fever syndrome (p, < 0.0001). When fragmented, HA can act as a trigger of the innate immune system and stimulate sterile fever and inflammation. The strong selection for the skin phenotype therefore appears to enrich for a pleiotropic mutation predisposing these dogs to a periodic fever syndrome. The identification of HA as a major risk factor for this canine disease raises the potential of this glycosaminoglycan as a risk factor for human periodic fevers and as an important driver of chronic inflammation.
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27. |
- Ricceri, Fulvio, et al.
(author)
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Risk of second primary malignancies in women with breast cancer: Results from the European prospective investigation into cancer and nutrition (EPIC)
- 2015
-
In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 137:4, s. 940-948
-
Journal article (peer-reviewed)abstract
- Women with a diagnosis of breast cancer are at increased risk of second primary cancers, and the identification of risk factors for the latter may have clinical implications. We have followed-up for 11 years 10,045 women with invasive breast cancer from a European cohort, and identified 492 second primary cancers, including 140 contralateral breast cancers. Expected and observed cases and Standardized Incidence Ratios (SIR) were estimated using Aalen-Johansen Markovian methods. Information on various risk factors was obtained from detailed questionnaires and anthropometric measurements. Cox proportional hazards regression models were used to estimate the role of risk factors. Women with breast cancer had a 30% excess risk for second malignancies (95% confidence interval-CI 18-42) after excluding contralateral breast cancers. Risk was particularly elevated for colorectal cancer (SIR, 1.71, 95% CI 1.43-2.00), lymphoma (SIR 1.80, 95% CI 1.31-2.40), melanoma (2.12; 1.63-2.70), endometrium (2.18; 1.75-2.70) and kidney cancers (2.40; 1.57-3.52). Risk of second malignancies was positively associated with age at first cancer, body mass index and smoking status, while it was inversely associated with education, post-menopausal status and a history of full-term pregnancy. We describe in a large cohort of women with breast cancer a 30% excess of second primaries. Among risk factors for breast cancer, a history of full-term pregnancy was inversely associated with the risk of second primary cancer. What's new? For the first time, researchers have used cohort data to show that people who survive breast cancer have a higher risk of developing another cancer later. By collecting data on 10,000 breast cancer patients over 11 years, these authors calculated a 30% boost in the patients' risk of developing a second primary malignancy, particularly colorectal cancer, lymphoma, melanoma, endometrial cancer, and kidney cancer. These findings, plus the data they collected on risk factors such as age, smoking, body mass index, and others, will help guide clinicians in screening procedures and follow up care for breast cancer patients.
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28. |
- Ritte, Rebecca, et al.
(author)
-
Height, age at menarche and risk of hormone receptor-positive and -negative breast cancer : A cohort study
- 2013
-
In: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 132:11, s. 2619-2629
-
Journal article (peer-reviewed)abstract
- Associations of breast cancer overall with indicators of exposures during puberty are reasonably well characterized; however, uncertainty remains regarding the associations of height, leg length, sitting height and menarcheal age with hormone receptor-defined malignancies. Within the European Prospective Investigation into Cancer and Nutrition cohort, Cox proportional hazards models were used to describe the relationships of adult height, leg length and sitting height and age at menarche with risk of estrogen and progesterone receptor negative (ER-PR-) (n = 990) and ER+PR+ (n = 3,524) breast tumors. Height as a single risk factor was compared to a model combining leg length and sitting height. The possible interactions of height, leg length and sitting height with menarche were also analyzed. Risk of both ER-PR- and ER+PR+ malignancies was positively associated with standing height, leg length and sitting height and inversely associated with increasing age at menarche. For ER+PR+ disease, sitting height (hazard ratios: 1.14[95% confidence interval: 1.081.20]) had a stronger risk association than leg length (1.05[1.001.11]). In comparison, for ER-PR- disease, no distinct differences were observed between leg length and sitting height. Women who were tall and had an early menarche (13 years) showed an almost twofold increase in risk of ER+PR+ tumors but no such increase in risk was observed for ER-PR- disease. Indicators of exposures during rapid growth periods were associated with risks of both HR-defined breast cancers. Exposures during childhood promoting faster development may establish risk associations for both HR-positive and negative malignancies. The stronger associations of the components of height with ER+PR+ tumors among older women suggest possible hormonal links that could be specific for postmenopausal women.
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29. |
- Ritte, Rebecca, et al.
(author)
-
Reproductive factors and risk of hormone receptor positive and negative breast cancer : a cohort study
- 2013
-
In: BMC Cancer. - : BioMed Central. - 1471-2407. ; 13, s. Article Number: 584-
-
Journal article (peer-reviewed)abstract
- Background: The association of reproductive factors with hormone receptor (HR)-negative breast tumors remains uncertain. Methods: Within the EPIC cohort, Cox proportional hazards models were used to describe the relationships of reproductive factors (menarcheal age, time between menarche and first pregnancy, parity, number of children, age at first and last pregnancies, time since last full-term childbirth, breastfeeding, age at menopause, ever having an abortion and use of oral contraceptives [OC]) with risk of ER-PR-(n = 998) and ER+PR+ (n = 3,567) breast tumors. Results: A later first full-term childbirth was associated with increased risk of ER+PR+ tumors but not with risk of ER-PR-tumors (= 35 vs. = 19 years HR: 1.47 [95% CI 1.15-1.88] p(trend) < 0.001 for ER+PR+ tumors; = 35 vs. = 19 years HR: 0.93 [95% CI 0.53-1.65] p(trend) = 0.96 for ER-PR-tumors; P-het = 0.03). The risk associations of menarcheal age, and time period between menarche and first full-term childbirth with ER-PR-tumors were in the similar direction with risk of ER+PR+ tumors (p(het) = 0.50), although weaker in magnitude and statistically only borderline significant. Other parity related factors such as ever a full-term birth, number of births, age-and time since last birth were associated only with ER+PR+ malignancies, however no statistical heterogeneity between breast cancer subtypes was observed. Breastfeeding and OC use were generally not associated with breast cancer subtype risk. Conclusion: Our study provides possible evidence that age at menarche, and time between menarche and first full-term childbirth may be associated with the etiology of both HR-negative and HR-positive malignancies, although the associations with HR-negative breast cancer were only borderline significant.
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30. |
- Sandling, Johanna K., et al.
(author)
-
Molecular pathways in patients with systemic lupus erythematosus revealed by gene-centred DNA sequencing
- 2021
-
In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 80:1, s. 109-117
-
Journal article (peer-reviewed)abstract
- Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease with extensive heterogeneity in disease presentation between patients, which is likely due to an underlying molecular diversity. Here, we aimed at elucidating the genetic aetiology of SLE from the immunity pathway level to the single variant level, and stratify patients with SLE into distinguishable molecular subgroups, which could inform treatment choices in SLE. Methods: We undertook a pathway-centred approach, using sequencing of immunological pathway genes. Altogether 1832 candidate genes were analysed in 958 Swedish patients with SLE and 1026 healthy individuals. Aggregate and single variant association testing was performed, and we generated pathway polygenic risk scores (PRS). Results: We identified two main independent pathways involved in SLE susceptibility: T lymphocyte differentiation and innate immunity, characterised by HLA and interferon, respectively. Pathway PRS defined pathways in individual patients, who on average were positive for seven pathways. We found that SLE organ damage was more pronounced in patients positive for the T or B cell receptor signalling pathways. Further, pathway PRS-based clustering allowed stratification of patients into four groups with different risk score profiles. Studying sets of genes with priors for involvement in SLE, we observed an aggregate common variant contribution to SLE at genes previously reported for monogenic SLE as well as at interferonopathy genes. Conclusions: Our results show that pathway risk scores have the potential to stratify patients with SLE beyond clinical manifestations into molecular subsets, which may have implications for clinical follow-up and therapy selection.
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31. |
- Sieri, Sabina, et al.
(author)
-
Dietary Fat Intake and Development of Specific Breast Cancer Subtypes.
- 2014
-
In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 106:5, s. 068-068
-
Journal article (peer-reviewed)abstract
- We prospectively evaluated fat intake as predictor of developing breast cancer (BC) subtypes defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 receptor (HER2), in a large (n = 337327) heterogeneous cohort of women, with 10062 BC case patients after 11.5 years, estimating BC hazard ratios (HRs) by Cox proportional hazard modeling. High total and saturated fat were associated with greater risk of ER(+)PR(+) disease (HR = 1.20, 95% confidence interval [CI] = 1.00 to 1.45; HR = 1.28, 95% CI = 1.09 to 1.52; highest vs lowest quintiles) but not ER(-)PR(-) disease. High saturated fat was statistically significantly associated with greater risk of HER2(-) disease. High saturated fat intake particularly increases risk of receptor-positive disease, suggesting saturated fat involvement in the etiology of this BC subtype.
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32. |
- Sonderby, Ida E., et al.
(author)
-
Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
- 2020
-
In: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
-
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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33. |
- 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
-
In: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 11:1
-
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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34. |
- Tham, Anne, et al.
(author)
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Efficacy and tolerability of antidepressants in people aged 65 years or older with major depressive disorder - A systematic review and a meta-analysis
- 2016
-
In: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 205, s. 1-12
-
Research review (peer-reviewed)abstract
- Background: There has been a steady increase in the prescription of antidepressants for the elderly. This study comprises a systematic review of randomized, placebo-controlled trials of antidepressants for treatment of depressive disorder in people aged 65 years or more. Methods: PubMed, EMBASE, Cochrane Library, CINAL, and PsycINFO were searched until May 2016. Where appropriate, the results were synthesized in meta-analyses. Results: Twelve trials met the inclusion criteria. For patients with major depressive disorder, selective serotonin re-uptake inhibitors (SSRI) were not superior to placebo in achieving remission (OR: 0.79, 95% CI: 0.61-1.03) or response (OR=0.86, 95% CI: 0.51-1.10) after 8 weeks of treatment (three trials). However, maintenance treatment with SSRIs was superior to placebo in preventing relapse (OR: 0.22, 95% CI: 0.13-0.36; NNT=5, 95% CI: 3-6; two trials). Duloxetine was superior to placebo in achieving remission (OR: 1.78, 95% CI: 1.20-2.65; NNT=9, 95% CI: 6-20; three trials) and response (OR: 1.83, 95% CI: 1.96-4.08; two trials) in recurrent major depression after 8 weeks, but increased the risk of adverse events that can be problematic in the elderly. Limitations: The quality of evidence was generally low or moderate, emphasizing the uncertainty of the results. Study populations only partly covered the heterogeneous population of elderly with depressed mood, limiting the generalizability. Conclusion: The results underscore the importance of close monitoring of the effects of antidepressants in treatment of elderly patients with a depressive disorder. Methods for early detection of non-responders and effective treatment options for this group are needed.
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35. |
- Tikk, Kaja, et al.
(author)
-
Circulating prolactin and breast cancer risk among pre- and postmenopausal women in the EPIC cohort
- 2014
-
In: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 25:7, s. 1422-1428
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Experimental and epidemiological evidence suggests that prolactin might play a role in the etiology of breast cancer. We analyzed the relationship of pre-diagnostic circulating prolactin levels with the risk of breast cancer by menopausal status, use of postmenopausal hormone replacement therapy (HRT) at blood donation, and by estrogen and progesterone receptor-status of the breast tumors. METHODS: Conditional logistic regression was used to analyze the data from a case-control study nested within the prospective European EPIC cohort, including 2250 invasive breast cancer and their matched control subjects. RESULTS: Statistically significant heterogeneity in the association of prolactin levels with breast cancer risk between women who were either pre- or postmenopausal at the time of blood donation was observed (Phet=0.04). Higher serum levels of prolactin were associated with significant increase in risk of breast cancer among postmenopausal women (ORQ4-Q1=1.29 [95%CI 1.05-1.58], Ptrend=0.09); however this increase in risk seemed to be confined to women who used postmenopausal HRT at blood donation (ORQ4-Q1=1.45 [95%CI 1.08-1.95], Ptrend=0.01), whereas no statistically significant association was found for the non-users of HRT (ORQ4-Q1 =1.11 [95%CI 0.83-1.49], Ptrend=0.80) (Phet=0.08). Among premenopausal women, a statistically non-significant inverse association was observed (ORQ4-Q1 =0.70 [95%CI 0.48-1.03], Ptrend=0.16). There was no heterogeneity in the prolactin-breast cancer association by hormone receptor status of the tumor. CONCLUSION: Our study indicates that higher circulating levels of prolactin among the postmenopausal HRT users at baseline may be associated with increased breast cancer risk.
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36. |
- Wang, Zhaoming, et al.
(author)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
-
In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
-
Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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37. |
- Adelöf, Julia, 1990, et al.
(author)
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PA28αβ overexpression enhances learning and memory of female mice without inducing 20S proteasome activity
- 2018
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In: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 19:1
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The proteasome system plays an important role in synaptic plasticity. Induction and maintenance of long term potentiation is directly dependent on selective targeting of proteins for proteasomal degradation. The 20S proteasome activator PA28αβ activates hydrolysis of small nonubiquitinated peptides and possesses protective functions upon oxidative stress and proteinopathy. The effect of PA28αβ activity on behavior and memory function is, however, not known. We generated a mouse model that overexpresses PA28α (PA28αOE) to understand PA28αβ function during healthy adult homeostasis via assessment of physiological and behavioral profiles, focusing on female mice. RESULTS: PA28α and PA28β protein levels were markedly increased in all PA28αOE tissues analyzed. PA28αOE displayed reduced depressive-like behavior in the forced swim test and improved memory/learning function assessed by intersession habituation in activity box and shuttle box passive avoidance test, with no significant differences in anxiety or general locomotor activity. Nor were there any differences found when compared to WT for body composition or immuno-profile. The cognitive effects of PA28αOE were female specific, but could not be explained by alterations in estrogen serum levels or hippocampal regulation of estrogen receptor β. Further, there were no differences in hippocampal protein expression of neuronal or synaptic markers between PA28αOE and WT. Biochemical analysis of hippocampal extracts demonstrated that PA28α overexpression did not increase PA28-20S peptidase activity or decrease K48-polyubiquitin levels. Instead, PA28αOE exhibited elevated efficiency in preventing aggregation in the hippocampus. CONCLUSIONS: This study reveals, for the first time, a connection between PA28αβ and neuronal function. We found that PA28α overexpressing female mice displayed reduced depressive-like behavior and enhanced learning and memory. Since the positive effects of PA28α overexpression arose without an activation of 20S proteasome capacity, they are likely independent of PA28αβ's role as a 20S proteasome activator and instead depend on a recognized chaperone-like function. These findings suggest that proteostasis in synaptic plasticity is more diverse than previously reported, and demonstrates a novel function of PA28αβ in the brain.
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38. |
- Ademuyiwa, Adesoji O., et al.
(author)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Journal article (peer-reviewed)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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39. |
- Ahlström, Christer, et al.
(author)
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Validating speed and road surface realism in VTI driving simulator III
- 2012
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Reports (other academic/artistic)abstract
- Nya simulatormodeller för vibrationer, ljud och grafik har utvecklats och implementerats i VTI:S fordonssimulator III. Syftet med denna studie är att validera simulatorn med avseende på hastighet och återgivandet av olika vägyteparametrar. Tjugofyra försökspersoner deltog i studien. De fick köra en och samma rutt i såväl simulator III som på verklig väg. Tre vägavsnitt med olika kvalitet på vägytan, från mycket slät till ganska ojämn, ingick i försöket. Såväl den objektiva förarparametern hastighet som olika subjektiva parametrar avseende förarens uppfattning om vägytans egenskaper (jämnhet, tysthet, komfort) jämfördes. Ett vägavsnitt med skiftande hastighetsgränser var av speciellt intresse. Ingen signifikant skillnad kunde noteras mellan körning i simulator och på verklig väg vare sig avseende hastighet (på avsitt med konstant hastighetsgräns) eller gradering av jämnhet och tysthet. För sträckan med skiftande hastighetsgränser fanns dock en signifikant skillnad mellan hastigheten i bil jämfört med hastigheten i simulator, trots liknande hastighetsprofiler. Såväl accelerationerna som retardationerna var snabbare i simulatorn. Vägkomforten graderades högre i bil än i simulator, men i båda fallen var tendensen den att slätare vägar gav högre värdering av komforten. Dessa resultat indikerar absolut validitet för graderingen av jämnhet och tysthet och för det objektiva måttet hastighet, medan relativ validitet indikerades för såväl hastighet vid skylt för hastighetsändring som för gradering av komfort.
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40. |
- Ali, Alaa M. G., et al.
(author)
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Alcohol Consumption and Survival after a Breast Cancer Diagnosis: A Literature-Based Meta-analysis and Collaborative Analysis of Data for 29,239 Cases
- 2014
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In: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 23:6, s. 934-945
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Journal article (peer-reviewed)abstract
- Background: Evidence for an association of alcohol consumption with prognosis after a diagnosis of breast cancer has been inconsistent. We have reviewed and summarized the published evidence and evaluated the association using individual patient data from multiple case cohorts. Methods: A MEDLINE search to identify studies published up to January 2013 was performed. We combined published estimates of survival time for "moderate drinkers" versus nondrinkers. An analysis of individual participant data using Cox regression was carried out using data from 11 case cohorts. Results: We identified 11 published studies suitable for inclusion in the meta-analysis. Moderate postdiagnosis alcohol consumption was not associated with overall survival [HR, 0.95; 95% confidence interval (CI), 0.85-1.05], but there was some evidence of better survival associated with prediagnosis consumption (HR, 0.80; 95% CI, 0.73-0.88). Individual data on alcohol consumption for 29,239 cases with 4,839 deaths were available from the 11 case cohorts, all of which had data on estrogen receptor (ER) status. For women with ER-positive disease, there was little evidence that pre-or postdiagnosis alcohol consumption is associated with breast cancer-specific mortality, with some evidence of a negative association with all-cause mortality. On the basis of a single study, moderate postdiagnosis alcohol intake was associated with a small reduction in breast cancer-specific mortality for women with ER-negative disease. There was no association with prediagnosis intake for women with ER-negative disease. Conclusion: There was little evidence that pre- or post-diagnosis alcohol consumption is associated with breast cancer-specific mortality for women with ER-positive disease. There was weak evidence that moderate post-diagnosis alcohol intake is associated with a small reduction in breast cancer-specific mortality in ER-negative disease. Impact: Considering the totality of the evidence, moderate postdiagnosis alcohol consumption is unlikely to have a major adverse effect on the survival of women with breast cancer. (C) 2014 AACR.
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41. |
- Allsopp, Benjamin, et al.
(author)
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Towards improved cover glasses for photovoltaic devices
- 2020
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In: Progress in Photovoltaics. - : John Wiley and Sons Ltd. - 1062-7995 .- 1099-159X. ; 28, s. 1187-1206
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Journal article (peer-reviewed)abstract
- For the solar energy industry to increase its competitiveness, there is a global drive to lower the cost of solar-generated electricity. Photovoltaic (PV) module assembly is material-demanding, and the cover glass constitutes a significant proportion of the cost. Currently, 3-mm-thick glass is the predominant cover material for PV modules, accounting for 10%–25% of the total cost. Here, we review the state-of-the-art of cover glasses for PV modules and present our recent results for improvement of the glass. These improvements were demonstrated in terms of mechanical, chemical and optical properties by optimizing the glass composition, including addition of novel dopants, to produce cover glasses that can provide (i) enhanced UV protection of polymeric PV module components, potentially increasing module service lifetimes; (ii) re-emission of a proportion of the absorbed UV photon energy as visible photons capable of being absorbed by the solar cells, thereby increasing PV module efficiencies and (iii) successful laboratory-scale demonstration of proof of concept, with increases of 1%–6% in Isc and 1%–8% in Ipm. Improvements in both chemical and crack resistance of the cover glass were also achieved through modest chemical reformulation, highlighting what may be achievable within existing manufacturing technology constraints. © 2020 The Authors.
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42. |
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43. |
- Anderbrant, Olle, et al.
(author)
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Electrophysiological responses of carrot psyllids (Trioza apicalis), in different phases of their life cycle, to volatile carrot and conifer compounds
- 2020
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In: Journal of Applied Entomology. - : Wiley. - 0931-2048 .- 1439-0418. ; 144:3, s. 236-240
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Journal article (peer-reviewed)abstract
- Carrot psyllids (Trioza apicalis) pose a constant threat to carrot production in parts of Europe, and treatments with chemical insecticides are common. To be able to develop alternative control tactics, more knowledge about the psyllid's host-finding behaviour and underlying physiology is needed. Using single-sensillum recordings from overwintered and non-overwintered males and females, we found essentially identical responses for the two groups and for both sexes. Using six compounds emanating from carrots or conifers, the psyllids' overwintering plants, and extracts of carrot leaves, five different olfactory sensory neuron classes could be distinguished from our high-quality recordings, viz. #1 responding strongly and exclusively to terpinene-4-ol, #2 responding strongly and most often exclusively to nonanal, #3 responding moderately strongly to terpinolene, #4 responding strongly to (Z)-3-hexenal and most often weaker to terpinolene, #5 responding exclusively to carrot extract.
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44. |
- Andersson, Anne, 1966-, et al.
(author)
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Adherence to adjuvant endocrine therapy after breast cancer in Sweden 2008-2010 : a nationwide survey
- 2019
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In: JOURNAL OF CLINICAL ONCOLOGY. - : American Society of Clinical Oncology. - 0732-183X. ; 37:15
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Conference paper (other academic/artistic)abstract
- Background: In estrogen receptor (ER) positive early breast cancer (EBC) adjuvant endocrine therapy (AET) is crucial to reduce recurrence and mortality. Previous studies have shown that adherence to AET is lower than expected and could negatively affect outcome. Since the year of 2000, BC patients in Sweden are treated in accordance to national guidelines. Treatment is offered at a low cost for the patient. The aim of the study was to estimate the adherence to AET in Sweden by regions and age groups. Methods: Women with a first primary EBC diagnosis 2008-2010 were identified through the Swedish Cancer Registry (SCR). Individual tumour and treatment data were retrieved from the Swedish National Breast Cancer Registry (SNBCR). Patients with ER negative tumours, small tumours (≤ 10 mm) and metastatic disease was excluded from the study since there were no indication to AET. Likewise, were individuals with AET registered to be administered by a third part excluded. Dispensed treatment from pharmacies was obtained through the Swedish Prescription Registry and medication possession rate (MPR) was calculated as number of dispensed doses divided by treatment duration in days. Good adherence to treatment in a patient was set at MPR ≥ 80 %. Adherence was calculated for 3 and 5 years. Results: Twenty-one thousand sixteen (21 016) individuals with a first primary BC between 2008 and 2010 was identified through SCR of which 20 596 were registered in the SNBCR. A total of 10 176 met the inclusion criteria in the study. Adherence after 3 years was 88.0 % and after 5 years 82.5 %. Adherence differed between regions in Sweden and was positively associated with age at diagnosis between 41-74 years. Urban areas had a lower adherence than rural areas (80.7 % vs 83.6 %; p= <0.001). Conclusions: Adherence to AET in Sweden was good, although there were differences by age and urban and rural areas. Further studies are needed to identify factors affecting differences in adherence, with the purpose of initiate actions to increase adherence to AET in ER positive EBC patients.
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45. |
- Andersson, Anne, et al.
(author)
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Camera-based Colour Contrast Evaluation
- 2012
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Reports (peer-reviewed)abstract
- This project studies whether or not a digital camera can be used to evaluate colour difference or colour contrast. When characterizing a test object that changes colour over time it is not always possible to do a normal colour measurement with a spectroradiometer. The alternative could be to use film or rapid fire photography to record the changes and extract the colour data from the digital information. This project involves development of a method where spectroradiometric data of a colour chart is compared to digital data taken from photos and film of the same colour chart using Photoshop. In each measurement 22 colours have been evaluated by calculating the colour difference between a direct spectroradiometric measurement of a single colour and data taken from Photoshop of that same colour. The data is compared in the CIELAB colour space using the ?E94 metric which should faithfully represent how the human eye perceives colour difference. Three sets of measurements are made .Two sets where the spectroradiometric data is compared to data from still photos, first with photos directly from the camera and then with RAW-data from the camera. The third measurement compared the spectroradiometric data with data from a frame from a video. The results show that the 22 colours are reproduced with varying degrees of accuracy in photos and video compared to a direct measurement using a spectroradiometer. For the two photo measurements the results span from ?E94 = 0.82 for the best colour reproduction to ?E94 = 17.01 for the worst reproduction. The average deviation was ?E94 = 7.48 and ?E94 = 8.46 respectively where a colour difference of ?E94 =1.0 is considered a just noticeable difference. For video the deviation spans from ?E94 = 4.89 to ?E94 = 18.11 with an average deviation of ?E94 = 11.59. ?E94 has also been used to evaluate how the colour contrast between two different colours differ between the spectroradiometric measurement and data from Photoshop. The results show that for photos the colour contrast deviates quite a bit between the two methods. A deeper evaluation of the video method shows that as long as the contrast between two colours is small the deviation compared to the spectroradiometric measurement will also be small.
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46. |
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47. |
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48. |
- Andersson, Anne, 1966-, et al.
(author)
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Family history of cancer as a risk factor for second malignancies after Hodgkin's lymphoma
- 2008
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 98:5, s. 1001-1005
-
Journal article (peer-reviewed)abstract
- This study estimated the risk of second primary malignancies after Hodgkin's lymphoma (HL) in relation to family history of cancer, age at diagnosis and latency, among 6946 patients treated for HL in Sweden in 1965–1995 identified through the Swedish Cancer Register (SCR). First-degree relatives (FDRs) to the HL patients and their malignancies were then ascertained together with their malignancies through the Multi-Generation Registry and SCR. The HL patient cohort was stratified on the number of FDRs with cancer, and standardised incidence ratios (SIRs) of developing SM were analysed. In the HL cohort, 781 SM were observed 1 year or longer after HL diagnosis. The risk for developing SM increased with the number of FDRs with cancer, SIRs being 2.26, 3.01, and 3.45 with 0, 1, or ≥2 FDRs with cancer, respectively. Hodgkin's lymphoma long-term survivors treated at a young age with a family history of cancer carry an increased risk for developing SM and may represent a subgroup where standardised screening for the most common cancer sites could be offered in a stringent surveillance programme.
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49. |
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50. |
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