| 1. |
- Antoniou, A. C., et al.
(författare)
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Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers : Implications for risk prediction
- 2010
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Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 70:23, s. 9742-9754
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Tidskriftsartikel (refereegranskat)abstract
- The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR = 1.10, 95% CI: 1.03-1.18, P = 0.006 and HR = 1.09, 95% CI: 1.01-1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P = 7 × 10-11 - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42% to 50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers.
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| 2. |
- Kemppinen, Julia, et al.
(författare)
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Microclimate, an important part of ecology and biogeography
- 2024
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Ingår i: GLOBAL ECOLOGY AND BIOGEOGRAPHY. - 1466-822X .- 1466-8238. ; 33:6
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Tidskriftsartikel (refereegranskat)abstract
- Brief introduction: What are microclimates and why are they important?Microclimate science has developed into a global discipline. Microclimate science is increasingly used to understand and mitigate climate and biodiversity shifts. Here, we provide an overview of the current status of microclimate ecology and biogeography in terrestrial ecosystems, and where this field is heading next.Microclimate investigations in ecology and biogeographyWe highlight the latest research on interactions between microclimates and organisms, including how microclimates influence individuals, and through them populations, communities and entire ecosystems and their processes. We also briefly discuss recent research on how organisms shape microclimates from the tropics to the poles.Microclimate applications in ecosystem managementMicroclimates are also important in ecosystem management under climate change. We showcase new research in microclimate management with examples from biodiversity conservation, forestry and urban ecology. We discuss the importance of microrefugia in conservation and how to promote microclimate heterogeneity.Methods for microclimate scienceWe showcase the recent advances in data acquisition, such as novel field sensors and remote sensing methods. We discuss microclimate modelling, mapping and data processing, including accessibility of modelling tools, advantages of mechanistic and statistical modelling and solutions for computational challenges that have pushed the state-of-the-art of the field.What's next?We identify major knowledge gaps that need to be filled for further advancing microclimate investigations, applications and methods. These gaps include spatiotemporal scaling of microclimate data, mismatches between macroclimate and microclimate in predicting responses of organisms to climate change, and the need for more evidence on the outcomes of microclimate management.
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| 3. |
- Gorasso, Vanessa, et al.
(författare)
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Burden of disease attributable to risk factors in European countries: a scoping literature review
- 2023
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Ingår i: Archives of Public Health. - 0778-7367 .- 2049-3258. ; 81:1
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Forskningsöversikt (refereegranskat)abstract
- Objectives: Within the framework of the burden of disease (BoD) approach, disease and injury burden estimates attributable to risk factors are a useful guide for policy formulation and priority setting in disease prevention. Considering the important differences in methods, and their impact on burden estimates, we conducted a scoping literature review to: (1) map the BoD assessments including risk factors performed across Europe; and (2) identify the methodological choices in comparative risk assessment (CRA) and risk assessment methods. Methods: We searched multiple literature databases, including grey literature websites and targeted public health agencies websites. Results: A total of 113 studies were included in the synthesis and further divided into independent BoD assessments (54 studies) and studies linked to the Global Burden of Disease (59 papers). Our results showed that the methods used to perform CRA varied substantially across independent European BoD studies. While there were some methodological choices that were more common than others, we did not observe patterns in terms of country, year or risk factor. Each methodological choice can affect the comparability of estimates between and within countries and/or risk factors, since they might significantly influence the quantification of the attributable burden. From our analysis we observed that the use of CRA was less common for some types of risk factors and outcomes. These included environmental and occupational risk factors, which are more likely to use bottom-up approaches for health outcomes where disease envelopes may not be available. Conclusions: Our review also highlighted misreporting, the lack of uncertainty analysis and the under-investigation of causal relationships in BoD studies. Development and use of guidelines for performing and reporting BoD studies will help understand differences, avoid misinterpretations thus improving comparability among estimates.
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| 4. |
- Maxwell, Christopher A., et al.
(författare)
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Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer
- 2011
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Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.
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| 5. |
- Bilterys, T., et al.
(författare)
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Predictors for physical activity and its change after active physical therapy in people with spinal pain and insomnia: Secondary analysis of a randomized controlled trial
- 2022
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Ingår i: Brazilian Journal of Physical Therapy. - : Elsevier BV. - 1413-3555. ; 26:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: In healthy people and people with nonspecific chronic spinal pain (nCSP) and/or insomnia, participation in physical activity on a regular basis has several physical and psychological health benefits. However, people with chronic conditions often tend to reduce physical activity participation which can lead to deconditioning over time. Currently, there are no known predictors for an (in)active lifestyle (before and after physical therapy treatment) in people with chronic spinal pain and comorbid insomnia. Objective: To examine predictors of pre-treatment moderate-to-vigorous physical activity (MVPA) and to examine determinants for a change in MVPA in response to 14-weeks of active physical therapy treatment in people with nonspecific chronic spinal pain (nCSP) and comorbid insomnia. Methods: Baseline data and post-treatment data were analyzed for 66 participants. A linear multiple regression analysis was conducted to examine which factors predict MVPA at baseline. Linear mixed-effects modeling was used to identify determinants for change in MVPA in response to an active physical therapy treatment. Results: Physical fatigue (b = -0.9; 95%CI: -1.59, -0.15), less limitations in functioning as a result of emotional problems (b = 0.1; 95%CI: 0.03, 0.10), mental fatigue (b = -1.0; 95%CI: -1.67, -0.43), lower general sleep quality (b= 0.7; 95%CI: 0.22, 1.17), and body mass index (b = -0.5; 95%CI: -0.93, -0.16) were significant predictors of baseline MVPA. The regression model explained 33.3% of the total variance in baseline MVPA. The change of MVPA in response to the treatment ranged from a decrease of 17.5 to an increase of 16.6 hours per week. No determinants for change in MVPA after treatment could be identified. Conclusion: People with nCSP and comorbid insomnia are more likely to engage in MVPA if they report, at baseline, lower sleep quality, fewer limitations in functioning resulting from emotional problems, lower body mass index, as well as less physical and mental fatigue.
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| 6. |
- Lenoir, D., et al.
(författare)
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Are Reports of Pain, Disability, Quality of Life, Psychological Factors, and Central Sensitization Related to Outcomes of Quantitative Sensory Testing in Patients Suffering From Chronic Whiplash Associated Disorders?
- 2022
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Ingår i: Clinical Journal of Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0749-8047 .- 1536-5409. ; 38:3, s. 159-172
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic whiplash associated disorders (CWAD) are characterized by long-lasting symptoms of neck pain occurring after an acceleration-deceleration injury. Central sensitization (CS) has been suggested as the possible underlying mechanism for these symptoms, and is characterized by changes in the central nervous system. Besides CS, psychological factors are believed to play an important role in the experience of (chronic) pain. Objective: Investigating the relationships between self-reported pain, disability, quality of life, psychological factors, and symptoms of CS; and electrical-based quantitative sensory testing (QST) outcomes in CWAD patients. Secondly, to investigate the differences in QST between CWAD patients and pain-free controls. Methods: Seventy-two individuals with CWAD and 55 pain-free controls underwent electrical stimuli-based QST. Detection and pain thresholds (EPT), temporal summation (TS), and conditioned pain modulation were examined. Spearman correlation and linear mixed models analyses were performed to assess, respectively, the hypothesized associations and group differences in QST. Results: The Pain Catastrophizing magnification subscale correlated with the left wrist EPT (r=-0.332; P=0.004), and the Pain Anxiety Symptom Scale-20 with the left wrist (r=-0.325; P=0.005) and ankle (r=-0.330; P=0.005) EPT. TS at the ankle correlated with the CS inventory (r=0.303; P=0.010), Short Form 36 pain subscale (r=-0.325; P=0.005), and Illness Perception Questionnaire revised consequences subscale (r=0.325; P=0.005). EPTs left (P=0.011) and right wrist (P=0.023) were lower in the CWAD group, but conditioned pain modulation and TS did not differ between groups. Conclusion: QST outcomes relate to psychological constructs, rather than to self-reported pain intensity and distribution. Local hyperalgesia was found in individuals with CWAD, but no differences in endogenous pain facilitation nor inhibition.
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