| 1. |
- Bravo, L, et al.
(author)
-
- 2021
-
swepub:Mat__t
|
|
| 2. |
- Tabiri, S, et al.
(author)
-
- 2021
-
swepub:Mat__t
|
|
| 3. |
- Thomas, HS, et al.
(author)
-
- 2019
-
swepub:Mat__t
|
|
| 4. |
|
|
| 5. |
- Niemi, MEK, et al.
(author)
-
- 2021
-
swepub:Mat__t
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Kanai, M, et al.
(author)
-
- 2023
-
swepub:Mat__t
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Khatri, C, et al.
(author)
-
Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
-
In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
-
Journal article (peer-reviewed)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
|
|
| 14. |
- Waldorf, Kristina M. Adams, et al.
(author)
-
Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain
- 2018
-
In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 24:3, s. 368-374
-
Journal article (peer-reviewed)abstract
- Zika virus (ZIKV) is a flavivirus with teratogenic effects on fetal brain, but the spectrum of ZIKV-induced brain injury is unknown, particularly when ultrasound imaging is normal. In a pregnant pigtail macaque (Macaca nemestrina) model of ZIKV infection, we demonstrate that ZIKV-induced injury to fetal brain is substantial, even in the absence of microcephaly, and may be challenging to detect in a clinical setting. A common and subtle injury pattern was identified, including (i) periventricular T2-hyperintense foci and loss of fetal noncortical brain volume, (ii) injury to the ependymal epithelium with underlying gliosis and (iii) loss of late fetal neuronal progenitor cells in the subventricular zone (temporal cortex) and subgranular zone (dentate gyrus, hippocampus) with dysmorphic granule neuron patterning. Attenuation of fetal neurogenic output demonstrates potentially considerable teratogenic effects of congenital ZIKV infection even without microcephaly. Our findings suggest that all children exposed to ZIKV in utero should receive long-term monitoring for neurocognitive deficits, regardless of head size at birth.
|
|
| 15. |
- de Blok, W.J.G., et al.
(author)
-
an overview of the MHONGOOSE survey: Observing nearby galaxies with MeerKAT
- 2016
-
In: Proceedings of Science. - 1824-8039.
-
Conference paper (peer-reviewed)abstract
- MHONGOOSE is a deep survey of the neutral hydrogen distribution in a representative sample of 30 nearby disk and dwarf galaxies with H I masses from ∼ 106 to ∼ 1011 M, and luminosities from MR ∼ 12 to MR ∼ −22. The sample is selected to uniformly cover the available range in log(MHI). Our extremely deep observations, down to H I column density limits of well below 1018 cm−2 — or a few hundred times fainter than the typical H I disks in galaxies — will directly detect the effects of cold accretion from the intergalactic medium and the links with the cosmic web. These observations will be the first ever to probe the very low-column density neutral gas in galaxies at these high resolutions. Combination with data at other wavelengths, most of it already available, will enable accurate modeling of the properties and evolution of the mass components in these galaxies and link these with the effects of environment, dark matter distribution, and other fundamental properties such as halo mass and angular momentum. MHONGOOSE can already start addressing some of the SKA-1 science goals and will provide a comprehensive inventory of the processes driving the transformation and evolution of galaxies in the nearby universe at high resolution and over 5 orders of magnitude in column density. It will be a Nearby Galaxies Legacy Survey that will be unsurpassed until the advent of the SKA, and can serve as a highly visible, lasting statement of MeerKAT’s capabilities.
|
|
| 16. |
- Huyghe, Jeroen R., et al.
(author)
-
Discovery of common and rare genetic risk variants for colorectal cancer
- 2019
-
In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
-
Journal article (peer-reviewed)abstract
- To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Dixon-Suen, Suzanne C, et al.
(author)
-
Physical activity, sedentary time and breast cancer risk : a Mendelian randomisation study
- 2022
-
In: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 56:20, s. 1157-1170
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.METHODS: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.RESULTS: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).CONCLUSION: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.
|
|
| 20. |
|
|
| 21. |
- Huyghe, Jeroen R, et al.
(author)
-
Genetic architectures of proximal and distal colorectal cancer are partly distinct
- 2021
-
In: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:7, s. 1325-1334
-
Journal article (peer-reviewed)abstract
- Objective: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.Design: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.Results: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.Conclusion: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
|
|
| 22. |
|
|
| 23. |
- Schmit, Stephanie L, et al.
(author)
-
Novel Common Genetic Susceptibility Loci for Colorectal Cancer.
- 2019
-
In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:2, s. 146-157
-
Journal article (peer-reviewed)abstract
- Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
|
|
| 24. |
|
|
| 25. |
- Bretman, Amanda, et al.
(author)
-
Systematic approaches to assessing high-temperature limits to fertility in animals
- 2024
-
In: Journal of Evolutionary Biology. - 1010-061X .- 1420-9101.
-
Journal article (peer-reviewed)abstract
- Critical thermal limits (CTLs) gauge the physiological impact of temperature on survival or critical biological function, aiding predictions of species range shifts and climatic resilience. Two recent Drosophila species studies, using similar approaches to determine temperatures that induce sterility (thermal fertility limits [TFLs]), reveal that TFLs are often lower than CTLs and that TFLs better predict both current species distributions and extinction probability. Moreover, many studies show fertility is more sensitive at less extreme temperatures than survival (thermal sensitivity of fertility [TSF]). These results present a more pessimistic outlook on the consequences of climate change. However, unlike CTLs, TFL data are limited to Drosophila, and variability in TSF methods poses challenges in predicting species responses to increasing temperature. To address these data and methodological gaps, we propose 3 standardized approaches for assessing thermal impacts on fertility. We focus on adult obligate sexual terrestrial invertebrates but also provide modifications for other animal groups and life-history stages. We first outline a gold-standard protocol for determining TFLs, focussing on the effects of short-term heat shocks and simulating more frequent extreme heat events predicted by climate models. As this approach may be difficult to apply to some organisms, we then provide a standardized TSF protocol. Finally, we provide a framework to quantify fertility loss in response to extreme heat events in nature, given the limitations in laboratory approaches. Applying these standardized approaches across many taxa, similar to CTLs, will allow robust tests of the impact of fertility loss on species responses to increasing temperatures. Graphical AbstractOverview of the systematic methods (A, C, and D) to simultaneously assay lethal limits and thermal fertility limits or (B and E) thermal sensitivity of fertility. These are most easily applied to laboratory settings but can be used for assessing the fertility of wild-caught animals that have been exposed to natural temperatures.
|
|
| 26. |
- Butler, Alexandra E., et al.
(author)
-
Diagnosing type 2 diabetes using Hemoglobin A1c : a systematic review and meta-analysis of the diagnostic cutpoint based on microvascular complications
- 2021
-
In: Acta Diabetologica. - : Springer. - 0940-5429 .- 1432-5233. ; 58:3, s. 279-300
-
Research review (peer-reviewed)abstract
- Aims: Diabetic microvascular complications of retinopathy, nephropathy and neuropathy may occur at hemoglobin A1c levels (HbA1c) below the 6.5% (48 mmol/mol) diagnostic threshold. Our objective was to assess the validity of the HbA1c diagnostic cutpoint of 6.5% based upon published evidence of the prevalence of retinopathy, nephropathy and neuropathy as markers of diabetes.Methods: Data Sources PubMed, Embase, Cochrane, Scopus and CINAHL from 1990-March 2019, grey literature sources. Study Selection All studies reported after 1990 (to ensure standardized HbA1c values) where HbA1c levels were presented in relation to prevalence of retinopathy, nephropathy or neuropathy in subjects not known to have diabetes. Data Extraction Studies were screened independently, data abstracted, and risk of bias appraised. Data Synthesis Data were synthesized using HbA1c categories of < 6.0% (< 42 mmol/mol), 6.0-6.4% (42-47 mmol/mol) and >= 6.5% (>= 48 mmol/mol). Random-effects meta-analyses were conducted for retinopathy, nephropathy and neuropathy prevalence stratified by HbA1c categories. Random-effects multivariable meta-regression was conducted to identify predictors of retinopathy prevalence and sources of between-study heterogeneity.Results: Pooled mean prevalence was: 4.0%(95% CI: 3.2-5.0%) for retinopathy, 10.5% (95% CI: 4.0-19.5%) for nephropathy, 2.5% (95% CI: 1.1-4.3%) for neuropathy. Mean prevalence when stratified for HbA1c < 6.0%, 6.0-6.4% and >= 6.5% was: retinopathy: 3.4% (95% CI: 1.8-5.4%), 2.3% (95% CI: 1.6-3.2%) and 7.8%(95% CI: 5.7-10.3%); nephropathy: 7.1% (95% CI: 1.7-15.9%), 9.6% (95% CI: 0.8-26.4%) and 17.1% (95% CI: 1.0-46.9%); neuropathy: 2.1% (95% CI: 0.0-6.8%), 3.4% (95% CI: 0.0-11.6%) and 2.8% (95% CI: 0.0-12.8%). Multivariable meta-regression showed HbA1c >= 6.5% (OR: 4.05; 95% CI: 1.92-8.57%), age > 55 (OR: 3.23; 95% CI 1.81-5.77), and African-American race (OR: 10.73; 95% CI: 4.34-26.55), to be associated with higher retinopathy prevalence. Marked heterogeneity in prevalence estimates was found across all meta-analyses (Cochran's Q-statistic p < 0.0001).Conclusions: The prevalence of nephropathy and moderate retinopathy was increased in subjects with HbA1c values >= 6.5% confirming the high specificity of this value for diagnosing T2DM; however, at HbA1c < 6.5% retinopathy increased at age > 55 years and, most strikingly, in African-Americans, suggesting there may be excess microvascular complication prevalence (particularly nephropathy) in individuals below the diabetes diagnostic threshold.
|
|
| 27. |
- Cooke, S.J., et al.
(author)
-
Developing a mechanistic understanding of fish migrations by linking telemetry with physiology, behavior, genomics and experimental biology: an interdisciplinary case study on adult fraser river sockeys salmon
- 2008
-
In: Fisheries. ; 33:7, s. 321-338
-
Journal article (peer-reviewed)abstract
- Fish migration represents one of the most complex and intriguing biological phenomena in the animal kingdom. How do fish migrate such vast distances? What are the costs and benefits of migration? Some of these fundamental questions have been addressed through the use of telemetry. However, telemetry alone has not and will not yield a complete understanding of the migration biology of fish or provide solutions to problems such as identifying physical barriers to migration or understanding potential impacts of climate change. Telemetry can be coupled with other tools and techniques to yield new insights into animal biology. Using Fraser River sockeye salmon (Oncorhynchus nerka) as a model, we summarize the advances that we have made in understanding salmonid migration biology through the integration of disciplines (i.e., interdisciplinary research) including physiology, behavior, functional genomics, and experimental biology. We also discuss opportunities for using large-scale telemetry arrays and taking a more experimental approach to studies of fish migration that use telemetry (i.e., intervention studies involving endocrine implants, simulated migration studies) rather than simply focusing on descriptive or correlational techniques. Only through integrative and interdisciplinary research will it be possible to understand the mechanistic basis of fish migrations and to predict and possibly mitigate the consequences of anthropogenic impacts. Telemetry is a tool that has the potential to integrate research across disciplines and between the lab and the field to advance the science of fish migration biology. The techniques that we have applied to the study of Pacific salmon are equally relevant to other fish taxa in both marine and freshwater systems as well as migratory animals beyond ichthyofauna. The interdisciplinary approach used here was essential to address a pressing and complex conservation problem association with sockeye salmon migration.
|
|
| 28. |
- de Gonzalez, Amy Berrington, et al.
(author)
-
Body-Mass Index and Mortality among 1.46 Million White Adults.
- 2010
-
In: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 363:23, s. 2211-2219
-
Journal article (peer-reviewed)abstract
- Background: A high body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) is associated with increased mortality from cardiovascular disease and certain cancers, but the precise relationship between BMI and all-cause mortality remains uncertain. Methods: We used Cox regression to estimate hazard ratios and 95% confidence intervals for an association between BMI and all-cause mortality, adjusting for age, study, physical activity, alcohol consumption, education, and marital status in pooled data from 19 prospective studies encompassing 1.46 million white adults, 19 to 84 years of age (median, 58). Results: The median baseline BMI was 26.2. During a median follow-up period of 10 years (range, 5 to 28), 160,087 deaths were identified. Among healthy participants who never smoked, there was a J-shaped relationship between BMI and all-cause mortality. With a BMI of 22.5 to 24.9 as the reference category, hazard ratios among women were 1.47 (95 percent confidence interval [CI], 1.33 to 1.62) for a BMI of 15.0 to 18.4; 1.14 (95% CI, 1.07 to 1.22) for a BMI of 18.5 to 19.9; 1.00 (95% CI, 0.96 to 1.04) for a BMI of 20.0 to 22.4; 1.13 (95% CI, 1.09 to 1.17) for a BMI of 25.0 to 29.9; 1.44 (95% CI, 1.38 to 1.50) for a BMI of 30.0 to 34.9; 1.88 (95% CI, 1.77 to 2.00) for a BMI of 35.0 to 39.9; and 2.51 (95% CI, 2.30 to 2.73) for a BMI of 40.0 to 49.9. In general, the hazard ratios for the men were similar. Hazard ratios for a BMI below 20.0 were attenuated with longer-term follow-up. Conclusions: In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality. All-cause mortality is generally lowest with a BMI of 20.0 to 24.9. N Engl J Med 2010;363:2211-9.
|
|
| 29. |
- English, Sinead, et al.
(author)
-
Adaptive use of information during growth can explain long-term effects of early life experiences
- 2016
-
In: American Naturalist. - : University of Chicago Press. - 0003-0147 .- 1537-5323. ; 187:5, s. 620-632
-
Journal article (peer-reviewed)abstract
- Development is a continuous process during which individuals gain information about their environment and adjust their phenotype accordingly. In many natural systems, individuals are particularly sensitive to early life experiences, even in the absence of later constraints on plasticity. Recent models have highlighted how the adaptive use of information can explain age-dependent plasticity. These models assume that information gain and phenotypic adjustments either cannot occur simultaneously or are completely independent. This assumption is not valid in the context of growth, where finding food results both in a size increase and learning about food availability. Here, we describe a simple model of growth to provide proof of principle that long-termeffects of early life experiences can arise through the coupled dynamics of information acquisition and phenotypic change in the absence of direct constraints on plasticity. The increase in reproductive value from gaining information and sensitivity of behavior to experiences declines across development. Early life experiences have longterm impacts on age of maturity, yet-due to compensatory changes in behavior-our model predicts no substantial effects on reproductive success. We discuss how the evolution of sensitive windows can be explained by experiences having short-term effects on informational and phenotypic states, which generate long-term effects on life-history decisions.
|
|
| 30. |
- Garcia-Closas, Montserrat, et al.
(author)
-
Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics
- 2008
-
In: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 4:4, s. e1000054-
-
Journal article (peer-reviewed)abstract
- A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
|
|
| 31. |
- Genkinger, J. M., et al.
(author)
-
Dairy products and pancreatic cancer risk : a pooled analysis of 14 cohort studies
- 2014
-
In: Annals of Oncology. - : OXFORD UNIV PRESS. - 0923-7534 .- 1569-8041. ; 25:6, s. 1106-1115
-
Research review (peer-reviewed)abstract
- .Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy products and constituents, may play a role in pancreatic carcinogenesis. In this pooled analysis of the primary data from 14 prospective cohort studies, 2212 incident pancreatic cancer cases were identified during follow-up among 862 680 individuals. Adjusting for smoking habits, personal history of diabetes, alcohol intake, body mass index (BMI), and energy intake, multivariable study-specific hazard ratios (MVHR) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards models and then pooled using a random effects model. There was no association between total milk intake and pancreatic cancer risk (MVHR = 0.98, 95% CI = 0.82-1.18 comparing a parts per thousand yen500 with 1-69.9 g/day). Similarly, intakes of low-fat milk, whole milk, cheese, cottage cheese, yogurt, and ice-cream were not associated with pancreatic cancer risk. No statistically significant association was observed between dietary (MVHR = 0.96, 95% CI = 0.77-1.19) and total calcium (MVHR = 0.89, 95% CI = 0.71-1.12) intake and pancreatic cancer risk overall when comparing intakes a parts per thousand yen1300 with < 500 mg/day. In addition, null associations were observed for dietary and total vitamin D intake and pancreatic cancer risk. Findings were consistent within sex, smoking status, and BMI strata or when the case definition was limited to pancreatic adenocarcinoma. Overall, these findings do not support the hypothesis that consumption of dairy foods, calcium, or vitamin D during adulthood is associated with pancreatic cancer risk.
|
|
| 32. |
- Haghighi, Mona, et al.
(author)
-
A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Journal article (peer-reviewed)abstract
- Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
|
|
| 33. |
- Key, T. J., et al.
(author)
-
Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies
- 2011
-
In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 105:5, s. 709-722
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. RESULTS: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. CONCLUSION: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk. British Journal of Cancer (2011) 105, 709-722. doi:10.1038/bjc.2011.254 www.bjcancer.com Published online 19 July 2011 (C) 2011 Cancer Research UK
|
|
| 34. |
|
|
| 35. |
- Mueller-Wohlfahrt, H. W., et al.
(author)
-
Terminology and classification of muscle injuries in sport: The Munich consensus statement
- 2013
-
In: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 47:6
-
Journal article (peer-reviewed)abstract
- Objective To provide a clear terminology and classification of muscle injuries in order to facilitate Methods Thirty native English-speaking scientists and team doctors of national and first division Results The response rate of the survey was 63%. The responses confirmed the marked variability in Conclusions A consistent English terminology as well as a comprehensive classification system for What are the new things Consensus definitions of the terminology which is used in the field of muscle
|
|
| 36. |
- Taborsky, Barbara, et al.
(author)
-
An evolutionary perspective on stress responses, damage and repair
- 2022
-
In: Hormones and Behavior. - : Elsevier BV. - 0018-506X .- 1095-6867. ; 142
-
Journal article (peer-reviewed)abstract
- Variation in stress responses has been investigated in relation to environmental factors, species ecology, life history and fitness. Moreover, mechanistic studies have unravelled molecular mechanisms of how acute and chronic stress responses cause physiological impacts (‘damage’), and how this damage can be repaired. However, it is not yet understood how the fitness effects of damage and repair influence stress response evolution. Here we study the evolution of hormone levels as a function of stressor occurrence, damage and the efficiency of repair. We hypothesise that the evolution of stress responses depends on the fitness consequences of damage and the ability to repair that damage. To obtain some general insights, we model a simplified scenario in which an organism repeatedly encounters a stressor with a certain frequency and predictability (temporal autocorrelation). The organism can defend itself by mounting a stress response (elevated hormone level), but this causes damage that takes time to repair. We identify optimal strategies in this scenario and then investigate how those strategies respond to acute and chronic exposures to the stressor. We find that for higher repair rates, baseline and peak hormone levels are higher. This typically means that the organism experiences higher levels of damage, which it can afford because that damage is repaired more quickly, but for very high repair rates the damage does not build up. With increasing predictability of the stressor, stress responses are sustained for longer, because the animal expects the stressor to persist, and thus damage builds up. This can result in very high (and potentially fatal) levels of damage when organisms are exposed to chronic stressors to which they are not evolutionarily adapted. Overall, our results highlight that at least three factors need to be considered jointly to advance our understanding of how stress physiology has evolved: (i) temporal dynamics of stressor occurrence; (ii) relative mortality risk imposed by the stressor itself versus damage caused by the stress response; and (iii) the efficiency of repair mechanisms.
|
|
| 37. |
- Taborsky, Barbara, et al.
(author)
-
Towards an Evolutionary Theory of Stress Responses
- 2021
-
In: Trends in Ecology & Evolution. - : Elsevier BV. - 0169-5347 .- 1872-8383. ; 36:1, s. 39-48
-
Research review (peer-reviewed)abstract
- All organisms have a stress response system to cope with environmental threats, yet its precise form varies hugely within and across individuals, populations, and species. While the physiological mechanisms are increasingly understood, how stress responses have evolved remains elusive. Here, we show that important insights can be gained from models that incorporate physiological mechanisms within an evolutionary optimality analysis (the 'evo-mecho' approach). Our approach reveals environmental predictability and physiological constraints as key factors shaping stress response evolution, generating testable predictions about variation across species and contexts. We call for an integrated research programme combining theory, experimental evolution, and comparative analysis to advance scientific understanding of how this core physiological system has evolved.
|
|
