| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 3. |
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| 7. |
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| 8. |
- Ferreira, MA, et al.
(författare)
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Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1741-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
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| 17. |
- Barnes, DR, et al.
(författare)
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Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores
- 2022
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 114:1, s. 109-122
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRecent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.Methods483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)–negative (PRSER-), or ER-positive (PRSER+) breast cancer risk.ResultsPRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.ConclusionsPopulation-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.
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| 18. |
- Chatzikonstantinou, T, et al.
(författare)
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COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study
- 2021
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 35:12, s. 3444-3454
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Tidskriftsartikel (refereegranskat)abstract
- Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.
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| 19. |
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| 20. |
- Dent, W. R. F., et al.
(författare)
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GASPS-A Herschel Survey of Gas and Dust in Protoplanetary Disks: Summary and Initial Statistics
- 2013
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 125:927, s. 477-505
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Tidskriftsartikel (refereegranskat)abstract
- We describe a large-scale far-infrared line and continuum survey of protoplanetary disk through to young debris disk systems carried out using the ACS instrument on the Herschel Space Observatory. This Open Time Key program, known as GASPS (Gas Survey of Protoplanetary Systems), targeted similar to 250 young stars in narrow wavelength regions covering the [OI] fine structure line at 63 mu m the brightest far-infrared line in such objects. A subset of the brightest targets were also surveyed in [OI]145 mu m, [CII] at 157 mu m, as well as several transitions of H2O and high-excitation CO lines at selected wavelengths between 78 and 180 mu m. Additionally, GASPS included continuum photometry at 70, 100 and 160 mu m, around the peak of the dust emission. The targets were SED Class II-III T Tauri stars and debris disks from seven nearby young associations, along with a comparable sample of isolated Herbig AeBe stars. The aim was to study the global gas and dust content in a wide sample of circumstellar disks, combining the results with models in a systematic way. In this overview paper we review the scientific aims, target selection and observing strategy of the program. We summarise some of the initial results, showing line identifications, listing the detections, and giving a first statistical study of line detectability. The [OI] line at 63 mu m was the brightest line seen in almost all objects, by a factor of similar to 10. Overall [OI]63 mu m detection rates were 49%, with 100% of HAeBe stars and 43% of T Tauri stars detected. A comparison with published disk dust masses (derived mainly from sub-mm continuum, assuming standard values of the mm mass opacity) shows a dust mass threshold for [OI] 63 mu m detection of similar to 10(-5) M-circle dot. Normalising to a distance of 140 pc, 84% of objects with dust masses >= 10(-5) M-circle dot can be detected in this line in the present survey; 32% of those of mass 10(-6)-10(-5) M-circle dot, and only a very small number of unusual objects with lower masses can be detected. This is consistent with models with a moderate UV excess and disk flaring. For a given disk mass, [OI] detectability is lower for M stars compared with earlier spectral types. Both the continuum and line emission was, in most systems, spatially and spectrally unresolved and centred on the star, suggesting that emission in most cases was from the disk. Approximately 10 objects showed resolved emission, most likely from outflows. In the GASPS sample, [OI] detection rates in T Tauri associations in the 0.3-4 Myr age range were similar to 50%. For each association in the 5-20 Myr age range, similar to 2 stars remain detectable in [OI]63 mu m, and no systems were detected in associations with age >20 Myr. Comparing with the total number of young stars in each association, and assuming a ISM-like gas/dust ratio, this indicates that similar to 18% of stars retain a gas-rich disk of total mass similar to 1 M-Jupiter for 1-4 Myr, 1-7% keep such disks for 5-10 Myr, but none are detected beyond 10-20 Myr. The brightest [OI] objects from GASPS were also observed in [OI]145 mu m, [CII]157 mu m and CO J = 18 - 17, with detection rates of 20-40%. Detection of the [CII] line was not correlated with disk mass, suggesting it arises more commonly from a compact remnant envelope.
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| 21. |
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| 25. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 26. |
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| 27. |
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| 28. |
- Hakkaart, C, et al.
(författare)
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Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 1061-
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Tidskriftsartikel (refereegranskat)abstract
- The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09–1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.
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| 29. |
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| 30. |
- Berry, S D, et al.
(författare)
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Application of the National Osteoporosis Foundation Guidelines to postmenopausal women and men: the Framingham Osteoporosis Study.
- 2010
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Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 21:1, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- We applied the 2008 National Osteoporosis Foundation (NOF) Guidelines to Framingham Osteoporosis Study participants and found nearly one half of Caucasian postmenopausal women and one sixth of men aged 50 years and older would be recommended for osteoporosis treatment. Given the high proportion of persons recommended for treatment, NOF Guidelines may need to be re-evaluated with respect to budget impact. INTRODUCTION: Little is known about the public health impact of the NOF Guidelines. Therefore, we determined the proportion of US Caucasians recommended for treatment of osteoporosis according to NOF Guidelines (2003 and 2008). METHODS: One thousand nine hundred and forty-six postmenopausal women and 1,681 men aged > or =50 years from the Framingham Study with information on bone mineral density (1987-2001) were included. Information on clinical predictors was used to estimate the 10-year probability of hip and major osteoporotic fracture by FRAX (version 3.0). RESULTS: Overall proportion of women meeting treatment criterion was less when the 2008 NOF Guidelines were applied (41.1%) compared with 2003 Guidelines (47.8%). The proportion of women aged <65 years meeting treatment criterion was much less when applying 2008 Guidelines (23.1% in 2003, 8.3% in 2008), whereas the proportion of women aged >75 years increased slightly (78.3% in 2003, 86.0% in 2008). Seventeen percent of men aged > or =50 years met treatment criterion (2.5% aged 50-64 years, 49.8% aged >75 years). CONCLUSIONS: Nearly one half of Caucasian postmenopausal women and one sixth of men aged 50 years and older would be recommended for osteoporosis treatment according to 2008 NOF Guidelines. Given the high proportion of persons recommended for treatment, NOF Guidelines may need to be re-evaluated with respect to budget impact.
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| 31. |
- Cooke, S.J., et al.
(författare)
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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
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Ingår i: Fisheries. ; 33:7, s. 321-338
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Tidskriftsartikel (refereegranskat)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.
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| 32. |
- Donaldson, M., et al.
(författare)
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Optimal Pubertal Induction in Girls with Turner Syndrome Using Either Oral or Transdermal Estradiol: A Proposed Modern Strategy
- 2019
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Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 91:3, s. 153-163
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most girls with Turner syndrome (TS) require pubertal induction with estrogen, followed by long term replacement. However, no adequately powered prospective studies comparing transdermal with oral 17 beta-estradiol administration exist. This reflects the difficulty of securing funding to study a rare condition with relatively low morbidity/mortality when competing against conditions such as cancer and vascular disease. Protocol Consensus: The TS Working Group of the European Society for Paediatric Endocrinology (ESPE) has agreed to both a 3-year oral and a 3-year transdermal regimen for pubertal induction. Prerequisites include suitable 17 beta-estradiol tablets and matrix patches to allow the delivery of incremental doses based on body weight. Study Proposal: An international prospective cohort study with single centre analysis is proposed in which clinicians and families are invited to choose either of the agreed regimens, usually starting at 11 years. We hypothesise that pubertal induction with transdermal estradiol will result in better outcomes for some key parameters. The primary outcome measure chosen is height gain during the induction period. Analysis: Assessment of the demographics and drop-out rates of patients choosing either oral or transdermal preparations; and appropriate analysis of outcomes including pubertal height gain, final height, liver enzyme and lipid profile, adherence/acceptability, cardiovascular health, including systolic and diastolic blood pressure and aortic root diameter and bone health. Conclusion: The proposed model of prospective data collection according to internationally agreed protocols aims to break the current impasse in obtaining evidence-based management for TS and could be applied to other rare paediatric endocrine conditions. (C) 2019 S. Karger AG, Basel
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| 33. |
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| 34. |
- Grudniewicz, A, et al.
(författare)
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Predatory journals: no definition, no defence
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 576:7786, s. 210-212
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Tidskriftsartikel (refereegranskat)
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| 35. |
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| 36. |
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| 38. |
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| 39. |
- Donaldson, J, et al.
(författare)
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The effectiveness of enzymatic replacement therapy measured by turbidimetry and the lipaemic index in exocrine pancreatic insufficient young, growing pigs, fed a high-fat diet.
- 2009
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Ingår i: Advances in Medical Sciences. - : Elsevier BV. - 1896-1126 .- 1898-4002. ; 54:1, s. 7-13
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Conventionally, the management of exocrine pancreatic insufficiency (EPI) involves the consumption of a specific diet as well as the replacement of pancreatic enzymes, the effectiveness of which is usually measured by a classical method of blood analyses of non-esterified fatty acids (NEFA) and triglycerides (TG). Dietary supplementation with a pancreatic enzyme preparation (PEP), in conjunction with a high-fat diet, on growth performance, digestibility and absorption (analysed using turbidimetry) of dietary fat in pigs with EPI was investigated.Materials/Methods: EPI was developed by surgical ligation of the pancreatic duct of six male pigs, 6 weeks of age. The pigs were fed a high fat diet (twice daily). A PEP containing 1800 mg entero-coated pancreatin was included in the high fat meals. Blood, urine and faecal samples were collected. The urine and faeces were analysed for dry matter, crude protein and fat content. The lipaemic index and plasma lipid profiles were assessed.Results: EPI completely stopped growth of the pigs. Treatment with PEP significantly increased (P<0.05) growth and body mass as well as the digestibility of dry matter and crude protein. PEP significantly improved the co-efficient of fat absorption, the lipaemic index (measured by turbidimetry methods) and caused significant changes in plasma nonesterified fatty acids and triglyceride concentrations.Conclusions: The short term enzymatic replacement therapy together with a high fat meal has immediate beneficial effects on diet digestibility and on the growth retardation observed in EPI pigs. The turbidimetry method used to measure lipaemic index is a reliable, quick and efficient technique in measuring plasma lipid profiles and thus a good tool for assessing fat absorption.
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| 40. |
- Fang, Li Tai, et al.
(författare)
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Establishing community reference samples, data and call sets for benchmarking cancer mutation detection using whole-genome sequencing
- 2021
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 39:9, s. 1151-1160
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Tidskriftsartikel (refereegranskat)abstract
- Tumor-normal paired DNA samples from a breast cancer cell line and a matched lymphoblastoid cell line enable calibration of clinical sequencing pipelines and benchmarking 'tumor-only' or 'matched tumor-normal' analyses. The lack of samples for generating standardized DNA datasets for setting up a sequencing pipeline or benchmarking the performance of different algorithms limits the implementation and uptake of cancer genomics. Here, we describe reference call sets obtained from paired tumor-normal genomic DNA (gDNA) samples derived from a breast cancer cell line-which is highly heterogeneous, with an aneuploid genome, and enriched in somatic alterations-and a matched lymphoblastoid cell line. We partially validated both somatic mutations and germline variants in these call sets via whole-exome sequencing (WES) with different sequencing platforms and targeted sequencing with >2,000-fold coverage, spanning 82% of genomic regions with high confidence. Although the gDNA reference samples are not representative of primary cancer cells from a clinical sample, when setting up a sequencing pipeline, they not only minimize potential biases from technologies, assays and informatics but also provide a unique resource for benchmarking 'tumor-only' or 'matched tumor-normal' analyses.
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| 41. |
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| 42. |
- Henriksen, Kristoffer, et al.
(författare)
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Athlete mental health in the Olympic/Paralympic quadrennium : a multi-societal consensus statement
- 2020
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Ingår i: International Journal of Sport and Exercise Psychology. - 1612-197X. ; 18:3, s. 391-408
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Tidskriftsartikel (refereegranskat)abstract
- This consensus statement is the product of the Second International Think Tank on Athlete Mental Health, held on the initiative of the International Society of Sport Psychology. The purposes of the Think Tank were to engage international sport psychology societies and organisations in a discussion about athlete mental health as embedded in an Olympic/Paralympic cycle, and to develop practical recommendations for sport organisations. An invited group of designated experts discussed applied experiences working with athletes within an Olympic and Paralympic environment. The Games and mental health are interrelated, because athletes committing whole-heartedly to an Olympic/Paralympic pursuit are at increased risk of disappointment, identity foreclosure, and high life stress. Dividing the quadrennial into three main phases (i.e., pre-, during-, and post-Games) participants discussed three topics for each phase: (1) the key opportunities and challenges; (2) the sport environment, and how it can nourish or malnourish athlete mental health; and (3) collaboration and communication within expert support teams. Each phase of the quadrennium presents specific challenges and opportunities, and mental health screening and support should be administered across all phases. However, the post-Games period is one of increased vulnerability, while at the same time, the returning staff is oftentimes exhausted and unavailable. Ideally, a specialised collaborative team should handle the post-Games mental health support. Initiatives are needed to (a) improve the psychological safety of pre-, during-, and post-Games high performance environments, (b) reduce unnecessary stress, (c) optimise recovery, (d) de-stigmatize mental health issues, and (e) increase help-seeking.
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| 43. |
- Hong, A. C., et al.
(författare)
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Uptake of Hydrogen Peroxide from the Gas Phase to Grain Boundaries: A Source in Snow and Ice
- 2023
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Ingår i: Environmental Science and Technology. - 0013-936X .- 1520-5851. ; 57:31, s. 11626-11633
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Tidskriftsartikel (refereegranskat)abstract
- This work shows that hydrogen peroxidereadily enters grainboundaries in ice and snow directly from the atmosphere. Acceleratedreaction rates in these reservoirs have been described with an impacton air quality and snow composition. Hydrogen peroxide is a primary atmospheric oxidant significantin terminating gas-phase chemistry and sulfate formation in the condensedphase. Laboratory experiments have shown an unexpected oxidation accelerationby hydrogen peroxide in grain boundaries. While grain boundaries arefrequent in natural snow and ice and are known to host impurities,it remains unclear how and to which extent hydrogen peroxide entersthis reservoir. We present the first experimental evidence for thediffusive uptake of hydrogen peroxide into grain boundaries directlyfrom the gas phase. We have machined a novel flow reactor system featuringa drilled ice flow tube that allows us to discern the effect of theice grain boundary content on the uptake. Further, adsorption to theice surface for temperatures from 235 to 258 K was quantified. Disentanglingthe contribution of these two uptake processes shows that the transferof hydrogen peroxide from the atmosphere to snow at temperatures relevantto polar environments is considerably more pronounced than previouslythought. Further, diffusive uptake to grain boundaries appears tobe a novel mechanism for non-acidic trace gases to fill the highlyreactive impurity reservoirs in snow's grain boundaries.
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| 44. |
- Hunter, Amanda, et al.
(författare)
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Effect of wood smoke exposure on vascular function and thrombus formation in healthy fire fighters
- 2014
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Ingår i: Particle and Fibre Toxicology. - : BioMed Central (BMC). - 1743-8977. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Myocardial infarction is the leading cause of death in fire fighters and has been linked with exposure to air pollution and fire suppression duties. We therefore investigated the effects of wood smoke exposure on vascular vasomotor and fibrinolytic function, and thrombus formation in healthy fire fighters. Methods: In a double-blind randomized cross-over study, 16 healthy male fire fighters were exposed to wood smoke (~1 mg/m3 particulate matter concentration) or filtered air for one hour during intermittent exercise. Arterial pressure and stiffness were measured before and immediately after exposure, and forearm blood flow was measured during intra-brachial infusion of endothelium-dependent and -independent vasodilators 4–6 hours after exposure. Thrombus formation was assessed using the ex vivo Badimon chamber at 2 hours, and platelet activation was measured using flow cytometry for up to 24 hours after the exposure. Results: Compared to filtered air, exposure to wood smoke increased blood carboxyhaemoglobin concentrations (1.3% versus 0.8%; P < 0.001), but had no effect on arterial pressure, augmentation index or pulse wave velocity (P > 0.05 for all). Whilst there was a dose-dependent increase in forearm blood flow with each vasodilator (P < 0.01 for all), there were no differences in blood flow responses to acetylcholine, sodium nitroprusside or verapamil between exposures (P > 0.05 for all). Following exposure to wood smoke, vasodilatation to bradykinin increased (P = 0.003), but there was no effect on bradykinin-induced tissue-plasminogen activator release, thrombus area or markers of platelet activation (P > 0.05 for all). Conclusions: Wood smoke exposure does not impair vascular vasomotor or fibrinolytic function, or increase thrombus formation in fire fighters. Acute cardiovascular events following fire suppression may be precipitated by exposure to other air pollutants or through other mechanisms, such as strenuous physical exertion and dehydration.
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| 46. |
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| 47. |
- Kovalchik, Stephanie A, et al.
(författare)
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Absolute Risk Prediction of Second Primary Thyroid Cancer Among 5-Year Survivors of Childhood Cancer.
- 2012
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Ingår i: Journal of Clinical Oncology. - 1527-7755.
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSEWe developed three absolute risk models for second primary thyroid cancer to assist with long-term clinical monitoring of childhood cancer survivors. PATIENTS AND METHODSWe used data from the Childhood Cancer Survivor Study (CCSS) and two nested case-control studies (Nordic CCSS; Late Effects Study Group). Model M1 included self-reported risk factors, model M2 added basic radiation and chemotherapy treatment information abstracted from medical records, and model M3 refined M2 by incorporating reconstructed radiation absorbed dose to the thyroid. All models were validated in an independent cohort of French childhood cancer survivors.ResultsM1 included birth year, initial cancer type, age at diagnosis, sex, and past thyroid nodule diagnosis. M2 added radiation (yes/no), radiation to the neck (yes/no), and alkylating agent (yes/no). Past thyroid nodule was consistently the strongest risk factor (M1 relative risk [RR ], 10.8; M2 RR, 6.8; M3 RR, 8.2). In the validation cohort, 20-year absolute risk predictions for second primary thyroid cancer ranged from 0.04% to 7.4% for M2. Expected events agreed well with observed events for each model, indicating good calibration. All models had good discriminatory ability (M1 area under the receiver operating characteristics curve [AUC ], 0.71; 95% CI, 0.64 to 0.77; M2 AUC, 0.80; 95% CI, 0.73 to 0.86; M3 AUC, 0.75; 95% CI, 0.69 to 0.82). CONCLUSIONWe developed and validated three absolute risk models for second primary thyroid cancer. Model M2, with basic prior treatment information, could be useful for monitoring thyroid cancer risk in childhood cancer survivors.
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| 48. |
- Mills, Nicholas L, et al.
(författare)
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Air pollution and atherothrombosis.
- 2007
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Ingår i: Inhal Toxicol. - : Informa UK Limited. - 1091-7691. ; 19 Suppl 1, s. 81-9
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Tidskriftsartikel (refereegranskat)
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| 49. |
- Mills, Nicholas L, et al.
(författare)
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Exposure to concentrated ambient particles does not affect vascular function in patients with coronary heart disease
- 2008
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Ingår i: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Sciences. - 0091-6765 .- 1552-9924. ; 116:6, s. 709-715
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Exposure to fine particulate air pollution is associated with increased cardiovascular morbidity and mortality. We previously demonstrated that exposure to dilute diesel exhaust causes vascular dysfunction in humans.OBJECTIVES: We conducted a study to determine whether exposure to ambient particulate matter causes vascular dysfunction. METHODS: Twelve male patients with stable coronary heart disease and 12 age-matched volunteers were exposed to concentrated ambient fine and ultrafine particles (CAPs) or filtered air for 2 hr using a randomized, double-blind cross-over study design. We measured peripheral vascular vasomotor and fibrinolytic function, and inflammatory variables-including circulating leukocytes, serum C-reactive protein, and exhaled breath 8-isoprostane and nitrotyrosine-6-8 hr after both exposures.RESULTS: Particulate concentrations (mean +/- SE) in the exposure chamber (190+/-37 microg/m(3)) were higher than ambient levels (31+/-8 microg/m(3)) and levels in filtered air (0.5+/-0.4 microg/m(3); p<0.001). Chemical analysis of CAPs identified low levels of elemental carbon. Exhaled breath 8-isoprostane concentrations increased after exposure to CAPs (16.9+/-8.5 vs. 4.9+/-1.2 pg/mL, p<0.05), but markers of systemic inflammation were largely unchanged. Although there was a dose-dependent increase in blood flow and plasma tissue plasminogen activator release (p<0.001 for all), CAPs exposure had no effect on vascular function in either group.CONCLUSIONS: Despite achieving marked increases in particulate matter, exposure to CAPs--low in combustion-derived particles--did not affect vasomotor or fibrinolytic function in either middle-aged healthy volunteers or patients with coronary heart disease. These findings contrast with previous exposures to dilute diesel exhaust and highlight the importance of particle composition in determining the vascular effects of particulate matter in humans.
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- Mills, Nicholas L, et al.
(författare)
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Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men with coronary heart disease
- 2007
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 357:11, s. 1075-1082
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Exposure to air pollution from traffic is associated with adverse cardiovascular events. The mechanisms for this association are unknown. We conducted a controlled exposure to dilute diesel exhaust in patients with stable coronary heart disease to determine the direct effect of air pollution on myocardial, vascular, and fibrinolytic function.METHODS: In a double-blind, randomized, crossover study, 20 men with prior myocardial infarction were exposed, in two separate sessions, to dilute diesel exhaust (300 mug per cubic meter) or filtered air for 1 hour during periods of rest and moderate exercise in a controlled-exposure facility. During the exposure, myocardial ischemia was quantified by ST-segment analysis using continuous 12-lead electrocardiography. Six hours after exposure, vasomotor and fibrinolytic function were assessed by means of intraarterial agonist infusions.RESULTS: During both exposure sessions, the heart rate increased with exercise (P<0.001); the increase was similar during exposure to diesel exhaust and exposure to filtered air (P=0.67). Exercise-induced ST-segment depression was present in all patients, but there was a greater increase in the ischemic burden during exposure to diesel exhaust (-22+/-4 vs. -8+/-6 millivolt seconds, P<0.001). Exposure to diesel exhaust did not aggravate preexisting vasomotor dysfunction, but it did reduce the acute release of endothelial tissue plasminogen activator (P=0.009; 35% decrease in the area under the curve).CONCLUSIONS: Brief exposure to dilute diesel exhaust promotes myocardial ischemia and inhibits endogenous fibrinolytic capacity in men with stable coronary heart disease. Our findings point to ischemic and thrombotic mechanisms that may explain in part the observation that exposure to combustion-derived air pollution is associated with adverse cardiovascular events.
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