| 1. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 11. |
- Lawrenson, Kate, et al.
(author)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)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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| 12. |
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| 13. |
- Hakkaart, C, et al.
(author)
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Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers
- 2022
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In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 1061-
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Journal article (peer-reviewed)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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| 14. |
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| 15. |
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| 16. |
- Ferreira, MA, et al.
(author)
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Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1741-
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Journal article (peer-reviewed)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. |
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| 19. |
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| 23. |
- Barnes, DR, et al.
(author)
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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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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 114:1, s. 109-122
-
Journal article (peer-reviewed)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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| 24. |
- Dent, W. R. F., et al.
(author)
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GASPS-A Herschel Survey of Gas and Dust in Protoplanetary Disks: Summary and Initial Statistics
- 2013
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In: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 125:927, s. 477-505
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Journal article (peer-reviewed)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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| 25. |
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| 26. |
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| 27. |
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| 28. |
- Donaldson, M., et al.
(author)
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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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In: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 91:3, s. 153-163
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Journal article (peer-reviewed)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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| 29. |
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| 30. |
- Chatzikonstantinou, T, et al.
(author)
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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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In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 35:12, s. 3444-3454
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Journal article (peer-reviewed)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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| 31. |
- Meade, F. C., et al.
(author)
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Bimodal magmatism produced by progressively inhibited crustal assimilation
- 2014
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 4199-
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Journal article (peer-reviewed)abstract
- The origin of bimodal (mafic-felsic) rock suites is a fundamental question in volcanology. Here we use major and trace elements, high-resolution Sr, Nd and Pb isotope analyses, experimental petrology and thermodynamic modelling to investigate bimodal magmatism at the iconic Carlingford Igneous Centre, Ireland. We show that early microgranites are the result of extensive assimilation of trace element-enriched partial melts of local metasiltstones into mafic parent magmas. Melting experiments reveal the crust is very fusible, but thermodynamic modelling indicates repeated heating events rapidly lower its melt-production capacity. Granite generation ceased once enriched partial melts could no longer form and subsequent magmatism incorporated less fertile restite compositions only, producing mafic intrusions and a pronounced compositional gap. Considering the frequency of bimodal magma suites in the North Atlantic Igneous Province, and the ubiquity of suitable crustal compositions, we propose 'progressively inhibited crustal assimilation' (PICA) as a major cause of bimodality in continental volcanism.
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| 32. |
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| 33. |
- Adlard, B., et al.
(author)
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Future directions for monitoring and human health research for the Arctic Monitoring and Assessment Programme
- 2018
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In: Global Health Action. - : Taylor & Francis. - 1654-9716 .- 1654-9880. ; 11:1
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Journal article (peer-reviewed)abstract
- For the last two and a half decades, a network of human health experts under the Arctic Monitoring and Assessment Program (AMAP) has produced several human health assessment reports. These reports have provided a base of scientific knowledge regarding environmental contaminants and their impact on human health in the Arctic. These reports provide scientific information and policy-relevant recommendations to Arctic governments. They also support international agreements such as the Stockholm Convention on Persistent Organic Pollutants (POPs) and the Minamata Convention on Mercury. Key topics discussed in this paper regarding future human health research in the circumpolar Arctic are continued contaminant biomonitoring, health effects research and risk communication. The objective of this paper is to describe knowledge gaps and future priorities for these fields.
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| 34. |
- Allinson, James P, et al.
(author)
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Changes in lung function in European adults born between 1884 and 1996 and implications for the diagnosis of lung disease: a cross-sectional analysis of ten population-based studies.
- 2022
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In: The Lancet. Respiratory medicine. - : Elsevier. - 2213-2619 .- 2213-2600. ; 10:1, s. 83-94
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Journal article (peer-reviewed)abstract
- During the past century, socioeconomic and scientific advances have resulted in changes in the health and physique of European populations. Accompanying improvements in lung function, if unrecognised, could result in the misclassification of lung function measurements and misdiagnosis of lung diseases. We therefore investigated changes in population lung function with birth year across the past century, accounting for increasing population height, and examined how such changes might influence the interpretation of lung function measurements.In our analyses of cross-sectional data from ten European population-based studies, we included individuals aged 20-94 years who were born between 1884 and 1996, regardless of previous respiratory diagnoses or symptoms. FEV1, forced vital capacity (FVC), height, weight, and smoking behaviour were measured between 1965 and 2016. We used meta-regression to investigate how FEV1 and FVC (adjusting for age, study, height, sex, smoking status, smoking pack-years, and weight) and the FEV1/FVC ratio (adjusting for age, study, sex, and smoking status) changed with birth year. Using estimates from these models, we graphically explored how mean lung function values would be expected to progressively deviate from predicted values. To substantiate our findings, we used linear regression to investigate how the FEV1 and FVC values predicted by 32 reference equations published between 1961 and 2015 changed with estimated birth year.Across the ten included studies, we included 243465 European participants (mean age 51·4 years, 95% CI 51·4-51·5) in our analysis, of whom 136275 (56·0%) were female and 107190 (44·0%) were male. After full adjustment, FEV1 increased by 4·8 mL/birth year (95% CI 2·6-7·0; p<0·0001) and FVC increased by 8·8 mL/birth year (5·7-12·0; p<0·0001). Birth year-related increases in the FEV1 and FVC values predicted by published reference equations corroborated these findings. This height-independent increase in FEV1 and FVC across the last century will have caused mean population values to progressively exceed previously predicted values. However, the population mean adjusted FEV1/FVC ratio decreased by 0·11 per 100 birth years (95% CI 0·09-0·14; p<0·0001).If current diagnostic criteria remain unchanged, the identified shifts in European values will allow the easier fulfilment of diagnostic criteria for lung diseases such as chronic obstructive pulmonary disease, but the systematic underestimation of lung disease severity.The European Respiratory Society, AstraZeneca, Chiesi Farmaceutici, GlaxoSmithKline, Menarini, and Sanofi-Genzyme.
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| 35. |
- Cooke, S.J., et al.
(author)
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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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In: Fisheries. ; 33:7, s. 321-338
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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.
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| 36. |
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| 37. |
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| 38. |
- Troll, Valentin R., et al.
(author)
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Fault-Controlled Magma Ascent Recorded in the Central Series of the Rum Layered Intrusion, NW Scotland
- 2020
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In: Journal of Petrology. - : Oxford University Press (OUP). - 0022-3530 .- 1460-2415. ; 61:10
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Journal article (peer-reviewed)abstract
- The Palaeogene layered ultrabasic intrusion of the Isle of Rum forms the hearth of the Rum Igneous Centre in NW-Scotland. The regional Long Loch Fault, which is widely held to represent the feeder system to the layered magma reservoir, dissects the intrusion and is marked by extensive ultrabasic breccias of various types. Here we explore the connection between the layered ultrabasic cumulate rocks and breccias of central Rum that characterize the fault zone (the ‘Central Series’) and evaluate their relationship with the Long Loch Fault system. We show that fault splays in the Central Series define a transtensional graben above the Long Loch Fault into which portions of the layered units subsided and collapsed to form the extensive breccias of central Rum. The destabilization of the cumulate pile was aided by intrusion of Ca-rich ultrabasic magmas along the faults, fractures and existing bedding planes, creating a widespread network of veins and dykelets that provided a further means of disintegration and block detachment. Enrichment in LREE and compositional zoning in intra cumulate interstices suggest that the collapsed cumulates were infiltrated by relatively evolved plagioclase-rich melt, which led to extensive re-crystallization of interstices. Clinopyroxene compositions in Ca-rich gabbro and feldspathic peridotite veins suggest that the intruding magma was also relatively water-rich, and that pyroxene crystallized dominantly below the current level of exposure. We propose that the Long Loch Fault opened and closed repeatedly to furnish the Rum volcano with a pulsing magma conduit. When the conduit was shut, pressure built up in the underlying plumbing system, but was released during renewed fault movements to permit dense and often crystal-rich ultrabasic magmas to ascend rapidly from depth. These spread laterally on arrival in the shallow Rum magma reservoir, supplying repetitive recharges of crystal-rich magma to assemble the rhythmic layering of the Rum layered intrusion.
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| 39. |
- Wang, Gang, et al.
(author)
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Spirometric phenotypes from early childhood to young adulthood : a Chronic Airway Disease Early Stratification study
- 2021
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In: ERJ Open Research. - : ERS Publications. - 2312-0541. ; 7:4
-
Journal article (peer-reviewed)abstract
- Background: The prevalences of obstructive and restrictive spirometric phenotypes, and their relation to early-life risk factors from childhood to young adulthood remain poorly understood. The aim was to explore these phenotypes and associations with well-known respiratory risk factors across ages and populations in European cohorts.Methods: We studied 49334 participants from 14 population-based cohorts in different age groups (⩽10, >10–15, >15–20, >20–25 years, and overall, 5–25 years). The obstructive phenotype was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) z-score less than the lower limit of normal (LLN), whereas the restrictive phenotype was defined as FEV1/FVC z-score ⩾LLN, and FVC z-score Results: The prevalence of obstructive and restrictive phenotypes varied from 3.2–10.9% and 1.8–7.7%, respectively, without clear age trends. A diagnosis of asthma (adjusted odds ratio (aOR=2.55, 95% CI 2.14–3.04), preterm birth (aOR=1.84, 1.27–2.66), maternal smoking during pregnancy (aOR=1.16, 95% CI 1.01–1.35) and family history of asthma (aOR=1.44, 95% CI 1.25–1.66) were associated with a higher prevalence of obstructive, but not restrictive, phenotype across ages (5–25 years). A higher current body mass index (BMI was more often observed in those with the obstructive phenotype but less in those with the restrictive phenotype (aOR=1.05, 95% CI 1.03–1.06 and aOR=0.81, 95% CI 0.78–0.85, per kg·m−2 increase in BMI, respectively). Current smoking was associated with the obstructive phenotype in participants older than 10 years (aOR=1.24, 95% CI 1.05–1.46).Conclusion: Obstructive and restrictive phenotypes were found to be relatively prevalent during childhood, which supports the early origins concept. Several well-known respiratory risk factors were associated with the obstructive phenotype, whereas only low BMI was associated with the restrictive phenotype, suggesting different underlying pathobiology of these two phenotypes.
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| 40. |
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| 41. |
- Allinson, James, et al.
(author)
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Collating data from major European population studies - The CADSET (Chronic airway disease early stratification) clinical research collaboration
- 2020
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 56:suppl 64
-
Journal article (other academic/artistic)abstract
- Background: European population cohorts continue to expand our understanding of chronic airways disease and inter-study collaboration may help address the inevitable limitations of study size, duration, era and geography. Towards this aim, CADSET has collated data from ten major general population European cohorts: Asklepios; Copenhagen City Heart Study; Copenhagen General Population Study; ECRHS; HUNT; LEAD; Lifelines, OLIN, Rotterdam Study and WSAS. We included males and females aged 20 to 95 years with baseline demographic and spirometry data.Results: Data from 262,829 individuals (44% male) from multiple European countries provided good coverage across all adult ages (Fig.1A). Recruitment occurred in every year from 1976 through 2020. 23% were current-smokers and 42% were never-smokers, a pattern varying with advancing age (Fig.1B). The prevalence of airflow limitation varied according to whether lower limit of normal (LLN) or <0.70 thresholds were applied, increasing with age if the latter was used (Fig.1C).Interpretation: These results fit with previous reports, however the size, geographical reach and span of recruitment provided by this collaboration provides a unique opportunity to explore chronic airways disease development. Together, we are now pursuing research questions previously beyond the scope of individual cohort studies.
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| 42. |
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| 43. |
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| 44. |
- Bertels, Xander, et al.
(author)
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Phenotyping asthma with airflow obstruction in middle-aged and older adults : a CADSET clinical research collaboration
- 2023
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In: BMJ open respiratory research. - : BMJ Publishing Group Ltd. - 2052-4439. ; 10:1
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The prevalence and clinical profile of asthma with airflow obstruction (AO) remain uncertain. We aimed to phenotype AO in population- and clinic-based cohorts.METHODS: This cross-sectional multicohort study included adults ≥50 years from nine CADSET cohorts with spirometry data (N=69 789). AO was defined as ever diagnosed asthma with pre-BD or post-BD FEV1/FVC <0.7 in population-based and clinic-based cohorts, respectively. Clinical characteristics and comorbidities of AO were compared with asthma without airflow obstruction (asthma-only) and chronic obstructive pulmonary disease (COPD) without asthma history (COPD-only). ORs for comorbidities adjusted for age, sex, smoking status and body mass index (BMI) were meta-analysed using a random effects model.RESULTS: The prevalence of AO was 2.1% (95% CI 2.0% to 2.2%) in population-based, 21.1% (95% CI 18.6% to 23.8%) in asthma-based and 16.9% (95% CI 15.8% to 17.9%) in COPD-based cohorts. AO patients had more often clinically relevant dyspnoea (modified Medical Research Council score ≥2) than asthma-only (+14.4 and +14.7 percentage points) and COPD-only (+24.0 and +5.0 percentage points) in population-based and clinic-based cohorts, respectively. AO patients had more often elevated blood eosinophil counts (>300 cells/µL), although only significant in population-based cohorts. Compared with asthma-only, AO patients were more often men, current smokers, with a lower BMI, had less often obesity and had more often chronic bronchitis. Compared with COPD-only, AO patients were younger, less often current smokers and had less pack-years. In the general population, AO patients had a higher risk of coronary artery disease than asthma-only and COPD-only (OR=2.09 (95% CI 1.26 to 3.47) and OR=1.89 (95% CI 1.10 to 3.24), respectively) and of depression (OR=1.41 (95% CI 1.19 to 1.67)), osteoporosis (OR=2.30 (95% CI 1.43 to 3.72)) and gastro-oesophageal reflux disease (OR=1.68 (95% CI 1.06 to 2.68)) than COPD-only, independent of age, sex, smoking status and BMI.CONCLUSIONS: AO is a relatively prevalent respiratory phenotype associated with more dyspnoea and a higher risk of coronary artery disease and elevated blood eosinophil counts in the general population compared with both asthma-only and COPD-only.
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| 45. |
- Burchardt, Steffi, et al.
(author)
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3 or 1? 3D cone-sheet architecture provides insight into the centre(s) of Ardnamurchan
- 2013
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Conference paper (peer-reviewed)abstract
- The Palaeogene Ardnamurchan igneous centre, NW Scotland, was a defining place for the development of classic concepts of cone-sheet, ring-dyke, and dyke emplacement. It holds therefore an iconic status among geologists and has influenced our understanding of subvolcanic structures fundamentally. We have used historic geological maps ofArdnamurchan to project the underlying three-dimensional (3D) cone-sheet structure. The results illustrate that a single elongate magma chamber likely acted as the source of the cone-sheet swarms, instead of the traditionally accepted model of three successive centres. Our finding is moreover consistent with recent sedimentological, geochemical, geophysical, and structural investigations that all support a ridge-like morphology for the Ardnamurchan volcano. This challenges the static model of cone-sheet emplacement that involves successive but independent centres in favour of a dynamical one that involves a single, but elongate magma chamber that is progressively evolving. The latter model reduces the lifetime required for the Ardnamurchan centre considerably.
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| 46. |
- Burchardt, Steffi, et al.
(author)
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Ardnamurchan 3D cone-sheet architecture explained by a single elongate magma chamber
- 2013
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 3, s. 2891-
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Journal article (peer-reviewed)abstract
- The Palaeogene Ardnamurchan central igneous complex, NW Scotland, was a defining place for the development of the classic concepts of cone-sheet and ring-dyke emplacement and has thus fundamentally influenced our thinking on subvolcanic structures. We have used the available structural information on Ardnamurchan to project the underlying three-dimensional (3D) cone-sheet structure. Here we show that a single elongate magma chamber likely acted as the source of the cone-sheet swarm(s) instead of the traditionally accepted model of three successive centres. This proposal is supported by the ridge-like morphology of the Ardnamurchan volcano and is consistent with the depth and elongation of the gravity anomaly underlying the peninsula. Our model challenges the traditional model of cone-sheet emplacement at Ardnamurchan that involves successive but independent centres in favour of a more dynamical one that involves a single, but elongate and progressively evolving magma chamber system.
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| 47. |
- Chang-Claude, Jenny, et al.
(author)
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Age at menarche and menopause and breast cancer risk in the International BRCA1/2 Carrier Cohort Study
- 2007
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In: Cancer Epidemiology Biomarkers and Prevention. - 1055-9965. ; 16:4, s. 740-746
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Journal article (peer-reviewed)abstract
- Background: Early menarche and late menopause are important risk factors for breast cancer, but their effects on breast cancer risk in BRCA1 and BRCA2 carriers are unknown. Methods: We assessed breast cancer risk in a large series of 1,187 BRCA1 and 414 BRCA2 carriers from the International BRCA1/2 Carrier Cohort Study. Rate ratios were estimated using a weighted Cox-regression approach. Results: Breast cancer risk was not significantly related to age at menopause {hazard ratio [HR] for menopause below age 35 years, 0.60 [95% confidence interval (95% CI), 0.25-1.44]; 35 to 40 years, 1.15 [0.65-2.04]; 45 to 54 years, 1.02 [0.65-1.60]; ≥55 years, 1.12 [0.12-5.02], as compared with premenopausal women}. However, there was some suggestion of a reduction in risk after menopause in BRCA2 carriers. There was some evidence of a protective effect of oophorectomy (HR, 0.56; 95% CI, 0.29-1.09) and a significant trend of decreasing risk with increasing time since oophorectomy, but no apparent effect of natural menopause. There was no association between age at menarche and breast cancer risk, nor any apparent association with the estimated total duration of breast mitotic activity. Conclusions: These results are consistent with other observations suggesting a protective effect of oophorectomy, similar in relative effect to that in the general population. The absence of an effect of age at natural menopause is, however, not consistent with findings in the general population and may reflect the different natural history of the disease in carriers.
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- Gawlik-Starzyk, Aneta M., et al.
(author)
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Availability, usage, and preferences of estradiol and progestogen preparations for puberty induction from a multicentral perspective
- 2024
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In: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826.
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Journal article (peer-reviewed)abstract
- Introduction: Natural oestrogen administration as oral or transdermal 17β-estradiol is recommended for pubertal induction in girls with hypogonadism. However, suitable low-dose formulations are not consistently available globally. This questionnaire study aimed to identify the current availability of oestrogen and progesterone preparations worldwide.Methods: Endorsed by the ESPE Turner Syndrome Working Group, the questionnaire targeted paediatric endocrinologists. Questions focused on accessibility of oral/transdermal 17β-estradiol and progestogen preparations. Responses were collected through a SurveyMonkey survey disseminated via ESPE channels, direct outreach, and conferences from June 2020 to December 2022.Results: Participation included 229 healthcare professionals from 45 countries. Oral and transdermal 17β-estradiol in adult dosage was highly accessible (86.5% and 84.3%), with transdermal administration the preferred form (62.8%). Most commonly available estradiol preparations included 50 μg patches (32 countries) and 1 or 2 mg tablets (65.8% and 71.1% countries). However, 0.5 mg 17β-estradiol tablets were available in only 20% of respondents from 8 countries. Patches delivering 14 or 25 μg/day of 17β-estradiol were available in 3 and 20 countries, respectively. Oral progestogen had widespread availability (96.0%) and preference (87.0%), while transdermal usage was limited to 15.2% of respondents.Conclusion: This study highlights global challenges in accessing suitable hormone preparations for female pubertal induction. In most countries, the lowest dose of the estradiol is 50 μg for patches and 2 mg for tablets. Appropriate low-dose 17β-estradiol tablets are much less available than low-dose patches. Our survey underscores the importance of adapting guidelines to local availability, and the need for improved accessibility to address these global disparities.
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