| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Murari, A., et al.
(författare)
-
A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
-
Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Patterson, Nick, et al.
(författare)
-
Large-scale migration into Britain during the Middle to Late Bronze Age
- 2022
-
Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
-
Tidskriftsartikel (refereegranskat)abstract
- Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
|
|
| 8. |
|
|
| 9. |
- Niemi, MEK, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 10. |
- Kanai, M, et al.
(författare)
-
- 2023
-
swepub:Mat__t
|
|
| 11. |
- Ahearn, Thomas U., et al.
(författare)
-
Common variants in breast cancer risk loci predispose to distinct tumor subtypes
- 2022
-
Ingår i: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
|
|
| 12. |
|
|
| 13. |
- Carbone, F., et al.
(författare)
-
Statistical study of electron density turbulence and ion-cyclotron waves in the inner heliosphere : Solar Orbiter observations
- 2021
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656
-
Tidskriftsartikel (refereegranskat)abstract
- Context. The recently released spacecraft potential measured by the RPW instrument on board Solar Orbiter has been used to estimate the solar wind electron density in the inner heliosphere. Aims. The measurement of the solar wind's electron density, taken in June 2020, has been analysed to obtain a thorough characterization of the turbulence and intermittency properties of the fluctuations. Magnetic field data have been used to describe the presence of ion-scale waves. Methods. To study and quantify the properties of turbulence, we extracted selected intervals. We used empirical mode decomposition to obtain the generalized marginal Hilbert spectrum, equivalent to the structure functions analysis, which additionally reduced issues typical of non-stationary, short time series. The presence of waves was quantitatively determined by introducing a parameter describing the time-dependent, frequency-filtered wave power. Results. A well-defined inertial range with power-law scalng was found almost everywhere in the sample studied. However, the Kolmogorov scaling and the typical intermittency effects are only present in fraction of the samples. Other intervals have shallower spectra and more irregular intermittency, which are not described by models of turbulence. These are observed predominantly during intervals of enhanced ion frequency wave activity. Comparisons with compressible magnetic field intermittency (from the MAG instrument) and with an estimate of the solar wind velocity (using electric and magnetic field) are also provided to give general context and help determine the cause of these anomalous fluctuations.
|
|
| 14. |
- Chust, T., et al.
(författare)
-
Observations of whistler mode waves by Solar Orbiter's RPW Low Frequency Receiver (LFR) : In-flight performance and first results
- 2021
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656
-
Tidskriftsartikel (refereegranskat)abstract
- Context. The Radio and Plasma Waves (RPW) instrument is one of the four in situ instruments of the ESA/NASA Solar Orbiter mission, which was successfully launched on February 10, 2020. The Low Frequency Receiver (LFR) is one of its subsystems, designed to characterize the low frequency electric (quasi-DC - 10 kHz) and magnetic (similar to 1 Hz-10 kHz) fields that develop, propagate, interact, and dissipate in the solar wind plasma. Combined with observations of the particles and the DC magnetic field, LFR measurements will help to improve the understanding of the heating and acceleration processes at work during solar wind expansion.Aims. The capability of LFR to observe and analyze a variety of low frequency plasma waves can be demontrated by taking advantage of whistler mode wave observations made just after the near-Earth commissioning phase of Solar Orbiter. In particular, this is related to its capability of measuring the wave normal vector, the phase velocity, and the Poynting vector for determining the propagation characteristics of the waves.Methods. Several case studies of whistler mode waves are presented, using all possible LFR onboard digital processing products, waveforms, spectral matrices, and basic wave parameters.Results. Here, we show that whistler mode waves can be very properly identified and characterized, along with their Doppler-shifted frequency, based on the waveform capture as well as on the LFR onboard spectral analysis.Conclusions. Despite the fact that calibrations of the electric and magnetic data still require some improvement, these first whistler observations show a good overall consistency between the RPW LFR data, indicating that many science results on these waves, as well as on other plasma waves, can be obtained by Solar Orbiter in the solar wind.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
- Dimmock, A. P., et al.
(författare)
-
Analysis of multiscale structures at the quasi-perpendicular Venus bow shock Results from Solar Orbiter's first Venus flyby
- 2022
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 660
-
Tidskriftsartikel (refereegranskat)abstract
- Context. Solar Orbiter is a European Space Agency mission with a suite of in situ and remote sensing instruments to investigate the physical processes across the inner heliosphere. During the mission, the spacecraft is expected to perform multiple Venus gravity assist maneuvers while providing measurements of the Venusian plasma environment. The first of these occurred on 27 December 2020, in which the spacecraft measured the regions such as the distant and near Venus magnetotail, magnetosheath, and bow shock. Aims. This study aims to investigate the outbound Venus bow shock crossing measured by Solar Orbiter during the first flyby. We study the complex features of the bow shock traversal in which multiple large amplitude magnetic field and density structures were observed as well as higher frequency waves. Our aim is to understand the physical mechanisms responsible for these high amplitude structures, characterize the higher frequency waves, determine the source of the waves, and put these results into context with terrestrial bow shock observations. Methods. High cadence magnetic field, electric field, and electron density measurements were employed to characterize the properties of the large amplitude structures and identify the relevant physical process. Minimum variance analysis, theoretical shock descriptions, coherency analysis, and singular value decomposition were used to study the properties of the higher frequency waves to compare and identify the wave mode. Results. The non-planar features of the bow shock are consistent with shock rippling and/or large amplitude whistler waves. Higher frequency waves are identified as whistler-mode waves, but their properties across the shock imply they may be generated by electron beams and temperature anisotropies. Conclusions. The Venus bow shock at a moderately high Mach number (similar to 5) in the quasi-perpendicular regime exhibits complex features similar to the Earth's bow shock at comparable Mach numbers. The study highlights the need to be able to distinguish between large amplitude waves and spatial structures such as shock rippling. The simultaneous high frequency observations also demonstrate the complex nature of energy dissipation at the shock and the important question of understanding cross-scale coupling in these complex regions. These observations will be important to interpreting future planetary missions and additional gravity assist maneuvers.
|
|
| 19. |
- Dixon-Suen, Suzanne C, et al.
(författare)
-
Physical activity, sedentary time and breast cancer risk : a Mendelian randomisation study
- 2022
-
Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 56:20, s. 1157-1170
-
Tidskriftsartikel (refereegranskat)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. |
- Escala-Garcia, Maria, et al.
(författare)
-
A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
- 2020
-
Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies similar to 7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
|
|
| 21. |
- Evans, Daniel L., et al.
(författare)
-
Buried solutions: How Maya urban life substantiates soil connectivity
- 2021
-
Ingår i: Geoderma. - : Elsevier BV. - 0016-7061. ; 387
-
Tidskriftsartikel (refereegranskat)abstract
- Soils are a pivot of sustainable development. Yet, urban planning decisions persist in compromising the usability of the urban soils resource. Urban land cover expansion to accommodate an increasing population results in soil sealing. Concealment of and physical obstructions to soils prevent urban populations from engaging with their soil dependency. The concept of soil connectivity recognises that nurturing mutually beneficial soil–society relations is an essential dimension for achieving soil security. The concentrated populations of urban environments acutely require productive soil–society relations and offer the greatest potential for enhancing soil connectivity. Soil connectivity remains notably under-researched, however, resulting in deficient evidence to substantiate exactly how soil connectivity can contribute to sustaining urban life. The entanglement of soil and urban development has been critical throughout history, but seldom recognised in soil security discourse. We review the manifestation of effective soil connectivity in Precolumbian lowland Maya tropical urbanism. Archaeological evidence reveals, first, that lowland Maya urban settlement patterns largely preserved the availability, proximity, and accessibility of soils in the subdivision and configuration of urban open space. Second, Maya urban life included practices that proactively contributed to the formation of soils by adding to the stock of soils and improving beneficial soil properties of the thin and often nutrient-poor soils resulting from the regionally dominant karstic lithology. Third, a range of Maya landscape modifications and engineering practices enabled the preservation and protection of soils within urban environments. We derive evidence-based insights on an urban tradition that endured for well over two millennia by incorporating intensive soil–society relationships to substantiate the concept of soil connectivity. Inspiring urban planning to stimulate soil connectivity through enhancing the engagement with soils in urban life would promote soil security.
|
|
| 22. |
|
|
| 23. |
- Falster, Daniel, et al.
(författare)
-
AusTraits, a curated plant trait database for the Australian flora
- 2021
-
Ingår i: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge.
|
|
| 24. |
- Fulton, Christopher J., et al.
(författare)
-
Macroalgal meadow habitats support fish and fisheries in diverse tropical seascapes
- 2020
-
Ingår i: Fish and Fisheries. - : Wiley. - 1467-2960 .- 1467-2979. ; 21:4, s. 700-717
-
Tidskriftsartikel (refereegranskat)abstract
- Canopy-forming macroalgae can construct extensive meadow habitats in tropical seascapes occupied by fishes that span a diversity of taxa, life-history stages and ecological roles. Our synthesis assessed whether these tropical macroalgal habitats have unique fish assemblages, provide fish nurseries and support local fisheries. We also applied a meta-analysis of independent surveys across 23 tropical reef locations in 11 countries to examine how macroalgal canopy condition is related to the abundance of macroalgal-associated fishes. Over 627 fish species were documented in tropical macroalgal meadows, with 218 of these taxa exhibiting higher local abundance within this habitat (cf. nearby coral reef) during at least one life-history stage. Major overlap (40%-43%) in local fish species richness among macroalgal and seagrass or coral reef habitats suggest macroalgal meadows may provide an important habitat refuge. Moreover, the prominence of juvenile fishes suggests macroalgal meadows facilitate the triphasic life cycle of many fishes occupying diverse tropical seascapes. Correlations between macroalgal canopy structure and juvenile abundance suggests macroalgal habitat condition can influence levels of replenishment in tropical fish populations, including the majority of macroalgal-associated fishes that are targeted by commercial, subsistence or recreational fisheries. While many macroalgal-associated fishery species are of minor commercial value, their local importance for food and livelihood security can be substantial (e.g. up to 60% of landings in Kenyan reef fisheries). Given that macroalgal canopy condition can vary substantially with sea temperature, there is a high likelihood that climate change will impact macroalgal-associated fish and fisheries.
|
|
| 25. |
|
|
| 26. |
- Gorski, Mathias, et al.
(författare)
-
Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
- 2022
-
Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639
-
Tidskriftsartikel (refereegranskat)abstract
- Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
|
|
| 27. |
- Graham, Daniel B., et al.
(författare)
-
Kinetic electrostatic waves and their association with current structures in the solar wind
- 2021
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656
-
Tidskriftsartikel (refereegranskat)abstract
- Context. A variety of kinetic electrostatic and electromagnetic waves develop in the solar wind and the relationship between these waves and larger scale structures, such as current sheets and ongoing turbulence, remain a topic of investigation. Similarly, the instabilities producing ion-acoustic waves in the solar wind are still an open question. Aims. The goals of this paper are to investigate electrostatic Langmuir and ion-acoustic waves in the solar wind at 0.5 AU and determine whether current sheets and associated streaming instabilities can produce the observed waves. The relationship between these waves and currents observed in the solar wind is investigated statistically. Methods. Solar Orbiter's Radio and Plasma Waves instrument suite provides high-resolution snapshots of the fluctuating electric field. The Low Frequency Receiver resolves the waveforms of ion-acoustic waves and the Time Domain Sampler resolves the waveforms of both ion-acoustic and Langmuir waves. Using these waveform data, we determine when these waves are observed in relation to current structures in the solar wind, estimated from the background magnetic field. Results. Langmuir and ion-acoustic waves are frequently observed in the solar wind. Ion-acoustic waves are observed about 1% of the time at 0.5 AU. The waves are more likely to be observed in regions of enhanced currents. However, the waves typically do not occur at current structures themselves. The observed currents in the solar wind are too small to drive instability by the relative drift between single ion and electron populations. When multi-component ion or electron distributions are present, the observed currents may be sufficient for instabilities to occur. Ion beams are the most plausible source of ion-acoustic waves in the solar wind. The spacecraft potential is confirmed to be a reliable probe of the background electron density when comparing the peak frequencies of Langmuir waves with the plasma frequency calculated from the spacecraft potential.
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
- Jowett, Geraldine M., et al.
(författare)
-
ILC1 drive intestinal epithelial and matrix remodelling
- 2021
-
Ingår i: Nature Materials. - : Springer Nature. - 1476-1122 .- 1476-4660. ; 20:2, s. 250-259
-
Tidskriftsartikel (refereegranskat)abstract
- Organoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we develop gut organoid cocultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines. We demonstrate that murine and human ILC1 secrete transforming growth factor β1, driving expansion of CD44v6+ epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial–mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest that they may exacerbate fibrosis and tumour growth when enriched in inflamed patient tissues.
|
|
| 33. |
- Jung, Audrey Y, et al.
(författare)
-
Distinct reproductive risk profiles for intrinsic-like breast cancer subtypes : pooled analysis of population-based studies
- 2022
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 114:12, s. 1706-1719
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER) positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear.METHODS: Analyses included up to 23,353 cases, and 71,072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2-like, HER2-enriched-like, and triple-negative) and by invasiveness. All statistical tests were 2-sided.RESULTS: Compared to nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2-like and HER2-enriched-like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46; for multiparous women with luminal A-like tumors 20-<25 years after last birth and 45-<50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95%CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95%CI = 0.79 to 1.34, for multiparous women 25 to < 30 years after last birth). Older age at first birth (P-heterogeneity<.001 for triple-negative compared to luminal-A like) and breastfeeding (P-heterogeneity<.001 for triple-negative compared to luminal-A like) were associated with lower risk of triple-negative but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like.CONCLUSION: This large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared to other subtypes, with implications for the understanding of disease etiology and risk prediction.
|
|
| 34. |
- Kanoni, Stavroula, et al.
(författare)
-
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
-
Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
|
|
| 35. |
- Kapoor, Pooja Middha, et al.
(författare)
-
Combined associations of a polygenic risk score and classical risk factors with breast cancer risk
- 2021
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 113:3, s. 329-337
-
Tidskriftsartikel (refereegranskat)abstract
- We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.
|
|
| 36. |
- Khotyaintsev, Yu, V, et al.
(författare)
-
Density fluctuations associated with turbulence and waves First observations by Solar Orbiter
- 2021
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656
-
Tidskriftsartikel (refereegranskat)abstract
- Aims. The aim of this work is to demonstrate that the probe-to-spacecraft potential measured by RPW on Solar Orbiter can be used to derive the plasma (electron) density measurement, which exhibits both a high temporal resolution and a high level of accuracy. To investigate the physical nature of the solar wind turbulence and waves, we analyze the density and magnetic field fluctuations around the proton cyclotron frequency observed by Solar Orbiter during the first perihelion encounter (similar to 0.5AU away from the Sun). Methods. We used the plasma density based on measurements of the probe-to-spacecraft potential in combination with magnetic field measurements by MAG to study the fields and density fluctuations in the solar wind. In particular, we used the polarization of the wave magnetic field, the phase between the compressible magnetic field and density fluctuations, and the compressibility ratio (the ratio of the normalized density fluctuations to the normalized compressible fluctuations of B) to characterize the observed waves and turbulence. Results. We find that the density fluctuations are 180 degrees out of phase (anticorrelated) with the compressible component of magnetic fluctuations for intervals of turbulence, whereas they are in phase for the circular-polarized waves. We analyze, in detail, two specific events with a simultaneous presence of left- and right-handed waves at di fferent frequencies. We compare the observed wave properties to a prediction of the three-fluid (electrons, protons, and alphas) model. We find a limit on the observed wavenumbers, 10(-6) < k < 7 > 10(-6) m(-1), which corresponds to a wavelength of 7 x 10(6) > lambda > 10(6) m. We conclude that it is most likely that both the leftand right-handed waves correspond to the low-wavenumber part (close to the cut-o ff at Omega(cHe++)) of the proton-band electromagnetic ion cyclotron (left-handed wave in the plasma frame confined to the frequency range Omega(cHe++) < omega < Omega(cp)) waves propagating in the outwards and inwards directions, respectively. The fact that both wave polarizations are observed at the same time and the identified wave mode has a low group velocity suggests that the double-banded events occur in the source regions of the waves.
|
|
| 37. |
- Kretzschmar, M., et al.
(författare)
-
Whistler waves observed by Solar Orbiter/RPW between 0.5 AU and 1 AU
- 2021
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656
-
Tidskriftsartikel (refereegranskat)abstract
- Context. Solar wind evolution differs from a simple radial expansion, while wave-particle interactions are assumed to be the major cause for the observed dynamics of the electron distribution function. In particular, whistler waves are thought to inhibit the electron heat flux and ensure the diffusion of the field-aligned energetic electrons (Strahl electrons) to replenish the halo population.Aims. The goal of our study is to detect and characterize the electromagnetic waves that have the capacity to modify the electron distribution functions, with a special focus on whistler waves.Methods. We carried out a detailed analysis of the electric and magnetic field fluctuations observed by the Solar Orbiter spacecraft during its first orbit around the Sun, between 0.5 and 1 AU. Using data from the Search Coil Magnetometer and electric antenna, both part of the Radio and Plasma Waves (RPW) instrumental suite, we detected the electromagnetic waves with frequencies above 3 Hz and determined the statistical distribution of their amplitudes, frequencies, polarization, and k-vector as a function of distance. Here, we also discuss the relevant instrumental issues regarding the phase between the electric and magnetic measurements as well as the effective length of the electric antenna.Results. An overwhelming majority of the observed waves are right-handed circularly polarized in the solar wind frame and identified as outwardly propagating quasi-parallel whistler waves. Their occurrence rate increases by a least a factor of 2 from 1 AU to 0.5 AU. These results are consistent with the regulation of the heat flux by the whistler heat flux instability. Near 0.5 AU, whistler waves are found to be more field-aligned and to have a smaller normalized frequency (f/f(ce)), larger amplitude, and greater bandwidth than at 1 AU.
|
|
| 38. |
- Middha, Pooja K., et al.
(författare)
-
A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry
- 2023
-
Ingår i: Breast Cancer Research. - : BioMed Central (BMC). - 1465-5411 .- 1465-542X. ; 25:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Genome-wide studies of gene-environment interactions (GxE) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide GxE analysis of similar to 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 x 10(-5) prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88-0.94). Conclusions Overall, the contribution of GxE interactions to the heritability of breast cancer is very small. At the population level, multiplicative GxE interactions do not make an important contribution to risk prediction in breast cancer.
|
|
| 39. |
- Ramdas, S., et al.
(författare)
-
A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
-
Tidskriftsartikel (refereegranskat)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
|
|
| 40. |
|
|
| 41. |
- Wang, Xiaoliang, et al.
(författare)
-
Genome-wide interaction analysis of menopausal hormone therapy use and breast cancer risk among 62,370 women
- 2022
-
Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values < 5 x 10(-8) as genome-wide significant, and p-values < 1 x 10(-5) as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants. None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values < 1 x 10(5). The strongest evidence was found for rs4674019 (p-value = 2.27 x 10(-7)), which showed genome-wide significant interaction (p-value = 3.8 x 10(-8)) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen-progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT-breast cancer risk association.
|
|
| 42. |
- Wilson, Shaun K., et al.
(författare)
-
The contribution of macroalgae-associated fishes to small-scale tropical reef fisheries
- 2022
-
Ingår i: Fish and Fisheries. - : Wiley. - 1467-2960 .- 1467-2979. ; 23:4, s. 847-861
-
Tidskriftsartikel (refereegranskat)abstract
- Macroalgae-dominated reefs are a prominent habitat in tropical seascapes that support a diversity of fishes, including fishery target species. To what extent, then, do macroalgal habitats contribute to small-scale tropical reef fisheries? To address this question we: (1) Quantified the macroalgae-associated fish component in catches from 133 small-scale fisheries, (2) Compared life-history traits relevant to fishing (e.g. growth, longevity) in macroalgal and coral-associated fishes, (3) Examined how macroalgae-associated species can influence catch diversity, trophic level and vulnerability and (4) Explored how tropical fisheries change with the expansion of macroalgal habitats using a case study of fishery-independent data for Seychelles. Fish that utilised macroalgal habitats comprise 24% of the catch, but very few fished species relied entirely on macroalgal or coral habitats post-settlement. Macroalgal and coral-associated fishes had similar life-history traits, although vulnerability to fishing declined with increasing contribution of macroalgae association to the catch, whilst mean trophic level and diversity peaked when macroalgal-associated fish accounted for 20%–30% of catches. The Seychelles case study revealed similar total fish biomass on macroalgal and coral reefs, although the biomass of primary target species increased as macroalgae cover expanded. Our findings reinforce that multiple habitat types are needed to support tropical fishery stability and sustainability. Whilst coral habitats have been the focus of tropical fisheries management, we show the potential for macroalgae-associated fish to support catch size and diversity in ways that reduce vulnerability to overfishing. This is pertinent to seascapes where repeated disturbances are facilitating the replacement of coral reef with macroalgal habitats.
|
|
| 43. |
- Winkler, TW, et al.
(författare)
-
Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
- 2022
-
Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 580-
-
Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
|
|
| 44. |
|
|
| 45. |
- Zanti, Maria, et al.
(författare)
-
A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants : Application to BRCA1 and BRCA2
- 2023
-
Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 2023
-
Tidskriftsartikel (refereegranskat)abstract
- A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity-findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.
|
|
