| 1. |
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| 2. |
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| 3. |
- Durno, C., et al.
(författare)
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Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance
- 2021
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 39:25
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals. PATIENTS AND METHODS Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation. RESULTS A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically (P < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively (P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance (P < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years. CONCLUSION Surveillance and early cancer detection are associated with improved OS for individuals with CMMRD.
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| 4. |
- Das, A., et al.
(författare)
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Genomic predictors of response to PD-1 inhibition in children with germline DNA replication repair deficiency
- 2022
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 28:1, s. 125-135
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Tidskriftsartikel (refereegranskat)abstract
- Cancers arising from germline DNA mismatch repair deficiency or polymerase proofreading deficiency (MMRD and PPD) in children harbour the highest mutational and microsatellite insertion–deletion (MS-indel) burden in humans. MMRD and PPD cancers are commonly lethal due to the inherent resistance to chemo-irradiation. Although immune checkpoint inhibitors (ICIs) have failed to benefit children in previous studies, we hypothesized that hypermutation caused by MMRD and PPD will improve outcomes following ICI treatment in these patients. Using an international consortium registry study, we report on the ICI treatment of 45 progressive or recurrent tumors from 38 patients. Durable objective responses were observed in most patients, culminating in a 3 year survival of 41.4%. High mutation burden predicted response for ultra-hypermutant cancers (>100 mutations per Mb) enriched for combined MMRD + PPD, while MS-indels predicted response in MMRD tumors with lower mutation burden (10–100 mutations per Mb). Furthermore, both mechanisms were associated with increased immune infiltration even in ‘immunologically cold’ tumors such as gliomas, contributing to the favorable response. Pseudo-progression (flare) was common and was associated with immune activation in the tumor microenvironment and systemically. Furthermore, patients with flare who continued ICI treatment achieved durable responses. This study demonstrates improved survival for patients with tumors not previously known to respond to ICI treatment, including central nervous system and synchronous cancers, and identifies the dual roles of mutation burden and MS-indels in predicting sustained response to immunotherapy. © 2022, The Author(s).
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| 5. |
- Pierre, M., et al.
(författare)
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The XXL survey : First results and future
- 2017
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Ingår i: Astronomical Notes - Astronomische Nachrichten. - : Wiley-VCH Verlagsgesellschaft. - 0004-6337 .- 1521-3994. ; 338:2-3, s. 334-341
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Tidskriftsartikel (refereegranskat)abstract
- The XXL survey currently covers two 25 deg(2) patches with XMM observations of similar to 10 ks. We summarize the scientific results associated with the first release of the XXL dataset, which occurred in mid-2016. We review several arguments for increasing the survey depth to 40 ks during the next decade of XMM operations. X-ray (z < 2) cluster, (z < 4) active galactic nuclei (AGN), and cosmic background survey science will then benefit from an extraordinary data reservoir. This, combined with deep multi-lambda observations, will lead to solid standalone cosmological constraints and provide a wealth of information on the formation and evolution of AGN, clusters, and the X-ray background. In particular, it will offer a unique opportunity to pinpoint the z > 1 cluster density. It will eventually constitute a reference study and an ideal calibration field for the upcoming eROSITA and Euclid missions.
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| 6. |
- Pierre, M., et al.
(författare)
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The XXL Survey I. Scientific motivations - XMM-Newton observing plan - Follow-up observations and simulation programme
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 592
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Tidskriftsartikel (refereegranskat)abstract
- Context. The quest for the cosmological parameters that describe our universe continues to motivate the scientific community to undertake very large survey initiatives across the electromagnetic spectrum. Over the past two decades, the Chandra and XMM-Newton observatories have supported numerous studies of X-ray-selected clusters of galaxies, active galactic nuclei (AGNs), and the X-ray background. The present paper is the first in a series reporting results of the XXL-XMM survey; it comes at a time when the Planck mission results are being finalised. Aims. We present the XXL Survey, the largest XMM programme totaling some 6.9 Ms to date and involving an international consortium of roughly 100 members. The XXL Survey covers two extragalactic areas of 25 deg(2) each at a point-source sensitivity of similar to 5 x 10(-15) erg s(-1) cm(-2) in the [0.5-2] keV band (completeness limit). The survey's main goals are to provide constraints on the dark energy equation of state from the space-time distribution of clusters of galaxies and to serve as a pathfinder for future, wide-area X-ray missions. We review science objectives, including cluster studies, AGN evolution, and large-scale structure, that are being conducted with the support of approximately 30 follow-up programmes. Methods. We describe the 542 XMM observations along with the associated multi-lambda and numerical simulation programmes. We give a detailed account of the X-ray processing steps and describe innovative tools being developed for the cosmological analysis. Results. The paper provides a thorough evaluation of the X-ray data, including quality controls, photon statistics, exposure and background maps, and sky coverage. Source catalogue construction and multi-lambda associations are briefly described. This material will be the basis for the calculation of the cluster and AGN selection functions, critical elements of the cosmological and science analyses. Conclusions. The XXL multi-lambda data set will have a unique lasting legacy value for cosmological and extragalactic studies and will serve as a calibration resource for future dark energy studies with clusters and other X-ray selected sources. With the present article, we release the XMM XXL photon and smoothed images along with the corresponding exposure maps.
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| 7. |
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| 8. |
- Guglielmo, V., et al.
(författare)
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The XXL Survey: XXII. the XXL-North spectrophotometric sample and galaxy stellar mass function in X-ray detected groups and clusters
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 620
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Tidskriftsartikel (refereegranskat)abstract
- Context. The fraction of galaxies bound in groups in the nearby Universe is high (50% at z ∼ 0). Systematic studies of galaxy properties in groups are important in order to improve our understanding of the evolution of galaxies and of the physical phenomena occurring within this environment. Aims. We have built a complete spectrophotometric sample of galaxies within X-ray detected, optically spectroscopically confirmed groups and clusters (G&C), covering a wide range of halo masses at z ≤ 0.6. Methods. In the context of the XXL survey, we analyse a sample of 164 G&C in the XXL-North region (XXL-N), at z ≤ 0.6, with a wide range of virial masses (1.24 × 1013 ≤ M500,scal(Mo) ≤ 6.63 × 1014) and X-ray luminosities ((2.27 × 1041 ≤ L500,scalXXL(erg-s-1) ≤ 2.15 × 1044)). The G&C are X-ray selected and spectroscopically confirmed. We describe the membership assignment and the spectroscopic completeness analysis, and compute stellar masses. As a first scientific exploitation of the sample, we study the dependence of the galaxy stellar mass function (GSMF) on global environment. Results. We present a spectrophotometric characterisation of the G&C and their galaxies. The final sample contains 132 G&C, 22 111 field galaxies and 2225 G&C galaxies with r-band magnitude <20. Of the G&C, 95% have at least three spectroscopic members, and 70% at least ten. The shape of the GSMF seems not to depend on environment (field versus G&C) or X-ray luminosity (used as a proxy for the virial mass of the system). These results are confirmed by the study of the correlation between mean stellar mass of G&C members and L500,scalXXL. We release the spectrophotometric catalogue of galaxies with all the quantities computed in this work. Conclusions. As a first homogeneous census of galaxies within X-ray spectroscopically confirmed G&C at these redshifts, this sample will allow environmental studies of the evolution of galaxy properties.
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| 9. |
- Albani, S, et al.
(författare)
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Twelve thousand years of dust : the Holocene global dust cycle constrained by natural archives
- 2015
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 11:6, s. 869-903
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Tidskriftsartikel (refereegranskat)abstract
- Mineral dust plays an important role in the climate system by interacting with radiation, clouds, and biogeochemical cycles. In addition, natural archives show that the dust cycle experienced variability in the past in response to global and local climate change. The compilation of the DIRTMAP paleodust datasets in the last two decades provided a target for paleoclimate models that include the dust cycle, following a time slice approach. We propose an innovative framework to organize a paleodust dataset that moves on from the positive experience of DIRTMAP and takes into account new scientific challenges, by providing a concise and accessible dataset of temporally resolved records of dust mass accumulation rates and particle grain-size distributions. We consider data from ice cores, marine sediments, loess/paleosol sequences, lake sediments, and peat bogs for this compilation, with a temporal focus on the Holocene period. This global compilation allows investigation of the potential, uncertainties and confidence level of dust mass accumulation rates reconstructions, and highlights the importance of dust particle size information for accurate and quantitative reconstructions of the dust cycle. After applying criteria that help to establish that the data considered represent changes in dust deposition, 43 paleodust records have been identified, with the highest density of dust deposition data occurring in the North Atlantic region. Although the temporal evolution of dust in the North Atlantic appears consistent across several cores and suggest that minimum dust fluxes are likely observed during the Early to mid-Holocene period (6000–8000 years ago), the magnitude of dust fluxes in these observations is not fully consistent, suggesting that more work needs to be done to synthesize datasets for the Holocene. Based on the data compilation, we used the Community Earth System Model to estimate the mass balance and variability of the global dust cycle during the Holocene, with dust load ranging from 17.1 to 20.5 Tg between 2000 and 10 000 years ago, and a minimum in the Early to Mid-Holocene (6000–8000 years ago).
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| 10. |
- Brennan, D. J., et al.
(författare)
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The cocaine- and amphetamine-regulated transcript mediates ligand-independent activation of ER alpha, and is an independent prognostic factor in node-negative breast cancer
- 2012
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 31:30, s. 3483-3494
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Tidskriftsartikel (refereegranskat)abstract
- Personalized medicine requires the identification of unambiguous prognostic and predictive biomarkers to inform therapeutic decisions. Within this context, the management of lymph node-negative breast cancer is the subject of much debate with particular emphasis on the requirement for adjuvant chemotherapy. The identification of prognostic and predictive biomarkers in this group of patients is crucial. Here, we demonstrate by tissue microarray and automated image analysis that the cocaine- and amphetamine-regulated transcript (CART) is expressed in primary and metastatic breast cancer and is an independent poor prognostic factor in estrogen receptor (ER)-positive, lymph node-negative tumors in two separate breast cancer cohorts (n = 690; P = 0.002, 0.013). We also show that CART increases the transcriptional activity of ER alpha in a ligand-independent manner via the mitogen-activated protein kinase pathway and that CART stimulates an autocrine/paracrine loop within tumor cells to amplify the CART signal. Additionally, we demonstrate that CART expression in ER-positive breast cancer cell lines protects against tamoxifen-mediated cell death and that high CART expression predicts disease outcome in tamoxifen-treated patients in vivo in three independent breast cancer cohorts. We believe that CART profiling will help facilitate stratification of lymph node-negative breast cancer patients into high- and low-risk categories and allow for the personalization of therapy. Oncogene (2012) 31, 3483-3494; doi:10.1038/onc.2011.519; published online 5 December 2011
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Perez, LG, et al.
(författare)
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TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 2608-
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Tidskriftsartikel (refereegranskat)abstract
- IL-22 has dual functions during tumorigenesis. Short term IL-22 production protects against genotoxic stress, whereas uncontrolled IL-22 activity promotes tumor growth; therefore, tight regulation of IL-22 is essential. TGF-β1 promotes the differentiation of Th17 cells, which are known to be a major source of IL-22, but the effect of TGF-β signaling on the production of IL-22 in CD4+ T cells is controversial. Here we show an increased presence of IL-17+IL-22+ cells and TGF-β1 in colorectal cancer compared to normal adjacent tissue, whereas the frequency of IL-22 single producing cells is not changed. Accordingly, TGF-β signaling in CD4+ T cells (specifically Th17 cells) promotes the emergence of IL-22-producing Th17 cells and thereby tumorigenesis in mice. IL-22 single producing T cells, however, are not dependent on TGF-β signaling. We show that TGF-β, via AhR induction, and PI3K signaling promotes IL-22 production in Th17 cells.
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| 15. |
- Vanhees, L, et al.
(författare)
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Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular risk factors : recommendations from the EACPR. Part II.
- 2012
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Ingår i: European journal of preventive cardiology. - : Oxford University Press (OUP). - 2047-4881 .- 2047-4873. ; 19:5, s. 1005-33
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Tidskriftsartikel (refereegranskat)abstract
- In a previous paper, as the first of a series of three on the importance of characteristics and modalities of physical activity (PA) and exercise in the management of cardiovascular health within the general population, we concluded that, in the population at large, PA and aerobic exercise capacity clearly are inversely associated with increased cardiovascular disease risk and all-cause and cardiovascular mortality and that a dose–response curve on cardiovascular outcome has been demonstrated in most studies. More and more evidence is accumulated that engaging in regular PA and exercise interventions are essential components for reducing the severity of cardiovascular risk factors, such as obesity and abdominal fat, high BP, metabolic risk factors, and systemic inflammation. However, it is less clear whether and which type of PA and exercise intervention (aerobic exercise, dynamic resistive exercise, or both) or characteristic of exercise (frequency, intensity, time or duration, and volume) would yield more benefit for each separate risk factor. The present paper, therefore, will review and make recommendations for PA and exercise training in the management of cardiovascular health in individuals with cardiovascular risk factors. The guidance offered in this series of papers is aimed at medical doctors, health practitioners, kinesiologists, physiotherapists and exercise physiologists, politicians, public health policy makers, and individual members of the public. Based on previous and the current literature overviews, recommendations from the European Association on Cardiovascular Prevention and Rehabilitation are formulated regarding type, volume, and intensity of PA and regarding appropriate risk evaluation during exercise in individuals with cardiovascular risk factors.
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| 16. |
- Boon, Hanneke, 1981-, et al.
(författare)
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Intravenous AICAR administration reduces hepatic glucose output and inhibits whole body lipolysis in type 2 diabetic patients
- 2008
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Ingår i: Diabetologia. - Heidelberg : Springer Berlin/Heidelberg. - 0012-186X .- 1432-0428. ; 51:10, s. 1893-1900
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: The 5'-AMP-activated protein kinase (AMPK) pathway is intact in type 2 diabetic patients and is seen as a target for diabetes treatment. In this study, we aimed to assess the impact of the AMPK activator 5-aminoimidazole-4-carboxamide riboside (AICAR) on both glucose and fatty acid metabolism in vivo in type 2 diabetic patients. METHODS: Stable isotope methodology and blood and muscle biopsy sampling were applied to assess blood glucose and fatty acid kinetics following continuous i.v. infusion of AICAR (0.75 mg kg(-1) min(-1)) and/or NaCl (0.9%) in ten male type 2 diabetic patients (age 64 +/- 2 years; BMI 28 +/- 1 kg/m(2)). RESULTS: Plasma glucose rate of appearance (R (a)) was reduced following AICAR administration, while plasma glucose rate of disappearance (R (d)) was similar in the AICAR and control test. Consequently, blood glucose disposal (R (d) expressed as a percentage of R (a)) was increased following AICAR infusion (p < 0.001). Accordingly, a greater decline in plasma glucose concentration was observed following AICAR infusion (p < 0.001). Plasma NEFA R (a) and R (d) were both significantly reduced in response to AICAR infusion, and were accompanied by a significant decline in plasma NEFA concentration. Although AMPK phosphorylation in skeletal muscle was not increased, we observed a significant increase in acetyl-CoA carboxylase phosphorylation (p < 0.001). CONCLUSIONS/INTERPRETATION: The i.v. administration of AICAR reduces hepatic glucose output, thereby lowering blood glucose concentrations in vivo in type 2 diabetic patients. Furthermore, AICAR administration stimulates hepatic fatty acid oxidation and/or inhibits whole body lipolysis, thereby reducing plasma NEFA concentration. © 2008 The Author(s).
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| 17. |
- Ercan, Ayse Bahar, et al.
(författare)
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Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study.
- 2024
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Ingår i: The Lancet Oncology. - 1470-2045. ; 25:5, s. 668-682
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Tidskriftsartikel (refereegranskat)abstract
- Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD.In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries. Clinical data were extracted from the IRRDC database, medical records, and physician-completed case record forms. The primary objective was to describe the clinical features, cancer spectrum, and biology of the condition. Secondary objectives included estimations of cancer incidence and of the impact of the specific mismatch-repair gene and genotype on cancer onset and survival, including after cancer surveillance and immunotherapy interventions.We analysed data from 201 patients (103 males, 98 females) enrolled between June 5, 2007 and Sept 9, 2022. Median age at diagnosis of CMMRD or a related cancer was 8·9 years (IQR 5·9-12·6), and median follow-up from diagnosis was 7·2 years (3·6-14·8). Endogamy among minorities and closed communities contributed to high homozygosity within countries with low consanguinity. Frequent dermatological manifestations (117 [93%] of 126 patients with complete data) led to a clinical overlap with neurofibromatosis type 1 (35 [28%] of 126). 339 cancers were reported in 194 (97%) of 201 patients. The cumulative cancer incidence by age 18 years was 90% (95% CI 80-99). Median time between cancer diagnoses for patients with more than one cancer was 1·9 years (IQR 0·8-3·9). Neoplasms developed in 15 organs and included early-onset adult cancers. CNS tumours were the most frequent (173 [51%] cancers), followed by gastrointestinal (75 [22%]), haematological (61 [18%]), and other cancer types (30 [9%]). Patients with CNS tumours had the poorest overall survival rates (39% [95% CI 30-52] at 10 years from diagnosis; log-rank p<0·0001 across four cancer types), followed by those with haematological cancers (67% [55-82]), gastrointestinal cancers (89% [81-97]), and other solid tumours (96% [88-100]). All cancers showed high mutation and microsatellite indel burdens, and pathognomonic mutational signatures. MLH1 or MSH2 variants caused earlier cancer onset than PMS2 or MSH6 variants, and inferior survival (overall survival at age 15 years 63% [95% CI 55-73] for PMS2, 49% [35-68] for MSH6, 19% [6-66] for MLH1, and 0% for MSH2; p<0·0001). Frameshift or truncating variants within the same gene caused earlier cancers and inferior outcomes compared with missense variants (p<0·0001). The greater deleterious effects of MLH1 and MSH2 variants as compared with PMS2 and MSH6 variants persisted despite overall improvements in survival after surveillance or immune checkpoint inhibitor interventions.The very high cancer burden and unique genomic landscape of CMMRD highlight the benefit of comprehensive assays in timely diagnosis and precision approaches toward surveillance and immunotherapy. These data will guide the clinical management of children and patients who survive into adulthood with CMMRD.The Canadian Institutes for Health Research, Stand Up to Cancer, Children's Oncology Group National Cancer Institute Community Oncology Research Program, Canadian Cancer Society, Brain Canada, The V Foundation for Cancer Research, BioCanRx, Harry and Agnieszka Hall, Meagan's Walk, BRAINchild Canada, The LivWise Foundation, St Baldrick Foundation, Hold'em for Life, and Garron Family Cancer Center.
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| 18. |
- Gaudet, Mia M., et al.
(författare)
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Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer
- 2010
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (, 40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (lambda) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values, 10 25 and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, p = 3: 8 x 10(-5)) and for rs311499 was 0.72 (95% CI 0.61-0.85, p = 6: 6 x 10(-5)). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, p = 1: 2 x 10(-8)). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.
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| 19. |
- Maitre, Léa, et al.
(författare)
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State-of-the-art methods for exposure-health studies: Results from the exposome data challenge event
- 2022
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 168
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Tidskriftsartikel (refereegranskat)abstract
- The exposome recognizes that individuals are exposed simultaneously to a multitude of different environmental factors and takes a holistic approach to the discovery of etiological factors for disease. However, challenges arise when trying to quantify the health effects of complex exposure mixtures. Analytical challenges include dealing with high dimensionality, studying the combined effects of these exposures and their interactions, integrating causal pathways, and integrating high-throughput omics layers. To tackle these challenges, the Barcelona Institute for Global Health (ISGlobal) held a data challenge event open to researchers from all over the world and from all expertises. Analysts had a chance to compete and apply state-of-the-art methods on a common partially simulated exposome dataset (based on real case data from the HELIX project) with multiple correlated exposure variables (P > 100 exposure variables) arising from general and personal environments at different time points, biological molecular data (multi-omics: DNA methylation, gene expression, proteins, metabolomics) and multiple clinical phenotypes in 1301 mother–child pairs. Most of the methods presented included feature selection or feature reduction to deal with the high dimensionality of the exposome dataset. Several approaches explicitly searched for combined effects of exposures and/or their interactions using linear index models or response surface methods, including Bayesian methods. Other methods dealt with the multi-omics dataset in mediation analyses using multiple-step approaches. Here we discuss features of the statistical models used and provide the data and codes used, so that analysts have examples of implementation and can learn how to use these methods. Overall, the exposome data challenge presented a unique opportunity for researchers from different disciplines to create and share state-of-the-art analytical methods, setting a new standard for open science in the exposome and environmental health field.
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| 20. |
- Adami, C., et al.
(författare)
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The XXL Survey VIII. MUSE characterisation of intracluster light in a z similar to 0.53 cluster of galaxies
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 592:A7
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Forskningsöversikt (refereegranskat)abstract
- Aims. Within a cluster, gravitational effects can lead to the removal of stars from their parent galaxies and their subsequent dispersal into the intracluster medium. Gas hydrodynamical effects can additionally strip gas and dust from galaxies; both gas and stars contribute to intracluster light (ICL). The properties of the ICL can therefore help constrain the physical processes at work in clusters by serving as a fossil record of the interaction history. Methods. The present study is designed to characterise this ICL for the first time in a similar to 10(14) M-circle dot and z similar to 0.53 cluster of galaxies from imaging and spectroscopic points of view. By applying a wavelet-based method to CFHT Megacam and WIRCAM images, we detect significant quantities of diffuse light and are able to constrain their spectral energy distributions. These sources were then spectroscopically characterised with ESO Multi Unit Spectroscopic Explorer (MUSE) spectroscopic data. MUSE data were also used to compute redshifts of 24 cluster galaxies and search for cluster substructures. Results. An atypically large amount of ICL, equivalent in i' to the emission from two brightest cluster galaxies, has been detected in this cluster. Part of the detected diffuse light has a very weak optical stellar component and apparently consists mainly of gas emission, while other diffuse light sources are clearly dominated by old stars. Furthermore, emission lines were detected in several places of diffuse light. Our spectral analysis shows that this emission likely originates from low-excitation parameter gas. Globally, the stellar contribution to the ICL is about 2.3 x 10(9) yr old even though the ICL is not currently forming a large number of stars. On the other hand, the contribution of the gas emission to the ICL in the optical is much greater than the stellar contribution in some regions, but the gas density is likely too low to form stars. These observations favour ram pressure stripping, turbulent viscous stripping, or supernovae winds as the origin of the large amount of intracluster light. Since the cluster appears not to be in a major merging phase, we conclude that ram pressure stripping is the most plausible process that generates the observed ICL sources. Conclusions. This is one of the first times that we are able to spectroscopically study diffuse light in such a distant and massive cluster, and it demonstrates the potential of MUSE observations for such studies.
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| 21. |
- Bergstrom, K, et al.
(författare)
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Core 1- and 3-derived O-glycans collectively maintain the colonic mucus barrier and protect against spontaneous colitis in mice.
- 2017
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Ingår i: Mucosal immunology. - : Elsevier BV. - 1935-3456 .- 1933-0219. ; 10, s. 91-103
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Tidskriftsartikel (refereegranskat)abstract
- Core 1- and 3-derived mucin-type O-glycans are primary components of the mucus layer in the colon. Reduced mucus thickness and impaired O-glycosylation are observed in human ulcerative colitis. However, how both types of O-glycans maintain mucus barrier function in the colon is unclear. We found that C1galt1 expression, which synthesizes core 1 O-glycans, was detected throughout the colon, whereas C3GnT, which controls core 3 O-glycan formation, was most highly expressed in the proximal colon. Consistent with this, mice lacking intestinal core 1-derived O-glycans (IEC C1galt1(-/-)) developed spontaneous colitis primarily in the distal colon, whereas mice lacking both intestinal core 1- and 3-derived O-glycans (DKO) developed spontaneous colitis in both the distal and proximal colon. DKO mice showed an early onset and more severe colitis than IEC C1galt1(-/-) mice. Antibiotic treatment restored the mucus layer and attenuated colitis in DKO mice. Mucins from DKO mice were more susceptible to proteolysis than wild-type mucins. This study indicates that core 1- and 3-derived O-glycans collectively contribute to the mucus barrier by protecting it from bacterial protease degradation and suggests new therapeutic targets to promote mucus barrier function in colitis patients.Mucosal Immunology advance online publication, 4 May 2016; doi:10.1038/mi.2016.45.
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| 22. |
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| 23. |
- Brovkin, Victor, et al.
(författare)
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Past abrupt changes, tipping points and cascading impacts in the Earth system
- 2021
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Ingår i: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 14:8, s. 550-558
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Forskningsöversikt (refereegranskat)abstract
- A synthesis of intervals of rapid climatic change evident in the geological record reveals some of the Earth system processes and tipping points that could lead to similar events in the future. The geological record shows that abrupt changes in the Earth system can occur on timescales short enough to challenge the capacity of human societies to adapt to environmental pressures. In many cases, abrupt changes arise from slow changes in one component of the Earth system that eventually pass a critical threshold, or tipping point, after which impacts cascade through coupled climate-ecological-social systems. The chance of detecting abrupt changes and tipping points increases with the length of observations. The geological record provides the only long-term information we have on the conditions and processes that can drive physical, ecological and social systems into new states or organizational structures that may be irreversible within human time frames. Here, we use well-documented abrupt changes of the past 30 kyr to illustrate how their impacts cascade through the Earth system. We review useful indicators of upcoming abrupt changes, or early warning signals, and provide a perspective on the contributions of palaeoclimate science to the understanding of abrupt changes in the Earth system.
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- Damineli, Augusto, et al.
(författare)
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The Long-term Spectral Changes of Eta Carinae : Are they Caused by a Dissipating Occulter as Indicated by CMFGEN Models?
- 2023
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Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 954
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Tidskriftsartikel (refereegranskat)abstract
- Eta Carinae (η Car) exhibits a unique set of P Cygni profiles with both broad and narrow components. Over many decades, the spectrum has changed-there has been an increase in observed continuum fluxes and a decrease in Fe II and H I emission-line equivalent widths. The spectrum is evolving toward that of a P Cygni star such as P Cygni itself and HDE 316285. The spectral evolution has been attributed to intrinsic variations such as a decrease in the mass-loss rate of the primary star or differential evolution in a latitudinal-dependent stellar wind. However, intrinsic wind changes conflict with three observational results: the steady long-term bolometric luminosity; the repeating X-ray light curve over the binary period; and the constancy of the dust-scattered spectrum from the Homunculus. We extend previous work that showed a secular strengthening of P Cygni absorptions by adding more orbital cycles to overcome temporary instabilities and by examining more atomic transitions. CMFGEN modeling of the primary wind shows that a time-decreasing mass-loss rate is not the best explanation for the observations. However, models with a small dissipating absorber in our line of sight can explain both the increase in brightness and changes in the emission and P Cygni absorption profiles. If the spectral evolution is caused by the dissipating circumstellar medium, and not by intrinsic changes in the binary, the dynamical timescale to recover from the Great Eruption is much less than a century, different from previous suggestions.
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