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| 342. |
- Bulik, CM, et al.
(författare)
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The Eating Disorders Genetics Initiative (EDGI): study protocol
- 2021
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Ingår i: BMC psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 21:1, s. 234-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe Eating Disorders Genetics Initiative (EDGI) is an international investigation exploring the role of genes and environment in anorexia nervosa, bulimia nervosa, and binge-eating disorder.MethodsA total of 14,500 individuals with eating disorders and 1500 controls will be included from the United States (US), Australia (AU), New Zealand (NZ), and Denmark (DK). In the US, AU, and NZ, participants will complete comprehensive online phenotyping and will submit a saliva sample for genotyping. In DK, individuals with eating disorders will be identified by the National Patient Register, and genotyping will occur using bloodspots archived from birth. A genome-wide association study will be conducted within EDGI and via meta-analysis with other data from the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED).DiscussionEDGI represents the largest genetic study of eating disorders ever to be conducted and is designed to rapidly advance the study of the genetics of the three major eating disorders (anorexia nervosa, bulimia nervosa, and binge-eating disorder). We will explicate the genetic architecture of eating disorders relative to each other and to other psychiatric and metabolic disorders and traits. Our goal is for EDGI to deliver “actionable” findings that can be transformed into clinically meaningful insights.Trial registrationEDGI is a registered clinical trial: clinicaltrials.govNCT04378101.
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| 343. |
- Garcia-Martin, E. Elena, et al.
(författare)
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Sources, Composition, and Export of Particulate Organic Matter Across British Estuaries
- 2023
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Ingår i: Journal of Geophysical Research - Biogeosciences. - : American Geophysical Union (AGU). - 2169-8953 .- 2169-8961. ; 128:4
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Tidskriftsartikel (refereegranskat)abstract
- Estuaries receive and process a large amount of particulate organic carbon (POC) prior to its export into coastal waters. Studying the origin of this POC is key to understanding the fate of POC and the role of estuaries in the global carbon cycle. Here, we evaluated the concentrations of POC, as well as particulate organic nitrogen (PON), and used stable carbon and nitrogen isotopes to assess their sources across 13 contrasting British estuaries during five different sampling campaigns over 1 year. We found a high variability in POC and PON concentrations across the salinity gradient, reflecting inputs, and losses of organic material within the estuaries. Catchment land cover appeared to influence the contribution of POC to the total organic carbon flux from the estuary to coastal waters, with POC contributions >36% in estuaries draining catchments with a high percentage of urban/suburban land, and <11% in estuaries draining catchments with a high peatland cover. There was no seasonal pattern in the isotopic composition of POC and PON, suggesting similar sources for each estuary over time. Carbon isotopic ratios were depleted (-26.7 +/- 0.42 parts per thousand, average +/- sd) at the lowest salinity waters, indicating mainly terrigenous POC (TPOC). Applying a two-source mixing model, we observed high variability in the contribution of TPOC at the highest salinity waters between estuaries, with a median value of 57%. Our results indicate a large transport of terrigenous organic carbon into coastal waters, where it may be buried, remineralized, or transported offshore. Plain Language Summary Estuaries transport and process a large amount terrigenous particulate organic matter (i.e., carbon and nitrogen) prior to its export to coastal waters. In order to understand the fate of organic carbon and the role of estuaries in the global carbon cycle it is essential to improve our knowledge on its composition, origin, and amount of carbon transported. We quantified the elemental concentrations and stable isotopes composition of carbon and nitrogen to quantify the amount of terrigenous particulate organic matter transported by 13 British estuaries, which drain catchments of diverse land cover under different hydrological conditions. We found a great variability in particulate organic carbon (POC) and particulate organic nitrogen concentrations across the salinity gradient, implying inputs, and losses of material within the estuaries. Each estuary had similar sources of particulate material throughout the year. In most of the estuaries, the POC had a terrigenous origin at the lowest salinity waters. The terrigenous organic carbon contribution decreased toward coastal waters with an average contribution of 57% at the highest salinity waters, indicating a large transport of terrigenous organic carbon into coastal waters.
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| 344. |
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| 345. |
- Granville, S, et al.
(författare)
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Optical conductivity and x-ray absorption and emission study of the band structure of MnN films
- 2005
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 72:20, s. 205127-
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Tidskriftsartikel (refereegranskat)abstract
- The band structure of MnN films prepared by ion assisted deposition has been investigated by optical conductivity and x-ray absorption and emission spectroscopies. X-ray diffraction and extended x-ray absorption fine structure show the films to be nanocrystalline but phase pure and exhibiting the known antiferromagnetic distorted rocksalt phase. X-ray emission spectroscopy of the N K-edge and x-ray absorption near edge spectroscopy of both the N K- and Mn L-edges are used to probe the occupied and empty densities of states, which compare well with the N(2p) and Mn(3d) partial densities of states calculated using the linearized muffin-tin orbital band structure method. A similar comparison is made between the measured optical conductivity and the calculated contribution from interband transitions. It is possible to associate the main features in the measured spectrum with corresponding ones in the calculated optical function. The major differences between calculated and measured spectra can be understood on the basis of a limited electron mean-free-path in these nanocrystalline films, which broadens the features in the joint density of states and relaxes the momentum conservation requirement. The calculated optical functions are analyzed in detail in terms of their dominant band-to-band contributions and in addition the polarization dependence is predicted. Temperature dependent conductivity measurements are also reported and show a clear metallic behavior and a weak Kondo-like low temperature anomaly.
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| 346. |
- Heinze, Karolin, et al.
(författare)
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Validated biomarker assays confirm ARID1A loss is confounded with MMR deficiency, CD8 TIL infiltration, and provides no independent prognostic value in endometriosis-associated ovarian carcinomas.
- 2021
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Ingår i: The Journal of pathology. - : Wiley. - 1096-9896 .- 0022-3417. ; 256:4, s. 388-401
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Tidskriftsartikel (refereegranskat)abstract
- ARID1A (BAF250a) is a component of the SWI/SNF chromatin modifying complex, plays an important tumour suppressor role, and is considered prognostic in several malignancies. However, in ovarian carcinomas there are contradictory reports on its relationship to outcome, immune response, and correlation with clinicopathological features. We assembled a series of 1,623 endometriosis-associated ovarian carcinomas, including 1,078 endometrioid (ENOC) and 545 clear cell (CCOC) ovarian carcinomas through combining resources of the Ovarian Tumor Tissue Analysis (OTTA) Consortium, the Canadian Ovarian Unified Experimental Resource (COEUR), local, and collaborative networks. Validated immunohistochemical surrogate assays for ARID1A mutations were applied to all samples. We investigated associations between ARID1A loss/mutation, clinical features, outcome, CD8+ tumour-infiltrating lymphocytes (CD8+ TIL), and DNA mismatch repair deficiency (MMRd). ARID1A loss was observed in 42% of CCOC and 25% of ENOC. We found no associations between ARID1A loss and outcomes, stage, age, or CD8+ TIL status in CCOC. Similarly, we found no association with outcome or stage in endometrioid cases. In ENOC, ARID1A loss was more prevalent in younger patients (p=0.012), and associated with MMRd (p<0.001), and presence of CD8+ TIL (p=0.008). Consistent with MMRd being causative of ARID1A mutations, in a subset of ENOC we also observed an association between ARID1A loss-of-function mutation as a result of small indels (p=0.035, versus single nucleotide variants). In ENOC, the association between ARID1A loss, CD8+ TIL, and age, appears confounded by MMRd status. Although this observation does not explicitly rule out a role for ARID1A influence on CD8+ TIL infiltration in ENOC, given current knowledge regarding MMRd, it seems more likely that effects are dominated by the hypermutation phenotype. This large dataset with consistently applied biomarker assessment now provides a benchmark for the prevalence of ARID1A loss-of-function mutations in endometriosis-associated ovarian cancers and brings clarity to the prognostic significance. This article is protected by copyright. All rights reserved.
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| 347. |
- Henley, B. J., et al.
(författare)
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A Tripole Index for the Interdecadal Pacific Oscillation
- 2015
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Ingår i: Climate Dynamics. - : Springer Science and Business Media LLC. - 0930-7575 .- 1432-0894. ; 45:11-12, s. 3077-3090
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Tidskriftsartikel (refereegranskat)abstract
- A new index is developed for the Interdecadal Pacific Oscillation, termed the IPO Tripole Index (TPI). The IPO is associated with a distinct ‘tripole’ pattern of sea surface temperature anomalies (SSTA), with three large centres of action and variations on decadal timescales, evident in the second principal component (PC) of low-pass filtered global SST. The new index is based on the difference between the SSTA averaged over the central equatorial Pacific and the average of the SSTA in the Northwest and Southwest Pacific. The TPI is an easily calculated, non-PC-based index for tracking decadal SST variability associated with the IPO. The TPI time series bears a close resemblance to previously published PC-based indices and has the advantages of being simpler to compute and more consistent with indices used to track the El Niño–Southern Oscillation (ENSO), such as Niño 3.4. The TPI also provides a simple metric in physical units of °C for evaluating decadal and interdecadal variability of SST fields in a straightforward manner, and can be used to evaluate the skill of dynamical decadal prediction systems. Composites of SST and mean sea level pressure anomalies reveal that the IPO has maintained a broadly stable structure across the seven most recent positive and negative epochs that occurred during 1870–2013. The TPI is shown to be a robust and stable representation of the IPO phenomenon in instrumental records, with relatively more variance in decadal than shorter timescales compared to Niño 3.4, due to the explicit inclusion of off-equatorial SST variability associated with the IPO. © 2015, Springer-Verlag Berlin Heidelberg.
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| 348. |
- Hodges, P. W., et al.
(författare)
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Building a Collaborative Model of Sacroiliac Joint Dysfunction and Pelvic Girdle Pain to Understand the Diverse Perspectives of Experts
- 2019
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Ingår i: PM&R. - : Wiley. - 1934-1482 .- 1934-1563. ; 11:Suppl. 1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pelvic girdle pain (PGP) and sacroiliac joint (SIJ) dysfunction/pain are considered frequent contributors to low back pain (LBP). Like other persistent pain conditions, PGP is increasingly recognized as a multifactorial problem involving biological, psychological, and social factors. Perspectives differ between experts and a diversity of treatments (with variable degrees of evidence) have been utilized. Objective: To develop a collaborative model of PGP that represents the collective view of a group of experts. Specific goals were to analyze structure and composition of conceptual models contributed by participants, to aggregate them into a metamodel, to analyze the metamodel's composition, and to consider predicted efficacy of treatments. Design: To develop a collaborative model of PGP, models were generated by invited individuals to represent their understanding of PGP using fuzzy cognitive mapping (FCM). FCMs involved proposal of components related to causes, outcomes, and treatments for pain, disability, and quality of life, and their connections. Components were classified into thematic categories. Weighting of connections was summed for components to judge their relative importance. FCMs were aggregated into a metamodel for analysis of the collective opinion it represented and to evaluate expected efficacy of treatments. Results: From 21 potential contributors, 14 (67%) agreed to participate (representing six disciplines and seven countries). Participants' models included a mean (SD) of 22 (5) components each. FCMs were refined to combine similar terms, leaving 89 components in 10 categories. Biomechanical factors were the most important in individual FCMs. The collective opinion from the metamodel predicted greatest efficacy for injection, exercise therapy, and surgery for pain relief. Conclusions: The collaborative model of PGP showed a bias toward biomechanical factors. Most efficacious treatments predicted by the model have modest to no evidence from clinical trials, suggesting a mismatch between opinion and evidence. The model enables integration and communication of the collection of opinions on PGP.
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| 349. |
- Kalla, R., et al.
(författare)
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Analysis of systemic epigenetic alterations in inflammatory bowel disease : defining geographical, genetic, and immune-inflammatory influences on the circulating methylome
- 2023
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 17:2, s. 170-184
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epigenetic alterations may provide valuable insights into gene-environment interactions play in the pathogenesis of Inflammatory Bowel Disease (IBD).METHODS: Genome-wide methylation was measured from peripheral blood using the Illumina 450k platform in a case-control study in an inception cohort (295 controls, 154 CD, 161 UC, 28 IBD-U) with covariates of age, sex, and cell counts, deconvoluted by the Houseman method. Genotyping was performed using Illumina HumanOmniExpressExome-8 BeadChips and gene expression using Ion AmpliSeq Human Gene Expression Core Panel. Treatment escalation was characterised by the need for biological agents or surgery after initial disease remission.RESULTS: A total of 137 differentially methylated positions (DMP) were identified in IBD, including VMP1/MIR21 (p=9.11×10 -15) and RPS6KA2 (6.43×10 -13); with consistency seen across Scandinavia and UK. Dysregulated loci demonstrate strong genetic influence, notably VMP1 (p=1.53×10 -15). Age acceleration is seen in IBD (coefficient 0.94, p<2.2x10 -16). Several immuno-active genes demonstrated highly significant correlations between methylation and gene expression in IBD, in particular OSM: IBD r -0.32, p 3.64×10 -7 vs. non-IBD r -0.14, p=0.77). Multi-omic integration of methylome, genome and transcriptome also implicate specific pathways that associate with immune activation, response and regulation at disease inception. At follow up, a signature of 3 DMPs (TAP1, TESPA1, RPTOR) associated with treatment escalation to biological agents or surgery (hazard ratio of 5.19 (CI:2.14-12.56, logrank p=9.70×10 -4).CONCLUSION: These data demonstrate consistent epigenetic alterations at diagnosis in European patients with IBD, providing insights into the pathogenetic importance and translational potential of epigenetic mapping in complex disease.
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