| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Abercrombie, Daniel, et al.
(författare)
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Dark Matter benchmark models for early LHC Run-2 Searches : Report of the ATLAS/CMS Dark Matter Forum
- 2020
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Ingår i: Physics of the Dark Universe. - : Elsevier BV. - 2212-6864. ; 27
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Tidskriftsartikel (refereegranskat)abstract
- This document is the final report of the ATLAS-CMS Dark Matter Forum, a forum organized by the ATLAS and CMS collaborations with the participation of experts on theories of Dark Matter, to select a minimal basis set of dark matter simplified models that should support the design of the early LHC Run-2 searches. A prioritized, compact set of benchmark models is proposed, accompanied by studies of the parameter space of these models and a repository of generator implementations. This report also addresses how to apply the Effective Field Theory formalism for collider searches and present the results of such interpretations.
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| 3. |
- Bergquist, Annika, et al.
(författare)
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Impact on follow-up strategies in patients with primary sclerosing cholangitis
- 2023
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Ingår i: Liver international (Print). - Chichester, United Kingdom : Wiley-Blackwell Publishing Inc.. - 1478-3223 .- 1478-3231. ; 43:1, s. 127-138
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Evidence for the benefit of scheduled imaging for early detection of hepatobiliary malignancies in primary sclerosing cholangitis (PSC) is limited. We aimed to compare different follow-up strategies in PSC with the hypothesis that regular imaging improves survival.METHODS: We collected retrospective data from 2,975 PSC patients from 27 centers. Patients were followed from the start of scheduled imaging or in case of clinical follow-up from January 1, 2000, until death or last clinical follow-up alive. The primary endpoint was all-cause mortality.RESULTS: A broad variety of different follow-up strategies were reported. All except one center used regular imaging, ultrasound (US) and/or magnetic resonance imaging (MRI). Two centers used scheduled ERCP in addition to imaging for surveillance purposes. The overall HR (CI95%) for death, adjusted for sex, age and start year of follow-up, were 0.61 (0.47-0.80) for scheduled imaging with and without ERCP; 0.64 (0.48-0.86) for US/MRI and 0.53 (0.37-0.75) for follow-up strategies including scheduled ERCP. The lower risk of death remained for scheduled imaging with and without ERCP after adjustment for cholangiocarcinoma (CCA) or high-grade dysplasia as a time-dependent covariate, HR 0.57 (0.44-0.75). Hepatobiliary malignancy was diagnosed in 175 (5.9%) of the patients at 7.9 years follow-up. Asymptomatic patients (25%) with CCA had better survival if scheduled imaging had been performed.CONCLUSIONS: Follow-up strategies vary considerably across centers. Scheduled imaging was associated with improved survival. Multiple factors may contribute to this result including early tumor detection and increased endoscopic treatment of asymptomatic benign biliary strictures.
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| 4. |
- Böttner, Christoph, et al.
(författare)
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Pockmarks in the Witch Ground Basin, Central North Sea
- 2019
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Ingår i: Geochemistry Geophysics Geosystems. - 1525-2027. ; 20:4, s. 1698-1719
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Tidskriftsartikel (refereegranskat)abstract
- Marine sediments host large amounts of methane (CH4), which is a potent greenhouse gas. Quantitative estimates for methane release from marine sediments are scarce, and a poorly constrained temporal variability leads to large uncertainties in methane emission scenarios. Here, we use 2-D and 3-D seismic reflection, multibeam bathymetric, geochemical, and sedimentological data to (I) map and describe pockmarks in the Witch Ground Basin (central North Sea), (II) characterize associated sedimentological and fluid migration structures, and (III) analyze the related methane release. More than 1,500 pockmarks of two distinct morphological classes spread over an area of 225 km(2). The two classes form independently from another and are corresponding to at least two different sources of fluids. Class 1 pockmarks are large in size (> 6 m deep, > 250 m long, and > 75 m wide), show active venting, and are located above vertical fluid conduits that hydraulically connect the seafloor with deep methane sources. Class 2 pockmarks, which comprise 99.5% of all pockmarks, are smaller (0.9-3.1 m deep, 26-140 m long, and 14-57 m wide) and are limited to the soft, fine-grained sediments of the Witch Ground Formation and possibly sourced by compaction-related dewatering. Buried pockmarks within the Witch Ground Formation document distinct phases of pockmark formation, likely triggered by external forces related to environmental changes after deglaciation. Thus, greenhouse gas emissions from pockmark fields cannot be based on pockmark numbers and present-day fluxes but require an analysis of the pockmark forming processes through geological time. Plain Language Summary Marine sediments host large amounts of methane (CH4), which is a potent greenhouse gas. The amount of methane released into the atmosphere is, however, largely unknown making it difficult to implement this methane source in climate models. Here we use geophysical, geochemical, and sedimentological data to map the distribution of fluid escape structures in the central North Sea. More than 1,500 pockmarks, which are circular to semicircular depressions of the seafloor, indicate fluid flow from the subsurface. There are two distinct morphological classes of pockmarks corresponding to at least two different fluid sources. Class 1 pockmarks are large, show active venting, and are located above vertical fluid conduits in the subsurface, which feed fluids from deeper strata. Class 2 pockmarks, which comprise 99.5% of all pockmarks, are smaller and limited to the soft sediments directly below the seafloor. Older pockmarks in the subsurface document distinct phases of pockmark formation, likely triggered by external forces after the retreat of ice in the North Sea. The amount of methane released from natural geological sources based on pockmark numbers may be wrong as these do not take into account the origin and composition of released fluids.
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| 5. |
- Böttner, Christoph, et al.
(författare)
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Pockmarks in the Witch Ground Basin, Central North Sea
- 2019
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Ingår i: Geochemistry Geophysics Geosystems. - : American Geophysical Union (AGU). - 1525-2027. ; 20:4, s. 1698-1719
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Tidskriftsartikel (refereegranskat)abstract
- Marine sediments host large amounts of methane (CH4), which is a potent greenhouse gas. Quantitative estimates for methane release from marine sediments are scarce, and a poorly constrained temporal variability leads to large uncertainties in methane emission scenarios. Here, we use 2-D and 3-D seismic reflection, multibeam bathymetric, geochemical, and sedimentological data to (I) map and describe pockmarks in the Witch Ground Basin (central North Sea), (II) characterize associated sedimentological and fluid migration structures, and (III) analyze the related methane release. More than 1,500 pockmarks of two distinct morphological classes spread over an area of 225 km2. The two classes form independently from another and are corresponding to at least two different sources of fluids. Class 1 pockmarks are large in size (>6 m deep, >250 m long, and >75 m wide), show active venting, and are located above vertical fluid conduits that hydraulically connect the seafloor with deep methane sources. Class 2 pockmarks, which comprise 99.5% of all pockmarks, are smaller (0.9–3.1 m deep, 26–140 m long, and 14–57 m wide) and are limited to the soft, fine-grained sediments of the Witch Ground Formation and possibly sourced by compaction-related dewatering. Buried pockmarks within the Witch Ground Formation document distinct phases of pockmark formation, likely triggered by external forces related to environmental changes after deglaciation. Thus, greenhouse gas emissions from pockmark fields cannot be based on pockmark numbers and present-day fluxes but require an analysis of the pockmark forming processes through geological time.
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| 6. |
- Fickert, Peter, et al.
(författare)
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Characterization of animal models for primary sclerosing cholangitis (PSC).
- 2014
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Ingår i: Journal of hepatology. - : Elsevier BV. - 1600-0641 .- 0168-8278. ; 60:6, s. 1290-1303
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Forskningsöversikt (refereegranskat)abstract
- Primary sclerosing cholangitis (PSC) is a chronic cholangiopathy characterized by biliary fibrosis, development of cholestasis and end stage liver disease, high risk of malignancy, and frequent need for liver transplantation. The poor understanding of its pathogenesis is also reflected in the lack of effective medical treatment. Well-characterized animal models are utterly needed to develop novel pathogenetic concepts and study new treatment strategies. Currently there is no consensus on how to evaluate and characterize potential PSC models, which makes direct comparison of experimental results and effective exchange of study material between research groups difficult. The International Primary Sclerosing Cholangitis Study Group (IPSCSG) has therefore summarized these key issues in a position paper proposing standard requirements for the study of animal models of PSC.
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| 7. |
- Fischer, Katrin, et al.
(författare)
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Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis
- 2017
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 23:5, s. 623-630
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Tidskriftsartikel (refereegranskat)abstract
- Adaptive thermogenesis is the process of heat generation in response to cold stimulation. It is under the control of the sympathetic nervous system, whose chief effector is the catecholamine norepinephrine (NE). NE enhances thermogenesis through beta 3-adrenergic receptors to activate brown adipose tissue and by 'browning' white adipose tissue. Recent studies have reported that alternative activation of macrophages in response to interleukin (IL)-4 stimulation induces the expression of tyrosine hydroxylase (TH), a key enzyme in the catecholamine synthesis pathway, and that this activation provides an alternative source of locally produced catecholamines during the thermogenic process. Here we report that the deletion of Th in hematopoietic cells of adult mice neither alters energy expenditure upon cold exposure nor reduces browning in inguinal adipose tissue. Bone marrow-derived macrophages did not release NE in response to stimulation with IL-4, and conditioned media from IL-4-stimulated macrophages failed to induce expression of thermogenic genes, such as uncoupling protein 1 (Ucp1), in adipocytes cultured with the conditioned media. Furthermore, chronic treatment with IL-4 failed to increase energy expenditure in wild-type, Ucp1(-/-) and interleukin-4 receptor-alpha double-negative (Il4ra(-/-)) mice. In agreement with these findings, adipose-tissue-resident macrophages did not express TH. Thus, we conclude that alternatively activated macrophages do not synthesize relevant amounts of catecholamines, and hence, are not likely to have a direct role in adipocyte metabolism or adaptive thermogenesis.
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| 8. |
- Hedin, Charlotte Rose Hawkey, et al.
(författare)
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Effects of Tumor Necrosis Factor Antagonists in Patients With Primary Sclerosing Cholangitis
- 2020
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 18:10, s. 2-2304
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Few patients with primary sclerosing cholangitis (PSC) and inflammatory bowel diseases (IBDs) are exposed to tumor necrosis factor (TNF) antagonists because of the often mild symptoms of IBD. We assessed the effects of anti-TNF agents on liver function in patients with PSC and IBD, and their efficacy in treatment of IBD. Methods: We performed a retrospective analysis of 141 patients with PSC and IBD receiving treatment with anti-TNF agents (infliximab or adalimumab) at 20 sites (mostly tertiary-care centers) in Europe and North America. We collected data on the serum level of alkaline phosphatase (ALP). IBD response was defined as either endoscopic response or, if no endoscopic data were available, clinical response, as determined by the treating clinician or measurements of fecal calprotectin. Remission was defined more stringently as endoscopic mucosal healing. We used linear regression analysis to identify factors associated significantly with level of ALP during anti-TNF therapy. Results: Anti-TNF treatment produced a response of IBD in 48% of patients and remission of IBD in 23%. There was no difference in PSC symptom frequency before or after drug exposure. The most common reasons for anti-TNF discontinuation were primary nonresponse of IBD (17%) and side effects (18%). At 3 months, infliximab-treated patients had a median reduction in serum level of ALP of 4% (interquartile range, reduction of 25% to increase of 19%) compared with a median 15% reduction in ALP in adalimumab-treated patients (interquartile range, reduction of 29% to reduction of 4%; P =.035). Factors associated with lower ALP were normal ALP at baseline (P <.01), treatment with adalimumab (P =.090), and treatment in Europe (P =.083). Conclusions: In a retrospective analysis of 141 patients with PSC and IBD, anti-TNF agents were moderately effective and were not associated with exacerbation of PSC symptoms or specific side effects. Prospective studies are needed to investigate the association between use of adalimumab and reduced serum levels of ALP further.
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| 9. |
- Karstens, Jens, et al.
(författare)
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Formation of the Figge Maar Seafloor Crater During the 1964 B1 Blowout in the German North Sea
- 2022
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Ingår i: Earth Science, Systems and Society. - : Frontiers Media SA. - 2634-730X. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- In 1964, exploration drilling in the German Sector of the North Sea hit a gas pocket at ∼2900 m depth below the seafloor and triggered a blowout, which formed a 550 m-wide and up to 38 m deep seafloor crater now known as Figge Maar. Although seafloor craters formed by fluid flow are very common structures, little is known about their formation dynamics. Here, we present 2D reflection seismic, sediment echosounder, and multibeam echosounder data from three geoscientific surveys of the Figge Maar blowout crater, which are used to reconstruct its formation. Reflection seismic data support a scenario in which overpressured gas ascended first through the lower part of the borehole and then migrated along steeply inclined strata and faults towards the seafloor. The focused discharge of gas at the seafloor removed up to 4.8 Mt of sediments in the following weeks of vigorous venting. Eyewitness accounts document that the initial phase of crater formation was characterized by the eruptive expulsion of fluids and sediments cutting deep into the substrate. This was followed by a prolonged phase of sediment fluidization and redistribution widening the crater. After fluid discharge ceased, the Figge Maar acted as a sediment trap reducing the crater depth to ∼12 m relative to the surrounding seafloor in 2018, which corresponds to an average sedimentation rate of ∼22,000 m3/yr between 1995 and 2018. Hydroacoustic and geochemical data indicate that the Figge Maar nowadays emits primarily biogenic methane, predominantly during low tide. The formation of Figge Maar illustrates hazards related to the formation of secondary fluid pathways, which can bypass safety measures at the wellhead and are thus difficult to control.
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| 10. |
- Kowdley, Kris V, et al.
(författare)
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A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis.
- 2018
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 67:5, s. 1890-1902
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Tidskriftsartikel (refereegranskat)abstract
- Obeticholic acid (OCA), a potent farnesoid X receptor agonist, was studied as monotherapy in an international, randomized, double-blind, placebo-controlled phase 2 study in patients with primary biliary cholangitis who were then followed for up to 6 years. The goals of the study were to assess the benefit of OCA in the absence of ursodeoxycholic acid, which is relevant for patients who are intolerant of ursodeoxycholic acid and at higher risk of disease progression. Patients were randomized and dosed with placebo (n = 23), OCA 10 mg (n = 20), or OCA 50 mg (n = 16) given as monotherapy once daily for 3months (1 randomized patient withdrew prior to dosing). The primary endpoint was the percent change in alkaline phosphatase from baseline to the end of the double-blind phase of the study. Secondary and exploratory endpoints included change from baseline to month 3/early termination in markers of cholestasis, hepatocellular injury, and farnesoid X receptor activation. Efficacy and safety continue to be monitored through an ongoing 6-year open-label extension (N = 28). Alkaline phosphatase was reduced in both OCA groups (median% [Q1, Q3], OCA 10 mg -53.9% [-62.5, -29.3], OCA 50 mg -37.2% [-54.8, -24.6]) compared to placebo (-0.8% [-6.4, 8.7]; P < 0.0001) at the end of the study, with similar reductions observed through 6years of open-label extension treatment. OCA improved many secondary and exploratory endpoints (including γ-glutamyl transpeptidase, alanine aminotransferase, conjugated bilirubin, and immunoglobulin M). Pruritus was the most common adverse event; 15% (OCA 10 mg) and 38% (OCA 50 mg) discontinued due to pruritus.OCA monotherapy significantly improved alkaline phosphatase and other biochemical markers predictive of improved long-term clinical outcomes. Pruritus increased dose-dependently with OCA treatment. Biochemical improvements were observed through 6 years of open-label extension treatment. (Hepatology 2017).
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| 11. |
- Kuliński, Karol, et al.
(författare)
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Biogeochemical functioning of the Baltic Sea
- 2022
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Ingår i: Earth System Dynamics. - : Copernicus GmbH. - 2190-4979 .- 2190-4987. ; 13, s. 633-685
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Forskningsöversikt (refereegranskat)abstract
- Location, specific topography, and hydrographic setting together with climate change and strong anthropogenic pressure are the main factors shaping the biogeochemical functioning and thus also the ecological status of the Baltic Sea. The recent decades have brought significant changes in the Baltic Sea. First, the rising nutrient loads from land in the second half of the 20th century led to eutrophication and spreading of hypoxic and anoxic areas, for which permanent stratification of the water column and limited ventilation of deep-water layers made favourable conditions. Since the 1980s the nutrient loads to the Baltic Sea have been continuously decreasing. This, however, has so far not resulted in significant improvements in oxygen availability in the deep regions, which has revealed a slow response time of the system to the reduction of the land-derived nutrient loads. Responsible for that is the low burial efficiency of phosphorus at anoxic conditions and its remobilization from sediments when conditions change from oxic to anoxic. This results in a stoichiometric excess of phosphorus available for organic-matter production, which promotes the growth of N2-fixing cyanobacteria and in turn supports eutrophication. This assessment reviews the available and published knowledge on the biogeochemical functioning of the Baltic Sea. In its content, the paper covers the aspects related to changes in carbon, nitrogen, and phosphorus (C, N, and P) external loads, their transformations in the coastal zone, changes in organic-matter production (eutrophication) and remineralization (oxygen availability), and the role of sediments in burial and turnover of C, N, and P. In addition to that, this paper focuses also on changes in the marine CO2 system, the structure and functioning of the microbial community, and the role of contaminants for biogeochemical processes. This comprehensive assessment allowed also for identifying knowledge gaps and future research needs in the field of marine biogeochemistry in the Baltic Sea. Copyright:
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| 12. |
- Liu, Jimmy Z, et al.
(författare)
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Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:6, s. 670-5
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Tidskriftsartikel (refereegranskat)abstract
- Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped using the Immunochip. We identified 12 genome-wide significant associations outside the human leukocyte antigen (HLA) complex, 9 of which were new, increasing the number of known PSC risk loci to 16. Despite comorbidity with inflammatory bowel disease (IBD) in 72% of the cases, 6 of the 12 loci showed significantly stronger association with PSC than with IBD, suggesting overlapping yet distinct genetic architectures for these two diseases. We incorporated association statistics from 7 diseases clinically occurring with PSC in the analysis and found suggestive evidence for 33 additional pleiotropic PSC risk loci. Together with network analyses, these findings add to the genetic risk map of PSC and expand on the relationship between PSC and other immune-mediated diseases.
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| 13. |
- Lynch, Kate D, et al.
(författare)
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Effects of Vedolizumab in Patients with Primary Sclerosing Cholangitis and Inflammatory Bowel Diseases.
- 2020
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Ingår i: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. - : Elsevier BV. - 1542-7714. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Gut-homing lymphocytes that express the integrin α4β7 and CCR9 might contribute to development of primary sclerosing cholangitis (PSC). Vedolizumab, which blocks the integrin α4β7, is used to treat patients with inflammatory bowel diseases (IBD), but there are few data on its efficacy in patients with PSC. We investigated the effects of vedolizumab in a large international cohort of patients with PSC and IBD.We collected data from European and North American centers participating in the International PSC Study Group from patients with PSC and IBD who received at least 3 doses of vedolizumab (n= 102; median vedolizumab treatment duration, 412 days). Demographic and clinical data were collected from baseline and during the follow-up period (until liver transplantation, death, or 56 days after the final vedolizumab infusion). We analyzed overall changes in biochemical features of liver and proportions of patients with reductions in serum levels of alkaline phosphatase (ALP) of 20% or more, from baseline through last follow-up evaluation. Other endpoints included response of IBD to treatment (improved, unchanged, or worsened, judged by the treating clinician, as well as endoscopic score) and liver-related outcomes.In the entire cohort, the median serum level of ALP increased from 1.54-fold the upper limit of normal at baseline to 1.64-fold the upper limit of normal at the last follow-up examination (P= .018); serum levels of transaminases and bilirubin also increased by a small amount between baseline and the last follow-up examination. Serum levels of ALP decreased by 20% or more in 21 patients (20.6%); only the presence of cirrhosis (odds ratio, 4.48; P= .019) was independently associated with this outcome. Of patients with available endoscopic data, 56.8% had a response of IBD to treatment. Liver-related events occurred in 21 patients (20.6%), including bacterial cholangitis, cirrhosis decompensation, or transplantation.In an analysis of patients with PSC and IBD in an international study group, we found no evidence for a biochemical response to vedolizumab, although serum level of ALP decreased by 20% or more in a subset of patients. Vedolizumab appears to be well tolerated and the overall response of IBD was the same as expected for patients without PSC.
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| 14. |
- Nayagam, Jeremy S, et al.
(författare)
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Maternal liver-related symptoms during pregnancy in primary sclerosing cholangitis.
- 2023
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Ingår i: JHEP reports : innovation in hepatology. - 2589-5559. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Although worsening liver-related symptoms during pregnancy can occur in primary sclerosing cholangitis (PSC), there are insufficient data to effectively counsel patients on their pre-conception risk and no clear recommendations on monitoring and management during pregnancy. We aimed to describe maternal liver-related symptoms in pregnancy, both before and after PSC diagnosis, and explore factors associated with worsening symptoms and liver-related outcomes.We conducted a multicentre retrospective observational study of females with PSC and known pregnancy with live birth, via the International PSC Study Group. We included 450 patients from 12 European centres. Data included clinical variables, liver-related symptoms (pruritus and/or cholangitis) during pregnancy, and liver biochemistry. A composite primary endpoint of transplant-free survival from time of PSC diagnosis was used.There were 266 pregnancies in 178 patients following PSC diagnosis. Worsening liver-related symptoms were reported in 66/228 (28.9%) pregnancies; they had a reduced transplant-free survival (p= 0.03), which retained significance on multivariate analysis (hazard ratio 3.02, 95% CI 1.24-7.35; p= 0.02).Abnormal biochemistry and/or liver-related symptoms (pruritus and/or cholangitis) were noted during pregnancy before PSC diagnosis in 21/167 (12.6%) patients. They had a reduced transplant-free survival from pregnancy (p= 0.01), which did not retain significance in a multivariable model (hazard ratio 1.10, 95% CI 0.43-2.85; p= 0.84).Liver-related symptoms are frequently encountered during pregnancies before the diagnosis of PSC, and pregnancy may expose the pre-clinical phase of PSC in some patients. Worsening liver-related symptoms were seen in a third of our cohort with known PSC during pregnancy; and this subgroup had a poorer prognosis, which may be related to more advanced liver disease at time of pregnancy and/or a more severe disease phenotype.Patients with PSC can develop worsening of their liver-related symptoms during pregnancy; however, risk factors for this and the long-term implications are not known. We identified that there is a significant risk of these symptoms in pregnancy, both before and after PSC has been diagnosed, particularly in patients with elevated alkaline phosphatase. Furthermore, our findings suggest that worsening symptoms during pregnancy may be associated with adverse long-term clinical outcomes of liver transplantation and death in patients with known PSC. This may be related to the presence of more advanced liver disease at time of pregnancy. This information can be used to counsel patients with PSC before conception and identify patients who need close follow-up after delivery.
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| 15. |
- Robinson, Adam H., et al.
(författare)
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Multiscale characterisation of chimneys/pipes : Fluid escape structures within sedimentary basins
- 2021
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Ingår i: International Journal of Greenhouse Gas Control. - : Elsevier BV. - 1750-5836 .- 1878-0148. ; 106
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Tidskriftsartikel (refereegranskat)abstract
- Evaluation of seismic reflection data has identified the presence of fluid escape structures cross-cutting overburden stratigraphy within sedimentary basins globally. Seismically-imaged chimneys/pipes are considered to be possible pathways for fluid flow, which may hydraulically connect deeper strata to the seabed. The properties of fluid migration pathways through the overburden must be constrained to enable secure, long-term subsurface carbon dioxide (CO2) storage. We have investigated a site of natural active fluid escape in the North Sea, the Scanner pockmark complex, to determine the physical characteristics of focused fluid conduits, and how they control fluid flow. Here we show that a multi-scale, multi-disciplinary experimental approach is required for complete characterisation of fluid escape structures. Geophysical techniques are necessary to resolve fracture geometry and subsurface structure (e.g., multi-frequency seismics) and physical parameters of sediments (e.g., controlled source electromagnetics) across a wide range of length scales (m to km). At smaller (mm to cm) scales, sediment cores were sampled directly and their physical and chemical properties assessed using laboratory-based methods. Numerical modelling approaches bridge the resolution gap, though their validity is dependent on calibration and constraint from field and laboratory experimental data. Further, time-lapse seismic and acoustic methods capable of resolving temporal changes are key for determining fluid flux. Future optimisation of experiment resource use may be facilitated by the installation of permanent seabed infrastructure, and replacement of manual data processing with automated workflows. This study can be used to inform measurement, monitoring and verification workflows that will assist policymaking, regulation, and best practice for CO2 subsurface storage operations.
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| 16. |
- Schramm, Christoph, et al.
(författare)
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Primary liver transplantation for autoimmune hepatitis: a comparative analysis of the European Liver Transplant Registry.
- 2010
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Ingår i: Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. - : Ovid Technologies (Wolters Kluwer Health). - 1527-6473. ; 16:4, s. 461-9
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Tidskriftsartikel (refereegranskat)abstract
- The principal aim of this study was to compare the probability of and potential risk factors for death and graft loss after primary adult and pediatric liver transplantation in patients undergoing transplantation for autoimmune hepatitis (AIH) to those in patients undergoing transplantation for primary biliary cirrhosis (PBC; used as the reference group) or alcoholic cirrhosis (used as an example of a nonautoimmune liver disease). The 5-year survival of patients undergoing transplantation for AIH (n = 827) was 0.73 [95% confidence interval (CI) = 0.67-0.77]. This was similar to that of patients undergoing transplantation for alcoholic cirrhosis (0.74, 95% CI = 0.72-0.76, n = 6424) but significantly worse than that of patients undergoing transplantation for PBC (0.83, 95% CI = 0.80-0.85, n = 1588). Fatal infectious complications occurred at an increased rate in patients with AIH (hazard ratio = 1.8, P = 0.002 with PBC as the reference). The outcome of pediatric AIH patients was similar to that of adult patients undergoing transplantation up to the age of 50 years. However, the survival of AIH patients undergoing transplantation beyond the age of 50 years (0.61 at 5 years, 95% CI = 0.51-0.70) was significantly reduced in comparison with the survival of young adult AIH patients (0.78 at 18-34 years, 95% CI = 0.70-0.86) and in comparison with the survival of patients of the same age group with PBC or alcoholic cirrhosis. In conclusion, age significantly affects patient survival after liver transplantation for AIH. The increased risk of dying of infectious complications in the early postoperative period, especially above the age of 50 years, should be acknowledged in the management of AIH patients with advanced-stage liver disease who are listed for liver transplantation. It should be noted that not all risk factors relevant to patient and graft survival could be analyzed with the European Liver Transplant Registry database.
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| 17. |
- Wynberg, Elke, et al.
(författare)
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Variability in white blood cell count during uncomplicated malaria and implications for parasite density estimation : a WorldWide Antimalarial Resistance Network individual patient data meta-analysis
- 2023
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Ingår i: Malaria Journal. - : Springer Nature. - 1475-2875. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: The World Health Organization (WHO) recommends that when peripheral malarial parasitaemia is quantified by thick film microscopy, an actual white blood cell (WBC) count from a concurrently collected blood sample is used in calculations. However, in resource-limited settings an assumed WBC count is often used instead. The aim of this study was to describe the variability in WBC count during acute uncomplicated malaria, and estimate the impact of using an assumed value of WBC on estimates of parasite density and clearance.Methods: Uncomplicated malaria drug efficacy studies that measured WBC count were selected from the WorldWide Antimalarial Resistance Network data repository for an individual patient data meta-analysis of WBC counts. Regression models with random intercepts for study-site were used to assess WBC count variability at presentation and during follow-up. Inflation factors for parasitaemia density, and clearance estimates were calculated for methods using assumed WBC counts (8000 cells/mu L and age-stratified values) using estimates derived from the measured WBC value as reference.Results: Eighty-four studies enrolling 27,656 patients with clinically uncomplicated malaria were included. Geometric mean WBC counts (x 1000 cells/mu L) in age groups < 1, 1-4, 5-14 and >= 15 years were 10.5, 8.3, 7.1, 5.7 and 7.5, 7.0, 6.5, 6.0 for individuals with falciparum (n = 24,978) and vivax (n = 2678) malaria, respectively. At presentation, higher WBC counts were seen among patients with higher parasitaemia, severe anaemia and, for individuals with vivax malaria, in regions with shorter regional relapse periodicity. Among falciparum malaria patients, using an assumed WBC count of 8000 cells/mu L resulted in parasite density underestimation by a median (IQR) of 26% (4-41%) in infants < 1 year old but an overestimation by 50% (16-91%) in adults aged = 15 years. Use of age-stratified assumed WBC values removed systematic bias but did not improve precision of parasitaemia estimation. Imprecision of parasite clearance estimates was only affected by the within-patient WBC variability over time, and remained < 10% for 79% of patients.Conclusions: Using an assumed WBC value for parasite density estimation from a thick smear may lead to underdiagnosis of hyperparasitaemia and could adversely affect clinical management; but does not result in clinically consequential inaccuracies in the estimation of the prevalence of prolonged parasite clearance and artemisinin resistance.
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