| 1. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 2. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 3. |
- Sawcer, Stephen, et al.
(författare)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 4. |
- Smith, Gustav, et al.
(författare)
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The Impact of Ancestry and Common Genetic Variants on QT Interval in African Americans.
- 2012
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Ingår i: Circulation: Cardiovascular Genetics. - 1942-325X. ; 5:6, s. 647-655
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: -Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death (SCD) and low incidence of atrial fibrillation in individuals of African ancestry. We tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia, as measured by the electrocardiographic QT interval. METHODS AND RESULTS: -First, individual estimates of African and European ancestry were inferred from genome-wide single nucleotide polymorphism (SNP) data in seven population-based cohorts of African Americans (n=12 097) and regressed on measured QT interval from electrocardiograms. Second, imputation was performed for 2.8 million SNPs and a genome-wide association (GWA) study of QT interval performed in ten cohorts (n=13 105). There was no evidence of association between genetic ancestry and QT interval (p=0.94). Genome-wide significant associations (p<2.5x10(-8)) were identified with SNPs at two loci, upstream of the genes NOS1AP (rs12143842, p=2x10(-15)) and ATP1B1 (rs1320976, p=2x10(-10)). The most significant SNP in NOS1AP was the same as the strongest SNP previously associated with QT interval in individuals of European ancestry. Low p-values (p<10(-5)) were observed for SNPs at several other loci previously identified in GWA studies in individuals of European ancestry, including KCNQ1, KCNH2, LITAF and PLN. CONCLUSIONS: -We observed no difference in duration of cardiac repolarization with global genetic indices of African ancestry. In addition, our GWA study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include African Americans.
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| 5. |
- Agic, Heda, et al.
(författare)
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Late Ediacaran occurrences of the organic-walled microfossils Granomarginata and flask-shaped Lagoenaforma collaris gen. et sp. nov.
- 2022
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Ingår i: Geological Magazine. - : Cambridge University Press. - 0016-7568 .- 1469-5081. ; 159:7, s. 1071-1092
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Tidskriftsartikel (refereegranskat)abstract
- New occurrences of flask-shaped and envelope-bearing microfossils, including the predominantly Cambrian taxon Granomarginata, are reported from new localities, as well as from earlier in time (Ediacaran) than previously known. The stratigraphic range of Granomarginata extends into the Cambrian System, where it had a cosmopolitan distribution. This newly reported Ediacaran record includes areas from Norway (Baltica), Newfoundland (Avalonia) and Namibia (adjacent to the Kalahari Craton), and puts the oldest global occurrence of Granomarginata in the Indreelva Member (< 563 Ma) of the Stahpogieddi Formation on the Digermulen Peninsula, Arctic Norway. Although Granomarginata is rare within the assemblage, these new occurrences together with previously reported occurrences from India and Poland, suggest a potentially widespread palaeogeographic distribution of Granomarginata through the middle-late Ediacaran interval. A new flask-shaped microfossil Lagoenaforma collaris gen. et sp. nov. is also reported in horizons containing Granomarginata from the Stahpogieddi Formation in Norway and the Dabis Formation in Namibia, and flask-shaped fossils are also found in the Gibbett Hill Formation in Newfoundland. The Granomarginata-Lagoenaforma association, in addition to a low-diversity organic-walled microfossil assemblage, occurs in the strata postdating the Shuram carbon isotope excursion, and may eventually be of use in terminal Ediacaran biostratigraphy. These older occurrences of Granomarginata add to a growing record of body fossil taxa spanning the Ediacaran-Cambrian boundary.
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| 6. |
- Agic, Heda, et al.
(författare)
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Life through an Ediacaran glaciation : Shale- and diamictite-hosted organic-walled microfossil assemblages from the late Neoproterozoic of the Tanafjorden area, northern Norway
- 2024
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Ingår i: Palaeogeography, Palaeoclimatology, Palaeoecology. - : Elsevier. - 0031-0182 .- 1872-616X. ; 635
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Tidskriftsartikel (refereegranskat)abstract
- New organic-walled microfossil (OWM) assemblages are reported from upper Neoproterozoic glacial and interglacial siliciclastic deposits in Finnmark, northern Norway. A nearly continuous sedimentary succession of the Vestertana Group contains two glaciogenic units, the Smalfjorden and Mortensnes formations, interpreted as end-Cryogenian Marinoan and Ediacaran glaciations, respectively. We investigated the OWM record in the Nyborg, Mortensnes, and St ' ahpogieddi formations to assess the impact of a glacial interval on the diversity of microscopic eukaryotes. A modified acid-extraction technique was applied to recover OWM from the diamictite matrix. The upper Nyborg Formation contains morphologically complex Doushantuo-Pertatataka acritarchs (DPA), restricting the age of the Nyborg Formation to early-mid Ediacaran. DPA occur below the dolostones that record a negative carbon isotope excursion correlated with the Shuram anomaly and below a glacial diamictite. A decline in species richness and compositional change is observed in the Mortensnes glacial assemblage. DPA are replaced by bacterial filaments and cell aggregates. The overlying Indreelva Member, St ' ahpogieddi Formation contains Ediacara-type biota and palaeopascichnids, but only a depauperate OWM assemblage of leiosphaerids and flask-shaped microfossils characteristic of the late Ediacaran.The succession of assemblages in the Vestertana Group demonstrates a turnover from large eukaryotic OWM to a microbial community in the glacial interval, to a low diversity post-glacial assemblage during the rise of macroscopic life. We compared the Vestertana record to global DPA occurrences. Although one DPA assemblage zone postdates the Shuram excursion, no DPA occur above Ediacaran glacial diamictites in successions where those deposits are present. Considering this, and the community changes in the Vestertana succession, we suggest that DPA were affected by the onset of an Ediacaran glaciation. Lastly, we combined the biostratigraphic markers in the Vestertana Group to constrain the age of the Mortensnes diamictite.
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| 7. |
- Agic, Heda, et al.
(författare)
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Life through the 'Varanger ice ages' : microfossil record of late Neoproterozoic glacial-interglacial units from arctic Norway
- 2018
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Ingår i: Geological Society of America <em>Abstracts with Programs</em>. - : Geological Society of America.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The late Neoproterozoic strata in Finnmark (Arctic Norway) provide a good sedimentary record of Neoproterozoic glaciations on the Baltica paleocontinent. The lower Vestertana Group exposed on the Digermulen Peninsula contains two glaciogenic units, the Smalfjord and Mortensnes formations. Chemostratigraphic correlation dated the Smalfjord diamictite to the Marinoan glaciation (650-635 Ma), yet its age was also proposed to be older, per correlation to glacial units in central and southern Scandinavia. The diamictites are bracketing shales and siltstones of the interglacial Nyborg Formation. Stratigraphic, paleontological, and sedimentological data are presented from the interglacial-glacial succession, investigated by the Digermulen Early Life Research Group. Palynological analysis yielded well-preserved organic-walled microfossils (OWM) from the Nyborg Fm., and from fine-grained diamictite matrix in the Mortensnes Fm. via a modified extraction method.The interglacial Nyborg Fm. hosts a moderate diversity assemblage of prokaryotic and eukaryotic OWM, as well as acanthomorphic acritarchs such as Ceratosphaeridium, ?Cavaspina, and a novel process-bearing form. Organically preserved, enigmatic multicellular eukaryotic fossils occur in the upper Nyborg Fm. The Mortensens glacial assemblage is less diverse and contains bacterial filaments, leiosphaerids, toroidal forms, and Micrhystridium-type minute acanthomorphs.The presence of Doushantuo-Pertatataka type acritarchs in the Nyborg Fm., and small acanthomorphs in the Mortensnes diamictite corroborate an early Ediacaran age for the interglacial-glacial succession on Digermulen. In addition to the trace fossil and body-fossil record of Ediacara-biota in the overlying Stáhpogieddi Formation, the microfossil biostratigraphy suggests Marinoan and Gaskiers glaciation equivalent ages of the Varanger glaciations in Finnmark. Protistan diversity in the succession declined through and following the glaciation, until late Ediacaran.
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| 8. |
- Agić, Heda, 1989-, et al.
(författare)
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Organically-preserved multicellular eukaryote from the early Ediacaran Nyborg Formation, Arctic Norway
- 2019
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Eukaryotic multicellularity originated in the Mesoproterozoic Era and evolved multiple times since, yet early multicellular fossils are scarce until the terminal Neoproterozoic and often restricted to cases of exceptional preservation. Here we describe unusual organically-preserved fossils from mudrocks, that provide support for the presence of organisms with differentiated cells (potentially an epithelial layer) in the late Neoproterozoic. Cyathinema digermulense gen. et sp. nov. from the Nyborg Formation, Vestertana Group, Digermulen Peninsula in Arctic Norway, is a new carbonaceous organ-taxon which consists of stacked tubes with cup-shaped ends. It represents parts of a larger organism (multicellular eukaryote or a colony), likely with greater preservation potential than its other elements. Arrangement of open-ended tubes invites comparison with cells of an epithelial layer present in a variety of eukaryotic clades. This tissue may have benefitted the organism in: avoiding overgrowth, limiting fouling, reproduction, or water filtration. C. digermulense shares characteristics with extant and fossil groups including red algae and their fossils, demosponge larvae and putative sponge fossils, colonial protists, and nematophytes. Regardless of its precise affinity, C. digermulense was a complex and likely benthic marine eukaryote exhibiting cellular differentiation, and a rare occurrence of early multicellularity outside of Konservat-Lagerstatten.
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| 9. |
- Agic, Heda, et al.
(författare)
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Unusual organic-walled microfossil from the late Neoproterozoic Nyborg Formation, Digermulen Peninsula, Arctic Norway
- 2017
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Ingår i: ISECT 2017.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The late Neoproterozoic Nyborg Formation is exposed in the Tanafjord area, Finnmark, Arctic Norway, on Digermulen and Varanger Peninsulas. The succession is composed of ~400 m of interbedded shales, siltstone and purple to grey sandstone, deposited between Neoproterozoic low latitude glacial deposits. The Nyborg Fm. lies on top of the Smalfjord diamictite, and is overlain by the Mortensnes diamictite (the latter was attributed to both Marinoan (650-635 Ma) and Gaskiers (579 Ma) glaciations) and the Ediacaran-Cambrian Stáhpogieddi Formation. Thus, the Nyborg Fm. represents late Neoproterozoic, probably the last Cryogenian interglacial interval. Presented material was collected in 2014 by members of Digermulen Early Life Research Group, from organic-rich, grey-green shales and siltstones of the Nyborg Mbr. D, uppermost Nyborg Fm. between Árasulluokta and Guvssájohka valleys. Organic-walled microfossils were extracted from shale via standard palynological acetolysis in hydrofluoric acid, and studied via light and scanning electron microscopy. Microfossils from the Nyborg Fm. include Synsphaeridium-type aggregated cells, unbranched bacterial filaments (Polythrichoides and Siphonophycus), sphaeromorph and envelope-bearing acritarchs (leiosphaerids, Stictosphaeridium, Simia), and previously unrecognized aggregated tubular microfossils. These taxa are long-ranging, but common in glacial-interglacial units worldwide, and thus broadly corroborate the Cryogenian age of the Nyborg sediments. The novel fossil, up to 300 μm in size, is a parenchymatous meshwork of interconnected organic-walled tubes that terminate in cup-shaped apices 4-11 µm in diameter. Irregular tube clusters are truncated both in macerates and in thin sections, suggesting post mortem transport. Elemental EDXS analysis indicates that extracted meshwork microfossils are predominantly composed of carbonaceous material and also associated with small amounts of titanium and vanadium. Considering the branching and adjoined body plan of carbonaceous fossil, it was likely multicellular and of eukaryotic affinity. As such, it may represent an important step in the evolution of complex multicellularity and morphological complexity several million years before the appearance of Ediacaran organisms.
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| 10. |
- Alimena, Juliette, et al.
(författare)
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Searching for long-lived particles beyond the Standard Model at the Large Hadron Collider
- 2020
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:9
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Tidskriftsartikel (refereegranskat)abstract
- Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton-proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments-as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER-to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.
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