| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Fitzmauric, C., et al.
(författare)
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Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived with Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017 : A Systematic Analysis for the Global Burden of Disease Study
- 2019
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 5:12, s. 1749-1768
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data.Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning.Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence.Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs).Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.
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| 4. |
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| 5. |
- Meyer, H., et al.
(författare)
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Overview of physics results from MAST towards ITER/DEMO and the MAST Upgrade
- 2013
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 53:10, s. 104008-
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Tidskriftsartikel (refereegranskat)abstract
- New diagnostic, modelling and plant capability on the Mega Ampere Spherical Tokamak (MAST) have delivered important results in key areas for ITER/DEMO and the upcoming MAST Upgrade, a step towards future ST devices on the path to fusion currently under procurement. Micro-stability analysis of the pedestal highlights the potential roles of micro-tearing modes and kinetic ballooning modes for the pedestal formation. Mitigation of edge localized modes (ELM) using resonant magnetic perturbation has been demonstrated for toroidal mode numbers n = 3, 4, 6 with an ELM frequency increase by up to a factor of 9, compatible with pellet fuelling. The peak heat flux of mitigated and natural ELMs follows the same linear trend with ELM energy loss and the first ELM-resolved T-i measurements in the divertor region are shown. Measurements of flow shear and turbulence dynamics during L-H transitions show filaments erupting from the plasma edge whilst the full flow shear is still present. Off-axis neutral beam injection helps to strongly reduce the redistribution of fast-ions due to fishbone modes when compared to on-axis injection. Low-k ion-scale turbulence has been measured in L-mode and compared to global gyro-kinetic simulations. A statistical analysis of principal turbulence time scales shows them to be of comparable magnitude and reasonably correlated with turbulence decorrelation time. T-e inside the island of a neoclassical tearing mode allow the analysis of the island evolution without assuming specific models for the heat flux. Other results include the discrepancy of the current profile evolution during the current ramp-up with solutions of the poloidal field diffusion equation, studies of the anomalous Doppler resonance compressional Alfven eigenmodes, disruption mitigation studies and modelling of the new divertor design for MAST Upgrade. The novel 3D electron Bernstein synthetic imaging shows promising first data sensitive to the edge current profile and flows.
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| 6. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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| 8. |
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| 9. |
- Bakken, TE, et al.
(författare)
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Comparative cellular analysis of motor cortex in human, marmoset and mouse
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 111-
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Tidskriftsartikel (refereegranskat)abstract
- The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch–seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.
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| 10. |
- Cozen, W., et al.
(författare)
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A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 3856-
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR) = 0.81, 95% confidence interval (95% CI) = 0.76-0.86, P-combined 3.5 x 10(-10)), located in intron 2 of TCF3 (also known as E2A), a regulator of B-and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.
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| 11. |
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| 12. |
- Enciso-Mora, Victor, et al.
(författare)
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A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3)
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1126-1130
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility loci for classical Hodgkin's lymphoma (cHL), we conducted a genome-wide association study of 589 individuals with cHL (cases) and 5,199 controls with validation in four independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL, odds ratio (OR) = 1.22, combined P = 1.91 × 10−8), 8q24.21 (rs2019960, PVT1, OR = 1.33, combined P = 1.26 × 10−13) and 10p14 (rs501764, GATA3, OR = 1.25, combined P = 7.05 × 10−8). Furthermore, we confirmed the role of the major histocompatibility complex in disease etiology by revealing a strong human leukocyte antigen (HLA) association (rs6903608, OR = 1.70, combined P = 2.84 × 10−50). These data provide new insight into the pathogenesis of cHL.
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| 13. |
- Klyushina, E. S., et al.
(författare)
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Signatures for Berezinskii-Kosterlitz-Thouless critical behavior in the planar antiferromagnet BaNi2V2O8
- 2021
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Ingår i: Physical Review B. - : American Physical Society (APS). - 2469-9950 .- 2469-9969. ; 104:6
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the critical properties of the spin-1 honeycomb antiferromagnet BaNi2V2O8, both below and above the ordering temperature T-N using neutron diffraction and muon spin rotation measurements. Our results characterize BaNi2V2O8 as a two-dimensional (2D) antiferromagnet across the entire temperature range, displaying a series of crossovers from 2D XY to 2D XXZ and then to 2D Heisenberg behavior with increasing temperature. In particular, the extracted critical exponent of the order parameter reveals a narrow temperature regime close to T-N, in which the system behaves as a 2D XY antiferromagnet. Above T-N, evidence for Berezinskii-Kosterlitz-Thouless behavior driven by vortex excitations is obtained from the scaling of the correlation length. Our experimental results are in agreement with classical and quantum Monte Carlo simulations performed using microscopic magnetic model Hamiltonians for BaNi2V2O8.
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| 14. |
- Lloyd-Price, Jason, et al.
(författare)
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Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases
- 2019
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 569:7758, s. 655-661
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Tidskriftsartikel (refereegranskat)abstract
- Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database (http://ibdmdb.org), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Danilovich, I. L., et al.
(författare)
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Co(NO3)(2) as an inverted umbrella-type chiral noncoplanar ferrimagnet
- 2020
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Ingår i: Physical Review B. - : AMER PHYSICAL SOC. - 2469-9950 .- 2469-9969. ; 102:9
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Tidskriftsartikel (refereegranskat)abstract
- The low-dimensional magnetic systems tend to reveal exotic spin-liquid ground states or form peculiar types of long-range order. Among systems of vivid interest are those characterized by the triangular motif in two dimensions. The realization of either ordered or disordered ground state in triangular, honeycomb, or kagome lattices is dictated by the competition of exchange interactions, also being sensitive to anisotropy and the spin value of magnetic ions. While the low-spin Heisenberg systems may arrive to a spin-liquid long-range entangled quantum state with emergent gauge structures, the high-spin Ising systems may establish the rigid noncollinear structures. Here, we present the case of chiral noncoplanar inverted umbrella-type ferrimagnet formed in cobalt nitrate Co(NO3)(2) below T-C = 3 K with the comparable spin and orbital contributions to the total magnetic moment.
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| 19. |
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| 20. |
- Gardner, T. A., et al.
(författare)
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Transparency and sustainability in global commodity supply chains
- 2019
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Ingår i: World Development. - : Elsevier BV. - 0305-750X .- 1873-5991. ; 121, s. 163-177
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Tidskriftsartikel (refereegranskat)abstract
- Over the last few decades rapid advances in processes to collect, monitor, disclose, and disseminate information have contributed towards the development of entirely new modes of sustainability governance for global commodity supply chains. However, there has been very little critical appraisal of the contribution made by different transparency initiatives to sustainability and the ways in which they can (and cannot)influence new governance arrangements. Here we seek to strengthen the theoretical underpinning of research and action on supply chain transparency by addressing four questions: (1)What is meant by supply chain transparency? (2)What is the relevance of supply chain transparency to supply chain sustainability governance? (3)What is the current status of supply chain transparency, and what are the strengths and weaknesses of existing initiatives? and (4)What propositions can be advanced for how transparency can have a positive transformative effect on the governance interventions that seek to strengthen sustainability outcomes? We use examples from agricultural supply chains and the zero-deforestation agenda as a focus of our analysis but draw insights that are relevant to the transparency and sustainability of supply chains in general. We propose a typology to distinguish among types of supply chain information that are needed to support improvements in sustainability governance, and illustrate a number of major shortfalls and systematic biases in existing information systems. We also propose a set of ten propositions that, taken together, serve to expose some of the potential pitfalls and undesirable outcomes that may result from (inevitably)limited or poorly designed transparency systems, whilst offering guidance on some of the ways in which greater transparency can make a more effective, lasting and positive contribution to sustainability.
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| 21. |
- Jacobs, Alan M., et al.
(författare)
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The Qualitative Transparency Deliberations : Insights and Implications
- 2021
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Ingår i: Perspectives on Politics. - 1537-5927 .- 1541-0986. ; 19:1, s. 171-208
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, a variety of efforts have been made in political science to enable, encourage, or require scholars to be more open and explicit about the bases of their empirical claims and, in turn, make those claims more readily evaluable by others. While qualitative scholars have long taken an interest in making their research open, reflexive, and systematic, the recent push for overarching transparency norms and requirements has provoked serious concern within qualitative research communities and raised fundamental questions about the meaning, value, costs, and intellectual relevance of transparency for qualitative inquiry. In this Perspectives Reflection, we crystallize the central findings of a three-year deliberative process-the Qualitative Transparency Deliberations (QTD)-involving hundreds of political scientists in a broad discussion of these issues. Following an overview of the process and the key insights that emerged, we present summaries of the QTD Working Groups' final reports. Drawing on a series of public, online conversations that unfolded at www.qualtd.net, the reports unpack transparency's promise, practicalities, risks, and limitations in relation to different qualitative methodologies, forms of evidence, and research contexts. Taken as a whole, these reports-the full versions of which can be found in the Supplementary Materials-offer practical guidance to scholars designing and implementing qualitative research, and to editors, reviewers, and funders seeking to develop criteria of evaluation that are appropriate-as understood by relevant research communities-to the forms of inquiry being assessed. We dedicate this Reflection to the memory of our coauthor and QTD working group leader Kendra Koivu.(1)
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| 22. |
- Lake, BB, et al.
(författare)
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A comparative strategy for single-nucleus and single-cell transcriptomes confirms accuracy in predicted cell-type expression from nuclear RNA
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 6031-
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Tidskriftsartikel (refereegranskat)abstract
- Significant heterogeneities in gene expression among individual cells are typically interrogated using single whole cell approaches. However, tissues that have highly interconnected processes, such as in the brain, present unique challenges. Single-nucleus RNA sequencing (SNS) has emerged as an alternative method of assessing a cell’s transcriptome through the use of isolated nuclei. However, studies directly comparing expression data between nuclei and whole cells are lacking. Here, we have characterized nuclear and whole cell transcriptomes in mouse single neurons and provided a normalization strategy to reduce method-specific differences related to the length of genic regions. We confirmed a high concordance between nuclear and whole cell transcriptomes in the expression of cell type and metabolic modeling markers, but less so for a subset of genes associated with mitochondrial respiration. Therefore, our results indicate that single-nucleus transcriptome sequencing provides an effective means to profile cell type expression dynamics in previously inaccessible tissues.
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| 23. |
- Shekelle, PG, et al.
(författare)
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Advancing the science of patient safety
- 2011
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Ingår i: Annals of internal medicine. - : American College of Physicians. - 1539-3704 .- 0003-4819. ; 154:10, s. 693-696
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Tidskriftsartikel (refereegranskat)
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| 24. |
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| 25. |
- Alafuzoff, I, et al.
(författare)
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A comparison of multiplex and simplex families with Alzheimer's disease/senile dementia of Alzheimer type within a well defined population.
- 1994
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Ingår i: Journal of neural transmission. Parkinson's disease and dementia section. - 0936-3076. ; 7:1, s. 61-72
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Tidskriftsartikel (refereegranskat)abstract
- A study was made on 150 clinically demented patients presenting at autopsy at Umeå University Hospital in Sweden. In 90 of the cases dementia was considered to be primary in nature and of these forty six per cent (41 cases), fulfilled both the clinical and histopathological criteria for the diagnosis of Alzheimer's disease/Senile dementia of Alzheimer type (AD/SDAT). The families of these 41 AD/SDAT cases were then studied, and a family history obtained through interviews with multiple family informants and from civil and medical records. Additional diseased family members suffering from progressive dementia (multiplex families) were observed in 12 probands out of 41 (29%). Multiplex families exhibited similar clinical and histopathological characteristics as simplex families containing a single affected individual. The secondary cases in the multiplex families exhibited similar demographic and clinical characteristics as the probands. 39% of the multiplex and 14% of the simplex cases had an early age of onset of the disease, that was under 65 years. The overall prevalence of progressive dementia disorders in the 41 families was 5.9%. The prevalence of a progressive dementia disorder was 11% in the multiplex families (14% for the early onset cases) and 3.5% in the simplex families (2% for the early onset cases). The prevalence of progressive dementia disorder for family members who had passed the mean age of the onset of the disease for their family, was 45% for multiplex and 18% for simplex families. Furthermore the incidence rate for dementia was significantly higher (p < 0.005) in multiplex families (5.5 per 1,000 person years) when compared to simplex families (2.5 per 1,000 person years). No differences could be seen in parental age at birth of the diseased when comparing the two sets of families. However in multiplex families the duration of the disease was significantly (p < 0.025) shorter, in subjects with parental age at birth over 35 years compared to those with a parental age under 35 years. The multiplex families contained significantly (p < 0.025) larger sibships; and showed a significantly lower age of onset for the disease (p < 0.001), and a significantly longer duration of disease (p < 0.05) compared to the simplex families. A significant intra familial correlation of age at disease onset was observed in both sets of the families.
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| 26. |
- Almqvist, E, et al.
(författare)
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Screening of amyloid precursor protein gene mutation (APP 717 Val-->Ile) in Swedish families with Alzheimer's disease.
- 1993
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Ingår i: Journal of neural transmission. Parkinson's disease and dementia section. - 0936-3076. ; 6:2, s. 151-6
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Tidskriftsartikel (refereegranskat)abstract
- Screening for the APP 717 Val-->Ile mutation in the amyloid precursor protein (APP) gene in 34 Swedish families with familial Alzheimer's disease (FAD), 16 sporadic cases of Alzheimer's disease and five patients with Down's syndrome (DS) failed to identify further cases of the mutation. These results suggests that the mutation is rare among Swedish families with Alzheimer's disease. In addition, we summarize present reports of the frequency of the mutation.
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| 27. |
- Battley, M., et al.
(författare)
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Hydroelastic behaviour of slam loaded composite hull panels
- 2008
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Ingår i: High Perform. Yacht Des. Conf., HPYD. - 9781622769124 ; , s. 37-46
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Konferensbidrag (refereegranskat)abstract
- The effects of stiffness on hydroelastic responses of composite marine hull panels subjected to water slamming loads have been experimentally characterised. Panels included a very flexible single skin laminate, a medium stiffness sandwich panel and a very stiff sandwich panel. Panels were tested at a deadrise angle of 10° for a range of water impact velocities from 0.5 to 7m/s in a Servo-hydraulic Slam Testing System. Results demonstrate that the panel stiffness has a significant effect on the responses of slam loaded composite panels. Flexible panels had reductions in the local velocity at the centre of the panel relative to the water, reducing peak pressures at the panel centre. Pressures increased near to the chine edge of the panel, possibly due to reductions in the local deadrise angle due to panel deformation. Such effects were particularly noticeable when the loading rate was of similar order to the first natural frequency of the panel. The implications of the effects of panel stiffness on effective pressure and panel structural response on composite structural design are discussed.
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| 28. |
- Berndt, Sonja, I, et al.
(författare)
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Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
- 2022
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Ingår i: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 36:12, s. 2835-2844
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Tidskriftsartikel (refereegranskat)abstract
- Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
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| 29. |
- Elofsson, Rolf, et al.
(författare)
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On the cavity receptor organ (X-organ or organ of Bellonci) of Artemia salina (Crustacea, Anostraca)
- 1971
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Ingår i: Zeitschrift für Zellforschung und mikroskopische Anatomie. ; 121, s. 319-326
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Tidskriftsartikel (refereegranskat)abstract
- The cavity receptor organ (previously X-organ or organ of Bellonci) of Artemia salina consists of ciliated neurons whose cilia protrude into a cavity beneath the cuticle. The neuronal dendrites penetrate a giant accompanying cell and epidermal cells before entering the cavity. The cavity beneath the cuticle, the ciliated neurons and the connexion with the medulla terminalis justifies a homologization with the frontal filament organ of cirripeds and the third unit of copepods. The term cavity receptor is suggested for this organ. It is hardly homologous with the second unit of copepods and the organs described for many malacostracans under the names of sensory pore X-organ or organ of Bellonci. The latter organs are very similar to the cavity receptor but have an internal cavity formed by glial cells.The cavity receptor organ was previously considered neurosecretory but in the light of the present knowledge it is rather sensory although a double function cannot be denied.
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| 30. |
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| 31. |
- Frampton, Matthew, et al.
(författare)
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Variation at 3p24.1 and 6q23.3 influences the risk of Hodgkin's lymphoma
- 2013
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- In addition to HLA, recent genome-wide association studies (GWASs) of Hodgkin's lymphoma (HL) have identified susceptibility loci for HL at 2p16.1, 8q24.21 and 10p14. In this study, we perform a GWAS meta-analysis with published GWAS (totalling 1,465 cases and 6,417 controls of European background), and follow-up the most significant association signals in 2,024 cases and 1,853 controls. A combined analysis identifies new HL susceptibility loci mapping to 3p24.1 (rs3806624; P = 1.14 x 10(-12), odds ratio (OR) = 1.26) and 6q23.3 (rs7745098; P = 3.42 x 10(-9), OR = 1.21). rs3806624 localizes 5' to the EOMES (eomesodermin) gene within a p53 response element affecting p53 binding. rs7745098 maps intergenic to HBS1L and MYB, a region previously associated with haematopoiesis. These findings provide further insight into the genetic and biological basis of inherited susceptibility to HL.
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| 32. |
- Furtak, Lukas J., et al.
(författare)
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A variable active galactic nucleus at z = 2.06 triply-imaged by the galaxy cluster MACS J0035.4−2015
- 2023
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 522:4, s. 5142-5151
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of a triply imaged active galactic nucleus (AGN), lensed by the galaxy cluster MACS J0035.4−2015 (z d = 0.352). The object is detected in Hubble Space Telescope imaging taken for the RELICS program. It appears to have a quasi-stellar nucleus consistent with a point-source, with a de-magnified radius of re ≲ 100 pc. The object is spectroscopically confirmed to be an AGN at z spec = 2.063 ± 0.005 showing broad rest-frame UV emission lines, and detected in both X-ray observations with Chandra and in ALCS ALMA band 6 (1.2 mm) imaging. It has a relatively faint rest-frame UV luminosity for a quasar-like object, MUV, 1450 = −19.7 ± 0.2. The object adds to just a few quasars or other X-ray sources known to be multiply lensed by a galaxy cluster. Some diffuse emission from the host galaxy is faintly seen around the nucleus, and there is a faint object nearby sharing the same multiple-imaging symmetry and geometric redshift, possibly an interacting galaxy or a star-forming knot in the host. We present an accompanying lens model, calculate the magnifications and time delays, and infer the physical properties of the source. We find the rest-frame UV continuum and emission lines to be dominated by the AGN, and the optical emission to be dominated by the host galaxy of modest stellar mass M✶ ≃ 109.2 M⊙. We also observe some variation in the AGN emission with time, which may suggest that the AGN used to be more active. This object adds a low-redshift counterpart to several relatively faint AGN recently uncovered at high redshifts with HST and JWST.
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| 33. |
- Karlsson, HKR, et al.
(författare)
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Relationship between serum amyloid A level and Tanis/SelS mRNA expression in skeletal muscle and adipose tissue from healthy and type 2 diabetic subjects
- 2004
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 53:6, s. 1424-1428
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Tidskriftsartikel (refereegranskat)abstract
- Tanis is a recently described protein reported to be a putative receptor for serum amyloid A and found to be dysregulated with diabetes in the Israeli sand rat Psamommys obesus. Tanis has also been identified as a selenoprotein, one of the first two identified membrane selenoproteins. We determined mRNA expression of the human homologue of Tanis, SelS/AD-015, in skeletal muscle and adipose tissue biopsies obtained from 10 type 2 diabetic patients and 11 age- and weight-matched healthy subjects. Expression of Tanis/SelS mRNA in skeletal muscle and adipose tissue biopsies was similar between diabetic and control subjects. A subset of subjects underwent a euglycemic-hyperinsulinemic clamp, and adipose tissue expression of Tanis/SelS was determined after in vivo insulin stimulation. Adipose tissue Tanis/SelS mRNA expression was unchanged after insulin infusion in control subjects, whereas Tanis/SelS mRNA increased in seven of eight subjects following insulin stimulation in diabetic subjects. Skeletal muscle and adipose tissue Tanis/SelS mRNA expression were positively correlated with plasma serum amyloid A. In conclusion, there is a strong trend toward upregulation of Tanis/SelS following insulin infusion in adipose tissue from type 2 diabetic subjects. Moreover, the positive relationship between Tanis mRNA and the acute-phase protein serum amyloid A suggests an interaction between innate immune system responses and Tanis expression in muscle and adipose tissue.
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| 34. |
- Klyushina, E. S., et al.
(författare)
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Investigation of the spin-1 honeycomb antiferromagnet BaNi2V2O8 with easy-plane anisotropy
- 2017
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Ingår i: Physical Review B. - : AMER PHYSICAL SOC. - 2469-9950 .- 2469-9969. ; 96:21
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Tidskriftsartikel (refereegranskat)abstract
- The magnetic properties of the two-dimensional, S = 1 honeycomb antiferromagnet BaNi2V2O8 have been comprehensively studied using dc susceptibility measurements and inelastic neutron scattering techniques. The magnetic excitation spectrum is found to be dispersionless within experimental resolution between the honeycomb layers, while it disperses strongly within the honeycomb plane where it consists of two gapped spin-wave modes. The magnetic excitations are compared to linear spin-wave theory allowing the Hamiltonian to be determined. The first-and second-neighbor magnetic exchange interactions are antiferromagnetic and lie within the ranges 10.90 meV <= J(n) <= 13.35 meV and 0.85 meV <= J(nn) <= 1.65 meV, respectively. The interplane coupling J(out) is four orders of magnitude weaker than the intraplane interactions, confirming the highly two-dimensional magnetic behavior of this compound. The sizes of the energy gaps are used to extract the magnetic anisotropies and reveal substantial easy-plane anisotropy and a very weak in-plane easy-axis anisotropy. Together these results reveal that BaNi2V2O8 is a candidate compound for the investigation of vortex excitations and Berezinsky-Kosterliz-Thouless phenomenon.
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| 35. |
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| 36. |
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| 37. |
- Morison, LD, et al.
(författare)
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In-depth characterisation of a cohort of individuals with missense and loss-of-function variants disrupting FOXP2
- 2023
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Ingår i: Journal of medical genetics. - : BMJ. - 1468-6244 .- 0022-2593. ; 60:6, s. 597-607
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Tidskriftsartikel (refereegranskat)abstract
- Heterozygous disruptions ofFOXP2were the first identified molecular cause for severe speech disorder: childhood apraxia of speech (CAS), and yet few cases have been reported, limiting knowledge of the condition.MethodsHere we phenotyped 28 individuals from 17 families with pathogenicFOXP2-only variants (12 loss-of-function, five missense variants; 14 males; aged 2 to 62 years). Health and development (cognitive, motor, social domains) were examined, including speech and language outcomes with the first cross-linguistic analysis of English and German.ResultsSpeech disorders were prevalent (23/25, 92%) and CAS was most common (22/25, 88%), with similar speech presentations across English and German. Speech was still impaired in adulthood, and some speech sounds (eg, ‘th’, ‘r’, ‘ch’, ‘j’) were never acquired. Language impairments (21/25, 84%) ranged from mild to severe. Comorbidities included feeding difficulties in infancy (10/26, 38%), fine (13/26, 50%) and gross (13/26, 50%) motor impairment, anxiety (5/27, 19%), depression (6/27, 22%) and sleep disturbance (10/24, 42%). Physical features were common (22/27, 81%) but with no consistent pattern. Cognition ranged from average to mildly impaired and was incongruent with language ability; for example, seven participants with severe language disorder had average non-verbal cognition.ConclusionsAlthough we identify an increased prevalence of conditions like anxiety, depression and sleep disturbance, we confirm that the consequences ofFOXP2dysfunction remain relatively specific to speech disorder, as compared with other recently identified monogenic conditions associated with CAS. Thus, our findings reinforce thatFOXP2provides a valuable entry point for examining the neurobiological bases of speech disorder.
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| 38. |
- Nishio, Akiyosho, et al.
(författare)
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Comparative studies of mitochondrial autoantibodies in sera and bile in primary biliary cirrhosis
- 1997
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 25:5, s. 1085-1089
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Tidskriftsartikel (refereegranskat)abstract
- Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by destruction of intrahepatic bile ducts. Although the pathogenesis of this disease is still unknown, high titers of antimitochondrial autoantibodies (AMA) have long been recognized in patient sera. However, little is known about the presence of AMA in bile. In this study, we investigated bile and sera from patients with PBC and healthy controls for the presence of AMA and mitochondrial autoantigens. AMA were detected in the bile of 17 of 19 patients (89.4%) with PBC; they were specifically directed against the pyruvate dehydrogenase complex (PDC-E2) in 15 of 19 patients (78.9%), to the branched-chain 2-oxo-acid dehydrogenase complex E2 (BCOADC-E2) in 6 of 19 patients (31.6%), and to the 2-oxoglutarate dehydrogenase complex E2 (OGDC-E2) in 1 of 19 patients (5.3%). In a comparative study of sera from the same patients, anti-PDC-E2 antibodies were found in 19 of 19 patients (100%), anti-BCOADC in 9 of 19 patients (47.3%), and anti-OGDC-E2 in 4 of 19 patients (21.1%) patients. AMA in bile were always found together with antibodies of corresponding specificities in the serum from the same patient. Immunoglobulin (Ig)A AMA were found in the bile of 9 of 19 patients (47.7%) with PBC; they were specifically directed against PDC-E2 in 8 of 19 patients (42.1%) and to BCOADC in 2 of 19 patients (10.5%). Epitope mapping of IgA anti-PDC-E2 antibodies indicated that, like serum autoantibodies, the immunodominant epitope is directed against the inner lipoyl domain of PDC-E2. The prevalence and antigen reactivity of IgA AMA in sera correlated completely with IgA AMA in bile. Autoantibodies against nuclear envelope pore proteins (gp210) were found in 1 of 8 (12.5%) sera of patients with PBC, but not in bile. Furthermore, and of particular interest, we detected the autoantigens, PDC-E2, OGDC-E2, and BCOADC-E2, in the bile of 12 of 19 patients (63.2%), 9 of 19 patients (47.4%), and 9 of 19 patients (47.4%), respectively; PDC-E2 was found in only 1 of 17 (5.9%) disease controls. Although the presence of AMA in bile may merely reflect the presence of these antibodies in sera, the simultaneous detection of mitochondrial autoantigens in bile suggests an increase of mitochondrial autoantigens at inflammatory sites. Such autoantigens, coupled with AMA, may augment the local immune response and disease progression.
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| 39. |
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| 40. |
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| 41. |
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| 42. |
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| 43. |
- Sud, Amit, et al.
(författare)
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Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1, s. 1892-1892
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Tidskriftsartikel (refereegranskat)abstract
- Several susceptibility loci for classical Hodgkin lymphoma have been reported. However, much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies, a new genome-wide association study, and replication totalling 5,314 cases and 16,749 controls. We identify risk loci for all classical Hodgkin lymphoma at 6q22.33 (rs9482849, P = 1.52 × 10-8) and for nodular sclerosis Hodgkin lymphoma at 3q28 (rs4459895, P = 9.43 × 10-17), 6q23.3 (rs6928977, P = 4.62 × 10-11), 10p14 (rs3781093, P = 9.49 × 10-13), 13q34 (rs112998813, P = 4.58 × 10-8) and 16p13.13 (rs34972832, P = 2.12 × 10-8). Additionally, independent loci within the HLA region are observed for nodular sclerosis Hodgkin lymphoma (rs9269081, HLA-DPB1*03:01, Val86 in HLA-DRB1) and mixed cellularity Hodgkin lymphoma (rs1633096, rs13196329, Val86 in HLA-DRB1). The new and established risk loci localise to areas of active chromatin and show an over-representation of transcription factor binding for determinants of B-cell development and immune response.
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| 44. |
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| 45. |
- Turnyanskiy, M., et al.
(författare)
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Measurement and control of the fast ion redistribution on MAST
- 2013
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 53:5, s. 053016-
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Tidskriftsartikel (refereegranskat)abstract
- Previous experiments on MAST and other tokamaks have indicated that the level of fast ion redistribution can exceed that expected from classical diffusion and that this level increases with beam power. In this paper we present a quantification of this effect in MAST plasmas using a recently commissioned scanning neutron camera. The observed fast ion diffusivity correlates with the amplitude of n = 1 energetic particle modes, indicating that they are the probable cause of the non-classical fast ion diffusion in MAST. Finally, it will be shown that broadening the fast ion pressure profile by the application of neutral beam injection at an off-axis location can mitigate the growth of these modes and result in the classical fast ion behaviour.
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| 46. |
- van der Most, Robbert G., et al.
(författare)
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Tumor eradication after cyclophosphamide depends on concurrent depletion of regulatory T cells: a role for cycling TNFR2-expressing effector-suppressor T cells in limiting effective chemotherapy
- 2009
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Ingår i: Cancer Immunology and Immunotherapy. - : Springer Science and Business Media LLC. - 1432-0851 .- 0340-7004. ; 58:8, s. 1219-1228
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Tidskriftsartikel (refereegranskat)abstract
- Tumor cell death potentially engages with the immune system. However, the efficacy of anti-tumor chemotherapy may be limited by tumor-driven immunosuppression, e.g., through CD25(+) regulatory T cells. We addressed this question in a mouse model of mesothelioma by depleting or reconstituting CD25(+) regulatory T cells in combination with two different chemotherapeutic drugs. We found that the efficacy of cyclophosphamide to eradicate established tumors, which has been linked to regulatory T cell depletion, was negated by adoptive transfer of CD25(+) regulatory T cells. Analysis of post-chemotherapy regulatory T cell populations revealed that cyclophosphamide depleted cycling (Ki-67(hi)) T cells, including foxp3(+) regulatory CD4(+) T cells. Ki-67(hi) CD4(+) T cells expressed increased levels of two markers, TNFR2 and ICOS, that have been associated with a maximally suppressive phenotype according to recently published studies. This suggest that cyclophosphamide depletes a population of maximally suppressive regulatory T cells, which may explain its superior anti-tumor efficacy in our model. Our data suggest that regulatory T cell depletion could be used to improve the efficacy of anti-cancer chemotherapy regimens. Indeed, we observed that the drug gemcitabine, which does not deplete cycling regulatory T cells, eradicates established tumors in mice only when CD25(+) CD4(+) T cells are concurrently depleted. Cyclophosphamide could be used to achieve regulatory T cell depletion in combination with chemotherapy.
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