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Sökning: WFRF:(Thom Simon)

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  • Engert, Andreas, et al. (författare)
  • The european hematology association roadmap for european hematology research : : A consensus document
  • 2016
  • Ingår i: Haematologica. - Ferrata Storti Foundation. - 0390-6078. ; 101:2, s. 115-208
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at ∈ European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better fu treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine ‘sections’ in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
  • Blösch, Günter, et al. (författare)
  • Twenty-three unsolved problems in hydrology (UPH) - a community perspective
  • 2019
  • Ingår i: Hydrological Sciences Journal. - TAYLOR & FRANCIS LTD. - 0262-6667 .- 2150-3435. ; 64:10, s. 1141-1158
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through online media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focused on the process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come.
  • Evangelou, Evangelos, et al. (författare)
  • Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
  • 2018
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
  • Tidskriftsartikel (refereegranskat)abstract
    • High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
  • Johnson, Toby, et al. (författare)
  • Blood Pressure Loci Identified with a Gene-Centric Array.
  • 2011
  • Ingår i: American Journal of Human Genetics. - 1537-6605. ; 89:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56 x 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery, and follow-up data identified SNPs significantly associated with BP at p < 8.56 x 10(-7) at four further loci (NPR3, FIFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.
  • Loisel, Julie, et al. (författare)
  • A database and synthesis of northern peatland soil properties and Holocene carbon and nitrogen accumulation
  • 2014
  • Ingår i: The Holocene. - SAGE Publications. - 0959-6836. ; 24:9, s. 1028-1042
  • Tidskriftsartikel (refereegranskat)abstract
    • Here, we present results from the most comprehensive compilation of Holocene peat soil properties with associated carbon and nitrogen accumulation rates for northern peatlands. Our database consists of 268 peat cores from 215 sites located north of 45 degrees N. It encompasses regions within which peat carbon data have only recently become available, such as the West Siberia Lowlands, the Hudson Bay Lowlands, Kamchatka in Far East Russia, and the Tibetan Plateau. For all northern peatlands, carbon content in organic matter was estimated at 42 +/- 3% (standard deviation) for Sphagnum peat, 51 +/- 2% for non-Sphagnum peat, and at 49 +/- 2% overall. Dry bulk density averaged 0.12 +/- 0.07 g/cm(3), organic matter bulk density averaged 0.11 +/- 0.05 g/cm(3), and total carbon content in peat averaged 47 +/- 6%. In general, large differences were found between Sphagnum and non-Sphagnum peat types in terms of peat properties. Time-weighted peat carbon accumulation rates averaged 23 +/- 2 (standard error of mean) g C/m(2)/yr during the Holocene on the basis of 151 peat cores from 127 sites, with the highest rates of carbon accumulation (25-28 g C/m(2)/yr) recorded during the early Holocene when the climate was warmer than the present. Furthermore, we estimate the northern peatland carbon and nitrogen pools at 436 and 10 gigatons, respectively. The database is publicly available at https://peatlands.lehigh.edu.
  • Simon, Geoff I., et al. (författare)
  • Impacts of Aging on Anemia Tolerance, Transfusion Thresholds, and Patient Blood Management
  • 2019
  • Ingår i: Transfusion Medicine Reviews. - W B SAUNDERS CO-ELSEVIER INC. - 0887-7963. ; 33:3, s. 154-161
  • Forskningsöversikt (övrigt vetenskapligt)abstract
    • Evidence-based patient blood management guidelines commonly recommend restrictive hemoglobin thresholds of 70 to 80 g/L for asymptomatic adults. However, most transfusion trials have enrolled adults across a broad age span, with few exclusive to older adults. Our recent meta-analysis of transfusion trials that focused on older adults paradoxically found lower mortality and fewer cardiac complications when these patients were managed using higher hemoglobin thresholds. We postulate that declining cardiac output with age contributes to deteriorating oxygen delivery capacity which impacts anemia-associated outcomes in older adults and propose a model to explain this age-related difference. We reviewed evidence concerning the pathophysiology of aging to explore the disparity in transfusion trial outcomes related to hemoglobin thresholds in different age groups. The literature was searched for normative cardiac output values at different ages in healthy adults. Using normative peak cardiac output data, we modeled oxygen delivery capacity in young, middle-aged, and older adults at a range of hemoglobin levels. Cardiovascular and pulmonary systems are impacted by age-related pathophysiological changes. Diminishing peak cardiac output associated with aging reduces the maximal oxygen delivery achievable under metabolic stress. Hence, at low hemoglobin levels, older adults are more susceptible to tissue hypoxia than younger adults. Our model predicts that an older adult with a hemoglobin of 100 g/L has a similar peak oxygen delivery capacity to a young adult with a hemoglobin of 70 g/L. Age-related pathophysiological changes provide some explanation as to why older adults have a lower tolerance for anemia than younger adults. This indicates the need for patient blood management hemoglobin thresholds specific to older as distinct from younger adults. The primary application of this model is in the consideration of patients rehabilitating to life outside hospital. It is important to note that pathophysiological changes associated with critical illness and major surgery are more complex than can be described in a simple model based on cardiac output and hemoglobin concentration. However, our review of oxygen transport and delivery in health and disease states allows the model to be considered in the context of treatment decisions for anemic adults in a range of hospital and community settings. (C) 2019 Elsevier Inc. All rights reserved.
  • Uhlmann, Eckart, et al. (författare)
  • Solutions for Sustainable Machining
  • 2017
  • Ingår i: Journal of manufacturing science and engineering. - American Society of Mechanical Engineers. - 1087-1357. ; 139:5, s. 051009-1-051009-7
  • Tidskriftsartikel (refereegranskat)abstract
    • The manufacturing industry contributes over 19% to the world’s greenhouse gas emissions (U.S. Energy Information Administration, 2008, “Rep: Annual Energy Review 2008,” Report No. DOE/EIA-0384; Diaz et al., 2010, “Environmental Analysis of Milling Machine Tool Use in Various Manufacturing Environments,” 2010 IEEE International Symposium on Sustainable Systems and Technology.) and 31% of the total energy consumed annually in the U.S. (Herzog, T., 2005, “World Greenhouse Gas Emissions in 2005,” World Resources Institute, Washington, DC 2 ; Diaz et al., 2010, “Environmental Analysis of Milling Machine Tool Use in Various Manufacturing Environments,” 2010 IEEE International Symposium on Sustainable Systems and Technology.). There is therefore an increasing demand for sustainable solutions for the production technology industry. At the Technische Universitat (TU) Berlin, Germany, a collaborative research center (CRC) is focusing on new solutions for the sustainable machining of high performance alloys, with developments from machine tool frames to cutting tool technology being undertaken. An innovative machine tool concept with a modular frame, which allows a high level of flexibility, has been developed. Furthermore, add-on upgrading systems for older machine tools, which are particularly relevant for developing countries, have been developed. These systems allow the accuracy of outdated machine tools to be increased, thus making the machine tools comparable to modern systems. Finally the cutting process also requires solutions for dry machining, as the use of cooling lubricant is environmentally damaging and a significant cost contributor in machining processes. Two solutions are being developed at the TU Berlin: an internally cooled cutting tool and a heating concept for ceramic tools to allow dry machining of high temperature alloys, for example, for the aerospace industry.
  • Uhlmann, Eckart, et al. (författare)
  • Sustainable Solutions for Machine Tool
  • 2017
  • Ingår i: Sustainable Manufacturing : Challenges, Solutions and Implementation Perspectives. - Cham : Springer. - 978-3-319-48513-3 - 978-3-319-48514-0 ; s. 47-69
  • Bokkapitel (övrigt vetenskapligt)abstract
    • Environmental, economic and social changes of any significant proportions cannot take place without a major shift in the manufacturing sector. In today’s manufacturing processes, economic efficiency is realised through high volumes with the use of specialised machine tools. Change in society, such as in the form of mobility and digitisation, requires a complete overhaul in terms of thinking in the manufacturing industry. Moreover, the manufacturing industry contributes over 19 % to the world’s greenhouse gas emissions. As a consequence of these issues, a demand for sustainable solutions in the production industry is increasing. In particular, the concept of “cost” in manufacturing processes and thus the “system boundaries” within the production of the future has to be changed. That is, a great number of aspects to the machine tool and production technology industries can be improved upon in order to achieve a more sustainable production environment. Within this chapter, the focus lies on microsystem technology enhanced modular machine tool frames, adaptive mechatronic components, as well as on internallycooled cutting tools. An innovative machine tool concept has been developed recently, featuring a modular machine tool frame using microsystem technology for communication within the frame, which allows for a high level of flexibility. Furthermore, add-on upgrading systems for outdated machine tools—which are particularly relevant for developing and emerging countries—are poised to gain in importance in the upcoming years. The system described here enables the accuracy of outdated machine tools to be increased, thus making these machine tools comparable to modern machine tool systems. Finally, the cutting process requires solutions for dry machining, as the use of cooling lubricants is environmentally damaging and a significant cost contributor in machining processes. One such solution is the use of internally cooled cutting tools.
  • Wain, Louise V., et al. (författare)
  • Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
  • 2017
  • Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 70:3, s. E4-e19
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
  • Warren, Helen R., et al. (författare)
  • Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk
  • 2017
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 49:3, s. 403-415
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.
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