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- Kontsevaya, Irina, et al.
(författare)
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Perspectives for systems biology in the management of tuberculosis
- 2021
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Ingår i: European Respiratory Review. - : European Respiratory Society (ERS). - 0905-9180 .- 1600-0617. ; 30:160
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Forskningsöversikt (refereegranskat)abstract
- Standardised management of tuberculosis may soon be replaced by individualised, precision medicine-guided therapies informed with knowledge provided by the field of systems biology. Systems biology is a rapidly expanding field of computational and mathematical analysis and modelling of complex biological systems that can provide insights into mechanisms underlying tuberculosis, identify novel biomarkers, and help to optimise prevention, diagnosis and treatment of disease. These advances are critically important in the context of the evolving epidemic of drug-resistant tuberculosis. Here, we review the available evidence on the role of systems biology approaches - human and mycobacterial genomics and transcriptomics, proteomics, lipidomics/metabolomics, immunophenotyping, systems pharmacology and gut microbiomes - in the management of tuberculosis including prediction of risk for disease progression, severity of mycobacterial virulence and drug resistance, adverse events, comorbidities, response to therapy and treatment outcomes. Application of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach demonstrated that at present most of the studies provide "very low" certainty of evidence for answering clinically relevant questions. Further studies in large prospective cohorts of patients, including randomised clinical trials, are necessary to assess the applicability of the findings in tuberculosis prevention and more efficient clinical management of patients.
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- Krege, Susanne, et al.
(författare)
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European consensus conference on diagnosis and treatment of germ cell cancer: A report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): Part I
- 2008
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 53:3, s. 478-496
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Forskningsöversikt (refereegranskat)abstract
- Objectives: The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, Amsterdam, The Netherlands. Methods: Medical oncologists, urological surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference, and incorporated the new data into updated and revised guidelines. As for the first meeting, the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. Results: The first part of the consensus paper describes the clinical presentation of the primary tumor, its treatment, the importance and treatment of testicular intraepithelial neoplasia (TIN), histological classification, staging and prognostic factors, and treatment of stage I seminoma and non-seminoma. Conclusions: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early- and advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged. (C) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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- Krege, Susanne, et al.
(författare)
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European consensus conference on diagnosis and treatment of germ cell cancer: A report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): Part II
- 2008
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 53:3, s. 497-513
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Forskningsöversikt (refereegranskat)abstract
- Objectives: The first consensus report that had been presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, The Netherlands. Methods: Medical oncologists, urologic surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference and incorporated the new data into updated and revised guidelines. As for the first meeting the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. Results: The second part of the consensus paper includes the treatment of metastasised disease, residual tumour resection, salvage therapy, follow-up, and late toxicities. Conclusions: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early-stage as well as of advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. in addition, the particular needs of testicular cancer survivors have been acknowledged. (C) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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- Martin, Scot T., et al.
(författare)
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Sources and properties of Amazonian aerosol particles
- 2010
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Ingår i: Reviews of Geophysics. - 8755-1209. ; 48, s. 2002-2002
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Forskningsöversikt (refereegranskat)abstract
- This review provides a comprehensive account of what is known presently about Amazonian aerosol particles and concludes by formulating outlook and priorities for further research. The review is organized to follow the life cycle of Amazonian aerosol particles. It begins with a discussion of the primary and secondary sources relevant to the Amazonian particle burden, followed by a presentation of the particle properties that characterize the mixed populations present over the Amazon Basin at different times and places. These properties include number and mass concentrations and distributions, chemical composition, hygroscopicity, and cloud nucleation ability. The review presents Amazonian aerosol particles in the context of natural compared to anthropogenic sources as well as variability with season and meteorology. This review is intended to facilitate an understanding of the current state of knowledge on Amazonian aerosol particles specifically and tropical continental aerosol particles in general and thereby to enhance future research in this area.
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- Hutchinson, David K., et al.
(författare)
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The Eocene-Oligocene transition : a review of marine and terrestrial proxy data, models and model data comparisons
- 2021
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 17:1, s. 269-315
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Forskningsöversikt (refereegranskat)abstract
- The Eocene-Oligocene transition (EOT) was a climate shift from a largely ice-free greenhouse world to an icehouse climate, involving the first major glaciation of Antarctica and global cooling occurring similar to 34 million years ago (Ma) and lasting similar to 790 kyr. The change is marked by a global shift in deep-sea delta O-18 representing a combination of deep-ocean cooling and growth in land ice volume. At the same time, multiple independent proxies for ocean temperature indicate sea surface cooling, and major changes in global fauna and flora record a shift toward more cold-climateadapted species. The two principal suggested explanations of this transition are a decline in atmospheric CO2 and changes to ocean gateways, while orbital forcing likely influenced the precise timing of the glaciation. Here we review and synthesise proxy evidence of palaeogeography, temperature, ice sheets, ocean circulation and CO2 change from the marine and terrestrial realms. Furthermore, we quantitatively compare proxy records of change to an ensemble of climate model simulations of temperature change across the EOT. The simulations compare three forcing mechanisms across the EOT: CO2 decrease, palaeogeographic changes and ice sheet growth. Our model ensemble results demonstrate the need for a global cooling mechanism beyond the imposition of an ice sheet or palaeogeographic changes. We find that CO2 forcing involving a large decrease in CO2 of ca. 40 % (similar to 325 ppm drop) provides the best fit to the available proxy evidence, with ice sheet and palaeogeographic changes playing a secondary role. While this large decrease is consistent with some CO2 proxy records (the extreme endmember of decrease), the positive feedback mechanisms on ice growth are so strong that a modest CO2 decrease beyond a critical threshold for ice sheet initiation is well capable of triggering rapid ice sheet growth. Thus, the amplitude of CO2 decrease signalled by our data-model comparison should be considered an upper estimate and perhaps artificially large, not least because the current generation of climate models do not include dynamic ice sheets and in some cases may be undersensitive to CO2 forcing. The model ensemble also cannot exclude the possibility that palaeogeographic changes could have triggered a reduction in CO2.
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- Lau, Dennis H., et al.
(författare)
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Novel mechanisms in the pathogenesis of atrial fibrillation: practical applications
- 2016
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Ingår i: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645. ; 37:20, s. 1573-
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Forskningsöversikt (refereegranskat)abstract
- Intensive research over the last few decades has seen significant advances in our understanding of the complex mechanisms underlying atrial fibrillation (AF). The epidemic of AF and related hospitalizations has been described as a rising tide with estimates of the global AF burden showing no sign of retreat. There is urgency for effective translational programs in this field to facilitate more individualized and targeted therapy to modify the abnormal atrial substrate responsible for the perpetuation of this arrhythmia. In this review, we chose to focus on several novel aspects of AF pathogenesis whereby practical applications in clinical practice are currently available or potentially not too far away. Specifically, we explored the contribution of atrial fibrosis, epicardial adipose tissue, autonomic nervous system, hyper-coagulability, and focal drivers to adverse atrial remodelling and AF persistence. We also highlighted the potential practical means of monitoring and targeting these factors to achieve better outcomes in patients suffering from this debilitating illness. Emerging data also support a new paradigm for targeting AF substrate with aggressive risk factor management. Finally, multi-disciplinary integrated care approach has shown great promise in improving cardiovascular outcomes of patients with AF along with potential cost savings.
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- Volkert, Dorothee, et al.
(författare)
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Management of Malnutrition in Older Patients : Current Approaches, Evidence and Open Questions
- 2019
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 8:7
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Forskningsöversikt (refereegranskat)abstract
- Malnutrition is widespread in older people and represents a major geriatric syndrome with multifactorial etiology and severe consequences for health outcomes and quality of life. The aim of the present paper is to describe current approaches and evidence regarding malnutrition treatment and to highlight relevant knowledge gaps that need to be addressed. Recently published guidelines of the European Society for Clinical Nutrition and Metabolism (ESPEN) provide a summary of the available evidence and highlight the wide range of different measures that can be taken-from the identification and elimination of potential causes to enteral and parenteral nutrition-depending on the patient's abilities and needs. However, more than half of the recommendations therein are based on expert consensus because of a lack of evidence, and only three are concern patient-centred outcomes. Future research should further clarify the etiology of malnutrition and identify the most relevant causes in order to prevent malnutrition. Based on limited and partly conflicting evidence and the limitations of existing studies, it remains unclear which interventions are most effective in which patient groups, and if specific situations, diseases or etiologies of malnutrition require specific approaches. Patient-relevant outcomes such as functionality and quality of life need more attention, and research methodology should be harmonised to allow for the comparability of studies.
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