| 1. |
- Engert, Andreas, et al.
(författare)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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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 (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and 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.
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| 2. |
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| 3. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 4. |
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| 5. |
- Pennells, Lisa, et al.
(författare)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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| 6. |
- Ahmed, Kamran, et al.
(författare)
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Development of a standardised training curriculum for robotic surgery: a consensus statement from an international multidisciplinary group of experts
- 2015
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Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 116:1, s. 93-101
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To explore the views of experts about the development and validation of a robotic surgery training curriculum, and how this should be implemented. Materials and methods: An international expert panel was invited to a structured session for discussion. The study was of a mixed design, including qualitative and quantitative components based on focus group interviews during the European Association of Urology (EAU) Robotic Urology Section (ERUS) (2012), EAU (2013) and ERUS (2013) meetings. After introduction to the aims, principles and current status of the curriculum development, group responses were elicited. After content analysis of recorded interviews generated themes were discussed at the second meeting, where consensus was achieved on each theme. This discussion also underwent content analysis, and was used to draft a curriculum proposal. At the third meeting, a quantitative questionnaire about this curriculum was disseminated to attendees to assess the level of agreement with the key points. Results: In all, 150 min (19 pages) of the focus group discussion was transcribed (21 316 words). Themes were agreed by two raters (median agreement kappa 0.89) and they included: need for a training curriculum (inter-rater agreement kappa 0.85); identification of learning needs (kappa 0.83); development of the curriculum contents (kappa 0.81); an overview of available curricula (kappa 0.79); settings for robotic surgery training ((kappa 0.89); assessment and training of trainers (kappa 0.92); requirements for certification and patient safety (kappa 0.83); and need for a universally standardised curriculum (kappa 0.78). A training curriculum was proposed based on the above discussions. Conclusion: This group proposes a multi-step curriculum for robotic training. Studies are in process to validate the effectiveness of the curriculum and to assess transfer of skills to the operating room.
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| 7. |
- Belmatoug, Nadia, et al.
(författare)
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Management and monitoring recommendations for the use of eliglustat in adults with type 1 Gaucher disease in Europe
- 2017
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Ingår i: European Journal of Internal Medicine. - : Elsevier BV. - 0953-6205. ; 37, s. 25-32
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Forskningsöversikt (refereegranskat)abstract
- Purpose: In Gaucher disease, diminished activity of the lysosomal enzyme, acid β-glucosidase, leads to accumulation of glucosylceramides and related substrates, primarily in the spleen, liver, and bone marrow. Eliglustat is an oral substrate reduction therapy approved in the European Union and the United States as a first-line treatment for adults with type 1 Gaucher disease who have compatible CYP2D6 metabolism phenotypes. A European Advisory Council of experts in Gaucher disease describes the characteristics of eliglustat that are distinct from enzyme augmentation therapy (the standard of care) and miglustat (the other approved substrate reduction therapy) and recommends investigations and monitoring for patients on eliglustat therapy within the context of current recommendations for Gaucher disease management. Results: Eliglustat is a selective, potent inhibitor of glucosylceramide synthase, the enzyme responsible for biosynthesis of glucosylceramides which accumulate in Gaucher disease. Extensive metabolism of eliglustat by CYP2D6, and, to a lesser extent, CYP3A of the cytochrome P450 pathway, necessitates careful consideration of the patient's CYP2D6 metaboliser status and use of concomitant medications which share metabolism by these pathways. Guidance on specific assessments and monitoring required for eliglustat therapy, including an algorithm to determine eligibility for eliglustat, are provided. Conclusions: As a first-line therapy for type 1 Gaucher disease, eliglustat offers eligible patients a daily oral therapy alternative to biweekly infusions of enzyme therapy. Physicians will need to carefully assess individual Gaucher patients to determine their appropriateness for eliglustat therapy. The therapeutic response to eliglustat and use of concomitant medications will require long-term monitoring.
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| 8. |
- Bischoff, Stephan C, et al.
(författare)
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Standard operating procedures for ESPEN guidelines and consensus papers
- 2015
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614 .- 1532-1983. ; 34:6, s. 1043-1051
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Tidskriftsartikel (refereegranskat)abstract
- The ESPEN Guideline standard operating procedures (SOP) is based on the methodology provided by the Association of Scientific Medical Societies of Germany (AWMF), the Scottish Intercollegiate Guidelines Network (SIGN), and the Centre for Evidence-based Medicine at the University of Oxford. The SOP is valid and obligatory for all future ESPEN-sponsored guideline projects aiming to generate high-quality guidelines on a regular basis. The SOP aims to facilitate the preparation of guideline projects, to streamline the consensus process, to ensure quality and transparency, and to facilitate the dissemination and publication of ESPEN guidelines. To achieve this goal, the ESPEN Guidelines Editorial board (GEB) has been established headed by two chairmen. The GEB will support and supervise the guideline processes and is responsible for the strategic planning of ESPEN guideline activities. Key elements of the SOP are the generation of well-built clinical questions according to the PICO system, a systemic literature search, a classification of the selected literature according to the SIGN evidence levels providing an evidence table, and a clear and straight-forward consensus procedure consisting of online voting's and a consensus conference. Only experts who meet the obligation to disclosure any potential conflict of interests and who are not employed by the Industry can participate in the guideline process. All recommendations will be graded according to the SIGN grading and novel outcome models besides biomedical endpoints. This approach will further extent the leadership of ESPEN in creating up-to-date and suitable for implementation guidelines and in sharing knowledge on malnutrition and clinical nutrition.
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| 9. |
- Bischoff, Stephan C, et al.
(författare)
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Towards a multidisciplinary approach to understand and manage obesity and related diseases
- 2017
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614 .- 1532-1983. ; 36:4, s. 917-938
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Forskningsöversikt (refereegranskat)abstract
- Overnutrition and sedentary lifestyle result in overweight or obesity defined as abnormal or excessive fat accumulation that may impair health. According to the WHO, the worldwide prevalence of obesity nearly doubled between 1980 and 2008. In 2008, over 50% of both men and women in the WHO European Region were overweight, and approximately 23% of women and 20% of men were obese. Comprehensive diagnostic and therapeutic approaches should include nutritional treatment to favor the best metabolic and nutritional outcome, as well as to induce potential disease-specific benefits from selected nutritional regimens. Obesity is usually accompanied by an increased muscle mass. This might explain why obesity, under particular circumstances such as cancer or high age, might have protective effects, a phenomenon named the 'obesity paradox'. However, loss of muscle mass or function can also occur, which is associated with poor prognosis and termed 'sarcopenic obesity'. Therefore, treatment recommendations may need to be individualized and adapted to co-morbidities. Since obesity is a chronic systemic disease it requires a multidisciplinary approach, both at the level of prevention and therapy including weight loss and maintenance. In the present personal review and position paper, authors from different disciplines including endocrinology, gastroenterology, nephrology, pediatrics, surgery, geriatrics, intensive care medicine, psychology and psychiatry, sports medicine and rheumatology, both at the basic science and clinical level, present their view on the topic and underline the necessity to provide a multidisciplinary approach, to address this epidemic.
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| 10. |
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| 11. |
- Cederholm, Tommy, et al.
(författare)
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ESPEN guidelines on definitions and terminology of clinical nutrition
- 2017
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Ingår i: Clinical Nutrition. - 0261-5614 .- 1532-1983. ; 36:1, s. 49-64
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundA lack of agreement on definitions and terminology used for nutrition-related concepts and procedures limits the development of clinical nutrition practice and research.ObjectiveThis initiative aimed to reach a consensus for terminology for core nutritional concepts and procedures.MethodsThe European Society of Clinical Nutrition and Metabolism (ESPEN) appointed a consensus group of clinical scientists to perform a modified Delphi process that encompassed e-mail communication, face-to-face meetings, in-group ballots and an electronic ESPEN membership Delphi round.ResultsFive key areas related to clinical nutrition were identified: concepts; procedures; organisation; delivery; and products. One core concept of clinical nutrition is malnutrition/undernutrition, which includes disease-related malnutrition (DRM) with (eq. cachexia) and without inflammation, and malnutrition/undernutrition without disease, e.g. hunger-related malnutrition. Over-nutrition (overweight and obesity) is another core concept. Sarcopenia and frailty were agreed to be separate conditions often associated with malnutrition. Examples of nutritional procedures identified include screening for subjects at nutritional risk followed by a complete nutritional assessment. Hospital and care facility catering are the basic organizational forms for providing nutrition. Oral nutritional supplementation is the preferred way of nutrition therapy but if inadequate then other forms of medical nutrition therapy, i.e. enteral tube feeding and parenteral (intravenous) nutrition, becomes the major way of nutrient delivery.ConclusionAn agreement of basic nutritional terminology to be used in clinical practice, research, and the ESPEN guideline developments has been established. This terminology consensus may help to support future global consensus efforts and updates of classification systems such as the International Classification of Disease (ICD). The continuous growth of knowledge in all areas addressed in this statement will provide the foundation for future revisions.
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| 12. |
- Kalman, Janos L, et al.
(författare)
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Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.
- 2019
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Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18years] vs adulthood [>18years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
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| 13. |
- Muelbert, Jose H., et al.
(författare)
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ILTER : The International Long-Term Ecological Research Network as a Platform for Global Coastal and Ocean Observation
- 2019
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Ingår i: Frontiers in Marine Science. - : Frontiers Media S.A.. - 2296-7745. ; 6
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Forskningsöversikt (refereegranskat)abstract
- Understanding the threats to global biodiversity and ecosystem services posed by human impacts on coastal and marine environments requires the establishment and maintenance of ecological observatories that integrate the biological, physical, geological, and biogeochemical aspects of ecosystems. This is crucial to provide scientists and stakeholders with the support and knowledge necessary to quantify environmental change and its impact on the sustainable use of the seas and coasts. In this paper, we explore the potential for the coastal and marine components of the International Long-Term Ecological Research Network (ILTER) to fill this need for integrated global observation, and highlight how ecological observations are necessary to address the challenges posed by climate change and evolving human needs and stressors within the coastal zone. The ILTER is a global network encompassing 44 countries and 700 research sites in a variety of ecosystems across the planet, more than 100 of which are located in coastal and marine environments (ILTER-CMS). While most of the ILTER-CMS were established after the year 2000, in some cases they date back to the early 1900s. At ILTER sites, a broad variety of abiotic and biotic variables are measured, which may feed into other global initiatives. The ILTER community has produced tools to harmonize and compare measurements and methods, allowing for data integration workflows and analyses between and within individual ILTER sites. After a brief historical overview of ILTER, with emphasis on the marine component, we analyze the potential contribution of the ILTER-CMS to global coastal and ocean observation, adopting the "Strength, Weakness, Opportunity and Threats (SWOT)" approach. We also identify ways in which the in situ parameters collected at ILTER sites currently fit within the Essential Ocean Variables framework (as proposed by the Framework for Ocean Observation recommendations) and provide insights on the use of new technology in long-term studies. Final recommendations point at the need to further develop observational activities at LTER sites and improve coordination among them and with external related initiatives in order to maximize their exploitation and address present and future challenges in ocean observations.
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| 14. |
- Paré, Bastien, et al.
(författare)
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Misfolded SOD1 pathology in sporadic Amyotrophic Lateral Sclerosis
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Aggregation of mutant superoxide dismutase 1 (SOD1) is a pathological hallmark of a subset of familial ALS patients. However, the possible role of misfolded wild type SOD1 in human ALS is highly debated. To ascertain whether or not misfolded SOD1 is a common pathological feature in non-SOD1 ALS, we performed a blinded histological and biochemical analysis of post mortem brain and spinal cord tissues from 19 sporadic ALS, compared with a SOD1 A4V patient as well as Alzheimer's disease (AD) and non-neurological controls. Multiple conformation-or misfolded-specific antibodies for human SOD1 were compared. These were generated independently by different research groups and were compared using standardized conditions. Five different misSOD1 staining patterns were found consistently in tissue sections from SALS cases and the SOD1 A4V patient, but were essentially absent in AD and non-neurological controls. We have established clear experimental protocols and provide specific guidelines for working, with conformational/misfolded SOD1-specific antibodies. Adherence to these guidelines will aid in the comparison of the results of future studies and better interpretation of staining patterns. This blinded, standardized and unbiased approach provides further support for a possible pathological role of misSOD1 in SALS.
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| 15. |
- Providencia, Rui, et al.
(författare)
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Usefulness of a clinical risk score to predict the response to cardiac resynchronization therapy
- 2018
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 260, s. 82-87
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Tidskriftsartikel (refereegranskat)abstract
- Background: Almost 1/3 of heart failure patients fail to respond to cardiac resynchronization therapy (CRT). A simple clinical score to predict who these patients are at the moment of referral or at time of implant may be of importance for early optimization of their management. Methods: Observational study. A risk score was derived from factors associated to CRT response. The derivation cohort was composed of 1301 patients implanted with a CRT defibrillator in a multi-center French cohort-study. External validation of this score and assessment of its association with CRT response and all-cause mortality and/or heart transplant was performed in 1959 CRT patients implanted in 4 high-volume European centers. Results: Independent predictors of CRT response in the derivation cohort were: female gender (OR = 2.08, 95% CI 1.26–3.45), NYHA class ≤ III (OR = 2.71, 95% CI 1.63–4.52), left ventricular ejection fraction ≥ 25% (OR = 1.75, 95% CI 1.27–2.41), QRS duration ≥ 150 ms (OR = 1.70, 95% CI 1.25–2.30) and estimated glomerular filtration rate ≥ 60 mL/min (OR = 2.01, 95% CI 1.48–2.72). Each was assigned 1 point. External validation showed good calibration (Hosmer–Lemeshow test-P = 0.95), accuracy (Brier score = 0.19) and discrimination (c-statistic = 0.67), with CRT response increasing progressively from 37.5% in patients with a score of 0 to 91.9% among those with score of 5 (Gamma for trend = 0.44, P < 0.001). Similar results were observed regarding all-cause mortality or heart transplant. Conclusion: The ScREEN score (Sex category, Renal function, ECG/QRS width, Ejection fraction and NYHA class) is composed of widely validated, easy to obtain predictors of CRT response, and predicts CRT response and overall mortality. It should be helpful in facilitating early consideration of alternative therapies for predicted non-responders to CRT therapy.
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| 16. |
- Raghavan, Maanasa, et al.
(författare)
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Genomic evidence for the Pleistocene and recent population history of Native Americans
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 349:6250
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Tidskriftsartikel (refereegranskat)abstract
- Howand when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we found that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (ka) and after no more than an 8000-year isolation period in Beringia. After their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 ka, one that is now dispersed across North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative "Paleoamerican" relict populations, including the historical Mexican Pericues and South American Fuego-Patagonians, are not directly related to modern Australo-Melanesians as suggested by the Paleoamerican Model.
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| 17. |
- Roche, Stephan, et al.
(författare)
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Graphene spintronics : the European Flagship perspective
- 2015
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Ingår i: Current Opinion in Chemical Engineering. - : Institute of Physics Publishing (IOPP). - 2211-3398. ; 2:3
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We review current challenges and perspectives in graphene spintronics, which is one of the most promising directions of innovation, given its room-temperature long-spin lifetimes and the ability of graphene to be easily interfaced with other classes of materials (ferromagnets, magnetic insulators, semiconductors, oxides, etc), allowing proximity effects to be harvested. The general context of spintronics is first discussed together with open issues and recent advances achieved by the Graphene Spintronics Work Package consortium within the Graphene Flagship project. Based on such progress, which establishes the state of the art, several novel opportunities for spin manipulation such as the generation of pure spin current (through spin Hall effect) and the control of magnetization through the spin torque phenomena appear on the horizon. Practical applications are within reach, but will require the demonstration of wafer-scale graphene device integration, and the realization of functional prototypes employed for determined applications such as magnetic sensors or nano-oscillators. This is a specially commissioned editorial from the Graphene Flagship Work Package on Spintronics. This editorial is part of the 2D Materials focus collection on 'Progress on the science and applications of two-dimensional materials,' published in association with the Graphene Flagship. It provides an overview of key recent advances of the spintronics work package as well as the mid-term objectives of the consortium.
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| 18. |
- Weimann, Arved, et al.
(författare)
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ESPEN guideline : Clinical nutrition in surgery
- 2017
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Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 36:3, s. 623-650
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Tidskriftsartikel (refereegranskat)abstract
- Early oral feeding is the preferred mode of nutrition for surgical patients. Avoidanc'e of any nutritional therapy bears the risk of underfeeding during the postoperative course after major surgery. Considering that malnutrition and underfeeding are risk factors for postoperative complications, early enteral feeding is especially relevant for any surgical patient at nutritional risk, especially for those undergoing upper gastrointestinal surgery. The focus of this guideline is to cover nutritional aspects of the Enhanced Recovery After Surgery (ERAS) concept and the special nutritional needs of patients undergoing major surgery, e.g. for cancer, and of those developing severe complications despite best perioperative care. From a metabolic and nutritional point of view, the key aspects of perioperative care include:integration of nutrition into the overall management of the patientavoidance of long periods of preoperative fastingre-establishment of oral feeding as early as possible after surgerystart of nutritional therapy early, as soon as a nutritional risk becomes apparentmetabolic control e.g. of blood glucosereduction of factors which exacerbate stress-related catabolism or impair gastrointestinal functionminimized time on paralytic agents for ventilator management in the postoperative periodearly mobilisation to facilitate protein synthesis and muscle function The guideline presents 37 recommendations for clinical practice.
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