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1.
  • Aad, G., et al. (author)
  • 2012
  • swepub:Mat__t (peer-reviewed)
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  • 2021
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  • 2017
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  • 2021
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  • Bravo, L, et al. (author)
  • 2021
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  • Tabiri, S, et al. (author)
  • 2021
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  • Glasbey, JC, et al. (author)
  • 2021
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  • Östling, Jörgen, et al. (author)
  • IL-17-high asthma with features of a psoriasis immunophenotype
  • 2019
  • In: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 144:5, s. 1198-1213
  • Journal article (peer-reviewed)abstract
    • Background: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required.Objective: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity.Methods: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes.Results: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and β-defensin.Conclusion: The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.
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  • Lauwers, E., et al. (author)
  • Potential human transmission of amyloid beta pathology: surveillance and risks
  • 2020
  • In: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 19:10, s. 872-878
  • Journal article (peer-reviewed)abstract
    • Studies in experimental animals show transmissibility of amyloidogenic proteins associated with prion diseases, Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases. Although these data raise potential concerns for public health, convincing evidence for human iatrogenic transmission only exists for prions and amyloid beta after systemic injections of contaminated growth hormone extracts or dura mater grafts derived from cadavers. Even though these procedures are now obsolete, some reports raise the possibility of iatrogenic transmission of amyloid beta through putatively contaminated neurosurgical equipment. Iatrogenic transmission of amyloid beta might lead to amyloid deposition in the brain parenchyma and blood vessel walls, potentially resulting in cerebral amyloid angiopathy after several decades. Cerebral amyloid angiopathy can cause life-threatening brain haemorrhages; yet, there is no proof that the transmission of amyloid can also lead to Alzheimer's dementia. Large, long-term epidemiological studies and sensitive, cost-efficient tools to detect amyloid are needed to better understand any potential routes of amyloid beta transmission and to clarify whether other similar proteopathic seeds, such as tau or alpha-synuclein, can also be transferred iatrogenically.
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  • Pedersen, S. S., et al. (author)
  • Internet-Delivered, Therapist-Assisted Treatment for Anxiety and Depression in Patients with Cardiovascular Disease : Evidence-Base and Challenges
  • 2023
  • In: Current Cardiology Reports. - : Springer Nature. - 1523-3782 .- 1534-3170. ; 25:6, s. 443-453
  • Journal article (peer-reviewed)abstract
    • Purpose of Review: This review focuses on the efficacy of internet-based psychological interventions for patients with cardiovascular disease (CVD) and comorbid anxiety and depression. Anxiety and depression comprise barriers for treatment adherence and are associated with poorer patient-reported and clinical outcomes, and greater health care costs.Recent Findings: Internet-based, therapist-assisted interventions targeting anxiety and depression can be as efficacious as face-to-face therapy and may have some advantages, as patients can do it from their own laptop/smartphone at home at a time of their convenience, which may facilitate a better integration in their lives.Summary: To enhance the field of internet-based therapy for patients with CVD, we need to involve patients in the development of interventions, focus on developing standards for adherence and assessment of fidelity, and assess and augment health literacy in patients to safeguard equality in health care.
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  • Stuiver, M., et al. (author)
  • The Governance of Multi-Use Platforms at Sea for Energy Production and Aquaculture: Challenges for Policy Makers in European Seas
  • 2016
  • In: Sustainability. - : MDPI AG. - 2071-1050. ; 8:4
  • Journal article (peer-reviewed)abstract
    • European seas are encountering an upsurge in competing marine activities and infrastructures. Traditional exploitation such as fisheries, tourism, transportation, and oil production are accompanied by new sustainable economic activities such as offshore windfarms, aquaculture, and tidal and wave energy. One proposed solution to overcome possible competing claims at sea lies in combining these economic activities as part of Multi-Use Platforms at Sea (MUPS). MUPS can be understood as areas at sea, designated for a combination of activities, either completely integrated in a platform or in shared marine space. MUPS can potentially benefit from each other in terms of infrastructure, maintenance, etc. Developing MUPS in the marine environment demands adequate governance. In this article, we investigate four European sites to find out how governance arrangements may facilitate or complicate MUPs. In particular, we apply a framework specifying policy, economic, social, technical, environmental, and legal (PESTEL) factors to explore governance arrangements in four case study sites in different sea basins around Europe ( the Mediterranean Sea, the Atlantic Ocean, the North Sea, and the Baltic Sea). The article concludes with policy recommendations on a governance regime for facilitating the development of MUPS in the future.
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26.
  • Tariq, K., et al. (author)
  • Sputum proteomic signature of gastro-oesophageal reflux in patients with severe asthma
  • 2019
  • In: Respiratory Medicine. - : Saunders Elsevier. - 0954-6111 .- 1532-3064. ; 150, s. 66-73
  • Journal article (peer-reviewed)abstract
    • Gastro-oesophageal reflux disease (GORD) has long been associated with poor asthma control without an established cause-effect relationship. 610 asthmatics (421 severe/88 mild-moderate) and 101 healthy controls were assessed clinically and a subset of 154 severe asthmatics underwent proteomic analysis of induced sputum using untargeted mass spectrometry, LC-IMS-MSE. Univariate and multiple logistic regression analyses (MLR) were conducted to identify proteins associated with GORD in this cohort. When compared to mild/moderate asthmatics and healthy individuals, respectively, GORD was three-and ten-fold more prevalent in severe asthmatics and was associated with increased asthma symptoms and oral corticosteroid use, poorer quality of life, depression/anxiety, obesity and symptoms of sino-nasal disease. Comparison of sputum proteomes in severe asthmatics with and without active GORD showed five differentially abundant proteins with described roles in antimicrobial defences, systemic inflammation and epithelial integrity. Three of these were associated with active GORD by multiple linear regression analysis: Ig lambda variable 1-47 (p = 0.017) and plasma protease C1 inhibitor (p = 0.043), both in lower concentrations, and lipocalin-1 (p = 0.034) in higher concentrations in active GORD. This study provides evidence which suggests that reflux can cause subtle perturbation of proteins detectable in the airways lining fluid and that severe asthmatics with GORD may represent a distinct phenotype of asthma.
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  • Borger van der Burg, B. L. S., et al. (author)
  • A systematic review and meta-analysis of the use of resuscitative endovascular balloon occlusion of the aorta in the management of major exsanguination
  • 2018
  • In: European Journal of Trauma and Emergency Surgery. - : Springer Berlin/Heidelberg. - 1863-9933 .- 1863-9941. ; 44:4, s. 535-550
  • Research review (peer-reviewed)abstract
    • BACKGROUND: Circulatory collapse is a leading cause of mortality among traumatic major exsanguination and in ruptured aortic aneurysm patients. Approximately 40% of patients die before hemorrhage control is achieved. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an adjunct designed to sustain the circulation until definitive surgical or endovascular repair. A systematic review was conducted for the current clinical use of REBOA in patients with hemodynamic instability and to discuss its potential role in improving prehospital and in-hospital outcome.METHODS: Systematic review and meta-analysis (1900-2017) using MEDLINE, Cochrane, EMBASE, Web of Science and Central and Emcare using the keywords "aortic balloon occlusion", "aortic balloon tamponade", "REBOA", and "Resuscitative Endovascular Balloon Occlusion" in combination with hemorrhage control, hemorrhage, resuscitation, shock, ruptured abdominal or thoracic aorta, endovascular repair, and open repair. Original published studies on human subjects were considered.RESULTS: A total of 490 studies were identified; 89 met criteria for inclusion. Of the 1436 patients, overall reported mortality was 49.2% (613/1246) with significant differences (p < 0.001) between clinical indications. Hemodynamic shock was evident in 79.3%, values between clinical indications showed significant difference (p < 0.001). REBOA was favored as treatment in trauma patients in terms of mortality. Pooled analysis demonstrated an increase in mean systolic pressure by almost 50 mmHg following REBOA use.CONCLUSION: REBOA has been used in trauma patients and ruptured aortic aneurysm patients with improvement of hemodynamic parameters and outcomes for several decades. Formal, prospective study is warranted to clarify the role of this adjunct in all hemodynamic unstable patients.
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  • Burg, Dominic, et al. (author)
  • Large-Scale Label-Free Quantitative Mapping of the Sputum Proteome
  • 2018
  • In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 17:6, s. 2072-2091
  • Journal article (peer-reviewed)abstract
    • Analysis of induced sputum supematant is a minimally invasive approach to study the epithelial lining fluid and, thereby, provide insight into normal lung biology and the pathobiology of lung diseases. We present here a novel proteomics approach to sputum analysis developed within the U-BIOPRED (unbiased biomarkers predictive of respiratory disease outcomes) international project. We present practical and analytical techniques to optimize the detection of robust biomarkers in proteomic studies. The normal sputum proteome was derived using data-independent HDMSE applied to 40 healthy nonsmoking participants, which provides an essential baseline from which to compare modulation of protein expression in respiratory diseases. The "core" sputum proteome (proteins detected in >= 40% of participants) was composed of 284 proteins, and the extended proteome (proteins detected in >= 3 participants) contained 1666 proteins. Quality control procedures were developed to optimize the accuracy and consistency of measurement of sputum proteins and analyze the distribution of sputum proteins in the healthy population. The analysis showed that quantitation of proteins by HDMSE is influenced by several factors, with some proteins being measured in all participants' samples and with low measurement variance between samples from the same patient. The measurement of some proteins is highly variable between repeat analyses, susceptible to sample processing effects, or difficult to accurately quantify by mass spectrometry. Other proteins show high interindividual variance. We also highlight that the sputum proteome of healthy individuals is related to sputum neutrophil levels, but not gender or allergic sensitization. We illustrate the importance of design and interpretation of disease biomarker studies considering such protein population and technical measurement variance.
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  • Drakvik, E., et al. (author)
  • Statement on advancing the assessment of chemical mixtures and their risks for human health and the environment
  • 2020
  • In: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 134
  • Journal article (peer-reviewed)abstract
    • The number of anthropogenic chemicals, manufactured, by-products, metabolites and abiotically formed transformation products, counts to hundreds of thousands, at present. Thus, humans and wildlife are exposed to complex mixtures, never one chemical at a time and rarely with only one dominating effect. Hence there is an urgent need to develop strategies on how exposure to multiple hazardous chemicals and the combination of their effects can be assessed. A workshop, “Advancing the Assessment of Chemical Mixtures and their Risks for Human Health and the Environment” was organized in May 2018 together with Joint Research Center in Ispra, EU-funded research projects and Commission Services and relevant EU agencies. This forum for researchers and policy-makers was created to discuss and identify gaps in risk assessment and governance of chemical mixtures as well as to discuss state of the art science and future research needs. Based on the presentations and discussions at this workshop we want to bring forward the following Key Messages: • We are at a turning point: multiple exposures and their combined effects require better management to protect public health and the environment from hazardous chemical mixtures. • Regulatory initiatives should be launched to investigate the opportunities for all relevant regulatory frameworks to include prospective mixture risk assessment and consider combined exposures to (real-life) chemical mixtures to humans and wildlife, across sectors. • Precautionary approaches and intermediate measures (e.g. Mixture Assessment Factor) can already be applied, although, definitive mixture risk assessments cannot be routinely conducted due to significant knowledge and data gaps. • A European strategy needs to be set, through stakeholder engagement, for the governance of combined exposure to multiple chemicals and mixtures. The strategy would include research aimed at scientific advancement in mechanistic understanding and modelling techniques, as well as research to address regulatory and policy needs. Without such a clear strategy, specific objectives and common priorities, research, and policies to address mixtures will likely remain scattered and insufficient. © 2019 The Authors
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  • Helfricht, A, et al. (author)
  • Loss of ZBTB24 impairs nonhomologous end-joining and class-switch recombination in patients with ICF syndrome
  • 2020
  • In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 217:11
  • Journal article (peer-reviewed)abstract
    • The autosomal recessive immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a genetically heterogeneous disorder. Despite the identification of the underlying gene defects, it is unclear how mutations in any of the four known ICF genes cause a primary immunodeficiency. Here we demonstrate that loss of ZBTB24 in B cells from mice and ICF2 patients affects nonhomologous end-joining (NHEJ) during immunoglobulin class-switch recombination and consequently impairs immunoglobulin production and isotype balance. Mechanistically, we found that ZBTB24 associates with poly(ADP-ribose) polymerase 1 (PARP1) and stimulates its auto-poly(ADP-ribosyl)ation. The zinc-finger in ZBTB24 binds PARP1-associated poly(ADP-ribose) chains and mediates the PARP1-dependent recruitment of ZBTB24 to DNA breaks. Moreover, through its association with poly(ADP-ribose) chains, ZBTB24 protects them from degradation by poly(ADP-ribose) glycohydrolase (PARG). This facilitates the poly(ADP-ribose)-dependent assembly of the LIG4/XRCC4 complex at DNA breaks, thereby promoting error-free NHEJ. Thus, we uncover ZBTB24 as a regulator of PARP1-dependent NHEJ and class-switch recombination, providing a molecular basis for the immunodeficiency in ICF2 syndrome.
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  • Jensen, Benjamin A H, et al. (author)
  • Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+ Tregs and improve metabolism
  • 2021
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
  • Journal article (peer-reviewed)abstract
    • Interactions between host and gut microbial communities are modulated by diets and play pivotal roles in immunological homeostasis and health. We show that exchanging the protein source in a high fat, high sugar, westernized diet from casein to whole-cell lysates of the non-commensal bacterium Methylococcus capsulatus Bath is sufficient to reverse western diet-induced changes in the gut microbiota to a state resembling that of lean, low fat diet-fed mice, both under mild thermal stress (T22 °C) and at thermoneutrality (T30 °C). Concomitant with microbiota changes, mice fed the Methylococcus-based western diet exhibit improved glucose regulation, reduced body and liver fat, and diminished hepatic immune infiltration. Intake of the Methylococcu-based diet markedly boosts Parabacteroides abundances in a manner depending on adaptive immunity, and upregulates triple positive (Foxp3+RORγt+IL-17+) regulatory T cells in the small and large intestine. Collectively, these data point to the potential for leveraging the use of McB lysates to improve immunometabolic homeostasis.
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  • Kehoe, Laura, et al. (author)
  • Make EU trade with Brazil sustainable
  • 2019
  • In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
  • Journal article (other academic/artistic)
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  • Lion, T., et al. (author)
  • The EuroChimerism concept for a standardized approach to chimerism analysis after allogeneic stem cell transplantation
  • 2012
  • In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 26:8, s. 1821-1828
  • Journal article (peer-reviewed)abstract
    • Hematopoietic stem cell transplantation is becoming an increasingly important approach to treatment of different malignant and non-malignant disorders. There is thus growing demand for diagnostic assays permitting the surveillance of donor/recipient chimerism posttransplant. Current techniques are heterogeneous, rendering uniform evaluation and comparison of diagnostic results between centers difficult. Leading laboratories from 10 European countries have therefore performed a collaborative study supported by a European grant, the EuroChimerism Concerted Action, with the aim to develop a standardized diagnostic methodology for the detection and monitoring of chimerism in patients undergoing allogeneic stem cell transplantation. Following extensive analysis of a large set of microsatellite/short tandem repeat (STR) loci, the EuroChimerism (EUC) panel comprising 13 STR markers was established with the aim to optimally meet the specific requirements of quantitative chimerism analysis. Based on highly stringent selection criteria, the EUC panel provides multiple informative markers in any transplant setting. The standardized STR-PCR tests permit detection of donor-or recipient-derived cells at a sensitivity ranging between 0.8 and 1.6%. Moreover, the EUC assay facilitates accurate and reproducible quantification of donor and recipient hematopoietic cells. Wide use of the European-harmonized protocol for chimerism analysis presented will provide a basis for optimal diagnostic support and timely treatment decisions.
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  • Papp, KA, et al. (author)
  • Early onset of action and efficacy of a combination of calcipotriene and betamethasone dipropionate in the treatment of psoriasis
  • 2003
  • In: Journal of American Academy of Dermatology. - : Elsevier BV. - 0190-9622. ; 48:1, s. 48-54
  • Journal article (peer-reviewed)abstract
    • Background: Calcipotriene and betamethasone dipropionate are topical treatments for psoriasis vulgaris. Their mode of action is different. Improved risk/benefit may result with concomitant use of the two compounds together. A new vehicle has been created with the objective of obtaining optimal stability of both calcipotriene and betamethasone dipropionate in the combination product. Objective. We compared the clinical efficacy of a fixed combination of calcipotriene and betamethasone clipropionate in a new vehicle to calcipotriene in the new vehicle, betamethasone in the new vehicle, and the new vehicle alone. Methods: This was an international, multicenter, prospective, randomized, double-blind, parallel-group, 4-week study in patients with psoriasis vulgaris amenable to topical treatment. Results. The mean percentage reduction in PASI from baseline to end of treatment was 73.2% in the combination group (n = 301), 48.8% in the calcipotriene group (n = 308), 63.1% in the betamethasone dipropionate group (n = 312) and 28.8% in the new vehicle group (n = 107), (P < .001). The mean percentage reduction in PASI during the first week was 48.1%, 28.4%, 41.4%, and 21.5%, respectively (P < .001). Conclusion: A combination product of calcipotriene 50 mug/g and betamethasone dipropionate 0.5 mg/g in the new vehicle shows superior efficacy with a more rapid onset of action than the new vehicle containing either constituent alone in the treatment of psoriasis vulgaris.
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  • Pipinato, A., et al. (author)
  • Prolonging the service life of steel truss bridges
  • 2018
  • In: Maintenance, Safety, Risk, Management and Life-Cycle Performance of Bridges. - : Taylor & Francis. ; , s. 489-496
  • Conference paper (peer-reviewed)abstract
    • Prolonging the life of existing steel trusses all over the world is a incoming necessity for all managing authorities wherever these structures have reached a particular state of use. The unsatisfactory behavior of these structures under the current type and increasing number of loads make clearer that innovative solutions are needed. For this purpose, the realization of different techniques are presented, in order to retrofit the actual load onto a structure conceived with historical codes, characterized by lower design live loads. The possibilities of retrofitting bridges with different solution studied in a recent research program are presented and compared in this study.
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  • Pipinato, A., et al. (author)
  • Steel bridge structural retrofit : Innovative and light-weight solutions
  • 2018
  • In: Life Cycle Analysis and Assessment in Civil Engineering: Towards an Integrated Vision. - : Taylor & Francis. ; , s. 2857-2867
  • Conference paper (peer-reviewed)abstract
    • Prolonging the life of existing steel trusses all over the world is a incoming necessity for all managing authorities wherever these structures have reached a particular state of use. The unsatisfactory behavior of these structures under the current type and increasing number of loads make clearer that innovative solutions are needed. For this purpose, the realization of different techniques are presented, in order to retrofit the actual load onto a structure conceived with historical codes, characterized by lower design live loads. The possibilities of retrofitting bridges with different solution studied in a recent research program are presented and compared in this study.
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  • Siddiqui, K. S., et al. (author)
  • A chemically modified α-amylase with a molten-globule state has entropically driven enhanced thermal stability
  • 2010
  • In: Protein Engineering Design & Selection. - : Oxford University Press (OUP). - 1741-0126 .- 1741-0134. ; 23:10, s. 769-780
  • Journal article (peer-reviewed)abstract
    • The thermostability properties of TAA were investigated by chemically modifying carboxyl groups on the surface of the enzyme with AMEs. The TAAMOD exhibited a 200 improvement in starch-hydrolyzing productivity at 60°C. By studying the kinetic, thermodynamic and biophysical properties, we found that TAAMOD had formed a thermostable, MG state, in which the unfolding of the tertiary structure preceded that of the secondary structure by at least 20°C. The X-ray crystal structure of TAAMOD revealed no new permanent interactions (electrostatic or other) resulting from the modification. By deriving thermodynamic activation parameters of TAAMOD, we rationalised that thermostabilisation have been caused by a decrease in the entropy of the transition state, rather than being enthalpically driven. Far-UV CD shows that the origin of decreased entropy may have arisen from a higher helical content of TAAMOD. This study provides new insight into the intriguing properties of an MG state resulting from the chemical modification of TAA.
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  • Sikonja, J, et al. (author)
  • Towards Achieving Equity and Innovation in Newborn Screening across Europe
  • 2022
  • In: International journal of neonatal screening. - : MDPI AG. - 2409-515X. ; 8:2
  • Journal article (peer-reviewed)abstract
    • Although individual rare disorders are uncommon, it is estimated that, together, 6000+ known rare diseases affect more than 30 million people in Europe, and present a substantial public health burden. Together with the psychosocial burden on affected families, rare disorders frequently, if untreated, result in a low quality of life, disability and even premature death. Newborn screening (NBS) has the potential to detect a number of rare conditions in asymptomatic children, providing the possibility of early treatment and a significantly improved long-term outcome. Despite these clear benefits, the availability and conduct of NBS programmes varies considerably across Europe and, with the increasing potential of genomic testing, it is likely that these differences may become even more pronounced. To help improve the equity of provision of NBS and ensure that all children can be offered high-quality screening regardless of race, nationality and socio-economic status, a technical meeting, endorsed by the Slovenian Presidency of the Council of the European Union, was held in October 2021. In this article, we present experiences from individual EU countries, stakeholder initiatives and the meeting’s final conclusions, which can help countries attempting to establish new NBS programmes or expand existing provision.
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