| 1. |
- Bousquet, J. Jean, et al.
(författare)
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Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
- 2019
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Ingår i: Clinical and Translational Allergy. - : BMC. - 2045-7022 .- 2045-7022. ; 9
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Forskningsöversikt (refereegranskat)abstract
- Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care.Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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| 2. |
- Torchia, Jonathon, et al.
(författare)
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Molecular subgroups of atypical teratoid rhabdoid tumours in children : an integrated genomic and clinicopathological analysis
- 2015
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 16:5, s. 569-582
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Tidskriftsartikel (refereegranskat)abstract
- Background Rhabdoid brain tumours, also called atypical teratoid rhabdoid tumours, are lethal childhood cancers with characteristic genetic alterations of SMARCB1/hSNF5. Lack of biological understanding of the substantial clinical heterogeneity of these tumours restricts therapeutic advances. We integrated genomic and clinicopathological analyses of a cohort of patients with atypical teratoid rhabdoid tumours to find out the molecular basis for clinical heterogeneity in these tumours. Methods We obtained 259 rhabdoid tumours from 37 international institutions and assessed transcriptional profiles in 43 primary tumours and copy number profiles in 38 primary tumours to discover molecular subgroups of atypical teratoid rhabdoid tumours. We used gene and pathway enrichment analyses to discover group-specific molecular markers and did immunohistochemical analyses on 125 primary tumours to evaluate clinicopathological significance of molecular subgroup and ASCL1-NOTCH signalling. Findings Transcriptional analyses identified two atypical teratoid rhabdoid tumour subgroups with differential enrichment of genetic pathways, and distinct clinicopathological and survival features. Expression of ASCL1, a regulator of NOTCH signalling, correlated with supratentorial location (p=0.004) and superior 5-year overall survival (35%, 95% CI 13-57, and 20%, 6-34, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0.033) in 70 patients who received multimodal treatment. ASCL1 expression also correlated with superior 5-year overall survival (34%, 7-61, and 9%, 0-21, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0.001) in 39 patients who received only chemotherapy without radiation. Cox hazard ratios for overall survival in patients with differential ASCL1 enrichment treated with chemotherapy with or without radiation were 2.02 (95% CI 1.04-3.85; p=0.038) and 3.98 (1.71-9.26; p=0.001). Integrated analyses of molecular subgroupings with clinical prognostic factors showed three distinct clinical risk groups of tumours with different therapeutic outcomes. Interpretation An integration of clinical risk factors and tumour molecular groups can be used to identify patients who are likely to have improved long-term radiation-free survival and might help therapeutic stratification of patients with atypical teratoid rhabdoid tumours.
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| 3. |
- Niklison-Chirou, Maria Victoria, et al.
(författare)
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TAp73 is a marker of glutamine addiction in medulloblastoma
- 2017
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Ingår i: Genes & Development. - : COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT. - 0890-9369 .- 1549-5477. ; 31:17, s. 1738-1753
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Tidskriftsartikel (refereegranskat)abstract
- Medulloblastoma is the most common solid primary brain tumor in children. Remarkable advancements in the understanding of the genetic and epigenetic basis of these tumors have informed their recent molecular classification. However, the genotype/phenotype correlation of the subgroups remains largely uncharacterized. In particular, the metabolic phenotype is of great interest because of its druggability, which could lead to the development of novel and more tailored therapies for a subset of medulloblastoma. p73 plays a critical role in a range of cellular metabolic processes. We show overexpression of p73 in a proportion of non-WNT medulloblastoma. In these tumors, p73 sustains cell growth and proliferation via regulation of glutamine metabolism. We validated our results in a xenograft model in which we observed an increase in survival time in mice on a glutamine restriction diet. Notably, glutamine starvation has a synergistic effect with cisplatin, a component of the current medulloblastoma chemotherapy. These findings raise the possibility that glutamine depletion can be used as an adjuvant treatment for p73-expressing medulloblastoma.
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| 4. |
- Schmale, Julia, et al.
(författare)
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Collocated observations of cloud condensation nuclei, particle size distributions, and chemical composition
- 2017
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Cloud condensation nuclei (CCN) number concentrations alongside with submicrometer particle number size distributions and particle chemical composition have been measured at atmospheric observatories of the Aerosols, Clouds, and Trace gases Research InfraStructure (ACTRIS) as well as other international sites over multiple years. Here, harmonized data records from 11 observatories are summarized, spanning 98,677 instrument hours for CCN data, 157,880 for particle number size distributions, and 70,817 for chemical composition data. The observatories represent nine different environments, e.g., Arctic, Atlantic, Pacific and Mediterranean maritime, boreal forest, or high alpine atmospheric conditions. This is a unique collection of aerosol particle properties most relevant for studying aerosol-cloud interactions which constitute the largest uncertainty in anthropogenic radiative forcing of the climate. The dataset is appropriate for comprehensive aerosol characterization (e.g., closure studies of CCN), model-measurement intercomparison and satellite retrieval method evaluation, among others. Data have been acquired and processed following international recommendations for quality assurance and have undergone multiple stages of quality assessment.
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| 5. |
- Schmale, Julia, et al.
(författare)
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Long-term cloud condensation nuclei number concentration, particle number size distribution and chemical composition measurements at regionally representative observatories
- 2018
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 18:4, s. 2853-2881
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Tidskriftsartikel (refereegranskat)abstract
- Aerosol-cloud interactions (ACI) constitute the single largest uncertainty in anthropogenic radiative forcing. To reduce the uncertainties and gain more confidence in the simulation of ACI, models need to be evaluated against observations, in particular against measurements of cloud condensation nuclei (CCN). Here we present a data set - ready to be used for model validation - of long-term observations of CCN number concentrations, particle number size distributions and chemical composition from 12 sites on 3 continents. Studied environments include coastal background, rural background, alpine sites, remote forests and an urban surrounding. Expectedly, CCN characteristics are highly variable across site categories. However, they also vary within them, most strongly in the coastal background group, where CCN number concentrations can vary by up to a factor of 30 within one season. In terms of particle activation behaviour, most continental stations exhibit very similar activation ratios (relative to particles 20nm) across the range of 0.1 to 1.0% supersaturation. At the coastal sites the transition from particles being CCN inactive to becoming CCN active occurs over a wider range of the supersaturation spectrum. Several stations show strong seasonal cycles of CCN number concentrations and particle number size distributions, e.g. at Barrow (Arctic haze in spring), at the alpine stations (stronger influence of polluted boundary layer air masses in summer), the rain forest (wet and dry season) or Finokalia (wildfire influence in autumn). The rural background and urban sites exhibit relatively little variability throughout the year, while short-term variability can be high especially at the urban site. The average hygroscopicity parameter, calculated from the chemical composition of submicron particles was highest at the coastal site of Mace Head (0.6) and lowest at the rain forest station ATTO (0.2-0.3). We performed closure studies based on -Köhler theory to predict CCN number concentrations. The ratio of predicted to measured CCN concentrations is between 0.87 and 1.4 for five different types of . The temporal variability is also well captured, with Pearson correlation coefficients exceeding 0.87. Information on CCN number concentrations at many locations is important to better characterise ACI and their radiative forcing. But long-term comprehensive aerosol particle characterisations are labour intensive and costly. Hence, we recommend operating migrating-CCNCs to conduct collocated CCN number concentration and particle number size distribution measurements at individual locations throughout one year at least to derive a seasonally resolved hygroscopicity parameter. This way, CCN number concentrations can only be calculated based on continued particle number size distribution information and greater spatial coverage of long-term measurements can be achieved.
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| 6. |
- Wölfl, Anne-Cathrin, et al.
(författare)
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Seafloor Mapping - The Challenge of a Truly Global Ocean Bathymetry
- 2019
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6
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Forskningsöversikt (refereegranskat)abstract
- Detailed knowledge of the shape of the seafloor is crucial to humankind. Bathymetry data is critical for safety of navigation and is used for many other applications. In an era of ongoing environmental degradation worldwide, bathymetry data (and the knowledge derived from it) play a pivotal role in using and managing the world's oceans in a way that is in accordance with the United Nations Sustainable Development Goal 14 - conserve and sustainably use the oceans, seas and marine resources for sustainable development. However, the vast majority of our oceans is still virtually unmapped, unobserved, and unexplored. Only a small fraction of the seafloor has been systematically mapped by direct measurement. The remaining bathymetry is predicted from satellite altimeter data, providing only an approximate estimation of the shape of the seafloor. Several global and regional initiatives are underway to change this situation. This paper presents a selection of these initiatives as best practice examples for bathymetry data collection, compilation and open data sharing as well as the Nippon Foundation-GEBCO (The General Bathymetric Chart of the Oceans) Seabed 2030 Project that complements and leverages these initiatives and promotes international collaboration and partnership. Several non-traditional data collection opportunities are looked at that are currently gaining momentum as well as new and innovative technologies that can increase the efficiency of collecting bathymetric data. Finally, recommendations are given toward a possible way forward into the future of seafloor mapping and toward achieving the goal of a truly global ocean bathymetry.
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