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- Heard, J. M., et al.
(författare)
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Availability, accessibility and delivery to patients of the 28 orphan medicines approved by the European Medicine Agency for hereditary metabolic diseases in the MetabERN network
- 2020
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Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The European Medicine Agency granted marketing approval to 164 orphan medicinal products for rare diseases, among which 28 products intended for the treatment of hereditary metabolic diseases. Taking advantage of its privileged connection with 69 healthcare centres of excellence in this field, MetabERN, the European Reference Network for hereditary metabolic diseases, performed a survey asking health care providers from 18 European countries whether these products are available on the market, reimbursed and therefore accessible for prescription, and actually delivered in their centre. Results Responses received from 52 centres (75%) concerned the design of treatment plans, the access to marketed products, and the barriers to delivery. Treatment options are always discussed with patients, who are often involved in their treatment plan. Most products (26/28) are available in most countries (15/18). Among the 15 broadly accessible products (88.5% of the centres), 9 are delivered to most patients (mean 70.1%), and the others to only few (16.5%). Among the 10 less accessible products (40.2% of the centres), 6 are delivered to many patients (66.7%), and 4 are rarely used (6.3%). Information was missing for 3 products. Delay between prescription and delivery is on average one month. Beside the lack of availability or accessibility, the most frequent reasons for not prescribing a treatment are patients' clinical status, characteristic, and personal choice. Conclusions Data collected from health care providers in the MetabERN network indicate that two-third of the orphan medicines approved by EMA for the treatment of hereditary metabolic diseases are accessible to treating patients, although often less than one-half of the patients with the relevant conditions actually received the approved product to treat their disease. Thus, in spite of the remarkable achievement of many products, patients concerned by EMA-approved orphan medicinal products have persistent unmet needs, which deserve consideration. The enormous investments made by the companies to develop products, and the high financial burden for the Member States to purchase these products emphasize the importance of a scrupulous appreciation of treatment value involving all stakeholders at early stage of development, before marketing authorization, and during follow up.
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- Lavesque, N., et al.
(författare)
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The "Spaghetti Project": the final identification guide to European Terebellidae (sensu lato) (Annelida, Terebelliformia)
- 2021
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Ingår i: European Journal of Taxonomy. - : Museum National D'Histoire Naturelle. - 2118-9773. ; 782, s. 108-156
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Tidskriftsartikel (refereegranskat)abstract
- This paper is the conclusion of the "Spaghetti Project" aiming to revise French species of Terebellidae sensu lato (s.l.) belonging to the five families: Polycirridae, Telothelepodidae, Terebellidae sensu stricto (s.s.), Thelepodidae and Trichobranchidae. During this project, 41 species were observed, 31 of them new for science: eight species of Polycirridae, eleven species of Terebellidae s.s., three species of Thelepodidae and nine species of Trichobranchidae. We provide a comprehensive key for all European species of terebellids with a focus on the important diagnostic characters for each family. Finally, we discuss issues on taxonomy, biodiversity and cryptic and pseudo-cryptic species of polychaetes in European waters, based on results obtained during this project.
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- Laforet, P., et al.
(författare)
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Deep morphological analysis of muscle biopsies from type III glycogenesis (GSDIII), debranching enzyme deficiency, revealed stereotyped vacuolar myopathy and autophagy impairment
- 2019
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Ingår i: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Glycogen storage disorder type III (GSDIII), or debranching enzyme (GDE) deficiency, is a rare metabolic disorder characterized by variable liver, cardiac, and skeletal muscle involvement. GSDIII manifests with liver symptoms in infancy and muscle involvement during early adulthood. Muscle biopsy is mainly performed in patients diagnosed in adulthood, as routine diagnosis relies on blood or liver GDE analysis, followed by AGL gene sequencing. The GSDIII mouse model recapitulate the clinical phenotype in humans, and a nearly full rescue of muscle function was observed in mice treated with the dual AAV vector expressing the GDE transgene. In order to characterize GSDIII muscle morphological spectrum and identify novel disease markers and pathways, we performed a large international multicentric morphological study on 30 muscle biopsies from GSDIII patients. Autophagy flux studies were performed in human muscle biopsies and muscles from GSDIII mice. The human muscle biopsies revealed a typical and constant vacuolar myopathy, characterized by multiple and variably sized vacuoles filled with PAS-positive material. Using electron microscopy, we confirmed the presence of large nonmembrane bound sarcoplasmic deposits of normally structured glycogen as well as smaller rounded sac structures lined by a continuous double membrane containing only glycogen, corresponding to autophagosomes. A consistent SQSTM1/p62 decrease and beclin-1 increase in human muscle biopsies suggested an enhanced autophagy. Consistent with this, an increase in the lipidated form of LC3, LC3II was found in patients compared to controls. A decrease in SQSTM1/p62 was also found in the GSDIII mouse model. In conclusion, we characterized the morphological phenotype in GSDIII muscle and demonstrated dysfunctional autophagy in GSDIII human samples. These findings suggest that autophagic modulation combined with gene therapy might be considered as a novel treatment for GSDIII.
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- Tadokoro, K., et al.
(författare)
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Problems with irradiators
- 2010
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Ingår i: Vox Sanguinis. - : Wiley. - 0042-9007 .- 1423-0410. ; 98:1, s. 78-84
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Tidskriftsartikel (refereegranskat)
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- Labrune, C., et al.
(författare)
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Characterization of the ecological quality of the coastal Gulf of Lions (NW Mediterranean). A comparative approach based on three biotic indices
- 2006
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Ingår i: Marine Pollution Bulletin. - : Elsevier BV. - 0025-326X. ; 52:1, s. 34-47
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Tidskriftsartikel (refereegranskat)abstract
- The ecological quality of the Gulf of Lions coast was assessed using three biotic indices (H', AMBI and BQI). The three indices correlated positively. The positive correlation between AMBI and BQI was surprising and was mostly due to the fact that the dominant species Ditrupa arietina featured a low ES50(0.05) but was classified in GI by AMBI. Both H' and BQI were efficient in distinguishing impacted from un-impacted sites but AMBI was not. Differences between H' and BQI were mainly due to the scale used to translate indices in terms of EcoQ. The three indices were able to detect the major changes in macrofauna composition, which occurred in the Bay of Banyuls-sur-Mer during the last 40 years. However, the interpretations of such changes in terms of EcoQ differed between indices. These results are discussed relative to the characteristics of the tested indices. (c) 2005 Elsevier Ltd. All rights reserved.
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