Improving the reliability of material databases using multiscale approaches

This article addresses the propagation of constitutive uncertainties between scales occurring in the multiscale modelling of fibre-reinforced composites. The amplification of such uncertainties through upward or downward transitions by a homogenisation model is emphasized and exemplified with the Mori-Tanaka model. In particular, the sensitivity to data uncertainty in the inverse determination of constituent parameters based on downward transitions is stressed on an example. Then a database improvement method, which exploits simultaneously the available information on constitutive uncertainties at all scales instead of just propagating those associated with one scale, is presented and shown to yield substantial reductions in uncertainty for both the constitutive parameters and the response of structures. The latter finding is demonstrated on two examples of structures, with significant gains in confidence obtained on both

Fatty acid composition of sulfate-reducing bacteria isolated from deep-sea hydrothermal vent (13° N, East Pacific Rise)

Five strains of vibrio-shaped, mesophilic sulfate-reducing bacteria were isolated from the deep-sea hydrothermal vent site at 13° N on the East Pacific Rise. Phospholipid analyses demonstrated a high percentage of branched-chain fatty acids, including the known biomarker for Desulfovibrio, in all five strains. The cell-wall lipids showed a fatty acid composition markedly different from the phospholipids. While straight-chain fatty acids were predominant the biomarker fatty acid was absent. Based on the morphological characteristics and the fatty acid composition, we tentatively have assigned the isolates to the genus Desulfovibrio

Lactoferrin is a survival factor for neutrophils in rheumatoid synovial fluid

Objectives. Lactoferrin is an iron-binding protein that is released from activated neutrophils at sites of inflammation and has anti-microbial as well as anti-inflammatory properties. This study set out to determine whether lactoferrin can delay neutrophil apoptosis and could act as a survival factor for neutrophils in SF

Reflection KK-matrices related to Temperley-Lieb RR-matrices

The general solutions of the reflection equation associated with Temperley-Lieb $R$-matrices are constructed. Their parametrization is defined and the Hamiltonians of corresponding integrable spin systems are given.Comment: 11 pages, no figures. References added and a few misprints corrected. To appear in Theoretical and Mathematical Physics (2011

Recommendations from the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL)

International audienceAbstractRare diseases are an important public health issue with high unmet need. The introduction of the EU Regulation on orphan medicinal products (OMP) has been successful in stimulating investment in the research and development of OMPs. Despite this advancement, patients do not have universal access to these new medicines. There are many factors that affect OMP uptake, but one of the most important is the difficulty of making pricing and reimbursement (P&R) decisions in rare diseases. Until now, there has been little consensus on the most appropriate assessment criteria, perspective or appraisal process. This paper proposes nine principles to help improve the consistency of OMP P&R assessment in Europe and ensure that value assessment, pricing and funding processes reflect the specificities of rare diseases and contribute to both the sustainability of healthcare systems and the sustainability of innovation in this field. These recommendations are the output of the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL), a collaboration between rare disease experts, patient representatives, academics, health technology assessment (HTA) practitioners, politicians and industry representatives. ORPH-VAL reached its recommendations through careful consideration of existing OMP P&R literature and through a wide consultation with expert stakeholders, including payers, regulators and patients. The principles cover four areas: OMP decision criteria, OMP decision process, OMP sustainable funding systems and European co-ordination. This paper also presents a guide to the core elements of value relevant to OMPs that should be consistently considered in all OMP appraisals. The principles outlined in this paper may be helpful in drawing together an emerging consensus on this topic and identifying areas where consistency in payer approach could be achievable and beneficial. All stakeholders have an obligation to work together to ensure that the promise of OMP’s is realised

Systematic review on the evaluation criteria of orphan medicines in Central and Eastern European countries.

BACKGROUND: In case of orphan drugs applicability of the standard health technology assessment (HTA) process is limited due to scarcity of good clinical and health economic evidence. Financing these premium priced drugs is more controversial in the Central and Eastern European (CEE) region where the public funding resources are more restricted, and health economic justification should be an even more important aspect of policy decisions than in higher income European countries. OBJECTIVES: To explore and summarize the recent scientific evidence on value drivers related to the health technology assessment of ODs with a special focus on the perspective of third party payers in CEE countries. The review aims to list all potentially relevant value drivers in the reimbursement process of orphan drugs. METHODS: A systematic literature review was performed; PubMed and Scopus databases were systematically searched for relevant publications until April 2015. Extracted data were summarized along key HTA elements. RESULTS: From the 2664 identified publications, 87 contained relevant information on the evaluation criteria of orphan drugs, but only 5 had direct information from the CEE region. The presentation of good clinical evidence seems to play a key role especially since this should be the basis of cost-effectiveness analyses, which have more importance in resource-constrained economies. Due to external price referencing of pharmaceuticals, the relative budget impact of orphan drugs is expected to be higher in CEE than in Western European (WE) countries unless accessibility of patients remains more limited in poorer European regions. Equity principles based on disease prevalence and non-availability of alternative treatment options may increase the price premium, however, societies must have some control on prices and a rationale based on multiple criteria in reimbursement decisions. CONCLUSIONS: The evaluation of orphan medicines should include multiple criteria to appropriately measure the clinical added value of orphan drugs. The search found only a small number of studies coming from CEE, therefore European policies on orphan drugs may be based largely on experiences in WE countries. More research should be done in the future in CEE because financing high-priced orphan drugs involves a greater burden for these countries