3,467 research outputs found

    Mesoscopic order and the dimentionality of long-range resonance energy transfer in supramolecular semiconductors

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    We present time-resolved photoluminescence measurements on two series of oligo-p-phenylenevinylene materials that self-assemble into supramolecular nanostructures with thermotropic reversibility in dodecane. One set of derivatives form chiral, helical stacks while the second set form less organised, frustrated stacks. Here we study the effects of supramolecular organisation on the resonance energy transfer rates. We measure these rates in nanoassemblies formed with mixed blends of oligomers and compare them with the rates predicted by Foerster theory. Our results and analysis show that control of supramolecular order in the nanometre lengthscale has a dominant effect on the efficiency and dimentionality of resonance energy transfer.Comment: 17 Pages, 5 Figures, Submitted to J. Chem. Phy

    New pricing models for generic medicines to ensure long-term sustainable competition in Europe

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    Funding Information: This study was funded by Medicines for Europe. Funding Information: CF and GG worked for Creativ-Ceutical (Which has been taken over by Putnam PHMR) which received funding from Medicines for Europe to undertake the study. SS has previously held the EGA Chair “European policy towards generic medicines”. Publisher Copyright: Copyright © 2023 Francois, Gawlik, Mestre-Ferrandiz, Pana, Perelman, Yfantopoulos and Simoens.Background: Price erosion of generic medicines over time as a result of existing pricing policies in combination with increasing operational costs of these products due to high inflation, undermine long-term sustainable competition in European off-patent medicines markets. Therefore, the aim of this study is to identify new potential pricing models for retail generic medicines in Europe, examine their pros and cons, and illustrate them with examples inside or outside the pharmaceutical sector. Methods: A targeted literature review, one-to-one interviews and a joint advisory board meeting with experts from five European countries were carried out to assess potential pricing models for generic medicines. Results: We identified ten pricing models that can be applied to generic medicines. The tiered pricing model is viewed as a sustainable solution ensuring competitiveness, but requires market monitoring using a supportive IT infrastructure. De-linking the price of generic medicines from that of the off-patent originator medicine prevents the originator from forcing generic medicines’ prices to unsustainable levels. Higher costs due to inflation can be compensated in the automatic indexation model. Other pricing models that have less implementation potential include the one-in-one/multiple-out model, tax credits, value-based pricing, volume for savings and guaranteed margin/fee models. The hypothecated tax and cost allocation models, which add a patient fee to generic medicines prices, are not likely to be socially acceptable. Conclusion: When considering a new pricing model for generic medicines, the impact on innovative medicines and the characteristics of the healthcare system in a given country need to be taken into account. Also, there is a need to continuously follow up the level of competition in off-patent medicines markets and to identify sustainability risks.publishersversionpublishe

    Model of collective fish behavior with hydrodynamic interactions

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    Fish schooling is often modeled with self-propelled particles subject to phenomenological behavioral rules. Although fish are known to sense and exploit flow features, these models usually neglect hydrodynamics. Here, we propose a novel model that couples behavioral rules with far-field hydrodynamic interactions. We show that (1) a new "collective turning" phase emerges, (2) on average, individuals swim faster thanks to the fluid, and (3) the flow enhances behavioral noise. The results of this model suggest that hydrodynamic effects should be considered to fully understand the collective dynamics of fish

    Evidence of an Intracellular Reservoir in the Nasal Mucosa of Patients with Recurrent Staphylococcus aureus Rhinosinusitis

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    Severe infections due to Staphylococcus aureus require prolonged therapy for cure, and relapse may occur even years after the first episode. Persistence of S. aureus may be explained, in part, by nasal carriage of S. aureus which occurs in a large percentage of healthy humans and represents a major source of systemic infection. However, the persistence of internalized S. aureus within mucosal cells has not been evaluated in humans. Here, we provide the first in vivo evidence of intracellular reservoirs of S. aureus in humans, which were assessed in endonasal mucosa specimens from patients suffering from recurrent S. aureus rhinosinusitis due to unique, patient-specific bacterial clonotypes. Heavily infected foci of intracellular bacteria located in nasal epithelium, glandular, and myofibroblastic cells were revealed by inverted confocal laser scan fluorescence and electron microscopic examination of posttherapy intranasal biopsy specimens from symptom-free patients undergoing surgery on the sinuses. Intracellular residence may provide a sanctuary for pathogenic bacteria by protecting them from host defense mechanisms and antibiotic treatment during acute, recurrent S. aureus rhinosinusiti

    Cost-effectiveness of CTC guided chemo- or endocrine therapy in ER+ HER2- metastatic breast cancer – results from a randomized controlled multicenter trial

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    Patients with metastatic, Estrogen Receptor (ER) positive, HER2-negative, breast cancer, before initiating CDK4/6 inhibitors, receive either single agent endocrine- or chemotherapy based on their clinical risk. In this first-ever trial-based economic evaluation of Circulating Tumor Cells (CTCs), the cost-effectiveness of standardizing the prescription of endocrine- or chemotherapy using a CTC count threshold (with >5 CTCs/7.5mL indicative of unfavorable disease outcomes) was compared to current clinical practice. N=755 ER+ HER2-patients, enrolled in 17 French centres, were randomized to CTC guided or standard of care and were treated according to either through the CTC score or clinical examination. Health state utilities were calculated by mapping the QLQ-C30 to EQ-5D utilities and used to calculate Quality-Adjusted Life Years (QALY) over a 2-year time horizon. Bootstrapping and additional sensitivity analyses were performed to quantify the impact of uncertainty. Health outcomes in both arms were similar, but costs were higher in the CTC guided arm (€19,403) compared to the usual care (€18,254), resulting in an ICER of €104,078/QALY in favor of usual care. However, when the analysis was performed for the clinically high- and low-risk groups separately, CTC enumeration could be a dominant strategy (cost saving) if treatment is de-escalated in clinically high-risk patients as indicated by CTC scores. However, the current analysis was based on the PFS and OS data reported in 2021 and long-term Overall Survival data is collected since then (JCO, 2023 in press). A further analysis of the health economic impact of CTC enumeration in clinically low and high-risk groups is therefore indicated

    The middle class in Argentina: Dynamics, characteristics and implications for public policies

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    L'Argentine est généralement considérée comme le pays typique de la classe moyenne en Amérique latine. Pourtant, si les crises successives qui ont frappé l'économie argentine au cours des quatre dernières décennies ont manifestement affecté à la fois la taille et la stabilité de sa classe moyenne, les études universitaires manquent quant aux conséquences de ces crises sur la stratification socio-économique et sur les préférences et les attentes de la classe moyenne. Le présent article comble cette lacune en se concentrant sur la période la plus récente. Pour ce faire, nous adoptons un plan de recherche original basé sur une combinaison d'enquêtes quantitatives, fondées sur des enquêtes auprès des ménages existantes et des matériaux qualitatifs originaux, qui vise à : (1) identifier la classe moyenne argentine et sa structure, ainsi que de décrire sa dynamique ; (2) examiner le comportement et les perceptions subjectives du groupe, ainsi que ses attentes en termes de politiques publiques ; et (3) évaluer dans quelle mesure la conception des politiques publiques et des stratégies du marché privé est influencée par la composition et la dynamique de la classe moyenne argentine. Premièrement, notre analyse montre que la tendance à la mobilité ascendante qui a été dominante jusqu'en 2007 et a conduit à l'expansion d'une nouvelle classe moyenne (inférieure) argentine s'est progressivement ralentie et même inversée après 2014. Deuxièmement, la mise en oeuvre d'une analyse en cluster nous a conduit à identifier cinq groupes distincts au sein de la classe moyenne argentine, confirmant ainsi son hétérogénéité. Troisièmement, l'enquête qualitative menée auprès de 40 individus issus de ménages de la classe moyenne à Buenos Aires et Tucuman fournit des comptes rendus détaillés des perceptions et attentes subjectives des différents segments de la classe moyenne argentine. Quatrièmement, notre analyse confirme que la classe moyenne argentine est hétérogène en termes d'orientations politiques. Enfin, une enquête institutionnelle qualitative menée auprès de 12 représentants d'institutions publiques et privées met en évidence la mise en oeuvre récente de programmes publics ou privés spécifiquement dédiés aux ménages de la classe moyenne

    A bridged low band gap A-D-A quaterthiophene as efficient donor for organic solar cells

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    International audience[small alpha],[small omega]-Bis(dicyanovinyl)quaterthiophene 1 with a median 4,4-diethyl-4H-cyclopenta[2,1-b:3,4-b[prime or minute]]dithiophene has been synthesized. UV-Vis absorption data show that the covalent bridging of the inner 2,2[prime or minute]-bithiophene leads to a significant reduction of the HOMO-LUMO gap essentially due to an increase of the HOMO level as confirmed by electrochemical and theoretical results. X-ray diffraction analysis of a single crystal of 1 shows that except for the out-of-plane ethyl groups, the conjugated system displays a quasi-planar geometry while the molecular packing exhibits strong [small pi]-stacking interactions and multiple short intermolecular contacts. Quaterthiophene 1 has been used as active donor material in organic solar cells of various architectures including bi-layer planar hetero-junctions and hybrid co-evaporated bulk hetero-junctions with C60 as electron acceptor material. A maximum conversion efficiency of 4.30% is obtained with a hybrid co-evaporated device. These results are discussed in terms of structure-properties relationships with reference to the open-chain parent [small alpha],[small omega]-bis(dicyanovinyl)quaterthiophene 2
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