930 research outputs found

    Preventive health care and payment systems to providers

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    Prevention has been a main issue of recent policy orientations in health care. This renews the interest on how different organizational designs and the definition of payment schemes to providers may affect the incentives to provide preventive health care. We present, both the normative and the positive analyses of the change from independent providers to integrated services. We show the evaluation of that change to depend on the particular way payment to providers is done. We focus on the externality resulting from referral decisions from primary to acute care providers. This makes our analysis complementary to most works in the literature allowing to address in a more direct way the issue of preventive health care.Preventive health care, payment systems to providers

    Molecular analysis of peptides from the GH loop of foot-and-mouth disease virus C-S30 using surface plasmon resonance: a role for kinetic rate constants

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    A foot-and-mouth disease virus (FMDV) field variant, isolate C-S30 (also named C-1-Barcelona), is known to contain four changes within the main antigenic site A (GH loop of capsid protein VP1, residues 136-150), at least one of which (Leu147 --> Val) involves a highly conserved position, critical for antibody recognition in the reference strain C-S8c1. However, immunoenzymatic analysis of FMDV C-S30 showed it was recognised by 4C4, a monoclonal antibody that specifically targets site A. This remarkable behaviour has led us to analyse the individual and combined contributions of the four mutations to the antigenicity of C-S30, by surface plasmon resonance (SPR) and enzyme-linked immunosorbent assay (ELISA) studies of pentadecapeptides displaying all possible combinations of the four replacements. Analysis of this family of C-S30-derived analogues shows a certain level of antibody recognition by SPR. In addition, SPR data suggest that kinetic rate constants provide an indirect measure, on the one hand, of paratope accessibility (association rate constant) and, on the other hand, of peptide fitness to the same paratope (dissociation rate constant)

    Surface plasmon resonance screening of synthetic peptides mimicking the immunodominant region of C-S8c1 foot-and-mouth disease virus

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    The main antigenic site (site A) of foot-and-mouth disease virus (FMDV, strain C-S8c1) may be adequately reproduced by a 15-peptide with the amino acid sequence H-YTASARGDLAHLTTT-NH2 (A15), corresponding to the residues 136-150 of the viral protein VPI. The effect of amino acid substitutions within A15 on its antigenicity towards monoclonal antibodies (MAb) raised against antigenic site A, has been studied by means of BIAcore technology, based on surface plasmon resonance (SPR). Although these antigenicities have previously been determined from enzyme-linked immunosorbent assays (ELISA), the SPR-based technique is superior in that it allows a fast and straightforward screening of antigens while simultaneously providing kinetic data of the antigen-antibody interaction. With a view to screening fairly large libraries of individual peptides, we have inverted the typical SPR experiment by immobilizing the MAb on the sensor surface and using peptides as soluble analytes. We report the validation of this approach through the screening of 44 site A peptides, with results generally in good agreement with the relative antigenicities previously determined by competition ELISA

    First paleomagnetic results of mid-to late Holocene sediments from Lake Issyk-Kul (Kyrgyzstan): Implications for paleosecular variation in central Asia

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    We present new paleomagnetic and rock magnetic data from mid and late Holocene sediments recovered in two gravity cores (C087 and C142a) from Lake Issyk-Kul (central Asia), for which independent radiocarbon-based age models are available. Our results indicate that sediments from core C087 are characterized by fine (pseudo single domain) magnetite grains and are reliable recorders of Holocene geomagnetic paleosecular variation (PSV) in central Asia, which is a region with poor data coverage. Similarity is found between the core C087 PSV record, which spans the last 5700 years, and the Lake Baikal PSV record, which is the only published Holocene central Asian PSV record of comparable length with an independent radiocarbon-based chronology. Our new results represent a step forward in constructing a reference PSV curve for central Asia that can be used to date sedimentary sequences. These results can also be used to improve the reliability and accuracy of global geomagnetic field models. We have not been able to disentangle past environmental changes in the Lake Issyk-Kul region based on rock magnetic properties, probably because the magnetite and hematite in the studied sediments have a mixed (fluvial and eolian) terrigenous origin. Copyright 2012 by the American Geophysical Union.Financial support for this research was provided through a CSIC JAE-Doc post-doctoral research contract (MGP), the GRACCIE (Spanish Consolider-Ingenio CSD2007-00067), APELIK (EU ICA2-CT-2000-10003), CGL2008-02203/BTE, and PALEONAO (CGL2010-15767/BTE) research projects.Peer Reviewe

    Quaternary evolution of the lower calore and middle volturno valleys (Southern Italy)

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    The lower Calore and middle Volturno valleys preserve stratigraphical and morphological evidence and tephrostratigraphic markers particularly suitable for reconstructing the long-term geomorphological evolution of the central-southern Apennines. Aim of our study is to identify the main steps of the Quaternary landscape evolution of these valley systems and to improve knowledge about the relationships between fluvial processes and tectonics, volcanic activity, climatic and human influences. To this purpose, we carried out an integrated geomorphological and chronostratigraphical analysis of identified fluvial landforms and related deposits, integrated by230Th/234U datings on travertines from the Telese Plain area. The study highlighted in particular: (1) fluvial sedimentation started in the Middle Pleistocene (~650 ka) within valleys that originated in the lower Pleistocene under the control of high-angle faults; (2) extensional tectonics acted during the Middle and Upper Pleistocene, driving the formation of the oldest fluvial terraces and alluvial fans, and persisted beyond the emplacement of the Campanian Ignimbrite pyroclastic deposits (~39 ka); and (3) from the late Upper Pleistocene onwards (<15 ka), the role of tectonics appears negligible, while climatic changes played a key role in the formation of three orders of valley floor terraces and the youngest alluvial fans

    Direct single-step surface plasmon resonance analysis of interactions between small peptides and immobilized monoclonal antibodies

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    Surface plasmon resonance (SPR) methods have been optimized to permit direct kinetic analysis of the antigenic peptide analytes interacting with immobilized monoclonal antibodies (mAbs). High reproducibility and a significant correlation between SPR and previous ELISA data on the same set of antibodies and peptides were observed. The kinetic data obtained provide further insight into the structure of the main antigenic site of foot-and-mouth disease virus (FMDV)

    Antigenicity modulation upon peptide cyclization: application to the GH loop of foot-and-mouth disease virus strain C-1-Barcelona

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    Foot-and-mouth disease virus (FMDV) isolate C-1-Barcelona (or C-S30) includes four replacements within its immunodominant site (GH loop, residues 136-150 of capsid protein VP1, YTTSTRGDLAHVTAT), relative to reference strain C-S8cl (YTASAR-GDLAHLTTT). Although one of the mutations in C-S30 ((147)Leu --> Val) is known to be detrimental for antibody recognition, reactivity of this isolate with the neutralizing monoclonal antibody (mAb) 4C4, raised against FMDV C-1-Brescia (GH loop: YTASTRGDLAHLTAT), was indistinguishable from those of strains C-S8cl or C-1-Brescia. A structural interpretation for these somewhat striking findings is available, based on the observation that 15-residue peptides reproducing the C-S30 and C-S8cl GH loops adopt very similar, quasi-circular, conformations in crystal complexes with 4C4. Nevertheless, surface plasmon resonance (SPR) kinetic analyses of the interactions between these peptides and three anti-GH loop mAbs have now revealed that the linear C-S30 peptides were less antigenic in solution than their C-S8cl and C-1-Brescia counterparts. We have, therefore, tried to modulate peptide antigenicity in solution by cyclization. Functional SPR and structural two dimensional proton nuclear magnetic resonance (2D-H-1 NMR) studies of both linear and cyclic peptide antigens are discussed here. Conformation seems to have an important role in peptide antigenicity, even when continuous (i.e. linear) antigenic sites are involved

    Sexual dimorphism in brown adipose tissue activation and white adipose tissue browning

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    The present narrative review gathers the studies reported so far, addressing sex differences in the effects of cold exposure, feeding pattern and age on brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. In rodents, when exposed to decreasing temperatures, females activate thermogenesis earlier. Results obtained in humans go in the same line, although they do not provide results as solid as those obtained in rodents. Regarding the effects of overfeeding, interesting sex differences on BAT thermogenic capacity have been reported, and the greater or lower sensitivity of each sex to this dietary situation seems to be dependent on the type of feeding. In the case of energy restriction, females are more sensitive than males. In addition, sex differences have also been observed in thermogenesis changes induced by phenolic compound administration. During sexual development, an increase in BAT mass and BAT activity takes place. This phenomenon is greater in boys than in girls, probably due to its relation to muscle-mass growth. The opposite situation takes place during ageing, a lifespan period where thermogenic capacity declines, this being more acute in men than in women. Finally, the vast majority of the studies have reported a higher susceptibility to developing WAT browning amongst females. The scarcity of results highlights the need for further studies devoted to analysing this issue, in order to provide valuable information for a more personalised approach
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