Valuation and modeling of EQ-5D-5L health states using a hybrid approach

Background: The EQ-5D instrument is the most widely used preference-based health-related quality of life questionnaire in cost-effectiveness analysis of health care technologies. Recently, a version called EQ-5D-5L with 5 levels on each dimension was developed. This manuscript explores the performance of a hybrid approach for the modeling of EQ-5D-5L valuation data. Methods: Two elicitation techniques, the composite time trade-off, and discrete choice experiments, were applied to a sample of the Spanish population (n=1000) using a computer-based questionnaire. The sampling process consisted of 2 stages: stratified sampling of geographic area, followed by systematic sampling in each area. A hybrid regression model combining composite time trade-off and discrete choice data was used to estimate the potential value sets using main effects as starting point. The comparison between the models was performed using the criteria of logical consistency, goodness of fit, and parsimony. Results: Twenty-seven participants from the 1000 were removed following the exclusion criteria. The best-fitted model included 2 significant interaction terms but resulted in marginal improvements in model fit compared to the main effects model. We therefore selected the model results with main effects as a potential value set for this methodological study, based on the parsimony criteria. The results showed that the main effects hybrid model was consistent, with a range of utility values between 1 and -0.224. Conclusion: This paper shows the feasibility of using a hybrid approach to estimate a value set for EQ-5D-5L valuation data.</p

Uncovering the host galaxy of the γ\gamma-ray-emitting narrow-line Seyfert 1 galaxy FBQS J1644+2619

The discovery of $\gamma$-ray emission from radio-loud narrow-line Seyfert 1 (NLSy1) galaxies has questioned the need for large black hole masses (> 10$^8$ M$_{\odot}$) to launch relativistic jets. We present near-infrared data of the $\gamma$-ray-emitting NLSy1 FBQS J1644+2619 that were collected using the camera CIRCE (Canarias InfraRed Camera Experiment) at the 10.4-m Gran Telescopio Canarias to investigate the structural properties of its host galaxy and to infer the black hole mass. The 2D surface brightness profile is modelled by the combination of a nuclear and a bulge component with a S\'ersic profile with index $n$ = 3.7, indicative of an elliptical galaxy. The structural parameters of the host are consistent with the correlations of effective radius and surface brightness against absolute magnitude measured for elliptical galaxies. From the bulge luminosity, we estimated a black hole mass of (2.1$\pm$0.2) $\times$10$^8$ M$_{\odot}$, consistent with the values characterizing radio-loud active galactic nuclei.Comment: 5 pages, 3 figures, 1 table. Monthly Notices of the Royal Astronomical Society Letter, Vol. 469, L11-L1

Fuzzy-Based Language Grounding of Geographical References : From Writers to Readers

Jose M. Alonso is Ramon y Cajal Researcher (RYC-2016-19802). This research was also funded by the Spanish Ministry of Science, Innovation and Universities (grants RTI2018-099646-BI00, TIN2017-84796-C2-1-R and TIN2017-90773-REDT) and the Galician Ministry of Education, University and Professional Training (grants ED431F2018/02, ED431C 2018/29 and “accreditation 2016-2019, ED431G/08”). All grants were co-funded by the European Regional Development Fund (ERDF/FEDER program).Peer reviewedPublisher PD

Outcome of protease inhibitor substitution with nevirapine in HIV-1 infected children

<p>Abstract</p> <p>Background</p> <p>Protease inhibitors (PIs) have been associated with metabolic complications. There is a trend to switch to simpler therapy to improve these disturbances. We report a case-series describing the effects in metabolic abnormalities in seven HIV-infected children, previously treated with protease inhibitor (PI) after switching to nevirapine.</p> <p>Methods</p> <p>Seven children with stable PI-containing regimen and a long lasting HIV-1 RNA < 50 copies/ml were switched to nevirapine. All patients were naïve to non nucleoside reverse transcriptase inhibitor. PIs were switched to nevirapine. Preentry nucleoside reverse transcriptase inhibitors were maintained. The substitution of PIs with nevirapine was made when the patient showed hyperlipidemia or lipodystrophy or the physician and/or the patient's willingness to simplify. Clinical, laboratory data and anthropometric parameters were assessed every 3 months. Dual-energy X-Ray absorptiometry scans (DXA) was performed at baseline and at 12 months.</p> <p>Results</p> <p>Seven HIV-infected children were enrolled. Median age: 130 months (99,177). Median baseline CD4%: 32%. All had HIV-1 RNA < 50 copies/ml. Median length of preentry PI-therapy was 47 months (28, 91). Median age at the beginning of nevirapine was 120 months (99,177). Median decrease in cholesterol in 7.2 mmol/L was observed (P = 0.09), from baseline to 12 months. HDL-cholesterol increased in 5.1 mmol/L (P = 0.03) throughout the study period. No significant changes were observed in DXA with regard to body fat, but changes in total body bone mineral content and lean body content were significant. CD4% remained stable. All patients but one maintained viral load < 50 copies/ml at 12 months. The patient with virologic failure referred bad adherence. Children referred to take medication more easily.</p> <p>Conclusion</p> <p>PI substitution with nevirapine improved lipid profile in our patients, although this strategy did not show significant changes in body fat or lipodystrophy.</p

U-Pb SHRIMP zircon dating of Grenvillian metamorphism in Western Sierras Pampeanas (Argentina) : correlation with the Arequipa-Antofalla craton and constraints on the extent of the Precordillera Terrane

The Sierras Pampeanas of Argentina, the largest outcrop of pre-Andean crystalline basement in southern South America, resulted from plate interactions along the proto-Andean margin of Gondwana, from as early as Mesoproterozoic to Late Paleozoic times (e.g., Ramos, 2004, and references therein). Two discrete Paleozoic orogenic belts have been recognized: the Early Cambrian Pampean belt in the eastern sierras, and the Ordovician Famatinian belt, which partially overprints it to the west (e.g., Rapela et al., 1998). In the Western Sierras Pampeanas, Mesoproterozoic igneous rocks (ca. 1.0–1.2 Ga) have been recognized in the Sierra de Pie de Palo (Fig. 1) (McDonough et al., 1993 M.R. McDonough, V.A. Ramos, C.E. Isachsen, S.A. Bowring and G.I. Vujovich, Edades preliminares de circones del basamento de la Sierra de Pie de Palo, Sierras Pampeanas occidentales de San Juán: sus implicancias para el supercontinente proterozoico de Rodinia, 12° Cong. Geol. Argentino, Actas vol. 3 (1993), pp. 340–342.McDonough et al., 1993, Pankhurst and Rapela, 1998 and Vujovich et al., 2004) that are time-coincident with the Grenvillian orogeny of eastern and northeastern North America (e.g., Rivers, 1997 and Corrievau and van Breemen, 2000). These Grenvillian-age rocks have been considered to be the easternmost exposure of basement to the Precordillera Terrane, a supposed Laurentian continental block accreted to Gondwana during the Famatinian orogeny (Thomas and Astini, 2003, and references therein). However, the boundaries of this Grenvillian belt are still poorly defined, and its alleged allochthoneity has been challenged (Galindo et al., 2004). Moreover, most of the Grenvillian ages so far determined relate to igneous protoliths, and there is no conclusive evidence for a Grenvillian orogenic belt, other than inferred from petrographic evidence alone (Casquet et al., 2001). We provide here the first evidence, based on U–Pb SHRIMP zircon dating at Sierra de Maz, for a Grenville-age granulite facies metamorphism, leading to the conclusion that a continuous mobile belt existed throughout the proto-Andean margin of Gondwana in Grenvillian times

Associations between olfactory pathway gene methylation marks, obesity features and dietary intakes

Abstract Background Olfaction is an important sense influencing food preferences, appetite, and eating behaviors. This hypothesis-driven study aimed to assess associations between olfactory pathway gene methylation signatures, obesity features, and dietary intakes. Methods A nutriepigenomic analysis was conducted in 474 adults from the Methyl Epigenome Network Association (MENA) project. Anthropometric measurements, clinical data, and serum metabolic profiles of the study population were obtained from structured databases of the MENA cohorts. Habitual dietary intake was assessed using a validated semiquantitative food frequency questionnaire. DNA methylation was measured in circulating white blood cells by microarray (Infinium Human Methylation 450 K BeadChips). FDR values (p < 0.0001) were used to select those CpGs that showed the best correlation with body mass index (BMI) and waist circumference (WC). Pathway analyses involving the characterization of genes involved in the olfactory transduction system were performed using KEGG and pathDIP reference databases. Results Overall, 15 CpG sites at olfactory pathway genes were associated with BMI (p < 0.0001) and WC (p < 0.0001) after adjustments for potential confounding factors. Together, methylation levels at the15 CpG sites accounted for 22% and 20% of the variability in BMI and WC (r 2 = 0.219, p < 0.001, and r 2 = 0.204, p < 0.001, respectively). These genes encompassed olfactory receptors (OR4D2, OR51A7, OR2T34, and OR2Y1) and several downstream signaling molecules (SLC8A1, ANO2, PDE2A, CALML3, GNG7, CALML6, PRKG1, and CAMK2D), which significantly regulated odor detection and signal transduction processes within the complete olfactory cascade, as revealed by pathway enrichment analyses (p = 1.94 × 10–10). Moreover, OR4D2 and OR2Y1 gene methylation patterns strongly correlated with daily intakes of total energy (p < 0.0001), carbohydrates (p < 0.0001), protein (p < 0.0001), and fat (p < 0.0001). Conclusions The results of this study suggest novel relationships between olfactory pathway gene methylation signatures, obesity indices, and dietary intakes

Nitric oxide deficiency decreases C-repeat binding factor-dependent and -independent induction of cold acclimation

[EN] Plant tolerance to freezing temperatures is governed by endogenous components and environmental factors. Exposure to low non-freezing temperatures is a key factor in the induction of freezing tolerance in the process called cold acclimation. The role of nitric oxide (NO) in cold acclimation was explored in Arabidopsis using triple nia1nia2noa1-2 mutants that are impaired in the nitrate-dependent and nitrate-independent pathways of NO production, and are thus NO deficient. Here, we demonstrate that cold-induced NO accumulation is required to promote the full cold acclimation response through C-repeat Binding Factor (CBF)-dependent gene expression, as well as the CBF-independent expression of other cold-responsive genes such as Oxidation-Related Zinc Finger 2 (ZF/OZF2). NO deficiency also altered abscisic acid perception and signaling and the cold-induced production of anthocyanins, which are additional factors involved in cold acclimation.We thank Isabel Lopez-Diaz and Esther Carrera for the hormone quantification carried out at the Plant Hormone Quantification Service, IBMCP, Valencia, Spain. This work was supported by grants from MINECO of Spain Government and FEDER EU funds [BIO2014-56067-P, BIO2017-82945-P to JL and BIO2016-79187-R to JS].Costa-Broseta, Á.; Perea-Resa, C.; Castillo, M.; Ruíz, MF.; Salinas, J.; Leon Ramos, J. (2019). Nitric oxide deficiency decreases C-repeat binding factor-dependent and -independent induction of cold acclimation. Journal of Experimental Botany. 70(12):3283-3296. https://doi.org/10.1093/jxb/erz115S328332967012Adams, S., & Carré, I. A. (2011). Downstream of the plant circadian clock: output pathways for the control of physiology and development. 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Blueprint for a european calciphylaxis registry initiative. the european calciphylaxis network (eucalnet)

Calcific uraemic arteriolopathy (CUA) is a rare disease and continues to be a clinical challenge. The typical course of CUA is characterized by painful skin discolouration and induration evolving to necrotic ulcerations. Medial calcification of cutaneous arterioles and extensive extracellular matrix remodelling are the hallmarks of CUA. The epidemiology and risk factors associated with this disease are still not fully understood. Moreover, CUA treatment strategies vary significantly among centres and expert recommendations are heterogeneous. Registries may provide important insights and information to increase our knowledge about epidemiology and clinical aspects of CUA and may help to optimize its therapeutic management. In 2006, we established an internet-based registry in Germany (www.calciphylaxie.de) to allow online notification of patients with established or suspected CUA. The registry includes a comprehensive database with questions covering >70 parameters and items regarding patient-related and laboratory data, clinical background and presentation as well as therapeutic strategies. The next phase will be to allow international patient registration via www.calciphylaxis.net as part of the multinational EuCalNet (European Calciphylaxis Network) initiative, which is supported by the ERA-EDTA scientific working group 'CKD-MBD'. Based on the valuable experience with the previous German CUA registry, EuCalNet will be a useful tool to collect data on the rare disease CUA and may become a basis for prospective controlled trials in the near future

Comparison between traditional and reverse periodization: swimming performance and specific strength values

International Journal of Swimming Kinetics 2(1): 87-96, 2013. Periodization of athletic training is conceptualized as a pedagogical process, which involves varying volume, intensity and frequency of training in attempt to optimize sporting performance. The primary purpose of this research was to compare changes in 100m swim performance (t100c), specific swim power output (SSP) and maximum drag charge (MDC), after 14 weeks of training traditional periodization (control) and reverse periodization (treatment). There were 26 volunteer swimmers (16.02±0.6 yrs. 1.72±9.3 cm 64.1±9.3 kg) divided in two groups traditional periodization (TP) and reverse periodization (RP). Results at the 14th week showed significant improvements (p\u3c0.05) in values of t100c (6.9%), SSP (20.9%) and MDC (10.0%) by RP above TP values. The results demonstrated that reverse periodization is specific and an efficient strategy of training for sprinters at time to reduce significantly load volume

Acerca de uma leitura geopolítica das relações entre Portugal e o Atlântico

O artigo pretende traçar uma breve perspectiva geopolítica da relação entre Portugal e o oceano Atlântico. Essa relação, embora sempre presente e importante, variou ao longo da nossa histó- ria. O autor, depois de tentar sumariamente caracterizar essas variações, analisa simplificadamente aquela relação no actual contexto do sistema global das relações internacionais. Dessa análise retira argumentos para afirmar que na ligação com o Atlântico poderão de novo ser encontradas as soluções mais adequadas para os nossos actuais problemas do desenvolvimento e da afirmação internacional, através da possível e desejável futura assumpção por Portugal de um papel de entreposto de importantes fluxos nas relações transatlânticas, em que as luso-brasileiras e as com a CPLP deverão desempenhar um papel centra