Investigating epidemiological distribution (temporality and intensity) of respiratory pathogens following COVID-19 de-escalation process in Catalonia, September 2016-June 2021: Analysis of regional surveillance data.

BACKGROUND: Following the low incidence rates of non-SARS-CoV-2 respiratory viruses registered during the strict lockdown enforced in the pandemic, a resurgence of several endemic viruses in Catalonia (Spain) was noted during the early summer of 2021. OBJECTIVES: In this study, we investigated whether the circulation of non-SARS-CoV-2 respiratory viruses in Catalonia, assessed by Microbiological Reporting System of Catalonia (MRSC) and the Epidemiological Surveillance Network of Catalonia, was affected by the strict lockdown measures, as well as, the implication of the Coronavirus Disease 19 (COVID-19) de-escalation process in the late season outbreaks registered during the 2020-2021 season. STUDY DESIGN: A retrospective comparison of epidemic patterns in the respiratory viruses' incidence, using regional public health surveillance data from MRSC, was performed between weeks 26/2016 to week 27/2021. Data were expressed as the weekly total number of test positivity for individual viruses. A segmented negative binomial regression model was conducted, with two parameters included (level and trend) for each segment of the time series (2020 pre-lockdown, 2020 post-lockdown and 2021). Results were reported as a unit changed in the strict lockdown. RESULTS: A total of 51588 confirmed cases of the different respiratory viruses were included in the analysis, the majority were influenza cases (63.7%). An immediate reduction in the weekly number of cases was observed in 2020 after the COVID-19 outbreak for human adenovirus virus (HAdV) (ß2 = -2.606; P <0.01), human parainfluenza virus (HPIV) (ß2 = -3.023; P <0.01), influenza virus (IFV) (ß2 = -1.259; P <0.01), but not for respiratory syncytial virus (RSV), where the number of cases remained unchanged. During 2020, a significant negative trend was found for RSV (ß3 = -0.170, P <0.01), and a positive trend for HAdV (ß3 = 0.075, P <0.01). During 2021, a significant reduction in the weekly number of cases was also observed for all respiratory viruses, and a borderline non-significant reduction for HPIV (ß3 = -0.027; P = 0.086). Moreover, significant positive trends were found for each viral pathogen, except for influenza during 2020-2021 season, where cases remained close to zero. The respiratory viruses increased activity and their late season epidemic start particularly affected children under 6 years old. CONCLUSIONS: Our data not only provides evidence that occurrence of different respiratory virus infections was affected by the strict lockdown taken against SARS-CoV-2 but it also shows a late resurgence of seasonal respiratory viruses' cases during the 2020-2021 season following the relaxation of COVID-19-targeted non-pharmaceutical interventions.

Report on the first two confirmed autochthonous cases of West Nile virus encephalitis in Catalonia, Spain.

BACKGROUND: West Nile virus (WNV) is a mosquito-borne flavivirus that can cause Central Nervous System infection in humans. Previous autochthonous cases of WNV encephalitis have been described in Spain, but none in Catalonia. MATERIALS AND METHODS: We report on the first two autochthonous cases of encephalitis in humans caused by the West Nile virus (WNV) diagnosed in Catalonia (northeastern region of Spain). RESULTS: An old married couple presented with clinical and biological signs compatible with viral encephalitis. Acute and convalescent serum samples showed IgM and IgG positivity for WNV. In addition, IgM was also detected in cerebrospinal fluid in the male patient. The serological results were later confirmed by microneutralization assays. CONCLUSIONS: WNV infection must be considered in patients presenting with meningoencephalitis with viral CSF characteristics when common pathogens are excluded.

Grafting of Anionic Decahydro-Closo-Decaborate Clusters on Keggin and Dawson-Type Polyoxometalates: Syntheses, Studies in Solution, DFT Calculations and Electrochemical Properties.

Herein we report the synthesis of a new class of compounds associating Keggin and Dawson-type Polyoxometalates (POMs) with a derivative of the anionic decahydro-closo-decaborate cluster [B10H10]2- through aminopropylsilyl ligand (APTES) acting as both a linker and a spacer between the two negatively charged species. Three new adducts were isolated and fully characterized by various NMR techniques and MALDI-TOF mass spectrometry, notably revealing the isolation of an unprecedented monofunctionalized SiW10 derivative stabilized through intramolecular H-H dihydrogen contacts. DFT as well as electrochemical studies allowed studying the electronic effect of grafting the decaborate cluster on the POM moiety and its consequences on the hydrogen evolution reaction (HER) properties.

Epidemiologic Features and Control Measures during Monkeypox Outbreak, Spain, June 2022.

During June 2022, Spain was one of the countries most affected worldwide by a multicountry monkeypox outbreak with chains of transmission without identified links to disease-endemic countries. We provide epidemiologic features of cases reported in Spain and the coordinated measures taken to respond to this outbreak.

Diagnostic Performance of Ag-RDTs and NAAT for SARS-CoV2 Identification in Symptomatic Patients in Catalonia.

The use of rapid antigenic tests (Ag-RDTs) to diagnose a SARS-CoV-2 infection has become a common practice recently. This study aimed to evaluate performance of Abbott PanbioTM Ag-RDTs with regard to nucleic acid amplification testing (NAAT) in the early stages of the disease. A cohort of 149,026 infected symptomatic patients, reported in Catalonia from November 2020 to January 2021, was selected. The positivity rates of the two tests were compared with respect to the dates of symptom onset. Ag-RDTs presented positivity rates of 84% in the transmission phases of the disease and 31% in the pre-symptomatic period, compared to 93% and 91%, respectively, for NAAT. The detection of many false negatives with Ag-RDTs during the pre-symptomatic period demonstrates the risk of virus dissemination with this diagnostic technique if used outside the symptomatic period.

Discovery of an Orally Efficacious Positive Allosteric Modulator of the Glucagon-like Peptide-1 Receptor.

The identification of LSN3318839, a positive allosteric modulator of the glucagon-like peptide-1 receptor (GLP-1R), is described. LSN3318839 increases the potency and efficacy of the weak metabolite GLP-1(9-36)NH2 to become a full agonist at the GLP-1R and modestly potentiates the activity of the highly potent full-length ligand, GLP-1(7-36)NH2. LSN3318839 preferentially enhances G protein-coupled signaling by the GLP-1R over ß-arrestin recruitment. Ex vivo experiments show that the combination of GLP-1(9-36)NH2 and LSN3318839 produces glucose-dependent insulin secretion similar to that of GLP-1(7-36)NH2. Under nutrient-stimulated conditions that release GLP-1, LSN3318839 demonstrates robust glucose lowering in animal models alone or in treatment combination with sitagliptin. From a therapeutic perspective, the biological properties of LSN3318839 support the concept that GLP-1R potentiation is sufficient for reducing hyperglycemia.

Prevalence and risks factors associated with ESBL-producing faecal carriage in a single long-term-care facility in Spain: emergence of CTX-M-24- and CTX-M-27-producing Escherichia coli ST131-H30R.

OBJECTIVES: To address the faecal carriage prevalence of antibiotic-multiresistant bacteria and associated risk factors in a public long-term care facility (LTCF). METHODS: A prospective study in a single government-funded LTCF of 300 residents in Ciudad Real, Spain. Residents' clinical and demographic data were collected, as well as recent antibiotic consumption in the institution. Each participant contributed a rectal swab, which was plated on selective and differential-selective media. Colonies were identified by MALDI-TOF and ESBL production was confirmed by the double-disc synergy method, with characterization of the molecular mechanism by PCR. Isolates were typed by PFGE and submitted for ST131 screening by PCR. RESULTS: Faecal carriage of ESBL-producing Enterobacterales was detected in 58 (31%) of 187 participants and previous infection by MDR bacteria was identified as a risk factor. The genes characterized were: blaCTX-M-15 (40.6%); blaCTX-M-14 (28.8%); blaCTX-M-27 (13.5%); and blaCTX-M-24 (10.1%). Some 56.4% of the isolates were grouped into the E. coli ST131 clone; 70.9% of these corresponded to the O25b serotype, 51.6% of them to Clade C1 (H30) and 12.9% to Clade C2 (H30Rx). Clade C1 isolates were mostly C1-M27, whereas the C2 sublineage was mainly related to the production of CTX-M-15. ST131-CTX-M-24 isolates (n = 6) corresponded to Clade A with serotype O16. CONCLUSIONS: A high prevalence of ESBL-producing Enterobacterales faecal carriage has been detected in a single LTCF, highlighting the emergence of ST131 Clade A-M24 and Clade C1-M27 lineages.

Unprecedented coupling reaction between two anionic species of a closo-decahydrodecaborate cluster and an Anderson-type polyoxometalate.

A novel decahydrodecaborate-functionalized Anderson type polyoxometalate has been synthesized and characterized in solution by ESI-MS, various NMR techniques and electrochemical methods. DFT studies provide strong support to understand the properties of this hybrid system.

Facilitadores de la participación e implementación de la subcohorte PELFI de familias inmigrantes / Facilitators of participation and implementation of the immigrant families' PELFI Sub-Cohort

Objetivo: PELFI es un estudio multicéntrico de cohortes de familias inmigradas en España. Los objetivos de este manuscrito son: 1) describir el reclutamiento, la recogida de información y las características sociodemográficas según origen y sexo de los participantes de las familias; y 2) valorar las estrategias de reclutamiento y recogida de información que facilitaron la participación en la subcohorte PELFI Badalona/SC. Método: Estudio descriptivo con una muestra de conveniencia de familias inmigrantes y autóctonas residentes en Badalona y Santa Coloma de Gramanet. Se encuestaron los padres, madres e hijos >16 años, y se realizaron exámenes médicos. Resultados: Participaron 115 familias. Entre las estrategias de reclutamiento, la bola de nieve logró el 69% de cooperación. La tasa de cooperación del estudio fue del 57,5% y de los exámenes médicos del 66,6%. La cooperación de las familias chinas fue del 38,5% y no se reclutaron hijos >16 años. El 28% de las encuestas se realizaron en fin de semana o por la noche. Las familias tenían un tiempo medio de residencia de 12,2 años. El 71,2% de los hijos >16 años tenían estudios secundarios finalizados. Los inmigrantes tenían una clase social más baja que los autóctonos (p<0,05) y las mujeres inmigradas menor nivel de estudios (p<0,05). Conclusiones: Interaccionar frecuentemente con la comunidad, utilizar simultáneamente distintas estrategias de reclutamiento, incorporar investigadores del mismo origen geográfico que los participantes, minimizar las barreras idiomáticas y ofrecer flexibilidad de tiempo y lugar facilitó la participación. Las familias chinas presentaron mayores dificultades. Las conclusiones facilitarán la implementación de futuras cohortes de características similares

Objective: PELFI is a multicentre cohort study of migrant families in Spain. The objectives of this manuscript were: 1) to describe the recruitment strategies, data collection and the main socio-demographic characteristics according to geographical origin and sex of participants of the families; and 2) to assess the recruitment and data collection strategies that facilitated participation in the basal assessment of the Badalona and Santa Coloma de Gramanet cohort. Method: Descriptive study on a convenience sample of migrant and native families residing in Badalona and Santa Coloma de Gramanet. Health interviews were conducted on fathers, mothers and children>16 years; and medical examinations were performed. Results: There were 115 participating families. Within the recruitment strategies, snow ball achieved 69% cooperation. The cooperation rate of the study was 57.5% and that of the clinical sub-sample was 66.6%. Cooperation rate of the Chinese families was 38.5% and Chinese children >16 years old were not recruited. Twenty-eight percent of the interviews were conducted at weekends or during the evening. Families had a mean of 12.2 years of residence. Seventy-one point two percent of the children >16 years had completed secondary studies. The migrants had lower social class than natives (p < 0.05) and the migrant women had lower levels of education (p < 0.05). Conclusions: Interacting frequently with the community, using different recruitment strategies simultaneously, incorporating researchers from the same geographical origin as participants, minimising language barriers and offering flexibility in conducting data collection facilitated the participation of the migrant families. The Chinese families presented greater difficulties. The study findings will facilitate the implementation of future cohort studies with similar characteristics

[Facilitators of participation and implementation of the immigrant families' PELFI Sub-Cohort]. / Facilitadores de la participación e implementación de la subcohorte PELFI de familias inmigrantes.

OBJECTIVE: PELFI is a multicentre cohort study of migrant families in Spain. The objectives of this manuscript were: 1) to describe the recruitment strategies, data collection and the main socio-demographic characteristics according to geographical origin and sex of participants of the families; and 2) to assess the recruitment and data collection strategies that facilitated participation in the basal assessment of the Badalona and Santa Coloma de Gramanet cohort. METHOD: Descriptive study on a convenience sample of migrant and native families residing in Badalona and Santa Coloma de Gramanet. Health interviews were conducted on fathers, mothers and children>16 years; and medical examinations were performed. RESULTS: There were 115 participating families. Within the recruitment strategies, snow ball achieved 69% cooperation. The cooperation rate of the study was 57.5% and that of the clinical sub-sample was 66.6%. Cooperation rate of the Chinese families was 38.5% and Chinese children >16 years old were not recruited. Twenty-eight percent of the interviews were conducted at weekends or during the evening. Families had a mean of 12.2 years of residence. Seventy-one point two percent of the children >16 years had completed secondary studies. The migrants had lower social class than natives (p < 0.05) and the migrant women had lower levels of education (p < 0.05). CONCLUSIONS: Interacting frequently with the community, using different recruitment strategies simultaneously, incorporating researchers from the same geographical origin as participants, minimising language barriers and offering flexibility in conducting data collection facilitated the participation of the migrant families. The Chinese families presented greater difficulties. The study findings will facilitate the implementation of future cohort studies with similar characteristics.

[PELFI Project: Recruitment and Sociodemographic Characteristics of Immigrant and Autochthonous Families from Alicante and Barcelona City Subcohorts]. / Proyecto PELFI: reclutamiento y características sociodemográficas de las familias inmigradas y autóctonas de las sub-cohortes de Alicante y Barcelona.

This study is a part of the multi-centre project "Platform of Longitudinal Studies of Immigrant Families (PELFI)" of the Immigration and Health Subprogram of the CIBER-ESP. It describes the field work and data collection of two sub-cohorts of immigrant and native families, and their main socio-demographic characteristics. Prospective observational cohort study in carried out in Barcelona and Alicante, Spain. The study population is a a non-probabilistic sample of 180 families of Colombian, Ecuadorian and Moroccan origin and 50 families of Spanish origin. We interviewed adults aged 18-65 years and adolescents aged 12-17 years in each family, through two questionnaires (adolescent/adult). The cooperation rate was 82.0% with an average recruitment rate of 1.3 families per day. In total, 250 families have been recruited, 82 from Ecuador, 82 from Colombia, 29 from Morocco and 57 from Spain. A total of 473 adults (59.8% women and 68.5% employed) were surveyed. Immigrant adults have an average of 13 years living in Spain. A total of 304 adolescents (53.9% female, 27.1% born in Spain but with immigrant parents) were surveyed. The combination of non-probabilistic techniques promoted access and improved recruitment speed. This study provides key information for the design and improvement of cohort studies with immigrant families.

Este artículo corresponde al "Proyecto de Estudios Longitudinales de Familias Inmigradas (PELFI)" del Subprograma de Inmigración y Salud del CIBERESP y describe el trabajo de campo basal y principales características socio-demográficas de dos sub-cohortes de familias inmigrantes y autóctonas. El diseño es observacional prospectivo. La población de estudio se definió como una muestra no probabilística de 180 familias de origen colombiano, ecuatoriano y marroquí y 50 españolas. Se entrevistó a a 473 personas adultas entre 18 y 65 años (59,8% mujeres, 68,5% ocupados/as) y a 304 adolescentes entre 12 y17 años (53,9% mujeres, 27,1% nacidos en España pero de padres inmigrados) de cada familia, mediante dos cuestionarios diseñados ad hoc. La tasa de cooperación fue del 82,0% con una velocidad media de reclutamiento de 1,3 familias diarias. En total, se reclutó a 250 familias, 82 procedentes de Ecuador, 82 de Colombia, 29 de Marruecos y 57 españolas. Los adultos inmigrados llevaban una media de 13 años en España. Las combinación de técnicas no probabilísticas permitió el acceso y velocidad de reclutamiento. Este estudio aporta información clave para el diseño y mejora de este tipo de cohortes en familias inmigradas.

Proyecto PELFI: reclutamiento y características sociodemográficas de las familias inmigradas y autóctonas de las subcohortes de Alicante y Barcelona / PELFI proyect: recruiment and sociodemographic characteristics of immigrant and autochthonous families from Alicante and Barcelona city subcohorts

Este artículo corresponde al 'Proyecto de Estudios Longitudinales de Familias Inmigradas (PELFI)' del Subprograma de Inmigración y Salud del CIBERESP y describe el trabajo de campo basal y principales características socio-demográficas de dos sub-cohortes de familias inmigrantes y autóctonas. El diseño es observacional prospectivo. La población de estudio se definió como una muestra no probabilística de 180 familias de origen colombiano, ecuatoriano y marroquí y 50 españolas. Se entrevistó a a 473 personas adultas entre 18 y 65 años (59,8% mujeres, 68,5% ocupados/ as) y a 304 adolescentes entre 12 y17 años (53,9% mujeres, 27,1% nacidos en España pero de padres inmigrados) de cada familia, mediante dos cuestionarios diseñados ad hoc. La tasa de cooperación fue del 82,0% con una velocidad media de reclutamiento de 1,3 familias diarias. En total, se reclutó a 250 familias, 82 procedentes de Ecuador, 82 de Colombia, 29 de Marruecos y 57 españolas. Los adultos inmigrados llevaban una media de 13 años en España. Las combinación de técnicas no probabilísticas permitió el acceso y velocidad de reclutamiento. Este estudio aporta información clave para el diseño y mejora de este tipo de cohortes en familias inmigradas (AU)

This study is a part of the multi-centre project 'Platform of Longitudinal Studies of Immigrant Families (PELFI)' of the Immigration and Health Subprogram of the CIBER-ESP. It describes the field work and data collection of two sub-cohorts of immigrant and native families, and their main socio-demographic characteristics. Prospective observational cohort study in carried out in Barcelona and Alicante, Spain. The study population is a a non-probabilistic sample of 180 families of Colombian, Ecuadorian and Moroccan origin and 50 families of Spanish origin. We interviewed adults aged 18-65 years and adolescents aged 12-17 years in each family, through two questionnaires (adolescent/ adult). The cooperation rate was 82.0% with an average recruitment rate of 1.3 families per day. In total, 250 families have been recruited, 82 from Ecuador, 82 from Colombia, 29 from Morocco and 57 from Spain. A total of 473 adults (59.8% women and 68.5% employed) were surveyed. Immigrant adults have an average of 13 years living in Spain. A total of 304 adolescents (53.9% female, 27.1% born in Spain but with immigrant parents) were surveyed. The combination of non-probabilistic techniques promoted access and improved recruitment speed. This study provides key information for the design and improvement of cohort studies with immigrant families (AU)

Multi-dimensional, non-contact metrology using trilateration and high resolution FMCW ladar.

Here we propose, describe, and provide experimental proof-of-concept demonstrations of a multidimensional, non-contact-length metrology system design based on high resolution (millimeter to sub-100 micron) frequency modulated continuous wave (FMCW) ladar and trilateration based on length measurements from multiple, optical fiber-connected transmitters. With an accurate FMCW ladar source, the trilateration-based design provides 3D resolution inherently independent of standoff range and allows self-calibration to provide flexible setup of a field system. A proof-of-concept experimental demonstration was performed using a highly stabilized, 2 THz bandwidth chirped laser source, two emitters, and one scanning emitter/receiver providing 1D surface profiles (2D metrology) of diffuse targets. The measured coordinate precision of <200 microns was determined to be limited by laser speckle issues caused by diffuse scattering of the targets.

Precision and accuracy testing of FMCW ladar-based length metrology.

The calibration and traceability of high-resolution frequency modulated continuous wave (FMCW) ladar sources is a requirement for their use in length and volume metrology. We report the calibration of FMCW ladar length measurement systems by use of spectroscopy of molecular frequency references HCN (C-band) or CO (L-band) to calibrate the chirp rate of the FMCW sources. Propagating the stated uncertainties from the molecular calibrations provided by NIST and measurement errors provide an estimated uncertainty of a few ppm for the FMCW system. As a test of this calibration, a displacement measurement interferometer with a laser wavelength close to that of our FMCW system was built to make comparisons of the relative precision and accuracy. The comparisons performed show <10 ppm agreement, which was within the combined estimated uncertainties of the FMCW system and interferometer.

[1,1-(η(2)-dppe)-3-(NC5H5)-closo-1,2-RhSB9H8]: conformational lability and reactivity with H2 upon protonation.

Metallaheteroboranes are versatile compounds that can be conveniently modified and eventually tailored by ligand modification at either the metal centre or the boron vertices. Recently, we have discovered that protonation of some rhodathiaboranes affords cationic clusters with interesting reaction chemistry. In order to tune the reactivity of some of these polyhedral boron-based compounds, we have prepared air-stable orange [1,1-(η(2)-dppe)-3-(NC5H5)-closo-1,2-RhSB9H8] (2) by the treatment of the known hydridorhodathiaborane [8,8,8-(H)(PPh3)2-9-(NC5H5)-nido-8,7-RhSB9H9] (1) with dppe. The new 11-vertex rhodathiaborane, 2, reacts readily with triflic acid (TfOH) in CH2Cl2 to give orange cationic [8,8-(η(2)-dppe)-9-(NC5H5)-nido-8,7-RhSB9H9](+) (3). VT NMR experiments have allowed the characterization of a structural closo ↔ nido tautomerism, which involves hapticity changes in the ligation of the {SB9H9-(NC5H5)} moiety to the {Rh(dppe)} fragment, with the proton moving between the Rh(1)-B(3) and the B(9)-B(10) edges of the closo- and nido-isomers, respectively. The proton enhances the stereochemical non-rigidity and Lewis acidity of 3 versus the neutral 2. This modification of the chemical and structural basis permits the efficient heterolytic splitting of the H-H bond, leading to the formation of new hydridorhodathiaborane isomers [8,8,8-(H)(η(2)-dppe)-µ-8,9-(H)-9-(NC5H5)-nido-8,7-RhSB9H10](+) ()4 that are in equilibrium with the reactants, H2 and 3.

[cycEVA study: case control study measuring influenza vaccine effectiveness in Spain, 2008-2013]. / Estudio cycEVA: casos y controles para la estimación de la efectividad de la vacuna antigripal en España, 2008-2013.

BACKGROUND: In Spain, influenza vaccine effectiveness (EV) is estimated since 2008-09 season through the cycEVA case-control study, the Spanish component of the European I-MOVE (Monitoring Influenza Vaccine Effectiveness in the EU/EEA) network. We aimed at describing cycEVA performance in its five consolidated editions 2008/09 -; 2012/13. METHODS: During the study period the following indicators were analysed: 1) the participation of sentinel general practitioners and pediatricians (MP), 2) the population studied and the study period, 3) the data quality and 4) the dissemination of the cycEVA results. Trend analysis of the indicators was done using the Cochran-Armitage test to compute the Annual Percentage Change (PCA). RESULTS: The number of participating MP increased from 164 in 2008-09 to 246 in the following editions. The percentage of MP recruiting at least one patient increased significantly annually (PCA = 15.33%). The percentage of recruited patients included into the analysis increased (PCA=5.91%) from 77% in 2008-09 to more than 95% in the following editions. The percentage of cycEVA patients contributing to the I-MOVE study ranged between 23% and 30% in the pilot and 2011-12 editions respectively.. Final results were disseminated in quartile 2 peer-reviewed journals and 2010-11 and 2011-12 preliminary EV estimates were published in quartile 1 journals. cycEVA publications received 97 citations. CONCLUSION: cycEVA study achieved more quality information, timely EV estimates and a higher impact of the results.

Estudio cycEVA: caos y controles para la estimación de la efectividad de la vacuna antigripal en España, 2008-2013 / cycEVA study: case control study Measuring influenza vaccine effectiveness in Spain, 2008-2013

Fundamentos: Desde 2008-09 la efectividad de la vacuna (EV) antigripal en España se estima con el estudio de casos y controles para la evaluación de la EV antigripal (cycEVA), componente español de la red europea (Influenza- Monitoring Vaccine Effectiveness (I-MOVE). El objetivo es describir la evolución del estudio cycEVAdurante las cinco temporadas del período 2008/09-2012/13. Métodos: Se analizaron los siguientes indicadores: 1) participación de los médicos/pediatras centinela (MP); 2) población y periodo de estudio, 3) calidad de los datos y 4) difusión de los resultados mediantes publicaciones. Se calculó el porcentaje anual de cambio constante de los indicadores analizándose su tendencia mediante el test de Cochran-Armitage. Resultados: El número de MP participantes aumentó de 164 en 2008-09 hasta 246 en ediciones posteriores. El porcentaje de médicos que reclutaron al menos un paciente experimentó un cambio anual significativo (PCA) del 15,33%. El porcentaje de pacientes reclutados incluidos en el análisis aumentó del 77% en 2008-09 a más del 95% en las siguientes ediciones (PCA=5,91%). El porcentaje de casos y controles participantes en cycEVA sobre el total de pacientes que contribuyeron al estudio europeo I-MOVE osciló entre el 23% en la edición piloto y 30% en la temporada 2011-12. Los resultados finales se difundieron en revistas científicas con un factor de impacto situado en el cuartil 2 y en 2010-11 y 2011-12 se publicaron resultados preliminares en revistas con un factor de impacto situado en el cuartil 1 (97 citas). Conclusiones: La experiencia del estudio cycEVA se reflejó en una mejora en la oportunidad e impacto de sus resultados, cruciales para orientar las recomendaciones anuales de vacunación antigripal (AU)

Background: In Spain, influenza vaccine effectiveness (EV) is estimated since 2008-09 season through the cycEVAcase-control study, the Spanish component of the European I-MOVE (Monitoring Influenza Vaccine Effectiveness in the EU/EEA) network.We aimed at describing cycEVAperformance in its five consolidated editions 2008/09 - 2012/13. Methods: During the study period the following indicators were analysed: 1) the participation of sentinel general practitioners and pediatricians (MP), 2) the population studied and the study period, 3) the data quality and 4) the dissemination of the cycEVA results. Trend analysis of the indicators was done using the Cochran-Armitage test to compute theAnnual Percentage Change (PCA). Results: The number of participatingMP increased from 164 in 2008-09 to 246 in the following editions. The percentage of MP recruiting at least one patient increased significantly annually (PCA = 15.33%). The percentage of recruited patients included into the analysis increased (PCA=5.91%) from 77% in 2008-09 to more than 95% in the following editions. The percentage of cycEVA patients contributing to the I-MOVE study ranged between 23% and 30% in the pilot and 2011-12 editions respectively.. Final results were disseminated in quartile 2 peer-reviewed journals and 2010-11 and 2011-12 preliminary EV estimates were published in quartile 1 journals. cycEVA publications received 97 citations. Conclusion: cycEVA study achieved more quality information, timely EV estimates and a higher impact of the results (AU)

GluK1 antagonists from 6-(carboxy)phenyl decahydroisoquinoline derivatives. SAR and evaluation of a prodrug strategy for oral efficacy in pain models.

The synthesis and structure-activity relationship of decahydroisoquinoline derivatives with various benzoic acid substitutions as GluK1 antagonists are described. Potent and selective antagonists were selected for a tailored prodrug approach in order to facilitate the evaluation of the new compounds in pain models after oral administration. Several diester prodrugs allowed for acceptable amino acid exposure and moderate efficacy in vivo.

GluK1 antagonists from 6-(tetrazolyl)phenyl decahydroisoquinoline derivatives: in vitro profile and in vivo analgesic efficacy.

We have explored the decahydroisoquinoline scaffold, bearing a phenyl tetrazole, as GluK1 antagonists with potential as oral analgesics. We have established the optimal linker atom between decahydroisoquinoline and phenyl rings and demonstrated an improvement of both the affinity for the GluK1 receptor and the selectivity against the related GluA2 receptor with proper phenyl substitution. In this Letter, we also disclose in vivo data that led to the discovery of LY545694·HCl, a compound with oral efficacy in two persistent pain models.

Design and synthesis of new tetrahydroquinolines derivatives as CETP inhibitors.

This letter describes the discovery and SAR optimization of tetrazoyl tetrahydroquinoline derivatives as potent CETP inhibitors. Compound 6m exhibited robust HDL-c increase in hCETP/hApoA1 double transgenic model and favorable pharmacokinetic properties.