La adaptación de España al modelo europeo de flexiseguridad en el empleo = Adaptation of Spain to the european model of the flexicurity in employment.

Los tradicionales modelos de gestión laboral en España se han tornado obsoletos ante la aparición de mercados de bienes y servicios cada vez más competitivos y que exigen de las empresas una mayor capacidad de adaptación a los nuevos contextos socioeconómicos. Desde instituciones de la Unión Europea se apuesta por una modernización de los mercados laborales de los estados miembros a través del denominado modelo de flexiseguridad en el empleo, si bien aún no se tiene una definición clara y concisa de este término. Dinamarca es el país presentado como modelo de flexiseguridad bien aplicada. La adaptación de la normativa laboral de cada Estado miembro a la flexiseguridad exige medidas distintas en cada país, debido a que las premisas de partida no son las mismas. En España, la reforma laboral era urgente al situarse con una de las tasas de paro más elevadas de la UE. Una pieza clave en el proceso de reformas lo constituye la Ley 3/2012, de 6 de julio, de medidas urgentes para la reforma del mercado laboral, cuyo principal objetivo era y sigue siendo flexibilizar el mercado de trabajo español para favorecer la creación de empleo y la contratación estable. No obstante, considerando la evolución de los datos de empleo desde la aprobación y entrada en vigor de la reforma laboral, ésta no ha resultado tan efectiva como cabía espera

Assessing the Impact of SARS-CoV-2 Lineages and Mutations on Patient Survival

Objectives: More than two years into the COVID-19 pandemic, SARS-CoV-2 still remains a global public health problem. Successive waves of infection have produced new SARS-CoV-2 variants with new mutations for which the impact on COVID-19 severity and patient survival is uncertain. Methods: A total of 764 SARS-CoV-2 genomes, sequenced from COVID-19 patients, hospitalized from 19th February 2020 to 30 April 2021, along with their clinical data, were used for survival analysis. Results: A significant association of B.1.1.7, the alpha lineage, with patient mortality (log hazard ratio (LHR) = 0.51, C.I. = [0.14,0.88]) was found upon adjustment by all the covariates known to affect COVID-19 prognosis. Moreover, survival analysis of mutations in the SARS-CoV-2 genome revealed 27 of them were significantly associated with higher mortality of patients. Most of these mutations were located in the genes coding for the S, ORF8, and N proteins. Conclusions: This study illustrates how a combination of genomic and clinical data can provide solid evidence for the impact of viral lineage on patient survival.Ministry of Science and Innovation, Spain (MICINN) Spanish Government PID2020117979RB-I00Instituto de Salud Carlos III European Commission European Commission IMP/00019Junta de Andalucia COVID-0012-2020 PS-2020-342European Social Fund (ESF) 871075Carlos Loucera PAIDI2020-DOC_0035

Effectiveness and tolerability of dolutegravir/lamivudine for the treatment of HIV-1 infection in clinical practice

Objectives: To assess the effectiveness and tolerability of dolutegravir (DTG)/lamivudine (3TC) among treatment-naive and virologically suppressed treatment-experienced individuals in the multicentre cohort of the Spanish HIV/AIDS Research Network (CoRIS) during the years 2018-2021. Methods: We used multivariable regression models to compare viral suppression (VS) [HIV RNA viral load (VL) <50 copies/mL] and the change in CD4 cell counts at 24 and 48 (±12) weeks after initiation with dolutegravir/lamivudine or other first-line ART regimens. Results: We included 2160 treatment-naive subjects, among whom 401 (18.6%) started with dolutegravir/lamivudine. The remaining subjects started bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide (TAF) (n = 949, 43.9%), DTG + FTC/tenofovir disoproxil fumarate (TDF) (n = 282, 13.1%), DTG/3TC/abacavir (ABC) (n = 255, 11.8%), darunavir (DRV)/cobicistat(COBI)/FTC/TAF (n = 147, 6.8%) and elvitegravir (EVG)/COBI/FTC/TAF (n = 126, 5.8%). At 24 and 48 weeks after starting dolutegravir/lamivudine, 91.4% and 93.8% of the subjects, respectively, achieved VS. The probability of achieving VS with dolutegravir/lamivudine was not significantly different compared with any other regimen at 24 or 48 weeks, with the exception of a lower chance of achieving VS at 24 weeks for DRV/COBI/FTC/TAF (adjusted OR: 0.47; 95% CI: 0.30-0.74) compared with dolutegravir/lamivudine.For the analysis of treatment-experienced virally suppressed subjects we included 1456 individuals who switched to dolutegravir/lamivudine, among whom 97.4% and 95.5% maintained VS at 24 and 48 weeks, respectively. During the first 48 weeks after dolutegravir/lamivudine initiation, 1.0% of treatment-naive and 1.5% of treatment-experienced subjects discontinued dolutegravir/lamivudine due to an adverse event. Conclusions: In this large multicentre cohort, effectiveness and tolerability of dolutegravir/lamivudine were high among treatment-naive and treatment-experienced subjects.This work was supported by (i) the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en Sida (RD06/006, RD12/0017/0018 and RD16/0002/0006) as part of the Plan Nacional I + D + i and co-financed by Instituto de Salud Carlos III-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), and (ii) ViiV Healthcare. The funders did not play any decision making role in the design, execution, analysis or reporting of the research.S

Integrated GWAS and Gene Expression Suggest ORM1 as a Potential Regulator of Plasma Levels of Cell-Free DNA and Thrombosis Risk

Plasma cell-free DNA (cfDNA) is a surrogate marker of neutrophil extracellular traps (NETs) that contribute to immunothrombosis. There is growing interest about the mechanisms underlying NET formation and elevated cfDNA, but little is known about the factors involved. We aimed to identify genes involved in the regulation of cfDNA levels using data from the Genetic Analysis of Idiopathic Thrombophilia (GAIT-2) Project. Imputed genotypes, whole blood RNA-Seq data, and plasma cfDNA quantification were available for 935 of the GAIT-2 participants from 35 families with idiopathic thrombophilia. We performed heritability and GWAS analysis for cfDNA. The heritability of cfDNA was 0.26 ( p  = 3.7 × 10 (−6) ), while the GWAS identified a significant association (rs1687391, p  = 3.55 × 10 (−10) ) near the ORM1 gene, on chromosome 9. An eQTL (expression quantitative trait loci) analysis revealed a significant association between the lead GWAS variant and the expression of ORM1 in whole blood ( p  = 6.14 × 10 (−9) ). Additionally, ORM1 expression correlated with levels of cfDNA ( p  = 4.38 × 10 (−4) ). Finally, genetic correlation analysis between cfDNA and thrombosis identified a suggestive association ( ρ (g)  = 0.43, p  = 0.089). All in all, we show evidence of the role of ORM1 in regulating cfDNA levels in plasma, which might contribute to the susceptibility to thrombosis through mechanisms of immunothrombosis

SARS-CoV-2 genome sequencing in Andalusia, methodology and study of variants

La incorporación de las técnicas de secuenciación genómica mediante secuenciación de nueva generación ha revolucionado la microbiología clínica, innovando y mejorando el diagnóstico clínico de las enfermedades infecciosas. Hoy en día, la secuenciación de genoma completo en enfermedades infecciosas tiene multitud de aplicaciones en virología, bacteriología, resistencia antibiótica, epidemiología y salud pública. Con la aparición del SARS-CoV-2, se ha visto subrayada la importancia del análisis y estudio de las secuencias genéticas. Desde la identificación inicial del SARS-CoV-2, hasta la fecha, se han compartido, a nivel mundial, más de 414.575 secuencias genómicas completas a través de bases de datos de acceso público. La capacidad de monitorizar la evolución viral casi en tiempo real tiene un impacto directo en la respuesta de salud pública a la pandemia de COVID-19. En este trabajo se presenta la importancia de la secuenciación genómica en microbiología, enfermedades infecciosas, epidemiología y salud pública, y se describe cómo se ha implementado la secuenciación de SARS-CoV-2 en Andalucía, y cuales son los principales resultados hasta la fecha.The incorporation of genomic sequencing techniques through next-generation sequencing has revolutionized clinical microbiology, innovating and improving the clinical diagnosis of infectious diseases. Today, whole genome sequencing in infectious diseases has many applications in virology, bacteriology, antibiotic resistance, epidemiology, and public health. With the appearance of SARS-CoV-2, the importance of the analysis and study of genetic sequences has been underlined. Since the initial identification of SARS-CoV-2, to date, more than 414,575 complete genomic sequences have been shared worldwide through public access databases. The ability to monitor viral evolution in near real time has a direct impact on the public health response to the COVID-19 pandemic. This paper presents the importance of genomic sequencing in microbiology, infectious diseases, epidemiology and public health, and describes how SARS-CoV-2 sequencing has been implemented in Andalusia, and what the main results are to date

Desarrollo de un laboratorio abierto de enjambres de robots autónomos de limpieza

[ES] En el corto plazo, la industria del robot autónomo y de los drones será un factor de desarrollo importante. Tanto la fabricación de los propios dispositivos, como del desarrollo del software que los hace funcionar serán actividades empresariales de importancia en el sector TIC. No obstante, el futuro de los robots de trabajo autónomo es colaborar unos con otros y con el entorno que los rodea (adaptación al contexto). Para ello, deben de ser capaces de interactuar con otros equipos mediante protocolos de comunicación y sistemas de razonamiento. Por ello, en este trabajo se presenta una experiencia encaminada a la obtención de un sistema de trabajo colaborativo para que un grupo/enjambre de robots autónomos de limpieza puedan trabajar de forma conjunta. La experiencia se basa en un laboratorio abierto que permite a los alumnos proponer y realizar sus propios desarrollos. En el trabajo se presentan tanto los aspectos metodológicos de la experiencia, como los avances que se han conseguido realizar hasta la fecha.Este trabajo ha sido parcialmente financiado por el Instituto Universitario de Tecnología Industrial de Asturias (IUTA) a través del proyecto "Desarrollo de un sistema de trabajo colaborativo de robots autónomos de limpieza”.Pozueco, L.; Sánchez, JA.; G. Tuero, A.; Melendi, D.; García Fernández, R.; G. Pañeda, X.; Asenjo, N.... (2018). Desarrollo de un laboratorio abierto de enjambres de robots autónomos de limpieza. En XIII Jornadas de Ingeniería telemática (JITEL 2017). Libro de actas. Editorial Universitat Politècnica de València. 356-362. https://doi.org/10.4995/JITEL2017.2017.6579OCS35636

Transmitted drug resistance to antiretroviral drugs in Spain during the period 2019–2021

To evaluate the prevalence of transmitted drug resistance (TDR) to nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTI, NNRTI), protease inhibitors (PI), and integrase strand transfer inhibitors (INSTI) in Spain during the period 2019-2021, as well as to evaluate transmitted clinically relevant resistance (TCRR) to antiretroviral drugs. Reverse transcriptase (RT), protease (Pro), and Integrase (IN) sequences from 1824 PLWH (people living with HIV) were studied. To evaluate TDR we investigated the prevalence of surveillance drug resistance mutations (SDRM). To evaluate TCRR (any resistance level >= 3), and for HIV subtyping we used the Stanford v.9.4.1 HIVDB Algorithm and an in-depth phylogenetic analysis. The prevalence of NRTI SDRMs was 3.8% (95% CI, 2.8%-4.6%), 6.1% (95% CI, 5.0%-7.3%) for NNRTI, 0.9% (95% CI, 0.5%-1.4%) for PI, and 0.2% (95% CI, 0.0%-0.9%) for INSTI. The prevalence of TCRR to NRTI was 2.1% (95% CI, 1.5%-2.9%), 11.8% for NNRTI, (95% CI, 10.3%-13.5%), 0.2% (95% CI, 0.1%-0.6%) for PI, and 2.5% (95% CI, 1.5%-4.1%) for INSTI. Most of the patients were infected by subtype B (79.8%), while the majority of non-Bs were CRF02_AG (n = 109, 6%). The prevalence of INSTI and PI resistance in Spain during the period 2019-2021 is low, while NRTI resistance is moderate, and NNRTI resistance is the highest. Our results support the use of integrase inhibitors as first-line treatment in Spain. Our findings highlight the importance of ongoing surveillance of TDR to antiretroviral drugs in PLWH particularly with regard to first-line antiretroviral therapy

Molecular and phylogenetic characterization of the monkeypox outbreak in the South of Spain

Until the May 2022 Monkeypox outbreak, which spread rapidly to many non-endemic countries, the virus was considered a viral zoonosis limited to some African countries. The Andalusian circuit of genomic surveillance was rapidly applied to characterize the Monkeypox outbreak in the South of Spain. Whole genome sequencing was used to obtain the genomic profiles of samples collected across the south of Spain, representative of all the provinces of Andalusia. Phylogenetic analysis was used to study the relationship of the isolates and the available sequences of the 2022 outbreak. Whole genome sequencing of a total of 160 monkeypox viruses from the different provinces that reported cases were obtained. Interestingly, we report the sequences of monkeypox viruses obtained from two patients who died. While one of the isolates bore no noteworthy mutations that explain a potential heightened virulence, in another patient the second consecutive genome sequence, performed after the administration of tecovirimat, uncovered a mutation within the A0A7H0DN30 gene, known to be a prime target for tecovirimat in its Vaccinia counterpart. In general, a low number of mutations were observed in the sequences reported, which were very similar to the reference of the 2022 outbreak (OX044336), as expected from a DNA virus. The samples likely correspond to several introductions of the circulating monkeypox viruses from the last outbreak. The virus sequenced from one of the two patients that died presented a mutation in a gene that bears potential connections to drug resistance. This mutation was absent in the initial sequencing prior to treatmentThis work was supported by Spanish Ministry of Science and Innovation (grants PID2020- 117979RB-I00 and FJC2021-046546-I), the Instituto de Salud Carlos III (ISCIII), co-funded with European Regional Development Funds (ERDF) (grant IMP/00019), it has also been funded by Consejería de Salud y Consumo, Junta de Andalucía (grants COVID-0012-2020), and by grant ELIXIR-CONVERGE - Connect and align ELIXIR Nodes to deliver sustainable FAIR lifescience data management services (AMD-871075-16), funded by EU – H2020.N

Detection of High Level of Co-Infection and the Emergence of Novel SARS CoV-2 Delta-Omicron and Omicron-Omicron Recombinants in the Epidemiological Surveillance of Andalusia

Recombination is an evolutionary strategy to quickly acquire new viral properties inherited from the parental lineages. The systematic survey of the SARS-CoV-2 genome sequences of the Andalusian genomic surveillance strategy has allowed the detection of an unexpectedly high number of co-infections, which constitute the ideal scenario for the emergence of new recombinants. Whole genome sequence of SARS-CoV-2 has been carried out as part of the genomic surveillance programme. Sample sources included the main hospitals in the Andalusia region. In addition to the increase of co-infections and known recombinants, three novel SARS-CoV-2 delta-omicron and omicron-omicron recombinant variants with two break points have been detected. Our observations document an epidemiological scenario in which co-infection and recombination are detected more frequently. Finally, we describe a family case in which co-infection is followed by the detection of a recombinant made from the two co-infecting variants. This increased number of recombinants raises the risk of emergence of recombinant variants with increased transmissibility and pathogenicity.This research was funded by Spanish Ministry of Science and Innovation (grant PID2020-117979RB-I00), the Instituto de Salud Carlos III (ISCIII), co-funded with European Regional Development Funds (ERDF) (grant IMP/00019), and has also been funded by Consejería de Salud y Familias, Junta de Andalucía (grants COVID-0012-2020, PS-2020-342 and IE19_259 FPS).Peer reviewe