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Biochar is a carbon-rich material that can be produced from waste biomass, making it a sustainable alternative to activated carbon. Biochar production is a carbon capture and storage strategy, and its physicochemical characteristics make it a useful additive for many processes, including the biological treatment of organic waste. Particularly, biochar has a high adsorbent capacity due to its high porosity, surface area and functional groups, which makes this material especially attractive in technologies with the presence of known inhibitors or that imply the emission of polluting compounds. In anaerobic digestion, its application improves the stability of the system against inhibition, increases the efficiency of the process, and allows the purification of biogas in situ. In composting, it reduces greenhouse gas and odor emissions and improves the quality of the compost obtained, increasing the nutrient content, immobilizing heavy metals, and reducing the presence of pathogenic microorganisms. Even so, the use of biochar in the biological treatment of organic waste is still an incipient field that requires research and consensus on key aspects such as the optimal dose of biochar, the transformation of the organic material over time, and its subsequent application as an amendment for the improvement of agricultural soils.

Background and Aims: Opioid-free anesthesia (OFA) provides adequate analgesia minimizing opioids. OFA has not been evaluated in laparoscopic radical prostatectomy (LRP). Our aim was to evaluate OFA feasibility and its effectiveness in LRP. Material and Methods: A quasi-experimental retrospective study of 55 adult patients undergoing LRP was performed from September 2020 until December 20223. Predefined protocols for either opioid-based anesthesia (OBA; with continuous remifentanil infusion) or OFA (continuous lidocaine, dexmedetomidine, and ketamine infusion) were followed. In both groups, wound infiltration was performed before skin incision. Primary outcome was postoperative pain management (numerical rating scale [NRS]) in the first 24 postoperative hours. Secondary outcomes were opioid consumption, start to sitting and ambulation, postoperative complications, and length of hospital stay. Results: OFA protocol patients had better median pain scores during movement at 1, 18 and 24 h, that is, 1 (interquartile range [IQR] 0–3) versus 2.5 (IQR 0–4), P = 0.047; 0 (IQR 0–1) versus 1 (IQR 0–2), P = 0.017; and 0 (IQR 0–0.25) versus 1 (IQR 0–2), P = 0.013, respectively. At 6 and 12 h, there were no statistically significant differences, that is, 0.5 (IQR 0–2) versus 1 (IQR 0–2), P = 0.908 and 1 (IQR 0–2) versus 0.5 (IQR 0–2), P = 0.929, respectively. Lower morphine requirements were recorded in the first 18 and 24 postoperative hours, that is, 0 (IQR 0–0) versus 1 (IQR 0–2.75) mg, P = 0.028 and 0 (IQR 0–2) versus 1.5 (IQR 0–3) mg, P = 0.012, respectively. Start to sitting and ambulation occurred earlier in the OFA group (P = 0.030 and P = 0.002, respectively). Linear regression showed that ambulation was independently associated with the analgesic technique (P = 0.034). Only one patient had postoperative nausea and vomiting (PONV) and belonged to the OBA group. There was no difference in total complications or the length of stay. Conclusion: In this study, OFA strategy was found to be safe, feasible, and provided adequate analgesia, minimizing the use of postoperative opioids, and was independently associated with earlier ambulation.

Background: Lung cancer remains the leading cause of cancer-related mortality worldwide with non-small cell lung cancer (NSCLC) accounting for the majority of cases. The stage of detection significantly influences survival rates with early-stage diagnosis offering the best prognosis. This study investigates the prognostic impact of the omega-6/omega-3 ratio and tumor infiltration by CD8+ lymphocytes and CD68+ macrophages on overall survival (OS) and disease-free survival (DFS) in NSCLC patients undergoing pulmonary resection. Methods: We conducted a retrospective analysis of 53 patients with early-stage NSCLC who underwent pulmonary resection between September 2017 and January 2020. The omega-6/omega-3 ratio was quantified using gas chromatography and spectrometry. Tumor infiltration by CD8 and CD68 was assessed through immunohistochemistry. Survival outcomes were evaluated using Kaplan-Meier and Cox regression analyses. Results: An increased omega-6/omega-3 ratio and higher CD68+ macrophage infiltration were associated with a trend towards worse OS and DFS in NSCLC patients, though these results did not reach statistical significance. CD8+ T-cell infiltration was associated with improved survival outcomes, confirming its role as a favorable prognostic marker. Comparative analysis with existing datasets revealed similar demographic and clinical characteristics, reinforcing the generalizability of our findings. Conclusions: The omega-6/omega-3 ratio and CD68+ macrophage infiltration serve as important factors potentially influencing prognosis in NSCLC patients undergoing pulmonary resection. These findings highlight the need for further research to refine the prognostic utility of these biomarkers and to explore therapeutic strategies targeting inflammation and immune cell infiltration.

Abstract Actin dynamics control early T-cell receptor (TCR) signalling during T-cell activation. However, the precise regulation of initial actin rearrangements is not completely understood. Here, we have investigated the regulatory role of the phosphatase Slingshot-1 (SSH1) in this process. Our data show that SSH1 rapidly polarises to nascent cognate synaptic contacts and later relocalises to peripheral F-actin networks organised at the mature immunological synapse. Knockdown of SSH1 expression by CRISPR/Cas9-mediated genome editing or small interfering RNA reveal a regulatory role for SSH1 in CD3ε conformational change, allowing Nck binding and proper downstream signalling and immunological synapse organisation. TCR triggering induces SSH1-mediated activation of actin dynamics through a mechanism mediated by Limk-1 inactivation. These data suggest that during early TCR activation, SSH1 is required for rapid F-actin rearrangements that mediate initial conformational changes of the TCR, integrin organisation and proximal signalling events for proper synapse organisation. Therefore, the SSH1 and Limk-1 axis is a key regulatory element for full T cell activation.

Resumen: La Sociedad Española de Neumología y Cirugía Torácica (SEPAR) ha celebrado en Valencia su 57° Congreso entre los días 6 y 8 de junio de 2024. El Congreso SEPAR es la reunión de referencia y punto de encuentro de toda la comunidad científica respiratoria, que permite conocer los principales avances científicos en esta área y propicia el entorno idóneo para crear lazos y afianzar vínculos. Este año, bajo el lema «Salud Respiratoria para todos», el Congreso SEPAR incidió en la importancia de concienciar a la población general sobre la importancia de cuidar y proteger nuestro sistema respiratorio. En esta revisión, ofrecemos un resumen de algunos de los aspectos más destacables tratados en seis áreas de interés seleccionadas: enfermedad pulmonar obstructiva crónica (EPOC), asma, enfermedades pulmonares intersticiales difusas (EPID), circulación pulmonar, sueño - ventilación y fisioterapia respiratoria. Abstract: The Spanish Society of Pneumology and Thoracic Surgery (SEPAR) has held its 57th Congress in Valencia from 6 to 8 of June 2024. The SEPAR Congress is the leading meeting for the entire respiratory scientific community, which allows learning about the main scientific advances in this area and provides the ideal situation to create and strengthen ties. This year, under the title “Respiratory Health for everybody”, the SEPAR Congress stressed the importance of raising awareness about the importance of caring for and protecting our respiratory system. In this review, we offer a summary of some notable issues addressed in six selected areas of interest: chronic obstructive pulmonary disease (COPD), asthma, interstitial lung diseases (ILDs), pulmonary vascular diseases, sleep and breathing disorders and respiratory physiotherapy.

Summary: Phytohormone abscisic acid (ABA) regulates key plant development and environmental stress responses. The ubiquitin-proteasome system tightly controls ABA signaling. CULLIN4-RING (CRL4) E3 ubiquitin ligases use the substrate receptor module CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP10)-DDB1-DET1-DDA1 (CDDD) to target Arabidopsis ABA receptor PYL8, acting as negative regulators of ABA responses. Conversely, ABA treatment attenuates PYL8 receptor degradation, although the molecular mechanism remained elusive. Here, we show that ABA promotes the disruption of CRL4-CDDD complexes, leading to PYL8 stabilization. ABA-mediated CRL4-CDDD dissociation likely involves an altered association between DDA1-containing complexes and the COP9 signalosome (CSN), a master regulator of the assembly of cullin-based E3 ligases, including CRL4-CDDD. Indeed, treatment with CSN inhibitor CSN5i-3 suppresses the ABA effect on CRL4-CDDD assembly. Our findings indicate that ABA stabilizes PYL8 by altering the dynamics of the CRL4-CDDD-CSN complex association, showing a regulatory mechanism by which a plant hormone inhibits an E3 ubiquitin ligase to protect its own receptors from degradation.

El libro reseñado analiza el papel crucial de la memoria en la conceptualización del patrimonio cultural, destacando su relevancia en el actual contexto social y cultural. El autor, González-Varas, profundiza en cómo la memoria influye en la significación del patrimonio, especialmente en una época donde lo participativo y social cobra mayor importancia. Partiendo de un enfoque crítico y reflexivo, el texto explora la interacción entre lo histórico y lo cultural, el impacto del holocausto en la memoria colectiva, y la influencia del arte en la conservación patrimonial. La memoria es presentada como un concepto dinámico y selectivo que filtra nuestra comprensión del pasado, abordando su interpretación como un acto creativo y ficcional. Se destaca la necesidad de construir puentes entre la ciencia y lo social para lograr una comprensión más profunda del patrimonio, abordando la ciencia como un proceso proyectivo que busca la verdad. El texto también introduce la noción de la ficción en la interpretación patrimonial, utilizando la hermenéutica para entender cómo la memoria, el tiempo y la autenticidad pueden redefinir el escenario patrimonial contemporáneo.

A partir del análisis diacrónico de las representaciones gráficas de la ciudad romana de Itálica, el artículo propone un procedimiento para la caracterización patrimonial de los paisajes culturales complementario a los ya ensayados desde los ámbitos académicos y administrativos. La relevancia de la dimensión paisajística de Itálica, tanto por razones de emplazamiento histórico y visibilidad, como por su potencialidad actual en la articulación espacial y cultural del área metropolitana de Sevilla, hacen de este caso de estudio un ejemplo paradigmático, evidenciando la aplicabilidad de esta metodología en el diseño y la planificación de las políticas culturales y de ordenación territorial. El ejercicio interpretativo realizado sobre una selección de imágenes muestra cómo se ha comprendido y comunicado el territorio de Itálica en cada etapa histórica -desde grabados a fotografías o collages- y permite comprobar cuáles son los atributos materiales e inmateriales que han perdurado en nuestro imaginario, participando en la construcción de la imagen simbólica de lo que hoy se reconoce como un paisaje cultural, más allá de la figura administrativa de protección y gestión.

En este trabajo se aborda la presencia del espacio (geográfico, ficcional y referencial) en la novela Caídos del cielo (1995) y en su posterior adaptación cinematográfica, La pistola de mi hermano (1997), ambas obras firmadas por Ray Loriga. El hecho de contar con la misma fuente creadora permite analizar de manera más precisa las especificidades de cada medio: literario y cinematográfico. En sendos casos se produce una “transposición espacial referencial”, término que proponemos para definir el proceso por el cual el espacio se construye a través de las referencias culturales. De este modo, se analiza la transposición de la cultura mítica norteamericana difundida a través del cine, la televisión y la música, principalmente, a los paisajes donde transcurre la historia, situados en territorio español, en un recorrido desde la urbe madrileña hasta el mar. El estudio centra su atención en las referencias culturales y territoriales que aparecen tanto en el lenguaje literario como en el cinematográfico, deteniéndose en los tres niveles de atribución de sentido al espacio del género road movie propuestos por Giampiero Frasca: la dimensión denotativa, la arquetípica y la simbólica. Esto permite concluir que, en la novela, la transposición se produce, en mayor medida, al utilizar referencias concretas (musicales, cinematográficas, literarias), mientras que en la película el estilo visual definido por el género tiene más peso a la hora de conformar el espacio referencial.

Introduction: Childhood excess weight is a growing public health problem. The aim of this study was to assess temporal trends in the prevalence of overweight, obesity and central obesity in schoolchildren aged 6–9 years in Spain between 2011 and 2019 based on demographic and socioeconomic characteristics. Methodology: The analysis included data from the 2011, 2015 and 2019 rounds of the cross-sectional observational and descriptive ALADINO study in schoolchildren of both sexes aged 6–9 years. We conducted a descriptive analysis of the trends in the prevalence of overweight and obesity (defined according to the criteria of the World Health Organization and the International Obesity Task Force) and of central obesity, in addition to associated demographic and socioeconomic variables. Results: Between 2011 and 2019, the prevalence of overweight (WHO criteria) decreased in boys aged 6, 7 and 8 years (by −5.4%, −5.7% and −5.3%, respectively) and boys whose parents had a higher educational attainment (by −5.3%). In relation to the socioeconomic level, overweight in boys declined at all income levels. However, between 2011 and 2019, both the prevalence of overweight in girls and the prevalence of obesity (applying the WHO and IOTF criteria) and the prevalence of central obesity in both sexes remained stable. Conclusions: The prevalence of overweight and the prevalence of obesity in schoolchildren aged 6–9 years in Spain remain high. Between 2011 and 2019, the prevalence of overweight in children aged 6–8 years and in children whose parents had university degrees decreased, whereas obesity in boys, overweight and obesity in girls and central obesity in both sexes remained stable. Resumen: Introducción: El exceso de peso infantil es un problema de salud pública creciente. El objetivo del trabajo es estudiar la evolución de la prevalencia de sobrepeso, obesidad y obesidad central en escolares de 6 a 9 años en España entre 2011 y 2019 según características demográficas y socioeconómicas. Metodología: Se incluyeron las rondas 2011, 2015 y 2019 del estudio observacional, descriptivo y transversal ALADINO en escolares de ambos sexos de 6 a 9 años. Se realizó un análisis descriptivo de la evolución de la prevalencia de sobrepeso y obesidad según los criterios de la Organización Mundial de la Salud (OMS) y la International Obesity Task Force (IOTF), así como obesidad central, y las variables demográficas y socioeconómicas asociadas. Resultados: Entre 2011 y 2019 se redujo la prevalencia de sobrepeso (critrerios OMS) en niños de 6, 7 y 8 años (−5,4, −5,7 y −5,3 puntos porcentuales respectivamente) y niños cuyos progenitores tenían estudios superiores (−5,3 puntos porcentuales). Por renta, el sobrepeso en niños se redujo en todos los niveles de ingresos. Sin embargo, entre 2011 y 2019, se mantuvieron estables tanto la prevalencia de sobrepeso en niñas como la prevalencia de obesidad según las referencias OMS e IOTF y la de obesidad central en ambos sexos. Conclusiones: Las prevalencias de sobrepeso y obesidad en escolares de 6 a 9 años en España siguen siendo altas. Entre 2011 y 2019 disminuyó la prevalencia de sobrepeso en niños de 6 a 8 años y aquellos cuyos progenitores tienen estudios universitarios, mientras que la obesidad en niños, el sobrepeso y la obesidad en niñas, y la obesidad central en ambos sexos han permanecido estables.

El artículo analiza la corrupción como un fenómeno complejo y con frecuencia ambiguo, relacionado con comportamientos y mentalidades individuales y colectivas, que son percibidos como ilegítimos o inmorales y, por lo tanto, desviados de normas establecidas. Más allá de un acercamiento reduccionista u objetivista a lugares comunes de la corrupción política, o a delitos tipificados por la ley, esta contribución pretende destacar la relevancia del análisis histórico del discurso en el estudio del tema. Este enfoque nos permite reconstruir contextos en los que se identifica la corrupción, así como analizar relatos, no siempre unánimes, sobre estas prácticas. El trabajo se adentra en una época lejana, pero a la vez cercana a nuestro tiempo, el último siglo la República romana. La evidencia nos permite evaluar críticamente aspectos fundamentales de la construcción retórica de la corrupción y de sus zonas grises, como la distinción, a menudo borrosa, entre regalo y soborno.

Abstract Background Epidermolysis bullosa (EB) comprises a group of rare types of genodermatoses characterized by extreme mucocutaneous fragility, leading to blistering and/or erosions, even with minimal trauma. Continuous care through wound management is an integral part of daily life for the families and individuals affected. The aim of this study was to assess the social reality and impacts on families of having minor members diagnosed with EB in Spain. Methods A qualitative methodology was employed, utilizing four focus groups entailing participation by 24 parents (19 mothers and five fathers) of minors diagnosed with EB in Spain. Results Negative impacts on the family nucleus were evident in four priority areas of analysis: sociorelational, economic‐labour, physical and psychoemotional, with significant differences observed based on the severity of the symptoms. Conclusion Impacts on the family nucleus are noticeable from birth, influencing all other daily life routines and complicating family planning and organization. There is an imperative need to enhance the availability of sociohealth resources and to adopt an interdisciplinary approach to address their biopsychosocial needs. Patient or Public Contribution The active participation of relatives of minors diagnosed with Epidermolysis Bullosa (EB) is invaluable to sociohealth professionals, legislators and researchers. A team member conducts their professional activities at DEBRA España (national patient association dedicated to enhancing the quality of life for individuals with EB and their families), actively engaging in all study phases.

The document of the International Theological Commission, “Synodality in the Life and Mission of the Church” (2018), sanctions an idea that has been gaining ground in recent decades: synodality is a structural dimension of the church. This essay assesses the biblical foundation that this document offers in terms of this constitutive rather than operational understanding of synodality. To fit all the theological pieces of the synodality puzzle together and give them biblical consistency, this article takes two steps. The first focuses on exploring the theological welding between the church understood from the Trinitarian Mystery (LG 1–8) and the church as the people of God (LG 9–17). Second, this propaedeutic operation builds a solid framework that allows us to justify why the ITC document brings up certain biblical quotations, to fit them into a coherent reflection and at the same time to present other passages that are absent in the document.

New information and communication technologies have a significant potential to increase the transparency of aquifer management and improve groundwater governance. This research experiments the introduction of a mobile application that allows users to transfer and share information about their groundwater extractions and receive agroclimatic information and groundwater data. It takes place in three different aquifers in Morocco, Portugal, and Spain, each with varied institutional frameworks. This research tests and evaluates the potential of enhanced information systems and citizen science applied to groundwater management and aims to identify some factors that facilitate or hinder their adoption and implementation. To do this, the researchers developed a 4-year plan based on surveys, semi-structured interviews, meetings, participatory workshops, and public round tables with local actors. The main lesson learned from the comparative analysis of these three experiences is that the use of enhanced information systems is more positively perceived, accepted, and adopted when an appropriate social and institutional framework exists and that the more consolidated this framework is, the easier they will be to implement and develop enhanced information systems.

Ante la escasez de estudios empíricos en relación con el componente crítico y su evaluación en el ámbito del aprendizaje de lenguas, este estudio examina el impacto de la autoevaluación en el desarrollo de la literacidad visual crítica (LVC) en el contexto de aprendizaje en línea del español como lengua adicional. La investigación se centra en una intervención didáctica que incorpora diversas herramientas para el fomento y la autoevaluación de la LVC y analiza los portafolios de aprendizaje de estudiantes de español de nivel B2 (según el MCER) como herramienta central para la práctica y autoevaluación de la LVC. Los resultados revelan que, al permitir a los estudiantes reflexionar sobre su desempeño en las prácticas de LVC, la autoevaluación no solo se convierte en un catalizador para la toma de conciencia y el progreso, sino que promueve procesos metarreflexivos y fortalece hábitos de aprendizaje continuo, proporcionando a los estudiantes las herramientas necesarias para monitorear su progreso. El estudio enfatiza la necesidad de la instrucción explícita sobre la criticidad y aboga por la integración de herramientas de evaluación formativa (autoevaluación, coevaluación) para cultivar una actitud crítica y reflexiva.

Presentación de la sección temática

Anaerobic digestion (AD) is a wide-spread strategy to manage organic waste and recover valuable products but faces some limitations that could be overcome with additives like biochar (BC). The production of BC defines its properties, which in turn determine its effect on AD performance and methane yield. In this study, three biochars (BC1, BC2 and BC3) were characterized using several techniques (SEM imaging, BET, GC, ICP and FTIR). The properties of BC were found to be defined both by the feedstock and the production process. The BC were then applied to the AD of the organic fraction of municipal solid waste (OFMSW) using three doses (1, 5% and 10% w/w TS). Compared to the control, there was an increase in methane production in BC3 at doses 1% and 5% (+15 and +30%, respectively) and a decrease in BC1 and BC2 at 1% (−33% and −19%, respectively). The decrease in biogas production was often paired with an increased methane content. A two-way ANOVA analysis showed that the interaction of biochar dose and type had a significant effect on methane yield, meaning that the effect of BC on AD cannot be predicted with the dose or the type alone. When a second substrate feeding was performed, no significant differences on methane production were observed among the experimental conditions. Key aspects to properly assess the economic viability of the process have been also discussed. Further experiments could help to fill knowledge gaps and clarify the roles of BC characteristics and dose on AD performance.

Atopic dermatitis is a cutaneous inflammatory disease characterized by intense pruritus, which is often underestimated despite its direct impact on patients’ health-related quality of life and the high burden it poses. The authors’ goal was to design a qualitative tool to guide patients and healthcare professionals in their assessment and interpretation of pruritus intensity using a numerical rating scale. The draft of this tool, henceforth “guideline”, was developed based on a systematic literature review and focus groups comprising patients and a scientific committee. This draft was validated with an independent group of patients and the final version was designed following their feedback. According to the results of the systematic review, pruritus impacts 6 health-related quality of life domains: sleep quality; emotional status; overall health-related quality of life; physical function; social/sexual activity; productivity, particularly affecting sleep quality and the emotional domain. Patients considered that physical function was the most strongly affected domain, followed by sleep quality and emotional well-being, establishing that a minimum pruritus intensity of 4 and 7 points impacts moderately and severely, respectively, on the different domains of patients’ health- related quality of life. The guideline may help patients and healthcare professionals to interpret and assess pruritus intensity using a numerical rating scale and to understand the impact of pruritus on patients’ health-related quality of life.

A medida que el régimen de Hitler penetraba en Alemania, el nacionalsocialismo se extendía también fuera de sus fronteras. El nazismo difundió sus ideales y organizaciones a casi todos los rincones del planeta, estableciéndose en lugares especialmente estratégicos como España. El archipiélago canario, convertido en un emplazamiento destacado en el Atlántico, recibió las huellas del nazismo desde muy temprano, a través de la actuación desplegada tanto por el Partido Nazi como por sus organizaciones económicas y socioculturales. El nacionalsocialismo penetró en la creciente colonia germana de Canarias y este fue especialmente activo durante la Segunda Guerra Mundial (1939-1945), cuando sus representantes y agentes movilizaron campañas políticas, propagandísticas y persuasorias, así como movimientos de inteligencia y actividades de vigilancia e intimidación. El principal objetivo de este artículo es analizar el establecimiento, la organización y la progresiva desintegración del nazismo en Canarias entre 1933 y 1945.

The cultural theory of heritage assets that was consolidated throughout the 20th century, and is still in force today, lies in the modulation of the concept of authenticity. It is a nomadic, controversial concept that has adapted to the spirit of the times. This review of the concept, drawing on international reference texts and charters in the field of heritage, allows us to specify a working process that facilitates its consideration in characterisation processes. To do so, case studies of significant cultural assets in terms of scale and complexity will be presented as resources. Through the implementation of the Theory of Value, the keys will be provided: criteria and methodology for intervening in heritage. This journey will be reflected more slowly in the study of the Palace of San Telmo (Seville, 17th–21st century). This is a building with a controversial material history, in which a series of attributions of value have been transmitted that correlate both with the theory of the conservation of cultural assets and with social appreciation and the criteria. This is the way to materially undertake a reflection on the authenticity of this heritage. This study provides the keys to intervening, conserving the values identified, and recognising authenticity as a reality that is constructed through the process and through the passage of time. A methodology that allows us to consider the capacity to continue and replace heritage as a project strategy in which what is yet to come can take place.

Abstract Background Vitamin C (vitC) enhances the activity of 2-oxoglutarate-dependent dioxygenases, including TET enzymes, which catalyse DNA demethylation, and Jumonji-domain histone demethylases. The epigenetic remodelling promoted by vitC improves the efficiency of induced pluripotent stem cell derivation, and is required to attain a ground-state of pluripotency in embryonic stem cells (ESCs) that closely mimics the inner cell mass of the early blastocyst. However, genome-wide DNA and histone demethylation can lead to upregulation of transposable elements (TEs), and it is not known how vitC addition in culture media affects TE expression in pluripotent stem cells. Results Here we show that vitC increases the expression of several TE families, including evolutionarily young LINE-1 (L1) elements, in mouse ESCs. We find that TET activity is dispensable for L1 upregulation, and that instead it occurs largely as a result of H3K9me3 loss mediated by KDM4A/C histone demethylases. Despite increased L1 levels, we did not detect increased somatic insertion rates in vitC-treated cells. Notably, treatment of human ESCs with vitC also increases L1 protein levels, albeit through a distinct, post-transcriptional mechanism. Conclusion VitC directly modulates the expression of mouse L1s and other TEs through epigenetic mechanisms, with potential for downstream effects related to the multiple emerging roles of L1s in cellular function.

Objectives: To evaluate the compassionate use of plitidepsin as an antiviral treatment in hospitalized immunocompromised adult patients with moderate-to-severe COVID-19. Design: Retrospective observational study of data —collected from January 01, 2021 to April 30, 2022— from 35 immunocompromised adult patients with COVID-19 non-eligible for other available antiviral treatments. Main outcome measures were time to respiratory recovery (SpFi ≥ 315); COVID-19-related 30-day-cumulative mortality after first plitidepsin infusion; and time to undetectable levels of viral RNA. Results: Thirty-three patients receiving a full course of plitidepsin (2.5 mg [n = 29] or 1.5 mg [n = 4]) were included. Most (69.7%) had a malignant hematologic disease and 27.3% had solid tumors. A total of 111 infusions were administered with lack of relevant safety events. Median time from plitidepsin initiation to SpFi ≥315 was 8 days (95% confidence interval [CI], 7-19). Median time to first negative reverse transcription-polymerase chain reaction for SARS-CoV-2 (cycle threshold >36) was 17 days (95% CI 13-25). Mortality rate was 16.3% (95% CI 3-37.3). Conclusion: These data support plitidepsin as a well-tolerated treatment that might have potential clinical and antiviral efficacy in COVID-19 immunocompromised patients.

The diagnosis of inflammatory bowel disease (IBD) in children and the need to distinguish between subtypes (Crohn’s disease (CD) and ulcerative colitis (UC)) requires lengthy investigative and invasive procedures. Non-invasive, rapid, and cost-effective tests to support these diagnoses are needed. Faecal volatile organic compounds (VOCs) are distinctive in IBD. VOC profiles can be rapidly determined using a gas chromatography–sensor device (OdoReader©). In an inception-cohort of children presenting with suspected IBD, we directly compared the diagnostic fidelity of faecal calprotectin (FCP, a non-specific protein marker of intestinal inflammation) with OdoReader© VOC profiles of children subsequently diagnosed with IBD with matched controls diagnosed with other gastrointestinal conditions. The OdoReader© was 82% (95% confidence interval 75–89%) sensitive and 71% (61–80%) specific but did not outperform FCP (sensitivity 93% (77–99%) and specificity 86% (67–96%); 250 µg/g FCP cut off) in the diagnosis of IBD from other gastrointestinal conditions when validated in a separate sample from the same cohort. However, unlike FCP and better than other similar technologies, the OdoReader© could distinguish paediatric CD from UC (up to 88% (82–93%) sensitivity and 80% (71–89%) specificity in the validation set) and justifies further validation in larger studies. A non-invasive test based on VOCs could help streamline and limit invasive investigations in children.

(1) Gender-based dating violence is common among adolescents. This violence has global repercussions and can have immediate and delayed consequences on health. Also, cases of dating violence and sexual abuse using technology are increasing. The aim of this research is to describe and understand the perceptions and experiences of Spanish university students aged 18 to 22, about gender-based dating violence and its perpetuation through social media. (2) A qualitative descriptive study was used, following the five consolidated criteria for reporting and publishing COREQ qualitative research. (3) The inductive analysis of the data obtained in the focus group session and the individual interviews of the twelve participants was organised into three major themes: the concept of gender violence that Spanish youth have, the education they have received on gender-based violence and whether they consider that social media are a way to exercise this type of violence. (4) Spanish youth have a broad vision of the attitudes and behaviours that make up gender-based dating violence in an affective relationship. The education received at home is of vital importance for young people, but not all receive it. Social media are frequent tools through which many young people perpetuate controlling partner violence and normalise aspects and situations of gender violence, making it necessary to stress them in prevention programs.

Autosomal dominant optic atrophy (ADOA) is a rare progressive disease mainly caused by mutations in OPA1, a nuclear gene encoding for a mitochondrial protein that plays an essential role in mitochondrial dynamics, cell survival, oxidative phosphorylation, and mtDNA maintenance. ADOA is characterized by the degeneration of retinal ganglion cells (RGCs). This causes visual loss, which can lead to legal blindness in many cases. Nowadays, there is no effective treatment for ADOA. In this article, we have established an isogenic human RGC model for ADOA using iPSC technology and the genome editing tool CRISPR/Cas9 from a previously generated iPSC line of an ADOA plus patient harboring the pathogenic variant NM_015560.3: c.1861C>T (p.Gln621Ter) in heterozygosis in OPA1. To this end, a protocol based on supplementing the iPSC culture media with several small molecules and defined factors trying to mimic embryonic development has been employed. Subsequently, the created model was validated, confirming the presence of a defect of intergenomic communication, impaired mitochondrial respiration, and an increase in apoptosis and ROS generation. Finally, we propose the analysis of OPA1 expression by qPCR as an easy read-out method to carry out future drug screening studies using the created RGC model. In summary, this model provides a useful platform for further investigation of the underlying pathophysiological mechanisms of ADOA plus and for testing compounds with potential pharmacological action.

Introduction: Childhood obesity is inversely associated with household socioeconomic status in high-income countries. Our aim was to explore the association between childhood weight status and household socioeconomic status in Spain in relation to family characteristics, perceptions and lifestyle habits and the school environment. Methods: We performed a descriptive analysis of child weight status according to family socioeconomic factors and mediating variables based on data from the ALADINO 2019 study in a sample of 16,665 schoolchildren representative of the population aged 6–9 years in Spain. Results: The prevalence of childhood obesity in households with low socioeconomic status (26.8% boys; 20.4% girls) was, in both sexes, twice as high as in those with higher socioeconomic status (12.1% boys; 8.7% girls). Unhealthy eating habits, sedentary lifestyles (mainly in girls) and the presence of screens in the bedroom (more prevalent in boys) were more frequent in school-aged children from low-income households. On the other hand, in the most disadvantaged households, a history of breastfeeding and physical activity (especially in girls) were less frequent. Similarly, schools attended by children from low-income households were less likely to have their own kitchens and indoor gymnasiums or offer sports activities. Conclusion: A lower household socioeconomic status was associated with poorer dietary and physical activity habits and certain characteristics of the family and school environments that mediate the inverse association between household socioeconomic status and the prevalence of childhood obesity. Girls were less physically active and reported more sedentary lifestyles, while boys had greater access to screens. Interventions to combat childhood obesity should address the identified inequalities. Resumen: Introducción: La obesidad infantil se asocia inversamente con el nivel socioeconómico familiar en países desarrollados. El objetivo es evaluar la asociación entre la situación ponderal infantil y el nivel socioeconómico familiar, según características familiares, percepciones, hábitos de vida y entorno escolar. Metodología: Análisis descriptivo de la situación ponderal infantil según factores socioeconómicos familiares y variables mediadoras en el estudio ALADINO 2019, en una muestra de 16.665 escolares representativa de la población escolar de 6 a 9 años en España. Resultados: La prevalencia de obesidad infantil en hogares de bajo nivel socioeconómico (26,8% niños; 20,4% niñas) era, en ambos sexos, el doble de la de los de mayor nivel (12,1% niños; 8,7% niñas). En escolares de familias de baja renta eran más frecuentes hábitos alimentarios poco saludables, el sedentarismo (principalmente en niñas) y la presencia de pantallas en la habitación (más en niños). Por el contrario, en hogares más desfavorecidos eran menos frecuentes el antecedente de lactancia materna y la práctica de actividad física (especialmente en niñas). La disponibilidad de cocina propia, actividades deportivas y gimnasio cubierto en los centros era también menos habitual para los escolares de familias de menor renta. Conclusiones: Un menor nivel socioeconómico del hogar se asocia con peores hábitos alimentarios y de actividad física y ciertas características del entorno familiar y el escolar, que a su vez median la asociación inversa que existe entre el nivel socioeconómico y la prevalencia de obesidad infantil. Las niñas realizan menos actividad física y presentan más sedentarismo mientras que los niños tienen más acceso a pantallas. Las intervenciones para combatir la obesidad infantil deben contemplar las desigualdades identificadas.

Even though athletes’ experience has been ascertained to shape the perception of quality in sports events, scarce studies have addressed this issue jointly with the intent to join in upcoming comparable sports challenges. (1) Background: The present research investigates how the experience determines the evaluation of the championship and future intentions. (2) Methods: The PLS (SEM) method was evaluated specifically for both novice and experienced duathlon participants, and secondly, the fsQCA methodology was applied with the intention to estimate combinatorial net effects to confirm the hypothesis proposed. (3) Results reveal that the overall quality is equally important for novice and experienced individuals as a determinant of future intentions. However, novices tend to value more positively all the dimensions analyzed, while experienced ones noted higher levels of demand. (4) These findings highlight the importance of designing adequate management strategies for the participants with different levels of performance.

Resumen Introducción: En Ceuta, el 82,3% de la población ha recibido al menos una vacuna contra la COVID-19. El 17,7% es reticente a recibir ninguna vacuna relacionada con esta enfermedad. El objetivo de este estudio es conocer el grado de rechazo y las causas del mismo hacia la vacunación contra la COVID-19 en trabajadores del ámbito sanitario de Hospital Universitario de Ceuta; además, poder comparar estos resultados con las causas en diferentes países y con otros sanitarios del mundo. Método: Se realizó un estudio descriptivo transversal donde se revisó la base de datos de los trabajadores excluyendo aquellos que sí habían recibido al menos una dosis de la vacuna. En aquellos donde no se tenía información o bien no habían recibido vacunación, se realizó una llamada telefónica. Se diseñó una base de datos con diferentes variables entre las que se incluyen: categoría profesional, sexo y edad. El análisis de los datos se llevó a cabo con Excel 2010. Resultados: De los 1009 trabajadores registrados, 17 de ellos confirmó no haber recibido ninguna vacuna: 6 enfermeros (35%), 6 médicos (35%), 3 administrativos (18%), 1 celador (6%) y 1 auxiliar de enfermería (6%). 35% lo atribuyó a causas médicas, 35% se encontraron reticentes a recibir la vacuna y 18% refirió tener anticuerpos contra el virus y por lo tanto, no deseó recibir la vacunación. Conclusiones: La causa más frecuente de no vacunación es el miedo (35%) tanto a los efectos secundarios como a la rapidez del desarrollo de la vacuna.

Background Fibrotic hypersensitivity pneumonitis (fHP) is an immune-mediated interstitial lung disease caused by sensitisation to chronic allergen inhalation. This study aimed to determine prognostic indicators of progression and mortality in fHP. Methods This was a retrospective, multicentre, observational, cross-sectional cohort study of consecutive patients diagnosed with fHP from 1 January 2012 to 31 December 2021. Multivariate Cox regression analyses were used to calculate hazard ratios (HRs) with 95% confidence intervals for predictors of progression and survival. Results A total of 403 patients were diagnosed with fHP: median (interquartile range) age 66.5 (14.0) years, 51.9% females and 55.1% never-smokers. The cause of fHP was mainly fungal (39.7%) or avian (41.4%). Lung biopsy was performed in 269 cases (66.7%). In the whole cohort the variables that were related to mortality or lung transplant were older age (HR 1.08; p

Obesity, a burgeoning global health crisis, has tripled in prevalence over the past 45 years, necessitating innovative research methodologies. Adipocytes, which are responsible for energy storage, play a central role in obesity. However, most studies in this field rely on animal models or adipocyte monolayer cell cultures, which are limited in their ability to fully mimic the complex physiology of a living organism, or pose challenges in terms of cost, time consumption, and ethical considerations. These limitations prompt a shift towards alternative methodologies. In response, here we show a 3D in vitro model utilizing the 3T3-L1 cell line, aimed at faithfully replicating the metabolic intricacies of adipocytes in vivo. Using a workable cell line (3T3-L1), we produced adipocyte spheroids and differentiated them in presence and absence of TNF-α. Through a meticulous proteomic analysis, we compared the molecular profile of our adipose spheroids with that of adipose tissue from lean and obese C57BL/6J mice. This comparison demonstrated the model's efficacy in studying metabolic conditions, with TNF-α treated spheroids displaying a notable resemblance to obese white adipose tissue. Our findings underscore the model's simplicity, reproducibility, and cost-effectiveness, positioning it as a robust tool for authentically mimicking in vitro metabolic features of real adipose tissue. Notably, our model encapsulates key aspects of obesity, including insulin resistance and an obesity profile. This innovative approach has the potential to significantly impact the discovery of novel therapeutic interventions for metabolic syndrome and obesity. By providing a nuanced understanding of metabolic conditions, our 3D model stands as a transformative contribution to in vitro research, offering a pathway for the development of small molecules and biologics targeting these pervasive health issues in humans.

Las políticas higienistas del siglo XVIII separaron al cementerio del templo, relegándolo a la periferia de la ciudad. Ya a principios del siglo XX, la ciudad funcional propuesta por los CIAM planteó una zonificación que ignoraba la conmemoración. Sin embargo, en los años 1930, una serie de proyectos funerarios encargados a arquitectos vinculados con localidades de tamaño moderado ofrecieron la oportunidad de elaborar una relación más estrecha entre la ciudad y el cementerio. Este artículo se propone comparar las propuestas de Jože Plečnik para Liubliana, Eslovenia, Willem Dudok para Hilversum, Holanda, y Francisco Salamone para Azul, Argentina, y examinar cómo sus cementerios fueron el punto de partida para configurar relaciones más estrechas con sus respectivos cascos urbanos y para dotar a esas localidades de una nueva identidad.

Tradicionalmente, los criterios para la evaluación de la oralidad han desatendido su carácter monológico o dialógico y han sido poco específicos en las habilidades interactivas. Nuestro objetivo es plantear un marco para la creación de criterios de evaluación relevantes para la interacción oral. Para ello, partimos de la pedagogía basada en el género y la aplicamos a los géneros orales interaccionales. A partir de estudios previos, observamos que los aprendices no distinguen los requerimientos específicos de una tarea de interacción oral. Por ello, realizamos una propuesta de criterios de evaluación basados en las familias de géneros discursivos. Nuestro fin es doble, por un lado, ofrecer a los docentes un marco que facilite la creación de criterios de evaluación específicos basados en géneros de una misma familia discursiva. Por otro lado, resaltar los criterios de evaluación concretos para la interacción oral para lograr un efecto washback que incluya dichos rasgos en las secuencias didácticas.

Objectives To examine the associations of cardiorespiratory fitness (VO2 max) and muscular strength with indicators related to the risk scale, such as perceived competence, sensation seeking, competitiveness, risk taking and risk perception in sports.Design Cross-sectional study.Setting High schools from the Region of Murcia (Spain).Participants Three-hundred-and-seventeen adolescents participated (mean age: 13.69±1.2 years old).Primary and secondary outcome measures Body mass, body height, Course-Navette test, upper limb strength and psychoeducational factors that determine the propensity towards sports accidents in school children, the Sports Accident Propensity Scale were evaluated. It was performance t-test for independent samples, stepwise multiple linear regression models and a multiple mediation analysis.Results The analysis showed significant differences with respect to sex in height, VO2 max, handgrip strength and in all factors of the questionnaire (p=0.02-

En este artículo vamos a analizar la redefinición a la que Hobbes somete en el Leviatán a los elementos esenciales de la hermenéutica bíblica protestante. Según el filósofo inglés definir las reglas que sirven para elaborar una exégesis adecuada, así como fijar el contenido que resulta de ello, es tarea del soberano, único intérprete autorizado de la Biblia. En base a estas ideas. Hobbes promueve la fundamentación de una nueva relación entre el poder civil y eclesial que le introduce como uno de los filósofos principales del debate teológico-político del siglo XVII.

Background Regional anesthesia techniques are commonly used for postoperative pain management during laparoscopic surgery. Our aim was to compare the analgesic efficacy of pre-incisional subcutaneous wound infiltration (WI) with that of the transversus abdominis plane (TAP) block as part of a multimodal analgesic approach in laparoscopic radical prostatectomy. Methods In this prospective, double-blinded, randomized controlled clinical trial, 60 patients were assigned to either TAP or WI group. The main outcome was acute postoperative pain control assessed using the mean numeric rating scale (NRS) at the 24 hours postoperatively. The secondary outcomes were opioid requirements, procedure-related complications, overall complications, and length of stay. Results In this study, 60 patients were randomized: 30 to TAP group and 28 to WI (two were excluded due to conversion to open surgery). We found no significant difference in the median (1Q, 3Q) NRS scores during the 24 h postoperatively neither at rest (TAP, 0 (0, 1) vs. WI, 0 (0, 1), P = 0.812), nor during movement (TAP, 1 (0, 2) vs. WI, 1 (0, 2), P = 0.708). There were no statistical differences in the postoperative intravenous morphine requirements in the TAP vs. WI groups during the same period (1.7 ± 3.1 vs. 1.8 ± 4.1 mg; P = 0.910). Only one patient in the TAP group presented with postoperative nausea and vomiting. Conclusions Both pre-incisional subcutaneous WI and TAP blockade were associated with very low pain scores as part of a non-opioid multimodal analgesic regimen in laparoscopic radical prostatectomy. This study did not demonstrate the benefits of WI over TAP.

Background: Despite the increasing number of ICU admissions among patients with solid tumours, there is a lack of tools with which to identify patients who may benefit from critical support. We aim to characterize the clinical profile and outcomes of patients with solid malignancies admitted to the ICU. Methods: Retrospective observational study of patients with cancer non-electively admitted to the ICU of the Hospital Clinic of Barcelona (Spain) between January 2019 and December 2019. Data regarding patient and neoplasm characteristics, ICU admission features and outcomes were collected from medical records. Results: 97 ICU admissions of 84 patients were analysed. Lung cancer (22.6%) was the most frequent neoplasm. Most of the patients had metastatic disease (79.5%) and were receiving oncological treatment (75%). The main reason for ICU admission was respiratory failure (38%). Intra-ICU and in-hospital mortality rates were 9.4% and 24%, respectively. Mortality rates at 1, 3 and 6 months were 19.6%, 36.1% and 53.6%. Liver metastasis, gastrointestinal cancer, hypoalbuminemia, elevated basal C-reactive protein, ECOG-PS greater than 2 at ICU admission, admission from ward and an APACHE II score over 14 were related to higher mortality. Functional status was severely affected at discharge, and oncological treatment was definitively discontinued in 40% of the patients. Conclusion: Medium-term mortality and functional deterioration of patients with solid cancers non-electively admitted to the ICU are high. Surrogate markers of cachexia, liver metastasis and poor ECOG-PS at ICU admission are risk factors for mortality.

Algunos restos del edificio GHJ de la Cité Balzac descansan, en el taller del arquitecto y artista Daniel Purroy, custodiados como parte de un proyecto artístico expuesto en la Nuit Blanche de 2013 en París. Elementos de su fachada prefabricada y algunos escombros evocan, por un lado, el origen racionalista del inmueble, tan anónimo como las siglas con las que fue bautizado; por otro, y a través de restos de diferentes papeles decorativos que adornaron su interior, son muestra de la personal vida de cada uno de sus moradores. Muchos de ellos contemplaron en 2012 el derribo del edificio en el que habían pasado parte de sus vidas. El artículo relata la vida de este edificio que superó su propia desaparición y cuyos restos fueron parte de una obra artística colaborativa en la que sus últimos moradores tuvieron un papel protagonista.

Summary: Background: Pseudomonas aeruginosa healthcare-associated infections are one of the top antimicrobial resistance threats world-wide. In order to analyze the current trends, we performed a Spanish nation-wide high-resolution analysis of the susceptibility profiles, the genomic epidemiology and the resistome of P. aeruginosa over a five-year time lapse. Methods: A total of 3.180 nonduplicated P. aeruginosa clinical isolates from two Spanish nation-wide surveys performed in October 2017 and 2022 were analyzed. MICs of 13 antipseudomonals were determined by ISO-EUCAST. Multidrug resistance (MDR)/extensively drug resistance (XDR)/difficult to treat resistance (DTR)/pandrug resistance (PDR) profiles were defined following established criteria. All XDR/DTR isolates were subjected to whole genome sequencing (WGS). Findings: A decrease in resistance to all tested antibiotics, including older and newer antimicrobials, was observed in 2022 vs 2017. Likewise, a major reduction of XDR (15.2% vs 5.9%) and DTR (4.2 vs 2.1%) profiles was evidenced, and even more patent among ICU isolates [XDR (26.0% vs 6.0%) and DTR (8.9% vs 2.6%)] (p

Background Systematic annual screening for sight-threatening diabetic retinopathy is established in several countries but is resource intensive. Personalised (individualised) medicine offers the opportunity to extend screening intervals for people at low risk of progression and to target high-risk groups. However, significant concern exists among all stakeholders around the safety of changing programmes. Evidence to guide decisions is limited, with, to the best of our knowledge, no randomised controlled trials to date. Objectives To develop an individualised approach to screening for sight-threatening diabetic retinopathy and test its acceptability, safety, efficacy and cost-effectiveness. To estimate the changing incidence of patient-centred outcomes. Design A risk calculation engine; a randomised controlled trial, including a within-trial cost-effectiveness study; a qualitative acceptability study; and an observational epidemiological cohort study were developed. A patient and public group was involved in design and interpretation. Setting A screening programme in an English health district of around 450,000 people. Participants People with diabetes aged ≥ 12 years registered with primary care practices in Liverpool. Interventions The risk calculation engine estimated each participant’s risk at each visit of progression to screen-positive diabetic retinopathy (individualised intervention group) and allocated their next appointment at 6, 12 or 24 months (high, medium or low risk, respectively). Main outcome measures The randomised controlled trial primary outcome was attendance at first follow-up assessing the safety of individualised compared with usual screening. Secondary outcomes were overall attendance, rates of screen-positive and sight-threatening diabetic retinopathy, and measures of visual impairment. Cost-effectiveness outcomes were cost/quality-adjusted life year and incremental cost savings. Cohort study outcomes were rates of screen-positive diabetic retinopathy and sight-threatening diabetic retinopathy. Data sources Local screening programme (retinopathy), primary care (demographic, clinical) and hospital outcomes. Methods A seven-person patient and public involvement group was recruited. Data were linked into a purpose-built dynamic data warehouse. In the risk assessment, the risk calculation engine used patient-embedded covariate data, a continuous Markov model, 5-year historical local population data, and most recent individual demographic, retina and clinical data to predict risk of future progression to screen-positive. The randomised controlled trial was a masked, two-arm, parallel assignment, equivalence randomised controlled trial, with an independent trials unit and 1 : 1 allocation to individualised screening (6, 12 or 24 months, determined by risk calculation engine at each visit) or annual screening (control). Cost-effectiveness was assessed using a within-trial analysis over a 2-year time horizon, including NHS and societal perspectives and costs directly observed within the randomised controlled trial. Acceptability was assessed by purposive sampling of 60 people with diabetes and 21 healthcare professionals with semistructured interviews analysed thematically; this was a constant comparative method until saturation. The cohort was an 11-year retrospective/prospective screening population data set. Results In the randomised controlled trial, 4534 participants were randomised: 2097 out of 2265 in the individualised arm (92.6%) and 2224 out of 2269 in the control arm (98.0%) remained after withdrawals. Attendance rates at first follow-up were equivalent (individualised 83.6%, control 84.7%) (difference –1.0%, 95% confidence interval –3.2% to 1.2%). Sight-threatening diabetic retinopathy detection rates were non-inferior: individualised 1.4%, control 1.7% (difference –0.3%, 95% confidence interval –1.1% to 0.5%). In the cost-effectiveness analysis, the mean differences in complete-case quality-adjusted life years (EuroQol-5 Dimensions, five-level version, and Health Utilities Index Mark 3) did not significantly differ from zero. Incremental cost savings per person not including treatment costs were from the NHS perspective £17.34 (confidence interval £17.02 to £17.67) and the societal perspective £23.11 (confidence interval £22.73 to £23.53). In the individualised arm, 43.2% fewer screening appointments were required. In terms of acceptability, changing to variable intervals was acceptable for the majority of people with diabetes and health-care professionals. Annual screening was perceived as unsustainable and an inefficient use of resources. Many people with diabetes and healthcare professionals expressed concerns that 2-year screening intervals may detect referable eye disease too late and might have a negative effect on perceptions about the importance of attendance and diabetes care. The 6-month interval was perceived positively. Among people with dementia, there was considerable misunderstanding about eye-related appointments and care. In the cohort study, the numbers of participants (total 28,384) rose over the 11 years (2006/7, n = 6637; 2016/17, n = 14,864). Annual incidences ranged as follows: screen-positive 4.4–10.6%, due to diabetic retinopathy 2.3–4.6% and sight-threatening diabetic retinopathy 1.3–2.2%. The proportions of screen-positive fell steadily but sight-threatening diabetic retinopathy rates remained stable. Limitations Our findings apply to a single city-wide established English screening programme of mostly white people with diabetes. The cost-effectiveness analysis was over a short timeline for a long-standing disease; the study, however, was designed to test the safety and effectiveness of the screening regimen, not the cost-effectiveness of screening compared with no screening. Cohort data collection was partly retrospective: data were unavailable on people who had developed sight-threatening diabetic retinopathy or died prior to 2013. Conclusions Our randomised controlled trial can reassure stakeholders involved in diabetes care that extended intervals and personalised screening is feasible, where data linkage is possible, and can be safely introduced in established screening programmes with potential cost savings compared with annual screening. Rates of screen-positive diabetic retinopathy and sight-threatening diabetic retinopathy are low and show consistent falls over time. Involvement of patients in research is crucial to success. Future work Future work could include external validation with other programmes followed by scale-up of individualised screening outside a research setting and economic modelling beyond the 2-year time horizon. Trial registration This trial is registered as ISRCTN87561257. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 11, No. 6. See the NIHR Journals Library website for further project information. Plain language summary Diabetic retinopathy remains a leading cause of vision loss for people with diabetes. Annual photographic screening allows early detection and prompt treatment in many countries. A new approach is to vary how often this is undertaken at each visit, after calculating each person’s risk of progression; we have called this ‘individualised’ screening. We tested this variable-interval risk-based approach against annual screening in a randomised controlled trial of 4534 people in Liverpool. Six-, 12- or 24-month intervals represented high, medium and low risks, respectively, of becoming screen-positive by the next appointment. With our patient and public involvement group, we designed a computer-based risk-calculation system using personal information from screening, general practitioners and hospitals. Attendance rates at the next screening appointment were similar in the individualised (84%) and annual (control) (85%) groups. Similar amounts of sight-threatening diabetic retinopathy were detected in the two arms (1.4% individualised, 1.7% control), with 43% fewer visits. In this study in a single geographical region, savings estimated to accrue to the NHS per person over 2 years were £17.34 and £23.11 for wider society, but estimates did not include treatment costs. During interviews, 60 people with diabetes and 21 healthcare professionals said that individualised screening would be acceptable because of increasing rates of diabetes and the chance to target high-risk people. Patients had anxieties about the reliability of the risk-calculation and restricting access, requesting opportunities for earlier screening if risks changed. Varying screening intervals based on a person’s own risk of progression appears feasible and safe. Low-risk people would be spared unnecessary appointments. Introducing an individualised approach could now move to wider testing and validation in other UK and international settings. The trial only ran for 2 years and was in a long-established programme with low rates of disease, so monitoring of attendance and retinopathy rates should be included as part of wider testing. Scientific summary Background Diabetic retinopathy remains the most common cause of visual impairment in working populations worldwide. Systematic annual screening to detect and treat sight-threatening diabetic retinopathy (STDR) is established in several countries including the United Kingdom (UK) and has greatly improved the detection of treatable disease. With the rapid increase in the prevalence of diabetes, new approaches to screening are required. Risk stratification, personalised (individualised) medicine, and clinical bioinformatics offer opportunities to extend the screening interval for people at low risk of progression and to target those at high risk. However there is significant concern among people with diabetes, healthcare professionals and health commissioners in the UK around the safety and acceptability of changing an established and successful programme. To ensure that health care is available for all it is imperative that it is not only efficacious but cost-efficient, that is, it delivers care at an affordable cost for commissioners. Evidence to guide these decisions is very limited and there are no randomised controlled trials (RCTs). Much of the data on prevalence and incidence of diabetic retinopathy and progression to more severe stages of disease come from the 1980s to 1990s and before the introduction of systematic screening and improvements in diabetes and blood pressure control. Data on the current progression rates in screening populations are limited and are reported variably. We conducted a programme of quantitative and qualitative research to develop and test the acceptability, safety, efficacy and cost-effectiveness of an individualised approach to screening for STDR. To provide data for future planning of early detection programmes and the design of future research studies we designed a longitudinal observational cohort study of the population of people with diabetes in Liverpool. We aimed to investigate the prevalence and incidence of the stages in the natural history of diabetic retinopathy, namely screen-positive, sight-threatening and treatable disease, and visual impairment, all key patient-centred outcomes in the disease. Changes to the programme and their implications A number of changes to the programme occurred in the early years. A systematic review was published at around the time of the programme start. We used these data to design aspects of the study and conducted a literature review instead. Data for the cohort study proved not to be available on people who had died prior to programme start. We adopted a mixed retrospective and prospective analysis but this added some difficulty in interpreting the findings. In 2016 resources were repurposed from the cohort study to support recruitment of the RCT, which was behind schedule. The scope of the cohort study was narrowed to focus only on the data available from the screening programme, meaning that we were unable to complete data collection on the patient-centred outcomes after sight-threatening retinopathy had been confirmed, namely treatment and visual impairment. Recruitment of non-attenders proved beyond the resources available and was abandoned. Further research is needed to address these unanswered questions. Methods The programme included the development of a bespoke data warehouse, the development of a risk-calculation engine, a RCT, a within-trial cost-effectiveness study, a qualitative study of acceptability, and an observational cohort study. We recruited and fully embedded a seven-person patient and public involvement group which was maintained throughout the programme. The setting was the screening programme of a single English health district (clinical commissioning group). All people with diabetes aged 12 years and over registered with general practices in the Liverpool city area were invited by letter to participate in the research programme. Consent was through an opt-out process. A purpose-built dynamic data warehouse was developed to support all aspects of the programme including bespoke processes addressing inconsistency in routinely collected data, multiple data platforms and lack of technical manuals. Data on eligible participants were sourced from primary care (demographic, clinical), Liverpool Diabetes Eye Screening Programme (retinopathy) and hospital outcomes (true screen-positive, STDR). Data were cross referenced against opt-out records before further use within the programme. A risk-calculation engine was developed for the assessment of individual risk of progressing to screen-positive using patient-focused covariate selection, a continuous-time Markov model, 5-year historical local population data, and the most recent individual demographic, retina and clinical data. The risk-calculation engine was linked to the data warehouse. The Patient and Public Involvement group determined the risk criterion of

In recent years, co-management has been highlighted in the scientific literature as fundamental strategy for groundwater control. However, the development of this institutional architecture is complex and presents important pitfalls and challenges. In this article we analyse the recent experience of co-management in the Requena-Utiel aquifer (Spain), based on a participatory action research. It aims to advance the co-management of groundwater by facilitating a consensus among users, as a basis on which to support future self-governance measures. We used a cognitive framing approach, developed through interviews with local stakeholders, to analyse the conflicting visions on the aquifer management; and we developed an interactive framing approach, through workshops, to achieve a shared understanding of aquifer co-management. The research demonstrates the usefulness of these approaches to promote collective action and co-management in groundwater. It showed the key role that information and transparency play in gaining shared understanding and improving co-management; but also the difficulties of users in establishing agreements that question the current status quo on the aquifer.

ABSTRACT We aimed to describe the characteristics and outcomes of biliary source bloodstream infections (BSIs) in oncological patients. Secondarily, we analyzed risk factors for recurrent BSI episodes. All episodes of biliary source BSIs in oncological patients were prospectively collected (2008–2019) and retrospectively analyzed. Logistic regression analyses were performed. A rule to stratify patients into risk groups for recurrent biliary source BSI was conducted. Four hundred biliary source BSIs were documented in 291 oncological patients. The most frequent causative agents were Escherichia coli (42%) and Klebsiella spp. (27%), and 86 (21.5%) episodes were caused by multidrug-resistant Gram-negative bacilli (MDR-GNB). The rates of MDR-GNB increased over time. Overall, 73 patients developed 118 recurrent BSI episodes. Independent risk factors for recurrent BSI episodes were prior antibiotic therapy (OR 3.781, 95% CI 1.906–7.503), biliary prosthesis (OR 2.232, 95% CI 1.157–4.305), prior admission due to suspected biliary source infection (OR 4.409, 95% CI 2.338–8.311), and BSI episode caused by an MDR-GNB (OR 2.857, 95% CI 1.389–5.874). With these variables, a score was generated that predicted recurrent biliary source BSI with an area under the receiver operating characteristic (ROC) curve of 0.819. Inappropriate empirical antibiotic treatment (IEAT) was administered in 23.8% of patients, and 30-d mortality was 19.5%. As a conclusion, biliary source BSI in oncological patients is mainly caused by GNB, with high and increasing MDR rates, frequent IEAT, and high mortality. Recurrent BSI episodes are frequent. A simple score to identify recurrent episodes was developed to potentially establish prophylactic strategies. IMPORTANCE This study shows that biliary source bloodstream infections (BSIs) in oncological patients are mainly caused by Gram-negative bacilli (GNB), with high and increasing rates of multidrug resistance. Importantly, recurrent biliary source BSI episodes were very frequent and associated with delays in chemotherapy, high rates of inappropriate empirical antibiotic therapy, and high 30-d mortality (19.5%). Using the variable independently associated with recurrent BSI episodes, a score was generated that predicted recurrent biliary source BSI with high accuracy. This score could be used to establish prophylactic strategies and lower the risk of relapsing episodes and the associated morbidity and mortality.

Objective To evaluate the impact of mobile vaccination units on COVID-19 vaccine uptake of the first dose, the percentage of vaccinated people among the total eligible population. We further investigate whether such an effect differed by deprivation, ethnicity and age.Design Synthetic control analysis.Setting The population registered with general practices (GPs) in nine local authority areas in Cheshire and Merseyside in Northwest England, UK.Intervention Mobile vaccination units that visited 37 sites on 54 occasions between 12 April 2021 and 28 June 2021. We defined intervention neighbourhoods as having their population weighted centroid located within 1 km of mobile vaccination sites (338 006 individuals). A weighted combination of neighbourhoods that had not received the intervention (1 495 582 individuals) was used to construct a synthetic control group.Outcome The weekly number of first-dose vaccines received among people aged 18 years and over as a proportion of the population.Results The introduction of a mobile vaccination unit into a neighbourhood increased the number of first vaccinations conducted in the neighbourhood by 25% (95% CI 21% to 28%) within 3 weeks after the first visit to a neighbourhood, compared with the synthetic control group. Interaction analyses showed smaller or no effect among older age groups, Asian and black ethnic groups, and the most socioeconomically deprived populations.Conclusions Mobile vaccination units are effective interventions for increasing vaccination uptake, at least in the short term. While mobile units can be geographically targeted to reduce inequalities, we found evidence that they may increase inequalities in vaccine uptake within targeted areas, as the intervention was less effective among groups that tended to have lower vaccination uptake. Mobile vaccination units should be used in combination with activities to maximise outreach with black and Asian communities and socioeconomically disadvantaged groups.

This Guide for Living Donor Kidney Transplantation (LDKT) has been prepared with the sponsorship of the Spanish Society of Nephrology (SEN), the Spanish Transplant Society (SET), and the Spanish National Transplant Organization (ONT). It updates evidence to offer the best chronic renal failure treatment when a potential living donor is available. The core aim of this Guide is to supply clinicians who evaluate living donors and transplant recipients with the best decision-making tools, to optimise their outcomes.Moreover, the role of living donors in the current KT context should recover the level of importance it had until recently. To this end the new forms of incompatible HLA and/or ABO donation, as well as the paired donation which is possible in several hospitals with experience in LDKT, offer additional ways to treat renal patients with an incompatible donor.Good results in terms of patient and graft survival have expanded the range of circumstances under which living renal donors are accepted. Older donors are now accepted, as are others with factors that affect the decision, such as a borderline clinical history or alterations, which when evaluated may lead to an additional number of transplantations.This Guide does not forget that LDKT may lead to risk for the donor. Pre-donation evaluation has to centre on the problems which may arise over the short or long-term, and these have to be described to the potential donor so that they are able take them into account. Experience over recent years has led to progress in risk analysis, to protect donors’ health. This aspect always has to be taken into account by LDKT programmes when evaluating potential donors.Finally, this Guide has been designed to aid decision-making, with recommendations and suggestions when uncertainties arise in pre-donation studies. Its overarching aim is to ensure that informed consent is based on high quality studies and information supplied to donors and recipients, offering the strongest possible guarantees. Resumen: Esta guía de recomendaciones para el TR de donante vivo (TRDV) es un documento elaborado con el patrocinio de la Sociedad Española de Nefrología, la Sociedad Española de Trasplantes y la Organización Nacional de Trasplantes que actualiza la calidad de la evidencia disponible para ofrecer el mejor tratamiento de la insuficiencia renal crónica cuando se disponga de un donante vivo potencial. El objetivo principal de esta guía es proporcionar a los profesionales con responsabilidad en los estudios previos del donante vivo y del receptor trasplantado, las mejores herramientas para tomar decisiones en beneficio del donante vivo y del receptor del trasplante.Además, en el contexto actual del TR, el donante vivo debe recuperar el protagonismo que alcanzó en un pasado reciente. Para ello, las nuevas modalidades de donación HLA y/o ABO incompatible, así como la donación cruzada disponibles en diversos centros con experiencia en TRDV, son oportunidades adicionales para el tratamiento de enfermos renales que tienen un donante incompatible.Los buenos resultados en supervivencia del paciente y del injerto están ampliando las circunstancias de aceptación de donantes vivos de riñón, incluyendo donantes de mayor edad y otros con algunos condicionantes que incluyen antecedentes o alteraciones límite que, cuando son evaluados con criterios objetivos, pueden aportar un numero adicional de trasplantes.No se ha obviado en esta guía que el TRDV puede representar algún riesgo para el que dona. Estos problemas que pueden aparecer a corto o largo plazo tienen que ser objeto principal de valoración previa a la donación y presentados al potencial donante para que en ejercicio de su autonomía los asuma o rechace. La experiencia acumulada en los últimos años ha permitido avanzar en el análisis de riesgos para preservar la salud de los donantes, aspecto que debe estar siempre presente en los responsables de programas de TRDV cuando se procede al estudio de idoneidad de un potencial donante.Finalmente, esta guía ha sido estructurada para facilitar la toma de decisiones con recomendaciones y sugerencias ante incertidumbres derivadas de los resultados en los exhaustivos estudios predonación. Y todo ello, con el objetivo de que el consentimiento informado que debe certificar la calidad de los estudios y la información proporcionada a donante y receptor, alcancen las mayores garantías posibles.