Unidades Centrales Científico-Técnicas

The Management and Uncertainties of Severe Accident (MUSA) project aimed to establish a harmonised approach for applying BEPU methods in severe accident analyses, with particular focus on the source term. The second work package “ Identification & Quantification of Uncertainty Sources” addressed one of the most crucial steps in BEPU analysis applying forward uncertainty propagation. Its main outcome is a knowledge-based matrix compiling over 600 uncertain input parameters related to source term assessment, including their associated models, phenomena, and (partial) quantifications. It was utilised and continuously updated in subsequent calculation work packages (Phebus FPT1, reactor and SFP case). First a consistent set of Figure of Merits, such as iodine and caesium release, was established. A systematic backward selection and characterisation approach of the associated uncertain input parameters was established, considering among others influencing phenomena, modelling choices, code capabilities, etc. While some parameters, such as shape factors, were common across codes - though different characterisations depending on code/user were provided - others were code-specific, appearing in only one or few codes. Establishing physically justifiable distributions proved challenging largely due to the scarcity of data and consequently heavy reliance on expert judgement and code-specific knowledge. Nevertheless, each parameter's characterisation had to be defendable on scientific grounds. In the absence of direct evidence, the characterisation was justified based on physical behaviour, while where direct association was not possible due to system complexity, on reasonable indirect evidence. This paper presents an overview of the work, main findings and conclusions, including the data base, and highlights key challenges and future research needs identified during the project. • Identification and quantification of uncertainty sources related to source term. • Systematic backward approach to select and quantify uncertain input parameters associated with the source term. • Comprehensive data base consisting of over 600 uncertain input parameters, including their quantification. • Scientifically defendable characterisation including justification. • Identification of future needs: further harmonisation, cross comparison as well as extension of the data base.

Hepatocyte growth factor (HGF)/hepatocyte growth factor receptor (MET) signaling plays a critical role during liver regeneration upon acute and chronic damage, and is therefore an interesting target for therapeutic intervention. Nevertheless, the molecular mechanisms underlying the pro-regenerative effects of HGF/MET signaling are not fully elucidated, particularly during cholestatic injury. Our aim was to analyze the impact of moderately enhanced MET on the hepatic response to cholestatic injury, and uncover the mechanisms behind it. For that, Alb-R26Met mice expressing a wild-type Met transgene in albumin-positive liver cells were fed with a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-supplemented diet, used as a model simulating human primary sclerosing cholangitis. Results indicate that increased MET expression diminished liver damage in DDC-fed mice, evidenced by lower serum levels of bilirubin and alkaline phosphatase, and decreased cell apoptosis. However, decreased ductular expansion was observed, which together with enhanced hepatocyte proliferation suggests that hepatocytes act as the main cellular defense. Both invivo and in vitro studies using Alb-R26Met liver-derived hepatocytes under cholestasis-simulated in vitro conditions demonstrated an enhanced upregulation of nuclear factor erythroid 2-related factor 2 (NRF2; encoded by the Nfe2l2 gene), parallel to an upregulation of glutathione biosynthesis enzymes, increased levels of glutathione, and decreased reactive oxygen species, along with decreased activation of transforming growth factor beta (TGF-β)-induced signaling. Consistently, MET transgenic hepatocytes were protected against TGF-β-induced oxidative stress and apoptosis in vitro. In conclusion, our work evidences that moderate upregulation of wild-typeMET in hepatocytes is sufficient to promote a strong antioxidant response in the liver that efficiently protects against chronic cholestasis, thus allowing optimal liver regeneration.

Blazar gamma-ray variability is predominantly stochastic and well described by red-noise processes. However, a subset of sources shows quasi-periodic oscillations (QPOs) on year-long timescales, whose physical origin remains debated. In high-synchrotron-peaked (HSP) blazars, departures from a single power-law gamma-ray spectrum, manifested as high-energy upturns in the GeV band, may probe emission mechanisms and the intrinsic duty cycle. We investigate the link between the 1.7 yr gamma-ray QPO in PKS 2155-304 and an exceptional spectral hardening event identified in the Fermi-LAT HSP blazar population. We analyze 17.4 years of Fermi-LAT data using 30-day binning, applying Singular Spectrum Analysis to mitigate red-noise effects and a Moving Block Bootstrap approach to quantify the correlation between photon flux and photon index. We find a statistically significant softer-when-brighter chromatic trend, supporting a geometric origin of the flux modulation. The spectral hardening event is phase-locked to the QPO trough, implying that the hardening signature is detectable only when geometrically boosted soft emission is suppressed at the flux minimum. We propose a Geometric Masking scenario in which jet geometry regulates the visibility of acceleration processes. These results favor a two-component jet structure and suggest that spectral hardening during low-flux states, even in non-periodic sources, may reveal jet physics otherwise obscured by relativistic amplification.

812 Background: Muscle-invasive bladder carcinoma (MIBC) is associated with high recurrence and mortality rates, and current neoadjuvant chemotherapy (NACT) regimens offer limited efficacy and considerable toxicity. These limitations underscore the need for reliable biomarkers to improve treatment management and patient outcomes. Metaproteomics profiling allows for the simultaneous characterisation of human and microbial proteins within tumors, offering a new perspective on patient-microbiota interactions in cancer. Our group has identified three microbiota-related metaproteomics clusters (Microbiota1-3) associated with response to NACT in MIBC. Our objective is to evaluate the prognostic relevance in terms of disease-free survival (DFS) of these microbiota-related metaproteomics clusters. Methods: Fifty-eight FFPE transurethral resection (TURBT) samples from patients diagnosed with MIBC were analyzed using data-independent acquisition (DIA) mass spectrometry. Protein identification was performed against a custom database including the human proteome and bacterial proteomes from bacteria genera identified by 16S rRNA gene sequencing in the same samples. After quality control, bacterial and human proteins were analyzed using Perseus software and probabilistic graphical models (PGMs) to identify functional relationships. Patients were classified into three metaproteomic clusters (Microbiota1-3) according to their tumor microbiota protein profiles by hierarchical clustering. Disease-free survival (DFS) was estimated by the Kaplan-Meier method and compared among clusters using the log-rank (Mantel-Cox) test. Results: Kaplan-Meier analysis revealed significant differences in DFS between the three defined metaproteomics subtypes (Microbiota1-3) (p=0.01). Patients classified as Microbiota3 had the most favorable DFS and a lower proportion of relapse events, with median DFS not reached during the follow-up period. This group was previously associated with a higher proportion of responders to NACT, consistent with the favorable DFS observed. In contrast, Microbiota2 was associated with earlier relapse and shorter DFS (median DFS: 23 months), in line with its higher proportion of non-responders to NACT. Conclusions: To our knowledge, this is the first metaproteomics study focused in biomarker discovery using FFPE samples from bladder carcinoma patients. Distinct MIBC metaproteomics profiles are associated with differential DFS following NACT. The identification of these three microbiota-related proteomics clusters highlights the potential prognostic relevance of the tumor-associated microbiota. These findings support metaproteomics as a promising approach for refining patient stratification and guiding future biomarker-driven strategies in bladder cancer.

PurposeTo characterize post-intensive care syndrome (PICS) in critical patients who survived COVID-19 during the first pandemic wave and to follow PICS symptoms during one year.Material and methodsProspective, observational, multicenter cohort study conducted in 11 Spanish ICUs. Critically ill adult patients who survived SARS-CoV-2 infection and met risk criteria for PICS were included. In-person follow-up was conducted at 3, 6, and 12 months after hospital discharge, assessing physical, cognitive, psychological, and nutritional aspects, quality of life and return to daily activities.ResultsA total of 227 patients were included, of which 120 (52.9%) completed the 3 follow-up visits. Hand dynamometry showed muscle weakness in 40.9% of patients at 3 months, with improvement over time. Anxiety, depression, post-traumatic stress disorder (PTSD) and cognitive impairment were observed in 32.9%, 24.3%, 13.8% and 46.1% of patients, respectively, at 3 months. While anxiety, depression and cognitive impairment slightly decreased over time, PTSD did not. Nutritional risk was significant at 3 months (42.4%), with gradually recovering (3.9% at 1 year). Patients' autonomy, and perception of physical and mental quality of life, improved over the months. At 3 months, 35% of patients had returned to work, and 58.3% at one year. A significant percentage of patients required assistance from physical therapy and mental health professionals after discharge.ConclusionSignificant impairment was observed in all areas of PICS in critically ill patients with COVID-19, with progressive improvement over one year of follow-up, with the adoption of physical, mental, cognitive, and nutritional support measures.

To evaluate crystalline lens (CL) and intraocular lens (IOL) tilt and decentration after uneventful femtosecond laser-assisted cataract surgery (FLACS) in Caucasian eyes. Clínica Miranza, Madrid, Spain. Retrospective, observational, interventional, nonrandomized, single-center study. This study included 125 consecutive eyes from 125 patients undergoing FLACS. CL and IOL tilt and decentration were assessed using the built-in analysis software of the CASIA2 anterior segment optical coherence tomography (AS-OCT) system. Univariate and multivariate regression analyses identified associations between biometric parameters and both CL and IOL tilt and decentration. A Pearson correlation coefficient evaluated the relationship between CL and IOL values. Differences across IOL platforms in relation to preoperative CL tilt and decentration were explored. Mean preoperative CL tilt was 5.20 ± 1.35 degrees, and decentration was 0.16 ± 0.09 mm. At 1 month postoperatively, mean IOL tilt was 5.08 ± 1.33 degrees and decentration was 0.23 ± 0.12 mm. CL tilt strongly correlated with IOL tilt ( R = 0.80, P < .0001), while CL and IOL decentration showed a moderate correlation ( R = 0.38, P < .0001). No significant correlation was found between IOL tilt and decentration ( R = 0.07, P = .439). Axial length was a significant predictor of both CL and IOL tilt. Age significantly predicted CL decentration and showed a modest association with IOL decentration. In Caucasian eyes undergoing FLACS, preoperative CL position correlates with postoperative IOL alignment. AS-OCT analysis of CL geometry may aid in predicting IOL behavior before cataract surgery.

This article examines the failure of the two most recent temporary housing programs implemented in Spain following two major disasters: the 2011 Lorca earthquake and the 2021 La Palma volcanic eruption. Despite differing hazard typologies, both cases resulted in incomplete and ultimately unsuccessful housing programs, with only 13 of the 60 planned units built in Lorca and 121 of the 200 planned units delivered in La Palma. Using a qualitative comparative case study approach, the research analyzes governance decisions, housing design, and implementation processes to assess their impact on the sustainability of post-disaster temporary housing. The analysis adopts the five dimensions of sustainability—environmental, economic, social, cultural, and institutional—as an integrated analytical framework for evaluating public management performance in post-disaster temporary housing. The findings show that early decision-making, shaped by political urgency, technical misjudgments, and the absence of adaptive governance, led to severe delays, cost overruns, inadequate and energy-inefficient construction, and the formation of marginalized settlements. This study concludes that the lack of regulatory frameworks, legal instruments, and operational protocols for temporary housing in Spain was a determining factor in both failures, generating vulnerability, prolonging recovery processes, and undermining sustainability across all five dimensions. By drawing lessons from these cases, this article contributes to debates on resilient and sustainable post-disaster recovery and highlights the urgent need for integrated regulatory frameworks for temporary housing in Spain.

Introduction

The microstructure of several reactor pressure vessel (RPV) model steels with varying contents of Ni, Mn and Si was examined using Transmission Electron Microscopy (TEM) before and after neutron irradiation conducted within the Lyra-10 program, up to 0.17 dpa at 286 °C. This study provides new insights into the synergistic effects of these alloying elements on irradiation-induced microstructural, particularly the density, size and distribution of dislocation loops. The results reveal a marked decrease in the density of visible dislocation loops with increasing Ni and Mn content, while the average loop size remains unaffected across all compositions. The effect of Mn seems to be more acute in the decrease of dislocation loop density and the trend is not influenced by variations in Si content. The observed reduction in dislocation loop density is hypothesized to be related to the formation of Mn-Ni-Si-rich solute clusters, which likely compete with loops for point defects or nucleate directly on them, hindering their growth. As a result, many dislocation loops fall below the resolution limit of TEM. These findings, supported by complementary techniques such as Atom Probe Tomography and Small-Angle Neutron Scattering, highlight the critical role of solute content in controlling irradiation-induced microstructures in the studied RPV steels.

This review investigates the decline in sperm DNA quality in humans and various animal species, with a focus on sperm DNA fragmentation (SDF), its impact on reproductive outcomes, and its management in the context of assisted reproduction. The review underscores the significance of universally observed phenomena in human reproduction and proposes the application of insights gained from human studies to enhance reproductive strategies in animals and endangered species, where sperm quality research is limited and gametes for assisted reproduction are scarce.Universal aspects of the nature and origin of sperm DNA damage and repair are examined. It emphasizes the analysis of DNA breaks related to biological factors, such as histone-to-protamine exchange, oxidative stress, DNase activity, environmental pressures, and the unavoidable effects of iatrogenic DNA damage, particularly affecting processes related to assisted reproduction. The mechanisms underlying the repair of persistent DNA breaks that reach oocytes transported by sperm are also discussed.Methodologies for assessing SDF and differentiating between single- and double-stranded DNA breaks are explained. Various strategies to mitigate high levels of SDF in the ejaculate have been explored, and their potential applications in both humans and animal species have been discussed.A key conclusion is that SDF assessment offers valuable insights into semen quality, particularly in the era of assisted reproduction and specifically in intracytoplasmic sperm injection (ICSI), where traditional sperm parameters such as concentration, motility, and membrane quality evaluation are less critical. The causes of high SDF levels are multifactorial and complex, necessitating the establishment of standard protocols to control its negative effects on assisted reproduction. This is especially pertinent for endangered species, for which information on male fertility factors is limited. In humans, personalized treatment is essential to optimize the retrieval of high-quality gametes during fertilization. Similarly, assisted reproductive strategies for endangered species must be tailored to the specific sperm characteristics of each species. Various strategies to improve sperm DNA quality are now available, many of which are designed to mimic natural sperm behaviour shaped by evolutionary selection processes unique to each species. Exploring the synergistic effects of these strategies could enhance sperm availability and efficacy during fertilization.