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A software technique based on approximate computing and redundancy is presented to mitigate radiation-induced soft errors in commercial off-the-shelf (COTS) microprocessors. Approximate computing relies on the capability of certain applications to accept imprecise results to improve efficiency by sacrificing its results in a controlled manner. Our approach avoids the time overhead derived from hardening while preserving the detection and correction rate. Experimental results show that we can detect and correct silent data corruption (SDC) events improving the cross section up to $160\times $ and keeping accuracy under control without compromising performance. In addition, an accuracy-aware layer is included to improve error mitigation and to provide a tradeoff between the number of tolerable errors and the necessary accuracy.

In this cross-sectional study, we analyzed data from the Survey of Risk Factors in a Secondary School Students (FRESC) representative survey among secondary school students aged 13 to 19 in the city of Barcelona. At all school grades, sexual harassment was more commonly reported by girls than by boys (17% of girls vs 4.2% of boys). The factors associated with sexual harassment were higher school grade, having a mental health disorder, cannabis abuse, and discrimination because of sexual orientation in girls and discrimination because of sexual orientation in boys. These findings highlight the potentially strong impact of sexual harassment on adolescents’ lives and underscore the importance of preventing this form of violence.

Atrial fibrillation is the most frequent chronic arrhythmia in patients with chronic kidney disease. Oral anticoagulation with vitamin K antagonists and now direct oral anticoagulants have been and are the fundamental pillars for the prevention of thromboembolic events. However, there are no randomized clinical trials on the risk-benefit profile of oral anticoagulation in patients with chronic kidney disease stage 5 on peritoneal dialysis and there is little evidence in the literature in this population.

Los inhibidores del cotransportador sodio-glucosa tipo 2 (iSGLT2) han demostrado su beneficio cardiovascular y renal en pacientes con diabetes mellitus tipo 2, insuficiencia cardiaca (IC) o enfermedad renal crónica (ERC). Desde los primeros estudios, con estos fármacos se objetivó un incremento inicial de los niveles de hemoglobina/hematocrito que se atribuyó a un aumento de la hemoconcentración asociados a su efecto diurético, aunque pronto se constató que aumentaban los niveles de eritropoyetina (EPO) y eritropoyesis, mejorando el metabolismo férrico. Los estudios de mediación objetivaron que el incremento de hemoglobina se asociaba estrechamente con los beneficios cardiorrenales de estas sustancias. En la presente revisión se discuten los mecanismos de mejora de la eritropoyesis y la implicación del aumento de hemoglobina sobre el beneficio pronóstico cardiorrenal de estos medicamentos.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated cardiovascular and renal benefits in patients with type 2 diabetes mellitus, heart failure, or chronic kidney disease. Since the first studies with these drugs, an initial increase in hemoglobin/hematocrit levels was observed, which was attributed to an increase in hemoconcentration associated with its diuretic effect, although it was early appearent that these drugs increased erythropoietin levels and erythropoiesis, and improved iron metabolism. Mediation studies found that the increase in hemoglobin was strongly associated with the cardiorenal benefits of these drugs. In this review, we discuss the mechanisms for improving erythropoiesis and the implication of the increase in hemoglobin on the cardiorenal prognostic benefit of these drugs.

La fibrilación auricular (FA) es la arritmia crónica más frecuente en pacientes con enfermedad renal crónica (ERC). La anticoagulación oral con antagonistas de la vitamina K (AVK) y actualmente los anticoagulantes orales de acción directa (ACOD) han sido el pilar fundamental para la prevención de eventos tromboembólicos. Sin embargo, no existen ensayos clínicos aleatorizados de su perfil riesgo-beneficio en pacientes con ERC estadio 5 en diálisis peritoneal (DP) y son pocas las evidencias en la literatura sobre esta población. El objetivo del estudio fue conocer la prevalencia, tratamiento y profesionales implicados en el manejo de la FA en DP en nuestro entorno mediante el análisis descriptivo de una encuesta enviada a diferentes unidades de DP de España. Se incluyeron en el estudio 1.403 pacientes en programa de DP, de los cuales 186 (13,2%) presentaban FA no valvular (FANV). Además, observamos que la valoración de los scorespara el inicio del tratamiento anticoagulante la realizaba mayoritariamente el cardiólogo (60% de los centros), así como la prescripción de anticoagulación (cardiólogo 47% o en conjunto con el nefrólogo 43%).

Experimental studies and clinical trials of nanoparticles for treating diseases are increasing continuously. However, the reach to the market does not correlate with these efforts due to the enormous cost, several years of development, and off-target effects like cardiotoxicity. Multicellular organisms such as the Caenorhabditis elegans(C. elegans) can bridge the gap between in vitroand vertebrate testing as they can provide extensive information on systemic toxicity and specific harmful effects through facile experimentation following 3R EU directives on animal use. Since the nematodes’ pharynx shares similarities with the human heart, we assessed the general and pharyngeal effects of drugs and polypyrrole nanoparticles (Ppy NPs) using C. elegans. The evaluation of FDA-approved drugs, such as Propranolol and Racepinephrine reproduced the arrhythmic behavior reported in humans and supported the use of this small animal model. Consequently, Ppy NPs were evaluated due to their research interest in cardiac arrhythmia treatments. The NPs’ biocompatibility was confirmed by assessing survival, growth and development, reproduction, and transgenerational toxicity in C. elegans. Interestingly, the NPs increased the pharyngeal pumping rate of C. elegansin two slow-pumping mutant strains, JD21 and DA464. Moreover, the NPs increased the pumping rate over time, which sustained up to a day post-excretion. By measuring pharyngeal calcium levels, we found that the impact of Ppy NPs on the pumping rate could be mediated through calcium signaling. Thus, evaluating arrhythmic effects in C. elegansoffers a simple system to test drugs and nanoparticles, as elucidated through Ppy NPs.

Anemia is a common complication of chronic kidney disease (CKD) and is associated with a decrease in quality of life and an increased risk of transfusions, morbidity and mortality, and progression of CKD. The Anemia Working Group of the Sociedad Española de Nefrología conducted a Delphi study among experts in anemia in CKD to agree on relevant unanswered questions by existing evidence. The RAND/UCLA consensus methodology was used. We defined 15 questions with a PICO structure, followed by a review in scientific literature databases. Statements to each question were developed based on that literature review. Nineteen experts evaluated them using an iterative Two-Round Delphi-like process. Sixteen statements were agreed in response to 8 questions related to iron deficiency and supplementation with Fe (impact and management of iron deficiency with or without anemia, iron deficiency markers, safety of i.v. iron) and 7 related to erythropoiesis stimulating agents (ESAs) and/or hypoxia-inducible factor stabilizers (HIF), reaching consensus on all of them (individualization of the Hb objective, impact and management of resistance to ESA, ESA in the immediate post-transplant period and HIF stabilizers: impact on ferrokinetics, interaction with inflammation and cardiovascular safety). There is a need for clinical studies addressing the effects of correction of iron deficiency independently of anemia and the impact of anemia treatment with various ESA on quality of life, progression of CKD and cardiovascular events.

Studies on the prevalence of anaemia in chronic kidney disease in adults not on dialysis (CKD-ND) and in dialysis programmes (CKD-D) in Spain are not recent or focus on certain subgroups. The aim of this study was to know the epidemiology and current treatment patterns of anaemia associated with CKD in Spain.

A software technique is presented to protect commercial multi-core microprocessors against radiation-induced soft errors. Important time overheads associated with conventional software redundancy techniques limit the feasibility of advanced critical electronic systems. In our approach, redundant bare-metal threads are used, so that critical computation is distributed over the different micro-processor cores. In doing so, software redundancy can be applied to commercial off-the-shelf (COTS) micro-processors without incurring high-performance penalties. The proposed technique was evaluated using a low-cost single board computer (SBC) [Raspberry Pi 4 (RPI4)] under neutron irradiation. The results showed that the redundant multi-threading (RMT) versions detected and recovered all the silent data corruption (SDC) events, and only increased HANG sensitivity with respect to the unhardened original versions. In addition, higher mean work-to-failure (MWTF) estimations are achieved with our bare-metal technique than with the state-of-the-art bare-metal software-based techniques that only implement temporal redundancy.

The use of state-of-the-art commercial processors such as graphical processing units (GPUs) is becoming increasingly common in the New Space industry to ensure high performance and power efficiency. However, commercial GPUs are not designed to operate in a harsh environment, and therefore, different protection techniques need to be applied to mitigate the effects of radiation, including those produced by single events. This article assesses the effectiveness of redundant kernel execution on tightly constrained embedded GPUs under proton irradiation, with results suggesting a significant improvement in the silent data corruption (SDC) cross Section without penalizing the stability of the whole system. In addition, the posterior error analysis shows that the CPU is the source of the majority of the events, which are mainly dominated by functional interrupts.

This study screened for Fabry disease (FD) in patients in hemodialysis (HD) in the region of Madrid (CAM) with a cross-sectional design to evaluate HD-prevalent patients, followed by a three-year period prospective design to analyze HD-incident patients.

La enfermedad renal diabética, frecuente en pacientes con diabetes mellitus tipo 2, se asocia con un marcado incremento de la morbimortalidad, especialmente cardiovascular, y de progresión a enfermedad renal crónica terminal. Hasta la fecha la reducción del riesgo cardiovascular y renal en esta población se ha basado en el control estricto de los factores de riesgo cardiovascular y en el uso de inhibidores del sistema renina-angiotensina. Mas recientemente los inhibidores del cotransportador sodio-glucosa tipo 2 han demostrado ofrecer protección cardiovascular y renal, pero el riesgo residual sigue siendo alto y su eficacia antihiperglucemiante es limitada en ERC moderada-severa.

This study screened for Fabry disease (FD) in patients in hemodialysis (HD) in the region of Madrid (CAM) with a cross-sectional design to evaluate HD-prevalent patients, followed by a three-year period prospective design to analyze HD-incident patients.

El presente artículo considera la inscripción rupestre dedicada a Nemedus Augustus en la cueva de La Griega (Pedraza, Segovia) con el objetivo de aportar algunas reflexiones sobre la interpretación de las divinidades con epíteto Augustus/a, su relación con el culto imperial y su presencia en el ámbito rural hispano. Se consideran otros testimonios epigráficos del uso del epíteto Augustus/Augusta en divinidades indígenas en la Península Ibérica, entendiendo que fue un mecanismo para su incorporación al panteón romano.

Skates are cartilaginous fish whose body plan features enlarged wing-like pectoral fins, enabling them to thrive in benthic environments1,2. However, the molecular underpinnings of this unique trait remain unclear. Here we investigate the origin of this phenotypic innovation by developing the little skate Leucoraja erinaceaas a genomically enabled model. Analysis of a high-quality chromosome-scale genome sequence for the little skate shows that it preserves many ancestral jawed vertebrate features compared with other sequenced genomes, including numerous ancient microchromosomes. Combining genome comparisons with extensive regulatory datasets in developing fins—including gene expression, chromatin occupancy and three-dimensional conformation—we find skate-specific genomic rearrangements that alter the three-dimensional regulatory landscape of genes that are involved in the planar cell polarity pathway. Functional inhibition of planar cell polarity signalling resulted in a reduction in anterior fin size, confirming that this pathway is a major contributor to batoid fin morphology. We also identified a fin-specific enhancer that interacts with several hoxagenes, consistent with the redeployment of hoxgene expression in anterior pectoral fins, and confirmed its potential to activate transcription in the anterior fin using zebrafish reporter assays. Our findings underscore the central role of genome reorganization and regulatory variation in the evolution of phenotypes, shedding light on the molecular origin of an enigmatic trait.

Background:Acute interstitial nephritis (AIN) is one of the chief causes of acute kidney injury (AKI). AIN might be produced by drugs, infections, autoimmune diseases, or can be idiopathic. Among these etiologies, drug-induced AIN (DI-AIN) is the dominant one in many countries. Even when DI-AIN is suspected, identification of the putative drug is challenging. Summary:DI-AIN is an increasingly common cause of AKI. Diagnosis continues to pose a challenge for physicians due to nonspecific clinical symptoms, and the fact that it can be triggered by a wide variety of medications. Furthermore, the gold standard for the diagnosis is kidney biopsy. All these aspects render the diagnosis more difficult. The withdrawal of the causative drug of DI-AIN is the centerpiece of the treatment, and if early restoration of original kidney function is not obtained, several studies support the treatment with steroids especially when they are started quickly. Key Messages:Almost all drugs have the potential to produce drug-induced acute interstitial nephritis (DI-AIN); however, antibiotics, nonsteroidal anti-inflammatory agents, and proton pump inhibitors account for the majority of the reported cases. DI-AIN is produced by an idiosyncratic delayed type IV hypersensitivity reaction, but the precise pathophysiological mechanism remains to be elucidated. DI-AIN symptoms are nonspecific, and most of the patients will present mild symptoms including malaise, nausea, and vomiting. The classical triad, associating fever, rash, and eosinophilia, is seldom present. Nonoliguric acute kidney injury is the main renal manifestation of DI-AIN. Tubular nonnephrotic range proteinuria is usually present. Diagnosis of DI-AIN relies on maintaining a high index of suspicion in those patients at greater risk, but kidney biopsy is required to confirm diagnosis. Histologically, AIN is characterized by the presence of an extensive interstitial infiltrate, mainly composed of lymphocytes and monocytes, but eosinophils, plasma cells, histiocytes, and polymorphonuclear cells can also be found. The withdrawal of the presumed causative drug of DI-AIN is the mainstay of the treatment. When there is no evidence of kidney function recovery after an interval of 5–7 days since interrupting the treatment with the suspected drug, several studies support the treatment with steroids, especially when they are promptly started. Early corticosteroids would decrease the inflammatory infiltrates of the kidney interstitium, thus preventing the risk of subsequent fibrosis.

Outsourcing processes in road freight transport constitute one of the most relevant operational features of this sector. However, the organisational articulation of these processes has not yet been studied in detail, due both to the opacity surrounding the collaborative relationships between companies and to their enormous complexity. Thus, this paper sets out, on the one hand, to identify the main subcontracting structures and information channels between companies and, on the other, to analyse the interdependent relationships between agents in road freight transport systems. In order to achieve these objectives, a case study was carried out using data from a survey of transport professionals in an area with a high concentration of logistics companies located on the border between Spain and France. The results reveal the enormous importance of outsourcing for the sector, where hierarchical structures and the selective transfer of information prevail over horizontal collaboration. They also show the existence of a complex network of collaborations, where some companies play central dynamising roles as opposed to other more peripheral roles.

As biodiesel is continuously aimed to be a better alternative to petroleum-based diesel fuel, the University of the Philippines Los Baños – Interdisciplinary Biofuels Research Studies Center (UPLB-IBRSC) continues to explore process conversion techniques to improve efficiencies in biodiesel production. In this study, the catalytic activity of potassium ferrate in the transesterification of canola oil and used cooking oil for biodiesel production at room temperature was examined for potential reduction in energy consumption. Parameters such as methanol-to-oil molar ratio, catalyst loading, and reaction time were varied to determine their effects on biodiesel yield and purity. Thin layer chromatography was applied to qualitatively analyze the biodiesel, while ImageJ software was used for purity determination. The characterization analysis confirmed that the refined canola oil used in the study has an acceptable FFA content of 0.06%. On the other hand, the used cooking oil showed an FFA content of 3.71%, which is beyond the desired limit of 2%. Hence, neutralization through the addition of potassium hydroxide was performed, resulting in a lowered FFA content of 0.86%. Experimental results of the parametric and optimization study on used cooking oil showed that an optimum conversion of 86.55% was achieved at a 2:1 methanol-to-oil molar ratio, 5 wt% catalyst loading, and 90 minutes reaction time. Consequently, a yield of 83.21% was attained using refined canola oil at the optimum conditions of 6:1 methanol-to-oil molar ratio, 3 wt% catalyst loading, and 69 minutes reaction time. Generally, findings show that catalyst loading and reaction time significantly affect the biodiesel yield and purity only up to a certain optimum value. The methanol-to-oil ratio, on the other hand, showed to have a significant inverse relationship on yield and purity. Compared to the typical biodiesel production process at 60 °C with up to two hours of reaction time, this study which describes a catalytic process at room temperature and a relatively shorter reaction time, showed the potential to reduce significantly the high energy consumption in biodiesel production.

The assessment of chemotherapy response in osteosarcoma (OS) based on the average percentage of viable cells is limited, as it overlooks the spatial heterogeneity of tumor cell response (foci of resistant cells), immune microenvironment, and bone microarchitecture. Despite the resulting positive classification for response to chemotherapy, some patients experience early metastatic recurrence, demonstrating that our conventional tools for evaluating treatment response are insufficient. We studied the interactions between tumor cells, immune cells (lymphocytes, histiocytes, and osteoclasts), and bone extracellular matrix (ECM) in 18 surgical resection samples of OS using multiplex and conventional immunohistochemistry (IHC: CD8, CD163, CD68, and SATB2), combined with multiscale characterization approaches in territories of good and poor response (GRT/PRT) to treatment. GRT and PRT were defined as subregions with <10% and ≥10% of viable tumor cells, respectively. Local correlations between bone ECM porosity and density of immune cells were assessed in these territories. Immune cell density was then correlated to overall patient survival. Two patterns were identified for histiocytes and osteoclasts. In poor responder patients, CD68 osteoclast density exceeded that of CD163 histiocytes but was not related to bone ECM load. Conversely, in good responder patients, CD163 histiocytes were more numerous than CD68 osteoclasts. For both of them, a significant negative local correlation with bone ECM porosity was found (P< .01). Moreover, in PRT, multinucleated osteoclasts were rounded and intermingled with tumor cells, whereas in GRT, they were elongated and found in close contact with bone trabeculae. CD8 levels were always low in metastatic patients, and those initially considered good responders rapidly died from their disease. The specific recruitment of histiocytes and osteoclasts within the bone ECM, and the level of CD8 represent new features of OS response to treatment. The associated prognostic signatures should be integrated into the therapeutic stratification algorithm of patients after surgery.

Diabetes is a major public health issue. Because lifetime risk, life expectancy, and years of life lost are meaningful metrics for clinical decision making, we aimed to estimate these measures for type 2 diabetes in the high-income setting.

Encapsulation of biomolecules using metal–organic frameworks (MOFs) to form stable biocomposites has been demonstrated to be a valuable strategy for their preservation and controlled release, which has been however restricted to specific electrostatic surface conditions. We present a Lewis-acid-mediated general in situstrategy that promotes the spontaneous MOF growth on a broad variety of proteins, for the first time, regardless of their surface nature. We demonstrate that MOFs based on cations exhibiting considerable inherent acidity such as MIL-100(Fe) enable efficient biomolecule encapsulation, including elusive alkaline proteins previously inaccessible by the well-developed in situazolate-based MOF encapsulation. Specifically, we prove the MIL-100(Fe) scaffold for the encapsulation of a group of proteins exhibiting very different isoelectric points (5 < pI < 11), allowing triggered release under biocompatible conditions and retaining their activity after exposure to denaturing environments. Finally, we demonstrate the potential of the myoglobin-carrying biocomposite to facilitate the delivery of O2into hypoxic human lung carcinoma A549 cells, overcoming hypoxia-associated chemoresistance.

Kidney cells are exposed to large changes in osmolarity and hence require efficient volume regulation. Volume-regulated anion channels (VRACs) mediate regulatory volume decrease, but their expression and function in the kidney remain enigmatic. VRACs, heterohexamers of LRRC8 proteins, also conduct metabolites. This paper describes the renal expression pattern of all five LRRC8 subunits and explores their roles in mouse models. Except for vasculature-restricted LRRC8C, all LRRC8 proteins are found along the nephron. Rather than in medulla, which experiences large osmolarity changes, VRACs are most highly expressed in proximal tubules, which have metabolite-conducting LRRC8A/D channels. Targeted disruption of either subunit injures the proximal tubule and produces Fanconi-like symptoms. VRACs may mediate nonspecific exit of organic compounds in this highly transporting nephron segment.

Background: Sexual violence (SV) is a public health problem with high prevalence among the young population. The use of formal resources for SV care (e.g. institutional services) is low in this age group. This study applies a framework of health assets to identify the factors that positively influence the search for support for SV among young people, the functions of that support and the level of proximity as articulated by both young people and professionals. Methods: A qualitative study was conducted through 38 semi-structured interviews with young people and professionals from SV resource centers and/or care services for the young population in Spain. A thematic theoretical analysis was conducted, embedded in inductive insights emerging from the data, following a particular adaptation of the constant comparative method, under the grounded theory approach. This analysis was carried out by coding the interview transcripts with the support of Atlas.ti. Results: Young women identified assets, categorized as feminist, that they believe they are essential in the search for formal support services for SV. However, unlike young men, they considered the police and judicial system to be barriers and not assets. There were also differences between the young people and professionals in identifying assets. Young people also considered their partner and traditional media as health assets, in contrast to professionals who did not identify these as such valuable resources in the help-seeking process. Informal assets, such as family, friends and the internet are considered close resources. In contrast, specialized care services for gender-based violence/SV and the judicial and police systems were perceived as more distant resources among the young interviewees. Conclusions: This study shows similarities and discrepancies among young women and men and SV response professionals in identifying assets for seeking SV support among youth. The study shows an inverse relationship between perceptions of proximity and the level of formality of the asset. This study also contributes to map the relationships and information exchanges between assets. It is advisable to inform professionals about the assets that professionals do not acknowledge, and about actions that allow young people to access formal resources.