Evaluating the Safety Profile of Non-Active Implantable Medical Devices Compared with Medicines

Recent safety issues involving non-active implantable medical devices (NAIMDs) have highlighted the need for better pre-market and post-market evaluation. Some stakeholders have argued that certain features of medicine safety evaluation should also be applied to medical devices. Our objectives were to compare the current processes and methodologies for the assessment of NAIMD safety profiles with those for medicines, identify potential gaps, and make recommendations for the adoption of new methodologies for the ongoing benefit–risk monitoring of these devices throughout their entire life cycle. A literature review served to examine the current tools for the safety evaluation of NAIMDs and those for medicines. We searched MEDLINE using these two categories. We supplemented this search with Google searches using the same key terms used in the MEDLINE search. Using a comparative approach, we summarized the new product design, development cycle (preclinical and clinical phases), and post-market phases for NAIMDs and drugs. We also evaluated and compared the respective processes to integrate and assess safety data during the life cycle of the products, including signal detection, signal management, and subsequent potential regulatory actions. The search identified a gap in NAIMD safety signal generation: no global program exists that collects and analyzes adverse events and product quality issues. Data sources in real-world settings, such as electronic health records, need to be effectively identified and explored as additional sources of safety information, particularly in some areas such as the EU and USA where there are plans to implement the unique device identifier (UDI). The UDI and other initiatives will enable more robust follow-up and assessment of long-term patient outcomes. The safety evaluation system for NAIMDs differs in many ways from those for drugs, but both systems face analogous challenges with respect to monitoring real-world usage. Certain features of the drug safety evaluation process could, if adopted and adapted for NAIMDs, lead to better and more systematic evaluations of the latter

Cohesin alters immune response gene expression primarily by transcriptional burst frequency modulation

Transcription is an intermittent process that occurs in bursts. The frequency and the number of messenger RNAs (mRNAs) produced by these bursts determine expression levels and shape cell-to-cell variability. Burst dynamics are modulated by productive encounters between enhancers and promoters, which can be facilitated by the cohesin complex through loop ex-trusion. In experimental systems, cohesin deficiency disrupts cell-type-specific expression pro-grams more severely than constitutive gene expression. Cohesin loss of function increases the self-renewal of hematopoietic progenitor stem cells (HPSCs), and cohesin-related mutations are frequent in cancers, such as AML. Cohesin defects in human AML, mouse HSPC and mature myeloid cells lead to a transcriptional state characterised by the reduced expression of inducible inflammatory genes and the elevated expression ofMyctargets and oxidative phosphorylation (OXPHOS) genes. In this thesis, I combine RNAseq, GROseq, scRNAseq, and smFISH to explore how cohesin depletion affects transcriptional parameters at steady-state and during cell-state transitions. Using primary macrophages as a model system, I find that loss of cohesin alters the dynamics of transcriptional bursts without measurably increasing cell-to-cell variability in scRNAseq. I show that expression changes triggered by LPS are primarily orchestrated through the modulation of burst frequencies, and this modulation is blunted in cohesin-deficient macrophages. An increase in burst frequency can have consequences not just for individual cells, but also for their neighbours. Specifically, the frequency of transcriptionalIfnb1bursts determines the number of cells that produceIfnb1-encoded type I interferon (IFN), which through paracrine signalling can alter IFN-dependent expression in neighbouring cells. Co-culture with cohesin-deficient macrophages reduces LPS-induced gene expression in wildtype (WT) macrophages, indicating that cohesin defects can buffer inflammatory responses and impair cell-state transitions due to the defective control of burst frequencies. I speculate that these features contribute to the somatic selection of cohesin mutations in cancer.Open Acces

Diferenciación por nivel de habilidad en varones y mujeres adultos

Despite the increasing importance of the ability-level differentiation hypothesis, no study has been conducted to clarify the role played by sex regarding this issue. A battery of cognitive tests was administered to a sample of 10,247 participants (6,068 males and 4,179 females). Results show a differentiation effect in males (around 2%) but not in females. Therefore, the ability-level differentiation hypothesis is substantiated for males onlyA pesar de la importancia creciente de la hipótesis de la diferenciación por nivel, ningún estudio se ha dirigido a clarificar el papel que la variable sexo juega con respecto a este asunto. En el presente estudio, una batería de pruebas cognitivas se administró a una muestra de 10.247 participantes (6.068 varones y 4.179 mujeres). Se encuentra un efecto de diferenciación en hombres (alrededor de un 2%), que no se replica en mujeres. Por consiguiente, la hipótesis de la diferenciación por nivel de habilidad sólo se mantiene en la muestra de varonesThis research was supported by a grant funded by the Spanish «Ministerio de Educación y Cultura», Grant Nº BSO2000-004

Abilities that explain the Intelligence decline: Evidence from the WAIS-III

Las puntuaciones en los tests de inteligencia declinan con la edad, aunque el grado de declive depende de la naturaleza, fluida o cristalizada, de los tests. Sin embargo, pocas investigaciones han abordado la pregunta de qué aptitudes cognitivas son responsables de tal declive. El presente estudio se centra en esta cuestión. La combinación del análisis factorial jerárquico (procedimiento Schmid-Leiman) y el método de vectores correlacionados permite responder a esta pregunta. Ambos procedimientos han sido utilizados para analizar la muestra de estandarización española del WAIS-III. Los resultados muestran que tanto g como el factor manipulativo son responsables del declive en las puntuaciones. El factor verbal (Gc) no da cuenta de tal declive. Por lo tanto, estos resultados suponen una matización del modelo de aptitudes vulnerables y sostenibles propuesto por HornIntelligence test’s scores decline with age, but such decline change for fluid and crystallized tests. However, little effort has been put to investigate what cognitive abilities are responsible for such decline. The present paper focuses on that issue. A hierarchical factor analysis (performed through the Schmid-Leiman transformation) followed by the method of correlated vectors let us to answer that question. Both procedures were applied to the Spanish standardization sample of the WAIS-III. Results show that g and performance factors are responsible for the decrease on the scores. The verbal factor (Gc) does not account for such decline. Therefore, results draw a more fined-grained view about the Horn’s model distinguishing vulnerable and sustainable cognitive abilitiesLa investigación contenida en este artículo ha sido financiada por un proyecto de investigación concedido por el Ministerio español de Ciencia y Tecnología (Ref: BSO2000-0043

Targetable mechanisms of epigenetic age acceleration and rejuvenation in cancer

Epigenetic clocks are mathematical models that estimate biological age based on DNA methylation patterns. These clocks are powerful tools in ageing research, offering insights into biological processes not captured by chronological age. While effective for healthy samples, current epigenetic clocks perform poorly on tumour data due to different epigenetic alteration patterns in cancer. This thesis aims to develop a novel cancer-specific epigenetic clock using DNA methylation from tumour samples to improve age prediction accuracy in cancer. The study involved evaluating existing epigenetic clocks, implementing a new one trained on pan-tissue cancer data, and comparing its performance with existing clocks. The new clock is an elastic net regression model trained on DNA methylation data from tumour samples across 32 cancer types in The Cancer Genomic Atlas (TCGA) projects. The necessity of this model arose after observing that current clocks, trained on healthy cell DNA methylation, underperformed in cancer settings. The new model outperformed others in predictive capability, showing high correlation between predicted and chronological age for cancer (Pearson R = 0.781) and healthy samples (Pearson R = 0.857). The importance of training on cancer versus healthy samples was evaluated using paired tumour-normal TCGA data, demonstrating that training on cancer data yields better age predictability. The new model shares minimal CpG sites with other clocks, having 5268 unique sites out of 5378. Despite being pan-tissue-based, it is effective for specific tissues, as shown by its predictability on external breast tissue DNA methylation data. It maintains high prediction accuracy even with significant missing data, performing well with up to 50% of predictive CpG sites missing (Pearson R > 0.7). The model only considers CpG sites shared among popular methylation arrays (N = 369,861), enhancing applicability, reliability, and efficiency for comprehensive age estimation. In conclusion, the new model's ability to predict age in both cancer and healthy samples based on cancer data training suggests that DNA methylation patterns may affect common age-related biological pathways, preserved even in cancer conditions. Further studies are needed to explore the functional impact of the predictive CpGs, evaluating their potential as age-related biomarkers for prognostic or therapeutic use in cancer. These findings highlight significant clinical implications, establishing the cancer epigenetic clock as a robust tool for age prediction, advancing early diagnosis, and personalized therapy in cancer settings. Integrating the epigenetic clock with multi-omic approaches will enhance understanding of molecular mechanisms in cancer, potentially linking age-related epigenetic patterns with genetic and molecular events driving cancer progression and treatment response

Advances in Behavioral Genetics Modeling Using Mplus: Applications of Factor Mixture Modeling to Twin Data

This article discusses new latent variable techniques developed by the authors. As an illustration, a new factor mixture model is applied to the monozygotic-dizygotic twin analysis of binary items measuring alcohol-use disorder. In this model, heritability is simultaneously studied with respect to latent class membership and within-class severity dimensions. Different latent classes of individuals are allowed to have different heritability for the severity dimensions. The factor mixture approach appears to have great potential for the genetic analyses of heterogeneous populations. Generalizations for longitudinal data are also outlined

Uso de museos y exposiciones de Madrid para el estudio del cambio social. Una propuesta de mejora en las prácticas docentes de los estudios de comunicación

Este proyecto de innovación docente se propone alinear las necesidades docentes de la enseñanza del Cambio Social, la necesaria formación en contenidos audiovisuales y la disposición de los museos y exposiciones de abrirse a público joven y convertirse en espacios formativos y de reflexión sobre el cambio social. Es clara la necesidad de las profesiones comunicativas de encontrar nichos de empleo

Personality in imprisoned and non-imprisoned people: evidence from the EPQ-R

There are several studies about the personality of convicted criminals. The PEN system has been one of the most frequently tested models. Eysenck (1977) predicted that criminals would show higher scores on P, E, and N. Some studies support that view, while others do not. However, sampling could help to explain the contradictory findings. The present study analysed 229 imprisoned and 322 non-imprisoned participants. Both samples were carefully selected. The imprisoned sample comprised all types of delinquents with a mean age of 32.57, while the non-imprisoned sample comprised participants with a mean age of 29.85. The EPQ-R was used to measure P, E, and N. The results show that the imprisoned sample scores higher on psychoticism, extraversion, and neuroticism. Moreover, while there are sex differences within the non-imprisoned sample, there are no such differences within the imprisoned sample. The latter result sugg ests that personality, but not the sex variable, could be related to antisocial behavior.Personalidad en población penitenciaria y no penitenciaria: resultados a partir del EPQ-R. Existen múltiples estudios acer ca de la Personalidad de los delincuentes. El sistema PEN es uno de los modelos más frecuentemente puestos a prueba. Eysenck (1977) predijo que los delincuentes puntuarían más alto en P, E y N. Algunos estudios apoyan esta idea, mientras que otros no. El muestreo de participantes puede ser una causa de las discrepancias. Por ello, el presente estudio analiza una muestra de 229 presos y 322 no presos. Ambas muestras han sido cuidadosamente seleccionadas. La muestra de presos incluye un amplio espectro de delincuentes con una media de edad de 32.57 y la muestra de no presos presenta una edad media de 29.85. Se aplica el EPQ-R para medir E, N y P. Los resultados muestran que los presos puntúan más alto en E, N y P. Además, mientras que se observan diferencias de sexo en la muestra de no presos, dichas diferencias de sexo desa parecen entre los presos. Este último resultado sugiere que no es el sexo sino la personalidad la variable que puede contribuir a explicar el comportamiento delictivo

Descriptive analysis of postmarket surveillance data for hip implants

Purpose: Recent safety issues involving medical devices have highlighted the need for better postmarket surveillance (PMS) evaluation. This article aims to describe and to assess the quality of the PMS data for a medical device and, finally, to provide recommendations to improve the data gathering process. Methods: A descriptive analysis of medical device reports (MDRs) on the use of MRA, a specific type of hip implant replacement submitted to the Food and Drug Administration Manufacturer and User Facility Device Experience database from 1 January 2008 to 31 December 2017. The number of reports was described as the number of MDRs per unique MDR number and stratified by different variables. The quality was assessed by the level of completeness of the collected PMS data. Results: The total number of reports related to MRA was 2377, and the number of MDRs per year ranged between 84 in 2009 and 452 in 2017. Most of the reports were reported by manufacturer Depuy Johnson & Johnson and were reported by a physician. In 44.9% of the reports, the device problem was reported as “Unknown.” When the device problem was known, in the majority of cases, it was related to an implant fracture. The quality of the collected data was assessed as low due to missing information. Conclusion: The underlying data should meet high quality standards to generate more evidence and to ensure a timely signal generation. This case study shows that the completeness and quality of the MDRs can be improved. The authors propose the development of tools to ensure a more dynamic complaint data collection to contribute to this enhancement

Metodologías alternativas y colaborativas en el uso de la fotografía analógica en períodos de crisis

El objetivo principal del proyecto Metodologías alternativas y colaborativas en el uso de la fotografía analógica en períodos de crisis era: “redescubrir un saber y una técnica que se encuentra olvidada y establecer una metodología colaborativa y nueva para su aprendizaje. Esto conlleva de forma física la recuperación de unas instalaciones de la Facultad de CC.INF. que se encontraban en estado de desuso” (memoria del proyecto de innovación docente 2016-2017, núm. 139)