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Incidence and prognosis of colorectal cancer after heart transplantation: data from the Spanish Post-Heart Transplant Tumor Registry
Get PDFIn this observational and multicenter study, that included all patients who underwent a heart transplantation (HT) in Spain from 1984 to 2018, we analyzed the incidence, management, and prognosis of colorectal cancer (CRC) after HT. Of 6,244 patients with a HT and a median follow-up of 8.8 years since the procedure, 116 CRC cases (11.5% of noncutaneous solid cancers other than lymphoma registered) were diagnosed, mainly adenocarcinomas, after a mean of 9.3 years post-HT. The incidence of CRC increased with age at HT from 56.6 per 100,000 person-years among under 45 year olds to 436.4 per 100,000 person-years among over 64 year olds. The incidence rates for age-at-diagnosis groups were significantly greater than those estimated for the general Spanish population. Curative surgery, performed for 62 of 74 operable tumors, increased the probability of patient survival since a diagnosis of CRC, from 31.6% to 75.7% at 2 years, and from 15.8% to 48.6% at 5 years, compared to patients with inoperable tumors. Our results suggest that the incidence of CRC among HT patients is greater than in the general population, increasing with age at HT
El cabildo eclesiástico de Lima y sus relaciones con el Estado en los primeros años de la República del Perú (1821-1835)
Get PDFDiscurso del Santo Padre Francisco a un grupo de empresarios de España
Get PDFLos actuales desequilibrios económicos y sociales apremian a proponer una economía que contribuya a resolver los grandes problemas que afectan al mundo
DNA methylation partially mediates antidiabetic effects of metformin on HbA1c levels in individuals with type 2 diabetes
Get PDFAims: Despite metformin being used as first-line pharmacological therapy for type 2 diabetes, its underlying
mechanisms remain unclear. We aimed to determine whether metformin altered DNA methylation in newlydiagnosed individuals with type 2 diabetes.
Methods and Results: We found that metformin therapy is associated with altered methylation of 26 sites in blood
from Scandinavian discovery and replication cohorts (FDR < 0.05), using MethylationEPIC arrays. The majority
(88%) of these 26 sites were hypermethylated in patients taking metformin for ~ 3 months compared to controls,
who had diabetes but had not taken any diabetes medication. Two of these blood-based methylation markers
mirrored the epigenetic pattern in muscle and adipose tissue (FDR < 0.05). Four type 2 diabetes-associated SNPs
were annotated to genes with differential methylation between metformin cases and controls, e.g., GRB10,
RPTOR, SLC22A18AS and TH2LCRR. Methylation correlated with expression in human islets for two of these
genes. Three metformin-associated methylation sites (PKNOX2, WDTC1 and MICB) partially mediate effects of
metformin on follow-up HbA1c levels. When combining methylation of these three sites into a score, which was
used in a causal mediation analysis, methylation was suggested to mediate up to 32% of metformin’s effects on
HbA1c.
Conclusion: Metformin-associated alterations in DNA methylation partially mediates metformin’s antidiabetic
effects on HbA1c in newly-diagnosed individuals with type 2 diabetes
Luis Pásara, Católicos, radicales y militantes: Cincuenta años de conflictos en la Iglesia peruana, La Siniestra Ensayos, Lima 2021, 250 pp. [RESEÑA]
Get PDFManfredi Merluzzi / Gaetano Sabatini/ Flavia Tudini (eds.), La Vergine contesa: Roma, l’Immacolata Concezione e l’universalismo della Monarchia Cattolica (secc. XVII-XIX), Viella, Roma 2022, 464 pp. [RESEÑA]
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Zein-based nanospheres and nanocapsules for the encapsulation and oral delivery of quercetin
Get PDFIn this study, the ability of zein nanospheres (NS) and zein nanocapsules containing wheat germ oil (NC) to
enhance the bioavailability and efficacy of quercetin was evaluated. Both types of nanocarriers had similar
physico-chemical properties, including size (between 230 and 250 nm), spherical shape, negative zeta potential,
and surface hydrophobicity. However, NS displayed a higher ability than NC to interact with the intestinal
epithelium, as evidenced by an oral biodistribution study in rats. Moreover, both types of nanocarriers offered
similar loading efficiencies and release profiles in simulated fluids. In C. elegans, the encapsulation of quercetin in
nanospheres (Q-NS) was found to be two twice more effective than the free form of quercetin in reducing lipid
accumulation. For nanocapsules, the presence of wheat germ oil significantly increased the storage of lipids in
C. elegans; although the incorporation of quercetin (Q-NC) significantly counteracted the presence of the oil.
Finally, nanoparticles improved the oral absorption of quercetin in Wistar rats, offering a relative oral
bioavailability of 26% and 57% for Q-NS and Q-NC, respectively, compared to a 5% for the control formulation.
Overall, the study suggests that zein nanocarriers, particularly nanospheres, could be useful in improving the
bioavailability and efficacy of quercetin
Diffeomorphic transformations for time series analysis: An efficient approach to nonlinear warping.
Get PDFThe proliferation and ubiquity of temporal data across many disciplines has sparked interest for similarity, classification and clustering methods specifically designed to handle time series data. A core issue when dealing with time series is determining their pairwise similarity, i.e., the degree to which a given time series resembles another. Traditional distance measures such as the Euclidean are not well-suited due to the time-dependent nature of the data.
Elastic metrics such as dynamic time warping (DTW) offer a promising approach, but are limited by their computational complexity, non-differentiability and sensitivity to noise and outliers.
This thesis proposes novel elastic alignment methods that use parametric & diffeomorphic warping transformations as a means of overcoming the shortcomings of DTW-based metrics. The proposed method is differentiable & invertible, well-suited for deep learning architectures, robust to noise and outliers, computationally efficient, and is expressive and flexible enough to capture complex patterns. Furthermore, a closed-form solution was developed for the gradient of these diffeomorphic transformations, which allows an efficient search in the parameter space, leading to better solutions at convergence.
Leveraging the benefits of these closed-form diffeomorphic transformations, this thesis proposes a suite of advancements that include:
(a) an enhanced temporal transformer network for time series alignment and averaging,
(b) a deep-learning based time series classification model to simultaneously align and classify signals with high accuracy,
(c) an incremental time series clustering algorithm that is warping-invariant, scalable and can operate under limited computational and time resources, and finally,
(d) a normalizing flow model that enhances the flexibility of affine transformations in coupling and autoregressive layers.
Taken together, these advancements demonstrate the versatility and potential of closed-form diffeomorphic transformations for a range of time series applications.
In summary, this thesis aims to enhance time-series tasks such as alignment, averaging, classification and clustering by leveraging the power of fast, efficient, parametric \& diffeomorphic warping methods.La proliferación y ubicuidad de los datos temporales en diversas disciplinas ha despertado un gran interés por los métodos de similitud, clasificación y agrupación diseñados específicamente para manejar series temporales. Uno de los principales desafíos al tratar con este tipo de datos es determinar su similitud. Las medidas de distancia tradicionales, como la euclídea, resultan inadecuadas debido a la naturaleza temporal de los datos. Métricas elásticas como la deformación temporal dinámica (DTW) ofrecen un enfoque correcto, pero están limitadas por su complejidad computacional, no diferenciabilidad y sensibilidad al ruido.
Esta tesis propone nuevos métodos de alineación elástica que emplean transformaciones de deformación paramétricas y difeomórficas para superar las limitaciones de las métricas basadas en DTW. El método propuesto es diferenciable e invertible, lo que lo hace adecuado para arquitecturas de aprendizaje profundo. Además, es robusto frente al ruido, computacionalmente eficiente y lo suficientemente expresivo y flexible como para capturar patrones complejos. Asimismo, se ha desarrollado una solución cerrada para el cálculo del gradiente de estas transformaciones difeomórficas, lo que permite una búsqueda eficiente en el espacio de parámetros y conduce a mejores soluciones en convergencia.
Aprovechando los beneficios de estas transformaciones difeomórficas de forma cerrada, esta tesis propone un conjunto de avances que incluyen:
(a) un transformador temporal vitaminado para la alineación y promediado de series temporales,
(b) un modelo de clasificación de series temporales basado en aprendizaje profundo para alinear y clasificar simultáneamente señales con alta precisión,
(c) un algoritmo incremental de agrupación de series temporales que es invariable a la deformación, escalable y puede funcionar con recursos computacionales limitados, y finalmente,
(d) un modelo de flujo normalizador que mejora la flexibilidad de las transformaciones afines en las capas de acoplamiento y autorregresivas.
En conjunto, estos avances demuestran la versatilidad y el potencial de las transformaciones difeomórficas en forma cerrada para diversas aplicaciones relacionadas con las series temporales.
En resumen, esta tesis pretende mejorar tareas como la alineación, el promediado, la clasificación y la agrupación de series temporales aprovechando la potencia y eficiencia de los métodos paramétricos de deformación difeomórfica
Do not do recommendations in different paediatric care settings
No full textIntroduction: There are many initiatives aimed at eliminating health care interventions of limited utility in clinical practice. The Committee on Care Quality and Patient Safety of the Spanish Association of Pediatrics has proposed the development of > recommenda-tions (DNDRs) to establish a series of practices to be avoided in the care of paediatric patients in primary, emergency, inpatient and home-based care. Material and methods: The project was carried out in 2 phases: a first phase in which possible DNDRs were proposed, and a second in which the final recommendations were established by consensus using the Delphi method. Recommendations were proposed and evaluated by mem-bers of the professional groups and paediatrics societies invited to participate in the project under the coordination of members of the Committee on Care Quality and Patient Safety. Results: A total of 164 DNDRs were proposed by the Spanish Society of Neonatology, the Spanish Association of Primary Care Paediatrics, the Spanish Society of Paediatric Emergency Medicine, the Spanish Society of Internal Hospital Paediatrics and the Medicines Committee of the Spanish Association of Pediatrics and the Spanish Group of Paediatric Pharmacy of the Spanish Society of Hospital Pharmacy. The initial set was limited to 42 DNDRs, and the selection over successive rounds yielded a final set of 25 DNDRs, with 5 DNDRs for each paediatrics group or society. Conclusions: This project allowed the selection and establishment by consensus of a series of recommendations to avoid unsafe, inefficient or low-value practices in different areas of paediatric care, which may contribute to improving the safety and quality of paediatric clinical practice. (c) 2023 Asociacion Espanola de Pediatria. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/)