A Framework for Simulating Home Control Networks

Non

Smart Nanoparticles as Advanced Anti-Akt Kinase Delivery Systems for Pancreatic Cancer Therapy

Pancreatic cancer is one of the deadliest cancers partly due to late diagnosis, poor drug delivery to the target site, and acquired resistance to therapy. Therefore, more effective therapies are urgently needed to improve the outcome of patients. In this work, we have tested self-assembling genetically engineered polymeric nanoparticles formed by elastin-like recombinamers (ELRs), carrying a small peptide inhibitor of the protein kinase Akt, in both PANC-1 and patient-derived pancreatic cancer cells (PDX models). Nanoparticle cell uptake was measured by flow cytometry, and subcellular localization was determined by confocal microscopy, which showed a lysosomal localization of these nanoparticles. Furthermore, metabolic activity and cell viability were significantly reduced after incubation with nanoparticles carrying the Akt inhibitor in a time- and dose-dependent fashion. Self-assembling 73 ± 3.2 nm size nanoparticles inhibited phosphorylation and consequent activation of Akt protein, blocked the NF-κB signaling pathway, and triggered caspase 3-mediated apoptosis. Furthermore, in vivo assays showed that ELR-based nanoparticles were suitable devices for drug delivery purposes with long circulating time and minimum toxicity. Hence, the use of these smart nanoparticles could lead to the development of more effective treatment options for pancreatic cancer based on the inhibition of Akt

Evolution of the silicon bottom cell photovoltaic behavior during III-V on Si multi-junction solar cells production

The evolution of the Si bulk minority carrier lifetime during the heteroepitaxial growth of III-V on Si multi-junction solar cell structures via metal-organic vapor phase epitaxy has been analyzed. Initially, the emitter formation produces important lifetime degradation. Nevertheless, a progressive recovery was observed during the growth of the metamorphic GaAsP/Si structure. A step-wise mechanism has been proposed to explain the lifetime evolution observed during this process. The initial lifetime degradation is believed to be related to the formation of thermally-induced defects within the Si bulk. These defects are subsequently passivated by fast-diffusing atomic hydrogen -coming from precursor (i.e. PH3 and AsH3) pyrolysis- during the subsequent III-V growth. These results indicate that the MOVPE environment used to create the III-V/Si solar cell structures has a dynamic impact on the minority carrier lifetime. Consequently, designing processes that promote the recovery of the lifetime is a must to support the production of high-quality III-V/Si solar cells

Temporal variability analysis reveals biases in electronic health records due to hospital process reengineering interventions over seven years

[EN] Objective To evaluate the effects of Process-Reengineering interventions on the Electronic Health Records (EHR) of a hospital over 7 years. Materials and methods Temporal Variability Assessment (TVA) based on probabilistic data quality assessment was applied to the historic monthly-batched admission data of Hospital La Fe Valencia, Spain from 2010 to 2016. Routine healthcare data with a complete EHR was expanded by processed variables such as the Charlson Comorbidity Index. Results Four Process-Reengineering interventions were detected by quantifiable effects on the EHR: (1) the hospital relocation in 2011 involved progressive reduction of admissions during the next four months, (2) the hospital services re-configuration incremented the number of inter-services transfers, (3) the care-services re-distribution led to transfers between facilities (4) the assignment to the hospital of a new area with 80,000 patients in 2015 inspired the discharge to home for follow up and the update of the pre-surgery planned admissions protocol that produced a significant decrease of the patient length of stay. Discussion TVA provides an indicator of the effect of process re-engineering interventions on healthcare practice. Evaluating the effect of facilities¿ relocation and increment of citizens (findings 1, 3¿4), the impact of strategies (findings 2¿3), and gradual changes in protocols (finding 4) may help on the hospital management by optimizing interventions based on their effect on EHRs or on data reuse. Conclusions The effects on hospitals EHR due to process re-engineering interventions can be evaluated using the TVA methodology. Being aware of conditioned variations in EHR is of the utmost importance for the reliable reuse of routine hospitalization data.F.J.P.B, C.S., J.M.G.G. and J.A.C. were funded Universitat Politecnica de Valencia, project "ANALISIS DE LA CALIDAD Y VARIABILIDAD DE DATOS MEDICOS". www.upv.es. J.M.G.G.is also partially supported by: Ministerio de Economia y Competitividad of Spain through MTS4up project (National Plan for Scientific and Technical Research and Innovation 2013-2016, No. DPI2016-80054-R); and European Commission projects H2020-SC1-2016-CNECT Project (No. 727560) and H2020-SC1-BHC-2018-2020 (No. 825750). The funders did not play any role in the study design, data collection and analysis, decision to publish, nor preparation of the manuscript.Perez-Benito, FJ.; Sáez Silvestre, C.; Conejero, JA.; Tortajada, S.; Valdivieso, B.; Garcia-Gomez, JM. (2019). Temporal variability analysis reveals biases in electronic health records due to hospital process reengineering interventions over seven years. PLoS ONE. 14(8):1-19. https://doi.org/10.1371/journal.pone.0220369S119148Aguilar-Savén, R. S. (2004). Business process modelling: Review and framework. International Journal of Production Economics, 90(2), 129-149. doi:10.1016/s0925-5273(03)00102-6Poulymenopoulou, M. 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IEEE; 2017. pp. 230–237. doi: https://doi.org/10.1109/PDCAT.2017.00045Chou, Y.-C., Chen, B.-Y., Tang, Y.-Y., Qiu, Z.-J., Wu, M.-F., Wang, S.-C., … Chuang, W.-C. (2010). Prescription-Filling Process Reengineering of an Outpatient Pharmacy. Journal of Medical Systems, 36(2), 893-902. doi:10.1007/s10916-010-9553-5Leu, J.-D., & Huang, Y.-T. (2009). An Application of Business Process Method to the Clinical Efficiency of Hospital. Journal of Medical Systems, 35(3), 409-421. doi:10.1007/s10916-009-9376-4Gand K. Investigating on Requirements for Business Model Representations: The Case of Information Technology in Healthcare. 2017 IEEE 19th Conference on Business Informatics (CBI). IEEE; 2017. pp. 471–480. doi: https://doi.org/10.1109/CBI.2017.36Ferreira, G. S. A., Silva, U. R., Costa, A. L., & Pádua, S. I. D. de D. (2018). The promotion of BPM and lean in the health sector: main results. Business Process Management Journal, 24(2), 400-424. doi:10.1108/bpmj-06-2016-0115Abdulrahman Jabour RM. Cancer Reporting: Timeliness Analysis and Process. 2016; Available: https://search.proquest.com/openview/4ecf737c5ef6d2d503e948df8031fe54/1?pq-origsite=gscholar&cbl=18750&diss=yHewitt M, Simone J V. Enhancing Data Systems to Improve the Quality of Cancer Care [Internet]. National Academy Press; 2000. Available: http://www.nap.edu/catalog/9970.htmlWeiskopf, N. G., & Weng, C. (2013). Methods and dimensions of electronic health record data quality assessment: enabling reuse for clinical research. Journal of the American Medical Informatics Association, 20(1), 144-151. doi:10.1136/amiajnl-2011-000681Saez C, Robles M, Garcia-Gomez JM. Comparative study of probability distribution distances to define a metric for the stability of multi-source biomedical research data. Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS. IEEE; 2013. pp. 3226–3229. doi: https://doi.org/10.1109/EMBC.2013.6610228Sáez, C., Rodrigues, P. 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Probabilistic methods for multi-source and temporal biomedical data quality assessment [Internet]. Thesis. Universitat Politècnica de València. 2016. doi: https://doi.org/10.4995/Thesis/10251/62188Amari S, Nagaoka H. Methods of Information Geometry [Internet]. Amer. Math. Soc. and Oxford Univ. Press. American Mathematical Society; 2000. Available: https://books.google.es/books?hl=es&lr=&id=vc2FWSo7wLUC&oi=fnd&pg=PR7&dq=Methods+of+Information+geometry&ots=4HmyCCY4PX&sig=2-dpCuwMQvEC1iREjxdfIX0yEls#v=onepage&q=MethodsofInformationgeometry&f=falseCsiszár, I., & Shields, P. C. (2004). Information Theory and Statistics: A Tutorial. Foundations and Trends™ in Communications and Information Theory, 1(4), 417-528. doi:10.1561/0100000004Lin, J. (1991). Divergence measures based on the Shannon entropy. IEEE Transactions on Information Theory, 37(1), 145-151. doi:10.1109/18.61115M.Cover T. Elements Of Information Theory Notes [Internet]. 2006. Available: http://books.google.fr/books?id=VWq5GG6ycxMC&printsec=frontcover&dq=intitle:Elements+of+Information+Theory&hl=&cd=1&source=gbs_api%5Cnpapers2://publication/uuid/BAF426F8-5A4F-44A4-8333-FA8187160D9BBrandes, U., & Pich, C. (s. f.). Eigensolver Methods for Progressive Multidimensional Scaling of Large Data. Lecture Notes in Computer Science, 42-53. doi:10.1007/978-3-540-70904-6_6Liaw, S. T., Rahimi, A., Ray, P., Taggart, J., Dennis, S., de Lusignan, S., … Talaei-Khoei, A. (2013). Towards an ontology for data quality in integrated chronic disease management: A realist review of the literature. International Journal of Medical Informatics, 82(1), 10-24. doi:10.1016/j.ijmedinf.2012.10.001Arts, D. G. T. (2002). Defining and Improving Data Quality in Medical Registries: A Literature Review, Case Study, and Generic Framework. Journal of the American Medical Informatics Association, 9(6), 600-611. doi:10.1197/jamia.m1087Bray, F., & Parkin, D. M. (2009). 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Workflow mining: discovering process models from event logs. IEEE Transactions on Knowledge and Data Engineering, 16(9), 1128-1142. doi:10.1109/tkde.2004.47Weijters AJMM, Van Der Aalst WMP, Alves De Medeiros AK. Process Mining with the HeuristicsMiner Algorithm [Internet]. Available: https://pdfs.semanticscholar.org/1cc3/d62e27365b8d7ed6ce93b41c193d0559d086.pdfShim, S. J., & Kumar, A. (2010). Simulation for emergency care process reengineering in hospitals. Business Process Management Journal, 16(5), 795-805. doi:10.1108/14637151011076476Svolba, G., & Bauer, P. (1999). Statistical Quality Control in Clinical Trials. Controlled Clinical Trials, 20(6), 519-530. doi:10.1016/s0197-2456(99)00029-xKahn, M. G., Raebel, M. A., Glanz, J. M., Riedlinger, K., & Steiner, J. F. (2012). A Pragmatic Framework for Single-site and Multisite Data Quality Assessment in Electronic Health Record-based Clinical Research. 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To err is human: building a safer health system. A report of the Committee on Quality of Health Care in America. 2000. p. 287. National Academies Press

Towards the implementation of laser engineered surface structures for electron cloud mitigation

The LHC operation has proven that the electron cloud could be a significant limiting factor in machine performance, in particular for future High Luminosity LHC (HL-LHC) beams. Electron clouds, generated by electron multipacting in the beam pipes, leads to beam instabilities and beam-induced heat load in cryogenic systems. Laser Engineered Surface Structures (LESS) is a novel surface treatment which changes the morphology of the internal surfaces of vacuum chambers. The surface modification results in a reduced secondary electron yield (SEY) and, consequently, in the eradication of the electron multipacting. Low SEY values of the treated surfaces and flexibility in choosing the laser parameters make LESS a promising treatment for future accelerators. LESS can be applied both in new and existing accelerators owing to the possibility of automated in-situ treatment. This approach has been developed and optimised for the LHC beam screens in which the electron cloud has to be mitigated before the HL-LHC upgrade. We will present the latest steps towards the implementation of LESS

Enfermedad de Hirschsprung, a propósito de un caso

Introduction: Hirschsprung's disease (HD) is within theclinical context one of Pediatric diseases that lowerIncidencehas, representing barely 2.7% of all of them, according todata from the American College of Pediatrics (ACP). However, its pathophysiologyand clinical behavior governed by the age of the patient are the main variablesthat complicate the diagnosis and give errors of up to 35%(ACP). The mortality of patients can amount up to 65% whenthe EH is complicated with a picture of Necrotizingenterocolitis, in a patient who has notbeen theeliminationof meconium within the first 12 hours of life must suspecteh, always takinginto account the patient's age and recallingthat preterm the same delay can be considered normal, while in the case oflarger aged patients the incidence of thedisease is lower, however the diagnostic probability should not be disregarded. Sepsis in abdominal origin andnecrotising enterocolitis are two of the major complicationsof which the physician should be prevented, even when, asreported in the present case, even patients who are opposedto the main factors of risk described in literature, such asage, can develop a HD box and a latent risk of complicationlikethe rest of patients that if shared these risk factors. Objective: To describe a case of Hirschsprung's disease. Material and methods: a descriptive, retrospective studyabout Hirschsprung's disease clinical case presenta-tion. Results: Describes a case of Hirschsprung's disease inpediatric patient with complications and resolution satisfactory quirurgica. Conclusions: The proper implementation of the clinicalmethod allows an accurate diagnosis and timely treatmentof Hirschsprung's disease.Introducción: La Enfermedad deHirschsprung (EH) es dentro del contexto clínico-quirúrgico una de las patologías pediátricas que menor incidencia posee, representando a penas el 2,7% de todas ellas según datos del Colegio Americano de Pediatría (ACP). Sin embargo, su fisiopatología y su comportamiento clínico regido por la edad del paciente son las principales variables que complican el diagnóstico y dan errores de hasta un 35% (ACP). La mortalidad de los pacientes puede ascender hasta un 65% cuando la EHse complica con un cuadro de enterocolitis necrotizante, en un paciente que no se ha conseguido la eliminación de meconio dentro de las 12 primeras horas de vida deberá sospecharse de EH, siempre tomando en cuenta la edad del pacientey recordando que en pretérminos el retraso del mismopuede considerarse normal, mientras que en el caso de pacientes más grandes de edadla incidencia de la patología es menor, sin embargo la probabilidad diagnóstica no debe de ser menospreciada. La sepsis de origen abdominal y enterocolitis necrotizante son dos de las grandes complicaciones de las cuales el médico debe estar prevenido, más aún, cuando, como se relata en el presente caso clínico, incluso pacientes que se contraponen a los principales factores de riesgo descritos por la literatura, como la edad, pueden desarrollar un cuadro de EH y tener un riesgo latente de complicación al igual que el resto de pacientes que si comparten dichos factores de riesgos. Objetivo: Describir un caso clínico de Enfermedad de Hirschsprung. Material y métodos: Se realizó un estudio descriptivo, retrospectivo, presentación de caso clínico sobre Enfermedad de Hirschsprung. Resultados: Se describe un caso de Enfermedad de Hirschsprung en paciente pediátrico con complicaciones y resolución quirpurgica satisfactoria. Conclusiones: La adecuada aplicación del método clínico permite un diagnóstico preciso y tratamiento oportuno de la Enfermedad de Hirschsprung

Enfermedad de Hirschsprung, a propósito de un caso

Introduction: Hirschsprung's disease (HD) is within theclinical context one of Pediatric diseases that lowerIncidencehas, representing barely 2.7% of all of them, according todata from the American College of Pediatrics (ACP). However, its pathophysiologyand clinical behavior governed by the age of the patient are the main variablesthat complicate the diagnosis and give errors of up to 35%(ACP). The mortality of patients can amount up to 65% whenthe EH is complicated with a picture of Necrotizingenterocolitis, in a patient who has notbeen theeliminationof meconium within the first 12 hours of life must suspecteh, always takinginto account the patient's age and recallingthat preterm the same delay can be considered normal, while in the case oflarger aged patients the incidence of thedisease is lower, however the diagnostic probability should not be disregarded. Sepsis in abdominal origin andnecrotising enterocolitis are two of the major complicationsof which the physician should be prevented, even when, asreported in the present case, even patients who are opposedto the main factors of risk described in literature, such asage, can develop a HD box and a latent risk of complicationlikethe rest of patients that if shared these risk factors. Objective: To describe a case of Hirschsprung's disease. Material and methods: a descriptive, retrospective studyabout Hirschsprung's disease clinical case presenta-tion. Results: Describes a case of Hirschsprung's disease inpediatric patient with complications and resolution satisfactory quirurgica. Conclusions: The proper implementation of the clinicalmethod allows an accurate diagnosis and timely treatmentof Hirschsprung's disease.Introducción: La Enfermedad deHirschsprung (EH) es dentro del contexto clínico-quirúrgico una de las patologías pediátricas que menor incidencia posee, representando a penas el 2,7% de todas ellas según datos del Colegio Americano de Pediatría (ACP). Sin embargo, su fisiopatología y su comportamiento clínico regido por la edad del paciente son las principales variables que complican el diagnóstico y dan errores de hasta un 35% (ACP). La mortalidad de los pacientes puede ascender hasta un 65% cuando la EHse complica con un cuadro de enterocolitis necrotizante, en un paciente que no se ha conseguido la eliminación de meconio dentro de las 12 primeras horas de vida deberá sospecharse de EH, siempre tomando en cuenta la edad del pacientey recordando que en pretérminos el retraso del mismopuede considerarse normal, mientras que en el caso de pacientes más grandes de edadla incidencia de la patología es menor, sin embargo la probabilidad diagnóstica no debe de ser menospreciada. La sepsis de origen abdominal y enterocolitis necrotizante son dos de las grandes complicaciones de las cuales el médico debe estar prevenido, más aún, cuando, como se relata en el presente caso clínico, incluso pacientes que se contraponen a los principales factores de riesgo descritos por la literatura, como la edad, pueden desarrollar un cuadro de EH y tener un riesgo latente de complicación al igual que el resto de pacientes que si comparten dichos factores de riesgos. Objetivo: Describir un caso clínico de Enfermedad de Hirschsprung. Material y métodos: Se realizó un estudio descriptivo, retrospectivo, presentación de caso clínico sobre Enfermedad de Hirschsprung. Resultados: Se describe un caso de Enfermedad de Hirschsprung en paciente pediátrico con complicaciones y resolución quirpurgica satisfactoria. Conclusiones: La adecuada aplicación del método clínico permite un diagnóstico preciso y tratamiento oportuno de la Enfermedad de Hirschsprung

Evidence of the association of BIN1 and PICALM with the AD risk in contrasting European populations

Recent genome-wide association studies have identified five loci (BIN1, CLU, CR1, EXOC3L2 and PICALM) as genetic determinants of Alzheimer’s disease (AD). We attempted to confirm the association between these genes and the AD risk in three contrasting European populations (from Finland, Italy and Spain). Since CLU and CR1 had already been analyzed in these populations, we restricted our investigation to BIN1, EXO2CL3 and PICALM. In a total of 2,816 AD cases and 2,706 controls, we unambiguously replicated the association of rs744373 (for BIN1) and rs541458 (for PICALM) polymorphisms with the AD risk (OR=1.26, 95% CI [1.15-1.38], p=2.9x10-7, and OR=0.80, 95% CI [0.74-0.88], p=4.6x10-7, respectively). In a meta-analysis, rs597668 (EXOC3L2) was also associated with the AD risk, albeit to a lesser extent (OR=1.19, 95% CI [1.06-1.32], p=2.0x10-3). However, this signal did not appear to be independent of APOE. In conclusion, we confirmed that BIN1 and PICALM are genetic determinants of AD, whereas the potential involvement of EXOC3L2 requires further investigation

Steric sea level variability (1993-2010) in an ensemble of ocean reanalyses and objective analyses

Quantifying the effect of the seawater density changes on sea level variability is of crucial importance for climate change studies, as the sea level cumulative rise can be regarded as both an important climate change indicator and a possible danger for human activities in coastal areas. In this work, as part of the Ocean Reanalysis Intercomparison Project, the global and regional steric sea level changes are estimated and compared from an ensemble of 16 ocean reanalyses and 4 objective analyses. These estimates are initially compared with a satellite-derived (altimetry minus gravimetry) dataset for a short period (2003–2010). The ensemble mean exhibits a significant high correlation at both global and regional scale, and the ensemble of ocean reanalyses outperforms that of objective analyses, in particular in the Southern Ocean. The reanalysis ensemble mean thus represents a valuable tool for further analyses, although large uncertainties remain for the inter-annual trends. Within the extended intercomparison period that spans the altimetry era (1993–2010), we find that the ensemble of reanalyses and objective analyses are in good agreement, and both detect a trend of the global steric sea level of 1.0 and 1.1 ± 0.05 mm/year, respectively. However, the spread among the products of the halosteric component trend exceeds the mean trend itself, questioning the reliability of its estimate. This is related to the scarcity of salinity observations before the Argo era. Furthermore, the impact of deep ocean layers is non-negligible on the steric sea level variability (22 and 12 % for the layers below 700 and 1500 m of depth, respectively), although the small deep ocean trends are not significant with respect to the products spread