The Modularisation Design Approach Applied to the ADAS Domain: The DESERVE Project Experience

The paper focuses on the innovative strength that the DESERVE platform has brought on the Advanced Driver Assistance Systems (ADAS) market in terms of major safety and economic affordability. DESERVE is a project aimed at designing and implementing a low-cost, integrated platform for ADAS: the creation of innovative software and hardware modules to be integrated in ADAS applications will pave the way to a standardization of the single components in order to achieve a full integration of diversified models despite their complexity. The achievement of such objective will end up in an increase of the reliability level of the system and in a cost reduction for ADAS functions and for development costs as well. In this paper the results of the application of the modularisation philosophy to the DESERVE platform architecture and to the human machine interface (HMI) concepts will be presented

Arqueología y antropología forense de la represión franquista en el territorio de la Agrupación Guerrillera de Levante y Aragón (1947-1948)

El presente trabajo resume las conclusiones alcanzadas hasta el momento en el marco del proyecto de investigación Recuperación de desaparecidos y represaliados por el franquismo durante el periodo guerrillero. Proyecto que surge desde la Oficina de Desaparecidos de la asociación La Gavilla Verde (Santa Cruz de Moya, Cuenca) en 2003 y que cuenta con Grupo Paleolab® en las tareas de recuperación e identificación de fosas comunes y desaparecidos. Se recogen los principales resultados de las exhumaciones y análisis bioantropológicos realizados en cinco fosas ubicadas en el territorio de actuación de la Agrupación Guerrillera de Levante y Aragón (AGLA) en las provincias de Cuenca y Teruel: La Ginebrosa (Teruel), Monroyo (Teruel), Alcalá de la Selva (Teruel), Fuertescusa (Cuenca) y Villarejo de la Peñuela (Cuenca). Los resultados obtenidos han permitido localizar e identificar a diez y seis desaparecidos, mientras que en dos casos no fue posible la recuperación de los mismos. En todos los casos estudiados, la arqueología y antropología forense han permitido conocer la dimensión real de la represión de la dictadura a finales de la década de los cuarenta, principalmente ejercida por la Guardia Civil.This paper tries to sum up the conclusions achieved until now within the framework of the research project Recovery of disappeared and victims of reprisal by Franco’s regime during guerrilla time. This is a project that comes up from the Office of Missing of the association “La Gavilla Verde” (Santa Cruz de Moya, Cuenca) in 2003. This counts with the group Paleolab in the tasks of recovering and identifying of common graves and disappeared people. Here, the main data of exhumation and of the bioanthropological analysis made in five common graves placed in the territory of performance of guerrilla groups called “Agrupación Guerrillera de Levante y Aragón (AGLA)” in provinces of Cuenca and Teruel: La Ginebrosa (Teruel), Monroyo (Teruel), Alcalá de la Selva (Teruel), Fuertescusa (Cuenca) y Villarejo de la Peñuela (Cuenca). The results obtained have achieved to locate and identify sixteen disappeared people. However, in two cases it was impossible to recover the bodies. In all the cases studied, the archaeology and the forensic anthropology has achieved to know the real dimension of the repression carried out by the dictatorship in the last years of the forties, mainly practiced by the civil guard

New markers for human ovarian cancer that link platinum resistance to the cancer stem cell phenotype and define new therapeutic combinations and diagnostic tools

BACKGROUND: Ovarian cancer is the leading cause of gynecologic cancer-related death, due in part to a late diagnosis and a high rate of recurrence. Primary and acquired platinum resistance is related to a low response probability to subsequent lines of treatment and to a poor survival. Therefore, a comprehensive understanding of the mechanisms that drive platinum resistance is urgently needed. METHODS: We used bioinformatics analysis of public databases and RT-qPCR to quantitate the relative gene expression profiles of ovarian tumors. Many of the dysregulated genes were cancer stem cell (CSC) factors, and we analyzed its relation to therapeutic resistance in human primary tumors. We also performed clustering and in vitro analyses of therapy cytotoxicity in tumorspheres. RESULTS: Using bioinformatics analysis, we identified transcriptional targets that are common endpoints of genetic alterations linked to platinum resistance in ovarian tumors. Most of these genes are grouped into 4 main clusters related to the CSC phenotype, including the DNA damage, Notch and C-KIT/MAPK/MEK pathways. The relative expression of these genes, either alone or in combination, is related to prognosis and provide a connection between platinum resistance and the CSC phenotype. However, the expression of the CSC-related markers was heterogeneous in the resistant tumors, most likely because there were different CSC pools. Furthermore, our in vitro results showed that the inhibition of the CSC-related targets lying at the intersection of the DNA damage, Notch and C-KIT/MAPK/MEK pathways sensitize CSC-enriched tumorspheres to platinum therapies, suggesting a new option for the treatment of patients with platinum-resistant ovarian cancer. CONCLUSIONS: The current study presents a new approach to target the physiology of resistant ovarian tumor cells through the identification of core biomarkers. We hypothesize that the identified mutations confer platinum resistance by converging to activate a few pathways and to induce the expression of a few common, measurable and targetable essential genes. These pathways include the DNA damage, Notch and C-KIT/MAPK/MEK pathways. Finally, the combined inhibition of one of these pathways with platinum treatment increases the sensitivity of CSC-enriched tumorspheres to low doses of platinum, suggesting a new treatment for ovarian cancerSpanish Ministry of Education FPU12/01380Spanish Ministry of Economy and Competitivity, Plan Estatal de I + D + I 2013–2016Spanish Ministry of Science, Innovation and Universities (RTI2018–097455-B-I00)CIBER de Cáncer (CD16/12/00275)Spanish Consejería de Salud of the Junta de Andalucia (PI-0397-2017

Amino modified metal-organic frameworks as pH-responsive nanoplatforms for safe delivery of camptothecin

[EN] MIL-100(Fe) and MIL-101(Fe) metal-organic frameworks (MOFs) are excellent vehicles for drug delivery systems (DDSs) due to their high biocompatibility and stability in physiological fluids, as well as their pore diameter in the mesoporous range. Although they are appropriate for the internal diffusion of 20-(S)-camptothecin (CPT), a strongly cytotoxic molecule with excellent antitumor activity, no stable delivery system has been proposed so far for this drug based in MOFs. We here present novel DDSs based in amine functionalized MIL-100(Fe) and MIL-101(Fe) nanoMOFs with covalently bonded CPT. These CPT nanoplatforms are able to incorporate almost 20% of this molecule and show high stability at physiological pH, with no non-specific release. Based on their surface charge, some of these CPT loaded nanoMOFs present improved cell internalization in in vitro experiments. Moreover, a strong response to acid pH is observed, with up to four fold drug discharge at pH 5, which boost intracellular release by endosomolytic activity. These novel DDSs will help to achieve safe delivery of the very cytotoxic CPT, allowing to reduce the therapeutic dose and minimizing drug secondary effects. (C) 2019 Elsevier Inc. All rights reserved.Financial support of the Spanish Ministry of Economy and Competitiveness (projects TEC2016-80976-R and SEV-2016-0683) is gratefully acknowledged. A.C.G. thanks the La Caixa Foundation for a Ph.D. scholarship. We fully appreciate the assistance of the Electron Microscopy Service of the Universitat Politecnica de Valencia.Cabrera-García, A.; Checa-Chavarria, E.; Rivero-Buceta, EM.; Moreno Manzano, V.; Fernandez Jover, E.; Botella Asuncion, P. (2019). Amino modified metal-organic frameworks as pH-responsive nanoplatforms for safe delivery of camptothecin. Journal of Colloid and Interface Science. 541:163-174. https://doi.org/10.1016/j.jcis.2019.01.042S16317454

Identification of clusters in multifocal electrophysiology recordings to maximize discriminant capacity (patients vs. control subjects)

Purpose To propose a new method of identifying clusters in multifocal electrophysiology (multifocal electroretinogram: mfERG; multifocal visual-evoked potential: mfVEP) that conserve the maximum capacity to discriminate between patients and control subjects. Methods The theoretical framework proposed creates arbitrary N-size clusters of sectors. The capacity to discriminate between patients and control subjects is assessed by analysing the area under the receiver operator characteristic curve (AUC). As proof of concept, the method is validated using mfERG recordings taken from both eyes of control subjects (n = 6) and from patients with multiple sclerosis (n = 15). Results Considering the amplitude of wave P1 as the analysis parameter, the maximum value of AUC = 0.7042 is obtained with N = 9 sectors. Taking into account the AUC of the amplitudes and latencies of waves N1 and P1, the maximum value of the AUC = 0.6917 with N = 8 clustered sectors. The greatest discriminant capacity is obtained by analysing the latency of wave P1: AUC = 0.8854 with a cluster of N = 12 sectors. Conclusion This paper demonstrates the effectiveness of a method able to determine the arbitrary clustering of multifocal responses that possesses the greatest capacity to discriminate between control subjects and patients when applied to the visual field of mfERG or mfVEP recordings. The method may prove helpful in diagnosing any disease that is identifiable in patients’ mfERG or mfVEP recordings and is extensible to other clinical tests, such as optical coherence tomography

Analysis of Patient Safety Incidents in Primary Care Reported in an Electronic Registry Application

Incident notification; Patient safety; Risk managementNotificació d'incident; Seguretat dels pacients; Gestió de riscNotificación de incidentes: Seguridad del paciente; Gestión de riesgoObjectives: (1) To describe the epidemiology of patient safety (PS) incidents registered in an electronic notification system in primary care (PC) health centres; (2) to define a risk map; and (3) to identify the critical areas where intervention is needed. Design: Descriptive analytical study of incidents reported from 1 January to 31 December 2018, on the TPSC Cloud™ platform (The Patient Safety Company) accessible from the corporate website (Intranet) of the regional public health service. Setting: 24 Catalan Institute of Health PC health centres of the Tarragona region (Spain). Participants: Professionals from the PC health centres and a Patient Safety Functional Unit. Measurements: Data obtained from records voluntarily submitted to an electronic, standardised and anonymised form. Data recorded: healthcare unit, notifier, type of incident, risk matrix, causal and contributing factors, preventability, level of resolution and improvement actions. Results: A total of 1544 reports were reviewed and 1129 PS incidents were analysed: 25.0% of incidents did not reach the patient; 66.5% reached the patient without causing harm, and 8.5% caused adverse events. Nurses provided half of the reports (48.5%), while doctors reported more adverse events (70.8%; p < 0.01). Of the 96 adverse events, 46.9% only required observation, 34.4% caused temporary damage that required treatment, 13.5% required (or prolonged) hospitalization, and 5.2% caused severe permanent damage and/or a situation close to death. Notably, 99.2% were considered preventable. The main critical areas were: communication (27.8%), clinical-administrative management (25.1%), care delivery (23.5%) and medicines (18.4%); few incidents were related to diagnosis (3.6%). Conclusions: PS incident notification applications are adequate for reporting incidents and adverse events associated with healthcare. Approximately 75% and 10% of incidents reach the patient and cause some damage, respectively, and most cases are considered preventable. Adequate and strengthened risk management of critical areas is required to improve PS

Insulin allergy and resistance successfully treated by desensitisation with Aspart insulin

A 25-year-old, with type I Diabetes Mellitus with a previous diagnosis of Protamine Allergy but not to human Insulin, started to notice anaphylactic reactions inmmediatly after bolus with Insulin. Skin prick and intradermal test were positive to all insulins. Skin tests to other potential allergens resulted negative. Examination after bolus of Human Insulin revealed urticaria. Daily insulin requirement were around 2-2,4 U/Kg/day. Slow desensitisation with Aspart insulin, the insulin with lowest size of skin test, was performed using subcutaneous insulin pump. Six months after the end of desensitisation his daily insulin requirement decreased to 0.8 U/Kg/day and oral corticosteroids are being reduced with no symptoms

Optimization of a class of tryptophan dendrimers that inhibit HIV replication leads to a selective, specific, and low-nanomolar inhibitor of clinical isolates of enterovirus A71

Tryptophan dendrimers that inhibit HIV replication by binding to the HIV envelope glycoproteins gp120 and gp41 have unexpectedly also proven to be potent, specific, and selective inhibitors of the replication of the unrelated enterovirus A71. Dendrimer 12, a consensus compound that was synthesized on the basis of the structure-activity relationship analysis of this series, is 3-fold more potent against the BrCr lab strain and, surprisingly, inhibits a large panel of clinical isolates in the low-nanomolar/high-picomolar range.This work has been supported by the Spanish MINECO (Project SAF2012-39760-C02-01, cofinanced by the FEDER program; Plan Nacional de Cooperación Público-Privada; and Subprograma INNPACTO IPT-2012-0213-060000, cofinanced by the FEDER program) and the Comunidad de Madrid (BIPEDD2-CM-S2010/BMD-2457). This work was also funded by EU FP7 (FP7/2007-2013) Project EUVIRNA under Grant408 Agreement 264286 by EU FP7 SILVER (Contract HEALTH-F3-2010- 260644), a grant from the Belgian Interuniversity Attraction Poles (IAP) Phase VII–P7/45 (BELVIR), and the EU FP7 Industry-Academia Partnerships and Pathways Project AIROPICO. The Spanish MEC/MINECO is also acknowledged for a grant to E.R.-B. L.S. was funded by China Scholarship Council (CSC) Grant 201403250056. We also acknowledge Charlotte Vanderheydt for help with the processing of the antiviral data.Peer Reviewe