Estudio del Palacio Arzobispal de Alcalá de Henares

El Palacio Arzobispal de Alcalá de Henares es un tesoro histórico del que quedan importantes restos que deben recuperarse y reubicarlos a su lugar original, reconstruyendo la parte del conjunto que aún es posible volver a levantar. En la actualidad, el terreno ocupado por el palacio no nos deja huellas de haber sido lo que fue y haber tenido el auge que tuvo. Su restauración sería un aporte importante en consonancia con las políticas de recuperación patrimonial que esta ciudad ha implementado en las últimas décadas. En particular, la historia de la fachada o pórtico renacentista del Ave María nos vincula directamente a la fundación de la ciudad de Alcalá de Henares y su proceso de urbanización como recinto fortificado y casco urbano amurallado durante los siglos IX y X, y su ampliación con nueva muralla en el siglo XV. El objetivo del trabajo fue generar un proyecto de restauración de dicha fachada. El trabajo realizado, recogió aportes y estrategias de diferentes disciplinas relacionadas con la restauración y de esta forma incluir todos los pasos necesarios que un conjunto monumental de fuerte impacto territorial y paisajístico, como lo es el Palacio Arzobispal de Alcalá de Henares, requiere para la restauración y rehabilitación.Tópico 1: Aspectos teóricos, históricos, legales, económicos y tecnológicos de la restauración y conservación de bienes patrimoniales

Translocated LPS Might Cause Endotoxin Tolerance in Circulating Monocytes of Cystic Fibrosis Patients

Cystic Fibrosis (CF) is an inherited pleiotropic disease that results from abnormalities in the gene codes of a chloride channel. The lungs of CF patients are chronically infected by several pathogens but bacteraemia have rarely been reported in this pathology. Besides that, circulating monocytes in CF patients exhibit a patent Endotoxin Tolerance (ET) state since they show a significant reduction of the inflammatory response to bacterial stimulus. Despite a previous description of this phenomenon, the direct cause of ET in CF patients remains unknown. In this study we have researched the possible role of microbial/endotoxin translocation from a localized infection to the bloodstream as a potential cause of ET induction in CF patients. Plasma analysis of fourteen CF patients revealed high levels of LPS compared to healthy volunteers and patients who suffer from Chronic Obstructive Pulmonary Disease. Experiments in vitro showed that endotoxin concentrations found in plasma of CF patients were enough to induce an ET phenotype in monocytes from healthy controls. In agreement with clinical data, we failed to detect bacterial DNA in CF plasma. Our results suggest that soluble endotoxin present in bloodstream of CF patients causes endotoxin tolerance in their circulating monocytes

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Hepatobiliary scintigraphy and kinetic growth rate predict liver failure after ALPPS: a multi-institutional study

Background: Post hepatectomy liver failure (PHLF) after ALPPS has been related to the discrepancy between liver volume and function. Pre-operative hepatobiliary scintigraphy (HBS) can predict post-operative liver function and guide when it is safe to proceed with major hepatectomy. Aim of this study was to evaluate the role of HBS in predicting PHLF after ALPPS, defining a safe cut-off. Methods: A multicenter retrospective study was approved by the ALPPS Registry. All patients selected for ALPPS between 2012 and 2018, were evaluated. Every patient underwent HBS during ALPPS evaluation. PHLF was reported according to ISGLS definition, considering grade B or C as clinically significant. Results: 98 patients were included. Thirteen patients experienced PHLF grade B or C (14%) following ALPPS-2. The HBS and the daily gain in volume (KGRFLR) of the future liver remnant (FLR) were significantly lower in PHLF B and C (p = .004 and .041 respectively). ROC curves indicated safe cut-offs of 4.1%/day (AUC = 0.68) for KGRFLR, and of 2.7 %/min/m2 (AUC = 0.75) for HBSFLR. Multivariate analysis confirmed these cut-offs as variables predicting PHLF after ALPPS-2. Conclusion: Patients presenting a KGRFLR ≤4.1%/day and a HBSFLR ≤2.7%/min/m2 are at high risk of PHLF and their second stage should be re-discussed

Hepatobiliary scintigraphy and kinetic growth rate predict liver failure after ALPPS : a multi-institutional study

Background: Post hepatectomy liver failure (PHLF) after ALPPS has been related to the discrepancy between liver volume and function. Pre-operative hepatobiliary scintigraphy (HBS) can predict postoperative liver function and guide when it is safe to proceed with major hepatectomy. Aim of this study was to evaluate the role of HBS in predicting PHLF after ALPPS, defining a safe cut-off. Methods: A multicenter retrospective study was approved by the ALPPS Registry. All patients selected for ALPPS between 2012 and 2018, were evaluated. Every patient underwent HBS during ALPPS evaluation. PHLF was reported according to ISGLS definition, considering grade B or C as clinically significant. Results: 98 patients were included. Thirteen patients experienced PHLF grade B or C (14%) following ALPPS-2. The HBS and the daily gain in volume (KGRFLR) of the future liver remnant (FLR) were significantly lower in PHLF B and C (p = .004 and .041 respectively). ROC curves indicated safe cut-offs of 4.1%/day (AUC = 0.68) for KGRFLR, and of 2.7 %/min/m(2) (AUC = 0.75) for HBSFLR. Multivariate analysis confirmed these cut-offs as variables predicting PHLF after ALPPS-2. Conclusion: Patients presenting a KGRFLR <4.1%/day and a HBSFLR <2.7%/min/m(2) are at high risk of PHLF and their second stage should be re-discussed

Consistency and reproducibility of next-generation sequencing in cytopathology: A second worldwide ring trial study on improved cytological molecular reference specimens

BACKGROUND: Artificial genomic reference standards in a cytocentrifuge/cytospin format with well-annotated genomic data are useful for validating next-generation sequencing (NGS) on routine cytopreparations. Here, reference standards were optimized to be stained by different laboratories before DNA extraction and to contain a lower number of cells (2 × 105 ). This was done to better reflect the clinical challenge of working with insufficient cytological material. METHODS: A total of 17 worldwide laboratories analyzed customized reference standard slides (slides A-D). Each laboratory applied its standard workflow. The sample slides were engineered to harbor epidermal growth factor receptor (EGFR) c.2235_2249del15 p.E746_A750delELREA, EGFR c.2369C>T p.T790M, Kirsten rat sarcoma viral oncogene homolog (KRAS) c.38G>A p.G13D, and B-Raf proto-oncogene, serine/threonine kinase (BRAF) c.1798_1799GT>AA p.V600K mutations at various allele frequencies (AFs). RESULTS: EGFR and KRAS mutation detection showed excellent interlaboratory reproducibility, especially on slides A and B (10% and 5% AFs). On slide C (1% AF), either the EGFR mutation or the KRAS mutation was undetected by 10 of the 17 laboratories (58.82%). A reassessment of the raw data in a second-look analysis highlighted the mutations (n = 10) that had been missed in the first-look analysis. BRAF c.1798_1799GT>AA p.V600K showed a lower concordance rate for mutation detection and AF quantification. CONCLUSIONS: The data show that the detection of low-abundance mutations is still clinically challenging and may require a visual inspection of sequencing reads to detect. Genomic reference standards in a cytocentrifuge/cytospin format are a valid tool for regular quality assessment of laboratories performing molecular studies on cytology with low-AF mutations.status: publishe

Observational research with adolescents: a framework for the management of the parental permission

<p>Abstract</p> <p>Background</p> <p>Waiving parent permission can be an option in some epidemiological and social research with adolescents. However, exemptions have not been uniformly considered or applied. Our aim is to critically assess the different factors that could be taken into account when making decisions about waiving active parental permission in observational research with adolescents.</p> <p>Discussion</p> <p>In some cases alternatives to parental permission could be applied to protect the rights of both adolescents and parents and also to assure the benefits to adolescents as a group that can come from appropriately conducted studies. However, the criteria of ensuring minimal risk can be difficult to define and apply and a distinction between harm and discomfort is reviewed. Waiving active parental permission could be acceptable when the risk of harm is minimal; when the research questions are related to an activity for which adolescents are not legally considered to be children; when the risk of harm or discomfort may increase if parental permission is required; and when risk of discomfort is low because the questionnaire is not potentially offensive for some adolescents and/or for some parents.</p> <p>Summary</p> <p>Stringent rules concerning parental permission in some studies could be detrimental to adolescents. A framework and a decision tree guide are proposed to help researchers and Research Ethics Committees in their decisions on whether active parental permission must be obtained.</p