Deceased donor-initiated Chains: first report of a successful deliberate case and its ethical implications

Background: The utilization of deceased donor kidneys to initiate chains of living donor kidney paired donation (KPD) has been proposed, although the potential gain of this practice needs to be quantified and the ethical implications must be addressed before starting its application. Methods: The gain of implementing deceased donor-initiated chains has been measured through a mathematical algorithm, using retrospective data on the pool of donor/recipient incompatible pairs at a single Center. Allocation rules of chain ending kidneys and characteristics/quality of the chain initiating kidney (CIK) are described. Results: the quantification of benefit analysis showed that with a pool of 69 kidneys from deceased donors and 16 pairs enrolled in the KPD program, over a period of 3 years it is possible to transplant 8/16 recipients (50%). Following the approval of the Bioethical Committee of the Veneto Region and the revision of the allocation policies by the Italian National Transplant Center, the first successful case has been performed. The waiting time of the recipient (male, 53 yo) after entering the program for the CIK with a kidney donor risk index (KDRI) equal to 0.61 and a kidney donor profile index (KDPI) of 3%, was 4 days. His willing donor (female, 53 yo) with a living kidney donor profile index (LKDPI) of 2, donated 2 days later to a chain ending recipient (male, 47 yo,) who had been on dialysis for 5 years. Conclusions: This is the first report of a deliberate deceased donor-initiated chain, which has been successfully performed. This has been made possible thanks to an extensive phase of evaluation of the ethical issues and allocation policy impact. This paper includes a preliminary efficacy assessment and the development a dedicated algorithm

Mechanisms of endothelial cell dysfunction in cystic fibrosis

Although cystic fibrosis (CF) patients exhibit signs of endothelial perturbation, the functions of the cystic fibrosis conductance regulator (CFTR) in vascular endothelial cells (EC) are poorly defined. We sought to uncover biological activities of endothelial CFTR, relevant for vascular homeostasis and inflammation. We examined cells from human umbilical cords (HUVEC) and pulmonary artery isolated from non-cystic fibrosis (PAEC) and CF human lungs (CF-PAEC), under static conditions or physiological shear. CFTR activity, clearly detected in HUVEC and PAEC, was markedly reduced in CF-PAEC. CFTR blockade increased endothelial permeability to macromolecules and reduced trans‑endothelial electrical resistance (TEER). Consistent with this, CF-PAEC displayed lower TEER compared to PAEC. Under shear, CFTR blockade reduced VE-cadherin and p120 catenin membrane expression and triggered the formation of paxillin- and vinculin-enriched membrane blebs that evolved in shrinking of the cell body and disruption of cell-cell contacts. These changes were accompanied by enhanced release of microvesicles, which displayed reduced capability to stimulate proliferation in recipient EC. CFTR blockade also suppressed insulin-induced NO generation by EC, likely by inhibiting eNOS and AKT phosphorylation, whereas it enhanced IL-8 release. Remarkably, phosphodiesterase inhibitors in combination with a β2 adrenergic receptor agonist corrected functional and morphological changes triggered by CFTR dysfunction in EC. Our results uncover regulatory functions of CFTR in EC, suggesting a physiological role of CFTR in the maintenance EC homeostasis and its involvement in pathogenetic aspects of CF. Moreover, our findings open avenues for novel pharmacology to control endothelial dysfunction and its consequences in CF

Com millorar la motivació dels estudiants en assignatures de perfil economètric? una mesura pràctica amb avaluació empírica de la seva efectivitat

Projecte: 2015PID-UB/013El projecte s’ha aplicat als alumnes de les assignatures obligatòries d’Econometria I i II del Grau d’Economia de la Facultat d’Economia i Empresa al curs 2015-2016. Atesos els problemes de motivació habituals que presenten els alumnes del nostre Grau, especialment en matèries de perfil quantitatiu, el projecte ha perseguit l’objectiu general de fomentar la motivació del estudiants i l’aprenentatge actiu dels mateixos. Per tal d’aconseguir-ho vam pensar que seria possible incrementar aquesta motivació si els propis alumnes fossin la mostra estadística per l’anàlisi i aplicació de les tècniques economètriques ensenyades a classe. Així, es va pretendre motivar la participació dels alumnes mitjançant la reflexió sobre els factors determinants teòrics del seu propi rendiment acadèmic. Per fer-ho, s’ha recollit en primer lloc una base de dades dels propis alumnes sobre el seu rendiment acadèmic i les seves característiques sociodemogràfiques i familiars. Posteriorment, els alumnes han emprat aquesta base de dades per tal de construir un model economètric a partir del qual han aplicat les eines estadístic-economètriques estudiades a classe per tal d’aconseguir explicar el seu rendiment acadèmic. Atès que ells mateixos han estat la mostra d’anàlisi i el tema a analitzar era del seu interès, la participació ha estat molt elevada. Els resultats finals han sigut positius ja que ha incrementat la participació a classe i la reflexió conjunta del tema analitzat tant des d’un punt de vista teòric com aplicat. Alhora, han millorat els rendiment acadèmic general

Extracting Parallel Corpora from Wikipedia on the basis of Phrase Level Bilingual Alignment

[EN] This paper presents a proposal for extracting parallel corpora from Wikipedia on the basis of statistical machine translation techniques. We have used word-level alignment models from IBM in order to obtain phrase-level bilingual alignments between documents pairs. We have manually annotated a set of test English-Spanish comparable documents in order to evaluate the model. The obtained results are encouraging.[ES] Este art'¿culo presenta una nueva t'ecnica de extracci'on de corpus paralelos de la Wikipedia mediante la aplicaci'on de t'ecnicas de traducci'on autom'atica estad'¿stica. En concreto, se han utilizado los modelos de alineamiento basados en palabras de IBM para obtener alineamientos biling¿ues a nivel de frase entre pares de documentos. Para su evaluaci'on se ha generado manualmente un conjunto de test formado por pares de documentos ingl'es-espa¿nol, obteni'endose resultados prometedores.Este trabajo se ha llevado a cabo en el marco del VLC/CAMPUS Microcluster on Multimodal Interaction in Intelligent Systems, financiado parcialmente por parte de la EC (FEDER/FSE; WIQEI IRSES no. 269180 / FP 7 Marie Curie People), por el MICINN como parte del proyecto Text-Enterprise 2.0 (TIN2009-13391-C04-03) en el Plan I+D+i, y por la beca 192021 del CONACyT. Tambi´en ha recibido apoyo por parte del EC (FEDER/FSE) y del MEC/MICINN bajo el programa MIPRCV “Consolider Ingenio 2010” (CSD2007-00018) y el proyecto iTrans2 (TIN2009-14511), por el MITyC en el marco del proyecto erudito.com (TSI-020110-2009-439), por la Generalitat Valenciana con las ayudas Prometeo/2009/014 y GV/2010/067, y por el “Vicerrectorado de Investigaci´on de la UPV” con la ayuda 20091027.Silvestre Cerdà, JA.; Garcia Martinez, MM.; Barrón Cedeño, LA.; Civera Saiz, J.; Rosso ., P. (2011). Extracción de Corpus Paralelos de la Wikipedia basada en la Obtención de Alineamientos Bilingües a Nivel de Frase. CEUR Workshop Proceedings. 824:14-21. http://hdl.handle.net/10251/27930S142182

Correction to: Effects of immune suppression for transplantation on inflammatory colorectal cancer progression (Oncogenesis, (2018), 7, 6, (46), 10.1038/s41389-018-0055-5)

At the time of publication, the html version of this paper contained an error; the authors Imerio Angriman and Lucrezia Furian were not tagged as equally contributing authors. This has now been fixed in the html version of the paper, the PDF was correct at the time of publication. Erratum for Effects of immune suppression for transplantation on inflammatory colorectal cancer progression. [Oncogenesis. 2018

Phenological model intercomparison for estimating grapevine budbreak date (Vitis vinifera L.) in Europe

Budbreak date in grapevine is strictly dependent on temperature, and the correct simulation of its occurrence is of great interest since it may have major consequences on the final yield and quality. In this study, we evaluated the reliability for budbreak simulation of two modeling approaches, the chilling-forcing (CF), which describes the entire dormancy period (endo-and eco-dormancy) and the forcing approach (F), which only describes the eco-dormancy. For this, we selected six phenological models that apply CF and F in dierent ways, which were tested on budbreak simulation of eight grapevine varieties cultivated at dierent latitudes in Europe. Although none of the compared models showed a clear supremacy over the others, models based on CF showed a generally higher estimation accuracy than F where fixed starting dates were adopted. In the latter models, the accurate simulation of budbreak was dependent on the selection of the starting date for forcing accumulation that changes according to the latitude, whereas CF models were independent. Indeed, distinct thermal requirements were found for the grapevine varieties cultivated in Northern and Southern Europe. This implies the need to improve modeling of the dormancy period to avoid under-or over-estimations of budbreak date under dierent environmental conditions. © 2020 by the authors

Phenological Model Intercomparison for Estimating Grapevine Budbreak Date (Vitis vinifera L.) in Europe

Budbreak date in grapevine is strictly dependent on temperature, and the correct simulation of its occurrence is of great interest since it may have major consequences on the final yield and quality. In this study, we evaluated the reliability for budbreak simulation of two modeling approaches, the chilling-forcing (CF), which describes the entire dormancy period (endo- and eco-dormancy) and the forcing approach (F), which only describes the eco-dormancy. For this, we selected six phenological models that apply CF and F in different ways, which were tested on budbreak simulation of eight grapevine varieties cultivated at different latitudes in Europe. Although none of the compared models showed a clear supremacy over the others, models based on CF showed a generally higher estimation accuracy than F where fixed starting dates were adopted. In the latter models, the accurate simulation of budbreak was dependent on the selection of the starting date for forcing accumulation that changes according to the latitude, whereas CF models were independent. Indeed, distinct thermal requirements were found for the grapevine varieties cultivated in Northern and Southern Europe. This implies the need to improve modeling of the dormancy period to avoid under- or over-estimations of budbreak date under different environmental conditions.This research was funded by the European Union’s Horizon 2020 Research and Innovation Programme, under the Clim4Vitis project: “Climate change impact mitigation for European viticulture: knowledge transfer for an integrated approach”, grant agreement no. 810176. It was also supported by FCT-Portuguese Foundation for Science and Technology, under the project UIDB/04033/2020 and the French National Research Agency (ANR) in the frame of the Investments for the Future Program, within the cluster of excellence COTE (ANR-10-LABX-45)

An isoform of the giant protein titin is a master regulator of human T lymphocyte trafficking

Response to multiple microenvironmental cues and resilience to mechanical stress are essential features of trafficking leukocytes. Here, we describe unexpected role of titin (TTN), the largest protein encoded by the human genome, in the regulation of mechanisms of lymphocyte trafficking. Human T and B lymphocytes express five TTN isoforms, exhibiting cell-specific expression, distinct localization to plasma membrane microdomains, and different distribution to cytosolic versus nuclear compartments. In T lymphocytes, the LTTN1 isoform governs the morphogenesis of plasma membrane microvilli independently of ERM protein phosphorylation status, thus allowing selectin-mediated capturing and rolling adhesions. Likewise, LTTN1 controls chemokine-triggered integrin activation. Accordingly, LTTN1 mediates rho and rap small GTPases activation, but not actin polymerization. In contrast, chemotaxis is facilitated by LTTN1 degradation. Finally, LTTN1 controls resilience to passive cell deformation and ensures T lymphocyte survival in the blood stream. LTTN1 is, thus, a critical and versatile housekeeping regulator of T lymphocyte trafficking

Por qué el desconfinamiento asimétrico es una buena idea

A lo largo del mes de marzo y principios del mes de abril de este año la epidemia de COVID-19 se transmitió de manera exponencial entre la población de Cataluña, con una ralentización en días posteriores posiblemente asociada a la implantación del confinamiento de la población