Smartphone Abuse Amongst Adolescents: The Role of Impulsivity and Sensation Seeking

Adolescence is the stage of development where the reward and emotional regulation systems are yet to be adjusted and where most excessive behaviors start, like smartphone abuse. In addition, in this evolutionary period adolescents are more susceptible to behavioral changes through specific interventions or educational programs. Thus, it is fundamental to analyze the personality profile of those adolescents showing excessive mobile phone usage to properly approach later prevention strategies. Impulsivity is one of the most repeated variables associated with teenage addictions, although it has been observed that not all impulsive behaviors need to be detrimental. The aim of this study is to analyze how impulsivity affects smartphone addiction directly, but also indirectly, by assessing its association with sensation seeking variables (thrill and adventure seeking, experience seeking, disinhibition, and boredom susceptibility) which are in turn decisive when using these technologies improperly. The sample was made up of 614 adolescents aged 13–18 attending secondary education from Burgos, Spain. Dickman Impulsivity Inventory, Sensation Seeking Scale, and Ad-hoc questionnaire on adolescent self-perception as to smartphone use were applied. Results show that 41.4% of participants admit to abusing smartphones sometimes, while 18.3% admit to abusing them more frequently and 24% to, at least ever, having defined themselves as smartphone addicts. Stepwise regression analysis revealed that gender (female), dysfunctional impulsivity and sensation seeking (disinhibition and thrill and adventure seeking) evidence 15.7% of variance in smartphone abuse. In addition, sensation seeking (thrill and adventure seeking, disinhibition, and boredom susceptibility) were found to mediate the relationship between dysfunctional impulsivity and smartphone abuse. Therefore, dysfunctional impulsivity was directly connected with teenage smartphone abuse, but also had an indirect stronger association through thrill and adventure seeking, disinhibition and boredom susceptibility

Determinants of Food Safety Level in Fruit and Vegetable Wholesalers’ Supply Chain: Evidence from Spain and France

Food safety management in short supply chains of fruit and vegetables, controlled by large retailers, has been widely studied in the literature. However, when it comes to traditional long supply chains, which include a greater number of intermediaries and wholesalers who, in some cases, play a dual role as resellers and producers, the mechanisms which promote the use of safety certifications have yet to be clearly defined. The present study intended to fill this gap in the literature and shed light on the food safety level that exists in this channel. In addition, this work attempted to identify the existence of differences between both sales systems. For this purpose, the empirical research studied the most important variables that influence the food safety level of some of the main European fruit and vegetable wholesalers. A survey was thus designed and later applied to Spanish and French intermediaries working in key wholesale markets and in the southeast of Spain, which is the leading commercialization area of these products in Europe. The results revealed the positive influence of specific customers (big retailers) on establishing stricter safety controls within wholesale companies. It was also observed that specific wholesalers also play an important role in the system, namely those dedicated to importing, but which are also responsible for quality and safety inspection of agri-food products exported from third countries into the European Union

Puerto Rico: Análisis de futuro de la isla ante los possibles cambios de su situación política

Màster Oficial d'Internacionalització, Facultat d'Economia i Empresa, Universitat de Barcelona, Curs: 2019-2020, Tutor: Xavier Fernández PonsEn el presente trabajo se realiza un análisis de los distintos escenarios que podrían darse en Puerto Rico si se realizase un nuevo plebiscito vinculante que derivase en un cambio de su estatus político. Para poder realizar este análisis se hace un estudio previo de la historia de Puerto Rico desde la época precolombina hasta la creación del Estado Libre Asociado y distintos análisis acerca de su actualidad social, económica y política, sobre el debate respecto a su estatus político y de los diferentes plebiscitos que se han realizado en la isla. También se incluye el estudio de una encuesta realizada a 55 puertorriqueños acerca de su opinión sobre el futuro político de su isla. Tras el análisis realizado se puede concluir que no existe una mejor solución para Puerto Rico a nivel social, político y económico porque las tres posibilidades existentes presentan pros y contras que se deben considerar, y que esta decisión no dependerá solo de los puertorriqueños, puesto que depende del gobierno de Estados Unidos que llegue a darse un cambio en el estatus político de Puerto Ric

Tumor targeted 4-1BB agonist antibody-albumin fusions with high affinity to FcRn induce anti-tumor immunity without toxicity.

Costimulation of tumor-infiltrating T lymphocytes by anti-4-1BB monoclonal antibodies (mAbs) has shown anti-tumor activity in human trials, but can be associated with significant off-tumor toxicities involving FcgR interactions. Here, we introduce albumin-fused mouse and human bispecific antibodies with clinically favorable pharmacokinetics designed to confine 4-1BB costimulation to the tumor microenvironment. These Fc-free 4-1BB agonists consist of an EGFR-specific VHH antibody, a 4-1BB-specific scFv, and a human albumin sequence engineered for high FcRn binding connected in tandem (LiTCo-Albu). We demonstrate in vitro cognate target engagement, EGFR-specific costimulatory activity, and FcRn-driven cellular recycling similar to non-fused FcRn high-binding albumin. The mouse LiTCo-Albu exhibited a prolonged circulatory half-life and in vivo tumor inhibition,with no indication of 4-1BBmAb-associated toxicity. Furthermore, we show a greater therapeutic effect when used in combination with PD-1-blocking mAbs. These findings demonstrate the feasibility of tumor-specific LiTCo- Albu antibodies for safe and effective costimulatory strategies in cancer immunotherapy.post-print2444 K

Overcoming CAR-Mediated CD19 Downmodulation and Leukemia Relapse with T Lymphocytes Secreting Anti-CD19 T-cell Engagers.

Chimeric antigen receptor (CAR)–modified T cells have revolutionized the treatment of CD19-positive hematologic malignancies. Although anti-CD19 CAR-engineered autologous T cells can induce remission in patients with B-cell acute lymphoblastic leukemia, a large subset relapse, most of them with CD19-positive disease. Therefore, new therapeutic strategies are clearly needed. Here, we report a comprehensive study comparing engineered T cells either expressing a second-generation anti-CD19 CAR (CART19) or secreting a CD19/CD3-targeting bispecific T-cell engager antibody (STAb-T19). We found that STAb-T19 cells are more effective than CAR-T19 cells at inducing cytotoxicity, avoiding leukemia escape in vitro, and preventing relapse in vivo. We observed that leukemia escape in vitro is associated with rapid and drastic CAR-induced internalization of CD19 that is coupled with lysosome-mediated degradation, leading to the emergence of transiently CD19-negative leukemic cells that evade the immune response of engineered CAR-T19 cells. In contrast, engineered STAb-T19 cells induce the formation of canonical immunologic synapses and prevent the CD19 downmodulation observed in anti- CD19 CAR-mediated interactions. Although both strategies show similar efficacy in short-term mouse models, there is a significant difference in a long-term patient-derived xenograft mouse model, where STAb-T19 cells efficiently eradicated leukemia cells, but leukemia relapsed after CAR-T19 therapy. Our findings suggest that the absence of CD19 downmodulation in the STAb-T19 strategy, coupled with the continued antibody secretion, allows an efficient recruitment of the endogenous T-cell pool, resulting in fast and effective elimination of cancer cells that may prevent CD19-positive relapses frequently associated with CAR-T19 therapies.post-print1691 K

gem-selective cross-dimerization and cross-trimerization of alkynes with silylacetylenes promoted by a Rhodium-Pyridine-N-heterocyclic carbene catalyst

The gem-selective cross-dimerization and -trimerization of silylacetylenes with alkynes through C[BOND]H activation using a rhodium(I)–pyridine–N-heterocyclic carbene catalyst have been developed. This reaction is applied to various aliphatic or aromatic terminal alkynes, internal alkynes, and gem-1,3-disubsituted enynes to afford the corresponding enynes and dienynes with high regio- and stereoselectivities and in good isolated yields (up to 91 %).Financial support from the Spanish Ministerio de Economía y Competitividad (MEC/FEDER) of Spain Project (CTQ2010-15221), the Diputación General de Aragón (E07), the KFUPMUNIZAR agreement, and CONSOLIDER INGENIO-2010, under the Project MULTICAT (CSD2009-00050) are gratefully acknowledged. L. R.-P. thanks CONACyT (Mexico, 186898 and 204033) for a postdoctoral fellowship.Peer Reviewe

The cell density effect in animal cell-based bioprocessing : Questions, insights and perspectives

Altres ajuts: acord transformatiu CRUE-CSICOne of the main challenges in the development of bioprocesses based on cell transient expression is the commonly reported reduction of cell specific productivity at increasing cell densities. This is generally known as the cell density effect (CDE). Many efforts have been devoted to understanding the cell metabolic implications to this phenomenon in an attempt to design operational strategies to overcome it. A comprehensive analysis of the main studies regarding the CDE is provided in this work to better define the elements comprising its cause and impact. Then, examples of methodologies and approaches employed to achieve successful transient expression at high cell densities (HCD) are thoroughly reviewed. A critical assessment of the limitations of the reported studies in the understanding of the CDE is presented, covering the leading hypothesis of the molecular implications. The overall analysis of previous work on CDE may offer useful insights for further research into manufacturing of biologics

DETERMINACIÓN DEL HIDROGRAMA UNITARIO PARA LA CUENCA DE LA QUEBRADA PADRE DE JESÚS, BOGOTÁ DC.

“En el presente trabajo se calculó el Hidrograma Unitario (HU) por los métodos sintéticos: triangular y curvilíneo y por el método matricial basado en mediciones de campo para la Quebrada Padre de Jesús, Bogotá D.C, con el fin de determinar la validez de los métodos sintéticos actualmente utilizados.

Efficient Rhodium-catalyzed multicomponent reaction for the synthesis of novel propargylamines

[{Rh(μ-Cl)(H)2(IPr)}2] (IPr = 1,3-bis-(2,6-diisopropylphenyl)imidazole-2-ylidene) was found to be an efficient catalyst for the synthesis of novel propargylamines by a one-pot three-component reaction between primary arylamines, aliphatic aldehydes, and triisopropylsilylacetylene. This methodology offers an efficient synthetic pathway for the preparation of secondary propargylamines derived from aliphatic aldehydes. The reactivity of [{Rh(μ-Cl)(H)2(IPr)}2] with amines and aldehydes was studied, leading to the identification of complexes [RhCl(CO)IPr(MesNH2)] (MesNH2 = 2,4,6-trimethylaniline) and [RhCl(CO)2IPr]. The latter shows a very low catalytic activity while the former brought about reaction rates similar to those obtained with [{Rh(μ-Cl)(H)2(IPr)}2]. Besides, complex [RhCl(CO)IPr(MesNH2)] reacts with an excess of amine and aldehyde to give [RhCl(CO)IPr{MesN[DOUBLE BOND]CHCH2CH(CH3)2}], which was postulated as the active species. A mechanism that clarifies the scarcely studied catalytic cycle of A3-coupling reactions is proposed based on reactivity studies and DFT calculations.This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO/FEDER) (CONSOLIDER INGENIO CSD2009-0050, CTQ2011-27593, CTQ2012-35665 and CTQ2013-42532-P projects) and the DGA/FSE-E07. The support from KFUPM-University of Zaragoza research agreement and the Centre of Research Excellence in Petroleum Refining & KFUPM is gratefully acknowledged. V. P. thankfully acknowledges the resources from the supercomputer >Memento>, technical expertise and assistance provided by BIFI-ZCAM (Universidad de Zaragoza). L.R.-P thanks to CONACyT for a postdoctoral fellowship (204033).Peer Reviewe

A PD-L1/EGFR bispecific antibody combines immune checkpoint blockade and direct anti-cancer action for an enhanced anti-tumor response.

Immune checkpoint blockade (ICB) with antibodies has shown durable clinical responses in a wide range of cancer types, but the overall response rate is still limited. Other effective therapeutic modalities to increase the ICB response rates are urgently needed. New bispecific antibody (bsAb) formats combining the ICB effect and a direct action on cancer cells could improve the efficacy of current immunotherapies. Here, we report the development of a PD-L1/EGFR symmetric bsAb by fusing a dual-targeting tandem trimmer body with the human IgG1 hinge and Fc regions. The bsAb was characterized in vitro and the antitumor efficacy was evaluated in humanized mice bearing xenografts of aggressive triple-negative breast cancer and lung cancer. The IgG-like hexavalent bsAb, designated IgTT-1E, was able to simultaneously bind both EGFR and PD-L1 antigens, inhibit EGF-mediated proliferation, effectively block PD-1/PD-L1 interaction, and induce strong antigen-specific antibody-dependent cellular cytotoxicity activity in vitro. Potent therapeutic efficacies of IgTT-1E in two different humanized mouse models were observed, where tumor growth control was associated with a significantly increased proportion of CD8+ T cells. These results support the development of IgTT-1E for the treatment of EGFR+ cancers.post-print3,06 M