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Escape rooms offer an immersive and engaging learning experience that encourages critical thinking, problem solving and teamwork. Although they have shown promising results in promoting student engagement in the teaching-learning process, they continue to operate as independent systems that are not fully integrated into educational environments. This work aims to detail the integration of educational escape rooms, based on international standards, with the typical central component of an educational setting - the learning management system (LMS). In order to proof this concept, we present the integration of a math escape room with the Moodle LMS using the Learning Tools Interoperability (LTI) specification. Currently, this specification comprises a set of Web services that enable seamless integration between learning platforms and external tools and is not limited to any specific LMS which fosters learning interoperability. With this implementation, a single sign-on ecosystem is created, where teachers and students can interact in a simple and immersive way. The major contribution of this work is to serve as an integration guide for other applications and in different domains.

This paper presents a study on the use of gamified educational escape rooms to foster the teaching-learning process of computer programming, based on an user type taxonomy. The ultimate goal of this work is to identify and validate the most suitable gamification elements and mechanics for each user profile, providing case studies that illustrate their implementation. The main contribution of this work is to guide the design process of educational escape rooms in any domain, by considering the needs, preferences, and motivations of different user types.

In this paper we study the poetic reclaim of the writer Miguel de Unamuno through three authors from the generation of 1936: Luis Rosales, Leopoldo Panero and Luis Felipe Vivanco. To carry out this analysis we have chosen three significant collections of poems by the authors studied: La casa encendida, Escrito a cada instante and Continuación de la vida. In the first place, we study how Unamuno's philosophy influenced the creation of the poetics of the post-war group. In the second place, we review how these three authors collect in their books the same sense of pain that Unamuno explains on Del sentimiento trágico de la vida., En este artículo estudiamos la influencia poética de Miguel de Unamuno en la generación del 36 a través de tres poetas: Luis Rosales, Leopoldo Panero y Luis Felipe Vivanco. Para llevar a cabo este análisis hemos seleccionado tres poemarios publicados en una fecha clave, 1949: La casa encendida, Escrito a cada instante y Continuación de la vida. En primer lugar, se analiza el papel de Unamuno en la configuración de la poética del 36, a partir del rescate de un ensayo fundamental para la generación escrito por Luis Rosales. Y, en segundo lugar, comentamos cómo estos tres autores están desarrollando el tema del dolor a partir de las coordenadas filosóficas expuestas en Del sentimiento trágico de la vida.

La obra de María Acuña, poeta extremeña que murió inédita, sale a la luz gracias a esta edición de Isabel Balseiro, en la que repasa la trayectoria de esta arrolladora escritora que se vio influida por los principales movimientos y ambientes del siglo XX, pero que, al igual que muchas otras mujeres, quedó olvidada en los estudios literarios. Este poemario supone una invitación a la lectura de la obra de Acuña, a la vez que una reivindicación del hueco que como escritora merece.

La obra de María Acuña, poeta extremeña que murió inédita, sale a la luz gracias a esta edición de Isabel Balseiro, en la que repasa la trayectoria de esta arrolladora escritora que se vio influida por los principales movimientos y ambientes del siglo XX, pero que, al igual que muchas otras mujeres, quedó olvidada en los estudios literarios. Este poemario supone una invitación a la lectura de la obra de Acuña, a la vez que una reivindicación del hueco que como escritora merece.

Next-generation sequencing (NGS) may enable more focused and highly personalized cancer treatment, with the National Comprehensive Cancer Network and European Society for Medical Oncology guidelines now recommending NGS for daily clinical practice for several tumor types. However, NGS implementation, and therefore patient access, varies across Europe; a multi-stakeholder collaboration is needed to establish the conditions required to improve this discrepancy. In that regard, we set up European Alliance for Personalised Medicine (EAPM)-led expert panels during the first half of 2021, including key stakeholders from across 10 European countries covering medical, economic, patient, industry, and governmental expertise. We describe the outcomes of these panels in order to define and explore the necessary conditions for NGS implementation into routine clinical care to enable patient access, identify specific challenges in achieving them, and make short- and long-term recommendations. The main challenges identified relate to the demand for NGS tests (governance, clinical standardization, and awareness and education) and supply of tests (equitable reimbursement, infrastructure for conducting and validating tests, and testing access driven by evidence generation). Recommendations made to resolve each of these challenges should aid multi-stakeholder collaboration between national and European initiatives, to complement, support, and mutually reinforce efforts to improve patient care.

Celiac disease (CD) is not considered a food allergy, it is an autoimmune disease characterized by an inflammatory process that involves the mucosa of the small intestine, due to the ingestion of gluten, thus reducing the absorption of essential nutrients for the good functioning of the organism. The only known treatment is a gluten-free diet, adopted for life and must be rigorous, complete, balanced and varied. However, in Brazil, we still find labeling errors, a serious circumstance, and the label is the way the celiac finds to protect himself from gluten and if there is an error, he will be induced to ingest the toxic antigen, causing his illness and causing injuries serious bodily injuries. Therefore, the objective of this study is to evaluate, through a literature review, the panorama of food labeling for celiac in Brazil. The databases of SCIELO, ANVISA, Ministry of Health, FENACELBRA, ASBAI, ACELBRA, MEDLINE, Google Scholar, and books were used as a research source, between November and March 2020. Therefore, the research confirmed that the legislation should be sufficient to promote alignment in the communication between the industry and the consumer and that Health Surveillance carries out interventions to eliminate, reduce or prevent risks, however, it is observed that corrective actions are still necessary so that patients with CD have access to safe food and that they can trust the words expressed on the packaging labels., A doença celíaca (DC) não é considerada uma alergia alimentar, trata-se de uma doença autoimune caracterizada por um processo inflamatório que envolve a mucosa do intestino delgado, em decorrência à ingestão de glúten, reduzindo assim a absorção dos nutrientes essenciais para o bom funcionamento do organismo. O único tratamento conhecido é a dieta isenta de glúten, adotada para toda a vida e deve ser rigorosa, completa, equilibrada e variada. Porém, no Brasil, ainda encontramos erros de rotulagem, circunstância grave, sendo que o rótulo é o modo que o celíaco encontra para se proteger do glúten e se há erro, será induzido a ingerir o antígeno tóxico, proporcionado o seu adoecimento e causando lesões corporais sérias. Sendo assim, o objetivo deste estudo é avaliar, através de uma revisão de literatura, o panorama da rotulagem de alimentos para celíacos no Brasil. Foram utilizadas como fonte de pesquisa as bases de dados da SCIELO, ANVISA, Ministério da Saúde, FENACELBRA, ASBAI, ACELBRA, MEDLINE, Google Acadêmico e livros, no período entre novembro e março de 2020. Logo, a pesquisa convalidou que a legislação deveria ser suficiente para promover um alinhamento na comunicação entre a indústria e o consumidor e que Vigilância Sanitária realiza intervenções para eliminar, diminuir ou prevenir riscos, porém observa-se que ainda é necessário a implementação de ações corretivas para que os portadores da DC tenham acesso a alimentação segura e que possam confiar nas palavras expressas nos rótulos das embalagens., La enfermedad celíaca (EC) no se considera una alergia alimentaria, es una enfermedad autoinmune caracterizada por un proceso inflamatorio que involucra la mucosa del intestino delgado, debido a la ingestión de gluten, reduciendo así la absorción de nutrientes esenciales para el bien funcionamiento del organismo. El único tratamiento conocido es una dieta sin gluten, adoptada de por vida y debe ser rigurosa, completa, equilibrada y variada. Sin embargo, en Brasil, todavía encontramos errores de etiquetado, una circunstancia grave, y la etiqueta es la forma en que el celíaco se protege del gluten y, si hay un error, será inducido a ingerir el antígeno tóxico, causando su enfermedad y causando lesiones. Lesiones corporales graves. Por lo tanto, el objetivo de este estudio es evaluar, a través de una revisión de la literatura, el panorama del etiquetado de alimentos para celíacos en Brasil. Las bases de datos de SCIELO, ANVISA, el Ministerio de Salud, FENACELBRA, ASBAI, ACELBRA, MEDLINE, Google Acholar y los libros se utilizaron como fuente de investigación, entre noviembre y marzo de 2020. Por lo tanto, la investigación confirmó que la legislación debería ser suficiente para promover una alineación en la comunicación entre la industria y el consumidor y que la Vigilancia de la Salud lleve a cabo intervenciones para eliminar, reducir o prevenir riesgos, sin embargo, se observa que las acciones correctivas aún son necesarias para que los pacientes con EC tengan acceso a alimentos seguros y que pueden confiar en las palabras expresadas en las etiquetas de los envases.

Celiac disease (CD) is not considered a food allergy, it is an autoimmune disease characterized by an inflammatory process that involves the mucosa of the small intestine, due to the ingestion of gluten, thus reducing the absorption of essential nutrients for the good functioning of the organism. The only known treatment is a gluten-free diet, adopted for life and must be rigorous, complete, balanced and varied. However, in Brazil, we still find labeling errors, a serious circumstance, and the label is the way the celiac finds to protect himself from gluten and if there is an error, he will be induced to ingest the toxic antigen, causing his illness and causing injuries serious bodily injuries. Therefore, the objective of this study is to evaluate, through a literature review, the panorama of food labeling for celiac in Brazil. The databases of SCIELO, ANVISA, Ministry of Health, FENACELBRA, ASBAI, ACELBRA, MEDLINE, Google Scholar, and books were used as a research source, between November and March 2020. Therefore, the research confirmed that the legislation should be sufficient to promote alignment in the communication between the industry and the consumer and that Health Surveillance carries out interventions to eliminate, reduce or prevent risks, however, it is observed that corrective actions are still necessary so that patients with CD have access to safe food and that they can trust the words expressed on the packaging labels., A doença celíaca (DC) não é considerada uma alergia alimentar, trata-se de uma doença autoimune caracterizada por um processo inflamatório que envolve a mucosa do intestino delgado, em decorrência à ingestão de glúten, reduzindo assim a absorção dos nutrientes essenciais para o bom funcionamento do organismo. O único tratamento conhecido é a dieta isenta de glúten, adotada para toda a vida e deve ser rigorosa, completa, equilibrada e variada. Porém, no Brasil, ainda encontramos erros de rotulagem, circunstância grave, sendo que o rótulo é o modo que o celíaco encontra para se proteger do glúten e se há erro, será induzido a ingerir o antígeno tóxico, proporcionado o seu adoecimento e causando lesões corporais sérias. Sendo assim, o objetivo deste estudo é avaliar, através de uma revisão de literatura, o panorama da rotulagem de alimentos para celíacos no Brasil. Foram utilizadas como fonte de pesquisa as bases de dados da SCIELO, ANVISA, Ministério da Saúde, FENACELBRA, ASBAI, ACELBRA, MEDLINE, Google Acadêmico e livros, no período entre novembro e março de 2020. Logo, a pesquisa convalidou que a legislação deveria ser suficiente para promover um alinhamento na comunicação entre a indústria e o consumidor e que Vigilância Sanitária realiza intervenções para eliminar, diminuir ou prevenir riscos, porém observa-se que ainda é necessário a implementação de ações corretivas para que os portadores da DC tenham acesso a alimentação segura e que possam confiar nas palavras expressas nos rótulos das embalagens., La enfermedad celíaca (EC) no se considera una alergia alimentaria, es una enfermedad autoinmune caracterizada por un proceso inflamatorio que involucra la mucosa del intestino delgado, debido a la ingestión de gluten, reduciendo así la absorción de nutrientes esenciales para el bien funcionamiento del organismo. El único tratamiento conocido es una dieta sin gluten, adoptada de por vida y debe ser rigurosa, completa, equilibrada y variada. Sin embargo, en Brasil, todavía encontramos errores de etiquetado, una circunstancia grave, y la etiqueta es la forma en que el celíaco se protege del gluten y, si hay un error, será inducido a ingerir el antígeno tóxico, causando su enfermedad y causando lesiones. Lesiones corporales graves. Por lo tanto, el objetivo de este estudio es evaluar, a través de una revisión de la literatura, el panorama del etiquetado de alimentos para celíacos en Brasil. Las bases de datos de SCIELO, ANVISA, el Ministerio de Salud, FENACELBRA, ASBAI, ACELBRA, MEDLINE, Google Acholar y los libros se utilizaron como fuente de investigación, entre noviembre y marzo de 2020. Por lo tanto, la investigación confirmó que la legislación debería ser suficiente para promover una alineación en la comunicación entre la industria y el consumidor y que la Vigilancia de la Salud lleve a cabo intervenciones para eliminar, reducir o prevenir riesgos, sin embargo, se observa que las acciones correctivas aún son necesarias para que los pacientes con EC tengan acceso a alimentos seguros y que pueden confiar en las palabras expresadas en las etiquetas de los envases.

Celiac disease (CD) is not considered a food allergy, it is an autoimmune disease characterized by an inflammatory process that involves the mucosa of the small intestine, due to the ingestion of gluten, thus reducing the absorption of essential nutrients for the good functioning of the organism. The only known treatment is a gluten-free diet, adopted for life and must be rigorous, complete, balanced and varied. However, in Brazil, we still find labeling errors, a serious circumstance, and the label is the way the celiac finds to protect himself from gluten and if there is an error, he will be induced to ingest the toxic antigen, causing his illness and causing injuries serious bodily injuries. Therefore, the objective of this study is to evaluate, through a literature review, the panorama of food labeling for celiac in Brazil. The databases of SCIELO, ANVISA, Ministry of Health, FENACELBRA, ASBAI, ACELBRA, MEDLINE, Google Scholar, and books were used as a research source, between November and March 2020. Therefore, the research confirmed that the legislation should be sufficient to promote alignment in the communication between the industry and the consumer and that Health Surveillance carries out interventions to eliminate, reduce or prevent risks, however, it is observed that corrective actions are still necessary so that patients with CD have access to safe food and that they can trust the words expressed on the packaging labels., A doença celíaca (DC) não é considerada uma alergia alimentar, trata-se de uma doença autoimune caracterizada por um processo inflamatório que envolve a mucosa do intestino delgado, em decorrência à ingestão de glúten, reduzindo assim a absorção dos nutrientes essenciais para o bom funcionamento do organismo. O único tratamento conhecido é a dieta isenta de glúten, adotada para toda a vida e deve ser rigorosa, completa, equilibrada e variada. Porém, no Brasil, ainda encontramos erros de rotulagem, circunstância grave, sendo que o rótulo é o modo que o celíaco encontra para se proteger do glúten e se há erro, será induzido a ingerir o antígeno tóxico, proporcionado o seu adoecimento e causando lesões corporais sérias. Sendo assim, o objetivo deste estudo é avaliar, através de uma revisão de literatura, o panorama da rotulagem de alimentos para celíacos no Brasil. Foram utilizadas como fonte de pesquisa as bases de dados da SCIELO, ANVISA, Ministério da Saúde, FENACELBRA, ASBAI, ACELBRA, MEDLINE, Google Acadêmico e livros, no período entre novembro e março de 2020. Logo, a pesquisa convalidou que a legislação deveria ser suficiente para promover um alinhamento na comunicação entre a indústria e o consumidor e que Vigilância Sanitária realiza intervenções para eliminar, diminuir ou prevenir riscos, porém observa-se que ainda é necessário a implementação de ações corretivas para que os portadores da DC tenham acesso a alimentação segura e que possam confiar nas palavras expressas nos rótulos das embalagens., La enfermedad celíaca (EC) no se considera una alergia alimentaria, es una enfermedad autoinmune caracterizada por un proceso inflamatorio que involucra la mucosa del intestino delgado, debido a la ingestión de gluten, reduciendo así la absorción de nutrientes esenciales para el bien funcionamiento del organismo. El único tratamiento conocido es una dieta sin gluten, adoptada de por vida y debe ser rigurosa, completa, equilibrada y variada. Sin embargo, en Brasil, todavía encontramos errores de etiquetado, una circunstancia grave, y la etiqueta es la forma en que el celíaco se protege del gluten y, si hay un error, será inducido a ingerir el antígeno tóxico, causando su enfermedad y causando lesiones. Lesiones corporales graves. Por lo tanto, el objetivo de este estudio es evaluar, a través de una revisión de la literatura, el panorama del etiquetado de alimentos para celíacos en Brasil. Las bases de datos de SCIELO, ANVISA, el Ministerio de Salud, FENACELBRA, ASBAI, ACELBRA, MEDLINE, Google Acholar y los libros se utilizaron como fuente de investigación, entre noviembre y marzo de 2020. Por lo tanto, la investigación confirmó que la legislación debería ser suficiente para promover una alineación en la comunicación entre la industria y el consumidor y que la Vigilancia de la Salud lleve a cabo intervenciones para eliminar, reducir o prevenir riesgos, sin embargo, se observa que las acciones correctivas aún son necesarias para que los pacientes con EC tengan acceso a alimentos seguros y que pueden confiar en las palabras expresadas en las etiquetas de los envases.

The purpose of this paper is to contextualize the social policy transformations in social services and health care system in the context of the economic and financial crisis and following intervention of the international monetary fund, the World Bank and the European Central Bank (Troika) in Portugal, over the past four years. We analyze the social emergency program, which replaced the national plan for social inclusion, and the implementation of the national integrated network for long term care. Based on the evidence of the results we reflect on these transformations in Social Work, highlighting the negative aspects and the challenges for this profession. To achieve these aims we analyzed documents, statistical data and research on this subject. In this context of scarcity and emergency interventions, Social Work is challenged to rethink itself as a sociopolitical profession, taking into account the temporality of the intervention, the allocation of resources and the training of professionals., Este artigo tem como finalidade contextualizar as transformações da política social na área da ação social e na área da saúde em tempo de crise económica e financeira e de intervenção do fundo monetário internacional, do banco mundial e do banco central europeu (Troika), em Portugal nos últimos quatro anos. Analisamos o programa de emergência social que substituiu o plano nacional de ação para a inclusão e a evolução da implementação da rede nacional de cuidados continuados integrados. A partir destas evidências refletimos sobre os outcomes destas transformações no Serviço Social, evidenciando os aspetos negativos e os desafios para a categoria profissional. Para atingir os objetivos optamos pela análise de documentos, dados estatísticos e estudos efetuados nestes últimos anos sobre esta temática. Consideramos que num contexto de escassez de recursos e de orientação da intervenção para a emergência, o Serviço Social é desafiado a repensar-se como profissão sociopolítica tendo em conta a temporalidade da intervenção, a alocação de recursos e a formação dos profissionais.

This paper analyzes Portugal’s health policy from the perspective of Social Work in time of austerity. We have identified the competencies and responsibilities of Social Work in the field of health and evidenced the trajectory of the National Health Service since its inception until its recent developments. Notably, changes occurred to the health policy during the economic crisis of the State between 2010 and 2015, and an analysis was made of the impact of these changes in Social Service, while considering scenarios where the scarcity of resources and privatization of the sector are both common facts. In order to achieve the goals we have set, we opted for an approach focused on documentary analysis, based on the experience of the authors (evidence-based practice)., Este artigo analisa a política de saúde em Portugal na perspetiva do Serviço Social em tempo de austeridade. Identificamos as competências e atribuições do Serviço Social na saúde e evidenciamos o trajeto do Serviço Nacional de Saúde, desde a sua génese até aos seus últimos desenvolvimentos. Salienta-se as alterações na política de saúde que ocorreram durante a crise económica-financeira do Estado entre 2010 e 2015 e reflecte-se sobre o impacto dessas mudanças no Serviço Social considerando, simultaneamente, cenários onde a escassez de recursos e o recurso à privatização do setor são uma realidade. Para atingir os objetivos a que nos propusemos optámos por uma metodologia centrada na análise documental e assente na experiência dos autores - evidence-based practice.

Up to 10% of cases of gastric cancer are familial, but so far, only mutations in CDH1 have been associated with gastric cancer risk. To identify genetic variants that affect risk for gastric cancer, we collected blood samples from 28 patients with hereditary diffuse gastric cancer (HDGC) not associated with mutations in CDH1 and performed whole-exome sequence analysis. We then analyzed sequences of candidate genes in 333 independent HDGC and non-HDGC cases. We identified 11 cases with mutations in PALB2, BRCA1, or RAD51C genes, which regulate homologous DNA recombination. We found these mutations in 2 of 31 patients with HDGC (6.5%) and 9 of 331 patients with sporadic gastric cancer (2.8%). Most of these mutations had been previously associated with other types of tumors and partially co-segregated with gastric cancer in our study. Tumors that developed in patients with these mutations had a mutation signature associated with somatic homologous recombination deficiency. Our findings indicate that defects in homologous recombination increase risk for gastric cancer.

The purpose of this paper is to contextualize the social policy transformations in social services and health care system in the context of the economic and financial crisis and following intervention of the international monetary fund, the World Bank and the European Central Bank (Troika) in Portugal, over the past four years. We analyze the social emergency program, which replaced the national plan for social inclusion, and the implementation of the national integrated network for long term care. Based on the evidence of the results we reflect on these transformations in Social Work, highlighting the negative aspects and the challenges for this profession. To achieve these aims we analyzed documents, statistical data and research on this subject. In this context of scarcity and emergency interventions, Social Work is challenged to rethink itself as a sociopolitical profession, taking into account the temporality of the intervention, the allocation of resources and the training of professionals., Este artigo tem como finalidade contextualizar as transformações da política social na área da ação social e na área da saúde em tempo de crise económica e financeira e de intervenção do fundo monetário internacional, do banco mundial e do banco central europeu (Troika), em Portugal nos últimos quatro anos. Analisamos o programa de emergência social que substituiu o plano nacional de ação para a inclusão e a evolução da implementação da rede nacional de cuidados continuados integrados. A partir destas evidências refletimos sobre os outcomes destas transformações no Serviço Social, evidenciando os aspetos negativos e os desafios para a categoria profissional. Para atingir os objetivos optamos pela análise de documentos, dados estatísticos e estudos efetuados nestes últimos anos sobre esta temática. Consideramos que num contexto de escassez de recursos e de orientação da intervenção para a emergência, o Serviço Social é desafiado a repensar-se como profissão sociopolítica tendo em conta a temporalidade da intervenção, a alocação de recursos e a formação dos profissionais.

This paper analyzes Portugal’s health policy from the perspective of Social Work in time of austerity. We have identified the competencies and responsibilities of Social Work in the field of health and evidenced the trajectory of the National Health Service since its inception until its recent developments. Notably, changes occurred to the health policy during the economic crisis of the State between 2010 and 2015, and an analysis was made of the impact of these changes in Social Service, while considering scenarios where the scarcity of resources and privatization of the sector are both common facts. In order to achieve the goals we have set, we opted for an approach focused on documentary analysis, based on the experience of the authors (evidence-based practice)., Este artigo analisa a política de saúde em Portugal na perspetiva do Serviço Social em tempo de austeridade. Identificamos as competências e atribuições do Serviço Social na saúde e evidenciamos o trajeto do Serviço Nacional de Saúde, desde a sua génese até aos seus últimos desenvolvimentos. Salienta-se as alterações na política de saúde que ocorreram durante a crise económica-financeira do Estado entre 2010 e 2015 e reflecte-se sobre o impacto dessas mudanças no Serviço Social considerando, simultaneamente, cenários onde a escassez de recursos e o recurso à privatização do setor são uma realidade. Para atingir os objetivos a que nos propusemos optámos por uma metodologia centrada na análise documental e assente na experiência dos autores - evidence-based practice.

Introduction and purpose of the study With this study we aimed to describe a "true world" picture of severe pae-diatric 'community-acquired' septic shock and establish the feasibility of a future prospective trial on early goal-directed therapy in children. During a 6-month to 1-year retrospective screening period in 16 emergency departments (ED) in 12 different countries, all children with severe sepsis and signs of decreased perfusion were included. Results A 270,461 paediatric ED consultations were screened, and 176 cases were identified. Significant comorbidity was present in 35.8 % of these cases. Intensive care admission was deemed necessary in 65.7 %, mechanical ventilation in 25.9 % and vasoactive medications in 42.9 %. The median amount of fluid given in the first 6 h was 30 ml/kg. The overall mortality in this sample was 4.5 %. Only 1.2 % of the survivors showed a substantial decrease in Paediatric Overall Performance Category (POPC). 'Severe' outcome (death or a decrease ≥2 in POPC) was significantly related (p0.01) to: any desaturation below 90 %, the amount of fluid given in the first 6 h, the need for and length of mechanical ventilation or vasoactive support, the use of dobutamine and a higher lactate or lower base excess but not to any variables of predisposition, infection or host response (as in the PIRO (Predisposition, Infection, Response, Organ dysfunction) concept). Conclusion The outcome in our samplewas very good.Many children received treatment early in their disease course, so avoiding subsequent intensive care. While certain variables predispose children to become septic and shocked, in our sample, only measures of organ dysfunction and concomitant treatment proved to be significantly related with outcome. We argue why future studies should rather be large multinational prospective observational trials and not necessarily randomised controlled trials.©2013 Springer-Verlag Berlin Heidelberg., SCOPUS: ar.j, info:eu-repo/semantics/published

Introduction and purpose of the study With this study we aimed to describe a "true world" picture of severe pae-diatric 'community-acquired' septic shock and establish the feasibility of a future prospective trial on early goal-directed therapy in children. During a 6-month to 1-year retrospective screening period in 16 emergency departments (ED) in 12 different countries, all children with severe sepsis and signs of decreased perfusion were included. Results A 270,461 paediatric ED consultations were screened, and 176 cases were identified. Significant comorbidity was present in 35.8 % of these cases. Intensive care admission was deemed necessary in 65.7 %, mechanical ventilation in 25.9 % and vasoactive medications in 42.9 %. The median amount of fluid given in the first 6 h was 30 ml/kg. The overall mortality in this sample was 4.5 %. Only 1.2 % of the survivors showed a substantial decrease in Paediatric Overall Performance Category (POPC). 'Severe' outcome (death or a decrease ≥2 in POPC) was significantly related (p0.01) to: any desaturation below 90 %, the amount of fluid given in the first 6 h, the need for and length of mechanical ventilation or vasoactive support, the use of dobutamine and a higher lactate or lower base excess but not to any variables of predisposition, infection or host response (as in the PIRO (Predisposition, Infection, Response, Organ dysfunction) concept). Conclusion The outcome in our samplewas very good.Many children received treatment early in their disease course, so avoiding subsequent intensive care. While certain variables predispose children to become septic and shocked, in our sample, only measures of organ dysfunction and concomitant treatment proved to be significantly related with outcome. We argue why future studies should rather be large multinational prospective observational trials and not necessarily randomised controlled trials.©2013 Springer-Verlag Berlin Heidelberg., SCOPUS: ar.j, info:eu-repo/semantics/published

The TNF-like ligands APRIL and BLyS are close relatives and share the capacity to bind the receptors TACI and BCMA. BLyS has been shown to play an important role in B cell homeostasis and autoimmunity, but the biological role of APRIL remains less well defined. Analysis of T cells revealed an activation-dependent increase in APRIL mRNA expression. We therefore generated mice expressing APRIL as a transgene in T cells. These mice appeared normal and showed no signs of B cell hyperplasia. Transgenic T cells revealed a greatly enhanced survival in vitro as well as enhanced survival of staphylococcal enterotoxin B-reactive CD4+ T cells in vivo, which both directly correlate with elevated Bcl-2 levels. Analysis of humoral responses to T cell-dependent antigens in the transgenic mice indicated that APRIL affects only IgM but not IgG responses. In contrast, T cell-independent type 2 (TI-2) humoral response was enhanced in APRIL transgenic mice. As TACI was previously reported to be indispensable for TI-2 antibody formation, these results suggest a role for APRIL/TACI interactions in the generation of this response. Taken together, our data indicate that APRIL is involved in the induction and/or maintenance of T and B cell responses.

Hematopoietic cell growth, differentiation, and chemotactic responses require coordinated action between cytokines and chemokines. Cytokines promote receptor oligomerization, followed by Janus kinase (JAK) kinase activation, signal transducers and transactivators of transcription (STAT) nuclear translocation, and transcription of cytokine-responsive genes. These include genes that encode a family of negative regulators of cytokine signaling, the suppressors of cytokine signaling (SOCS) proteins. After binding their specific receptors, chemokines trigger receptor dimerization and activate the JAK/STAT pathway. We show that SOCS3 overexpression or up-regulation, stimulated by a cytokine such as growth hormone, impairs the response to CXCL12, measured by Ca2+ flux and chemotaxis in vitro and in vivo. This effect is mediated by SOCS3 binding to the CXC chemokine receptor 4 receptor, blocking JAK/STAT and G i pathways, without interfering with cell surface chemokine receptor expression. The data provide clear evidence for signaling cross-talk between cytokine and chemokine responses in building a functional immune system.

This article reflects on how to design social work education for internationally diverse cohorts of students. It draws on insights from a Master program for social work practitioners from around the world that has been delivered by a partnership of five European universities since 2013. Three particular issues are explored: developing curricula that achieve a local–global balance and emphasize the significance of context sensitivity in social work; the need for teaching approaches that promote dialogue, critical analysis, and student well-being; the importance of providing students with a strong identity, value base, and connection to the global social work profession. The article is targeted at social work educators involved in international and cross-country teaching as well as scholars interested in debates about the balance of local–global dimensions in social work.