Terapia dos erros com aprendizagem móvil e gamificação: estudo comparativo em espanhol dos negócios

This research paper compares the results of an analysis of the evolution of written interlanguage in two groups of learners of Spanish as a foreign language (sfl). The participants wrote four essays throughout a semester, each one followed by an error-therapy session, respectively. The test group did the therapies through online platform Kahoot, which introduces gamification and allows the mobile learning methodology, while the control group did traditional activities on paper. The teachers marked the mistakes in the texts using the minimal marking criterion (Haswell, 1983), and the students then proceeded to correct their own errors. Although both methods had positive results, the test group shows a more remarkable evolution in terms of reducing the number of errors in each text.Este artículo de investigación compara los resultados de un análisis sobre la evolución de la interlengua escrita de dos grupos de aprendientes de español como lengua extranjera (ele). Los participantes realizaron cuatro redacciones a lo largo de un semestre seguidas respectivamente de una sesión de terapia de errores. El grupo de prueba realizó las terapias mediante la plataforma online Kahoot, que introduce la gamificación y permite la metodología mobile learning, mientras que el grupo de control realizó actividades tradicionales en papel. Las profesoras señalaron los errores de las redacciones mediante el criterio minimal marking (Haswell, 1983) y seguidamente los estudiantes procedieron a su autocorrección. Aunque con los dos métodos se obtuvieron resultados positivos, el grupo de prueba muestra una evolución más notable en cuanto a la reducción del número de errores de cada escrito.Este artigo de pesquisa compara as descobertas de uma análise sobre a evolução da interlíngua escrita de dois grupos de aprendentes de espanhol como língua estrangeira (ele). Os participantes realizaram quatro textos ao longo do semestre seguidos cada um de uma sessão de terapia de erros. O grupo de prova realizou a terapia por meio da plataforma online Kahoot, que introduz a gamificação e possibilita a metodologia mobile learning, enquanto o grupo de controle realizou atividades tradicionais em papel. As professoras assinalaram os erros das escritas por meio do critério minimal marking (Haswell, 1983) e em seguida os estudantes auto-corrigiram seus textos. Ainda que as duas metodologias obtiveram resultado positivos, o grupo de prova apresentou uma evolução mais evidente ao respeito da redução no número de erros de cada texto

Bal tool in flexible manufacturing systems

A tool for performance evaluation, called BAL, will be presented in this paper. The BAL tool works with systems specification by means of the timed process algebra BTC so that it is able to consider the duration of actions and the context (resources) in which processes are executed. BAL begins by first making the syntactic analysis of the system specification, and then draws up its relevant transition graph by applying the rules of the operational semantics and solves a performance optimization problem relevant to the minimization of the maximum completion time. We will then consider the application of BAL in Flexible Manufacturing Systems (FMS)

EVI1 as a Prognostic and Predictive Biomarker of Clear Cell Renal Cell Carcinoma

The transcription factor EVI1 plays an oncogenic role in several types of neoplasms by promoting aggressive cancer features. EVI1 contributes to epigenetic regulation and transcriptional control, and its overexpression has been associated with enhanced PI3K-AKT-mTOR signaling in some settings. These observations raise the possibility that EVI1 influences the prognosis and everolimus-based therapy outcome of clear cell renal cell carcinoma (ccRCC). Here, gene expression and protein immunohistochemical studies of ccRCC show that EVI1 overexpression is associated with advanced disease features and with poorer outcome-particularly in the CC-e.3 subtype defined by The Cancer Genome Atlas. Overexpression of an oncogenic EVI1 isoform in RCC cell lines confers substantial resistance to everolimus. The EVI1 rs1344555 genetic variant is associated with poorer survival and greater progression of metastatic ccRCC patients treated with everolimus. This study leads us to propose that evaluation of EVI1 protein or gene expression, and of EVI1 genetic variants may help improve estimates of prognosis and the benefit of everolimus-based therapy in ccRCC

Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis

Biomarcador; Histamina; LimfangioleiomiomatosiBiomarcador; Histamina; LinfangioleiomiomatosisBiomarker; Histamine; LymphangioleiomyomatosisInhibition of mTOR is the standard of care for lymphangioleiomyomatosis (LAM). However, this therapy has variable tolerability and some patients show progressive decline of lung function despite treatment. LAM diagnosis and monitoring can also be challenging due to the heterogeneity of symptoms and insufficiency of non-invasive tests. Here, we propose monoamine-derived biomarkers that provide preclinical evidence for novel therapeutic approaches. The major histamine-derived metabolite methylimidazoleacetic acid (MIAA) is relatively more abundant in LAM plasma, and MIAA values are independent of VEGF-D. Higher levels of histamine are associated with poorer lung function and greater disease burden. Molecular and cellular analyses, and metabolic profiling confirmed active histamine signaling and metabolism. LAM tumorigenesis is reduced using approved drugs targeting monoamine oxidases A/B (clorgyline and rasagiline) or histamine H1 receptor (loratadine), and loratadine synergizes with rapamycin. Depletion of Maoa or Hrh1 expression, and administration of an L-histidine analog, or a low L-histidine diet, also reduce LAM tumorigenesis. These findings extend our knowledge of LAM biology and suggest possible ways of improving disease management.This research was supported by AELAM, The LAM Foundation (Seed Grant 2019), Instituto de Salud Carlos III grants PI15/00854, PI18/01029, and ICI19/00047 (co-funded by European Regional Development Fund (ERDF), a way to build Europe), Generalitat de Catalunya SGR grants 2014-364 and 2017-449, the CERCA Program, and ZonMW-TopZorg grant 842002003. C.L.M. acknowledges the financial support (PRA-2017-51 project) of the University of Pisa. A.U.K. is supported by Nottingham Trent University’s Independent Fellowship Scheme

Asociaciones de moluscos de fondos sedimentarios circalitorales y batiales del norte del mar de Alborán

Molluscan assemblages from shelf and slope soft bottoms of the Alboran Sea have been sampled with a beam trawl during 2014 and 2015 MEDITS expeditions. A total of 134 spp. of molluscs (shell size > 3 mm) were identified, being gastropods the most diverse and dominant group. Four main depth related assemblages were detected in multivariate analyses and characterized by (1) Turritella communis, Chamelea striatula and Nucula sulcata for the inner shelf, (2) Timoclea ovata, Clelandella miliaris and Neopycnodonte cochlear for the outer shelf, (3) Nassarius ovoideus, Calumbonella suturale and N. sulcata for the upper slope and (4) Abra longicallus, Euspira fusca and Aporrhais serresianus for the middle slope. Species richness and abundance decreased with depth, unlike evenness and Shannon-Wiener diversity which displayed an opposite pattern. A higher spatial variability was detected for the shelf, indicating that more assemblages may occur at this level and further sampling is needed for covering all sedimentary habitat types of the Alboran Sea.Versión del edito

Adiciones y revisiones al Atlas de la flora vascular silvestre de Burgos, VIII

Se mencionan 44 táxones con citas y comentarios referidos a su existencia en la provincia de Burgos. De ellos 3 suponen una novedad para el catálogo provincial.44 Taxa with either quotations or remarks, related to their existence within the province of Burgos, are mentioned. 3 out of these aforementioned ones mean a novelty value for the provincial catalogue

Tumor xenograft modeling identifies an association between TCF4 loss and breast cancer chemoresistance

Understanding the mechanisms of cancer therapeutic resistance is fundamental to improving cancer care. There is clear benefit from chemotherapy in different breast cancer settings; however, knowledge of the mutations and genes that mediate resistance is incomplete. In this study, by modeling chemoresistance in patientderived xenografts (PDXs), we show that adaptation to therapy is genetically complex and identify that loss of transcription factor 4 (TCF4; also known as ITF2) is associated with this process. A triple-negative BRCA1-mutaied PDX was used to study the genetics of chemoresistance. The PDX was treated in parallel with four chemotherapies for five iterative cycles. Exome sequencing identified few genes with de novo or enriched mutations in common among the different therapies, whereas many common depleted mutations/ genes were observed. Analysis of somatic mutations from The Cancer Genome Atlas (TCGA) supported the prognostic relevance of the identified genes. A mutation in TCF4 was found de novo in all treatments, and analysis of drug sensitivity profiles across cancer cell lines supported the link to chemoresistance. Loss of TCF4 conferred chemoresistance in breast cancer cell models, possibly by altering cell cycle regulation. Targeted sequencing in chemoresistant tumors identified an intronic variant of TCF4 that may represent an expression quantitative trait locus associated with relapse outcome in TCGA. Immunohistochemical studies suggest a common loss of nuclear TCF4 expression post-chemotherapy. Together, these results from tumor xenograft modeling depict a link between altered TCF4 expression and breast cancer chemoresistance

Invasive Fusariosis in Nonneutropenic Patients, Spain, 2000-2015

Invasive fusariosis (IF) is associated with severe neutropenia in patients with concurrent hematologic conditions. We conducted a retrospective observational study to characterize the epidemiology of IF in 18 Spanish hospitals during 2000-2015. In that time, the frequency of IF in nonneutropenic patients increased from 0.08 cases per 100,000 admissions in 2000-2009 to 0.22 cases per 100,000 admissions in 2010-2015. Nonneutropenic IF patients often had nonhematologic conditions, such as chronic cardiac or lung disease, rheumatoid arthritis, history of solid organ transplantation, or localized fusariosis. The 90-day death rate among nonneutropenic patients (28.6%) and patients with resolved neutropenia (38.1%) was similar. However, the death rate among patients with persistent neutropenia (91.3%) was significantly higher. We used a multivariate Cox regression analysis to characterize risk factors for death: persistent neutropenia was the only risk factor for death, regardless of antifungal therapy

Oral versus intramuscular administration of vitamin B12 for vitamin B12 deficiency in primary care : a pragmatic, randomised, non-inferiority clinical trial (OB12)

The trial was financed by Ministerio de Sanidad y Consumo Español through their call for independent clinical research, Orden Ministerial SAS/2377, 2010 (EC10-115, EC10-116, EC10-117, EC10-119, EC10-122); CAIBER—Spanish Clinical Research Network, Instituto de Salud Carlos III (ISCIII) (CAI08/010044); and Gerencia Asistencial de Atención Primaria de Madrid. This study is also supported by the Spanish Clinical Research Network (SCReN), funded by ISCIII-Subdirección General de Evaluación y Fomento de la Investigación, project number PT13/0002/0007, within the National Research Program I+D+I 2013-2016 and co-funded with European Union ERDF funds (European Regional Development Fund). This project received a grant for the translation and publication of this article from the Foundation for Biomedical Research and Innovation in Primary Care (FIIBAP) Call 2017 for grants to promote research programs.Objectives To compare the effectiveness of oral versus intramuscular (IM) vitamin B12 (VB12) in patients aged ≥65 years with VB12 deficiency. Design Pragmatic, randomised, non-inferiority, multicentre trial in 22 primary healthcare centres in Madrid (Spain). Participants 283 patients ≥65 years with VB12 deficiency were randomly assigned to oral (n=140) or IM (n=143) treatment arm. Interventions The IM arm received 1 mg VB12 on alternate days in weeks 1–2, 1 mg/week in weeks 3–8 and 1 mg/month in weeks 9–52. The oral arm received 1 mg/day in weeks 1–8 and 1 mg/week in weeks 9–52. Main outcomes Serum VB12 concentration normalisation (≥211 pg/mL) at 8, 26 and 52 weeks. Non-inferiority would be declared if the difference between arms is 10% or less. Secondary outcomes included symptoms, adverse events, adherence to treatment, quality of life, patient preferences and satisfaction. Results The follow-up period (52 weeks) was completed by 229 patients (80.9%). At week 8, the percentage of patients in each arm who achieved normal B12 levels was well above 90%; the differences in this percentage between the oral and IM arm were −0.7% (133 out of 135 vs 129 out of 130; 95% CI: −3.2 to 1.8; p>0.999) by per-protocol (PPT) analysis and 4.8% (133 out of 140 vs 129 out of 143; 95% CI: −1.3 to 10.9; p=0.124) by intention-to-treat (ITT) analysis. At week 52, the percentage of patients who achieved normal B12 levels was 73.6% in the oral arm and 80.4% in the IM arm; these differences were −6.3% (103 out of 112 vs 115 out of 117; 95% CI: −11.9 to −0.1; p=0.025) and −6.8% (103 out of 140 vs 115 out of 143; 95% CI: −16.6 to 2.9; p=0.171), respectively. Factors affecting the success rate at week 52 were age, OR=0.95 (95% CI: 0.91 to 0.99) and having reached VB12 levels ≥281 pg/mL at week 8, OR=8.1 (95% CI: 2.4 to 27.3). Under a Bayesian framework, non-inferiority probabilities (Δ>−10%) at week 52 were 0.036 (PPT) and 0.060 (ITT). Quality of life and adverse effects were comparable across groups. 83.4% of patients preferred the oral route. Conclusions Oral administration was no less effective than IM administration at 8 weeks. Although differences were found between administration routes at week 52, the probability that the differences were below the non-inferiority threshold was very low.Publisher PDFPeer reviewe

Lymphangioleiomyomatosis biomarkers linked to lung metastatic potential and cell stemness

Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-ß3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM