Efecto de la probabilidad de errores durante la acción de ataque de esgrima

El propósito de este estudio ha sido comprobar el efecto que tiene la probabilidad de que surja el error durante la realización de una acción de ataque en esgrima, sobre los parámetros temporales de las respuestas de reacción (TRR) y la velocidad de desplazamiento del centro de masas (CM). Han participado 17 esgrimistas (14 hombres y 3 mujeres), con una experiencia en competición regional de más de cinco años. Para el registro de los datos, se han utilizado dos plataformas de fuerza, operando a 500 Hz, una cámara de vídeo, a 210 Hz y un cronómetro electrónico adaptado al sistema de cableado de las armas. Una señal electrónica se utilizó para sincronizar temporalmente todos los registros. Para la situación experimental donde no existía incertidumbre durante la acción (CIA), los esgrimistas tenían que realizar un ataque simple con fondo lo más rápidamente posible al aparecer un círculo en el centro del plastrón (E1), intentando situar la punta de la espada dentro del círculo. Para la situación experimental donde existía incertidumbre debida a la posibilidad de error (CIA), los esgrimistas tenían los mismos objetivos que en la situación anterior, aunque debían de inhibir la acción de ataque a otra de defensiva, en el caso de que el círculo desapareciera del plastrón durante la acción. Los resultados ponen de manifiesto que, cuando existe la posibilidad de error durante la realización del ataque en esgrima, se incrementan los parámetros temporales de la respuesta de reacción (TR y TM) y disminuye la velocidad de ejecución.The main aim of this study has been to verify the effect that has the probability from which the mistake arises during the accomplishment of an action of assault in fencing, on the temporary parameters of the answers of reaction (TRR) and the speed of displacement of the center of masses (CM). 17 fencers (14 men and 3 women), with an experience in regional competition of more than five years took part in this study. Two force platforms, operating to 500 Hz have been in used, a video camera, to 210 Hz and an electronic chronometer adapted to the system of wired up of the weapon for the record of the data. An electronic sign was used for synchronizing temporarily all the records. For the experimental situation where uncertainty did not exist during the action (CIA), the fencers had to realize a simple assault with lunge as rapidly as possible when a circle appeared in the center of the plastron (E1), trying to place the top of the sword inside the circle. For the experimental situation where there existed uncertainty due to the possibility of mistake (CIA), the fencers had the same aims that in the previous situation, though they must disable the action of assault to other one of defensive, in case the circle was disappearing of the plastron during the action. The results reveal that, when the possibility of mistake exists during the accomplishment of the assault in fencing, there are increased the temporary parameters of the response of reaction (TR and TM) and it diminishes the speed of execution.Peer Reviewe

Efecto de la probabilidad de errores durante la acción de ataque de esgrima

El propósito de este estudio ha sido comprobar el efecto que tiene la probabilidad de que surja el error durante la realización de una acción de ataque en esgrima, sobre los parámetros temporales de las respuestas de reacción (TRR) y la velocidad de desplazamiento del centro de masas (CM). Han participado 17 esgrimistas (14 hombres y 3 mujeres), con una experiencia en competición regional de más de cinco años. Para el registro de los datos, se han utilizado dos plataformas de fuerza, operando a 500 Hz, una cámara de vídeo, a 210 Hz y un cronómetro electrónico adaptado al sistema de cableado de las armas. Una señal electrónica se utilizó para sincronizar temporalmente todos los registros. Para la situación experimental donde no existía incertidumbre durante la acción (CIA), los esgrimistas tenían que realizar un ataque simple con fondo lo más rápidamente posible al aparecer un círculo en el centro del plastrón (E1), intentando situar la punta de la espada dentro del círculo. Para la situación experimental donde existía incertidumbre debida a la posibilidad de error (CIA), los esgrimistas tenían los mismos objetivos que en la situación anterior, aunque debían de inhibir la acción de ataque a otra de defensiva, en el caso de que el círculo desapareciera del plastrón durante la acción. Los resultados ponen de manifiesto que, cuando existe la posibilidad de error durante la realización del ataque en esgrima, se incrementan los parámetros temporales de la respuesta de reacción (TR y TM) y disminuye la velocidad de ejecución.The main aim of this study has been to verify the effect that has the probability from which the mistake arises during the accomplishment of an action of assault in fencing, on the temporary parameters of the answers of reaction (TRR) and the speed of displacement of the center of masses (CM). 17 fencers (14 men and 3 women), with an experience in regional competition of more than five years took part in this study. Two force platforms, operating to 500 Hz have been in used, a video camera, to 210 Hz and an electronic chronometer adapted to the system of wired up of the weapon for the record of the data. An electronic sign was used for synchronizing temporarily all the records. For the experimental situation where uncertainty did not exist during the action (CIA), the fencers had to realize a simple assault with lunge as rapidly as possible when a circle appeared in the center of the plastron (E1), trying to place the top of the sword inside the circle. For the experimental situation where there existed uncertainty due to the possibility of mistake (CIA), the fencers had the same aims that in the previous situation, though they must disable the action of assault to other one of defensive, in case the circle was disappearing of the plastron during the action. The results reveal that, when the possibility of mistake exists during the accomplishment of the assault in fencing, there are increased the temporary parameters of the response of reaction (TR and TM) and it diminishes the speed of execution.Peer Reviewe

Elraglusib (9-ING-41), a selective small-molecule inhibitor of glycogen synthase kinase-3 beta, reduces expression of immune checkpoint molecules PD-1, TIGIT and LAG-3 and enhances CD8+ T cell cytolytic killing of melanoma cells

Background Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase with multiple roles in tumour growth, cell invasion and metastasis. We have previously established GSK-3 as an upstream regulator of PD-1 gene expression in CD8 + T cells and demonstrated that GSK-3 inhibition is as effective as anti-PD-1 mAb blockade in controlling tumour growth. Elraglusib (9-ING-41) is a specific small-molecule inhibitor of GSK-3β with clinical activity in patients with advanced cancers, including a patient with refractory melanoma whose response provided the rationale for the current study. Methods The B16 melanoma mouse model was used to observe the effect of elraglusib on tumour growth either as a single agent or in combination (simultaneously and sequentially) with anti-PD-1 mAb treatment. B16 tumour cells were implanted in either the flank, brain or both locations, and Kaplan–Meier plots were used to depict survival and significance determined using log rank tests. Expression of the immune checkpoint molecules, TIGIT, LAG-3 and PD-1, was evaluated using flow cytometry alongside expression of the chemokine receptor, CXCR3. Further evaluation of PD-1 expression was determined through RT-qPCR and immunohistochemistry. Results We demonstrated that elraglusib has a suppressive effect against melanoma as a single agent and enhanced anti-PD-1 therapy. There was a synergistic effect when elraglusib was used in combination with anti-PD-1 mAb, and an even greater effect when used as sequential therapy. Suppression of tumour growth was associated with a reduced expression of immune checkpoint molecules, PD-1, TIGIT and LAG-3 with upregulation of CXCR3 expression. Conclusions These data highlight the potential of elraglusib as an immune-modulatory agent and demonstrate the benefit of a sequential approach with immune checkpoint inhibition followed by GSK-3β inhibition in melanoma and provide a rationale for clinical investigation of elraglusib combined with immune checkpoint inhibitory molecules, including those targeting PD-1, TIGIT and LAG-3. This has several potential implications for current immunotherapy regimes, including possibly reducing the intensity of anti-PD-1 mAb treatment needed for response in patients receiving elraglusib, especially given the benign adverse event profile of elraglusib observed to date. Based on these data, a clinical study of elraglusib, an anti-PD-1 mAb and chemotherapy is ongoing (NCT NCT05239182)

How to trigger emergence and self-organisation in Learning Networks

The original publication is available at www.springerlink.com. Brouns, F., Fetter, S., & Van Rosmalen, P. (2009). How to trigger emergence and self-organisation in Learning Networks. In R. Koper (Ed.), Learning Network Services for Professional Development (pp. 57-72). Berlin, Germany: Springer Verlag.In the current chapter, we describe an example of a peer support Learning Network Service based on the mechanism of peer tutoring in ad-hoc transient communities.The work on this publication has been sponsored in part by the TENCompetence Integrated Project that is funded by the European Commission's 6th Framework Programme, priority IST/Technology Enhanced Learning. Contract 027087 [http://www.tencompetence.org

A Survey of Volunteered Open Geo-Knowledge Bases in the Semantic Web

Over the past decade, rapid advances in web technologies, coupled with innovative models of spatial data collection and consumption, have generated a robust growth in geo-referenced information, resulting in spatial information overload. Increasing 'geographic intelligence' in traditional text-based information retrieval has become a prominent approach to respond to this issue and to fulfill users' spatial information needs. Numerous efforts in the Semantic Geospatial Web, Volunteered Geographic Information (VGI), and the Linking Open Data initiative have converged in a constellation of open knowledge bases, freely available online. In this article, we survey these open knowledge bases, focusing on their geospatial dimension. Particular attention is devoted to the crucial issue of the quality of geo-knowledge bases, as well as of crowdsourced data. A new knowledge base, the OpenStreetMap Semantic Network, is outlined as our contribution to this area. Research directions in information integration and Geographic Information Retrieval (GIR) are then reviewed, with a critical discussion of their current limitations and future prospects

Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium.

BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research

Heterogeneity of luminal breast cancer characterised by immunohistochemical expression of basal markers

Background: Luminal A breast cancer defined as hormone receptor positive and human epidermal growth factor receptor 2 (HER2) negative is known to be heterogeneous. Previous study showed that luminal A tumours with the expression of basal markers ((cytokeratin (CK) 5 or CK5/6) or epidermal growth factor receptor (EGFR)) were associated with poorer prognosis compared with those that stained negative for basal markers. Prompted by this study, we assessed whether tumour characteristics and risk factors differed by basal marker status within luminal A tumours. Methods: We pooled 5040 luminal A cases defined by immunohistochemistry (4490 basal-negative ((CK5 (or CK5/6))− and EGFR−) and 550 basal-positive ((CK5 (or CK5/6+)) or EGFR+)) from eight studies participating in the Breast Cancer Association Consortium. Case–case comparison was performed using unconditional logistic regression. Results: Tumour characteristics and risk factors did not vary significantly by the expression of basal markers, although results suggested that basal-positive luminal tumours tended to be smaller and node negative, and were more common in women with a positive family history and lower body mass index. Conclusions: Most established breast cancer risk factors were similar in basal-positive and basal-negative luminal A tumours. The non-significant but suggestive differences in tumour features and family history warrant further investigations

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK

Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1

High-risk mutations in several genes predispose to both colorectal cancer (CRC) and endometrial cancer (EC). We therefore hypothesised that some lower-risk genetic variants might also predispose to both CRC and EC. Using CRC and EC genome-wide association series, totalling 13,265 cancer cases and 40,245 controls, we found that the protective allele [G] at one previously-identified CRC polymorphism, rs2736100 near TERT, was associated with EC risk (odds ratio (OR) = 1.08, P = 0.000167); this polymorphism influences the risk of several other cancers. A further CRC polymorphism near TERC also showed evidence of association with EC (OR = 0.92; P = 0.03). Overall, however, there was no good evidence that the set of CRC polymorphisms was associated with EC risk, and neither of two previously-reported EC polymorphisms was associated with CRC risk. A combined analysis revealed one genome-wide significant polymorphism, rs3184504, on chromosome 12q24 (OR = 1.10, P = 7.23 × 10−9) with shared effects on CRC and EC risk. This polymorphism, a missense variant in the gene SH2B3, is also associated with haematological and autoimmune disorders, suggesting that it influences cancer risk through the immune response. Another polymorphism, rs12970291 near gene TSHZ1, was associated with both CRC and EC (OR = 1.26, P = 4.82 × 10−8), with the alleles showing opposite effects on the risks of the two cancers