135,986 research outputs found

    La mujer en el deporte: aspectos jurídico-penales en el deporte femenino = Women in sports: legal-criminal aspects in women’s sports

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    El presente trabajo supone una aproximaci√≥n a aquellas cuestiones jur√≠dicas que inciden de forma espec√≠fica en el deporte femenino, haciendo un especial hincapi√© en ciertas relaciones que pueden nacer entre la pr√°ctica deportiva femenina y el Derecho penal. En un primer lugar, se parte de una contextualizaci√≥n de la posici√≥n de la mujer, su evoluci√≥n desde el apartamiento total hacia el reconocimiento actual y, asimismo, se entrelaza esta sucesi√≥n de acontecimientos con la incidencia que ha tenido y puede tener a futuro el deporte en el recorrido hacia la igualdad de mujeres y hombres. Posteriormente se analiza de forma concreta la legislaci√≥n espa√Īola m√°s relevante en materia de g√©nero y aquella relativa a la prevenci√≥n de la violencia, el racismo, la xenofobia y la intolerancia en el deporte. Por √ļltimo, partiendo de ese punto, se estudian aquellas cuestiones que afectan de manera directa y espec√≠fica a las mujeres en el deporte, tales como la discriminaci√≥n por raz√≥n de embarazo de la mujer deportista, las singulares formas de dopaje en el deporte femenino y la controversia entre los conceptos de sexo biol√≥gico e identidad de g√©nero y sus consecuencias en el deporte

    What is the importance of sperm subpopulations?

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    .The study of sperm subpopulations spans three decades. The origin, meaning, and practical significance, however, are less clear. Current technology for assessing sperm morphology (CASA-Morph) and motility (CASA-Mot) has enabled the accurate evaluation of these features, and there are many options for data classification. Subpopulations could occur as a result of the stage of development of each spermatozoon in the subpopulation. Spermatogenesis might contribute to the production of these subpopulations. Insights from evolutionary biology and recent molecular research are indicative of the diversity among male gametes that could occur from unequal sharing of transcripts and other elements through cytoplasmic bridges between spermatids. Sperm cohorts exiting the gonads would contain different RNA and protein contents, affecting the spermatozoon physiology and associations with the surrounding environmental milieu. Subsequently, these differences could affect how spermatozoa interact with the environmental milieu (maturation, mixing with seminal plasma, and interacting with the environmental milieu, or female genital tract and female gamete). The emergence of sperm subpopulations as an outcome of evolution, related to the reproductive strategies of the species, genital tract structures, and copulatory and fertilization processes. This kind of approach in determining the importance of sperm subpopulations in fertilization capacity should have a practical impact for conducting reproductive technologies, inspiring and enabling new ways for the more efficient use of spermatozoa in the medical, animal breeding, and conservation fields. This manuscript is a contribution to the Special Issue in memory of Dr. Duane GarnerS

    Interactive Sonic Environments: Sonic artwork via gameplay experience

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    The purpose of this study is to investigate the use of video-game technology in the design and implementation of interactive sonic centric artworks, the purpose of which is to create and contribute to the discourse and understanding of its effectiveness in electro-acoustic composition highlighting the creative process. Key research questions include: How can the language of electro-acoustic music be placed in a new framework derived from videogame aesthetics and technology? What new creative processes need to be considered when using this medium? Moreover, what aspects of 'play' should be considered when designing the systems? The findings of this study assert that composers and sonic art practitioners need little or no coding knowledge to create exciting applications and the myriad of options available to the composer when using video-game technology is limited only by imagination. Through a cyclic process of planning, building, testing and playing these applications the project revealed advantages and unique sonic opportunities in comparison to other sonic art installations. A portfolio of selected original compositions, both fixed and open are presented by the author to complement this study. The commentary serves to place the work in context with other practitioners in the field and to provide compositional approaches that have been taken

    Balancing the urban stomach: public health, food selling and consumption in London, c. 1558-1640

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    Until recently, public health histories have been predominantly shaped by medical and scientific perspectives, to the neglect of their wider social, economic and political contexts. These medically-minded studies have tended to present broad, sweeping narratives of health policy's explicit successes or failures, often focusing on extraordinary periods of epidemic disease viewed from a national context. This approach is problematic, particularly in studies of public health practice prior to 1800. Before the rise of modern scientific medicine, public health policies were more often influenced by shared social, cultural, economic and religious values which favoured maintaining hierarchy, stability and concern for 'the common good'. These values have frequently been overlooked by modern researchers. This has yielded pessimistic assessments of contemporary sanitation, implying that local authorities did not care about or prioritise the health of populations. Overly medicalised perspectives have further restricted historians' investigation and use of source material, their interpretation of multifaceted and sometimes contested cultural practices such as fasting, and their examination of habitual - and not just extraordinary - health actions. These perspectives have encouraged a focus on reactive - rather than preventative - measures. This thesis contributes to a growing body of research that expands our restrictive understandings of pre-modern public health. It focuses on how public health practices were regulated, monitored and expanded in later Tudor and early Stuart London, with a particular focus on consumption and food-selling. Acknowledging the fundamental public health value of maintaining urban foodways, it investigates how contemporaries sought to manage consumption, food production waste, and vending practices in the early modern City's wards and parishes. It delineates the practical and political distinctions between food and medicine, broadly investigates the activities, reputations of and correlations between London's guild and itinerant food vendors and licensed and irregular medical practitioners, traces the directions in which different kinds of public health policy filtered up or down, and explores how policies were enacted at a national and local level. Finally, it compares and contrasts habitual and extraordinary public health regulations, with a particular focus on how perceptions of and actual food shortages, paired with the omnipresent threat of disease, impacted broader aspects of civic life

    P469 Infliximab for induction of medically-induced remission in Crohn’s disease: a Cochrane systematic review

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    Background Infliximab is a monoclonal antibody that binds and neutralizes tumour necrosis factor-alpha, which is present in high levels in the blood serum, mucosa and stool of patients with Crohn‚Äôs disease (CD). We sought to determine the effectiveness and safety of infliximab in inducing remission in patients with CD. Methods On 31 August 2021, we searched CENTRAL, CINAHL, ClinicalTrials.gov, Embase, MEDLINE, and WHO ICTRP with no language, date, publication status, or document type limitations. We included randomized controlled trials (RCTs) in which infliximab was compared to placebo or another active comparator in adult (18 and over) patients with active CD. The review authors independently conducted data extraction and ‚ÄėRisk of bias‚Äô assessment of the included studies. We expressed dichotomous and continuous outcomes as risk ratios and mean differences with 95% confidence intervals. We assessed the certainty of the evidence using GRADE methodology. The primary outcome was the proportion of patients who achieved clinical remission. Results We included 9 RCTs (1130 participants). Three studies compared multiple arms with different infliximab doses (between 5mg and 20mg/kg) to placebo. Two studies each with three arms compared azathioprine and placebo, infliximab and placebo, or infliximab and azathioprine combined. One study compared infliximab with biosimilar CT-P13. One study compared infliximab and azathioprine with steroids and azathioprine and only infliximab if no response. The final study compared a single dose (5mg/kg) of infliximab to placebo. In all trials that didn‚Äôt require a purine analogue to be given to both study groups, they allowed such concomitant use in both groups. There is evidence that infliximab combined with azathioprine is superior to azathioprine combined with placebo in inducing clinical remission for CD (RR 1.97, 95% CI 1.60‚Äď2.42, moderate certainty evidence downgraded due to risk of bias, NNT = 3). Sensitivity analysis considering a fixed effects model and then removing a study where most received azathioprine in both groups instead of all, had no impact on the result, which remained significant. There is evidence that there may be no difference in withdrawals from adverse events between infliximab combined with azathioprine and azathioprine combined with placebo when inducing clinical remission for CD (RR 0.74, 95% CI 0.29‚Äď1.86, low certainty evidence downgraded due to serious imprecision). The evidence is uncertain for all other comparisons and outcomes due to imprecision from small sample sizes. Conclusion There is evidence that infliximab with azathioprine is probably better than azathioprine, however the remaining data is based on limited total patient numbers and offers limited scope for meta-analysis

    Cyber-threat landscape of border control infrastructures

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    Various events in recent decades, such as the 9/11 tragedy and the European migration crisis, have highlighted the critical nature of robust borders and the impact of associated attacks on their integrity. However, it is unclear as to the extent to which cyber-attacks can threaten border operations. Interestingly, no extensive research has been conducted into this topic, possibly due to the complexity and diversity of border controls. This paper specifies the cyber-threat landscape of border control infrastructures to assist professionals in assessing the relevant cybersecurity risks. Border control infrastructures are complex environments and relevant risks might not be easily identified. To investigate the cyber-threat landscape of these infrastructures, a mixed research method, combining qualitative and quantitative results, and using border-related expert interviews and risk analysis investigation was chosen. Key contributions of this work include the classification of a widespread set of border assets, the description of the profiles of threat actors and their potential synergies, the specification of a threat taxonomy applicable to all border types, and the identification of potential areas of vulnerability. Moreover, through the risk analysis investigations, exemplary input is developed to guide professionals while applying a risk assessment methodology in the context of border control infrastructures. The paper concludes with future directions addressed to policy makers and border professionals

    The Idiosyncrasy of Involuntary Musical Imagery Repetition (IMIR) Experiences: The Role of Tempo and Lyrics

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    Involuntary musical imagery repetition (IMIR), colloquially known as ‚Äúearworms,‚ÄĚ is a form of musical imagery that arises involuntarily and repeatedly in the mind. A growing number of studies, based on retrospective reports, suggest that IMIR experiences are associated with certain musical features, such as fast tempo and the presence of lyrics, and with individual differences in music training and engagement. However, research to date has not directly assessed the effect of such musical features on IMIR and findings about individual differences in music training and engagement are mixed. Using a cross-sectional design (Study 1, n = 263), we examined IMIR content in terms of tempo (fast, slow) and presence of lyrics (instrumental, vocal), and IMIR characteristics (frequency, duration of episode and section) in relation to 1) the musical content (tempo and lyrics) individuals most commonly expose themselves to (music-listening habits), and 2) music training and engagement. We also used an experimental design (Study 2, n = 80) to test the effects of tempo (fast or slow) and the presence of lyrics (instrumental or vocal) on IMIR retrieval and duration. Results from Study 1 showed that the content of music that individuals are typically exposed to with regard to tempo and lyrics predicted and resembled their IMIR content, and that music engagement, but not music training, predicted IMIR frequency. Music training was, however, shown to predict the duration of IMIR episodes. In the experiment (Study 2), tempo did not predict IMIR retrieval, but the presence of lyrics influenced IMIR duration. Taken together, our findings suggest that IMIR is an idiosyncratic experience primed by the music-listening habits and music engagement of the individual

    The Time Devil runs amok: How I improved my creative practice by adopting a multimodal approach for a specific audience.

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    This research illustrates how teacher-writers can improve their craft and pedagogy by writing for a specific audience, namely school children. It also illustrates why they might do so. It interrogates what was learnt from an innovative collaboration between a university teacher-education department, an inner-city secondary school and the United Kingdom‚Äôs National Maritime Museum (NMM). Multimodality (Barnard 2019) inspired the project: local spaces, institutional settings, historical objects, photographs, pictures, time-travelling films and narratives motivated the teacher-writer and participants to read and respond imaginatively to the world. The author found that the project caused him to ‚Äúremediate‚ÄĚ his own practice: to transfer ‚Äúexisting skills in order to tackle new genres‚ÄĚ (Barnard 2019: 121). This process enabled him to become a more effective writer and teacher. The research shows that the problem of multimodal overload ‚Äď having too much choice regarding what to write about and the many forms writing can take ‚Äď can be circumnavigated if participants are given both autonomy and constraints. It illustrates in some depth how the concept of reciprocity is vital to adopt if writers are to improve their craft

    Medicina personalizada en lactantes con cáncer: Estudio farmacogenético de polimorfismos relacionados con toxicidad y respuesta a la quimioterapia

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    Introducci√≥n La farmacogen√©tica es una herramienta de la ‚ÄúMedicina personalizada‚ÄĚ que contribuye a optimizar los tratamientos antineopl√°sicos, adapt√°ndolos a las caracter√≠sticas gen√©ticas particulares de cada individuo, maximizando su eficacia y minimizando su toxicidad. El lactante con c√°ncer es un paciente de particular vulnerabilidad y sus comorbilidades tiene una especial repercusi√≥n vital. El estudio farmacogen√©tico en esta poblaci√≥n resulta pionero y novedoso en nuestro medio. La identificaci√≥n de marcadores predictivos espec√≠ficos permitir√° individualizar m√°s la terap√©utica en esta poblaci√≥n tan fr√°gil y mejorar en consecuencia su calidad de vida y su pron√≥stico vital. Material y m√©todos Estudio de cohortes ambispectivo de pacientes oncol√≥gicos entre 1 y 18 meses de edad, receptores de quimioterapia en el Hospital La Fe de Valencia, en el periodo comprendido entre enero 2007 y agosto 2019. La parte retrospectiva comprende hasta diciembre 2015, el estudio prospectivo desde enero 2016 hasta agosto 2019. En primer lugar, se realiza un an√°lisis descriptivo de variables epidemiol√≥gicas, cl√≠nico/biol√≥gicas, terap√©uticas y pron√≥sticas de 72 pacientes con dichas caracter√≠sticas. Se describe la toxicidad derivada de sus 578 ciclos de quimioterapia (37 variables cl√≠nicas), el tiempo de seguimiento y su supervivencia (meses). En segundo lugar, se realiza un estudio anal√≠tico cuyo objetivo es correlacionar los polimorfismos gen√©ticos relacionados con la quimioterapia de 64 de los pacientes, la toxicidad grave secundaria al tratamiento (‚Č• grado 3 seg√ļn CTAE 4.0) y su supervivencia. El genotipado se realiza en el Centro Nacional de Genotipado (CEGEN) mediante la tecnolog√≠a MassArray (AgenaBioscience), previa configuraci√≥n de un panel farmacogen√©tico pedi√°trico en base a las evidencias recogidas en la base de datos PharmGKB, fichas t√©cnicas de los medicamentos y consorcios internacionales expertos. El an√°lisis estad√≠stico descriptivo se realiza con los programas Excel 2016 y R: las variables cualitativas con el recuento num√©rico (porcentaje) y las variables cuantitativas como mediana +/- rango intercuart√≠lico ante ausencia de normalidad en la distribuci√≥n de los datos (p <0,05, prueba de Kolmogorov-Smirnov). En el an√°lisis de supervivencia se utiliza el estimador Kaplan-Meier. El an√°lisis estad√≠stico anal√≠tico de correlaci√≥n entre polimorfismos y toxicidad se realiza mediante regresi√≥n log√≠stica penalizada por Elastic Net empleando R. El an√°lisis estad√≠stico anal√≠tico de correlaci√≥n entre polimorfismos y reca√≠da/muerte se realiza mediante regresi√≥n de Cox penalizada por Elastic Net. Resultados Las variables epidemiol√≥gicas, cl√≠nico/biol√≥gicas y terap√©uticas de los pacientes de la muestra son consecuentes con las descritas en la literatura del lactante con c√°ncer. Las neoplasias con mayor impacto negativo en la supervivencia son la leucemia mielobl√°stica aguda y los tumores del sistema nervioso central. La toxicidad m√°s prevalente es hematol√≥gica, digestiva e infecciosa. Existe correlaci√≥n entre la toxicidad grave secundaria a los quimioter√°picos en forma de anemia, neutropenia y/o trombopenia y 46 polimorfismos gen√©ticos diferentes. As√≠ mismo se encuentra asociaci√≥n estad√≠sticamente significativa entre la supervivencia global y la supervivencia libre de enfermedad y ciertos polimorfismos gen√©ticos (26 y 13 respectivamente). Los polimorfismos obtenidos pertenecen a genes encargados del transporte (6 genes) y metabolismo (17 genes) de los f√°rmacos, de la reparaci√≥n del material gen√©tico y la supresi√≥n tumoral (5 genes) y de otras funciones biol√≥gicas (4 genes). Conclusi√≥n Los resultados del presente estudio muestran correlaci√≥n estad√≠stica entre 46 polimorfismos de genes implicados en la cin√©tica farmacol√≥gica y la reparaci√≥n del material gen√©tico y la variabilidad en la toxicidad quimioter√°pica y supervivencia de pacientes lactantes con c√°ncer. En definitiva, aportaciones de la farmacogen√©tica que pueden contribuir a la optimizaci√≥n del tratamiento antineopl√°sico en esta poblaci√≥n particular y a la predicci√≥n de sus riesgos, de especial impacto en los supervivientes del c√°ncer infantil

    Uso de las histonas circulantes y sus modificaciones post-traduccionales como biomarcadores en sepsis y shock séptico

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    La sepsis es una afecci√≥n potencialmente mortal causada por una respuesta anormal del hu√©sped a una infecci√≥n, produciendo respuestas fisiol√≥gicas alteradas que da√Īan los propios tejidos del paciente y pueden provocar disfunci√≥n org√°nica e incluso la muerte. Asimismo, algunos pacientes s√©pticos progresan a shock s√©ptico, caracterizado por alteraciones circulatorias, celulares y metab√≥licas sustanciales que aumentan el riesgo de mortalidad. A pesar de que la sepsis se caracteriza por un mal funcionamiento del sistema inmunol√≥gico, lo que a su vez conduce a una respuesta inmune alterada e inmunosupresi√≥n, la alta complejidad de la fisiopatolog√≠a de la sepsis requiere una mayor investigaci√≥n para comprender las respuestas inmunes que ocurren durante la sepsis. Asimismo, las histonas extracelulares circulantes han ganado relevancia como mediadores citot√≥xicos en la sepsis, ya que act√ļan como patrones moleculares asociados a da√Īo, que inducen estr√©s oxidativo y activan el inflamasoma NLRP3. Estos mecanismos median la activaci√≥n de la piroptosis, un mecanismo de muerte celular programada que produce inflamaci√≥n mediante la expresi√≥n de IL-18, IL-1ő≤ and IL-1őĪ. Sin embargo, a pesar de la evidencia de activaci√≥n del inflamasoma en las c√©lulas inmunes durante la sepsis, se desconoce si las histonas extracelulares son capaces de activar los inflamasomas endoteliales y sus consecuencias. En este trabajo destacamos el papel previamente desconocido de las histonas extracelulares, mediando la activaci√≥n del inflamasoma NLRP3 y la piroptosis en las c√©lulas endoteliales, contribuyendo a la disfunci√≥n endotelial y la desregulaci√≥n de la respuesta inmune mediada por el endotelio. Asimismo, tambi√©n demostramos c√≥mo la acetilaci√≥n de histonas disminuye la activaci√≥n de la piroptosis. Adem√°s, demostramos que la piroptosis se produce en pacientes con shock s√©ptico y los niveles de histonas circulantes se correlacionan con la expresi√≥n de citoquinas proinflamatorias y citoquinas piropt√≥ticas, la liberaci√≥n de factores de adhesi√≥n endotelial y la gravedad de la enfermedad. Proponemos la piroptosis mediada por histonas como un nuevo objetivo para desarrollar intervenciones cl√≠nicas. De manera similar, hemos analizado las respuestas inmunorelacionadas que ocurren durante las primeras etapas de la sepsis con el objetivo de proporcionar nuevos datos comparando las cantidades de citoquinas, inmunomoduladores y otros mediadores endoteliales en pacientes cr√≠ticamente enfermos no s√©pticos, s√©pticos y de shock s√©ptico. Nuestro enfoque ayudar√° a caracterizar r√°pidamente las respuestas inmunes alteradas en pacientes s√©pticos y de shock s√©ptico ingresados en la Unidad de Cuidados Intensivos. Finalmente analizamos el papel de la metilaci√≥n del ADN en el control del sistema inmune s√©ptico. Nuestros resultados demostraron el papel central de la metilaci√≥n del ADN modulando la respuesta molecular en los pacientes de shock s√©ptico y contribuyendo a la inmunosupresi√≥n, a trav√©s de la alteraci√≥n de los patrones de metilaci√≥n de los promotores de IL-10 y TREM-2.Sepsis is a life-threatening condition caused by an abnormal host response to an infection that produce altered physiological responses which damages own tissues of the patient and can result in organ dysfunction and in some cases death. Likewise, a subset of septic patients progresses to septic shock, characterized by substantial circulatory, cellular and metabolic abnormalities, which substantially increase the risk of mortality. Sepsis is characterized by a malfunction of the immune system and it can lead to an altered immune response and immunosuppression. Moreover, the high complexity of the pathophysiology of sepsis requires of further investigation to characterize the immune responses in sepsis and septic shock. Likewise, circulating extracellular histones have gained relevance as cytotoxic mediators in sepsis pathophysiology, since they act as damage-associated molecular patterns, which induce oxidative stress and activate NLRP3 inflammasome. Subsequently, inflammasome mediates pyroptosis activation, a programmed cell death mechanism that produces inflammation through the release of IL-18, IL-1ő≤ and IL-1őĪ. However, despite inflammasome activation may occur in immune cells during sepsis, it is unknown if this process also takes place in endothelial cells and particularly whether extracellular histones are capable of activating endothelial inflammasomes and their consequences. In this work we highlight a previously unknown role for extracellular histones, that mediates the activation of NLRP3 inflammasome and pyroptosis in endothelial cells by contributing to endothelial dysfunction and the dysregulation of the immune response mediated by endothelium. Likewise, we demonstrated how histone acetylation decreases pyroptosis activation. Furthermore, we show how pyroptosis occurs in septic shock patients and how circulating histone levels correlate with the expression of pro-inflammatory and pyroptotic cytokines, the release of endothelial adhesion factors and septic shock severity. We propose histone-mediated pyroptosis as a new target to develop clinical interventions. Similarly, we have analyzed the immune-related responses occurring during the early stages of sepsis with the aim of providing new data by comparing the amounts of cytokines, immune modulators and other endothelial mediators in critically-ill non-septic patients, septic and septic shock patients. Our approach will help to rapidly characterize the altered immune responses in septic and septic shock patients admitted in the Intensive Care Unit. Finally, we also analyzed the role of DNA methylation in the control of septic immune system. Our results demonstrated the central role of DNA methylation modulating the molecular response in septic shock patients and contributing to immunosuppression, through the alteration of DNA methylation patterns of IL-10 and TREM2 promoters
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