Assessing protocol adherence in a clinical trial with ordered treatment regimens: Quantifying the pragmatic, randomized optimal platelet and plasma ratios (PROPPR) trial experience

AbstractBackgroundMedication dispensing errors are common in clinical trials, and have a significant impact on the quality and validity of a trial. Therefore, the definition, calculation and evaluation of such errors are important for supporting a trial’s conclusions. A variety of medication dispensing errors can occur. In this paper, we focus on errors in trials where the intervention includes multiple therapies that must be given in a pre-specified order that varies across treatment arms and varies in duration.MethodsThe Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial was a Phase III multi-site, randomized trial to compare the effectiveness and safety of 1:1:1 transfusion ratios of plasma and platelets to red blood cells with a 1:1:2 ratio. In this trial, these three types of blood products were to be transfused in a pre-defined order that differed by treatment arm. In this paper, we present approaches from the PROPPR trial that we used to define and calculate the occurrence of out of order blood transfusion errors. We applied the proposed method to calculate protocol adherence to the specified order of transfusion in each treatment arm.ResultsUsing our proposed method, protocol adherence was greater in the 1:1:1 group than in the 1:1:2 group (96% vs 93%) (p<0.0001), although out of order transfusion errors in both groups were low. Final transfusion ratios of plasma to platelets to red blood cells for the 1:1:1 ratio group was 0.93:1.32:1, while the transfusion ratio for the 1:1:2 ratio group was 0.48:0.48:1.ConclusionsOverall, PROPPR adherence to blood transfusion order pre-specified in the protocol was high, and the required order of transfusions for the 1:1:2 group was more difficult to achieve. The approaches proposed in this manuscript were useful in evaluating the PROPPR adherence and are potentially useful for other trials where a specific treatment orders with varying durations must be maintained

Structure of the Polycomb Group Protein PCGF1 in Complex with BCOR Reveals Basis for Binding Selectivity of PCGF Homologs

SummaryPolycomb-group RING finger homologs (PCGF1, PCGF2, PCGF3, PCGF4, PCGF5, and PCGF6) are critical components in the assembly of distinct Polycomb repression complex 1 (PRC1)-related complexes. Here, we identify a protein interaction domain in BCL6 corepressor, BCOR, which binds the RING finger- and WD40-associated ubiquitin-like (RAWUL) domain of PCGF1 (NSPC1) and PCGF3 but not of PCGF2 (MEL18) or PCGF4 (BMI1). Because of the selective binding, we have named this domain PCGF Ub-like fold discriminator (PUFD). The structure of BCOR PUFD bound to PCGF1 reveals that (1) PUFD binds to the same surfaces as observed for a different Polycomb group RAWUL domain and (2) the ability of PUFD to discriminate among RAWULs stems from the identity of specific residues within these interaction surfaces. These data show the molecular basis for determining the binding preference for a PCGF homolog, which ultimately helps determine the identity of the larger PRC1-like assembly

La auditoría interna en el sector textil: un oficio tácito en las tecnologías disruptivas

When the companies and productive units of the economic sectors manage to minimize the existing gaps between the complexities of the external sector and the internal dynamics through media mechanisms. It is possible to make a harmony, this means that, the evaluative fact of the categories allows to identify which are the faults that the company presents and in which action must be taken to change in the management and it is more competitive. Under this position, this presentation aims to present the proposal of a tool and instrument, mediated by the use of ICT, that allows characterizing the internal audit processes in the selected localities (Tunjuelito and Antonio Nariño) specifically Policarpa and La Alqueria neighborhoods in the city of Bogotá, through visits and field work in various research and pedagogical conferences: in this way, to achieve awareness among the population about the importance of the study, thus facilitating their active participation in research, and contributing to the design of research strategies. Improvement, according to the findings, where in the end there are not only lessons learned for the sector, but also for the entire educational and professional community of the disciplinary area, which allow a positive impact on the environment, on this occasion of the selected sector.Cuando las empresas y unidades productivas de los sectores económicos logran disminuir las brechas entre las complejidades del sector externo y las dinámicas internas a través de mecanismos mediáticos es posible alcanzar la armonía, lo cual significa que el hecho evaluativo de las categorías permite identificar cuáles son las fallas que presenta la empresa y en qué campo se debe actuar para cambiar la gestión de forma que sea más competitiva. A partir de esta postura el presente artículo propone una herramienta mediada por el uso de las TIC que permita caracterizar los procesos de auditoría interna en las localidades seleccionadas (Tunjuelito y Antonio Nariño), específicamente en los barrios Policarpa y La Alquería en la ciudad de Bogotá, mediante visitas y trabajos de campo en diversas jornadas investigativas y pedagógicas, y de esa manera sensibilizar a la población en cuanto a la importancia del estudio, facilitando así su participación activa en la investigación, y aportando en el diseño de estrategias de mejora, según los hallazgos, donde al final queden lecciones aprendidas, no sólo para el sector sino para toda la comunidad educativa y profesional del área disciplinar, que permitan impactar positivamente el entorno, en esta ocasión del sector seleccionado

Higher media multi-tasking activity is associated with smaller gray-matter density in the anterior cingulate cortex

Media multitasking, or the concurrent consumption of multiple media forms, is increasingly prevalent in today’s society and has been associated with negative psychosocial and cognitive impacts. Individuals who engage in heavier media-multitasking are found to perform worse on cognitive control tasks and exhibit more socio-emotional difficulties. However, the neural processes associated with media multi-tasking remain unexplored. The present study investigated relationships between media multitasking activity and brain structure. Research has demonstrated that brain structure can be altered upon prolonged exposure to novel environments and experience. Thus, we expected differential engagements in media multitasking to correlate with brain structure variability. This was confirmed via Voxel-Based Morphometry (VBM) analyses: Individuals with higher Media Multitasking Index (MMI) scores had smaller gray matter density in the anterior cingulate cortex (ACC). Functional connectivity between this ACC region and the precuneus was negatively associated with MMI. Our findings suggest a possible structural correlate for the observed decreased cognitive control performance and socio-emotional regulation in heavy media-multitaskers. While the cross-sectional nature of our study does not allow us to specify the direction of causality, our results brought to light novel associations between individual media multitasking behaviors and ACC structure differences

Reactividad árido-álcali en áridos empleados para hormigón

The aim of this work is to contribute to the knowledge of the interactions between aggregates and the components of the interstitial phase of concrete and to determine whether those aggregates that are subsequently used in the manufacture of concrete are reagents and are therefore likely to undergo a progressive deterioration of their initial properties. An initial petrographic study of each aggregate is performed in order to be able to determine its subsequent behaviour and reactivity under the influence of various factors. The potential reactivity of different silicaceous aggregates (slates, gneiss, hornfels, granites, quartzite and serpentine) is then determined by a chemical method for evaluating the potential reactivity of aggregates and an accelerated method in mortar specimens, and finally the surface reactivity is investigated. The results of these studies suggest that some aggregates are able to react with the components of the interstitial phase of concrete. The existence of this kind of interaction is confirmed by the results of the surface investigations before and after the basic reaction.Este trabajo pretende contribuir al conocimiento de las reacciones de interacción entre los áridos y los componentes de la fase intersticial del hormigón y determinar si estos áridos, empleados posteriormente en la fabricación del hormigón, son reactivos y por tanto susceptibles de provocar una disminución progresiva de sus propiedades iniciales. Para la caracterización de cada árido se ha realizado un estudio petrográfico, fundamental a la hora de determinar su posterior comportamiento en términos de reactividad frente a diversos factores. Seguidamente, se ha analizado la reactividad potencial de diferentes áridos silicatados (pizarras, gneis, corneanas, granitos, cuarcita y serpentina) mediante los dos métodos normalizados existentes: el método químico para la determinación de la reactividad potencial de áridos y el método acelerado en probetas de mortero; y para contrastar ambos hemos seguido el método de la reactividad superficial. Los resultados determinan que algunos áridos son susceptibles de reaccionar con los componentes de la fase intersticial de hormigón. La observación de su textura antes y después del ataque denota la existencia de esta interacción

The Rise and Fall of "Respectable" Spanish Liberalism, 1808-1923: An Explanatory Framework

The article focuses on the reasons behind both the consolidation of what I have termed “respectable” liberalism between the 1830s and the 1840s and its subsequent decline and fall between 1900 and 1923. In understanding both processes I study the links established between “respectable” liberals and propertied elites, the monarchy, and the Church. In the first phase these links served to consolidate the liberal polity. However, they also meant that many tenets of liberal ideology were compromised. Free elections were undermined by the operation of caciquismo, monarchs established a powerful position, and despite the Church hierarchy working with liberalism, the doctrine espoused by much of the Church was still shaped by the Counter-Reformation. Hence, “respectable” liberalism failed to achieve a popular social base. And the liberal order was increasingly denigrated as part of the corrupt “oligarchy” that ruled Spain. Worse still, between 1916 and 1923 the Church, monarch, and the propertied elite increasingly abandoned the liberal Monarchist Restoration. Hence when General Primo de Rivera launched his coup the rug was pulled from under the liberals’ feet and there was no one to cushion the fall

The British Influence in the Birth of Spanish Sport

Sports started to gain relevance in Spain around the end of the nineteenth century and the beginning of the twentieth century as a leisure and health option of the upper classes imported from Britain. Its early development was intertwined with the spread of other kinds of physical activities with much more tradition on the continent: gymnastics and physical education. First played by the ruling classes – aristocracy and high bourgeoisie – sports permeated towards petty bourgeoisie and middle classes in urban areas such as Madrid, Barcelona, San Sebastián and Santander. This pattern meant that the expansion of sports was unavoidably tied to the degree of industrialisation and cultural modernisation of the country. Since 1910, and mainly during the 1920s, sport grew in popularity as a spectacle and, toa much lesser degree, as a practice among the Spanish population