Evolution of Our Understanding of XIAP Deficiency

X-linked inhibitor of apoptosis (XIAP) deficiency is a rare inborn error of immunity first described in 2006. XIAP deficiency is characterised by immune dysregulation and a broad spectrum of clinical manifestations, including haemophagocytic lymphohistiocytosis (HLH), inflammatory bowel disease (IBD), hypogammaglobulinemia, susceptibility to infections, splenomegaly, cytopaenias, and other less common autoinflammatory phenomena. Since the first description of the disease, many XIAP deficient patients have been identified and our understanding of the disease has grown. Over 90 disease causing mutations have been described and more inflammatory disease manifestations, such as hepatitis, arthritis, and uveitis, are now well-recognised. Recently, following the introduction of reduced intensity conditioning (RIC), outcomes of allogeneic haematopoietic stem cell transplantation (HSCT), the only curative treatment option for XIAP deficiency, have improved. The pathophysiology of XIAP deficiency is not fully understood, however it is known that XIAP plays a role in both the innate and adaptive immune response and in immune regulation, most notably through modulation of tumour necrosis factor (TNF)-receptor signalling and regulation of NLRP3 inflammasome activity. In this review we will provide an up to date overview of both the clinical aspects and pathophysiology of XIAP deficiency

Britain, Bulgaria and benefits:the political rhetoric of European (dis)integration

This chapter considers the political controversy in Britain over the lifting of restrictions of freedom of movement on European Union (EU) citizens from Bulgaria and Romania in January 2014. The response of the then Conservative-Liberal Democrat Coalition Government centred on altering the rules on the payment of welfare benefits to potential new EU immigrants such that they would not be entitled to claim these benefits for 3 months after entry to the United Kingdom. This policy led to a split in the coalition, with the Liberal Democrat leadership claiming that it was a panicked move by the majority Conservative coalition partner, and moreover that it was a blatant attempt to appeal the electorate in an effort to be seen to be doing something to stop the welfare benefit system from being abused by ‘foreigners’. The backdrop to this political fracas centred on the economic contribution of East European immigrants to Britain and the claim and counterclaim over the issues jobs, welfare benefits and services such as English language support in schools. These contentious issues are examined in terms of an analysis of online comments to posted in reaction to a political interview with Vince Cable, the Liberal Democrat business secretary, who claimed that the Conservatives were attempting to placate public disquiet over immigration as a response to the rising popularity of the United Kingdom Independence Party

Time-Resolved X-Ray Tomography of a Fluidized Bed of Geldart A Particles

This paper discusses the influence of fines on the size of bubbles moving through a 23 cm ID fluidized bed of Geldart A particles imaged with an X-ray Tomographic Scanner. In earlier work [1], the bubble distribution in a fluidized bed of Geldart B particles was shown. The current study using Geldart A particles is more challenging to the reconstruction algorithm, since there are more bubbles, and they are smaller in size. We study the influence of adding fines (i.e. particles \u3c= 45 micron) to the system. When adding a mass fraction of fines of 24%, we find a decrease of the average bubble of 40% of the size for the original powder, in line with earlier results from pressure probes and optical probes [2]. We find that the entire distribution of the bubble sizes shifts to smaller values

Factores asociados con la intención de fumar y el inicio del hábito tabáquico en escolares: resultados del estudio ESFA en Barcelona

ResumenObjetivoDescribir los factores asociados con el consumo de tabaco y la intención de fumar en el futuro en una muestra representativa de escolares de primer curso de educación secundaria en Barcelona.Sujetos y métodosSe seleccionaron 37 escuelas al azar para participar en la evaluación de un programa europeo de prevención del tabaquismo (European Smoking prevention Frame Approach, proyecto ESFA). En estas escuelas 1.041 alumnos de primer curso de Enseñanza Secundaria Obligatoria (ESO) contestaron a un cuestionario diseñado por la Universidad de Maastricht para estudiar las actitudes y conductas relacionadas con diversos comportamientos, incluyendo el consumo de tabaco.ResultadosEl 9,8% de los chicos y el 12,6% de las chicas manifestaron fumar de forma regular u ocasional. Entre los no fumadores, un 61,4% de los chicos y un 73,3% de las chicas declararon tener intención de fumar en el futuro. En los chicos, los determinantes del consumo son la norma social (odds ratio [OR] = 2,5; intervalo de confianza [IC] del 95%, 1,2–5,2), el consumo de tabaco por parte de los hermanos (OR = 2,4; IC del 95%, 1,1–5,2), las actitudes contrarias al consumo (OR = 0,3; IC del 95%, 0,1–0,6), la práctica de deporte en el tiempo libre (OR = 0,3; IC del 95%, 0,1–0,7) y el dinero semanal disponible (OR = 3,2; IC del 95%, 1,5–6,8), mientras que la intención únicamente se asoció de forma significativa a las actitudes contrarias (OR = 0,3; IC del 95%, 0,2–0,5). Para las chicas, el consumo se asoció a la presión (OR = 2,5; IC del 95%, 1,2–5,0) y el consumo (OR = 6,0; IC del 95%, 2,4–15,4) por parte de los amigos, y las actitudes contrarias (OR = 0,2; IC del 95%, 0,1–0,4), mientras que la intención se halla asociada a las actitudes contrarias (OR = 0,4; IC del 95%, 0,2–0,6) y pasar tiempo libre en la calle (OR = 2,1; IC del 95%, 1,3–3,5).ConclusionesLos resultados corroboran la necesidad de abordar simultáneamente los distintos factores relacionados con el inicio del tabaquismo, incluyendo las actitudes, la influencia de las personas del entorno inmediato y la utilizacion del tiempo libre.SummaryObjectiveTo describe the factors asssociated with smoking and intention to smoke among a representative sample of firstgrade pupils of secondary education (12–13 years old) in Barcelona.Subjects and methods37 secondary schools were randomly selected to evaluate the impact of a European-wide smoking prevention program (European Smoking prevention Frame Approach, ESFA project). In these schools, 1041 pupils of first grade of secondary education responded to a questionnaire designed at the University of Maastricht to study life-style attitudes and behaviours, mainly smoking.Results9.8% of boys and 12.6% of girls declared to smoke either regulary or ocasionally. Among the no-smokers, 61.4% of the boys and 73.3% of the girls reported to have the intention to smoke in the future. Among the boys, factors associated with smoking included social norms (odds ratio [OR] = 2.5; 95% confidence interval [CI]: 1.2–5.2), smoking by siblings (OR = 2.4; 95% CI, 1.1–5.2), attitudes against smoking (OR = 0.3; 95% CI, 0.1–0.6), practicing some sports in the leisure time (OR = 0.3; 95% CI, 0.1–0.7) and having more available pocket money (OR = 3.2; 95% CI, 1.5–6.8). Intention to smoke was only related to attitudes (OR = 0.3; 95% CI, 0.2–0.5). Among girls, smoking was associated to perceived pressure to smoke (OR = 2.5; 95% CI, 1.2–5.0), consumption by friends (OR = 6.0; 95% CI, 2.4–15.4) and attitudes against smoking (OR = 0.2; 95% CI, 0.1–0.4), while intention was only associated to attitudes (OR = 0.4; 95% CI, 0.2–0.6) and hanging out in the street in the leisure time (OR = 2.2; 95% CI, 0.3–3.5).ConclusionsThe results stress the need to deal simultaneoulsy with the different factors associated to smoking initiation and attitude shaping, including cognitive factors, environmental factors, and patterns of leisure time utilization

Comparison of optical probes and X-ray tomography for bubble characterization in fluidized bed methanation reactors

The performance of many fluidized bed reactors strongly depends on the bubble behavior since they influence the mass transfer to the dense phase where the catalyst is present. An example is the methanation in a fluidized bed that allows for conversion of unsaturated hydrocarbons in the gasification gas without catalyst deactivation [1]. The BFB reactor is a very challenging step in the process chain to produce SNG out of biomass as feedstock since next to the bubble behavior a lot of other parameters like temperature, pressure, particle size, attrition of the catalyst, internals, bed height and reactor diameter etc. affect the overall performance. The focus of this research work lies on the determination of the bubble properties which are an important factor to model a bubbling fluidized methanation reactor in order to predict and optimize its performance and to support its scale-up [2]. Tomographic methods such as X-ray measurements are often used to characterize bubbles in a fluidized bed. Compared to intrusive measurement, e.g. optical probing, this method possesses the advantage of measuring bubbles throughout the entire cross section. However, X-ray measurements cannot be applied to all installation, especially not in large scale plants. For these purpose, we have developed optical probes that can be employed to investigate the fluidization state in a hot pilot scale reactor. A main drawback of the optical measurements lies in their locally limited detection of the hydrodynamic pattern since they are only able to measure at one point in the reactor. Therefore, conclusions on the bubble behavior of the whole cross section based on optical measurements are not easy to derive. To compare the influence of the measurement method on the measured bubble properties, in the scope of this study, an artificial optical signal is created out of the existing X-ray measurement data set for a cold flow model of the pilot scale methanation reactor. The obtained bubble properties of both methods (i.e. evaluation of the derived artificial optical probe signal and image reconstruction based on the original X-ray tomographic data) are compared with regard to the hold-up, bubble rise velocity and the bubble size (for the X-ray method) or chord length (for the optical evaluation method), respectively. The process to obtain an artificial optical signal is depicted in Figure 1. The comparison shows that for the evaluation of optical probe data, statistical effects have to be considered carefully. The detected mean chord length of the optical method does not represent the mean bubble size determined by the X-ray method. Moreover, also a difference in the bubble rise velocity was detected for some fluidization states. This knowledge may be the basis for the derivation of a statistically sound method to calculate different hydrodynamic properties in fluidized bed reactors based on optical probe measurements. Please click Additional Files below to see the full abstract