222 research outputs found
Anti-TNFα treatment after surgical resection for Crohn's disease is effective despite previous pharmacodynamic failure
No full textBackground: The outcome of patients with Crohn's disease who failed anti-tumor necrosis factor alpha (anti-TNF alpha) therapy despite adequate serum drug levels (pharmacodynamic failure) is unclear. We aimed to assess such pediatric patients who underwent intestinal resection and were re-treated with the same anti-TNF alpha agent postoperatively.
Methods: Pediatric patients with Crohn's disease who underwent intestinal resection and were treated with anti-TNF alpha agents postoperatively were assessed retrospectively. Patients were stratified to those with preoperative anti-TNF alpha pharmacodynamic failure and those with no preoperative antiTNF alpha treatment.
Results: A total of 53 children were included, 18 with pharmacodynamic failure and 35 controls. Median age at intestinal resection was 14.8 years with 23 (43%) girls. The median time from intestinal resection to anti-TNF alpha initiation was 8 months (interquartile range 4-14 months). At the time of postoperative anti-TNF alpha initiation there were no differences in clinical, laboratory, and anthropometric measures between groups. Similar proportions of patients from both groups were in clinical remission on anti-TNF alpha treatment after 12 months and at the end of follow-up (1.8 years, interquartile range, 1-2.9 years): 89% versus 88.5% and 83% versus 80% for pharmacodynamic failure patients and controls, respectively; P = 0.9. No significant differences were observed at 14 weeks and 12 months of postoperative anti-TNF alpha treatment including endoscopic remission rate and fecal calprotectin. Both groups significantly improved all measures during postoperative anti-TNF alpha treatment.
Conclusions: Pediatric patients with Crohn's disease who failed anti-TNF alpha therapy despite adequate drug levels and underwent intestinal resection can be re-treated with the same agent for postoperative recurrence with high success rate similar to that of anti-TNF alpha naive patients
Antibiotic-perturbed microbiota and the role of probiotics
No full textThe disruptive effect of antibiotics on the composition and function of the human microbiota is well established. However, the hypothesis that probiotics can help restore the antibiotic-disrupted microbiota has been advanced, with little consideration of the strength of evidence supporting it. Some clinical data suggest that probiotics can reduce antibiotic-related side effects, including Clostridioides difficile-associated diarrhoea, but there are no data that causally link these clinical effects to microbiota protection or recovery. Substantial challenges hinder attempts to address this hypothesis, including the absence of consensus on the composition of a ‘normal’ microbiota, non-standardized and evolving microbiome measurement methods, and substantial inter-individual microbiota variation. In this Review, we explore these complexities. First, we review the known benefits and risks of antibiotics, the effect of antibiotics on the human microbiota, the resilience and adaptability of the microbiota, and how microbiota restoration might be defined and measured. Subsequently, we explore the evidence for the efficacy of probiotics in preventing disruption or aiding microbiota recovery post-antibiotic treatment. Finally, we offer insights into the current state of research and suggest directions for future research
Bouwen van een weerstation in het basisonderwijs
No full textMeer ‘bètajongeren’ krijgen we alleen wanneer we aantrekkelijk onderwijs aanbieden. Ondersteund door een subsidie van de Europese Commissie, hebben teams uit zes Europese landen zich ingespannen om onderwijsmateriaal te ontwikkelen over natuur- en techniekonderwijs. Binnen dit project, genaamd CoReflect, moest elke lessenserie worden beproefd in ten minste twee landen. Zo kon worden ontdekt of een lessenserie die goed werkte in bijvoorbeeld Cyprus ook gemakkelijk kon worden ingezet in Zweedse scholen. In dit artikel beschrijven we de lessenserie Het weer
Agent-Based Modeling of Culture's Consequences for Trade
No full textIn this thesis, culture is interpreted as a property of a group of people who share the meaning they attach to symbols, have a common way of expressing their opinions and feelings, and share value systems to judge what is good or bad. The unwritten rules of a culture govern the interpretation of observations and emotions and how to react appropriately. The rules are embedded in an individuals’ mind, form childhood on, by interactions with group members. People often are not aware of differences between their own unwritten rules and those of people having a different cultural background. This may result in unwarranted distrust or unwarranted trust, with serious consequences for the future of relationships. Cultural differences are known to have their effects on trade. Signals that indicate benevolence and trustworthiness of a trade partner in one’s own culture may be interpreted differently by people having a different cultural background. Hofstede (2001) has identified five dimensions of cultural differences: ? Given ingroup relation with relatives and community members may have a different impact on professional relationships in different cultures. ? The impact of hierarchical relationships on the freedom of action of trade partners may be different across cultures. ? Some cultures are oriented toward cooperation and care-taking; others are oriented toward performance and competition. ? Xenophobia is a wide-spread phenomenon in some cultures, while people in other cultures may be more open to the unknown. ? In some cultures people are anxious to keep up their status and display their societal success, while in other cultures thrift and perseverance are seen as virtues. Cultural differences may have their effects in trade on the acceptability of potential partners, on progress and success of negotiations, and on the extent to which partners live up to the negotiated contracts. In a research project Meijer (2009) developed a gaming simulation to study the role of trust in supply networks of food products. The game is called the TRUST & TRACING game. In this game, the producers are informed about product quality. The other players either have to trust the suppliers on their quality statements, or they can have the products traced by an independent authority, but the latter will cost them a fee. In addition to the financial considerations, they must take into account that showing distrust may bring damage to their relationships. Experiments with human subjects in different cultures have shown that the considerations lead to different actions in different countries. It was also found that the inclination to grab an opportunity to defect was different across countries. The subject of this thesis is a computer simulation of the TRUST & TRACING GAME. The purposes of the computer simulation are: ? Validation of theories about, implemented in models of, the players’ behaviors ? testing of hypotheses about relations of rules of the game and parameters of individual players with aggregated game statistics, ? the design of useful game configurations to be played with human players. In the computer simulation the players’ rolls are realized by software agents. The questions which are answered in this thesis concern the modeling of culture’s consequences for the decisions taken by the agents. Such an agent is a computer program which simulates the behavior of human players. In a multi-agent simulation a group of software agents is acting and interacting simultaneously. Autonomy is an important property of software agents. The agents decide what to do; there is no central computer program that imposes decisions on them. Important functions of agents in the present simulation are to approach new potential trade partners, to negotiate about a transaction and to exchange proposals, and, when the negotiation has ended successfully, to exchange products, and to decide and request a trace to be performed. The agents’ decision mechanisms are implemented according to models and data available from scientific literature. To model the influence of culture on the decision making, an expert systems approach is taken, using the Synthetic Cultures according to Hofstede en Pedersen (1999). To develop an expert system, knowledge engineers represent knowledge about some domain of application as a set of rules that can be interpreted by a computer system. Since culture is considered as a set of rules, such an approach is a natural way to model it. The development of expert systems always is an interdisciplinary project. In this case the work of Geert Hofstede has been used and an expert on this work and on Synthetic Cultures has been involved in the formulation of the rules. Synthetic Cultures are imaginary cultures in which the effects of a single dimension of culture are emphasized, isolated from the effects of the other dimensions. The purpose is to make the differences related to that dimension teachable. In reality the differences may be less pronounced and may be mixed with differences related with the other dimensions. In this thesis an approach has been elaborated to compute the simultaneous effect of several dimensions. The approach is based on the principle of weak disjunction, which implies that, if several dimensions have a similar effect, only the strongest effects counts. For instance, if dimension A would have an effect of 75% and dimension B would have an effect of 25%, then their simultaneous effect would be 75%. Expert systems must at least have face validity. An expert in the domain of application mustaccept the decisions that the system produces and the reasoning that leads to these decisions, as being believable. For this purpose computations for specific cases can be made, of which the results are judged by the expert. Further, the results of sensitivity analysis can be judged by an expert. Sensitivity analysis of a model is performed by studying how model outputs vary in relation with systematic variation of input parameter. In addition to face validity, the model must be tested empirically. To that end outputs from gaming simulations with human participants can be compared with outputs from multi-agent simulations. For example, Meijer et al. (2006) found different outcomes from the TRUST & TRACING game between games played in the United States and in the Netherlands. Compared with the Dutch, American players are found to be more eager to buy top quality products, have a stronger inclination to opportunism, anticipate to a greater extent on their partners to defect, and have a stronger preference for quality certification. These differences where reproduced by the multi-agent simulation. The main question of this research is, whether an expert systems approach is feasible to develop a valid model of cultural differentiation in multi-agent simulations, to be applied in research with gaming simulations. The conclusions are: 1. Effects of dimensions of culture can be modeled as an expert system based on Synthetic Cultures. Modeling the simultaneous effects of several dimensions as an expert system proved not feasible: the complexity exceeded the intellectual powers of both expert and modeler. 2. The simultaneous effect of several dimensions can be modeled by weak disjunction of effects. The results have face validity and have empirically been verified for a limited number of cases. 3. Sensitivity analysis of this model is a complex undertaking if both cultural parameters and other parameters are simultaneously varied, because of the strong interactions between these types of parameters. When only the culture parameters are varied (with a fixed setting of the other parameters), or only the other parameters are varied (in a fixed cultural setting), straightforward sensitivity analysis is feasible. Furthermore, it was found that the sensitivity of aggregate model outputs may greatly differ from sensitivity of individual level outputs: parameters that do not affect the aggregate system performance, may affect results of individual agents. 4. This thesis proves that multi-agent simulation is a potent instrument to be used in research with gaming simulations, in particular for the purpose of validation of behavioral models. A problematic issue is, that similarity of the outputs of gaming simulations and multi-agent simulations is no sound proof that the agent correctly implements the human decision making mechanism. This issue is known as under-determination. A validation method is proposed, which builds on the model’s composed structure. Under-determination can be avoided by separate validation of the components in micro-games. The results of this research contribute to the methodology of cultural adaptation of intelligent software agents. This is relevant for the development of research instruments (like the TRUST & TRACING game), educational and training applications to make people aware of cultural differences, and affective human-computer interfaces in a globalizing world.MediamaticsElectrical Engineering, Mathematics and Computer Scienc
Peritonitis After Endoscopic Caecostomy With a Chait Trapdoor Catheter: What Lessons Can Be Learned?
No full textComposition and stability of intestinal microbiota of healthy children within a Dutch population
No full textNumerous diseases linked to microbial imbalance can be traced back to childhood, illustrating the impact of the juvenile microbiota development from infancy toward adulthood. However, knowledge on this subject is currently very limited. The primary aim of this study was to characterize composition and short- and long-term stability of the intestinal microbiota in healthy children. Between November 2011 and June 2014, 61 children 2 to 18 yr of age from different areas in The Netherlands were included and instructed to collect fecal samples weekly, for 6 wk, and a follow-up sample after 18 mo. The intergenic spacer profiling technique (IS-pro) was used to analyze all available fecal samples. Microbial diversity was calculated by the Shannon diversity index and individual compositional stability by comparing all collection time points. Microbial stability varied per phylum (P < 0.0005), declined rapidly in a short time period, and subsequently stabilized on the long run with very gradual variation, leading to an overall compositional stability of 70% on average over a period of 18 mo. Higher species diversity was correlated to a higher overall compositional stability (P < 0.001). We observed an age-independent bacterial shared core consisting of a limited number of species. In conclusion, in this study, we showed that microbial composition stability in children varied per phylum, at both short-term and long-term intervals. Healthy children seem to share a microbiome core consisting of a limited number of species.-De Meij, T. G. J., Budding, A. E., de Groot, E. F. J., Jansen, F. M., Kneepkens, C. M. F., Benninga, M. A., Penders, J., van Bodegraven, A. A., Savelkoul, P. H. M. Composition and stability of intestinal microbiota of healthy children within a Dutch population
Clinical spectrum of paediatric coeliac disease: A 10-year single-centre experience
No full textThis study was undertaken to gain insight in the clinical spectrum of paediatric coeliac disease (CD) in a Dutch teaching hospital. We retrospectively compared the frequency of CD in children with a wide spectrum of complaints with and without CD antibodies in serum and were interested if certain complaints are more pathognomonic for CD. Furthermore, we expected that over a period of 10-year incidence rates of CD would have increased and shifted towards an atypical presentation with more non-gastrointestinal symptoms with increasing age. A retrospective, single-centre, case-control study was performed. All patients who presented at the Department of Paediatrics, Tergooi Hospital, with symptoms suspected for CD were eligible for inclusion during the study period from 1 January 2007 till 31 December 2016. Children were diagnosed with CD according to the 2005 and 2012 ESPGHAN guideline between 2007 and 2016, respectively. Demographic data, presenting symptoms, prevalence of associated conditions and serology results were examined. A total of 105 new cases of paediatric CD were observed, with an average of 10 new cases each year. The calculated incidence was 21.09 (CI 17.49–25.22)/100,000 under 18 years of age. About 40% were infants and toddlers, predominantly presenting with gastrointestinal symptoms. Primary and high school children had more display of atypical symptoms (p = 0.001, p = 0.017) and nongastrointestinal symptoms (p = 0.009, p = 0.009) than infants and toddlers. In 8.6% of the CD patients, mostly primary school aged female patients, the serology was repeated at least once in time to become positive. The median time for serology to become positive was 609 days (range 140–1054). Conclusion: As it is well known, our study supports the increasing notion of a shift in the clinical spectrum of presenting symptoms in paediatric CD towards an atypical presentation, with more non-gastrointestinal symptoms and a diagnosis at a later age in a Dutch population, whereas the number of new cases did not increase over the years
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