250 research outputs found

    Requirements for a Nutrition Education Demonstrator

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    [Context and Motivation] Development of innovative ICT-based applications is a complex process involving collaboration of all relevant disciplines. This complexity arises due to differences in terminology, knowledge and often also the ways of working between developers in the disciplines involved. [Question/problem] Advances in each discipline bring a rich design environment of theories, models, methods and techniques. Making a selection from these makes the development of distributed applications very challenging, often requiring a holistic approach to address the needs of the disciplines involved. This paper describes early stage requirements acquisition of a mobile nutrition education demonstrator which supports overweight persons in adopting healthier dietary behaviour. [Principal idea/results] We present a novel way to combine and use known requirements acquisition methods involving a two stage user needs analysis based on scenarios which apply a theory-based model of behavioural change and are onstructed in two phases. The first phase scenarios specify an indicative description reflecting the use of the transtheoretical model of behavioural change. In the second phase, a handshake protocol adds elements of optative system-oriented descriptions to the scenarios such that the intended system can support the indicative description. [Contribution] The holistic and phased approach separates design concerns to which each of the disciplines contributes with their own expertise and domain principles. It preserves the applied domain principles in the design and it bridges gaps in terminology, knowledge and ways of working

    A Nationwide Retrospective Analysis of Out-of-Hospital Pediatric Cardiopulmonary Resuscitation Treated by Helicopter Emergency Medical Service in the Netherlands

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    Contains fulltext : 243898.pdf (Publisher’s version ) (Open Access)OBJECTIVE: There is generally limited but conflicting literature on the incidence, causes, and outcomes of pediatric out-of-hospital cardiac arrest. This study was performed to determine the incidence and outcome of pediatric out-of-hospital cardiac arrest reported by all helicopter emergency medical services in the Netherlands and to provide a description of causes and treatments and, in particular, a description of the specific interventions that can be performed by a physician-staffed helicopter emergency medical service. METHODS: A retrospective analysis was performed of all documented pediatric (0 < 18 years of age) out-of-hospital cardiac arrests from July 2015 to July 2017, attended by all 4 Dutch helicopter emergency medical service teams. RESULTS: Two hundred two out-of-hospital cardiac arrests were identified. The overall incidence in the Netherlands is 3.5 out-of-hospital cardiac arrests in children per 100,000 pediatric inhabitants. The overall survival rate for out-of-hospital cardiac arrest was 11.4%. Eleven (52%) of the survivors were in the drowning group and between 12 and 96 months of age. CONCLUSION: Helicopter emergency medical services are frequently called to pediatric out-of-hospital cardiac arrests in the Netherlands. The survival rate is normal to high compared with other countries. The 12- to 96-month age group and drowning seem to have a relatively favorable outcome

    Autosis is a Na+,K+-ATPase-regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia-ischemia.

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    A long-standing controversy is whether autophagy is a bona fide cause of mammalian cell death. We used a cell-penetrating autophagy-inducing peptide, Tat-Beclin 1, derived from the autophagy protein Beclin 1, to investigate whether high levels of autophagy result in cell death by autophagy. Here we show that Tat-Beclin 1 induces dose-dependent death that is blocked by pharmacological or genetic inhibition of autophagy, but not of apoptosis or necroptosis. This death, termed "autosis," has unique morphological features, including increased autophagosomes/autolysosomes and nuclear convolution at early stages, and focal swelling of the perinuclear space at late stages. We also observed autotic death in cells during stress conditions, including in a subpopulation of nutrient-starved cells in vitro and in hippocampal neurons of neonatal rats subjected to cerebral hypoxia-ischemia in vivo. A chemical screen of ~5,000 known bioactive compounds revealed that cardiac glycosides, antagonists of Na(+),K(+)-ATPase, inhibit autotic cell death in vitro and in vivo. Furthermore, genetic knockdown of the Na(+),K(+)-ATPase α1 subunit blocks peptide and starvation-induced autosis in vitro. Thus, we have identified a unique form of autophagy-dependent cell death, a Food and Drug Administration-approved class of compounds that inhibit such death, and a crucial role for Na(+),K(+)-ATPase in its regulation. These findings have implications for understanding how cells die during certain stress conditions and how such cell death might be prevented

    On the complexity of strongly connected components in directed hypergraphs

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    We study the complexity of some algorithmic problems on directed hypergraphs and their strongly connected components (SCCs). The main contribution is an almost linear time algorithm computing the terminal strongly connected components (i.e. SCCs which do not reach any components but themselves). "Almost linear" here means that the complexity of the algorithm is linear in the size of the hypergraph up to a factor alpha(n), where alpha is the inverse of Ackermann function, and n is the number of vertices. Our motivation to study this problem arises from a recent application of directed hypergraphs to computational tropical geometry. We also discuss the problem of computing all SCCs. We establish a superlinear lower bound on the size of the transitive reduction of the reachability relation in directed hypergraphs, showing that it is combinatorially more complex than in directed graphs. Besides, we prove a linear time reduction from the well-studied problem of finding all minimal sets among a given family to the problem of computing the SCCs. Only subquadratic time algorithms are known for the former problem. These results strongly suggest that the problem of computing the SCCs is harder in directed hypergraphs than in directed graphs.Comment: v1: 32 pages, 7 figures; v2: revised version, 34 pages, 7 figure

    Characteristics, management and outcome of prehospital pediatric emergencies by a Dutch HEMS

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    Background: In prehospital care, the Helicopter Emergency Medical Service (HEMS) can be dispatched for critically injured or ill children. However, little detail is known about dispatches for children, in terms of the incidence of prehospital interventions and overall mortality. The primary objective of this study is to provide an overview of pediatric patient characteristics and incidence of interventions. Methods: A retrospective chart review of all patients ≤ 17 years who received medical care by Rotterdam HEMS from 2012 until 2017 was carried out. Results: During the study period, 1905 pediatric patients were included. 59.1% of patients were male and mean age was 6.1 years with 53.2% of patients aged ≤ 3 years. 53.6% were traumatic patients and 49.7% were non-traumatic patients. 18.8% of patients were intubated. Surgical procedures were performed in 0.9%. Medication was administered in 58.1% of patients. Cardiopulmonary resuscitation (CPR) was necessary in 12.9% of patients, 19.9% were admitted to the intensive care unit and 14.0% needed mechanical ventilation. Overall mortality was 9.5%. Mortality in trauma patients was 5.5% and in non-trauma group 15.3%. 3.9% of patients died at the scene. Conclusions: Patients attended by HEMS are at high risk of prehospital interventions like CPR or intubation. EMS has little exposure to critically ill or injured children. Hence, HEMS expertise is required to perform critical procedures. Trauma patients had higher survival rates than non-traumatic patients. This may be explained by underlying illnesses in non-traumatic patients and CPR as reason for dispatch. Further research is needed to identify options for improving prehospital care in the non trauma pediatric patients

    General practice activity in Australia 2012-13

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    Patients with chronic granulomatous disease (CGD) have a mutated NADPH complex resulting in defective production of reactive oxygen species; these patients can develop severe colitis and are highly susceptible to invasive fungal infection. In NADPH oxidase-deficient mice, autophagy is defective but inflammasome activation is present despite lack of reactive oxygen species production. However, whether these processes are mutually regulated in CGD and whether defective autophagy is clinically relevant in patients with CGD is unknown. Here, we demonstrate that macrophages from CGD mice and blood monocytes from CGD patients display minimal recruitment of microtubule-associated protein 1 light chain 3 (LC3) to phagosomes. This defect in autophagy results in increased IL-1β release. Blocking IL-1 with the receptor antagonist (anakinra) decreases neutrophil recruitment and T helper 17 responses and protects CGD mice from colitis and also from invasive aspergillosis. In addition to decreased inflammasome activation, anakinra restored autophagy in CGD mice in vivo, with increased Aspergillus-induced LC3 recruitment and increased expression of autophagy genes. Anakinra also increased Aspergillus-induced LC3 recruitment from 23\% to 51\% (P < 0.01) in vitro in monocytes from CGD patients. The clinical relevance of these findings was assessed by treating CGD patients who had severe colitis with IL-1 receptor blockade using anakinra. Anakinra treatment resulted in a rapid and sustained improvement in colitis. Thus, inflammation in CGD is due to IL-1-dependent mechanisms, such as decreased autophagy and increased inflammasome activation, which are linked pathological conditions in CGD that can be restored by IL-1 receptor blockade

    Helminth infection reactivates latent γ-herpesvirus via cytokine competition at a viral promoter

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    Mammals are coinfected by multiple pathogens that interact through unknown mechanisms. We found that helminth infection, characterized by the induction of the cytokine interleukin-4 (IL-4) and the activation of the transcription factor Stat6, reactivated murine γ-herpesvirus infection in vivo. IL-4 promoted viral replication and blocked the antiviral effects of interferon-γ (IFNγ) by inducing Stat6 binding to the promoter for an important viral transcriptional transactivator. IL-4 also reactivated human Kaposi's sarcoma-associated herpesvirus from latency in cultured cells. Exogenous IL-4 plus blockade of IFNγ reactivated latent murine γ-herpesvirus infection in vivo, suggesting a "two-signal" model for viral reactivation. Thus, chronic herpesvirus infection, a component of the mammalian virome, is regulated by the counterpoised actions of multiple cytokines on viral promoters that have evolved to sense host immune status
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