160 research outputs found

    Assessing the Vulnerability of the Fiber Infrastructure to Disasters

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    Communication networks are vulnerable to natural disasters, such as earthquakes or floods, as well as to physical attacks, such as an electromagnetic pulse (EMP) attack. Such real-world events happen in specific geographical locations and disrupt specific parts of the network. Therefore, the geographical layout of the network determines the impact of such events on the network's connectivity. In this paper, we focus on assessing the vulnerability of (geographical) networks to such disasters. In particular, we aim to identify the most vulnerable parts of the network. That is, the locations of disasters that would have the maximum disruptive effect on the network in terms of capacity and connectivity. We consider graph models in which nodes and links are geographically located on a plane. First, we consider a simplistic bipartite graph model and present a polynomial-time algorithm for finding a worst-case vertical line segment cut. We then generalize the network model to graphs with nodes at arbitrary locations. We model the disaster event as a line segment or a disk and develop polynomial-time algorithms that find a worst-case line segment cut and a worst-case circular cut. Finally, we obtain numerical results for a specific backbone network, thereby demonstrating the applicability of our algorithms to real-world networks. Our novel approach provides a promising new direction for network design to avert geographical disasters or attacks.United States. Defense Threat Reduction Agency (Grant HDTRA1-07-1-0004)United States. Defense Threat Reduction Agency (Grant HDTRA09-1-005)United States. Defense Threat Reduction Agency (Grant HDTRA1-09-1-0057)National Science Foundation (U.S.) (Grant CNS-1017800)National Science Foundation (U.S.) (Grant CNS0830961)National Science Foundation (U.S.) (Grant CNS-1018379)National Science Foundation (U.S.) (Grant CNS-1054856)National Science Foundation (U.S.) (Grant CNS-0626781)American Society for Engineering Education. National Defense Science and Engineering Graduate FellowshipNational Science Foundation (U.S.) (Grant EEC-0812072

    Feature Selection via Coalitional Game Theory

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    How Art Therapists Observe Mental Health Using Formal Elements in Art Products: Structure and Variation as Indicators for Balance and Adaptability

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    In clinical practice, formal elements of art products are regularly used in art therapy observation to obtain insight into clients’ mental health and provide directions for further treatment. Due to the diversity of formal elements used in existing studies and the inconsistency in the interpretation, it is unclear which formal elements contribute to insight into clients’ mental health. In this qualitative study using Constructivist Grounded Theory, eight art therapists were interviewed in-depth to identify which formal elements they observe, how they describe mental health and how they associate formal elements with mental health. Findings of this study show that art therapists in this study observe the combination of movement, dynamic, contour and repetition (i.e., primary formal elements) with mixture of color, figuration and color saturation (i.e., secondary formal elements). Primary and secondary elements interacting together construct the structure and variation of the art product. Art therapists rarely interpret these formal elements in terms of symptoms or diagnosis. Instead, they use concepts such as balance and adaptability (i.e., self-management, openness, flexibility, and creativity). They associate balance, specifically being out of balance, with the severity of the clients’ problem and adaptability with clients’ strengths and resources. In the conclusion of the article we discuss the findings’ implications for practice and further research

    Infliximab in young paediatric IBD patients : it is all about the dosing

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    Infliximab (IFX) is administered intravenously using weight-based dosing (5 mg/kg) in inflammatory bowel disease (IBD) patients. Our hypothesis is that especially young children need a more intensive treatment regimen than the current weight-based dose administration. We aimed to assess IFX pharmacokinetics (PK), based on existing therapeutic drug monitoring (TDM) data in IBD patients = 10 years). Median age was 8.3 years (IQR 6.9-8.9) in YP compared with 14.3 years (IQR 12.8-15.6) in OP at the start of IFX. At the start of maintenance treatment, 72% of YP had trough levels below therapeutic range (< 5.4 mu g/mL). After 1 year of scheduled IFX maintenance treatment, YP required a significantly higher dose per 8 weeks compared with OP (YP; 9.0 mg/kg (IQR 5.0-12.9) vs. OP; 5.5 mg/kg (IQR 5.0-9.3);p < 0.001). The chance to develop antibodies to infliximab was relatively lower in OP than YP (0.329 (95% CI - 1.2 to - 1.01);p < 0.001), while the overall duration of response to IFX was not significantly different (after 2 years 53% (n = 29) in YP vs. 58% (n = 45) in OP;p = 0.56). Conclusion: Intensification of the induction scheme is suggested for PIBD patients aged < 10 years. What is Known

    Glucose-6-phosphate dehydrogenase deficiency and long-term risk of immune-related disorders

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    IntroductionGlucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymatic disorder that is particularly prevalent in Africa, Asia, and the Middle East. This study aimed to assess the long-term health risks associated with G6PD deficiency.MethodsA retrospective cohort study was conducted using data from a national healthcare provider in Israel (Leumit Health Services). A total of 7,473 G6PD-deficient individuals were matched with 29,892 control subjects in a 1:4 ratio, based on age, gender, socioeconomic status, and ethnic groups. The exposure of interest was recorded G6PD diagnosis or positive G6PD diagnostic test. The main outcomes and measures included rates of infectious diseases, allergic conditions, and autoimmune disorders between 2002 and 2022.ResultsSignificantly increased rates were observed for autoimmune disorders, infectious diseases, and allergic conditions in G6PD-deficient individuals compared to the control group. Specifically, notable increases were observed for rheumatoid arthritis (odds ratio [OR] 2.41, p&lt;0.001), systemic lupus erythematosus (OR 4.56, p&lt;0.001), scleroderma (OR 6.87, p&lt;0.001), pernicious anemia (OR 18.70, p&lt;0.001), fibromyalgia (OR 1.98, p&lt;0.001), Graves’ disease (OR 1.46, p=0.001), and Hashimoto’s thyroiditis (OR 1.26, p=0.001). These findings were supported by elevated rates of positive autoimmune serology and higher utilization of medications commonly used to treat autoimmune conditions in the G6PD-deficient group.DiscussionIn conclusion, individuals with G6PD deficiency are at a higher risk of developing autoimmune disorders, infectious diseases, and allergic conditions. This large-scale observational study provides valuable insights into the comprehensive association between G6PD deficiency and infectious and immune-related diseases. The findings emphasize the importance of considering G6PD deficiency as a potential risk factor in clinical practice and further research is warranted to better understand the underlying mechanisms of these associations

    Successful dietary therapy in paediatric Crohn’s disease is associated with shifts in bacterial dysbiosis and inflammatory metabotype towards healthy controls

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    Background and aims: Nutritional therapy with the Crohn’s Disease Exclusion Diet + Partial Enteral Nutrition [CDED+PEN] or Exclusive Enteral Nutrition [EEN] induces remission and reduces inflammation in mild-to-moderate paediatric Crohn’s disease [CD]. We aimed to assess if reaching remission with nutritional therapy is mediated by correcting compositional or functional dysbiosis. Methods: We assessed metagenome sequences, short chain fatty acids [SCFA] and bile acids [BA] in 54 paediatric CD patients reaching remission after nutritional therapy [with CDED + PEN or EEN] [NCT01728870], compared to 26 paediatric healthy controls. Results: Successful dietary therapy decreased the relative abundance of Proteobacteria and increased Firmicutes towards healthy controls. CD patients possessed a mixture of two metabotypes [M1 and M2], whereas all healthy controls had metabotype M1. M1 was characterised by high Bacteroidetes and Firmicutes, low Proteobacteria, and higher SCFA synthesis pathways, and M2 was associated with high Proteobacteria and genes involved in SCFA degradation. M1 contribution increased during diet: 48%, 63%, up to 74% [Weeks 0, 6, 12, respectively.]. By Week 12, genera from Proteobacteria reached relative abundance levels of healthy controls with the exception of E. coli. Despite an increase in SCFA synthesis pathways, remission was not associated with increased SCFAs. Primary BA decreased with EEN but not with CDED+PEN, and secondary BA did not change during diet. Conclusion: Successful dietary therapy induced correction of both compositional and functional dysbiosis. However, 12 weeks of diet was not enough to achieve complete correction of dysbiosis. Our data suggests that composition and metabotype are important and change quickly during the early clinical response to dietary intervention. Correction of dysbiosis may therefore be an important future treatment goal for CD

    The NlpD Lipoprotein Is a Novel Yersinia pestis Virulence Factor Essential for the Development of Plague

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    Yersinia pestis is the causative agent of plague. Previously we have isolated an attenuated Y. pestis transposon insertion mutant in which the pcm gene was disrupted. In the present study, we investigated the expression and the role of pcm locus genes in Y. pestis pathogenesis using a set of isogenic surE, pcm, nlpD and rpoS mutants of the fully virulent Kimberley53 strain. We show that in Y. pestis, nlpD expression is controlled from elements residing within the upstream genes surE and pcm. The NlpD lipoprotein is the only factor encoded from the pcm locus that is essential for Y. pestis virulence. A chromosomal deletion of the nlpD gene sequence resulted in a drastic reduction in virulence to an LD50 of at least 107 cfu for subcutaneous and airway routes of infection. The mutant was unable to colonize mouse organs following infection. The filamented morphology of the nlpD mutant indicates that NlpD is involved in cell separation; however, deletion of nlpD did not affect in vitro growth rate. Trans-complementation experiments with the Y. pestis nlpD gene restored virulence and all other phenotypic defects. Finally, we demonstrated that subcutaneous administration of the nlpD mutant could protect animals against bubonic and primary pneumonic plague. Taken together, these results demonstrate that Y. pestis NlpD is a novel virulence factor essential for the development of bubonic and pneumonic plague. Further, the nlpD mutant is superior to the EV76 prototype live vaccine strain in immunogenicity and in conferring effective protective immunity. Thus it could serve as a basis for a very potent live vaccine against bubonic and pneumonic plague
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