475 research outputs found

    Conjunctions of Among Constraints

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    Many existing global constraints can be encoded as a conjunction of among constraints. An among constraint holds if the number of the variables in its scope whose value belongs to a prespecified set, which we call its range, is within some given bounds. It is known that domain filtering algorithms can benefit from reasoning about the interaction of among constraints so that values can be filtered out taking into consideration several among constraints simultaneously. The present pa- per embarks into a systematic investigation on the circumstances under which it is possible to obtain efficient and complete domain filtering algorithms for conjunctions of among constraints. We start by observing that restrictions on both the scope and the range of the among constraints are necessary to obtain meaningful results. Then, we derive a domain flow-based filtering algorithm and present several applications. In particular, it is shown that the algorithm unifies and generalizes several previous existing results.Comment: 15 pages plus appendi

    Plasmodium chabaudi limits early Nippostrongylus brasiliensis-induced pulmonary immune activation and Th2 polarization in co-infected mice

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    <p>Abstract</p> <p>Background</p> <p>Larvae of several common species of parasitic nematodes obligately migrate through, and often damage, host lungs. The larvae induce strong pulmonary Type 2 immune responses, including T-helper (Th)2 cells as well as alternatively activated macrophages (AAMφ) and associated chitinase and Fizz/resistin family members (ChaFFs), which are thought to promote tissue repair processes. Given the prevalence of systemic or lung-resident Type 1-inducing pathogens in geographical areas in which nematodes are endemic, we wished to investigate the impact of concurrent Type 1 responses on the development of these Type 2 responses to nematode larval migration. We therefore infected BALB/c mice with the nematode <it>Nippostrongylus brasiliensis</it>, in the presence or absence of <it>Plasmodium chabaudi chabaudi </it>malaria parasites. Co-infected animals received both infections on the same day, and disease was assessed daily before immunological measurements were taken at 3, 5, 7 or 20 days post-infection.</p> <p>Results</p> <p>We observed that the nematodes themselves caused transient loss of body mass and red blood cell density, but co-infection then slightly ameliorated the severity of malarial anaemia. We also tracked the development of immune responses in the lung and thoracic lymph node. By the time of onset of the adaptive immune response around 7 days post-infection, malaria co-infection had reduced pulmonary expression of ChaFFs. Assessment of the T cell response demonstrated that the Th2 response to the nematode was also significantly impaired by malaria co-infection.</p> <p>Conclusion</p> <p><it>P. c. chabaudi </it>co-infection altered both local and lymph node Type 2 immune activation due to migration of <it>N. brasiliensis </it>larvae. Given recent work from other laboratories showing that <it>N. brasiliensis</it>-induced ChaFFs correlate to the extent of long-term lung damage, our results raise the possibility that co-infection with malaria might alter pulmonary repair processes following nematode migration. Further experimentation in the co-infection model developed here will reveal the longer-term consequences of the presence of both malaria and helminths in the lung.</p

    Effects of two behavioral cardiac rehabilitation interventions on physical activity:A randomized controlled trial

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    Background: Standard cardiac rehabilitation (CR) is insufficient to help patients achieve an active lifestyle. The effects of two advanced and extended behavioral CR interventions on physical activity (PA) and sedentary behavior (SB) were assessed.Methods: In total, 731 patients with ACS were randomized to 1) 3 months of standard CR (CR-only); 2) 3 months of standard CR with three pedometer-based, face-to-face PA group counseling sessions followed by 9 months of after care with three general lifestyle, face-to-face group counseling sessions (CR+F); or 3) 3 months of standard CR, followed by 9 months of aftercare with five to six general lifestyle, telephonic counseling sessions (CR + T). An accelerometer recorded PA and SB at randomization, 3 months, 12 months, and 18 months.Results: The CR+ F group did not improve their moderate-to-vigorous intensity PA (MVPA) or SB time compared to CR-only (between-group difference= 0.24% MVPA, P= 0.349; and 0.39% SB, P= 0.529). However, step count (between-group difference = 513 steps/day, P = 0.021) and time in prolonged MVPA (OR = 2.14, P= 0.054) improved at 3 months as compared to CR-only. The improvement in prolonged MVPA was maintained at 18 months (OR = 1.91, P = 0.033). The CR + T group did not improve PA or SB compared to CR-only.Conclusions: Adding three pedometer-based, face-to-face group PA counseling sessions to standard CR increased daily step count and time in prolonged MVPA. The latter persisted at 18 months. A telephonic after-care program did not improve PA or SB. Although after-care should be optimized to improve long-term adherence, face-to-face group counseling with objective PA feedback should be added to standard CR. (C) 2017 Elsevier B.V. All rights reserved

    Narrative-based computational modelling of the Gp130/JAK/STAT signalling pathway.

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    BACKGROUND: Appropriately formulated quantitative computational models can support researchers in understanding the dynamic behaviour of biological pathways and support hypothesis formulation and selection by "in silico" experimentation. An obstacle to widespread adoption of this approach is the requirement to formulate a biological pathway as machine executable computer code. We have recently proposed a novel, biologically intuitive, narrative-style modelling language for biologists to formulate the pathway which is then automatically translated into an executable format and is, thus, usable for analysis via existing simulation techniques. RESULTS: Here we use a high-level narrative language in designing a computational model of the gp130/JAK/STAT signalling pathway and show that the model reproduces the dynamic behaviour of the pathway derived by biological observation. We then "experiment" on the model by simulation and sensitivity analysis to define those parameters which dominate the dynamic behaviour of the pathway. The model predicts that nuclear compartmentalisation and phosphorylation status of STAT are key determinants of the pathway and that alternative mechanisms of signal attenuation exert their influence on different timescales. CONCLUSION: The described narrative model of the gp130/JAK/STAT pathway represents an interesting case study showing how, by using this approach, researchers can model biological systems without explicitly dealing with formal notations and mathematical expressions (typically used for biochemical modelling), nevertheless being able to obtain simulation and analysis results. We present the model and the sensitivity analysis results we have obtained, that allow us to identify the parameters which are most sensitive to perturbations. The results, which are shown to be in agreement with existing mathematical models of the gp130/JAK/STAT pathway, serve us as a form of validation of the model and of the approach itself

    The Long-Term Effects of the Youth Crime Prevention Program “New Perspectives” on Delinquency and Recidivism

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    New Perspectives (NP) aims to prevent persistent criminal behavior. We examined the long-term effectiveness of NP and whether the effects were moderated by demographic and delinquency factors. At-risk youth aged 12 to 19 years were randomly assigned to the intervention group (NP, n = 47) or care as usual (CAU, n = 54). Official and self-report data were collected to assess recidivism. NP was not more effective in reducing delinquency levels and recidivism than CAU. Also, no moderator effects were found. The overall null effects are discussed, including further research and policy implications

    Effects of a Dedicated Cardiac Rehabilitation Program for Patients With Obesity on Body Weight, Physical Activity, Sedentary Behavior, and Physical Fitness:The OPTICARE XL Randomized Controlled Trial

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    OBJECTIVE: Previously published results of the OPTICARE XL open label randomized controlled trial showed no added value of OPTICARE XL CR, a dedicated cardiac rehabilitation (CR) program for patients with obesity, with respect to health-related quality of life (primary outcome). This clinical trial studied the effects of OPTICARE XL CR on several secondary outcomes, which included body weight, physical activity, sedentary behavior, and physical fitness. METHODS: Patients with coronary artery disease or atrial fibrillation and body mass index ≥ 30 were randomized to OPTICARE XL CR (n = 102) or standard CR (n = 99). OPTICARE XL CR was a 1-year group intervention, specifically designed for patients with obesity that included aerobic and strength exercise, behavioral coaching, and an aftercare program. Standard CR consisted of a 6- to 12-week group aerobic exercise program, supplemented with cardiovascular lifestyle education. Study end points included body weight, physical activity, sedentary behavior (accelerometer), and physical fitness (6-Minute Walk Test and handgrip strength), which were evaluated 6 months after the end of CR (primary endpoint) and 3 months after the start of CR. RESULTS: Six months after completion of either program, improvements in body weight, physical activity, sedentary behavior, and physical fitness were similar between the groups. Three months after CR start, patients randomized to OPTICARE XL CR showed greater weight loss (mean change = -3.6 vs -1.8 kg) and a larger improvement in physical activity (+880 vs +481 steps per day) than patients randomized to standard CR. CONCLUSION: Patients allocated to OPTICARE XL CR lost significantly more body weight and showed promising results with respect to physical activity 3 months after the start of CR; however, these short-term results were not expanded or sustained in the longer term. IMPACT: Patients with obesity do not benefit from standard CR programs. The new OPTICARE XL CR program showed its effects in the short term on weight loss and physical activity, and, therefore, redesign of the aftercare phase is recommended.</p
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