2,167 research outputs found

    Using microsimulation feedback for trip adaptation for realistic traffic in Dallas

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    This paper presents a day-to-day re-routing relaxation approach for traffic simulations. Starting from an initial planset for the routes, the route-based microsimulation is executed. The result of the microsimulation is fed into a re-router, which re-routes a certain percentage of all trips. This approach makes the traffic patterns in the microsimulation much more reasonable. Further, it is shown that the method described in this paper can lead to strong oscillations in the solutions.Comment: Accepted by International Journal of Modern Physics C. Complete postscript version including figures in http://www-transims.tsasa.lanl.gov/research_team/papers

    The contribution of OCTN1/2 variants within the IBD5 locus to disease susceptibility and severity in Crohn's disease

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    Background and Aims: Recent data suggest that polymorphisms in the organic cation transporter (OCTN) genes OCTN1 (SLC22A4) and OCTN2 (SLC22A5) represent disease-causing mutations within the IBD5 locus (chromosome 5q31). We investigated associations with disease susceptibility, phenotype, and evidence for epistasis with CARD15 in 679 patients with Crohn’s disease (CD) or ulcerative colitis (UC). Methods: A total of 374 patients with CD, 305 patients with UC, and 294 healthy controls (HCs) were studied. Genotyping for single nucleotide polymorphisms IGR2096, IGR2198, and IGR2230, OCTN1 variant (SLC22A4 1672C→T), and OCTN2 variant (SLC22A5 −207G→C) was performed using the TaqMan system. Results: The IBD5 OCTN1 and OCTN2 polymorphisms were in strong linkage disequilibrium (D′, >0.959). IGR2198 variant allele frequency (49.1% vs 40.8%; P = .0046) and homozygosity (21% vs 14.8%; P = .044) were associated with CD versus HCs. Variant allelic frequency of OCTN1 (53.6% vs 43%; P = .0008) and OCTN2 (56.1% vs 48.4%; P = .0092) polymorphisms and homozygosity for the OCTN1/2-TC haplotype (28.4% vs 16%; P = .0042) were associated with CD versus HCs. IGR2198 homozygosity and TC homozygosity were associated with stricturing/penetrating disease at follow-up (P = .011 and P = .011, respectively) and disease progression (P = .038 and P = .049, respectively) on univariate analysis and with need for surgery on multivariate analysis (P = .016 and P = .004, respectively). In the absence of the IBD5 risk haplotype, no association of OCTN1/2 variants with CD was detected. No associations were seen with UC. Conclusions: The IBD5 locus influences susceptibility, progression, and need for surgery in CD. However, the contribution of OCTN1/2 variants is not independent of the IBD5 haplotype; a causative role for these genes remains plausible but is not yet proven. Further genetic, functional, and expression data are now required. </p

    Shape-specific activation of occipital cortex in an early blind echolocation expert

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    We have previously reported that an early-blind echolocating individual (EB) showed robust occipital activation when he identified distant, silent objects based on echoes from his tongue clicks (Thaler, Arnott, & Goodale, 2011). In the present study we investigated the extent to which echolocation activation in EB's occipital cortex reflected general echolocation processing per se versus feature-specific processing. In the first experiment, echolocation audio sessions were captured with in-ear microphones in an anechoic chamber or hallway alcove as EB produced tongue clicks in front of a concave or flat object covered in aluminum foil or a cotton towel. All eight echolocation sessions (2 shapes×2 surface materials×2 environments) were then randomly presented to him during a sparse-temporal scanning fMRI session. While fMRI contrasts of chamber versus alcove-recorded echolocation stimuli underscored the importance of auditory cortex for extracting echo information, main task comparisons demonstrated a prominent role of occipital cortex in shape-specific echo processing in a manner consistent with latent, multisensory cortical specialization. Specifically, relative to surface composition judgments, shape judgments elicited greater BOLD activity in ventrolateral occipital areas and bilateral occipital pole. A second echolocation experiment involving shape judgments of objects located 20° to the left or right of straight ahead activated more rostral areas of EB's calcarine cortex relative to location judgments of those same objects and, as we previously reported, such calcarine activity was largest when the object was located in contralateral hemispace. Interestingly, other echolocating experts (i.e., a congenitally blind individual in Experiment 1, and a late blind individual in Experiment 2) did not show the same pattern of feature-specific echo-processing calcarine activity as EB, suggesting the possible significance of early visual experience and early echolocation training. Together, our findings indicate that the echolocation activation in EB's occipital cortex is feature-specific, and that these object representations appear to be organized in a topographic manner

    Parahippocampal cortex is involved in material processing via echoes in blind echolocation experts

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    Some blind humans use sound to navigate by emitting mouth-clicks and listening to the echoes that reflect from silent objects and surfaces in their surroundings. These echoes contain information about the size, shape, location, and material properties of objects. Here we present results from an fMRI experiment that investigated the neural activity underlying the processing of materials through echolocation. Three blind echolocation experts (as well as three blind and three sighted non-echolocating control participants) took part in the experiment. First, we made binaural sound recordings in the ears of each echolocator while he produced clicks in the presence of one of three different materials (fleece, synthetic foliage, or whiteboard), or while he made clicks in an empty room. During fMRI scanning these recordings were played back to participants. Remarkably, all participants were able to identify each of the three materials reliably, as well as the empty room. Furthermore, a whole brain analysis, in which we isolated the processing of just the reflected echoes, revealed a material-related increase in BOLD activation in a region of left parahippocampal cortex in the echolocating participants, but not in the blind or sighted control participants. Our results, in combination with previous findings about brain areas involved in material processing, are consistent with the idea that material processing by means of echolocation relies on a multi-modal material processing area in parahippocampal cortex

    ADRIC: Adverse Drug Reactions In Children - a programme of research using mixed methods

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    Aims To comprehensively investigate the incidence, nature and risk factors of adverse drug reactions (ADRs) in a hospital-based population of children, with rigorous assessment of causality, severity and avoidability, and to assess the consequent impact on children and families. We aimed to improve the assessment of ADRs by development of new tools to assess causality and avoidability, and to minimise the impact on families by developing better strategies for communication. Review methods Two prospective observational studies, each over 1 year, were conducted to assess ADRs in children associated with admission to hospital, and those occurring in children who were in hospital for longer than 48 hours. We conducted a comprehensive systematic review of ADRs in children. We used the findings from these studies to develop and validate tools to assess causality and avoidability of ADRs, and conducted interviews with parents and children who had experienced ADRs, using these findings to develop a leaflet for parents to inform a communication strategy about ADRs. Results The estimated incidence of ADRs detected in children on admission to hospital was 2.9% [95% confidence interval (CI) 2.5% to 3.3%]. Of the reactions, 22.1% (95% CI 17% to 28%) were either definitely or possibly avoidable. Prescriptions originating in the community accounted for 44 out of 249 (17.7%) of ADRs, the remainder originating from hospital. A total of 120 out of 249 (48.2%) reactions resulted from treatment for malignancies. Off-label and/or unlicensed (OLUL) medicines were more likely to be implicated in an ADR than authorised medicines [relative risk (RR) 1.67, 95% CI 1.38 to 2.02; p  48 hours, the overall incidence of definite and probable ADRs based on all admissions was 15.9% (95% CI 15.0 to 16.8). Opiate analgesic drugs and drugs used in general anaesthesia (GA) accounted for > 50% of all drugs implicated in ADRs. The odds ratio of an OLUL drug being implicated in an ADR compared with an authorised drug was 2.25 (95% CI 1.95 to 2.59; p < 0.001). Risk factors identified were exposure to a GA, age, oncology treatment and number of medicines. The systematic review estimated that the incidence rates for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children [pooled estimate of 2.9% (95% CI 2.6% to 3.1%)] and from 0.6% to 16.8% of all children exposed to a drug during hospital stay. New tools to assess causality and avoidability of ADRs have been developed and validated. Many parents described being dissatisfied with clinician communication about ADRs, whereas parents of children with cancer emphasised confidence in clinician management of ADRs and the way clinicians communicated about medicines. The accounts of children and young people largely reflected parents’ accounts. Clinicians described using all of the features of communication that parents wanted to see, but made active decisions about when and what to communicate to families about suspected ADRs, which meant that communication may not always match families’ needs and expectations. We developed a leaflet to assist clinicians in communicating ADRs to parents. Conclusion The Adverse Drug Reactions In Children (ADRIC) programme has provided the most comprehensive assessment, to date, of the size and nature of ADRs in children presenting to, and cared for in, hospital, and the outputs that have resulted will improve the management and understanding of ADRs in children and adults within the NHS. Recommendations for future research: assess the values that parents and children place on the use of different medicines and the risks that they will find acceptable within these contexts; focusing on high-risk drugs identified in ADRIC, determine the optimum drug dose for children through the development of a gold standard practice for the extrapolation of adult drug doses, alongside targeted pharmacokinetic/pharmacodynamic studies; assess the research and clinical applications of the Liverpool Causality Assessment Tool and the Liverpool Avoidability Assessment Tool; evaluate, in more detail, morbidities associated with anaesthesia and surgery in children, including follow-up in the community and in the home setting and an assessment of the most appropriate treatment regimens to prevent pain, vomiting and other postoperative complications; further evaluate strategies for communication with families, children and young people about ADRs; and quantify ADRs in other settings, for example critical care and neonatology

    Re-Inventing Public Education:The New Role of Knowledge in Education Policy-Making

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    This article focuses on the changing role of knowledge in education policy making within the knowledge society. Through an examination of key policy texts, the Scottish case of Integrated Children Services provision is used to exemplify this new trend. We discuss the ways in which knowledge is being used in order to re-configure education as part of a range of public services designed to meet individuals' needs. This, we argue, has led to a 'scientization' of education governance where it is only knowledge, closely intertwined with action (expressed as 'measures') that can reveal problems and shape solutions. The article concludes by highlighting the key role of knowledge policy and governance in orienting education policy making through a re-invention of the public role of education
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