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Our analysis of data from a nationally representative survey of adults shows that beliefs in whether the January 6th insurrection was justifiable and whether it required investigation through the creation of the U.S. House Select Committee are inexorably steeped in affective partisanship and racial resentment. It is easy to attribute the insurrection to partisan machinations, but evidence shows that racial resentment is the dominant explanation: this includes the fact that allegations of election fraud were centered on districts with large African American and Latino populations; that many of the insurrectionists were white nationalists, racists, and members of radical right-wing groups; and that a large proportion of the electorate had voted to retain a president who fueled whites’ sense of victimization by African Americans and other minorities. We argue that reactions to the legitimacy of the January 6th insurrection have become an example of how racial resentment fuels affective partisanship.

This essay posits that justice is the core value epitomizing our moment. Justice is violated when positive outcomes are undeserved, and the felt sense of injustice motivates a need for retribution. Because politics involves allocation (distribution and redistribution), deservingness is a core appraisal of “who gets what” and therefore justice is fundamental for politics. This is especially germane to race, ethnicity, and politics scholars. I present a few core tenets of justice theory, and argue that political science can take advantage of the moment to engage the concept of justice; especially as it relates to the study of racial attitudes and the identification of racial enablers—those ostensible non-racists who facilitate the status quo. Summarily, I propose that justice can unify debates over prejudice and politics, and advance our scholarly understanding of how well-intentioned people—regardless of their identities, or ideological or partisan labels—can facilitate racism, racial inequality, and injustice.

Racial reckoning in response to racial injustice has compelled individuals, organizations, and institutions to acknowledge and adopt policies that actively challenge racial injustice. A central tenet of this era of reckoning is that it is no longer acceptable to ignore racist behaviors and expressions. To the extent that active opposition to racial prejudice is an effective strategy for individuals to pursue, we examine individual inclinations to act on matters of racial prejudice. We argue that in spite of best intentions, the motivation to act against racism, what we call “antiracism action orientation,” can be disrupted by system-justifying beliefs that raise questions about deservingness, legitimize the status quo, and therefore defend inaction. Survey data from the 2020 Congressional Election Study show that antiracism action orientation is strongest among African Americans, and those with more positive affect toward racial-ethnic minorities, and supporters of change. Among Whites, racial resentment dominates the motivations for antiracism to the point that typical political allies like Democrats, liberals, and those who acknowledge White privilege reduce their antiracism action orientation to lower levels than Republicans, conservatives, and deniers of White privilege. We conclude that most Americans, but especially Whites, have a high bar for change, making racism an ongoing American dilemma because of both racial attitudes and the costs of change.

Americans’ trust in government is lower than ever. However, while all groups have seen a decline in trust since the 1960s, the gap in trust between racial and ethnic minorities and Whites in this period has varied not only in size but also in direction. At times, racial and ethnic minorities have actually had higher rates of trust than Whites, contradicting the broad assumptions in research about race and political trust. Explanations of the causes of trust in government that emphasize institutional experience and early socialization would not predict this outcome. We propose that an underutilized component in the study of race and political trust is perceived justice. On one hand, racial and ethnic minorities’ sensitivity to institutional injustice often leads to lower rates of trust. On the other hand, when racial and ethnic minorities perceive there are greater opportunities for racial progress, which signal that widespread harm can be repaired, their political trust tends to increase, sometimes to levels that exceed those for Whites. The interplay between political realities that shape perceived justice as well as political hope for racial progress likely creates the variable longitudinal patterns of racial and ethnic differences in trust.

This study examines how members of the public frame artificial intelligence (AI) along with how news use predicts “frames in mind” for AI. The study also tests whether news use, science fiction viewing, and discussing technology influence attitudes toward AI independently and in conjunction with one another. The analyses use data from a nationally representative online panel survey. Respondents invoked social progress and Pandora’s box frames for AI, and technology news use predicted mentioning each frame. Use of technology news also predicted change in support for AI, while science fiction viewing and discussing technology were conditionally related to such change.

BACKGROUND AND AIMS: Thromboprophylaxis use in paediatric inflammatory bowel disease [IBD] is inconsistent. Current guidelines only support treating children with acute severe colitis with risk factors. We convened an international RAND panel to explore thromboprophylaxis in paediatric IBD inpatients in the context of new evidence. METHODS: We convened a geographically diverse 14-person panel of paediatric gastroenterologists alongside supporting experts. An online survey was sent before an online meeting. Panellists were asked to rate the appropriateness of thromboprophylaxis in hospitalised paediatric IBD patients via 27 scenarios of varying ages, gender, and phenotype, with and without thrombotic risk factors. Anonymised results were presented at the meeting. A second modified survey was distributed to all panellists present at the meeting. Results from the second survey constitute the RAND panel results. The validated RAND disagreement index defined disagreement when ≥ 1. RESULTS: The combined outcome of thromboprophylaxis being considered appropriate until discharge and inappropriate to withhold was seen in 20 of 27 scenarios, including: all patients with new-onset acute severe colitis; all flares of known ulcerative colitis, irrespective of risk factors except in pre-pubescent patients with limited disease and no risk factors; and all Crohn's patients with risk factors. Disagreement was seen in five scenarios regarding Crohn's without risk factors, where outcomes were already uncertain. CONCLUSIONS: RAND panels are an established method to assess expert opinion in areas of limited evidence. This work therefore constitutes neither a guideline nor a consensus; however, the findings suggest a need to re-evaluate the role of thromboprophylaxis in future guidelines.

This research note examines how framing influences attitudes toward artificial intelligence (AI). It uses an experiment embedded in a nationally representative online survey to test the effects of text-based frames and visuals on opinion about developing, funding, and banning AI. Participants exposed to a “social progress” frame reported greater support for AI than those exposed to a “Pandora’s box” frame. Images (virtual assistants, personal robots, menacing movie AIs, or none) did not influence opinion by themselves but interacted with textual frames to do so. The results extend our understanding of framing effects on public attitudes toward emerging technologies.

BACKGROUND: It is important to identify patients with monogenic IBD as management may differ from classical IBD. In this position statement we formulate recommendations for the use of genomics in evaluating potential monogenic causes of IBD across age groups. METHODS: The consensus included paediatric IBD specialists from the Paediatric IBD Porto group of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and specialists from several monogenic IBD research consortia. We defined key topics and performed a systematic literature review to cover indications, technologies (targeted panel, exome and genome sequencing), gene panel setup, cost-effectiveness of genetic screening, and requirements for the clinical care setting. We developed recommendations that were voted upon by all authors and Porto group members (32 voting specialists). RESULTS: We recommend next-generation DNA-sequencing technologies to diagnose monogenic causes of IBD in routine clinical practice embedded in a setting of multidisciplinary patient care. Routine genetic screening is not recommended for all IBD patients. Genetic testing should be considered depending on age of IBD-onset (infantile IBD, very early-onset IBD, paediatric or young adult IBD), and further criteria, such as family history, relevant comorbidities, and extraintestinal manifestations. Genetic testing is also recommended in advance of hematopoietic stem cell transplantation. We developed a diagnostic algorithm that includes a gene panel of 75 monogenic IBD genes. Considerations are provided also for low resource countries. CONCLUSIONS: Genomic technologies should be considered an integral part of patient care to investigate patients at risk for monogenic forms of IBD.

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis.

BACKGROUND AND AIM Acute severe colitis (ASC) is one of the few emergencies in pediatric gastroenterology. Tight monitoring and timely medical and surgical interventions may improve outcomes and minimize morbidity and mortality. We aimed to standardize daily treatment of ASC in children through detailed recommendations and practice points which are based on a systematic review of the literature and consensus of experts. METHODS These guidelines are a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Fifteen predefined questions were addressed by working subgroups. An iterative consensus process, including 2 face-to-face meetings, was followed by voting of the national representatives of ECCO and all members of the Paediatric Inflammatory Bowel Disease (IBD) Porto group of ESPGHAN (43 voting experts). RESULTS A total of 24 recommendations and 43 practice points were endorsed with a consensus rate of at least 91% regarding diagnosis, monitoring, and management of ASC in children. A summary flowchart is presented based on daily scoring of the Paediatric Ulcerative Colitis Activity Index. Several topics have been altered since the previous 2011 guidelines and from those published in adults. DISCUSSION These guidelines standardize the management of ASC in children in an attempt to optimize outcomes of this intensive clinical scenario.

BACKGROUND The contemporary management of ambulatory ulcerative colitis (UC) continues to be challenging with ∼20% of children needing a colectomy within childhood years. We thus aimed to standardize daily treatment of pediatric UC and inflammatory bowel diseases (IBD)-unclassified through detailed recommendations and practice points. METHODS These guidelines are a joint effort of the European Crohn's and Colitis Organization (ECCO) and the Paediatric IBD Porto group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). An extensive literature search with subsequent evidence appraisal using robust methodology was performed before 2 face-to-face meetings. All 40 included recommendations and 86 practice points were endorsed by 43 experts in Paediatric IBD with at least an 88% consensus rate. RESULTS These guidelines discuss how to optimize the use of mesalamine (including topical), systemic and locally active steroids, thiopurines and, for more severe disease, biologics. The use of other emerging therapies and the role of surgery are also covered. Algorithms are provided to aid therapeutic decision-making based on clinical assessment and the Paediatric UC Activity Index (PUCAI). Advice on contemporary therapeutic targets incorporating the use of calprotectin and the role of therapeutic drug monitoring are presented, as well as other management considerations around pouchitis, extraintestinal manifestations, nutrition, growth, psychology, and transition. A brief section on disease classification using the PIBD-classes criteria and IBD-unclassified is also part of these guidelines. CONCLUSIONS These guidelines provide a guide to clinicians managing children with UC and IBD-unclassified management to provide modern management strategies while maintaining vigilance around appropriate outcomes and safety issues.

BACKGROUND: Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. METHODS: This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34,819 patients (19,713 with Crohn's disease, 14,683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype-phenotype associations across 156,154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. FINDINGS: After quality control, the primary analysis included 29,838 patients (16,902 with Crohn's disease, 12,597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease sho

Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34,819 patients (19,713 with Crohn's disease, 14,683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype-phenotype associations across 156,154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. After quality control, the primary analysis included 29,838 patients (16,902 with Crohn's disease, 12,597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with dis

Background: Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. Methods This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34,819 patients (19,713 with Crohn's disease, 14,683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype-phenotype associations across 156,154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. Findings: After quality control, the primary analysis included 29,838 patients (16,902 with Crohn's disease, 12,597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease show

OBJECTIVES: The diagnostic accuracy of faecal calprotectin (FC) concentration for paediatric inflammatory bowel disease (IBD) is well described at the population level, but not at the individual level. We reassessed the diagnostic accuracy of FC in children with suspected IBD and developed an individual risk prediction rule using individual patient data. METHODS: MEDLINE, EMBASE, DARE, and MEDION databases were searched to identify cohort studies evaluating the diagnostic performance of FC in paediatric patients suspected of having IBD. A standard study-level meta-analysis was performed. In an individual patient data meta-analysis, we reanalysed the diagnostic accuracy on a merged patient dataset. Using logistic regression analysis we investigated whether and how the FC value and patient characteristics influence the diagnostic precision. A prediction rule was derived for use in clinical practice and implemented in a spreadsheet calculator. RESULTS: According to the study-level meta-analysis (9 studies, describing 853 patients), FC has a high overall sensitivity of 0.97 (95% confidence interval [CI] 0.92-0.99) and a specificity of 0.70 (0.59-0.79) for diagnosing IBD. In the patient-level pooled analysis of 742 patients from 8 diagnostic accuracy studies, we calculated that at an FC cutoff level of 50 μg/g there would be 17% (95% CI 15-20) false-positive and 2% (1-3) false-negative results. The final logistic regression model was based on individual data of 545 patients and included both FC level and age. The area under the receiver operating characteristic curve of this derived prediction model was 0.92 (95% CI 0.89-0.94). CONCLUSIONS: In high-prevalence circumstances, FC can be used as a noninvasive biomarker of paediatric IBD with only a small risk of missing cases. To quantify the individual patients' risk, we developed a simple prediction model based on FC concentration and age. Although the derived prediction rule cannot substitute the clinical diagnostic proce

Graphs have become ubiquitous structures to encode geographic knowledge online. The Semantic Web’s linked open data, folksonomies, wiki websites and open gazetteers can be seen as geo-knowledge graphs, that is labeled graphs whose vertices represent geographic concepts and whose edges encode the relations between concepts. To compute the semantic similarity of concepts in such structures, this article defines the network-lexical similarity measure (NLS). This measure estimates similarity by combining two complementary sources of information: the network similarity of vertices and the semantic similarity of the lexical definitions. NLS is evaluated on the OpenStreetMap Semantic Network, a crowdsourced geo-knowledge graph that describes geographic concepts. The hybrid approach outperforms both network and lexical measures, obtaining very strong correlation with the similarity judgments of human subjects.

Autoimmune diseases (AIDs) are polygenic diseases affecting 7-10% of the population in the Western Hemisphere with few effective therapies. Here, we quantify the heritability of paediatric AIDs (pAIDs), including JIA, SLE, CEL, T1D, UC, CD, PS, SPA and CVID, attributable to common genomic variations (SNP-h(2)). SNP-h(2) estimates are most significant for T1D (0.863±s.e. 0.07) and JIA (0.727±s.e. 0.037), more modest for UC (0.386±s.e. 0.04) and CD (0.454±0.025), largely consistent with population estimates and are generally greater than that previously reported by adult GWAS. On pairwise analysis, we observed that the diseases UC-CD (0.69±s.e. 0.07) and JIA-CVID (0.343±s.e. 0.13) are the most strongly correlated. Variations across the MHC strongly contribute to SNP-h(2) in T1D and JIA, but does not significantly contribute to the pairwise rG. Together, our results partition contributions of shared versus disease-specific genomic variations to pAID heritability, identifying pAIDs with unexpected risk sharing, while recapitulating known associations between autoimmune diseases previously reported in adult cohorts.

Background: The combination of the severity of pediatric-onset inflammatory bowel disease (IBD) phenotypes and the need for intense medical treatment may increase the risk of malignancy and mortality, but evidence regarding the extent of the problem is scarce. Therefore, the Porto Pediatric IBD working group of ESPGHAN conducted a multinational-based survey of cancer and mortality in pediatric IBD. Methods: A survey among pediatric gastroenterologists of 20 European countries and Israel on cancer and/or mortality in the pediatric patient population with IBD was undertaken. One representative from each country repeatedly contacted all pediatric gastroenterologists from each country for reporting retrospectively cancer and/or mortality of pediatric patients with IBD after IBD onset, during 2006-2011. Results: We identified 18 cases of cancers and/or 31 deaths in 44 children (26 males) who were diagnosed with IBD (ulcerative colitis, n = 21) at a median age of 10.0 years (inter quartile range, 3.0-14.0). Causes of mortality were infectious (n = 14), cancer (n = 5), uncontrolled disease activity of IBD (n = 4), procedure-related (n = 3), other non-IBD related diseases (n = 3), and unknown (n = 2). The most common malignancies were hematopoietic tumors (n = 11), of which 3 were hepatosplenic T-cell lymphoma and 3 Ebstein-Barr virus-associated lymphomas. Conclusions: Cancer and mortality in pediatric IBD are rare, but cumulative rates are not insignificant. Mortality is primarily related to infections, particularly in patients with 2 or more immunosuppressive agents, followed by cancer and uncontrolled disease. At least 6 lymphomas were likely treatment-associated by virtue of their phenotype.

In geographic information science and semantics, the computation of semantic similarity is widely recognised as key to supporting a vast number of tasks in information integration and retrieval. By contrast, the role of geo-semantic relatedness has been largely ignored. In natural language processing, semantic relatedness is often confused with the more specific semantic similarity. In this article, we discuss a notion of geo-semantic relatedness based on Lehrer’s semantic fields, and we compare it with geo-semantic similarity. We then describe and validate the Geo Relatedness and Similarity Dataset (GeReSiD), a new open dataset designed to evaluate computational measures of geo-semantic relatedness and similarity. This dataset is larger than existing datasets of this kind, and includes 97 geographic terms combined into 50 term pairs rated by 203 human subjects. GeReSiD is available online and can be used as an evaluation baseline to determine empirically to what degree a given computational model approximates geo-semantic relatedness and similarity.

Computational measures of semantic similarity between geographic terms provide valuable support across geographic information retrieval, data mining, and information integration. To date, a wide variety of approaches to geo-semantic similarity have been devised. A judgment of similarity is not intrinsically right or wrong, but obtains a certain degree of cognitive plausibility, depending on how closely it mimics human behavior. Thus selecting the most appropriate measure for a specific task is a significant challenge. To address this issue, we make an analogy between computational similarity measures and soliciting domain expert opinions, which incorporate a subjective set of beliefs, perceptions, hypotheses, and epistemic biases. Following this analogy, we define the semantic similarity ensemble (SSE) as a composition of different similarity measures, acting as a panel of experts having to reach a decision on the semantic similarity of a set of geographic terms. The approach is evaluated in comparison to human judgments, and results indicate that an SSE performs better than the average of its parts. Although the best member tends to outperform the ensemble, all ensembles outperform the average performance of each ensemble's member. Hence, in contexts where the best measure is unknown, the ensemble provides a more cognitively plausible approach., Comment: Special feature on Semantic and Conceptual Issues in GIS (SeCoGIS)

Over the past decade, rapid advances in web technologies, coupled with innovative models of spatial data collection and consumption, have generated a robust growth in geo-referenced information, resulting in spatial information overload. Increasing 'geographic intelligence' in traditional text-based information retrieval has become a prominent approach to respond to this issue and to fulfill users' spatial information needs. Numerous efforts in the Semantic Geospatial Web, Volunteered Geographic Information (VGI), and the Linking Open Data initiative have converged in a constellation of open knowledge bases, freely available online. In this article, we survey these open knowledge bases, focusing on their geospatial dimension. Particular attention is devoted to the crucial issue of the quality of geo-knowledge bases, as well as of crowdsourced data. A new knowledge base, the OpenStreetMap Semantic Network, is outlined as our contribution to this area. Research directions in information integration and Geographic Information Retrieval (GIR) are then reviewed, with a critical discussion of their current limitations and future prospects.

The linked open data (LOD) paradigm has emerged as a promising approach to structuring and sharing geospatial information. One of the major obstacles to this vision lies in the difficulties found in the automatic integration between heterogeneous vocabularies and ontologies that provides the semantic backbone of the growing constellation of open geo-knowledge bases. In this article, we show how to utilize WordNet as a semantic hub to increase the integration of LOD. With this purpose in mind, we devise Voc2WordNet, an unsupervised mapping technique between a given vocabulary and WordNet, combining intensional and extensional aspects of the geographic terms. Voc2WordNet is evaluated against a sample of human-generated alignments with the OpenStreetMap (OSM) Semantic Network, a crowdsourced geospatial resource, and the GeoNames ontology, the vocabulary of a large digital gazetteer. These empirical results indicate that the approach can obtain high precision and recall., Comment: 21 pages, 1 figure

Objective Mutations in the nucleotide-binding oligomerisation domain-containing protein 2 (NOD2) gene remain the strongest genetic determinants for Crohn's disease (CD). Having previously identified vimentin as a novel NOD2-interacting protein, the authors aimed to investigate the regulatory effects of vimentin on NOD2 function and the association of variants in Vim with CD susceptibility. Design Coimmunoprecipitation, fluorescent microscopy and fractionation were used to confirm the interaction between NOD2 and vimentin. HEK293 cells stably expressing wild-type NOD2 or a NOD2 frameshift variant (L1007fs) and SW480 colonic epithelial cells were used alongside the vimentin inhibitor, withaferin A (WFA), to assess effects on NOD2 function using the nuclear factor-kappaB (NF-κB) reporter gene, green fluorescent protein-LC3-based autophagy, and bacterial gentamicin protection assays. International genome-wide association meta-analysis data were used to test for associations of single-nucleotide polymorphisms in Vim with CD susceptibility. Results The leucine-rich repeat domain of NOD2 contained the elements required for vimentin binding; CD-associated polymorphisms disrupted this interaction. NOD2 and vimentin colocalised at the cell plasma membrane, and cytosolic mislocalisation of the L1007fs and R702W variants correlated with an inability to interact with vimentin. Use of WFA demonstrated that vimentin was required for NOD2-dependent NF-κB activation and muramyl dipeptide-induced autophagy induction, and that NOD2 and vimentin regulated the invasion and survival properties of a CD-associated adherent-invasive Escherichia coli strain. Genetic analysis revealed an association signal across the haplotype block containing Vim. Conclusion Vimentin is an important regulator of NOD2 function and a potential novel therapeutic target in the treatment of CD. In addition, Vim is a candidate susceptibility gene for CD, supporting the functional data., Contributor: IIBDGC the International IBD Genetics Consortium http://www.ibdgenetics.org/groups.html

BACKGROUND AND AIMS: Pediatric ulcerative colitis (UC) shares many features with adult-onset disease but there are some unique considerations; therefore, therapeutic approaches have to be adapted to these particular needs. We aimed to formulate guidelines for managing UC in children based on a systematic review (SR) of the literature and a robust consensus process. The present article is a product of a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). METHODS: A group of 27 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to ESPGHAN and ECCO members. A list of 23 predefined questions were addressed by working subgroups based on a SR of the literature. RESULTS: A total of 40 formal recommendations and 68 practice points were endorsed with a consensus rate of at least 89% regarding initial evaluation, how to monitor disease activity, the role of endoscopic evaluation, medical and surgical therapy, timing and choice of each medication, the role of combined therapy, and when to stop medications. A management flowchart, based on the Pediatric Ulcerative Colitis Activity Index (PUCAI), is presented. CONCLUSIONS: These guidelines provide clinically useful points to guide the management of UC in children. Taken together, the recommendations offer a standardized protocol that allows effective, timely management and monitoring of the disease course, while acknowledging that each patient is unique.

Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

Pediatric ulcerative colitis (UC) shares many features with adult-onset disease but there are some unique considerations; therefore, therapeutic approaches have to be adapted to these particular needs. We aimed to formulate guidelines for managing UC in children based on a systematic review (SR) of the literature and a robust consensus process. The present article is a product of a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN).

Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.

Continuing advances in digital image capture and storage are resulting in a proliferation of imagery and associated problems of information overload in image domains. In this work we present a framework that supports image management using an interactive approach that captures and reuses task-based contextual information. Our framework models the relationship between images and domain tasks they support by monitoring the interactive manipulation and annotation of task-relevant imagery. During image analysis, interactions are captured and a task context is dynamically constructed so that human expertise, proficiency and knowledge can be leveraged to support other users in carrying out similar domain tasks using case-based reasoning techniques. In this article we present our framework for capturing task context and describe how we have implemented the framework as two image retrieval applications in the geo-spatial and medical domains. We present an evaluation that tests the efficiency of our algorithms for retrieving image context information and the effectiveness of the framework for carrying out goal-directed image tasks. © 2010 Springer Science+Business Media, LLC.

As Digital TV subscribers are offered more and more channels, it is becoming increasingly difficult for them to locate the right programme information at the right time. The personalized Electronic Programme Guide (pEPG) is one solution to this problem; it leverages artificial intelligence and user profiling techniques to learn about the viewing preferences of individual users in order to compile personalized viewing guides that fit their individual preferences. Very often the limited availability of profiling information is a key limiting factor in such personalized recommender systems. For example, it is well known that collaborative filtering approaches suffer significantly from the sparsity problem, which exists because the expected item-overlap between profiles is usually very low. In this article we address the sparsity problem in the Digital TV domain. We propose the use of data mining techniques as a way of supplementing meagre ratings-based profile knowledge with additional item-similarity knowledge that can be automatically discovered by mining user profiles. We argue that this new similarity knowledge can significantly enhance the performance of a recommender system in even the sparsest of profile spaces. Moreover, we provide an extensive evaluation of our approach using two large-scale, state-of-the-art online systems—PTVPlus, a personalized TV listings portal and Físchlár, an online digital video library system.

Este artigo estabelece uma postura crítica e analítica em relação às abordagens baseadas em microatividades para se entender a estratégia. Argumenta-se que tais abordagens trazem desafios teóricos e empíricos importantes. Argumenta-se também contra a tendência ao reducionismo, sem igual ênfase nas influências contextuais que configuram a estratégia em um nível micro. Finalmente, o artigo defende uma abordagem mais internacional e comparativa para os estudos da estratégia em um nível micro. This paper takes a critical and evaluative stance toward micro-activity-based approaches to understanding strategy. It argues that such approaches bring with them important theoretical and empirical challenges. The paper argues against a tendency to reductionism without equal emphasis to the contextual influences that bound micro-strategising. Finally, the paper argues for a more international and comparative approach to micro-strategy studies than has currently been the case.

The “Físchlár” systems are a family of tools for capturing, analysis, indexing, browsing, searching and summarisation of digital video information. Físchlár-News-Stories, described in this paper, is one of those systems, and provides access to a growing archive of broadcast TV news. Físchlár-News-Stories has several notable features including the fact that it automatically records TV news and segments a broadcast news program into stories, eliminating advertisements and credits at the start/end of the broadcast. Físchlár-News-Stories supports access to individual stories via calendar lookup, text search through closed captions, automatically-generated links between related stories, and personalised access using a personalisation and recommender system based on collaborative filtering. Access to individual news stories is supported either by browsing keyframes with synchronised closed captions, or by playback of the recorded video. One strength of the Físchlár-News-Stories system is that it is actually used, in practice, daily, to access news. Several aspects of the Físchlár systems have been published before, bit in this paper we give a summary of the Físchlár-News-Stories system in operation by following a scenario in which it is used and also outlining how the underlying system realises the functions it offers.

Business and other organizations in Britain were revisited to study the outcomes of implementing 55 strategic (major) decisions. These were a subsample of 150 cases studied previously when the decisions were made. Chief executives and directors (that is, presidents and vice presidents and equivalent) were interviewed about what happened. A series of factors that appear to contribute to success and failure is being elucidated. These reasons for good or bad performance can better inform senior managements in the future and be an aid to more successful decision making.

Las decisiones estratégicas moldean el curso tomado por una organización, sea ésta parte del sector público y del sector privado. En este artículo se reporta un análisis de 150 casos de toma de decisiones estratégicas en organizaciones de propiedad tanto pública como privada. Se identifican tres tipos de procesos de toma de decisiones, esporádicos, fluidos y constreñidos. Se examinan las diferencias debidas a la naturaleza de la materia sujeta a decisión y a la naturaleza de la organización. Se describen las diferencias en la inclinación a procesos de toma de decisión esporádicos por parte de la administración de organizaciones de propiedad pública.