Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility

Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 × 10-8 in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 × 10-6 overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides.

A genome-wide asociation study identifies new psoriasis susceptibility loci and an interaction betwEn HLA-C and ERAP1

To identify new susceptibility loci for psoriasis, we undertOk a genome-wide asociation study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified asociations at eight previously unreported genomic loci. Seven loci harbored genes with recognized iMune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These asociations were replicated in 9,079 European samples (six loci with a combined P < 5-10 -8 and two loci with a combined P < 5-10-7). We also report compeLing evidence for an interaction betwEn the HLA-C and ERAP1 loci (combined P = 6.95-10-6). ERAP1 plays an important role in MHC claS I peptide proceSing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk aLele. Our findings implicate pathways that integrate epidermal barrier dysfunction with iNate and adaptive iMune dysregulation in psoriasis pathogenesis.

Understanding file access mechanisms for embedded ubicomp collaboration interfaces

This paper explores the nature of interfaces to support people in accessing their files at tabletop displays embedded in the environment. To do this, we designed a study comparing people's interaction with two very different classes of file system access interface: Focus, explicitly designed for tabletops, and the familiar hierarchical Windows Explorer. In our within-subjects double-crossover study, participants collaborated on 4 planning tasks. Based on video, logs, questionnaires and interviews, we conclude that both classes of interface have a place. Notably, Focus contributed to improved collaboration and more efficient use of the workspace than with Explorer. Our results inform a set of recommendations for future interfaces enabling this important class of interaction -- supporting access to files for collaboration at tabletop devices embedded in an ubicomp environment.

How talk and interaction unfold in a digitally enabled preschool classroom

The use of mobile digital devices, such as laptops and tablets, has implications for how teachers interact with young students within the institutional context of educational settings. This article examines language and participation in a digitally enabled preschool classroom as students engage with teachers and peers. Ethnomethodology, conversation analysis and membership categorization analysis are used to explicate video-recorded episodes of students (aged 3-5 years) interacting while using a laptop and a tablet. Attending to the sequential organization (when, how) and the context relevance (where) of talk and interaction, analysis shows how the intersection of interactions involving the teacher, students and digital devices, shape the ways that talk and interactions unfold. Analysis found that the teacher-student interactions were jointly arranged around a participation framework that included: 1) the teacher’s embodied action that mobilizes an accompanying action by a student, 2) allocation of turn-taking and participation while using a digital device and, 3) the affordances of the digital device in relation to the participants’ social organization. In this way, it is possible to understand not just what a digital device is or does, but the affordances of what it makes possible in constituting teachers’ and students’ social and learning relationships.

Criminal histories of crash and non-crash involved Queensland speeding offenders: Evidence supporting the idea that we drive as we live

Evidence increasingly suggests that our behaviour on the road mirrors our behaviour across other aspects of our life. The idea that we drive as we live, described by Tillman and Hobbs more than 65 years ago when examining off-road behaviours of taxi drivers (1949), is the focus of the current paper. As part of a larger study examining the impact of penalty changes on a large cohort of Queensland speeding offenders, criminal (lifetime) and crash history (10 year period) data for a sub-sample of 1000 offenders were obtained. Based on the ‘drive as we live’ maxim, it was hypothesised that crash-involved speeding offenders would be more likely to have a criminal history than non-crash involved offenders. Overall, only 30% of speeding offenders had a criminal history. However, crash-involved offenders were significantly more likely to have a criminal history (49.4%) than non-crash involved offenders (28.6%), supporting the hypothesis. Furthermore, those deemed ‘most at fault’ in a crash were the group most likely to have at least one criminal offence (52.2%). When compared to the non-crash involved offenders, those deemed ‘not most at fault’ in a crash were also more likely to have had at least one criminal offence (46.5%). Therefore, when compared to non-crash involved speeding offenders, those offenders involved in a crash were more likely to have been convicted of at least one criminal offence, irrespective of whether they were deemed ‘most at fault’ in that crash. Implications for traffic offender management and policing are discussed.

Supporting the development and deployment of sustainable energy technologies through targeted scientific training

Sustainable energy technologies rely heavily on advanced materials and modern engineering controls. These promising new technologies cannot be reliably deployed without ensuring that there is a sufficient “capacity,” i.e., trained technical personnel with the expertise to implement, monitor, and maintain the energy infrastructure. This same capacity is critical to the local development of new technologies, especially those that respond directly to regional priorities, strengths, and needs. One way to build capacity is through targeted programs that integrate the training and development of locals at an advanced technical level. In practical terms, these programs usually produce a small number of highly educated individuals with skills in science and engineering. The goal of Part VI of this book is to highlight contributing factors in successfully operating capacity building programs.

Using conceptual tool for intuitive interaction to design intuitive website for SME in India : A case study

Statistical reports of SMEs Internet usage from various countries indicate a steady growth. However, deeper investigation of SME’s e-commerce adoption and usage reveals that a number of SMEs fail to realize the full potential of e-commerce. Factors such as lack of tools and models in Information Systems and Information Technology for SMEs, and lack of technical expertise and specialized knowledge within and outside the SME have the most effect. This study aims to address the two important factors in two steps. First, introduce the conceptual tool for intuitive interaction. Second, explain the implementation process of the conceptual tool with the help of a case study. The subject chosen for the case study is a real estate SME from India. The design and development process of the website for the real estate SME was captured in this case study and the duration of the study was four months. Results indicated specific benefits for web designers and SME business owners. Results also indicated that the conceptual tool is easy to use without the need for technical expertise and specialized knowledge.

Understanding the use of a bug tracking system in a global software development setup

Bug fixing is a highly cooperative work activity where developers, testers, product managers and other stake-holders collaborate using a bug tracking system. In the context of Global Software Development (GSD), where software development is distributed across different geographical locations, we focus on understanding the role of bug trackers in supporting software bug fixing activities. We carried out a small-scale ethnographic fieldwork in a software product team distributed between Finland and India at a multinational engineering company. Using semi-structured interviews and in-situ observations of 16 bug cases, we show that the bug tracker 1) supported information needs of different stake holder, 2) established common-ground, and 3) reinforced issues related to ownership, performance and power. Consequently, we provide implications for design around these findings.

Identifying and addressing equivocal trouble in understanding within classroom interaction

Maintaining intersubjectivity is crucial for accomplishing coordinated social action. Although conversational repair is a recognised defence of intersubjectivity and routinely used to address ostensible sources of trouble in social interaction, it is less clear how people address more equivocal trouble. This study uses conversation analysis to examine preschool classroom interaction, focusing on practices used to identify and address such trouble. Repair is found to be a recurrent frontline practice for addressing equivocal trouble, occasioning space for further information that might enable identifying a specific trouble source. Where further information is forthcoming, a range of strategies are subsequently employed to address the trouble. Where this is not possible or does not succeed, a secondary option is to progress a broader activity-in-progress. This allows for the possibility of another opportunity to identify and address the trouble. Given misunderstandings can jeopardise interactants’ ability to mutually accomplish courses of action, these practices defend intersubjectivity against the threat of equivocal trouble.

Stress analysis of carotid atheroma in a transient ischaemic attack patient using the MRI-based fluid-structure interaction method

Rupture of atherosclerotic plaque is a major cause of mortality. Plaque stress analysis, based on patient-specific multisequence in vivo MRI, can provide critical information for the understanding of plaque rupture and could eventually lead to plaque rupture prediction. However, the direct link between stress and plaque rupture is not fully understood. In the present study, the plaque from a patient who recently experienced a transient ischaemic attack (TIA) was studied using a fluid-structure interaction method to quantify stress distribution in the plaque region based on in vivo MR images. The results showed that wall shear stress is generally low in the artery with a slight increase at the plaque throat owing to minor luminal narrowing. The oscillatory shear index is much higher in the proximal part of the plaque. Both local wall stress concentrations and the relative stress variation distribution during a cardiac cycle indicate that the actual plaque rupture site is collocated with the highest rupture risk region in the studied patient.

Fluid-structure interaction study on human arterial plaque with patient specific geometry and boundary conditions

Atherosclerotic plaque rupture has been extensively considered as the leading cause of death in western countries. It is believed that high stresses within plaque can be an important factor on triggering the rupture of the plaque. Stress analysis in the coronary and carotid arteries with plaque have been developed by many researchers from 2D to 3-D models, from structure analysis only to the Fluid-Structure Interaction (FSI) models[1].

Simulation of the interaction between blood flow and atherosclerotic plaque

It has been well accepted that over 50% of cerebral ischemic events are the result of rupture of vulnerable carotid atheroma and subsequent thrombosis. Such strokes are potentially preventable by carotid interventions. Selection of patients for intervention is currently based on the severity of carotid luminal stenosis. It has been, however, widely accepted that luminal stenosis alone may not be an adequate predictor of risk. To evaluate the effects of degree of luminal stenosis and plaque morphology on plaque stability, we used a coupled nonlinear time-dependent model with flow-plaque interaction simulation to perform flow and stress/strain analysis for stenotic artery with a plaque. The Navier-Stokes equations in the Arbitrary Lagrangian-Eulerian (ALE) formulation were used as the governing equations for the fluid. The Ogden strain energy function was used for both the fibrous cap and the lipid pool. The plaque Principal stresses and flow conditions were calculated for every case when varying the fibrous cap thickness from 0.1 to 2mm and the degree of luminal stenosis from 10% to 90%. Severe stenosis led to high flow velocities and high shear stresses, but a low or even negative pressure at the throat of the stenosis. Higher degree of stenosis and thinner fibrous cap led to larger plaque stresses, and a 50% decrease of fibrous cap thickness resulted in a 200% increase of maximum stress. This model suggests that fibrous cap thickness is critically related to plaque vulnerability and that, even within presence of moderate stenosis, may play an important role in the future risk stratification of those patients when identified in vivo using high resolution MR imaging.

How critical is fibrous cap thickness to carotid plaque stability? A flow-plaque interaction model

Background and Purpose Acute cerebral ischemic events are associated with rupture of vulnerable carotid atheroma and subsequent thrombosis. Factors such as luminal stenosis and fibrous cap thickness have been thought to be important risk factors for plaque rupture. We used a flow-structure interaction model to simulate the interaction between blood flow and atheromatous plaque to evaluate the effect of the degree of luminal stenosis and fibrous cap thickness on plaque vulnerability. Methods A coupled nonlinear time-dependent model with a flow-plaque interaction simulation was used to perform flow and stress/strain analysis in a stenotic carotid artery model. The stress distribution within the plaque and the flow conditions within the vessel were calculated for every case when varying the fibrous cap thickness from 0.1 to 2 mm and the degree of luminal stenosis from 10% to 95%. A rupture stress of 300 kPa was chosen to indicate a high risk of plaque rupture. A 1-sample t test was used to compare plaque stresses with the rupture stress. Results High stress concentrations were found in the plaques in arteries with >70% degree of stenosis. Plaque stresses in arteries with 30% to 70% stenosis increased exponentially as fibrous cap thickness decreased. A decrease of fibrous cap thickness from 0.4 to 0.2 mm resulted in an increase of plaque stress from 141 to 409 kPa in a 40% degree stenotic artery. Conclusions There is an increase in plaque stress in arteries with a thin fibrous cap. The presence of a moderate carotid stenosis (30% to 70%) with a thin fibrous cap indicates a high risk for plaque rupture. Patients in the future may be risk stratified by measuring both fibrous cap thickness and luminal stenosis.

Serendipitous road trips: Enhancing tourists’ experiences through social interaction

Driving can be a lonely activity. While there has been a lot of research and technical inventions concerning car-to-car communication and passenger entertainment, there is still little work concerning connecting drivers. Whereas tourism is very much a social activity, drive tourists have few options to communicate with fellow travellers. The proposed project is placed at the intersection of tourism and driving and aims to enhance the trip experience during driving through social interaction. This thesis explores how a mobile application that allows instant messaging between travellers sharing similar context can add to road trip experiences. To inform the design of such an application, the project adopted the principle of the user-centred design process. User needs were assessed by running an ideation workshop and a field trip. Findings of both studies have shown that tourists have different preferences and diverse attitudes towards contacting new people. Yet all participants stressed the value of social recommendations. Based on those results and a later expert review, three prototype versions of the system were created. A prototyping session with potential end users highlighted the most important features including the possibility to view user profiles, choose between text and audio input and receive up-to-date information. An implemented version of the prototype was evaluated in an exploratory study to identify usability related problems in an actual use case scenario as well as to find implementation bugs. The outcomes of this research are relevant for the design of future mobile tourist guides that leverage from benefits of social recommendations.

Supporting mindful planners in a mindless system: Limitations to the emotional turn in planning practice

Despite widespread acknowledgment within planning scholarship that emotion – both present in knowledge and a form of knowledge – is integral to lived experience and the judgement of planners, it is often sidelined within planning practice. The extent to which mainstream planning has been able or willing to accommodate emotions remains constrained and the emotions of planners and the public remain an unacknowledged but pervasive presence. Antonio Ferreira recently highlighted in this journal the importance of attending to emotions at the level of the individual planner through the concept of mindfulness. We argue this approach must be complemented by an acknowledgement of the structural and institutional limitations of including emotions in planning practice. Drawing from the emotional geographies literature to describe a social-spatial conceptualisation of emotion, we highlight ontological and practical tensions associated with the achievement of the ‘emotional turn’ and advance a more purposeful engagement with emotion in mainstream planning practice.