Health effects of daily airborne particle dose in children : direct association between personal dose and respiratory health effects

Air pollution is a widespread health problem associated with respiratory symptoms. Continuous exposure monitoring was performed to estimate alveolar and tracheobronchial dose, measured as deposited surface area, for 103 children and to evaluate the long-term effects of exposure to airborne particles through spirometry, skin prick tests and measurement of exhaled nitric oxide (eNO). The mean daily alveolar deposited surface area dose received by children was 1.35×103 mm2. The lowest and highest particle number concentrations were found during sleeping and eating time. A significant negative association was found between changes in pulmonary function tests and individual dose estimates. Significant differences were found for asthmatics, children with allergic rhinitis and sensitive to allergens compared to healthy subjects for eNO. Variation is a child’s activity over time appeared to have a strong impact on respiratory outcomes, which indicates that personal monitoring is vital for assessing the expected health effects of exposure to particles.

BWW ontology as a lens on IS design theory: Extending the design science research roadmap

The Design Science Research Roadmap (DSR-Roadmap) [1] aims to give detailed methodological guidance to novice researchers in Information Systems (IS) DSR. Focus group evaluation, one phase of the overall study, of the evolving DSR-Roadmap revealed that a key difficulty faced by both novice and expert researchers in DSR, is abstracting design theory from design. This paper explores the extension of the DSR-Roadmap by employing IS deep structure ontology (BWW [2-4]) as a lens on IS design to firstly yield generalisable design theory, specifically 'IS Design Theory' (ISDT) elements [5]. Consideration is next given to the value of BWW in the application of the design theory by practitioners. Results of mapping BWW constructs to ISDT elements suggest that the BWW is promising as a common language between design researchers and practitioners, facilitating both design theory and design implementation

Measuring IS-support : a conceptual model

This paper reports on a conceptual model of a larger research effort proceeding from a central interest in the importance of assessing the IS-Support provided to key-user groups. This study conceptualised a new multidimensional IS-Support construct with four dimensions: training, documentation, assistance and authorisation, which form the overarching construct – IS-Support. We argue that a holistic measure for assessing IS-Support should consist of dimensions, and measures, that together assess the variety of the support provided to IS key-user groups. The proposed IS-Support construct is defined as the support the IS key-user groups receive to increase their capabilities in utilising information systems within the organisation. With two interrelated phases, conceptualisation phase and validation phase, to rigorously hypothesise and validate a measurement model, the IS-Support model, proposed in this study, is intended to include the characteristics of analytic theory.

The design science research roadmap : in progress evaluation

Although Design Science Research (DSR) is now an accepted approach to research in the Information Systems (IS) discipline, consensus on the methodology of DSR has yet to be achieved. Lack of a comprehensive and detailed methodology for Design Science Research (DSR) in the Information System (IS) discipline is a main issue. Prior research (the parent-study) aimed to remedy this situation and resulted in the DSR-Roadmap (Alturki et al., 2011a). Continuing empirical validation and revision of the DSR-Roadmap strives towards a methodology with appropriate levels of detail, integration, and completeness for novice researchers to efficiently and effectively conduct and report DSR in IS. The sub-study reported herein contributes to this larger, ongoing effort. This paper reports results from a formative evaluation effort of the DSR-Roadmap conducted using focus group analysis. Generally, participants endorsed the utility and intuitiveness of the DSR-Roadmap, while also suggesting valuable refinements. Both parent-study and sub-study make methodological contributions. The parent-study is the first attempt of utilizing DSR to develop a research methodology showing an example of how to use DSR in research methodology construction. The sub-study demonstrates the value of the focus group method in DSR for formative product evaluation.

Information quality in social media : a conceptual model

Social Media (SM) is increasingly being integrated with business information in decision making. Unique characteristics of social media (e.g. wide accessibility, permanence, global audience, recentness, and ease of use) raise new issues with information quality (IQ); quite different from traditional considerations of IQ in information systems (IS) evaluation. This paper presents a preliminary conceptual model of information quality in social media (IQnSM) derived through directed content analysis and employing characteristics of analytic theory in the study protocol. Based in the notion of ‘fitness for use’, IQnSM is highly use and user centric and is defined as “the degree to which information is suitable for doing a specified task by a specific user, in a certain context”. IQnSM is operationalised as hierarchical, formed by the three dimensions (18 measures): intrinsic quality, contextual quality and representational quality. A research plan for empirically validating the model is proposed.

Functional analysis of missense variants in the TRESK (KCNK18) K+ channel

A loss of function mutation in the TRESK K2P potassium channel (KCNK18), has recently been linked with typical familial migraine with aura. We now report the functional characterisation of additional TRESK channel missense variants identified in unrelated patients. Several variants either had no apparent functional effect, or they caused a reduction in channel activity. However, the C110R variant was found to cause a complete loss of TRESK function, yet is present in both sporadic migraine and control cohorts, and no variation in KCNK18 copy number was found. Thus despite the previously identified association between loss of TRESK channel activity and migraine in a large multigenerational pedigree, this finding indicates that a single non-functional TRESK variant is not alone sufficient to cause typical migraine and highlights the genetic complexity of this disorder. Migraine is a common, disabling neurological disorder with a genetic, environmental and in some cases hormonal component. It is characterized by attacks of severe, usually unilateral and throbbing headache, can be accompanied by nausea, vomiting and photophobia and is clinically divided into two main subtypes, migraine with aura (MA) when a migraine is accompanied by transient and reversible focal neurological symptoms and migraine without aura (MO)1. The multifactorial and clinical heterogeneity of the disorder have considerably hindered the identification of common migraine susceptibility genes and most of our current understanding comes from the studies of familial hemiplegic migraine (FHM), a rare monogenic autosomal dominant form of MA2. So far, the three susceptibility genes that have been convincingly identified in FHM families all encode ion channels or transporters: CACNA1A encoding the α1 subunit of the Cav2.1 calcium channel3, SCN1A encoding the Nav1.1 sodium channel4 and ATP1A2 encoding the α2 subunit of the Na+/K+ pump5. It is believed that mutations in these genes may lead to increased efflux of glutamate and potassium in the synapse and thereby cause migraine by rendering the brain more susceptible to cortical spreading depression (CSD)6 which is thought to play a role in initiating a migraine attack7,8. However, these genes have not to date been implicated in common forms of migraine9. Nevertheless, current opinion suggests that typical migraine, like FHM, is also disorder of neuronal excitability, ion homeostasis and neurotransmitter release10,11,12. Mutations in the SLC4A4 gene encoding the sodium-bicarbonate cotransporter NBCe1, have recently been implicated in several different forms of migraine13, and a variety of genes involved in glutamate homeostasis (PGCP, MTDH14 and LRP115) and a cation channel (TRPM8)15 have also recently been implicated in migraine via genome-wide association studies. Ion channels are therefore highly likely to play an important role in the pathogenesis of typical migraine. TRESK (KCNK18), is a member of the two-pore domain (K2P) family of potassium channels involved in the control of cellular electrical excitability16. Regulation of TRESK activity by the calcium-dependent phosphatase calcineurin17, as well as its expression in dorsal root ganglia (DRG)18 and trigeminal ganglia (TG)19,20 has led to a proposed role for this channel in a variety of pain pathways. In a recent study, a frameshift mutation (F139Wfsx24) in TRESK was identified in a large multigenerational pedigree where it co-segregated perfectly with typical MA and a significant genome-wide linkage LOD score of 3.0. Furthermore, functional analysis revealed that this mutation caused a complete loss of TRESK function and that the truncated subunit was also capable of down regulating wild-type channel function. This therefore highlighted KCNK18 as potentially important candidate gene and suggested that TRESK dysfunction might play a possible role in the pathogenesis of familial migraine with visual aura20. Additional screening for KCNK18 mutations in unrelated sporadic migraine and control cohorts also identified a number of other missense variants; R10G, A34V, C110R, S231P and A233V20. The A233V variant was found only in the control cohort, whilst A34V was identified in a single Australian migraine proband for which family samples were not available, but it was not detected in controls. By contrast, the R10G, C110R, and S231P variants were found in both migraineurs and controls in both cohorts. In this study, we have investigated the functional effect of these variants to further probe the potential association of TRESK dysfunction with typical migraine.

A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura

Migraine with aura is a common, debilitating, recurrent headache disorder associated with transient and reversible focal neurological symptoms. A role has been suggested for the two-pore domain (K2P) potassium channel, TWIK-related spinal cord potassium channel (TRESK, encoded by KCNK18), in pain pathways and general anaesthesia. We therefore examined whether TRESK is involved in migraine by screening the KCNK18 gene in subjects diagnosed with migraine. Here we report a frameshift mutation, F139WfsX24, which segregates perfectly with typical migraine with aura in a large pedigree. We also identified prominent TRESK expression in migraine-salient areas such as the trigeminal ganglion. Functional characterization of this mutation demonstrates that it causes a complete loss of TRESK function and that the mutant subunit suppresses wild-type channel function through a dominant-negative effect, thus explaining the dominant penetrance of this allele. These results therefore support a role for TRESK in the pathogenesis of typical migraine with aura and further support the role of this channel as a potential therapeutic target.

Complex cognitive interactions in a badly designed world : Investigating the underlying causes of collisions between distinct road users

Collisions between distinct road users (e.g. drivers and riders, drivers and cyclists) make a substantial contribution to the road trauma burden. Although evidence suggests different road users interpret the same road situations contrarily, it is not clear how their situation awareness differs, nor is it clear which differences might lead to conflicts. This article presents the findings from an on-road study which was conducted to examine driver, cyclist and motorcyclist situation awareness in different road environments. The findings suggest that drivers, motorcyclists, and cyclists develop markedly different situational understandings even when operating in the same road environments. Examination of these differences indicate that they are likely to be compatible along arterial roads, shopping strips and at roundabouts, but that they may create conflicts between the different road users at intersections. The key role of road design in supporting compatible situation awareness and behaviour across different road users is discussed.

Investigating the factors influencing cyclist awareness and behaviour : an on-road study of cyclist situation awareness

Situation awareness, ones understanding of ‘what is going on’, is a critical commodity for road users. Although the concept has received much attention in the driving context, situation awareness in vulnerable road users, such as cyclists, remains unexplored. This paper presents the findings from an exploratory on-road study of cyclist situation awareness, the aim of which was to explore how cyclists develop situation awareness, what their situation awareness comprises, and what the causes of degraded cyclist situation awareness may be. Twenty participants cycled a pre-defined urban on-road study route. A range of data were collected, including verbal protocols, forward scene video and rear video, and a network analysis procedure was used to describe and assess cyclist situation awareness. The analysis produced a number of key findings regarding cyclist situation awareness, including the potential for cyclists’ awareness of other road users to be degraded due to additional situation awareness and decision making requirements that are placed on them in certain road situations. Strategies for improving cyclists’ situation awareness are discussed.

Lane filtering and situation awareness in motorcyclists : an on-road proof of concept study

In Victoria, as in other jurisdictions, there is very little research on the potential risks and benefits of lane filtering by motorcyclists, particularly from a road safety perspective. This on-road proof of concept study aimed to investigate whether and how lane filtering influences motorcycle rider situation awareness at intersections and to address factors that need to be considered for the design of a larger study in this area. Situation awareness refers to road users’ understanding of ‘what is going on’ around them and is a critical commodity for safe performance. Twenty-five experienced motorcyclists rode their own instrumented motorcycle around an urban test route in Melbourne whilst providing verbal protocols. Lane filtering occurred in 27% of 43 possible instances in which there were one or more vehicles in the traffic queue and the traffic lights were red on approach to the intersection. A network analysis procedure, based on the verbal protocols provided by motorcyclists, was used to identify differences in motorcyclist situation awareness between filtering and non-filtering events. Although similarities in situation awareness across filtering and nonfiltering motorcyclists were found, the analysis revealed some differences. For example, filtering motorcyclists placed more emphasis on the timing of the traffic light sequence and on their own actions when moving to the front of the traffic queue, whilst non-filtering motorcyclists paid greater attention to traffic moving through the intersection and approaching from behind. Based on the results of this study, the paper discusses some methodological and theoretical issues to be addressed in a larger study comparing situation awareness between filtering and non-filtering motorcyclists.

Awesome foursome? The compatibility of situation awareness across drivers, riders, cyclists, and pedestrians

Collisions between distinct road users (e.g. drivers and motorcyclists) make a substantial contribution to the road trauma burden. Although evidence suggests distinct road users interpret the same road situations differently, it is not clear how road users’ situation awareness differs, nor is it clear which differences might lead to conflicts. This article presents the findings from an on-road study which examined driver, cyclist, motorcyclist and pedestrian situation awareness at intersections. The findings suggest that situation awareness at intersection is markedly different across the four road user groups studied, and that some of these differences may create conflicts between the different road users. The findings also suggest that the causes of the differences identified relate to road design and road user experience. In closing, the key role of road design and training in supporting safe interactions between distinct road users is discussed.

Interactions between cars and motorcycles testing underlying concepts through integration of on-road and simulator studies

We conducted on-road and simulator studies to explore the mechanisms underpinning driver-rider crashes. In Study 1 the verbal protocols of 40 drivers and riders were assessed at intersections as part of a 15km on-road route in Melbourne. Network analysis of the verbal transcripts highlighted key differences in the situation awareness of drivers and riders at intersections. In a further study using a driving simulator we examined in car drivers the influence of acute exposure to motorcyclists. In a 15 min simulated drive, 40 drivers saw either no motorcycles or a high number of motorcycles in the surrounding traffic. In a subsequent 45-60 min drive, drivers were asked to detect motorcycles in traffic. The proportion of motorcycles was manipulated so that there was either a high (120) or low (6) number of motorcycles during the drive. Those drivers exposed to a high number of motorcycles were significantly faster at detecting motorcycles. Fundamentally, the incompatible situation awareness at intersections by drivers and riders underpins the conflicts. Study 2 offers some suggestion for a countermeasure here, although more research around schema and exposure training to support safer interactions is needed.

The effect of organ motion of radiotherapy plans

Organ motion as a result of respiration is an important field of research for medical physics. Knowledge of magnitude and direction of this motion is necessary to allow for more accurate radiotherapy treatment planning. This will result in higher doses to the tumour whilst sparing healthy tissue. This project involved human trials, where the radiation therapy patient's kidneys were CT scanned under three different conditions; whilst free breathing (FB), breath-hold at normal tidal inspiration (BHIN), and breath-hold at normal tidal expiration (BHEX). The magnitude of motion was measured by recording the outline of the kidney from a Beam's Eye View (BEV). The centre of mass of this 2D shape was calculated for each set using "ImageJ" software and the magnitude of movement determined from the change in the centroid's coordinates between the BHIN and BHEX scans. The movement ranged from, for the left and right kidneys, 4-46mm and 2-44mm in the superior/inferior (axial) plane, 1-21mm and 2- 16mm in the anterior/posterior (coronal) plane, and 0-6mm and 0-8mm in the lateral/medial (sagittal) plane. From exhale to inhale, the kidneys tended to move inferiorly, anteriorly and laterally. A standard radiotherapy plan, designed to treat the para-aortics with opposed lateral fields was performed on the free breathing (planning) CT set. The field size and arrangement was set up using the same parameters for each subject. The prescription was to deliver 45 Gray in 25 fractions. This field arrangement and prescription was then copied over to the breath hold CT sets, and the dosimetric differences were compared using Dose Volume Histograms (DVH). The point of comparison for the three sets was recorded as the percentage volume of kidney receiving less than or equal to 10 Gray. The QUASAR respiratory motion phantom was used with the range of motion determined from the human study. The phantom was imaged, planned and treated with a linear accelerator with dose determined by film. The effect of the motion was measured by the change in the penumbra of the film and compared to the penumbra from the treatment planning system.

Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma : clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study

Background The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant pleural mesothelioma have, to our knowledge, not been assessed in a randomised trial. We aimed to assess the clinical outcomes of patients who were randomly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical Surgery (MARS) feasibility study. Methods MARS was a multicentre randomised controlled trial in 12 UK hospitals. Patients aged 18 years or older who had pathologically confirmed mesothelioma and were deemed fit enough to undergo trimodal therapy were included. In a prerandomisation registration phase, all patients underwent induction platinum-based chemotherapy followed by clinical review. After further consent, patients were randomly assigned (1:1) to EPP followed by postoperative hemithorax irradiation or to no EPP. Randomisation was done centrally with computer-generated permuted blocks stratified by surgical centre. The main endpoints were feasibility of randomly assigning 50 patients in 1 year (results detailed in another report), proportion randomised who received treatment, proportion eligible (registered) who proceeded to randomisation, perioperative mortality, and quality of life. Patients and investigators were not masked to treatment allocation. This is the principal report of the MARS study; all patients have been recruited. Analyses were by intention to treat. This trial is registered, number ISRCTN95583524. Findings Between Oct 1, 2005, and Nov 3, 2008, 112 patients were registered and 50 were subsequently randomly assigned: 24 to EPP and 26 to no EPP. The main reasons for not proceeding to randomisation were disease progression (33 patients), inoperability (five patients), and patient choice (19 patients). EPP was completed satisfactorily in 16 of 24 patients assigned to EPP; in five patients EPP was not started and in three patients it was abandoned. Two patients in the EPP group died within 30 days and a further patient died without leaving hospital. One patient in the no EPP group died perioperatively after receiving EPP off trial in a non-MARS centre. The hazard ratio [HR] for overall survival between the EPP and no EPP groups was 1·90 (95% CI 0·92-3·93; exact p=0·082), and after adjustment for sex, histological subtype, stage, and age at randomisation the HR was 2·75 (1·21-6·26; p=0·016). Median survival was 14·4 months (5·3-18·7) for the EPP group and 19·5 months (13·4 to time not yet reached) for the no EPP group. Of the 49 randomly assigned patients who consented to quality of life assessment (EPP n=23; no EPP n=26), 12 patients in the EPP group and 19 in the no EPP group completed the quality of life questionnaires. Although median quality of life scores were lower in the EPP group than the no EPP group, no significant differences between groups were reported in the quality of life analyses. There were ten serious adverse events reported in the EPP group and two in the no EPP group. Interpretation In view of the high morbidity associated with EPP in this trial and in other non-randomised studies a larger study is not feasible. These data, although limited, suggest that radical surgery in the form of EPP within trimodal therapy offers no benefit and possibly harms patients. Funding Cancer Research UK (CRUK/04/003), the June Hancock Mesothelioma Research Fund, and Guy's and St Thomas' NHS Foundation Trust. © 2011 Elsevier Ltd.

Exploring schema-driven differences in situation awareness between road users : an on-road study of driver, cyclist and motorcyclist situation awareness

Collisions between different road users make a substantial contribution to road trauma. Although evidence suggests that different road users interpret the same road situations differently, it is not clear how road users' situation awareness differs, nor is it clear which differences might lead to conflicts. This article presents the findings from an on-road study conducted to examine driver, motorcyclist and cyclist situation awareness in different road environments. The findings suggest that, in addition to minor differences in the structure of different road users' situation awareness (i.e. amount of information and how it is integrated), the actual content of situation awareness in terms of road user schemata, the resulting interaction with the world and the information underpinning situation awareness is markedly different. Further examination indicates that the differences are likely to be compatible along arterial roads, shopping strips and at roundabouts, but that they may create conflicts between different road users at intersections. Interventions designed to support compatible situation awareness and behaviour between different road users are discussed. Practitioner Summary: Incompatible situation awareness plays a key role in collisions between different road users (e.g. drivers and motorcyclists). This on-road study examined situation awareness in drivers, motorcyclists and cyclists, identifying the key differences and potential conflicts that arise. The findings are used to propose interventions designed to enhance the compatibility of situation awareness between road users.