Characterisation of carotid atheroma in symptomatic and asymptomatic patients using high resolution MRI

Background and purpose: To prospectively evaluate differences in carotid plaque characteristics in symptomatic and asymptomatic patients using high resolution MRI. Methods: 20 symptomatic and 20 asymptomatic patients, with at least 50% carotid stenosis as determined by Doppler ultrasound, underwent preoperative in vivo multispectral MRI of the carotid arteries. Studies were analysed both qualitatively and quantitatively in a randomised manner by two experienced readers in consensus, blinded to clinical status, and plaques were classified according to the modified American Heart Association (AHA) criteria. Results: After exclusion of poor quality images, 109 MRI sections in 18 symptomatic and 19 asymptomatic patients were available for analysis. There were no significant differences in mean luminal stenosis severity (72.9% vs 67.6%; p = 0.09) or plaque burden (median plaque areas 50 mm2 vs 50 mm 2; p = 0.858) between the symptomatic and asymptomatic groups. However, symptomatic lesions had a higher incidence of ruptured fibrous caps (36.5% vs 8.7%; p = 0.004), haemorrhage or thrombus (46.5% vs 14.0%; p<0.001), large necrotic lipid cores (63.8% vs 28.0%; p = 0.002) and complicated type VI AHA lesions (61.5% vs 28.1%; p = 0.001) compared with asymptomatic lesions. The MRI findings of plaque haemorrhage or thrombus had an odds ratio of 5.25 (95% CI 2.08 to 13.24) while thin or ruptured fibrous cap (as opposed to a thick fibrous cap) had an odds ratio of 7.94 (95% CI 2.93 to 21.51) for prediction of symptomatic clinical status. Conclusions: There are significant differences in plaque characteristics between symptomatic and asymptomatic carotid atheroma and these can be detected in vivo by high resolution MRI.

In vivo non-invasive high resolution MR-based method for the determination of the elastic modulus of arterial vessels

The mechanical properties of arterial walls have long been recognized to play an essential role in the development and progression of cardiovascular disease (CVD). Early detection of variations in the elastic modulus of arteries would help in monitoring patients at high cardiovascular risk stratifying them according to risk. An in vivo, non-invasive, high resolution MR-phase-contrast based method for the estimation of the time-dependent elastic modulus of healthy arteries was developed, validated in vitro by means of a thin walled silicon rubber tube integrated into an existing MR-compatible flow simulator and used on healthy volunteers. A comparison of the elastic modulus of the silicon tube measured from the MRI-based technique with direct measurements confirmed the method's capability. The repeatability of the method was assessed. Viscoelastic and inertial effects characterizing the dynamic response of arteries in vivo emerged from the comparison of the pressure waveform and the area variation curve over a period. For all the volunteers who took part in the study the elastic modulus was found to be in the range 50-250 kPa, to increase during the rising part of the cycle, and to decrease with decreasing pressure during the downstroke of systole and subsequent diastole.

Identifying vulnerable carotid plaques in vivo using high resolution magnetic resonance imaging-based finite element analysis

Object. Individuals with carotid atherosclerosis develop symptoms following rupture of vulnerable plaques. Biomechanical stresses within this plaque may increase vulnerability to rupture. In this report the authors describe the use of in vivo carotid plaque imaging and computational mechanics to document the magnitude and distribution of intrinsic plaque stresses. Methods. Ten (five symptomatic and five asymptomatic) individuals underwent plaque characterization magnetic resonance (MR) imaging. Plaque geometry and composition were determined by multisequence review. Intrinsic plaque stress profiles were generated from 3D meshes by using finite element computational analysis. Differences in principal (shear) stress between normal and diseased sections of the carotid artery and between symptomatic and asymptomatic plaques were noted. Results. There was a significant difference in peak principal stress between diseased and nondiseased segments of the artery (mean difference 537.65 kPa, p < 0.05). Symptomatic plaques had higher mean stresses than asymptomatic plaques (627.6 kPa compared with 370.2 kPa, p = 0.05), which were independent of luminal stenosis and plaque composition. Conclusions. Significant differences in plaque stress exist between plaques from symptomatic individuals and those from asymptomatic individuals. The MR imaging-based computational analysis may therefore be a useful aid to identification of vulnerable plaques in vivo.

Assessment of inflammatory burden contralateral to the symptomatic carotid stenosis using high-resolution ultrasmall, superparamagnetic iron oxide-enhanced MRI

BACKGROUND AND PURPOSE It is well known that the vulnerable atheromatous plaque has a thin, fibrous cap and large lipid core with associated inflammation. This inflammation can be detected on MRI with use of a contrast medium, Sinerem, an ultrasmall superparamagnetic iron oxide (USPIO). Although the incidence of macrophage activity in asymptomatic disease appears low, we aimed to explore the incidence of MRI-defined inflammation in asymptomatic plaques in patients with known contralateral symptomatic disease. METHODS Twenty symptomatic patients underwent multisequence MRI before and 36 hours after USPIO infusion. Images were manually segmented into quadrants, and the signal change in each quadrant was calculated after USPIO administration. A mixed mathematical model was developed to compare the mean signal change across all quadrants in the 2 groups. Patients had a mean symptomatic stenosis of 77% compared with 46% on their asymptomatic side, as measured by conventional angiography. RESULTS There were 11 (55%) men, and the median age was 72 years (range, 53 to 84 years). All patients had risk factors consistent with severe atherosclerotic disease. All symptomatic carotid stenoses had inflammation, as evaluated by USPIO-enhanced imaging. On the contralateral sides, inflammatory activity was found in 19 (95%) patients. Contralaterally, there were 163 quadrants (57%) with a signal loss after USPIO when compared with 217 quadrants (71%) on the symptomatic side (P=0.007). CONCLUSIONS - This study adds weight to the argument that atherosclerosis is a truly systemic disease. It suggests that investigation of the contralateral side in patients with symptomatic carotid stenosis can demonstrate inflammation in 95% of plaques, despite a mean stenosis of only 46%. Thus, inflammatory activity may be a significant risk factor in asymptomatic disease in patients who have known contralateral symptomatic disease. Patients with symptomatic carotid disease should have their contralateral carotid artery followed up.

Validation of a 4DOF manoeuvring model of a high-speed vehicle-passenger trimaran

This paper presents the validation of a manoeuvring model for a novel 127m-vehicle-passenger trimaran via full scale trials. The adopted structure of the model is based on a model previously proposed in the literature with some simplifications. The structure of the model is discussed. Then initial parameter estimates are computed, and the final set of parameters are obtained via adjustments based on engineering judgement and application of a genetic algorithm so as to match the data of the trials. The validity of the model is also assessed with data from a trial different from the one use for the parameter adjustment. The model shows good agreement with the trial data.

Re-thinking teacher quality in high-poverty schools in Australia

As is the case globally, Australian schools that serve high-poverty communities most often employ the least experienced, least prepared teachers. Beginning with a discussion of poverty in Australia this chapter draws on 6 years of learnings from Australia's National Exceptional Teachers for Disadvantaged Schools (NETDS) program to examine how social justice can be taught within a mainstream Initial Teacher Education program in an increasingly neoliberal climate where teacher education curriculum around social justice struggles to find a place within the current discourses of quality teaching and its preoccupations with standards, accountability, and high-stakes testing.

Traffic and nucleation events as main sources of ultrafine particles in high-insolation developed world cities

Road traffic emissions are often considered the main source of ultrafine particles (UFP, diameter smaller than 100 nm) in urban environments. However, recent studies worldwide have shown that - in high-insolation urban regions at least - new particle formation events can also contribute to UFP. In order to quantify such events we systematically studied three cities located in predominantly sunny environments: Barcelona (Spain), Madrid (Spain) and Brisbane (Australia). Three long term datasets (1-2 years) of fine and ultrafine particle number size distributions (measured by SMPS, Scanning Mobility Particle Sizer) were analysed. Compared to total particle number concentrations, aerosol size distributions offer far more information on the type, origin and atmospheric evolution of the particles. By applying k-Means clustering analysis, we categorized the collected aerosol size distributions in three main categories: “Traffic” (prevailing 44-63% of the time), “Nucleation” (14-19%) and “Background pollution and Specific cases” (7-22%). Measurements from Rome (Italy) and Los Angeles (California) were also included to complement the study. The daily variation of the average UFP concentrations for a typical nucleation day at each site revealed a similar pattern for all cities, with three distinct particle bursts. A morning and an evening spike reflected traffic rush hours, whereas a third one at midday showed nucleation events. The photochemically nucleated particles burst lasted 1-4 hours, reaching sizes of 30-40 nm. On average, the occurrence of particle size spectra dominated by nucleation events was 16% of the time, showing the importance of this process as a source of UFP in urban environments exposed to high solar radiation. On average, nucleation events lasting for 2 hours or more occurred on 55% of the days, this extending to >4hrs in 28% of the days, demonstrating that atmospheric conditions in urban environments are not favourable to the growth of photochemically nucleated particles. In summary, although traffic remains the main source of UFP in urban areas, in developed countries with high insolation urban nucleation events are also a main source of UFP. If traffic-related particle concentrations are reduced in the future, nucleation events will likely increase in urban areas, due to the reduced urban condensation sinks.

Post-school needs of young people with high-functioning Autism Spectrum Disorder

This study describes the post-school circumstances and service needs of older teenagers and adults with high-functioning Autism Spectrum Disorder, living in Queensland, Australia. The respondents were 95 parents. Results indicated that the majority of the young people lived in the family home and were unemployed. Of those who worked, 56% had unskilled jobs. They were estimated to spend a significant proportion of their time engaged in solitary, technology-based activities, and comparatively little time in employment or socialising. Parents rated employment support as the greatest service priority for their sons and daughters, followed by specialised support to assist with completing post-school education and training, assistance to support the transition from high school to adulthood, and social skills training.

Enhancing skill acquisition and expertise in high performance programmes

Our research programme with elite athletes has investigated and implemented learning design from an ecological dynamics perspective, examining its effects on movement coordination and control and the acquisition of expertise. Ecological dynamics is a systemsoriented theoretical rationale for understanding the emergent relations in a complex system formed by each performer and a performance environment. This approach has identified the individual-environment relationship as the relevant scale of analysis for modelling how processes of perception, cognition and action underpin expert performance in sport (Davids et al., 2014; Zelaznik, 2014). In this chapter we elucidate key concepts from ecological dynamics and exemplify how they have informed our understanding of relevant psychological processes including: movement coordination and its acquisition, learning and transfer, impacting on practice task design in high performance programmes.

Algorithm of medication review in frail older people: Focus on minimizing the use of high-risk medications

Aim Frail older people typically suffer several chronic diseases, receive multiple medications and are more likely to be institutionalized in residential aged care facilities. In such patients, optimizing prescribing and avoiding use of high-risk medications might prevent adverse events. The present study aimed to develop a pragmatic, easily applied algorithm for medication review to help clinicians identify and discontinue potentially inappropriate high-risk medications. Methods The literature was searched for robust evidence of the association of adverse effects related to potentially inappropriate medications in older patients to identify high-risk medications. Prior research into the cessation of potentially inappropriate medications in older patients in different settings was synthesized into a four-step algorithm for incorporation into clinical assessment protocols for patients, particularly those in residential aged care facilities. Results The algorithm comprises several steps leading to individualized prescribing recommendations: (i) identify a high-risk medication; (ii) ascertain the current indications for the medication and assess their validity; (iii) assess if the drug is providing ongoing symptomatic benefit; and (iv) consider withdrawing, altering or continuing medications. Decision support resources were developed to complement the algorithm in ensuring a systematic and patient-centered approach to medication discontinuation. These include a comprehensive list of high-risk medications and the reasons for inappropriateness, lists of alternative treatments, and suggested medication withdrawal protocols. Conclusions The algorithm captures a range of different clinical scenarios in relation to potentially inappropriate medications, and offers an evidence-based approach to identifying and, if appropriate, discontinuing such medications. Studies are required to evaluate algorithm effects on prescribing decisions and patient outcomes.

Meta-analysis of telomere length in 19 713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect

Telomere length (TL) has been associated with aging and mortality, but individual differences are also influenced by genetic factors, with previous studies reporting heritability estimates ranging from 34 to 82%. Here we investigate the heritability, mode of inheritance and the influence of parental age at birth on TL in six large, independent cohort studies with a total of 19 713 participants. The meta-analysis estimate of TL heritability was 0.70 (95% CI 0.64–0.76) and is based on a pattern of results that is highly similar for twins and other family members. We observed a stronger mother–offspring (r=0.42; P-value=3.60 × 10−61) than father–offspring correlation (r=0.33; P-value=7.01 × 10−5), and a significant positive association with paternal age at offspring birth (β=0.005; P-value=7.01 × 10−5). Interestingly, a significant and quite substantial correlation in TL between spouses (r=0.25; P-value=2.82 × 10−30) was seen, which appeared stronger in older spouse pairs (mean age ≥55 years; r=0.31; P-value=4.27 × 10−23) than in younger pairs (mean age<55 years; r=0.20; P-value=3.24 × 10−10). In summary, we find a high and very consistent heritability estimate for TL, evidence for a maternal inheritance component and a positive association with paternal age.

High-density fine-mapping of a chromosome 10q26 linkage peak suggests association between endometriosis and variants close to CYP2C19

OBJECTIVE To refine a previously reported linkage peak for endometriosis on chromosome 10q26, and conduct follow-up analyses and a fine-mapping association study across the region to identify new candidate genes for endometriosis. DESIGN Case-control study. SETTING Academic research. PATIENT(S) Cases=3,223 women with surgically confirmed endometriosis; controls=1,190 women without endometriosis and 7,060 population samples. INTERVENTION(S) Analysis of 11,984 single nucleotide polymorphisms on chromosome 10. MAIN OUTCOME MEASURE(S) Allele frequency differences between cases and controls. RESULT(S) Linkage analyses on families grouped by endometriosis symptoms (primarily subfertility) provided increased evidence for linkage (logarithm of odds score=3.62) near a previously reported linkage peak. Three independent association signals were found at 96.59 Mb (rs11592737), 105.63 Mb (rs1253130), and 124.25 Mb (rs2250804). Analyses including only samples from linkage families supported the association at all three regions. However, only rs11592737 in the cytochrome P450 subfamily C (CYP2C19) gene was replicated in an independent sample of 2,079 cases and 7,060 population controls. CONCLUSION(S) The role of the CYP2C19 gene in conferring risk for endometriosis warrants further investigation.

A systematic literature review of alcohol education programmes in middle and high school settings (2000-2014)

Purpose Social marketing benchmark criteria were used to understand the extent to which single-substance alcohol education programmes targeting adolescents in middle and high school settings sought to change behaviour, utilised theory, included audience research and applied the market segmentation process. The paper aims to discuss these issues. Design/methodology/approach A systematic literature review retrieved a total of 1,495 identified articles; 565 duplicates were removed. The remaining 930 articles were then screened. Articles detailing formative research or programmes targeting multiple substances, parents, families and/or communities, as well as elementary schools and universities were excluded. A total of 31 articles, encompassing 16 qualifying programmes, were selected for detailed evaluation. Findings The majority of alcohol education programmes were developed on the basis of theory and achieved short- and medium-term behavioural effects. Importantly, most programmes were universal and did not apply the full market segmentation process. Limited audience research in the form of student involvement in programme design was identified. Research limitations/implications This systematic literature review focused on single-substance alcohol education programmes targeted at middle and high school student populations, retrieving studies back to the year 2000. Originality/value The results of this systematic literature review indicate that application of the social marketing benchmark criteria of market segmentation and audience research may represent an avenue for further extending alcohol education programme effectiveness in middle and high school settings.

A high-density association screen of 155 ion transport genes for involvement with common migraine

The clinical overlap between monogenic Familial Hemiplegic Migraine (FHM) and common migraine subtypes, and the fact that all three FHM genes are involved in the transport of ions, suggest that ion transport genes may underlie susceptibility to common forms of migraine. To test this leading hypothesis, we examined common variation in 155 ion transport genes using 5257 single nucleotide polymorphisms (SNPs) in a Finnish sample of 841 unrelated migraine with aura cases and 884 unrelated non-migraine controls. The top signals were then tested for replication in four independent migraine case-control samples from the Netherlands, Germany and Australia, totalling 2835 unrelated migraine cases and 2740 unrelated controls. SNPs within 12 genes (KCNB2, KCNQ3, CLIC5, ATP2C2, CACNA1E, CACNB2, KCNE2, KCNK12, KCNK2, KCNS3, SCN5A and SCN9A) with promising nominal association (0.00041 < P < 0.005) in the Finnish sample were selected for replication. Although no variant remained significant after adjusting for multiple testing nor produced consistent evidence for association across all cohorts, a significant epistatic interaction between KCNB2 SNP rs1431656 (chromosome 8q13.3) and CACNB2 SNP rs7076100 (chromosome 10p12.33) (pointwise P = 0.00002; global P = 0.02) was observed in the Finnish case-control sample. We conclude that common variants of moderate effect size in ion transport genes do not play a major role in susceptibility to common migraine within these European populations, although there is some evidence for epistatic interaction between potassium and calcium channel genes, KCNB2 and CACNB2. Multiple rare variants or trans-regulatory elements of these genes are not ruled out.

Increasing attractiveness of high-end products

An important decision brand managers have to make when positioning their products in a retail setting is to whether price new line extensions at parity or let products vary in the price/quality spectrum. Despite the growing interest in vertical line extension issues, there has been little research investigating how product-line length affects extension favorability. Therefore, this paper investigates the framing effect that a product line price structure has on consumer judgments of vertical extensions and, in particular, of upscale extensions. A basic proposition of this research is that the parent brand price range affects the perceived or psychological distance between extension and parent brand, influencing extension favorability ratings. In two experiments, it is shown that positioning an upscale extension in the context of a wide product-line will lead to higher consistency perceptions between the parent brand and a new upscale extension than an equivalent upscale extension positioned in the context of a narrow parent brand product-line.