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.

Correlation of carotid atheromatous plaque inflammation with biomechanical stress: Utility of USPIO enhanced MR imaging and finite element analysis

Objective: The aim of this study was to explore whether there is a relationship between the degree of MR-defined inflammation using ultra small super-paramagnetic iron oxide (USPIO) particles, and biomechanical stress using finite element analysis (FEA) techniques, in carotid atheromatous plaques. Methods and Results: 18 patients with angiographically proven carotid stenoses underwent multi-sequence MR imaging before and 36 h after USPIO infusion. T2 * weighted images were manually segmented into quadrants and the signal change in each quadrant normalised to adjacent muscle was calculated after USPIO administration. Plaque geometry was obtained from the rest of the multi-sequence dataset and used within a FEA model to predict maximal stress concentration within each slice. Subsequently, a new statistical model was developed to explicitly investigate the form of the relationship between biomechanical stress and signal change. The Spearman's rank correlation coefficient for USPIO enhanced signal change and maximal biomechanical stress was -0.60 (p = 0.009). Conclusions: There is an association between biomechanical stress and USPIO enhanced MR-defined inflammation within carotid atheroma, both known risk factors for plaque vulnerability. This underlines the complex interaction between physiological processes and biomechanical mechanisms in the development of carotid atheroma. However, this is preliminary data that will need validation in a larger cohort of patients.

Structural analysis and magnetic resonance imaging predict plaque vulnerability: A study comparing symptomatic and asymptomatic individuals

Background: More than half of all cerebral ischemic events are the result of rupture of extracranial plaques. The clinical determination of carotid plaque vulnerability is currently based solely on luminal stenosis; however, it has been increasingly suggested that plaque morphology and biomechanical stress should also be considered. We used finite element analysis based on in vivo magnetic resonance imaging (MRI) to simulate the stress distributions within plaques of asymptomatic and symptomatic individuals. Methods: Thirty nonconsecutive subjects (15 symptomatic and 15 asymptomatic) underwent high-resolution multisequence in vivo MRI of the carotid bifurcation. Stress analysis was performed based on the geometry derived from in vivo MRI of the carotid artery at the point of maximal stenosis. The finite element analysis model considered plaque components to be hyperelastic. The peak stresses within the plaques of symptomatic and asymptomatic individuals were compared. Results: High stress concentrations were found at the shoulder regions of symptomatic plaques, and the maximal stresses predicted in this group were significantly higher than those in the asymptomatic group (508.2 ± 193.1 vs 269.6 ± 107.9 kPa; P = .004). Conclusions: Maximal predicted plaque stresses in symptomatic patients were higher than those predicted in asymptomatic patients by finite element analysis, suggesting the possibility that plaques with higher stresses may be more prone to be symptomatic and rupture. If further validated by large-scale longitudinal studies, biomechanical stress analysis based on high resolution in vivo MRI could potentially act as a useful tool for risk assessment of carotid atheroma. It may help in the identification of patients with asymptomatic carotid atheroma at greatest risk of developing symptoms or mild-to-moderate symptomatic stenoses, which currently fall outside current clinical guidelines for intervention.

Survival, growth and quality of life in children after orthotopic liver transplantation: A 5 year experience

The aims of this study were to investigate outcome and to evaluate areas of potential ongoing concern after orthotopic liver transplantation (OLT) in children. Actuarial survival in relation to age and degree of undernutrition at the time of OLT was evaluated in 53 children (age 0.58-14.2 years) undergoing OLT for endstage liver disease. Follow-up studies of growth and quality of life were undertaken in those with a minimum follow-up period of 12 months (n = 26). The overall 3 year actuarial survival was 70%. Survival rates did not differ between age groups (actuarial 2 year survival for ages <1, 1-5 and >5 years were 70, 70 and 69% respectively) but did differ according to nutritional status at OLT (actuarial 2 year survival for children with Z scores for weight <-1 was 57%, >-1 was 95%; P = 0.004). Significant catch-up weight gain was observed by 18 months post-transplant, while height improved less rapidly. Quality of life (assessed by Vineland Adaptive Behaviour Scales incorporating socialization, daily living skills, communication and motor skills) was good (mean composite score 91 ± 19). All school-aged children except one were attending normal school. Two children had mild to moderate intellectual handicap related to post-operative intracerebral complications. Satisfactory long-term survival can be achieved after OLT in children regardless of age but the importance of pre-operative nutrition is emphasized. Survivors have an excellent chance of a good quality of life and of satisfactory catch-up weight gain and growth.

Sampling accuracy of reef resource inventory technique

A new technique called the reef resource inventory (RRI) was developed to map the distribution and abundance of benthos and substratum on reefs. The rapid field sampling technique uses divers to visually estimate the percentage cover of categories of benthos and substratum along 2x20 in plotless strip-transects positioned randomly over the tops, and systematically along the edge of reefs. The purpose of this study was to compare the relative sampling accuracy of the RRI against the line intercept transect technique (LIT), an international standard for sampling reef benthos and substratum. Analysis of paired sampling with LIT and RRI at 51 sites indicated sampling accuracy was not different (P > 0.05) for 8 of the 12 benthos and substratum categories used in the study. Significant differences were attributed to small-scale patchiness and cryptic coloration of some benthos; effects associated with sampling a sparsely distributed animal along a line versus an area; difficulties in discriminating some of the benthos and substratum categories; and differences due to visual acuity since LIT measurements were taken by divers close to the seabed whereas RRI measurements were taken by divers higher in the water column. The relative cost efficiency of the RRI technique was at least three times that of LIT for all benthos and substratum categories and as much as 10 times higher for two categories. These results suggest that the RRI can be used to obtain reliable and accurate estimates of relative abundance of broad categories of reef benthos and substratum.

Impaired physical function associated with childhood obesity: How should we intervene?

- Background This study examined relationships between adiposity, physical functioning and physical activity. - Methods Obese (N=107) and healthy-weight (N=132) children aged 10-13 years underwent assessments of percent body fat (%BF, dual energy X-ray absorptiometry), knee extensor strength (KE, isokinetic dynamometry), cardiorespiratory fitness (CRF, peak oxygen uptake by cycle ergometry), physical health-related quality of life (HRQOL), worst pain intensity and walking capacity [six-minute walk (6MWT)]. Structural equation modelling was used to assess relationships between variables. - Results Moderate relationships were observed between %BF and 6MWT, KE strength corrected for mass and CRF relative to mass (r -.36 to -.69, P≤.007). Weak relationships were found between: %BF and physical HRQOL (r -.27, P=.008); CRF relative to mass and physical HRQOL (r -.24, P=.003); physical activity and 6MWT (r .17, P=.004). Squared multiple correlations showed that 29.6% variance in physical HRQOL was explained by %BF, pain and CRF relative to mass, while 28% variance in 6MWT was explained by %BF and physical activity. - Conclusions It appears that children with a higher body fat percentage have poorer KE strength, CRF and overall physical functioning. Reducing percent fat appears to be the best target to improve functioning. However, a combined approach to intervention, targeting reductions in body fat percentage, pain and improvements in physical activity and CRF may assist physical functioning.

Getting mad may not mean getting even: The influence of drivers' ethical ideologies on driving anger and related behaviour

The current study explored the influence of moral values (measured by ethical ideology) on self-reported driving anger and aggressive driving responses. A convenience sample of drivers aged 17-73 years (n = 280) in Queensland, Australia, completed a self-report survey. Measures included sensation seeking, trait aggression, driving anger, endorsement of aggressive driving responses and ethical ideology (Ethical Position Questionnaire, EPQ). Scores on the two underlying dimensions of the EPQ idealism (highI/lowI) and relativism (highR/lowR) were used to categorise drivers into four ideological groups: Situationists (highI/highR); Absolutists (highI/lowR); Subjectivists (lowI/highR); and Exceptionists (lowI/lowR). Mean aggressive driving scores suggested that exceptionists were significantly more likely to endorse aggressive responses. After accounting for demographic variables, sensation seeking and driving anger, ethical ideological category added significantly, though modestly to the prediction of aggressive driving responses. Patterns in results suggest that those drivers in ideological groups characterised by greater concern to avoid affecting others negatively (i.e. highI, Situationists, Absolutists) may be less likely to endorse aggressive driving responses, even when angry. In contrast, Subjectivists (lowI, HighR), reported the lowest levels of driving anger yet were significantly more likely to endorse aggressive responses. This provides further insight into why high levels of driving anger may not always translate into more aggressive driving.

Higher intensity exercise helps cancer survivors remain motivated

Purpose The aim of the present study was to determine if exercise intensity impacts upon the psychosocial responses of breast and prostate cancer survivors to a rehabilitation program. Methods Eighty-seven prostate and 72 breast cancer survivors participated in an 8-week exercise and supportive group psychotherapy intervention (n=84) or control (n=75) group. Intervention participants were randomized to low-to-moderate intensity exercise (LIG; n=44; 60–65 % VO2peak, 50–65 % one repetition maximum (1RM)) or moderate-to-high intensity exercise (HIG; n=40; 75–80 % VO2peak, 65–80 % 1RM) while controls continued usual care. Before and after the 8 weeks, all participants completed the Functional Assessment of Cancer Therapy-Breast or -Prostate to assess quality of life (QOL) and Behavioural Regulations of Exercise Version 2 for exercise motivation. Intervention participants also completed a follow-up assessment 4 months post-intervention. Results All three groups improved in QOL from baseline to post-intervention, with no significant differences. From postintervention to follow-up, the LIG and HIG similarly maintained QOL scores. Between baseline and post-intervention, both intervention arms improved their motivation to exercise compared to the controls (p=0.004). At the 4-month followup, the HIG had maintained their overall exercise motivation (p<0.001) and both domains of intrinsic motivation (identified regulation, p=0.047; intrinsic regulation, p=0.007); however, the LIG had regressed. Conclusions The structured intervention was successful at improving autonomous exercise motivation, regardless of exercise intensity. However, only those participants who had exercised at a higher intensity sustained their improvement. Intervention participation did not improve QOL more than controls. Implications for Cancer Survivors Higher-intensity exercise is more likely to result in more sustainable increases in motivation to exercise among cancer survivors.

The acceptability, usability and short-term outcomes of Get Real: A web-based program for psychotic-like experiences (PLEs)

Background Psychotic-like experiences (PLEs) are subclinical delusional ideas and perceptual disturbances that have been associated with a range of adverse mental health outcomes. This study reports a qualitative and quantitative analysis of the acceptability, usability and short term outcomes of Get Real, a web program for PLEs in young people. Methods Participants were twelve respondents to an online survey, who reported at least one PLE in the previous 3 months, and were currently distressed. Ratings of the program were collected after participants trialled it for a month. Individual semi-structured interviews then elicited qualitative feedback, which was analyzed using Consensual Qualitative Research (CQR) methodology. PLEs and distress were reassessed at 3 months post-baseline. Results User ratings supported the program's acceptability, usability and perceived utility. Significant reductions in the number, frequency and severity of PLE-related distress were found at 3 months follow-up. The CQR analysis identified four qualitative domains: initial and current understandings of PLEs, responses to the program, and context of its use. Initial understanding involved emotional reactions, avoidance or minimization, limited coping skills and non-psychotic attributions. After using the program, participants saw PLEs as normal and common, had greater self-awareness and understanding of stress, and reported increased capacity to cope and accept experiences. Positive responses to the program focused on its normalization of PLEs, usefulness of its strategies, self-monitoring of mood, and information putting PLEs into perspective. Some respondents wanted more specific and individualized information, thought the program would be more useful for other audiences, or doubted its effectiveness. The program was mostly used in low-stress situations. Conclusions The current study provided initial support for the acceptability, utility and positive short-term outcomes of Get Real. The program now requires efficacy testing in randomized controlled trials.

Automatic ICD-10 classification of cancers from free-text death certificates

Objective Death certificates provide an invaluable source for cancer mortality statistics; however, this value can only be realised if accurate, quantitative data can be extracted from certificates – an aim hampered by both the volume and variable nature of certificates written in natural language. This paper proposes an automatic classification system for identifying cancer related causes of death from death certificates. Methods Detailed features, including terms, n-grams and SNOMED CT concepts were extracted from a collection of 447,336 death certificates. These features were used to train Support Vector Machine classifiers (one classifier for each cancer type). The classifiers were deployed in a cascaded architecture: the first level identified the presence of cancer (i.e., binary cancer/nocancer) and the second level identified the type of cancer (according to the ICD-10 classification system). A held-out test set was used to evaluate the effectiveness of the classifiers according to precision, recall and F-measure. In addition, detailed feature analysis was performed to reveal the characteristics of a successful cancer classification model. Results The system was highly effective at identifying cancer as the underlying cause of death (F-measure 0.94). The system was also effective at determining the type of cancer for common cancers (F-measure 0.7). Rare cancers, for which there was little training data, were difficult to classify accurately (F-measure 0.12). Factors influencing performance were the amount of training data and certain ambiguous cancers (e.g., those in the stomach region). The feature analysis revealed a combination of features were important for cancer type classification, with SNOMED CT concept and oncology specific morphology features proving the most valuable. Conclusion The system proposed in this study provides automatic identification and characterisation of cancers from large collections of free-text death certificates. This allows organisations such as Cancer Registries to monitor and report on cancer mortality in a timely and accurate manner. In addition, the methods and findings are generally applicable beyond cancer classification and to other sources of medical text besides death certificates.

Anticipating Chinese Tourists Arrivals in Australia: A Time Series Analysis

Given the growing importance of the Chinese tourist market to Australia, an understanding of Chinese tourists' arrival patterns is essential to accurate forecasting of future arrivals. Drawing on 25 years of records (1991-2015), this study developed a time-series model of monthly arrivals of Chinese tourists in Australia. The model reflects the exponentially increasing trend and strong seasonality of arrivals. Excellent results from validation of the model's forecasts endorsed this time-series model's potential in the policy prescription and management practice of Australian tourism industries.

Models of care in geriatric oncology nursing

Objectives To review models of care for older adults with cancer, with a focus on the role of the oncology nurse in geriatric oncology care. International exemplars of geriatric oncology nursing care are discussed. Data source Published peer reviewed literature, web-based resources, professional society materials, and the authors' experience. Conclusion Nursing care for older patients with cancer is complex and requires integrating knowledge from multiple disciplines that blends the sciences of geriatrics, oncology, and nursing. and which recognizes the dimensions of quality of life. Implications for Nursing Practice: Oncology nurses can benefit from learning key skills of comprehensive geriatric screening and assessment to improve the care they provide for older adults with cancer.

Solutions for archiving data in long-term studies: A reply to Whitlock et al.

In our recent paper [1], we discussed some potential undesirable consequences of public data archiving (PDA) with specific reference to long-term studies and proposed solutions to manage these issues. We reaffirm our commitment to data sharing and collaboration, both of which have been common and fruitful practices supported for many decades by researchers involved in long-term studies. We acknowledge the potential benefits of PDA (e.g., [2]), but believe that several potential negative consequences for science have been underestimated [1] (see also 3 and 4). The objective of our recent paper [1] was to define practices to simultaneously maximize the benefits and minimize the potential unwanted consequences of PDA.

Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants

OBJECTIVE To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation. METHODS We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping. RESULTS We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p = 6.4 x 10(-28) for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p = 2.7 x 10(-20) for the CE score in MO). CONCLUSIONS Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype.

Functional evaluation of genetic variants associated with endometriosis near GREB1

STUDY QUESTION: Do DNA variants in the growth regulation by estrogen in breast cancer 1 (GREB1) region regulate endometrial GREB1 expression and increase the risk of developing endometriosis in women? SUMMARY ANSWER: We identified new single nucleotide polymorphisms (SNPs) with strong association with endometriosis at the GREB1 locus although we did not detect altered GREB1 expression in endometriosis patients with defined genotypes. WHAT IS ALREADY KNOWN: Genome-wide association studies have identified the GREB1 region on chromosome 2p25.1 for increasing endometriosis risk. The differential expression of GREB1 has also been reported by others in association with endometriosis disease phenotype. STUDY DESIGN, SIZE, DURATION: Fine mapping studies comprehensively evaluated SNPs within the GREB1 region in a large-scale data set (>2500 cases and >4000 controls). Publicly available bioinformatics tools were employed to functionally annotate SNPs showing the strongest association signal with endometriosis risk. Endometrial GREB1 mRNA and protein expression was studied with respect to phases of the menstrual cycle (n = 2-45 per cycle stage) and expression quantitative trait loci (eQTL) analysis for significant SNPs were undertaken for GREB1 [mRNA (n = 94) and protein (n = 44) in endometrium]. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants in this study are females who provided blood and/or endometrial tissue samples in a hospital setting. The key SNPs were genotyped using Sequenom MassARRAY. The functional roles and regulatory annotations for identified SNPs are predicted by various publicly available bioinformatics tools. Endometrial GREB1 expression work employed qRT-PCR, western blotting and immunohistochemistry studies. MAIN RESULTS AND THE ROLE OF CHANCE: Fine mapping results identified a number of SNPs showing stronger association (0.004 < P < 0.032) with endometriosis risk than the original GWAS SNP (rs13394619) (P = 0.034). Some of these SNPs were predicted to have functional roles, for example, interaction with transcription factor motifs. The haplotype (a combination of alleles) formed by the risk alleles from two common SNPs showed significant association (P = 0.026) with endometriosis and epistasis analysis showed no evidence for interaction between the two SNPs, suggesting an additive effect of SNPs on endometriosis risk. In normal human endometrium, GREB1 protein expression was altered depending on the cycle stage (significantly different in late proliferative versus late secretory, P < 0.05) and cell type (glandular epithelium, not stromal cells). However, GREB1 expression in endometriosis cases versus controls and eQTL analyses did not reveal any significant changes. LIMITATIONS, REASONS FOR CAUTION: In silico prediction tools are generally based on cell lines different to our tissue and disease of interest. Functional annotations drawn from these analyses should be considered with this limitation in mind. We identified cell-specific and hormone-specific changes in GREB1 protein expression. The lack of a significant difference observed following our GREB1 expression studies may be the result of moderate power on mixed cell populations in the endometrial tissue samples. WIDER IMPLICATIONS OF THE FINDINGS: This study further implicates the GREB1 region on chromosome 2p25.1 and the GREB1 gene with involvement in endometriosis risk. More detailed functional studies are required to determine the role of the novel GREB1 transcripts in endometriosis pathophysiology. STUDY FUNDING/COMPETING INTERESTS: Funding for this work was provided by NHMRC Project Grants APP1012245, APP1026033, APP1049472 and APP1046880. There are no competing interests.