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A large alkaptonuria (AKU) cohort was studied to better characterise the poorly understood phenotype of aortic stenosis of rare disease AKU.Eighty-one patients attended the National Alkaptonuria Centre (NAC) between 2007 and 2020. Nine only attended once. Fifty-one attended more than once and received nitisinone 2 mg daily. Twenty-one attended at least twice without receiving nitisinone. Assessments included questionnaire analysis, standard transthoracic echocardiography, as well as photographs of ochronotic pigment in eyes and ears at baseline when 2 mg nitisinone was commenced, and yearly thereafter. Blood and urine samples were collected for chemical measurement. The prevalence of aortic stenosis and aortic valve replacement were 22.2 and 6.2% in the current group. Aortic maximum velocity (Vmax) was directly related to varying degrees to age (R = 0.58, p 0.001), systolic blood pressure (R = 0.32, p 0.05), serum homogentisic acid (sHGA) (R = 0.28, p 0.05), ochronosis scores (R = 0.72, p 0.001), and alkaptonuria severity score index (AKUSSI) (R = 0.58, p 0.001) on linear regression analysis. Age and ochronosis scores were significantly related to Vmax on multiple regression analysis (p 0.005). Nitisinone decreased sHGA, 24-h urine HGA (uHGAAortic valve disease is highly prevalent in this NAC cohort, and strongly associated with ochronosis and disease severity. Nitisinone decreases ochronosis and had a similar significant effect on Vmax.

BACKGROUND Hepatosteatosis (HS) has been associated with cardiovascular disorders in the general population. We sought to investigate whether HS is a marker of cardiovascular disease (CVD) risk in HIV-positive individuals, given that metabolic syndrome is implicated in the increasing CVD burden in this population. AIMS To investigate the association of HS with CVD in HIV-positive and HIV-negative individuals. METHODS AND RESULTS We analyzed computed tomography (CT) images of 1306 subjects of whom 209 (16%) were HIV-positive and 1097 (84%) HIV-negative. CVD was quantified by the presence of coronary calcification from both dedicated cardiac CT and nondedicated thorax CT. HS was diagnosed from CT data sets in those with noncontrast dedicated cardiac CT and those with venous phase liver CT using previously validated techniques. Previous liver ultrasound was also assessed for the presence of HS. The HIV-positive group had lower mean age (P < 0.005), higher proportions of male sex (P < 0.005), and more current smokers (P < 0.005). The HIV-negative group had higher proportions of hypertension (P < 0.005), type II diabetes (P = 0.032), dyslipidemia (P < 0.005), statin use (P = 0.008), and HS (P = 0.018). The prevalence of coronary calcification was not significantly different between the groups. Logistic regression (LR) demonstrated that in the HIV-positive group, increasing age [odds ratio (OR): 1.15, P < 0.005], male sex (OR 3.37, P = 0.022), and HS (OR 3.13, P = 0.005) were independently associated with CVD. In the HIV-negative group, increasing age (OR: 1.11, P < 0.005), male sex (OR 2.97, P < 0.005), current smoking (OR 1.96, P < 0.005), and dyslipidemia (OR 1.66, P = 0.03) were independently associated with CVD. Using a machine learning random forest algorithm to assess the variables of importance, the top 3 variables of importance in the HIV-positive group were age, HS, and male sex. In the HIV-negative group, the top 3 variables were age, hypertension and male sex. The LR models predicted CVD well, with the mean area under the receiver operator curve (AUC) for the HIV-positive and HIV-negative cohorts being 0.831 [95% confidence interval (CI): 0.713 to 0.928] and 0.786 (95% CI: 0.735 to 0.836), respectively. The random forest models outperformed LR models, with a mean AUC in HIV-positive and HIV-negative populations of 0.877 (95% CI: 0.775 to 0.959) and 0.828 (95% CI: 0.780 to 0.873) respectively, with differences between both methods being statistically significant. CONCLUSION In contrast to the general population, HS is a strong and independent predictor of CVD in HIV-positive individuals. This suggests that metabolic dysfunction may be attributable to the excess CVD risk seen with these patient groups. Assessment of HS may help accurate quantification of CVD risk in HIV-positive patients.

Funding Acknowledgements Type of funding sources: None. onbehalf Liverpool Multiparametric Imaging Collaboration Background Coronary artery calcium (CAC) score is a well-established technique for stratifying an individual’s cardiovascular disease (CVD) risk. Several well-established registries have incorporated CAC scoring into CVD risk prediction models to enhance accuracy. Hepatosteatosis (HS) has been shown to be an independent predictor of CVD events and can be measured on non-contrast computed tomography (CT). We sought to undertake a contemporary, comprehensive assessment of the influence of HS on CAC score alongside traditional CVD risk factors. In patients with HS it may be beneficial to offer routine CAC screening to evaluate CVD risk to enhance opportunities for earlier primary prevention strategies. Methods We performed a retrospective, observational analysis at a high-volume cardiac CT centre analysing consecutive CT coronary angiography (CTCA) studies. All patients referred for investigation of chest pain over a 28-month period (June 2014 to November 2016) were included. Patients with established CVD were excluded. The cardiac findings were reported by a cardiologist and retrospectively analysed by two independent radiologists for the presence of HS. Those with CAC of zero and those with CAC greater than zero were compared for demographic and cardiac risks. A multivariate analysis comparing the risk factors was performed to adjust for the presence of established risk factors. A binomial logistic regression model was developed to assess the association between the presence of HS and increasing strata of CAC. Results In total there were 1499 patients referred for CTCA without prior evidence of CVD. The assessment of HS was completed in 1195 (79.7%) and CAC score was performed in 1103 (92.3%). There were 466 with CVD and 637 without CVD. The prevalence of HS was significantly higher in those with CVD versus those without CVD on CTCA (51.3% versus 39.9%, p = 0.007). Male sex (50.7% versus 36.1% p= HS was associated with increasing strata of CAC score compared with CAC of zero (CAC score 1-100 OR1.47, p = 0.01, CAC score 101-400 OR:1.68, p = 0.02, CAC score >400 OR 1.42, p = 0.14). This association became non-significant in the highest strata of CAC score. Conclusion We found a significant association between the increasing age, male sex, diabetes and HS with the presence of CAC. HS was also associated with a more severe phenotype of CVD based on the multinomial logistic regression model. Although the association reduced for the highest strata of CAC (CAC score >400) this likely reflects the overall low numbers of patients within this group and is likely a type II error. Based on these findings it may be appropriate to offer routine CVD risk stratification techniques in all those diagnosed with HS.

Background: Most chronic diseases are strongly associated with four modifiable behaviours: smoking, alcohol consumption, low fruit and vegetable consumption and physical inactivity. When established early in life, these lifestyle factors could persist in adulthood and predict the incidence of chronic diseases. Little is known about how these behaviours cluster together, and what factors are associated with their prevalence and clustering in individuals. The objective of this study was to ascertain the association between sociodemographic and personal factors and clustering of multiple health-risk behaviours in young people in the city of Brighton and Hove (population, 274,000) in Southeast England. Methods: Data from the Brighton and Hove Safe and Well at School Surveys (2011-2014) were analysed to examine the clustering of these behaviours in Year 10 and 11 pupils (n=10,099; aged 14-16 year). The results were weighted and studied in the context of sociodemographic/personal characteristics: gender, ethnicity, sexual orientation, deprivation, school year, feeling safe at school, enjoying school, been bullied at school, health problems, family problems, feeling happy, feeling anxious and feeling lonely. Results: The majority (97%) of pupils were engaged in either one or more unhealthy behaviours: about 58% were engaged in 1-2 and 39% were engaged in 3-4 unhealthy behaviours, respectively. Multiple regression analysis showed that a number of factors were significantly associated with the clustering of 3-4 health-risk behaviours in young people. These included: being in Year 11 (OR=2.0, 95% CI, 1.8-2.2), family problems (1.8, 1.6-2.0), being female (1.7, 1.5-1.9), not enjoying school (1.6, 1.4-1.8), and rarely/never feeling happy (1.3, 1.0-1.6). Conclusions: These findings highlight the need for modifications in community-based and in-school health and wellbeing programmes to decrease the prevalence and clustering of multiple health-risk behaviours in young people. Main messages: There is a need for effective programmes for young people to increase their awareness about health impacts of smoking and alcohol consumption, and beneficial effects of healthy diet and exercise. The study also highlights areas which require particular considerations while designing these programmes for young people.

An experimental and theoretical analysis of multiple-quantum (MQ)-like artifacts in 2D NMR spectra of water is presented and discussed. During the t 1 domain, either magnetic field gradients or Q -switching techniques, were used to minimize radiation damping effects. Nevertheless, a myriad of MQ artifacts, in excess of Δm = ± 20, were observed in the indirectly detected t 1 domain. The source of these MQ-like artifacts has been traced, rather surprisingly, to radiation damping in the t 2 domain. This conclusion was reached experimentally, using Q -switching experiments in both the t 1 and t 2 domains, and confirmed theoretically, using a modification of the radiation damping theory of Vlassenbroek et al., J. Chem. Phys. 103 (1995) 5886.

Recently, Warren and co-workers have shown that double quantum, gradient selective, 2D NMR experiments can give rise to apparently unreconcilable double quantum signals and intermolecular cross peaks. These experiments have been used to challenge the basic assumptions of room temperature NMR. We re-examine the gradient-induced multiple spin echo explanation, first discussed by Warren. It is shown that simple analytical explanations can be provided for (i) double quantum peaks, (ii) cross correlation peaks, (iii) the amplitudes of the observed cross peaks, and (iv) the disappearance of the cross peaks when the solvent and solute are placed in different tubes.

Transient magnetic fields were measured for W, Os and Pt ions traversing iron hosts with average velocities in the range from approximately 1.6v0 to 4.8v0 (v0=c/137, Bohr velocity). Transient fields for W and Os in Fe are consistent with behaviour found for lighter rare-earth ions and are about 20% stronger than those for Pt in Fe over the majority of the velocity range examined. A measurement was made to confirm that possible heavy-ion beam induced attenuations of the transient field are negligible for low-velocity Pt ions excited by Ni beams. Results are discussed in terms of both empirical and model-based parameterizations of the transient field strength.