Texture Analysis of Cardiovascular Magnetic Resonance Cine Images differentiates etiologies of left ventricular hypertrophy

BACKGROUND: Textural analysis (TA) shows promise as radiological biomarker. The use of native TA in the field of cardiology is unproven. We hypothesized that Cardiovascular Magnetic Resonance pre-contrast bSSFP cine images could be analysed using TA software; TA features would differentiate different aetiologies of disease causing increased myocardial wall thickness (left ventricular hypertrophy {LVH}) and indicate the severity of myocardial tissue abnormality. METHOD: A mid short axis pre-contrast cine frame of 216 cases (50 hypertrophic cardiomyopathy (predominantly LVOTO sub type) (HCM), 52 cardiac amyloid (predominantly AL sub-type) (CA), 68 aortic stenosis (AS), 15 hypertensive with LVH (HTN+LVH) and 31 healthy volunteers (HV)) underwent CMRTA using TexRAD (TexRAD Ltd, Cambridge, UK). Among HV, 16/ 31 were scanned twice to form a test-retest reproducibility cohort. CMRTA comprised a filtration-histogram technique to extract and quantify features using 6 parameters. RESULTS: Test-retest analysis in HV showed a medium filter (3mm) was the most reproducible (intra-class correlation of 0.9 for kurtosis and skewness and 0.8 for mean and SD). Disease cohorts were statistically different (p<0.001) to health for all parameters. Pair wise comparisons of CMRTA parameters showed kurtosis and skewness consistently significant in ranking degree of difference from HV (greatest to least); CA, HCM, LVH+HTN, AS (p<0.001). Similarly mean, SD, entropy and mean positive pixel (MPP) were consistent in ranking degree of difference from HV; HCM, CA, AS and HTN+LVH. CONCLUSION: Radiomic features of bSSFP CMR data sets, derived using TA, show promise in discriminating between aetiologies of LVH

Opicapone in UK clinical practice: effectiveness, safety and cost analysis in patients with Parkinson's disease.

Aim: This subanalysis of the OPTIPARK study aimed to confirm the effectiveness and safety of opicapone in patients with Parkinson's disease and motor fluctuations in clinical practice specifically in the UK and to assess the impact of opicapone on treatment costs. Methods: Patients received opicapone added to levodopa for 6 months. Clinical outcomes were assessed at 3 and 6 months and treatment costs at 6 months. Results: Most patients' general condition improved at 3 months, with sustained improvements reported at 6 months. Opicapone improved motor and non-motor symptoms at both timepoints, was generally well tolerated and reduced total treatment costs by GBP 3719. Conclusion: Opicapone added to levodopa resulted in clinical improvements and reduced treatment costs across UK clinical practice

Reappraising myocardial fibrosis in severe aortic stenosis: an invasive and non-invasive study in 133 patients

Aims: To investigate myocardial fibrosis (MF) in a large series of severe aortic stenosis (AS) patients using invasive biopsy and non-invasive imaging. Methods and results: One hundred thirty-three patients with severe, symptomatic AS accepted for surgical aortic valve replacement underwent cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) and extracellular volume fraction (ECV) quantification. Intra-operative left ventricular (LV) biopsies were performed by needle or scalpel, yielding tissue with (n = 53) and without endocardium (n = 80), and compared with 10 controls. Myocardial fibrosis occurred in three patterns: (i) thickened endocardium with a fibrotic layer; (ii) microscopic scars, with a subendomyocardial predominance; and (iii) diffuse interstitial fibrosis. Collagen volume fraction (CVF) was elevated (P < 0.001) compared with controls, and higher (P < 0.001) in endocardium-containing samples with a decreasing CVF gradient from the subendocardium (P = 0.001). Late gadolinium enhancement correlated with CVF (P < 0.001) but not ECV. Both LGE and ECV correlated independently (P < 0.001) with N-terminal pro-brain natriuretic peptide and high-sensitivity-troponin T. High ECV was also associated with worse LV remodelling, left ventricular ejection fraction and functional capacity. Combining high ECV and LGE better identified patients with more adverse LV remodelling, blood biomarkers and histological parameters, and worse functional capacity than each parameter alone. Conclusion: Myocardial fibrosis in severe AS is complex, but three main patterns exist: endocardial fibrosis, microscars (mainly in the subendomyocardium), and diffuse interstitial fibrosis. Neither histological CVF nor the CMR parameters ECV and LGE capture fibrosis in its totality. A combined, multi-parametric approach with ECV and LGE allows best stratification of AS patients according to the response of the myocardial collagen matrix

Reverse Myocardial Remodeling Following Valve Replacement in Patients With Aortic Stenosis

BACKGROUND: Left ventricular (LV) hypertrophy, a key process in human cardiac disease, results from cellular (hypertrophy) and extracellular matrix expansion (interstitial fibrosis). OBJECTIVES: This study sought to investigate whether human myocardial interstitial fibrosis in aortic stenosis (AS) is plastic and can regress. METHODS: Patients with symptomatic, severe AS (n = 181; aortic valve area index 0.4 ± 0.1 cm2/m2) were assessed pre-aortic valve replacement (AVR) by echocardiography (AS severity, diastology), cardiovascular magnetic resonance (CMR) (for volumes, function, and focal or diffuse fibrosis), biomarkers (N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T), and the 6-min walk test. CMR was used to measure the extracellular volume fraction (ECV), thereby deriving matrix volume (LV mass × ECV) and cell volume (LV mass × [1 - ECV]). Biopsy excluded occult bystander disease. Assessment was repeated at 1 year post-AVR. RESULTS: At 1 year post-AVR in 116 pacemaker-free survivors (age 70 ± 10 years; 54% male), mean valve gradient had improved (48 ± 16 mm Hg to 12 ± 6 mm Hg; p < 0.001), and indexed LV mass had regressed by 19% (88 ± 26 g/m2to 71 ± 19 g/m2; p < 0.001). Focal fibrosis by CMR late gadolinium enhancement did not change, but ECV increased (28.2 ± 2.9% to 29.9 ± 4.0%; p < 0.001): this was the result of a 16% reduction in matrix volume (25 ± 9 ml/m2to 21 ± 7 ml/m2; p < 0.001) but a proportionally greater 22% reduction in cell volume (64 ± 18 ml/m2to 50 ± 13 ml/m2; p < 0.001). These changes were accompanied by improvement in diastolic function, N-terminal pro-B-type natriuretic peptide, 6-min walk test results, and New York Heart Association functional class. CONCLUSIONS: Post-AVR, focal fibrosis does not resolve, but diffuse fibrosis and myocardial cellular hypertrophy regress. Regression is accompanied by structural and functional improvements suggesting that human diffuse fibrosis is plastic, measurable by CMR and a potential therapeutic target. (Regression of Myocardial Fibrosis After Aortic Valve Replacement; NCT02174471)

Estimation of heterogeneity in malaria transmission by stochastic modelling of apparent deviations from mass action kinetics

<p>Abstract</p> <p>Background</p> <p>Quantifying heterogeneity in malaria transmission is a prerequisite for accurate predictive mathematical models, but the variance in field measurements of exposure overestimates true micro-heterogeneity because it is inflated to an uncertain extent by sampling variation. Descriptions of field data also suggest that the rate of <it>Plasmodium falciparum </it>infection is not proportional to the intensity of challenge by infectious vectors. This appears to violate the principle of mass action that is implied by malaria biology. Micro-heterogeneity may be the reason for this anomaly. It is proposed that the level of micro-heterogeneity can be estimated from statistical models that estimate the amount of variation in transmission most compatible with a mass-action model for the relationship of infection to exposure.</p> <p>Methods</p> <p>The relationship between the entomological inoculation rate (EIR) for falciparum malaria and infection risk was reanalysed using published data for cohorts of children in Saradidi (western Kenya). Infection risk was treated as binomially distributed, and measurement-error (Poisson and negative binomial) models were considered for the EIR. Models were fitted using Bayesian Markov chain Monte Carlo algorithms and model fit compared for models that assume either mass-action kinetics, facilitation, competition or saturation of the infection process with increasing EIR.</p> <p>Results</p> <p>The proportion of inocula that resulted in infection in Saradidi was inversely related to the measured intensity of challenge. Models of facilitation showed, therefore, a poor fit to the data. When sampling error in the EIR was neglected, either competition or saturation needed to be incorporated in the model in order to give a good fit. Negative binomial models for the error in exposure could achieve a comparable fit while incorporating the more parsimonious and biologically plausible mass action assumption. Models that assume negative binomial micro-heterogeneity predict lower incidence of infection at a given average exposure than do those assuming exposure to be uniform. The negative binomial model moreover provides an estimate of the variance of the within-cohort distribution of the EIR and hence of within cohort heterogeneity in exposure.</p> <p>Conclusion</p> <p>Apparent deviations from mass action kinetics in parasite transmission can arise from spatial and temporal heterogeneity in the inoculation rate, and from imprecision in its measurement. For parasites like <it>P. falciparum</it>, where there is no plausible biological rationale for deviations from mass action, this provides a strategy for estimating true levels of heterogeneity, since if mass-action is assumed, the within-population variance in exposure becomes identifiable in cohort studies relating infection to transmission intensity. Statistical analyses relating infection to exposure thus provide a valid general approach for estimating heterogeneity in transmission but only when they incorporate mass action kinetics and shrinkage estimates of exposure. Such analyses make it possible to include realistic levels of heterogeneity in dynamic models that predict the impact of control measures on transmission intensity.</p

Predictive validity of the CriSTAL tool for short-term mortality in older people presenting at Emergency Departments: a prospective study

© 2018, The Author(s). Abstract: To determine the validity of the Australian clinical prediction tool Criteria for Screening and Triaging to Appropriate aLternative care (CRISTAL) based on objective clinical criteria to accurately identify risk of death within 3 months of admission among older patients. Methods: Prospective study of ≥ 65 year-olds presenting at emergency departments in five Australian (Aus) and four Danish (DK) hospitals. Logistic regression analysis was used to model factors for death prediction; Sensitivity, specificity, area under the ROC curve and calibration with bootstrapping techniques were used to describe predictive accuracy. Results: 2493 patients, with median age 78–80 years (DK–Aus). The deceased had significantly higher mean CriSTAL with Australian mean of 8.1 (95% CI 7.7–8.6 vs. 5.8 95% CI 5.6–5.9) and Danish mean 7.1 (95% CI 6.6–7.5 vs. 5.5 95% CI 5.4–5.6). The model with Fried Frailty score was optimal for the Australian cohort but prediction with the Clinical Frailty Scale (CFS) was also good (AUROC 0.825 and 0.81, respectively). Values for the Danish cohort were AUROC 0.764 with Fried and 0.794 using CFS. The most significant independent predictors of short-term death in both cohorts were advanced malignancy, frailty, male gender and advanced age. CriSTAL’s accuracy was only modest for in-hospital death prediction in either setting. Conclusions: The modified CriSTAL tool (with CFS instead of Fried’s frailty instrument) has good discriminant power to improve prognostic certainty of short-term mortality for ED physicians in both health systems. This shows promise in enhancing clinician’s confidence in initiating earlier end-of-life discussions

Serum methylarginines and spirometry-measured lung function in older adults

Rationale: Methylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in animal models of lung disease but have not previously been examined for their association with spirometric measures of lung function in humans. Objectives: This study measured serum concentrations of asymmetric and symmetric dimethylarginine in a representative sample of older community-dwelling adults and determined their association with spirometric lung function measures. Methods: Data on clinical, lifestyle, and demographic characteristics, methylated arginines, and L-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults from the Hunter Community Study. The five key lung function measures included as outcomes were Forced Expiratory Volume in 1 second, Forced Vital Capacity, Forced Expiratory Volume in 1 second to Forced Vital Capacity ratio, Percent Predicted Forced Expiratory Volume in 1 second, and Percent Predicted Forced Vital Capacity. Measurements and Main Results: In adjusted analyses there were statistically significant independent associations between a) higher asymmetric dimethylarginine, lower Forced Expiratory Volume in 1 second and lower Forced Vital Capacity; and b) lower L-arginine/asymmetric dimethylarginine ratio, lower Forced Expiratory Volume in 1 second, lower Percent Predicted Forced Expiratory Volume in 1 second and lower Percent Predicted Forced Vital Capacity. By contrast, no significant associations were observed between symmetric dimethylarginine and lung function. Conclusions: After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum asymmetric dimethylarginine was independently associated with a reduction in key measures of lung function. Further research is needed to determine if methylarginines predict the decline in lung function

Microsatellites Reveal a High Population Structure in Triatoma infestans from Chuquisaca, Bolivia

Chagas disease is a protozoan infection caused by the parasite Trypanosoma cruzi. Chagas is prevalent throughout Central and South America, and it remains a chief concern in Bolivia. A movement that began in 1991 called the Southern Cone Initiative has been successful in reducing the incidence of Chagas disease in the Southern Cone countries of Argentina, Brazil, Chile, and Uruguay; but due to socio-economic and other factors, incidence remains high in Bolivia. The most important mode of transmission of T. cruzi to humans and other mammals is through feces of triatomine bugs. Thus, disease control and transmission prevention focus on elimination of triatomine vectors, and more specifically in Bolivia, it focuses on the elimination of Triatoma infestans. This study focuses on T. infestans in the Department of Chuquisaca, Bolivia. Ten highly variable microsatellite markers were used to analyze the population structure of insects collected in different towns. Statistical analyses show that T. infestans are highly structured, which means that they colonize on a small geographic scale. The results also suggest little active dispersal. These findings should be implemented during control efforts so that insecticide spraying focuses on geographic areas of colonization and re-colonization

Silicon-based spin and charge quantum computation

Silicon-based quantum-computer architectures have attracted attention because of their promise for scalability and their potential for synergetically utilizing the available resources associated with the existing Si technology infrastructure. Electronic and nuclear spins of shallow donors (e.g. phosphorus) in Si are ideal candidates for qubits in such proposals due to the relatively long spin coherence times. For these spin qubits, donor electron charge manipulation by external gates is a key ingredient for control and read-out of single-qubit operations, while shallow donor exchange gates are frequently invoked to perform two-qubit operations. More recently, charge qubits based on tunnel coupling in P$_2^+$ substitutional molecular ions in Si have also been proposed. We discuss the feasibility of the building blocks involved in shallow donor quantum computation in silicon, taking into account the peculiarities of silicon electronic structure, in particular the six degenerate states at the conduction band edge. We show that quantum interference among these states does not significantly affect operations involving a single donor, but leads to fast oscillations in electron exchange coupling and on tunnel-coupling strength when the donor pair relative position is changed on a lattice-parameter scale. These studies illustrate the considerable potential as well as the tremendous challenges posed by donor spin and charge as candidates for qubits in silicon.Comment: Review paper (invited) - to appear in Annals of the Brazilian Academy of Science