Naresuan University Journal
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Simulations for single-dish intensity mapping experiments
No full textH I intensity mapping is an emerging tool to probe dark energy. Observations of the redshifted H I signal will be contaminated by instrumental noise, atmospheric and Galactic foregrounds. The latter is expected to be four orders of magnitude brighter than the H I emission we wish to detect. We present a simulation of single-dish observations including an instrumental noise model with 1/f and white noise, and sky emission with a diffuse Galactic foreground and H I emission. We consider two foreground cleaning methods: spectral parametric fitting and principal component analysis. For a smooth frequency spectrum of the foreground and instrumental effects, we find that the parametric fitting method provides residuals that are still contaminated by foreground and 1/f noise, but the principal component analysis can remove this contamination down to the thermal noise level. This method is robust for a range of different models of foreground and noise, and so constitutes a promising way to recover the H I signal from the data. However, it induces a leakage of the cosmological signal into the subtracted foreground of around 5 per cent. The efficiency of the component separation methods depends heavily on the smoothness of the frequency spectrum of the foreground and the 1/f noise. We find that as long as the spectral variations over the band are slow compared to the channel width, the foreground cleaning method still works
Towards more Realistic Clinical Trial Simulation: Establishing Inter-Correlations between Several Cytochrome P450 Enzyme Abundances in Human Liver
No full textObjectives: Success of clinical trial simulations greatly depends on identifying and incorporating true anatomical and physiological covariates when generating virtual populations. Recently, the inter-correlations between CYP450 (and UGT) metabolising enzymes in human liver microsomes have been reported [1, 2]. These data enable population-based PBPK models to more realistically assign CYP/UGT abundances when generating virtual subjects using Correlated Monte Carlo sampling. This work aims at using reported data in [1, 2] to determine CYP450 enzymes covariance matrix of multivariate probability distribution function and compare the distributions against the currently generated data in Simcyp Simulator version 14. Methods: The marginal distributions of each CYP450 are assumed to be log-normal and are checked by obtaining normal plots for the log transformed abundance value. The correlation and covariance matrices for the whole dataset have been calculated using R Package (v 3.1.2). Eigenvalues of the covariance matrix have been tested for positivity and if negative eigenvalues occurred, then the nearest positive definite covariance matrix has been calculated. A new correlated sample has been obtained by calculating the Cholesky decomposition [3] of the nearest positive definite covariance matrix and this sample has been transformed into its original log-normal marginal distribution. A virtual population matching the real population demographics has been generated using the Simcyp Simulator v 14 and the results were compared with Monte Carlo sampling data. Results: Multivariate Cramer-Test shows dissimilarity between the empirical distributions of the correlated and uncorrelated samples with 95% CI critical T-statistic of 141.565 vs observed: 9269.496. Kernel density estimate visually showed the differences between the two distributions. Conclusions: Incorporation of the correlated CYP450 enzyme abundances when generating virtual subjects enables PBPK simulators to generate more realistic virtual population which can improve clinical study design and prediction of clinical outcome during drug development. Further research is needed to establish various transporters abundances inter-correlations which can have a significant impact on the drug concentration at the site of action and as a result on drug safety and efficacy. References: [1] Brahim Achour, Matthew R. Russel, Jill Barber, and Amin Rostami-Hodjegan, Simultaneous Quantification of the Abundance of Several Cytochrome P450 and Uridine 59-Diphospho-Glucuronosyltransferase Enzymes in Human Liver Microsomes Using Multiplexed Targeted Proteomics, Drug Metab Dispos 42:500–510 (2014) [2] Brahim Achour, Jill Barber, and Amin Rostami-Hodjegan, Expression of Hepatic Drug-Metabolizing Cytochrome P450 Enzymes and Their Intercorrelations: A Meta-Analysis, Drug Metab Dispos 42:1349–1356 (2014) [3] Günther Hämmerlin, Karl-Heinz Hoffmann, Numerical Mathematics, Springer-Verlag New York Inc. (1991
Associations of financial strain and income with depressive and anxiety disorders.
No full textBACKGROUND: Previous research has shown socioeconomic inequality in prevalence and onset of depressive disorders. It is not yet clear whether perceived financial strain is associated with depressive and/or anxiety disorders in addition to an objective indicator, such as income. This study examines whether financial strain is associated with the prevalence and onset/recurrence of depressive and/or anxiety disorders, above income.METHODS: Data are from the Netherlands Study of Depression and Anxiety. Associations between financial strain, income and presence of depressive and/or anxiety disorder at baseline were assessed among 2937 participants (18-65???years). Impact of financial strain and income on 4-year onset/recurrence of depressive and/or anxiety disorders were examined among 1250 participants without a depressive or anxiety disorder at baseline. Depressive and anxiety disorders were determined with the Composite-International-Diagnostic-Interview. Financial strain and income were assessed in an interview.RESULTS: Participants with mild or severe financial strain had higher odds of being depressed (OR=1.68, 95{\%} CI 1.35 to 2.09; OR=3.88, 95{\%} CI 2.58 to 5.81) or remitted (OR=1.56, 95{\%} CI 1.24 to 1.96; OR=1.99, 95{\%} CI 1.27 to 3.11) at baseline compared with healthy controls, after adjusting for income. Mild or severe financial strain was not associated with onset/recurrence of depressive and/or anxiety disorders during follow-up (OR=1.08, 95{\%} CI 0.83 to 1.42; OR=1.05, 95{\%} CI 0.64 to 1.73).CONCLUSIONS: Financial strain was associated with having a depressive and/or anxiety disorder, above the effect of income. Healthcare and social services should be alert to this association, even for higher income households. However, financial strain and income were not related with 4-year onset/recurrence of depressive and/or anxiety disorders
Detecting laryngopharyngeal reflux in patients with upper airways symptoms: Symptoms, signs or salivary pepsin?
No full textBACKGROUND: Laryngopharyngeal reflux (LPR) can induce laryngeal hyper-responsiveness, a unifying feature underlying chronic cough and vocal cord dysfunction. The diagnosis of LPR currently relies on invasive oesophageal pH impedance testing. We compared symptoms, laryngeal signs and salivary pepsin as potential diagnostic methods for identifying LPR in patients with upper airway symptoms. METHODS: Symptoms were assessed using the Reflux Symptom Index (RSI) and signs of laryngeal inflammation quantified using the Reflux Finding Score (RFS) during laryngoscopy. Saliva samples were analysed for the presence of pepsin. A sub-group of patients with severe symptoms and signs of LPR were investigated with oesophageal pH monitoring and impedance study. RESULTS: Seventy eight patients with chronic cough and/or suspected vocal cord dysfunction were recruited, mean (SD) age, 54.6 (15.6) years. The majority (87%) had significant symptoms of reflux (RSI>13). There were clinical signs of LPR (RFS>7) in 51% of cases. Pepsin was detected in the saliva of 63% of subjects and 78% of those with a high RFS. Salivary pepsin had a sensitivity of 78% and specificity of 53% for predicting a high RFS. There was a correlation between the RSI and RFS (r = 0.51, p <0.001) and between the severity of laryngeal inflammation and the concentration of pepsin (r = 0.28, p = 0.01). All cases investigated with pH-impedance study had objective evidence of proximal reflux. CONCLUSION: Salivary pepsin may be used as a screening adjunct to supplement the RFS in the clinical workup of patients with extra-oesophageal symptoms and upper respiratory tract presentations of reflux
