Bayesian and Meta- Analyses of Cell-Cycle Gene Expression Data

Gene expression experiments conducted under a variety of conditions can allow for concurrent tests of more than one hypothesis. It is common for such experiments to be conducted independently by different researchers, using possibly different microarray platforms. In the second and fourth chapter of this thesis, we propose a differential meta-analytic procedure to pool the data from various sources and test the relative significance of the hypotheses under consideration. The specific application made in this thesis is to 10 time-course cell-cycle experiments on fission yeast S. Pombe (Oliva et al., 2005; Peng et al., 2005; Rustici et al., 2004), and the hypotheses of interest concern the question of differential expression and periodic regulation of genes. Besides addressing the above differential meta-analysis issue, we explore how time-course gene expression data can be used to test for periodicity. In this context, the commonly used procedures for testing include the Permutation test by de Lichtenberg et al. (2005) and the G-test by Fisher (1929), both of which are designed to evaluate periodicity against noise; however, it is possible that a given gene may have expression that is neither cyclic, nor just noise. In the third chapter, we introduce an Empirical Bayes approach to test for periodicity and compare its performance in terms of sensitivity and specificity with that of the other two methods through simulations and by application to the S. Pombe cell-cycle gene expression data. We use ‘conserved’ and ‘cycling’ genes by Lu et al. (2007) to assess the sensitivity, and CESR genes by Chen et al. (2003) to assess the specificity of our method. Kocak, M., Zhang, G., Narasimhan, G., George, E.O., Pyne, S. (2010) use George and Mudholkar’ (1983) ‘Difference of Two Logit-Sums’ method to pool bivariate P-values across independent experiments, assuming independence within a pair. We propose a Bayesian approach for pooling bivariate P-values across independent experiments, which accounts for potential correlation between paired P-values. We will investigate the operating characteristics of the Bayesian method trough simulations and apply it to the S. Pombe cell-cycle data

Dynamic simulation of chemical plant

A CSSL- type modular FORTRAN package, called ACES, has been developed to assist in the simulation of the dynamic behaviour of chemical plant. ACES can be harnessed, for instance, to simulate the transients in startups or after a throughput change. ACES has benefited from two existing simulators. The structure was adapted from ICL SLAM and most plant models originate in DYFLO. The latter employs sequential modularisation which is not always applicable to chemical engineering problems. A novel device of twice- round execution enables ACES to achieve general simultaneous modularisation. During the FIRST ROUND, STATE-VARIABLES are retrieved from the integrator and local calculations performed. During the SECOND ROUND, fresh derivatives are estimated and stored for simultaneous integration. ACES further includes a version of DIFSUB, a variable-step integrator capable of handling stiff differential systems. ACES is highly formalised . It does not use pseudo steady- state approximations and excludes inconsistent and arbitrary features of DYFLO. Built- in debug traps make ACES robust. ACES shows generality, flexibility, versatility and portability, and is very convenient to use. It undertakes substantial housekeeping behind the scenes and thus minimises the detailed involvement of the user. ACES provides a working set of defaults for simulation to proceed as far as possible. Built- in interfaces allow for reactions and user supplied algorithms to be incorporated . New plant models can be easily appended. Boundary- value problems and optimisation may be tackled using the RERUN feature. ACES is file oriented; a STATE can be saved in a readable form and reactivated later. Thus piecewise simulation is possible. ACES has been illustrated and verified to a large extent using some literature-based examples. Actual plant tests are desirable however to complete the verification of the library. Interaction and graphics are recommended for future work

Dynamic simulation of chemical plant

A CSSL- type modular FORTRAN package, called ACES, has been developed to assist in the simulation of the dynamic behaviour of chemical plant. ACES can be harnessed, for instance, to simulate the transients in startups or after a throughput change. ACES has benefited from two existing simulators. The structure was adapted from ICL SLAM and most plant models originate in DYFLO. The latter employs sequential modularisation which is not always applicable to chemical engineering problems. A novel device of twice- round execution enables ACES to achieve general simultaneous modularisation. During the FIRST ROUND, STATE-VARIABLES are retrieved from the integrator and local calculations performed. During the SECOND ROUND, fresh derivatives are estimated and stored for simultaneous integration. ACES further includes a version of DIFSUB, a variable-step integrator capable of handling stiff differential systems. ACES is highly formalised . It does not use pseudo steady- state approximations and excludes inconsistent and arbitrary features of DYFLO. Built- in debug traps make ACES robust. ACES shows generality, flexibility, versatility and portability, and is very convenient to use. It undertakes substantial housekeeping behind the scenes and thus minimises the detailed involvement of the user. ACES provides a working set of defaults for simulation to proceed as far as possible. Built- in interfaces allow for reactions and user supplied algorithms to be incorporated . New plant models can be easily appended. Boundary- value problems and optimisation may be tackled using the RERUN feature. ACES is file oriented; a STATE can be saved in a readable form and reactivated later. Thus piecewise simulation is possible. ACES has been illustrated and verified to a large extent using some literature-based examples. Actual plant tests are desirable however to complete the verification of the library. Interaction and graphics are recommended for future work

Effects of water immersion on the recovery of upper and lower body anaerobic power following a wrestling session

The aim of this study was to examine effects of cold-water immersion after exercise on powerresponses of wrestlers. Twenty elite male wrestlers were formed by similar age, height, weight and fitness parameters. The wrestling training session included a 60-minute of vigorous exercise. It consisted of warm-up exercises, standing technical and tactical exercises that mostly allocates arm and leg muscles. Vertical jump height, ropes climb height, and delayed onset of soreness was measured before, after, 24 h and 48 hors after the wrestling training. Cold-water immersion caused decrements in power loss at each follow-up time in comparison to a thermo neutral immersion.  It can be suggested that the longer time needed for power to return to normal levels after cold treatment and assessment of varied contraction types may present a more broad demonstration of muscle function and consequential capacity for dynamic exercise following exercise-induced muscle damage

Mean Platelet Volume to Platelet ratio as a promising marker of hepatosteatosis

Aim: Hepatosteatosis confers increased lipid accumulation in the hepatocytes which is associated with inflammation. Hemogram parameters, such as mean platelet volume (MPV) and MPV to platelet ratio (MPR) are proposed as novel inflammatory markers in recent studies. We aimed to compare MPR of subjects with hepatosteatosis to those in healthy controls. Methods: Patient admissions to our clinic with a diagnosis of hepatosteatosis were retrospectively analyzed MPR values compared to those in healthy controls. Results: Mean MPR of hepatosteatosis group (0,04 ± 0,01fL/mm3) was significantly higher than the MPR of control subjects (0,03 ± 0,01 fL/mm3) (p=0.04). A Pearson’s Correlation analyze was revealed significant correlations between MPR and fasting plasma glucose (r=0.26, p=0.004) and between MPR and LDL-cholesterol (r=0.19, p=0.04). Conclusion: An elevated MPR should alert physicians for hepatosteatosis in otherwise healthy subjects. Therefore, calculation of MPR by automatic hemogram analyzers is advised

Mean Platelet volume to platelet and red cell distribution width to platelet ratios in Irritable Bowel Syndrome

Aim: Irritable Bowel syndrome (IBS) is a common gastrointestinal disease worldwide with a broad spectrum of symptoms. In present retrospective study, we aimed to compare mean platelet volume to platelet ratio (MPR) and red cell distribution width to platelet ratio (RPR) values of IBS patients to those of healthy subjects. Methods: Patients whom followed up in internal medicine clinic of our institution between 2014 January to 2018 January were enrolled to the study. IBS subjects divided into constipation dominant or diarrhea dominant IBS groups. Healthy individuals visited our outpatient clinics for a check-up were enrolled as control group. Results: Median MPR of the constipation IBS, diarrhea IS and control groups were 0,034 (0,02-0,06), 0,034 (0,02-0,06), and 0,028 (0,01-0,05), respectively. The difference between groups was statistically significant (p=0.004). Conclusion: We think that elevated MPR in a patient with typical symptoms of IBS could be helpful in the diagnosis of the disease. Therefore, we suggest automatic calculation of MPR in hemogram assays. &nbsp

Serum uric acid level is associated with type 2 diabetes mellitus and diabetic regulation

Aim: Serum uric acid is a risk factor for cardiovascular and renal diseases. The role of uric acid as a renal and cardiac risk factor is more prominent in subjects with diabetes mellitus and hypertension. In present retrospective analyze, we aimed to compare serum uric acid levels of subjects with well and poorly controlled type 2 diabetes mellitus (T2DM) and healthy population. Methods: Patients with T2DM, who admitted to outpatient clinics of our institution between April 2017 and January 2018 were retrospectively analyzed. Diabetic subjects grouped into well or poorly regulated T2DM groups according to the HbA1c level (patients with an HbA1c lower than 7% were grouped as well regulated while others grouped as poorly regulated T2DM). Control subjects were healthy individuals whom asked for a routine check-up in our institution. Clinical and laboratory parameters of the study groups compared. Results: Serum uric acid levels of well-controlled T2DM, poorly controlled T2DM and control groups were 5.9±1, 6.7±1.8 and 4.3±1 mg/dL, respectively (p<0.001). Post Hoc analysis revealed that uric acid levels of well controlled diabetics were significantly lower than the uric acid levels of poorly controlled diabetics (p=0.04) and significantly higher than that of the control subjects (p<0.001). Conclusion: We suggest that elevated uric acid indicates a cellular level of damage and can be used as a prognostic indicator of pre-diabetes and T2DM. &nbsp

Serum Uric acid is correlated with HbA1c levels in type 2 diabetes mellitus

Aims: Uric acid is the product of purine metabolism and elevated serum uric acid levels are associated with many metabolic conditions. In present retrospective analysis, we aimed to compare serum uric acid levels of well controlled type 2 diabetic subjects to those of poorly controlled type 2 DM patients. Methods: Medical database of type 2 diabetic subjects whom admitted to outpatient clinics of our institution, between January 2017 and August 2017, were retrospectively analyzed. Patients with a HbA1c level lower than 7,5% were classified as well controlled and others were classified as poorly controlled type 2 DM group. Uric acid levels of the groups were compared. Results: Serum uric acid level of well controlled and poorly controlled diabetics were 4.1 (2,8-5,9) mg/dl and 5,9 (4-9,6) mg/dl, respectively. The difference was statistically significant (p<0.001). A Pearson’s correlation test was revealed that serum uric acid was strongly and positively correlated with HbA1c (r=0.81, p<0.001). Conclusion: Serum uric acid levels worsen in poorly controlled type 2 diabetic subjects. Since HbA1c levels reflects changes in 3 months period, variations in serum uric acid levels could be used as a predictor of diabetic control level in shorter time periods

Maximum likelihood estimation of reviewers' acumen in central review setting: categorical data

Successfully evaluating pathologists' acumen could be very useful in improving the concordance of their calls on histopathologic variables. We are proposing a new method to estimate the reviewers' acumen based on their histopathologic calls. The previously proposed method includes redundant parameters that are not identifiable and results are incorrect. The new method is more parsimonious and through extensive simulation studies, we show that the new method relies less on the initial values and converges to the true parameters. The result of the anesthetist data set by the new method is more convincing

The Correlation between Changes in Biochemical Parameters and Central Macular Thickness in Patients with Non-Proliferative Diabetic Retinopathy

This study aimed at evaluating the correlation between changes in Hemoglobin A1c (HbA1c) and fasting serum lipids, and Central Macular Thickness (CMT) in patients with Non-Proliferative Diabetic Retinopathy (NPDR). In the current research, both eyes of 68 patients with mild or moderate NPDR, without clinically significant macular edema, were studied. Levels of fasting serum lipids, HbAlc, and CMT were measured during the first visit and at the end of the follow-up period (3 months). For statistical analysis, CMTs of each eye were studied and the correlation of changes was investigated. Additionally, the direction of changes in CMT for each eye was determined, and whether the changes in both eyes were symmetrical was investigated. Out of 68 patients, 24 were male and 44 were female. The mean CMT of all eyes was 290.05 ± 48.90 µm during the first visit and 286.80 ± 37.57 µm on the 3rd month follow-up. The mean HbAlc was 8.71 ± 1.82% at first visit to the hospital and the mean HbAlc was 8.39 ± 1.65% at the final visit. Although the changes in HbA1c and CMT during the follow-up period were statistically insignificant, the correlation of these 2 values was statistically significant (p=0.01). However, amongst l3 patients, the CMTs were asymmetrically changed in each eye during the follow-up period. To the best of the author’s knowledge, this was the first study, which indicated a significant correlation in changes of CMT and HbA1c, even amongst patients with low-grade diabetic retinopathy. Demonstration of asymmetric changes in CMT of each treatment-naive eye of the same patient, during changes in systemic conditions, was another important finding of this study