Christos Argyropoulos | University of New Mexico School of Medicine (original) (raw)

Papers by Christos Argyropoulos

Research paper thumbnail of Modeling bias and variation in the stochastic processes of small RNA sequencing

The use of RNA-seq as the preferred method for the discovery and validation of small RNA biomark-... more The use of RNA-seq as the preferred method for the discovery and validation of small RNA biomark-ers has been hindered by high quantitative variability and biased sequence counts. In this paper we develop a statistical model for sequence counts that accounts for ligase bias and stochastic variation in sequence counts. This model implies a linear quadratic relation between the mean and variance of sequence counts. Using a large number of sequencing datasets, we demonstrate how one can use the generalized additive models for location, scale and shape (GAMLSS) distributional regression framework to calculate and apply empirical correction factors for ligase bias. Bias correction could remove more than 40% of the bias for miRNAs. Empirical bias correction factors appear to be nearly constant over at least one and up to four orders of magnitude of total RNA input and independent of sample composition. Using synthetic mixes of known composition, we show that the GAMLSS approach can analyze differential expression with greater accuracy , higher sensitivity and specificity than six existing algorithms (DESeq2, edgeR, EBSeq, limma, DSS, voom) for the analysis of small RNA-seq data.

Research paper thumbnail of Revisiting the Middle Molecule Hypothesis of Uremic Toxicity: A Systematic Review of Beta 2 Microglobulin Population Kinetics and Large Scale Modeling of Hemodialysis Trials In Silico

PLOS ONE, 2016

Beta-2 Microglobulin (β2M) is a prototypical "middle mol... more Beta-2 Microglobulin (β2M) is a prototypical "middle molecule" uremic toxin that has been associated with a higher risk of death in hemodialysis patients. A quantitative description of the relative importance of factors determining β2M concentrations among patients with impaired kidney function is currently lacking. Herein we undertook a systematic review of existing studies reporting patient level data concerning generation, elimination and distribution of β2M in order to develop a population model of β2M kinetics. We used this model and previously determined relationships between predialysis β2M concentration and survival, to simulate the population distribution of predialysis β2M and the associated relative risk (RR) of death in patients receiving conventional thrice-weekly hemodialysis with low flux (LF) and high flux (HF) dialyzers, short (SD) and long daily (LD) HF hemodialysis sessions and on-line hemodiafiltration at different levels of residual renal function (RRF). We identified 9 studies of 106 individuals and 156 evaluations of or more compartmental kinetic parameters of β2M. These studies used a variety of experimental methods to determine β2M kinetics ranging from isotopic dilution to profiling of intra/inter dialytic concentration changes. Most of the patients (74/106) were on dialysis with minimal RRF, thus facilitating the estimation of non-renal elimination kinetics of β2M. In large scale (N = 10000) simulations of individuals drawn from the population of β2M kinetic parameters, we found that, higher dialytic removal materially affects β2M exposures only when RRF (renal clearance of β2M) was below 2 ml/min. In patients initiating conventional HF hemodialysis, total loss of RRF was predicted to be associated with a RR of death of more than 20%. Hemodiafiltration and daily dialysis may decrease the high risk of death of anuric patients by 10% relative to conventional, thrice weekly HF dialysis. Only daily long sessions of hemodialysis consistently reduced mortality risk between 7-19% across the range of β2M generation rate. Preservation of RRF should be considered one of the therapeutic goals of hemodialysis practice. Randomized controlled trials of novel dialysis modalities may require large sample sizes to detect an effect on clinical outcomes even if they enroll anuric patients. The developed population model for β2M may allow personalization of hemodialysis prescription and/or facilitate the design of such studies by identifying patients with higher β2M generation rate.

Research paper thumbnail of Hypertonicity: Pathophysiologic Concept and Experimental Studies

Cureus, 2016

Disturbances in tonicity (effective osmolarity) are the major clinical disorders affecting cell v... more Disturbances in tonicity (effective osmolarity) are the major clinical disorders affecting cell volume. Cell shrinking secondary to hypertonicity causes severe clinical manifestations and even death. Quantitative management of hypertonic disorders is based on formulas computing the volume of hypotonic fluids required to correct a given level of hypertonicity. These formulas have limitations. The major limitation of the predictive formulas is that they represent closed system calculations and have been tested in anuric animals. Consequently, the formulas do not account for ongoing fluid losses during development or treatment of the hypertonic disorders. In addition, early comparisons of serum osmolality changes predicted by these formulas and observed in animals infused with hypertonic solutions clearly demonstrated that hypertonicity creates new intracellular solutes causing rises in serum osmolality higher than those predicted by the formulas. The mechanisms and types of intracellular solutes generated by hypertonicity and the effects of the solutes have been studied extensively in recent times. The solutes accumulated intracellularly in hypertonic states have potentially major adverse effects on the outcomes of treatment of these states. When hypertonicity was produced by the infusion of hypertonic sodium chloride solutions, the predicted and observed changes in serum sodium concentration were equal. This finding justifies the use of the predictive formulas in the management of hypernatremic states.

Research paper thumbnail of Restoration of High-Frequency Glucose Entrained Insulin Oscillations in Obese Subjects with Type 2 Diabetes Mellitus Following BPD

Surgery for Obesity and Related Diseases, 2016

Minimal glucose infusions are known to entrain insulin oscillations in patients with normal gluco... more Minimal glucose infusions are known to entrain insulin oscillations in patients with normal glucose tolerance (NGT) but not in patients with type 2 diabetes (T2D). To investigate whether weight loss after a version of biliopancreatic diversion (BPD) can restore the glucose entrainment of high-frequency insulin oscillations in morbidly obese NGT or T2D patients. University Hospital, Greece. We prospectively studied 9 NGT controls (body mass index [BMI] 23.3±1.6 kg/m(2)), 9 obese NGT patients (BMI 51.1±12.7 kg/m(2)), and 9 obese T2D patients (BMI 56.8±11.6 kg/m(2)). Patients were studied before and 1.5 years after BPD. Insulin was sampled every minute for 90 minutes. Glucose (6 mg/kg weight) was infused every 10 minutes for 1 minute. Regularity of insulin pulses was estimated by autocorrelation analysis, spectral analysis, approximate entropy/sample entropy (ApEn/SampEn), and insulin pulsatility by deconvolution analysis. Postoperatively, glucose and insulin concentrations of NGT and T2D patients decreased to control levels and BMI to 31.3±6.3 for NGT patients and 34.9±9.9 kg/m(2) for T2D patients. Preoperatively, glucose entrainment was absent in all T2D and in 4 NGT patients as assessed with spectral analysis and in 8 and 4, respectively, as assessed with autocorrelation and deconvolution analysis. Postoperatively, it was restored to normal in all patients. ApEn/SampEn decreased significantly only in the T2D group postoperatively. BPD restores the glucose entrainment of high-frequency insulin oscillations in obese NGT and T2D patients after marked weight loss and normalizes glucose levels and insulin sensitivity, thus demonstrating recovery of β-cell glucose sensing.

Research paper thumbnail of Mapping an inhibitory peptide binding site to construct a molecular model of the alpha subunit of the epithelial sodium channel

The Faseb Journal, Apr 1, 2010

Research paper thumbnail of Argyropoulos C & Mouzaki A. 2006. Immunosuppressive drugs in HIV disease. Curr. Top. Med. Chem., 6(16):1769-1789

Research paper thumbnail of Of means standard deviations and blood pressure trials

The Winnower, May 10, 2015

Research paper thumbnail of Objective and subjective sleep disorders in automated peritoneal dialysis

Canadian Journal of Kidney Health and Disease, 2016

Automated peritoneal dialysis (APD) is one of the fastest growing dialysis modalities. It is unkn... more Automated peritoneal dialysis (APD) is one of the fastest growing dialysis modalities. It is unknown whether sleep and mood are disturbed while performing repeated overnight exchanges. In this report, we aim to describe and compare the prevalence of sleep-disordered breathing (SDB), periodic limb movements (PLMS), poor sleep quality (SQ), and depression among APD patients compared with stages 3b-5 (estimated glomerular filtration rate ≤44 ml/min/1.73 m2) chronic kidney disease (CKD) and hemodialysis (HD) patients. This is a cross-sectional, descriptive study. Study participants were recruited from outpatient nephrology clinics, local dialysis centers, and the Thomas E. Starzl Transplant Institute in Western Pennsylvania between April 2004 and July 2009. There were 186 participants in this study including 22 APD patients, 89 CKD patients, and 75 HD patients. In-home polysomnography was performed and two questionnaires were completed, the Pittsburgh Sleep Quality Index (PSQI) and the Patient Health Questionnaire-9 (PHQ-9). SDB and PLMS were quantified by in-home unattended polysomnography; poor SQ was defined by a score >5 on the PSQI, and the presence of moderate to severe depression was defined by a score >5 on the PHQ-9. The APD patients had a median age of 37.5 years, were predominantly female (72.7 %), and had a median body mass index (BMI) of 23.8 kg/m2. In univariate analyses, APD patients had significantly lower apnea-hypopnea index compared to HD patients by 12.2 points (likelihood ratio test p = 0.008) and revealed the least percent of TST with nocturnal hypoxemia compared to CKD patients by 2.7 points, respectively (likelihood ratio test p = 0.01). The APD group had also significantly greater stages 3 to 4 sleep compared to the CKD patients by 8.6 points (likelihood ratio test p = 0.009). In multivariate analyses and after adjustment for age, gender, race, and BMI, both APD and HD patients had higher average PSQI scores than CKD patients by 2.54 and 2.22 points, respectively (likelihood ratio test p = 0.005). No other comparisons of sleep parameters among groups reached statistical significance. The limitations of this study are the small sample size of the APD population and the demographic and clinical differences among the three study groups. Despite differences in univariate analyses, after multivariate adjustment, APD patients had similar sleep parameters and sleep architecture and as poor SQ and symptoms of depression as HD patients. Future studies with larger APD cohorts are needed.

Research paper thumbnail of A proposal of a novel segmentation technique of microarray images

The user has requested enhancement of the downloaded file. All in-text references underlined in b... more The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the original document and are linked to publications on ResearchGate, letting you access and read them immediately.

Research paper thumbnail of Dialyzer Reuse and Outcomes of High Flux Dialysis

PloS one, 2015

The bulk of randomized trial evidence for the expanding use of High Flux (HF) hemodialysis worldw... more The bulk of randomized trial evidence for the expanding use of High Flux (HF) hemodialysis worldwide comes from two randomized controlled trials, one of which (HEMODIALYSIS, HEMO) allowed, while the other (Membrane Outcomes Permeability, MPO) excluded, the reuse of membranes. It is not known whether dialyzer reuse has a differential impact on outcomes with HF vs low flyx (LF) dialyzers. Proportional Hazards Models and Joint Models for longitudinal measures and survival outcomes were used in HEMO to analyze the relationship between β2-microglobulin (β2M) concentration, flux, and reuse. Meta-analysis and regression techniques were used to synthesize the evidence for HF dialysis from HEMO and MPO. In HEMO, minimally reused (< 6 times) HF dialyzers were associated with a hazard ratio (HR) of 0.67 (95% confidence interval, 95%CI: 0.48-0.92, p = 0.015), 0.64 (95%CI: 0.44 - 0.95, p = 0.03), 0.61 (95%CI: 0.41 - 0.90, p = 0.012), 0.53 (95%CI: 0.28 - 1.02, p = 0.057) relative to minimally ...

Research paper thumbnail of Uncovering Fine Structure in Gene Expression Profile by Maximum Entropy Modeling of cDNA Microarray Images and Kernel Density Methods

Handbook of Research on Systems Biology Applications in Medicine, 2009

The presentation and interpretation of microarray-based genome-wide gene expression profiles as c... more The presentation and interpretation of microarray-based genome-wide gene expression profiles as complex biological entities are considered to be problematic due to their featureless, dense nature. Furthermore microarray images are characterized by significant background ...

Research paper thumbnail of Analysis of time to event outcomes in randomized controlled trials by generalized additive models

PloS one, 2015

Randomized Controlled Trials almost invariably utilize the hazard ratio calculated with a Cox pro... more Randomized Controlled Trials almost invariably utilize the hazard ratio calculated with a Cox proportional hazard model as a treatment efficacy measure. Despite the widespread adoption of HRs, these provide a limited understanding of the treatment effect and may even provide a biased estimate when the assumption of proportional hazards in the Cox model is not verified by the trial data. Additional treatment effect measures on the survival probability or the time scale may be used to supplement HRs but a framework for the simultaneous generation of these measures is lacking. By splitting follow-up time at the nodes of a Gauss Lobatto numerical quadrature rule, techniques for Poisson Generalized Additive Models (PGAM) can be adopted for flexible hazard modeling. Straightforward simulation post-estimation transforms PGAM estimates for the log hazard into estimates of the survival function. These in turn were used to calculate relative and absolute risks or even differences in restricte...

Research paper thumbnail of The hazards of the changing hazard of dialysis modalities

Kidney international, 2014

The impact of the dialysis modality on patient survival has received considerable epidemiological... more The impact of the dialysis modality on patient survival has received considerable epidemiological attention, with most studies suggesting an early benefit favoring peritoneal dialysis over hemodialysis. Kumar et al. report the relative outcomes of the two modalities in incident patients followed by an accountable care organization. Using advanced statistical techniques for non-proportional hazards survival models, the authors corroborate the early benefit of peritoneal dialysis for the first 3 years and equivalent outcomes thereafter.

Research paper thumbnail of Multicenter Epidemiological Study to Assess the Population of CKD Patients in Greece: Results from the PRESTAR Study

PLoS ONE, 2014

Chronic Kidney Disease (CKD) is a relatively common condition not only associated with increased ... more Chronic Kidney Disease (CKD) is a relatively common condition not only associated with increased morbidity and mortality but also fuelling End Stage Renal Disease (ESRD). Among developed nations, Greece has one of the highest ESRD incidence rates, yet there is limited understanding of the epidemiology of earlier stages of CKD. Cross-sectional survey of pre-dialysis CKD outpatients in nephrology clinics in the National Health Care system between October 2009 and October 2010. Demographics, cause of CKD, blood pressure, level of renal function, duration of CKD and nephrology care, and specialty of referral physician were collected and analyzed. Different methods for estimating renal function (Cockroft-Gault [CG], CKD-Epi and MDRD) and staging CKD were assessed for agreement. A total of 1,501 patients in 9 centers were enrolled. Diabetic nephropathy was the most common nephrologist assigned cause of CKD (29.7%). In total, 36.5% of patients had self-referred to the nephrologist; patients with diabetes or serum creatinine above 220 µmol/l (eGFR&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;40 ml/min/1.73 m2) were more likely to have been referred by a physician. Agreement between MDRD and CKD-Epi, but not between CG, the other estimating equations, was excellent. There was substantial heterogeneity with respect to renal diagnoses, referral patterns and blood pressure among participating centers. In this first epidemiologic assessment of CKD in Greece, we documented delayed referral and high rates of self-referral among patients with CKD. eGFR reporting, currently offered by a limited number of laboratories, may facilitate detection of CKD at an earlier, more treatable stage.

Research paper thumbnail of HCV-Associated Membranoproliferative Glomerulonephritis

HCV Infection and Cryoglobulinemia, 2011

Research paper thumbnail of FPGA Implementation of Spiking Neural Network

1st Conference on Embedded Systems, Computational Intelligence and Telematics in Control, 2012

ABSTRACT Spiking Neural Networks (SNN) have optimal characteristics for hardware implementation. ... more ABSTRACT Spiking Neural Networks (SNN) have optimal characteristics for hardware implementation. They can communicate among neurons using spikes, which in terms of logic resources, means a single bit, reducing the logic occupation in a device. Additionally, SNN are similar in performance compared to other neural Artificial Neural Network (ANN) architectures such as Multilayer Perceptron, and others. SNN are very similar to those found in the biological neural system, having weights and delays as adjustable parameters. This work describes the chosen models for the implemented SNN: Spike Response Model (SRM) and temporal coding is used. FPGA implementation using VHDL language is also described, detailing logic resources usage and speed of operation for a simple pattern recognition problem.

Research paper thumbnail of Correction: Cytoskeletal Rearrangements in Synovial Fibroblasts as a Novel Pathophysiological Determinant of Modeled Rheumatoid Arthritis

PLoS Genetics, 2005

Rheumatoid arthritis is a chronic inflammatory disease with a high prevalence and substantial soc... more Rheumatoid arthritis is a chronic inflammatory disease with a high prevalence and substantial socioeconomic burden. Despite intense research efforts, its aetiology and pathogenesis remain poorly understood. To identify novel genes and/or cellular pathways involved in the pathogenesis of the disease, we utilized a well-recognized tumour necrosis factor-driven animal model of this disease and performed high-throughput expression profiling with subtractive cDNA libraries and oligonucleotide microarray hybridizations, coupled with independent statistical analysis. This twin approach was validated by a number of different methods in other animal models of arthritis as well as in human patient samples, thus creating a unique list of disease modifiers of potential therapeutic value. Importantly, and through the integration of genetic linkage analysis and Gene Ontology-assisted functional discovery, we identified the gelsolin-driven synovial fibroblast cytoskeletal rearrangements as a novel pathophysiological determinant of the disease.

Research paper thumbnail of Operational criteria for selecting a cDNA microarray data normalization algorithm

Oncology Reports, 2006

Microarray technology allows gene expression profiling at a global level. Many algorithms for the... more Microarray technology allows gene expression profiling at a global level. Many algorithms for the normalization of raw microarray data have been proposed, but no attempt has yet been made to propose operationally verifiable criteria for their comparative evaluation, which is necessary for the selection of the most appropriate method for a given dataset. This study develops a set of operational criteria for assessing the impact of various normalization algorithms in terms of accuracy (bias), precision (variance) and over-fitting (information reduction). The use of these criteria is illustrated by applying the three most widely used algorithms (global median normalization, spiked-in based normalization and lowess) on a specifically designed, multiply-controlled dataset.

Research paper thumbnail of Successful treatment with thalidomide in a liver transplant recipient with giant esophageal ulcers

Liver Transplantation, 2006

Research paper thumbnail of Three-Dimensional Imaging Reveals Ureteric and Mesenchymal Defects in Fgfr2-Mutant Kidneys

Journal of the American Society of Nephrology, 2009

Current techniques to morphologically characterize the processes of nephrogenesis and ureteric br... more Current techniques to morphologically characterize the processes of nephrogenesis and ureteric branching during kidney development have many limitations. Here, we used in vivo three-dimensional analysis to study renal development in mice lacking fibroblast growth factor receptor 2 in the ureteric bud (Fgfr2 UBϪ/Ϫ ) and in littermate controls. We found that Fgfr2 UBϪ/Ϫ mice have more severe defects in ureteric branching morphogenesis than previously reported, including significantly fewer branches and tips than control mice. Furthermore, these mice had decreased ureteric volume and surface area and longer ureteric segments than control mice. We also observed previously unrecognized abnormalities in nephrogenesis, including a gradual increase in volume and surface area during maturation from renal vesicles to mature nephrons, in the mutant mice. Finally, we quantified many events of normal renal development that are either difficult or impossible to measure without this three-dimensional technique. In summary, the three-dimensional approach is a powerful and quantitative means to characterize branching morphogenesis and nephrogenesis.

Research paper thumbnail of Modeling bias and variation in the stochastic processes of small RNA sequencing

The use of RNA-seq as the preferred method for the discovery and validation of small RNA biomark-... more The use of RNA-seq as the preferred method for the discovery and validation of small RNA biomark-ers has been hindered by high quantitative variability and biased sequence counts. In this paper we develop a statistical model for sequence counts that accounts for ligase bias and stochastic variation in sequence counts. This model implies a linear quadratic relation between the mean and variance of sequence counts. Using a large number of sequencing datasets, we demonstrate how one can use the generalized additive models for location, scale and shape (GAMLSS) distributional regression framework to calculate and apply empirical correction factors for ligase bias. Bias correction could remove more than 40% of the bias for miRNAs. Empirical bias correction factors appear to be nearly constant over at least one and up to four orders of magnitude of total RNA input and independent of sample composition. Using synthetic mixes of known composition, we show that the GAMLSS approach can analyze differential expression with greater accuracy , higher sensitivity and specificity than six existing algorithms (DESeq2, edgeR, EBSeq, limma, DSS, voom) for the analysis of small RNA-seq data.

Research paper thumbnail of Revisiting the Middle Molecule Hypothesis of Uremic Toxicity: A Systematic Review of Beta 2 Microglobulin Population Kinetics and Large Scale Modeling of Hemodialysis Trials In Silico

PLOS ONE, 2016

Beta-2 Microglobulin (β2M) is a prototypical &amp;amp;amp;amp;amp;amp;amp;amp;quot;middle mol... more Beta-2 Microglobulin (β2M) is a prototypical &amp;amp;amp;amp;amp;amp;amp;amp;quot;middle molecule&amp;amp;amp;amp;amp;amp;amp;amp;quot; uremic toxin that has been associated with a higher risk of death in hemodialysis patients. A quantitative description of the relative importance of factors determining β2M concentrations among patients with impaired kidney function is currently lacking. Herein we undertook a systematic review of existing studies reporting patient level data concerning generation, elimination and distribution of β2M in order to develop a population model of β2M kinetics. We used this model and previously determined relationships between predialysis β2M concentration and survival, to simulate the population distribution of predialysis β2M and the associated relative risk (RR) of death in patients receiving conventional thrice-weekly hemodialysis with low flux (LF) and high flux (HF) dialyzers, short (SD) and long daily (LD) HF hemodialysis sessions and on-line hemodiafiltration at different levels of residual renal function (RRF). We identified 9 studies of 106 individuals and 156 evaluations of or more compartmental kinetic parameters of β2M. These studies used a variety of experimental methods to determine β2M kinetics ranging from isotopic dilution to profiling of intra/inter dialytic concentration changes. Most of the patients (74/106) were on dialysis with minimal RRF, thus facilitating the estimation of non-renal elimination kinetics of β2M. In large scale (N = 10000) simulations of individuals drawn from the population of β2M kinetic parameters, we found that, higher dialytic removal materially affects β2M exposures only when RRF (renal clearance of β2M) was below 2 ml/min. In patients initiating conventional HF hemodialysis, total loss of RRF was predicted to be associated with a RR of death of more than 20%. Hemodiafiltration and daily dialysis may decrease the high risk of death of anuric patients by 10% relative to conventional, thrice weekly HF dialysis. Only daily long sessions of hemodialysis consistently reduced mortality risk between 7-19% across the range of β2M generation rate. Preservation of RRF should be considered one of the therapeutic goals of hemodialysis practice. Randomized controlled trials of novel dialysis modalities may require large sample sizes to detect an effect on clinical outcomes even if they enroll anuric patients. The developed population model for β2M may allow personalization of hemodialysis prescription and/or facilitate the design of such studies by identifying patients with higher β2M generation rate.

Research paper thumbnail of Hypertonicity: Pathophysiologic Concept and Experimental Studies

Cureus, 2016

Disturbances in tonicity (effective osmolarity) are the major clinical disorders affecting cell v... more Disturbances in tonicity (effective osmolarity) are the major clinical disorders affecting cell volume. Cell shrinking secondary to hypertonicity causes severe clinical manifestations and even death. Quantitative management of hypertonic disorders is based on formulas computing the volume of hypotonic fluids required to correct a given level of hypertonicity. These formulas have limitations. The major limitation of the predictive formulas is that they represent closed system calculations and have been tested in anuric animals. Consequently, the formulas do not account for ongoing fluid losses during development or treatment of the hypertonic disorders. In addition, early comparisons of serum osmolality changes predicted by these formulas and observed in animals infused with hypertonic solutions clearly demonstrated that hypertonicity creates new intracellular solutes causing rises in serum osmolality higher than those predicted by the formulas. The mechanisms and types of intracellular solutes generated by hypertonicity and the effects of the solutes have been studied extensively in recent times. The solutes accumulated intracellularly in hypertonic states have potentially major adverse effects on the outcomes of treatment of these states. When hypertonicity was produced by the infusion of hypertonic sodium chloride solutions, the predicted and observed changes in serum sodium concentration were equal. This finding justifies the use of the predictive formulas in the management of hypernatremic states.

Research paper thumbnail of Restoration of High-Frequency Glucose Entrained Insulin Oscillations in Obese Subjects with Type 2 Diabetes Mellitus Following BPD

Surgery for Obesity and Related Diseases, 2016

Minimal glucose infusions are known to entrain insulin oscillations in patients with normal gluco... more Minimal glucose infusions are known to entrain insulin oscillations in patients with normal glucose tolerance (NGT) but not in patients with type 2 diabetes (T2D). To investigate whether weight loss after a version of biliopancreatic diversion (BPD) can restore the glucose entrainment of high-frequency insulin oscillations in morbidly obese NGT or T2D patients. University Hospital, Greece. We prospectively studied 9 NGT controls (body mass index [BMI] 23.3±1.6 kg/m(2)), 9 obese NGT patients (BMI 51.1±12.7 kg/m(2)), and 9 obese T2D patients (BMI 56.8±11.6 kg/m(2)). Patients were studied before and 1.5 years after BPD. Insulin was sampled every minute for 90 minutes. Glucose (6 mg/kg weight) was infused every 10 minutes for 1 minute. Regularity of insulin pulses was estimated by autocorrelation analysis, spectral analysis, approximate entropy/sample entropy (ApEn/SampEn), and insulin pulsatility by deconvolution analysis. Postoperatively, glucose and insulin concentrations of NGT and T2D patients decreased to control levels and BMI to 31.3±6.3 for NGT patients and 34.9±9.9 kg/m(2) for T2D patients. Preoperatively, glucose entrainment was absent in all T2D and in 4 NGT patients as assessed with spectral analysis and in 8 and 4, respectively, as assessed with autocorrelation and deconvolution analysis. Postoperatively, it was restored to normal in all patients. ApEn/SampEn decreased significantly only in the T2D group postoperatively. BPD restores the glucose entrainment of high-frequency insulin oscillations in obese NGT and T2D patients after marked weight loss and normalizes glucose levels and insulin sensitivity, thus demonstrating recovery of β-cell glucose sensing.

Research paper thumbnail of Mapping an inhibitory peptide binding site to construct a molecular model of the alpha subunit of the epithelial sodium channel

The Faseb Journal, Apr 1, 2010

Research paper thumbnail of Argyropoulos C & Mouzaki A. 2006. Immunosuppressive drugs in HIV disease. Curr. Top. Med. Chem., 6(16):1769-1789

Research paper thumbnail of Of means standard deviations and blood pressure trials

The Winnower, May 10, 2015

Research paper thumbnail of Objective and subjective sleep disorders in automated peritoneal dialysis

Canadian Journal of Kidney Health and Disease, 2016

Automated peritoneal dialysis (APD) is one of the fastest growing dialysis modalities. It is unkn... more Automated peritoneal dialysis (APD) is one of the fastest growing dialysis modalities. It is unknown whether sleep and mood are disturbed while performing repeated overnight exchanges. In this report, we aim to describe and compare the prevalence of sleep-disordered breathing (SDB), periodic limb movements (PLMS), poor sleep quality (SQ), and depression among APD patients compared with stages 3b-5 (estimated glomerular filtration rate ≤44 ml/min/1.73 m2) chronic kidney disease (CKD) and hemodialysis (HD) patients. This is a cross-sectional, descriptive study. Study participants were recruited from outpatient nephrology clinics, local dialysis centers, and the Thomas E. Starzl Transplant Institute in Western Pennsylvania between April 2004 and July 2009. There were 186 participants in this study including 22 APD patients, 89 CKD patients, and 75 HD patients. In-home polysomnography was performed and two questionnaires were completed, the Pittsburgh Sleep Quality Index (PSQI) and the Patient Health Questionnaire-9 (PHQ-9). SDB and PLMS were quantified by in-home unattended polysomnography; poor SQ was defined by a score &amp;amp;amp;amp;amp;amp;gt;5 on the PSQI, and the presence of moderate to severe depression was defined by a score &amp;amp;amp;amp;amp;amp;gt;5 on the PHQ-9. The APD patients had a median age of 37.5 years, were predominantly female (72.7 %), and had a median body mass index (BMI) of 23.8 kg/m2. In univariate analyses, APD patients had significantly lower apnea-hypopnea index compared to HD patients by 12.2 points (likelihood ratio test p = 0.008) and revealed the least percent of TST with nocturnal hypoxemia compared to CKD patients by 2.7 points, respectively (likelihood ratio test p = 0.01). The APD group had also significantly greater stages 3 to 4 sleep compared to the CKD patients by 8.6 points (likelihood ratio test p = 0.009). In multivariate analyses and after adjustment for age, gender, race, and BMI, both APD and HD patients had higher average PSQI scores than CKD patients by 2.54 and 2.22 points, respectively (likelihood ratio test p = 0.005). No other comparisons of sleep parameters among groups reached statistical significance. The limitations of this study are the small sample size of the APD population and the demographic and clinical differences among the three study groups. Despite differences in univariate analyses, after multivariate adjustment, APD patients had similar sleep parameters and sleep architecture and as poor SQ and symptoms of depression as HD patients. Future studies with larger APD cohorts are needed.

Research paper thumbnail of A proposal of a novel segmentation technique of microarray images

The user has requested enhancement of the downloaded file. All in-text references underlined in b... more The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the original document and are linked to publications on ResearchGate, letting you access and read them immediately.

Research paper thumbnail of Dialyzer Reuse and Outcomes of High Flux Dialysis

PloS one, 2015

The bulk of randomized trial evidence for the expanding use of High Flux (HF) hemodialysis worldw... more The bulk of randomized trial evidence for the expanding use of High Flux (HF) hemodialysis worldwide comes from two randomized controlled trials, one of which (HEMODIALYSIS, HEMO) allowed, while the other (Membrane Outcomes Permeability, MPO) excluded, the reuse of membranes. It is not known whether dialyzer reuse has a differential impact on outcomes with HF vs low flyx (LF) dialyzers. Proportional Hazards Models and Joint Models for longitudinal measures and survival outcomes were used in HEMO to analyze the relationship between β2-microglobulin (β2M) concentration, flux, and reuse. Meta-analysis and regression techniques were used to synthesize the evidence for HF dialysis from HEMO and MPO. In HEMO, minimally reused (< 6 times) HF dialyzers were associated with a hazard ratio (HR) of 0.67 (95% confidence interval, 95%CI: 0.48-0.92, p = 0.015), 0.64 (95%CI: 0.44 - 0.95, p = 0.03), 0.61 (95%CI: 0.41 - 0.90, p = 0.012), 0.53 (95%CI: 0.28 - 1.02, p = 0.057) relative to minimally ...

Research paper thumbnail of Uncovering Fine Structure in Gene Expression Profile by Maximum Entropy Modeling of cDNA Microarray Images and Kernel Density Methods

Handbook of Research on Systems Biology Applications in Medicine, 2009

The presentation and interpretation of microarray-based genome-wide gene expression profiles as c... more The presentation and interpretation of microarray-based genome-wide gene expression profiles as complex biological entities are considered to be problematic due to their featureless, dense nature. Furthermore microarray images are characterized by significant background ...

Research paper thumbnail of Analysis of time to event outcomes in randomized controlled trials by generalized additive models

PloS one, 2015

Randomized Controlled Trials almost invariably utilize the hazard ratio calculated with a Cox pro... more Randomized Controlled Trials almost invariably utilize the hazard ratio calculated with a Cox proportional hazard model as a treatment efficacy measure. Despite the widespread adoption of HRs, these provide a limited understanding of the treatment effect and may even provide a biased estimate when the assumption of proportional hazards in the Cox model is not verified by the trial data. Additional treatment effect measures on the survival probability or the time scale may be used to supplement HRs but a framework for the simultaneous generation of these measures is lacking. By splitting follow-up time at the nodes of a Gauss Lobatto numerical quadrature rule, techniques for Poisson Generalized Additive Models (PGAM) can be adopted for flexible hazard modeling. Straightforward simulation post-estimation transforms PGAM estimates for the log hazard into estimates of the survival function. These in turn were used to calculate relative and absolute risks or even differences in restricte...

Research paper thumbnail of The hazards of the changing hazard of dialysis modalities

Kidney international, 2014

The impact of the dialysis modality on patient survival has received considerable epidemiological... more The impact of the dialysis modality on patient survival has received considerable epidemiological attention, with most studies suggesting an early benefit favoring peritoneal dialysis over hemodialysis. Kumar et al. report the relative outcomes of the two modalities in incident patients followed by an accountable care organization. Using advanced statistical techniques for non-proportional hazards survival models, the authors corroborate the early benefit of peritoneal dialysis for the first 3 years and equivalent outcomes thereafter.

Research paper thumbnail of Multicenter Epidemiological Study to Assess the Population of CKD Patients in Greece: Results from the PRESTAR Study

PLoS ONE, 2014

Chronic Kidney Disease (CKD) is a relatively common condition not only associated with increased ... more Chronic Kidney Disease (CKD) is a relatively common condition not only associated with increased morbidity and mortality but also fuelling End Stage Renal Disease (ESRD). Among developed nations, Greece has one of the highest ESRD incidence rates, yet there is limited understanding of the epidemiology of earlier stages of CKD. Cross-sectional survey of pre-dialysis CKD outpatients in nephrology clinics in the National Health Care system between October 2009 and October 2010. Demographics, cause of CKD, blood pressure, level of renal function, duration of CKD and nephrology care, and specialty of referral physician were collected and analyzed. Different methods for estimating renal function (Cockroft-Gault [CG], CKD-Epi and MDRD) and staging CKD were assessed for agreement. A total of 1,501 patients in 9 centers were enrolled. Diabetic nephropathy was the most common nephrologist assigned cause of CKD (29.7%). In total, 36.5% of patients had self-referred to the nephrologist; patients with diabetes or serum creatinine above 220 µmol/l (eGFR&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;40 ml/min/1.73 m2) were more likely to have been referred by a physician. Agreement between MDRD and CKD-Epi, but not between CG, the other estimating equations, was excellent. There was substantial heterogeneity with respect to renal diagnoses, referral patterns and blood pressure among participating centers. In this first epidemiologic assessment of CKD in Greece, we documented delayed referral and high rates of self-referral among patients with CKD. eGFR reporting, currently offered by a limited number of laboratories, may facilitate detection of CKD at an earlier, more treatable stage.

Research paper thumbnail of HCV-Associated Membranoproliferative Glomerulonephritis

HCV Infection and Cryoglobulinemia, 2011

Research paper thumbnail of FPGA Implementation of Spiking Neural Network

1st Conference on Embedded Systems, Computational Intelligence and Telematics in Control, 2012

ABSTRACT Spiking Neural Networks (SNN) have optimal characteristics for hardware implementation. ... more ABSTRACT Spiking Neural Networks (SNN) have optimal characteristics for hardware implementation. They can communicate among neurons using spikes, which in terms of logic resources, means a single bit, reducing the logic occupation in a device. Additionally, SNN are similar in performance compared to other neural Artificial Neural Network (ANN) architectures such as Multilayer Perceptron, and others. SNN are very similar to those found in the biological neural system, having weights and delays as adjustable parameters. This work describes the chosen models for the implemented SNN: Spike Response Model (SRM) and temporal coding is used. FPGA implementation using VHDL language is also described, detailing logic resources usage and speed of operation for a simple pattern recognition problem.

Research paper thumbnail of Correction: Cytoskeletal Rearrangements in Synovial Fibroblasts as a Novel Pathophysiological Determinant of Modeled Rheumatoid Arthritis

PLoS Genetics, 2005

Rheumatoid arthritis is a chronic inflammatory disease with a high prevalence and substantial soc... more Rheumatoid arthritis is a chronic inflammatory disease with a high prevalence and substantial socioeconomic burden. Despite intense research efforts, its aetiology and pathogenesis remain poorly understood. To identify novel genes and/or cellular pathways involved in the pathogenesis of the disease, we utilized a well-recognized tumour necrosis factor-driven animal model of this disease and performed high-throughput expression profiling with subtractive cDNA libraries and oligonucleotide microarray hybridizations, coupled with independent statistical analysis. This twin approach was validated by a number of different methods in other animal models of arthritis as well as in human patient samples, thus creating a unique list of disease modifiers of potential therapeutic value. Importantly, and through the integration of genetic linkage analysis and Gene Ontology-assisted functional discovery, we identified the gelsolin-driven synovial fibroblast cytoskeletal rearrangements as a novel pathophysiological determinant of the disease.

Research paper thumbnail of Operational criteria for selecting a cDNA microarray data normalization algorithm

Oncology Reports, 2006

Microarray technology allows gene expression profiling at a global level. Many algorithms for the... more Microarray technology allows gene expression profiling at a global level. Many algorithms for the normalization of raw microarray data have been proposed, but no attempt has yet been made to propose operationally verifiable criteria for their comparative evaluation, which is necessary for the selection of the most appropriate method for a given dataset. This study develops a set of operational criteria for assessing the impact of various normalization algorithms in terms of accuracy (bias), precision (variance) and over-fitting (information reduction). The use of these criteria is illustrated by applying the three most widely used algorithms (global median normalization, spiked-in based normalization and lowess) on a specifically designed, multiply-controlled dataset.

Research paper thumbnail of Successful treatment with thalidomide in a liver transplant recipient with giant esophageal ulcers

Liver Transplantation, 2006

Research paper thumbnail of Three-Dimensional Imaging Reveals Ureteric and Mesenchymal Defects in Fgfr2-Mutant Kidneys

Journal of the American Society of Nephrology, 2009

Current techniques to morphologically characterize the processes of nephrogenesis and ureteric br... more Current techniques to morphologically characterize the processes of nephrogenesis and ureteric branching during kidney development have many limitations. Here, we used in vivo three-dimensional analysis to study renal development in mice lacking fibroblast growth factor receptor 2 in the ureteric bud (Fgfr2 UBϪ/Ϫ ) and in littermate controls. We found that Fgfr2 UBϪ/Ϫ mice have more severe defects in ureteric branching morphogenesis than previously reported, including significantly fewer branches and tips than control mice. Furthermore, these mice had decreased ureteric volume and surface area and longer ureteric segments than control mice. We also observed previously unrecognized abnormalities in nephrogenesis, including a gradual increase in volume and surface area during maturation from renal vesicles to mature nephrons, in the mutant mice. Finally, we quantified many events of normal renal development that are either difficult or impossible to measure without this three-dimensional technique. In summary, the three-dimensional approach is a powerful and quantitative means to characterize branching morphogenesis and nephrogenesis.