Search results for: type approval
6803 Expression of Interferon-Lambda Receptor-(IFN-λRα) in Mononuclear Phagocyte Cells (MPCs) Is Influenced by the Levels of Newly Discovered Type III IFN-λ4 in Vitro
Authors: Hashaam Akhtar
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IFNλR1 and IL10R2 collectively construct a heterodimer, which is an acknowledged functional receptor for all type III interferons (IFNs). Expression of IFNλR1 is highly tissue specific, which can help in making type III IFNs a drug of choice as comparable to its analogue, type I IFNs, for treating hepatitis C in the near future. Although, expression of IFNλR1 also varies with the concentration of type I IFNs, but in this study it was shown that the expression of IFNλR1 varies with the protein titers of IFN-α, IFN-λ3 and the newly discovered IFN-λ4. High dosage of IFN-α reduces the expression of IFNλR1 in HepG2 cells, which can affect the antiviral activity of type III IFNs in vivo. We premeditated an experimental strategy to differentiate monocytes into dendritic cells (DCs), type I and type II macrophages in vitro and quantified the expression of the IFNλR1 by qPCR. The exposure of newly discovered IFN-λ4 to macrophages and DCs also raised the expression of its own receptor, which shows that expression of IFN-λ4 protein in hepatitis C patient may augment type I treatment and help ease off viral titers. The results of this study may contribute in some understanding towards the mechanisms involved in the selective expression of IFNLR1 and exceptionalities associated with the receptor.Keywords: IFNLR1, Interferon Lambda 4 (IFN-λ4), Mononuclear Phagocyte Cells (MPCs), expression
Procedia PDF Downloads 3596802 Modeling Optimal Lipophilicity and Drug Performance in Ligand-Receptor Interactions: A Machine Learning Approach to Drug Discovery
Authors: Jay Ananth
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The drug discovery process currently requires numerous years of clinical testing as well as money just for a single drug to earn FDA approval. For drugs that even make it this far in the process, there is a very slim chance of receiving FDA approval, resulting in detrimental hurdles to drug accessibility. To minimize these inefficiencies, numerous studies have implemented computational methods, although few computational investigations have focused on a crucial feature of drugs: lipophilicity. Lipophilicity is a physical attribute of a compound that measures its solubility in lipids and is a determinant of drug efficacy. This project leverages Artificial Intelligence to predict the impact of a drug’s lipophilicity on its performance by accounting for factors such as binding affinity and toxicity. The model predicted lipophilicity and binding affinity in the validation set with very high R² scores of 0.921 and 0.788, respectively, while also being applicable to a variety of target receptors. The results expressed a strong positive correlation between lipophilicity and both binding affinity and toxicity. The model helps in both drug development and discovery, providing every pharmaceutical company with recommended lipophilicity levels for drug candidates as well as a rapid assessment of early-stage drugs prior to any testing, eliminating significant amounts of time and resources currently restricting drug accessibility.Keywords: drug discovery, lipophilicity, ligand-receptor interactions, machine learning, drug development
Procedia PDF Downloads 766801 Kidney Stones in Individuals Living with Diabetes Mellitus at King Abdul-Aziz Medical City - Tertiary Care Center, Jeddah, Saudi Arabia: A Retrospective Cohort Study
Authors: Suhaib Radi, Ibrahim Basem Nafadi, Abdullah Ahmed Alsulami, Nawaf Faisal Halabi, Abdulrhman Abdullah Alsubhi, Sami Wesam Maghrabi, Waleed Saad Alshehri
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Background: Kidney stones greatly affect individuals. The range of these effects regarding multiple kidney stone factors (size, presence of obstruction, and modality of treatment) in stone formers with and without diabetes has not been well explored in the literature to the best of the author's knowledge. Our goal is to investigate this unexplored correlation between diabetes and kidney stones by conducting a Cohort retrospective study to precisely evaluate the effects of this condition and the existence of complications in adult individuals with diabetes in Saudi Arabia in comparison to a non-diabetic control group. Methodology: This is a retrospective cohort study aiming to evaluate the range of effects of kidney stones in stone formers in a group of adults diagnosed with type 2 diabetes mellitus and adults without diabetes between 2017 and 2019 in Jeddah, Saudi Arabia. An IRB approval has been granted for this study. The data was analyzed using SPSS. The data was collected from the 1st of December 2022 until the 1st of March 2023. Results: A total of 254 individuals diagnosed with kidney stones were included, 127 of whom were adult individuals with type 2 diabetes, and 127 were non-diabetics. Our study shows that the individuals affected with diabetes were more likely to have larger kidney stones in comparison to individuals without diabetes (13.12 mm vs. 10.53 mm, p-value = 0.03). Moreover, individuals with hypertension and dyslipidemia also had significantly larger stones. On the other hand, no significant difference was found in the presence of obstruction and modality of treatment between the two groups. Conclusion: This study done in Saudi Arabia found that individuals with kidney stones who concurrently had diabetes formed larger kidney stones, and they were also found to have other comorbidities such as HTN, dyslipidemia, obesity, and renal disease. The significance of these findings could assist in the future of primary and secondary prevention of renal stones.Keywords: kidney stone, type 2 DM, metabolic syndrome, lithotripsy
Procedia PDF Downloads 756800 Interval Type-2 Fuzzy Vibration Control of an ERF Embedded Smart Structure
Authors: Chih-Jer Lin, Chun-Ying Lee, Ying Liu, Chiang-Ho Cheng
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The main objective of this article is to present the semi-active vibration control using an electro-rheological fluid embedded sandwich structure for a cantilever beam. ER fluid is a smart material, which cause the suspended particles polarize and connect each other to form chain. The stiffness and damping coefficients of the ER fluid can be changed in 10 micro seconds; therefore, ERF is suitable to become the material embedded in the tunable vibration absorber to become a smart absorber. For the ERF smart material embedded structure, the fuzzy control law depends on the experimental expert database and the proposed self-tuning strategy. The electric field is controlled by a CRIO embedded system to implement the real application. This study investigates the different performances using the Type-1 fuzzy and interval Type-2 fuzzy controllers. The Interval type-2 fuzzy control is used to improve the modeling uncertainties for this ERF embedded shock absorber. The self-tuning vibration controllers using Type-1 and Interval Type-2 fuzzy law are implemented to the shock absorber system. Based on the resulting performance, Internal Type-2 fuzzy is better than the traditional Type-1 fuzzy control for this vibration control system.Keywords: electro-rheological fluid, semi-active vibration control, shock absorber, type 2 fuzzy control
Procedia PDF Downloads 4136799 Ocular Complications in Type 1 Diabetes Mellitus in Zahedan: A Tropical Region in Southeast of Iran
Authors: Mohammad Hossain Validad, Maryam Nakhaei-Moghadam, Monire Mahjoob
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Introduction: The prevalence of type 1 diabetes is increasing worldwide, and given the role of ethnicity and race in complications of diabetes, this study was designed to evaluate the ocular complications of type 1 diabetes mellitus in Zahedan. Methods: This prospective cross-sectional study was conducted on Type 1 diabetic children that referred to Alzahra Eye Hospital. All patients had a dilated binocular indirect ophthalmoscopy using a +90 D condensing lens and slit-lamp biomicroscopy. Age, gender, onset, duration of diabetes, and HbA1c level were recorded. Results: 76 type 1 diabetes patients with an age of 11.93 ± 3.76 years participated in this study. Out of 76 patients with diabetes, 19 people (25%) had ocular complications. There was a significant difference in age (P=0.01) and disease duration (P=0.07) between the two groups with and without ocular complications. Odd ratios for ocular complications with age and duration of diabetes were 1.32 and 1.32, respectively. Conclusion: Cataract was the most common ocular complication in type 1 diabetes in Zahedan, a tropical region that was significantly related to the duration of the disease and the age of the patients.Keywords: diabet mellitus type one, cataract, ocular complication, hemoglobin A1C
Procedia PDF Downloads 156798 Offering a Model for Selecting the Most Suitable Type of Thinking for Managers
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The purpose of this paper is to design an applied framework for strategic thinking which can be applied in all managerial levels and all types of organizational environments. No special applied frame has been presented for this thinking. This paper presents a theoretical framework for the thinking type of a manager by making a historical research and studying the scientific documents about thinking of a strategist. In the new theoretical framework it has been tried to suggest the best type of thinking for a strategist after analyzing the environment of his decisions. So, in this framework, the traditional viewpoint about strategic thinking, which has considered it as a special type of right-brain thinking against other types of right-brain thinking and suggested it for a strategist, was put aside and suggests that the strategist should use a suitable type of thinking under different conditions.Keywords: strategic thinking, systemic thinking, lateral thinking, intuitive thinking, hybrid thinking
Procedia PDF Downloads 3076797 Theoretical Study on the Forced Vibration of One Degree of Freedom System, Equipped with Inerter, under Load-Type or Displacement-Type Excitation
Authors: Barenten Suciu
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In this paper, a theoretical study on the forced vibration of one degree of freedom system equipped with inerter, working under load-type or displacement-type excitation, is presented. Differential equations of movement are solved under cosinusoidal excitation, and explicit relations for the magnitude, resonant magnitude, phase angle, resonant frequency, and critical frequency are obtained. Influence of the inertance and damping on these dynamic characteristics is clarified. From the obtained results, one concludes that the inerter increases the magnitude of vibration and the phase angle of the damped mechanical system. Moreover, the magnitude ratio and difference of phase angles are not depending on the actual type of excitation. Consequently, such kind of similitude allows for the comparison of various theoretical and experimental results, which can be broadly found in the literature.Keywords: displacement-type excitation, inerter, load-type excitation, one degree of freedom vibration, parallel connection
Procedia PDF Downloads 1826796 Pattern Of Polymorphism SLC22A1 Gene In Children With Diabetes Mellitus Type 2
Authors: Elly Usman, S. Dante, Diah Purnamasari
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Type 2 diabetes mellitus ( T2DM ) is a syndrome characterized by a state of increased blood sugar levels due to chronic disorders of insulin secretion by pancreatic beta cells and insulin action or a combination of both. The organic cation transporter 1, encoded by the SLC22A1 gene, responsible for the uptake of the antihyperglycemic drug, metformin, in the hepatocyte. We assessed whether a genetic variation in the SLC22A1 gene was associated with the glucose - lowering effect of metformin. Method case study research design. Samples are children with type 2 diabetes mellitus who meet the inclusion criteria. The results proportions SLC22A1 gene polymorphisms in children with diabetes mellitus type 2 amounted to 52.04 % at position 400T/C, there is one heterozygous and one at position 595T/C Conclusion The presence of SLC22A1 gene polymorphisms in children with diabetes mellitus type 2.Keywords: diabetes Mellitus type 2, metformin, organic cation transporter 1, pharmacogenomics
Procedia PDF Downloads 3956795 Caputo-Type Fuzzy Fractional Riccati Differential Equations with Fuzzy Initial Conditions
Authors: Trilok Mathur, Shivi Agarwal
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This paper deals with the solutions of fuzzy-fractional-order Riccati equations under Caputo-type fuzzy fractional derivatives. The Caputo-type fuzzy fractional derivatives are defined based on Hukuhura difference and strongly generalized fuzzy differentiability. The Laplace-Adomian-Pade method is used for solving fractional Riccati-type initial value differential equations of fractional order. Moreover, we also displayed some examples to illustrate our methods.Keywords: Caputo-type fuzzy fractional derivative, Fractional Riccati differential equations, Laplace-Adomian-Pade method, Mittag Leffler function
Procedia PDF Downloads 3666794 Dissection of the Impact of Diabetes Type on Heart Failure across Age Groups: A Systematic Review of Publication Patterns on PubMed
Authors: Nazanin Ahmadi Daryakenari
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Background: Diabetes significantly influences the risk of heart failure. The interplay between distinct types of diabetes, heart failure, and their distribution across various age groups remains an area of active exploration. This study endeavors to scrutinize the age group distribution in publications addressing Type 1 and Type 2 diabetes and heart failure on PubMed while also examining the evolving publication trends. Methods: We leveraged E-utilities and RegEx to search and extract publication data from PubMed using various mesh terms. Subsequently, we conducted descriptive statistics and t-tests to discern the differences between the two diabetes types and the distribution across age groups. Finally, we analyzed the temporal trends of publications concerning both types of diabetes and heart failure. Results: Our findings revealed a divergence in the age group distribution between Type 1 and Type 2 diabetes within heart failure publications. Publications discussing Type 2 diabetes and heart failure were more predominant among older age groups, whereas those addressing Type 1 diabetes and heart failure displayed a more balanced distribution across all age groups. The t-test revealed no significant difference in the means between the two diabetes types. However, the number of publications exploring the relationship between Type 2 diabetes and heart failure has seen a steady increase over time, suggesting an escalating interest in this area. Conclusion: The dissection of publication patterns on PubMed uncovers a pronounced association between Type 2 diabetes and heart failure within older age groups. This highlights the critical need to comprehend the distinct age group differences when examining diabetes and heart failure to inform and refine targeted prevention and treatment strategies.Keywords: Type 1 diabetes, Type 2 diabetes, heart failure, age groups, publication patterns, PubMed
Procedia PDF Downloads 606793 Estimation of Stress-Strength Parameter for Burr Type XII Distribution Based on Progressive Type-II Censoring
Authors: A. M. Abd-Elfattah, M. H. Abu-Moussa
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In this paper, the estimation of stress-strength parameter R = P(Y < X) is considered when X; Y the strength and stress respectively are two independent random variables of Burr Type XII distribution. The samples taken for X and Y are progressively censoring of type II. The maximum likelihood estimator (MLE) of R is obtained when the common parameter is unknown. But when the common parameter is known the MLE, uniformly minimum variance unbiased estimator (UMVUE) and the Bayes estimator of R = P(Y < X) are obtained. The exact condence interval of R based on MLE is obtained. The performance of the proposed estimators is compared using the computer simulation.Keywords: Burr Type XII distribution, progressive type-II censoring, stress-strength model, unbiased estimator, maximum-likelihood estimator, uniformly minimum variance unbiased estimator, confidence intervals, Bayes estimator
Procedia PDF Downloads 4286792 An Invertebrate-Type Lysozyme from Chinese Mitten Crab Eriocheir Sinensis: Cloning and Characterization
Authors: Fengmei Li, Li Xu, Guoliang Xia
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Lysozyme is a catalytic enzyme that performs bacterial cell lysis by cleaving the β-1,4-glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine of peptidoglycan in cell walls. In the present study, an invertebrate-type (i-type) lysozyme gene was cloned from Chinese mitten crab Eriocheir sinensis (designated as EsLysozyme) based on PCR-based rapid amplification of cDNA ends (RACE) technology. The full-length cDNA of EsLysozyme was of 831 bp. SMART and SIGNALP 3.0 program analysis revealed that EsLysozyme contained a signal peptide and a destabilase domain. The five amino acid residues (Tyr63, Trp64, Tyr91, His110, Pro114) and the conserved motif GSLSCG(P/Y)FQI and CL(E/L/R/H)C(I/M)C in i-type lysozymes were also found in EsLysozyme. The high similarity of EsLysozyme with L. vannamei lysozymes and phylogenetic analysis suggested that EsLysozyme should be a new member of i-type lysozyme family.Keywords: i-type lysozyme, Eriocheir sinensis, cloning, characterization
Procedia PDF Downloads 2636791 Synthesis and Characterisation of New Heteropolyanion Substitute by CO2+
Authors: Ouahiba Bechiri, Mostefa Abbessi
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In recent year, polyoxometallates are intensely being explored because of their applications as new materiels, structural aesthetics, catalysts, and biologically active compounds. heteropolyanions of general formulae [X2M18O62] n- (X= heteroatom, e.g. P, Si) and (M=W, Mo), known as Dawson-type anions, constitue a special class of polyoxometallate compounds. In this present work, cobalt substituted heteropolyanion Dawson-type [HP2W15Mo3CoO61] were synthesized and characterized by IR spectroscopy, 31 P NMR, cyclic voltammetry.Keywords: heteropolyanions, nanomaterials, Dawson-type, characterization
Procedia PDF Downloads 2276790 Altered L-Type Calcium Channel Activity in Atrioventricular Nodal Myocytes from Rats with Streptozotocin-Induced Type I Diabetes Mellitus
Authors: Kathryn H. Yull, Lina T. Al Kury, Frank Christopher Howarth
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Cardiovascular diseases are frequently reported in patients with Type-1 Diabetes mellitus (DM). In addition to changes in cardiac muscle inotropy, electrical abnormalities are also commonly observed in these patients. In the present study, using streptozotocin (STZ) rat model of Type-1 DM, we have characterized the changes in L-type calcium channel activity in single atrioventricular nodal (AVN) myocytes. Ionic currents were recorded from AVN myocytes isolated from the hearts of control rats and from those with STZ-induced diabetes. Patch-clamp recordings were used to assess changes in cellular electrical activity in individual myocytes. Type-1 DM significantly altered the cellular characteristics of L-type calcium current (ICaL). A reduction in peak ICaL density was observed, with no corresponding changes in the activation parameters of the current. ICaL also exhibited faster time-dependent inactivation in AVN myocytes from diabetic rats. A negative shift in the voltage dependence of inactivation was also evident. These findings demonstrate that experimentally–induced type-1 DM significantly alters AVN L-type calcium channel cellular electrophysiology. The changes in ion channel activity may underlie the abnormalities in the cardiac electrical function that contribute to the high mortality levels in patients with DM.Keywords: cardiac, ion-channel, diabetes, atrioventricular node, calcium channel
Procedia PDF Downloads 3126789 IL-21 Production by CD4+ Effector T Cells and Frequency of Circulating Follicular Helper T Cells Are Increased in Type 1 Diabetes Patients
Authors: Ferreira RC, Simons HZ, Thompson WS, Cutler AJ, Dopico XC, Smyth DJ, Mashar M, Schuilenburg H, Walker NM, Dunger DB, Wallace C, Todd JA, Wicker LS, Pekalski ML
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Type 1 diabetes is caused by autoimmune destruction of insulin-secreting beta cells in the pancreas. T cells are known to play an important role in this immune-mediated destruction; however, there is no general consensus regarding alterations in cytokine production or T cell subsets in peripheral blood of patients with type 1 diabetes. Using polychromatic flow cytometry of peripheral blood mononuclear cells (PBMCs), we assessed production of the proinflammatory cytokines IL-21, IFN-γ and IL-17 by memory CD4 T effector (Teff) cells in 69 patients with type 1 diabetes and 61 healthy donors. We found a 21.9% (95% CI 5.8, 40.2; p = 3.9 × 10(-3)) higher frequency of IL-21(+) CD45RA(-) memory CD4(+) Teffs in patients with type 1 diabetes (geometric mean 5.92% [95% CI 5.44, 6.44]) compared with healthy donors (geometric mean 4.88% [95% CI 4.33, 5.50]). In a separate cohort of 30 patients with type 1 diabetes and 32 healthy donors, we assessed the frequency of circulating T follicular helper (Tfh) cells in whole blood. Consistent with the increased production of IL-21, we also found a 14.9% increase in circulating Tfh cells in the patients with type 1 diabetes (95% CI 2.9, 26.9; p = 0.016). Analysis of IL-21 production by PBMCs from a subset of 46 of the 62 donors immunophenotyped for Tfh showed that frequency of Tfh cells was associated with the frequency of IL-21+ cells (r2 = 0.174, p = 0.004). These results indicate that increased IL-21 production is likely to be an aetiological factor in the pathogenesis of type 1 diabetes that could be considered as a potential therapeutic target.Keywords: T follicular helper cell, IL-21, IL-17, type 1 diabetes
Procedia PDF Downloads 3536788 First-Principles Density Functional Study of Nitrogen-Doped P-Type ZnO
Authors: Abdusalam Gsiea, Ramadan Al-habashi, Mohamed Atumi, Khaled Atmimi
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We present a theoretical investigation on the structural, electronic properties and vibrational mode of nitrogen impurities in ZnO. The atomic structures, formation and transition energies and vibrational modes of (NO3)i interstitial or NO4 substituting on an oxygen site ZnO were computed using ab initio total energy methods. Based on Local density functional theory, our calculations are in agreement with one interpretation of bound-excition photoluminescence for N-doped ZnO. First-principles calculations show that (NO3)i defects interstitial or NO4 substituting on an Oxygen site in ZnO are important suitable impurity for p-type doping in ZnO. However, many experimental efforts have not resulted in reproducible p-type material with N2 and N2O doping. by means of first-principle pseudo-potential calculation we find that the use of NO or NO2 with O gas might help the experimental research to resolve the challenge of achieving p-type ZnO.Keywords: DFF, nitrogen, p-type, ZnO
Procedia PDF Downloads 4376787 The Effect of Program Type on Mutation Testing: Comparative Study
Authors: B. Falah, N. E. Abakouy
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Due to its high computational cost, mutation testing has been neglected by researchers. Recently, many cost and mutants’ reduction techniques have been developed, improved, and experimented, but few of them has relied the possibility of reducing the cost of mutation testing on the program type of the application under test. This paper is a comparative study between four operators’ selection techniques (mutants sampling, class level operators, method level operators, and all operators’ selection) based on the program code type of each application under test. It aims at finding an alternative approach to reveal the effect of code type on mutation testing score. The result of our experiment shows that the program code type can affect the mutation score and that the programs using polymorphism are best suited to be tested with mutation testing.Keywords: equivalent mutant, killed mutant, mutation score, mutation testing, program code type, software testing
Procedia PDF Downloads 5266786 Characteristics of Ozone Generated from Dielectric Barrier Discharge Plasma Actuators
Authors: R. Osada, S. Ogata, T. Segawa
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Dielectric barrier discharge plasma actuators (DBD-PAs) have been developed for active flow control devices. However, it is necessary to reduce ozone produced by DBD toward practical applications using DBD-PAs. In this study, variations of ozone concentration, flow velocity, power consumption were investigated by changing exposed electrodes of DBD-PAs. Two exposed electrode prototypes were prepared: span-type with exposed electrode width of 0.1 mm, and normal-type with width of 5 mm. It was found that span-type shows lower power consumption and higher flow velocity than that of normal-type at Vp-p = 4.0-6.0 kV. Ozone concentration of span-type higher than normal-type at Vp-p = 4.0-8.0 kV. In addition, it was confirmed that catalyst located in downstream from the exposed electrode can reduce ozone concentration between 18 and 42% without affecting the induced flow.Keywords: dielectric barrier discharge plasma actuators, ozone diffusion, PIV measurement, power consumption
Procedia PDF Downloads 2186785 Real-world Characterization of Treatment Intensified (Add-on to Metformin) Adults with Type 2 Diabetes in Pakistan: A Multi-center Retrospective Study (Converge)
Authors: Muhammad Qamar Masood, Syed Abbas Raza, Umar Yousaf Raja, Imran Hassan, Bilal Afzal, Muhammad Aleem Zahir, Atika Shaheer
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Background: Cardiovascular disease (CVD) is a major burden among people with type 2 diabetes (T2D) with 1 in 3 reported to have CVD. Therefore, understanding real-world clinical characteristics and prescribing patterns could help in better care. Objective: The CONVERGE (Cardiovascular Outcomes and Value in the Real world with GLP-1RAs) study characterized demographics and medication usage patterns in T2D intensified (add-on to metformin) overall population. The data were further divided into subgroups {dipeptidyl peptidase-4 inhibitors (DPP-4is), sulfonylureas (SUs), insulins, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is)}, according to the latest prescribed antidiabetic agent (ADA) in India/Pakistan/Thailand. Here, we report findings from Pakistan. Methods: A multi-center retrospective study utilized data from medical records between 13-Sep-2008 (post-market approval of GLP-1RAs) and 31-Dec-2017 in adults (≥18-year-old). The data for this study were collected from 05 centers / institutes located in major cities of Pakistan, including Karachi, Lahore, Islamabad, and Multan. These centers included National Hospital, Aga Khan University Hospital, Diabetes Endocrine Clinic Lahore, Shifa International Hospital, Mukhtar A Sheikh Hospital Multan. Data were collected at start of medical record and at 6 or 12-months prior to baseline based on variable type; analyzed descriptively. Results: Overall, 1,010 patients were eligible. At baseline, overall mean age (SD) was 51.6 (11.3) years, T2D duration was 2.4 (2.6) years, HbA1c was 8.3% (1.9) and 35% received ≥1CVD medications in the past 1-year (before baseline). Most frequently prescribed ADAs post-metformin were DPP-4is and SUs (~63%). Only 6.5% received GLP-1RAs and SGLT-2is were not available in Pakistan during the study period. Overall, it took a mean of 4.4 years and 5 years to initiate GLP-1RAs and SGLT-2is, respectively. In comparison to other subgroups, more patients from GLP-1RAs received ≥3 types of ADA (58%), ≥1 CVD medication (64%) and had higher body mass index (37kg/m2). Conclusions: Utilization of GLP-1RAs and SGLT-2is was low, took longer time to initiate and not before trying multiple ADAs. This may be due to lack of evidence for CV benefits for these agents during the study period. The planned phase 2 of the CONVERGE study can provide more insights into utilization and barriers to prescribe GLP-1RAs and SGLT-2is post 2018 in Pakistan.Keywords: type 2 diabetes, GLP-1RA, treatment intensification, cardiovascular disease
Procedia PDF Downloads 246784 Formulation of Corrector Methods from 3-Step Hybid Adams Type Methods for the Solution of First Order Ordinary Differential Equation
Authors: Y. A. Yahaya, Ahmad Tijjani Asabe
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This paper focuses on the formulation of 3-step hybrid Adams type method for the solution of first order differential equation (ODE). The methods which was derived on both grid and off grid points using multistep collocation schemes and also evaluated at some points to produced Block Adams type method and Adams moulton method respectively. The method with the highest order was selected to serve as the corrector. The convergence was valid and efficient. The numerical experiments were carried out and reveal that hybrid Adams type methods performed better than the conventional Adams moulton method.Keywords: adam-moulton type (amt), corrector method, off-grid, block method, convergence analysis
Procedia PDF Downloads 5896783 Lyapunov Type Inequalities for Fractional Impulsive Hamiltonian Systems
Authors: Kazem Ghanbari, Yousef Gholami
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This paper deals with study about fractional order impulsive Hamiltonian systems and fractional impulsive Sturm-Liouville type problems derived from these systems. The main purpose of this paper devotes to obtain so called Lyapunov type inequalities for mentioned problems. Also, in view point on applicability of obtained inequalities, some qualitative properties such as stability, disconjugacy, nonexistence and oscillatory behaviour of fractional Hamiltonian systems and fractional Sturm-Liouville type problems under impulsive conditions will be derived. At the end, we want to point out that for studying fractional order Hamiltonian systems, we will apply recently introduced fractional Conformable operators.Keywords: fractional derivatives and integrals, Hamiltonian system, Lyapunov-type inequalities, stability, disconjugacy
Procedia PDF Downloads 3296782 Scientific and Regulatory Challenges of Advanced Therapy Medicinal Products
Authors: Alaa Abdellatif, Gabrièle Breda
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Background. Advanced therapy medicinal products (ATMPs) are innovative therapies that mainly target orphan diseases and high unmet medical needs. ATMP includes gene therapy medicinal products (GTMP), somatic cell therapy medicinal products (CTMP), and tissue-engineered therapies (TEP). Since legislation opened the way in 2007, 25 ATMPs have been approved in the EU, which is about the same amount as the U.S. Food and Drug Administration. However, not all of the ATMPs that have been approved have successfully reached the market and retained their approval. Objectives. We aim to understand all the factors limiting the market access to very promising therapies in a systemic approach, to be able to overcome these problems, in the future, with scientific, regulatory and commercial innovations. Further to recent reviews that focus either on specific countries, products, or dimensions, we will address all the challenges faced by ATMP development today. Methodology. We used mixed methods and a multi-level approach for data collection. First, we performed an updated academic literature review on ATMP development and their scientific and market access challenges (papers published between 2018 and April 2023). Second, we analyzed industry feedback from cell and gene therapy webinars and white papers published by providers and pharmaceutical industries. Finally, we established a comparative analysis of the regulatory guidelines published by EMA and the FDA for ATMP approval. Results: The main challenges in bringing these therapies to market are the high development costs. Developing ATMPs is expensive due to the need for specialized manufacturing processes. Furthermore, the regulatory pathways for ATMPs are often complex and can vary between countries, making it challenging to obtain approval and ensure compliance with different regulations. As a result of the high costs associated with ATMPs, challenges in obtaining reimbursement from healthcare payers lead to limited patient access to these treatments. ATMPs are often developed for orphan diseases, which means that the patient population is limited for clinical trials which can make it challenging to demonstrate their safety and efficacy. In addition, the complex manufacturing processes required for ATMPs can make it challenging to scale up production to meet demand, which can limit their availability and increase costs. Finally, ATMPs face safety and efficacy challenges: dangerous adverse events of these therapies like toxicity related to the use of viral vectors or cell therapy, starting material and donor-related aspects. Conclusion. As a result of our mixed method analysis, we found that ATMPs face a number of challenges in their development, regulatory approval, and commercialization and that addressing these challenges requires collaboration between industry, regulators, healthcare providers, and patient groups. This first analysis will help us to address, for each challenge, proper and innovative solution(s) in order to increase the number of ATMPs approved and reach the patientsKeywords: advanced therapy medicinal products (ATMPs), product development, market access, innovation
Procedia PDF Downloads 506781 Hypoglycemic Coma in Elderly Patients with Diabetes mellitus
Authors: D. Furuya, H. Ryujin, S. Takahira, Y. Sekine, Y. Oya, K. Sonoda, H. Ogawa, Y. Nomura, R. Maruyama, H. Kim, T. Kudo, A. Nakano, T. Saruta, S. Sugita, M. Nemoto, N. Tanahashi
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Purpose: To study the clinical characteristics of hypoglycemic coma in adult patients with type 1 or type 2 diabetes mellitus (DM). Methods: Participants in this retrospective study comprised 91 patients (54 men, 37 women; mean age ± standard deviation, 71.5 ± 12.6 years; range, 42-97 years) brought to our emergency department by ambulance with disturbance of consciousness in the 7 years from April 2007 to March 2014. Patients with hypoglycemia caused by alcoholic ketoacidosis, nutrition disorder, malignancies and psychological disorder were excluded. Results: Patients with type 1 (8 of 91) or type 2 DM (83 of 91) were analyzed. Mean blood sugar level was 31.6 ± 10.4 in all patients. A sulfonylurea (SU) was more commonly used in elderly (>75 years old; n=44)(70.5%) than in younger patients (36.2%, p < 0.05). Cases showing prolonged unconsciousness (range, 1 hour to 21 days; n=30) included many (p < 0.05) patients with dementia (13.3%; 0.5% without dementia) and fewer (p < 0.05) patients with type 1 DM (0%; 13.1% in type 2 DM). Specialists for DM (n=33) used SU less often (24.2%) than general physicians (69.0%, p < 0.05). Conclusion: In cases of hypoglycemic coma, SU was frequently used in elderly patients with DM.Keywords: hypoglycemic coma, Diabetes mellitus, unconsciousness, elderly patients
Procedia PDF Downloads 4556780 The Organizational Commitment of the Public Enterprises in Thailand
Authors: Routsukol Sunalai
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The purpose of this study is to examine the impact of public enterprise reform policy on the attributes of organizational commitments in the public energy enterprises in Thailand. It compares three structural types of public energy enterprises: Totally state-owned public enterprises (type I), partially transformed public enterprises (type II), and totally transformed public enterprises (type III), based on the degree of state partially transformed public enterprises (type II), and totally transformed public enterprises (type III),based on the degree of reformed organizations, by analyzing the presence of the desirable attributes of organizational commitment as perceived by employees. Findings indicate that there are statistically significant differences in the level of some dimensions of organizational commitment (affective commitment and normative commitment) between the three types of public energy enterprises. The lack of a structural type difference holds for only continuance commitment. The results also indicate empirical evidence concerning the causal relationship between the antecedents and including organizational commitment also.Keywords: management control, organizational commitment, public enterprises in Thailand, public enterprise reform
Procedia PDF Downloads 2616779 A Formal Verification Approach for Linux Kernel Designing
Authors: Zi Wang, Xinlei He, Jianghua Lv, Yuqing Lan
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Kernel though widely used, is complicated. Errors caused by some bugs are often costly. Statically, more than half of the mistakes occur in the design phase. Thus, we introduce a modeling method, KMVM (Linux Kernel Modeling and verification Method), based on type theory for proper designation and correct exploitation of the Kernel. In the model, the Kernel is separated into six levels: subsystem, dentry, file, struct, func, and base. Each level is treated as a type. The types are specified in the structure and relationship. At the same time, we use a demanding path to express the function to be implemented. The correctness of the design is verified by recursively checking the type relationship and type existence. The method has been applied to verify the OPEN business of VFS (virtual file system) in Linux Kernel. Also, we have designed and developed a set of security communication mechanisms in the Kernel with verification.Keywords: formal approach, type theory, Linux Kernel, software program
Procedia PDF Downloads 966778 Apolipoprotein E Gene Polymorphism and Its Association with Cardiovascular Heart Disease Risk Factors in Type 2 Diabetes Mellitus
Authors: Amani Ashari, Julia Omar, Arif Hashim, Shahrul Hamid
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Apolipoprotein E (APOE) gene polymorphism has influence on serum lipids which relates to cardiovascular risk. The purpose of this study was to determine the frequency distribution of APOE alleles among Malaysian Type 2 Diabetes Mellitus (DM) patients with and without coronary artery disease (CAD) and their association with serum lipid profiles. A total of 115 patients were recruited in which 78 patients had Type 2 DM without CAD and 37 patients had Type 2 DM with CAD. The APOE polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The APOE ɛ3 allele was the most common one in both groups. There was no significant association between the APOE genotypes and the CAD status in Type 2 DM using Pearson χ2 test. Further analysis indicated there were no significant differences in all lipid parameters between E2, E3 and E4 subgroups in both groups. The study showed that the E4 allele carriers of Type 2 DM with CAD patients had higher LDL-C level and lower HDL-C level compared to the other allele carriers. However, analyses showed these levels were not statistically different. The study also showed that the Type 2 DM with CAD group with E2 allele had higher triglyceride (TG). In conclusion, further study with larger sample size is needed to confirm role of E4 as a marker of CAD among Type 2 DM patients in Malaysian population.Keywords: Apolipoprotein E, diabetes mellitus, cardiovascular disease, lipids
Procedia PDF Downloads 2686777 Vertically Grown P–Type ZnO Nanorod on Ag Thin Film
Authors: Jihyun Park, Tae Il Lee, Jae-Min Myoung
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A Silver (Ag) thin film is introduced as a template and doping source for vertically aligned p–type ZnO nanorods. ZnO nanorods were grown using a ammonium hydroxide based hydrothermal process. During the hydrothermal process, the Ag thin film was dissolved to generate Ag ions in the solution. The Ag ions can contribute to doping in the wurzite structure of ZnO and the (111) grain of Ag thin film can be the epitaxial temporal template for the (0001) plane of ZnO. Hence, Ag–doped p–type ZnO nanorods were successfully grown on the substrate, which can be an electrode or semiconductor for the device application. To demonstrate the potentials of this idea, p–n diode was fabricated and its electrical characteristics were demonstrated.Keywords: hydrothermal process, Ag–doped ZnO nanorods, p–type ZnO
Procedia PDF Downloads 4386776 Evaluation of Best-Fit Probability Distribution for Prediction of Extreme Hydrologic Phenomena
Authors: Karim Hamidi Machekposhti, Hossein Sedghi
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The probability distributions are the best method for forecasting of extreme hydrologic phenomena such as rainfall and flood flows. In this research, in order to determine suitable probability distribution for estimating of annual extreme rainfall and flood flows (discharge) series with different return periods, precipitation with 40 and discharge with 58 years time period had been collected from Karkheh River at Iran. After homogeneity and adequacy tests, data have been analyzed by Stormwater Management and Design Aid (SMADA) software and residual sum of squares (R.S.S). The best probability distribution was Log Pearson Type III with R.S.S value (145.91) and value (13.67) for peak discharge and Log Pearson Type III with R.S.S values (141.08) and (8.95) for maximum discharge in Jelogir Majin and Pole Zal stations, respectively. The best distribution for maximum precipitation in Jelogir Majin and Pole Zal stations was Log Pearson Type III distribution with R.S.S values (1.74&1.90) and then Pearson Type III distribution with R.S.S values (1.53&1.69). Overall, the Log Pearson Type III distributions are acceptable distribution types for representing statistics of extreme hydrologic phenomena in Karkheh River at Iran with the Pearson Type III distribution as a potential alternative.Keywords: Karkheh River, Log Pearson Type III, probability distribution, residual sum of squares
Procedia PDF Downloads 1706775 Point Estimation for the Type II Generalized Logistic Distribution Based on Progressively Censored Data
Authors: Rana Rimawi, Ayman Baklizi
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Skewed distributions are important models that are frequently used in applications. Generalized distributions form a class of skewed distributions and gain widespread use in applications because of their flexibility in data analysis. More specifically, the Generalized Logistic Distribution with its different types has received considerable attention recently. In this study, based on progressively type-II censored data, we will consider point estimation in type II Generalized Logistic Distribution (Type II GLD). We will develop several estimators for its unknown parameters, including maximum likelihood estimators (MLE), Bayes estimators and linear estimators (BLUE). The estimators will be compared using simulation based on the criteria of bias and Mean square error (MSE). An illustrative example of a real data set will be given.Keywords: point estimation, type II generalized logistic distribution, progressive censoring, maximum likelihood estimation
Procedia PDF Downloads 1676774 Identifying Promoters and Their Types Based on a Two-Layer Approach
Authors: Bin Liu
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Prokaryotic promoter, consisted of two short DNA sequences located at in -35 and -10 positions, is responsible for controlling the initiation and expression of gene expression. Different types of promoters have different functions, and their consensus sequences are similar. In addition, their consensus sequences may be different for the same type of promoter, which poses difficulties for promoter identification. Unfortunately, all existing computational methods treat promoter identification as a binary classification task and can only identify whether a query sequence belongs to a specific promoter type. It is desired to develop computational methods for effectively identifying promoters and their types. Here, a two-layer predictor is proposed to try to deal with the problem. The first layer is designed to predict whether a given sequence is a promoter and the second layer predicts the type of promoter that is judged as a promoter. Meanwhile, we also analyze the importance of feature and sequence conversation in two aspects: promoter identification and promoter type identification. To the best knowledge of ours, it is the first computational predictor to detect promoters and their types.Keywords: promoter, promoter type, random forest, sequence information
Procedia PDF Downloads 163