Modeling gene regulatory networks through data integration

Modeling gene regulatory networks has become a problem of great interest in biology and medical research. Most common methods for learning regulatory dependencies rely on observations in the form of gene expression data. In this dissertation, computational models for gene regulation have been developed based on constrained regression by integrating comprehensive gene expression data for M. tuberculosis with genome-scale ChIP-Seq interaction data. The resulting models confirmed predictive power for expression in independent stress conditions and identified mechanisms driving hypoxic adaptation and lipid metabolism in M. tuberculosis. I then used the regulatory network model for M. tuberculosis to identify factors responding to stress conditions and drug treatments, revealing drug synergies and conditions that potentiate drug treatments. These results can guide and optimize design of drug treatments for this pathogen. I took the next step in this direction, by proposing a new probabilistic framework for learning modular structures in gene regulatory networks from gene expression and protein-DNA interaction data, combining the ideas of module networks and stochastic blockmodels. These models also capture combinatorial interactions between regulators. Comparisons with other network modeling methods that rely solely on expression data, showed the essentiality of integrating ChIP-Seq data in identifying direct regulatory links in M. tuberculosis. Moreover, this work demonstrates the theoretical advantages of integrating ChIP-Seq data for the class of widely-used module network models. The systems approach and statistical modeling presented in this dissertation can also be applied to problems in other organisms. A similar approach was taken to model the regulatory network controlling genes with circadian gene expression in Neurospora crassa, through integrating time-course expression data with ChIP-Seq data. The models explained combinatorial regulations leading to different phase differences in circadian rhythms. The Neurospora crassa network model also works as a tool to manipulate the phases of target genes

Video game training in traumatic brain injury patients: an exploratory case report study using eye tracking

Remediation of attentional impairments is an essential component of cognitive rehabilitation after traumatic brain injury (TBI). Evidence from healthy participants has demonstrated attentional improvement following playing an action video game. This exploratory study investigated its application in TBI participants in a multiple baselines single case experimental design (SCED). Saccadic eye movements, recognized as the visible indicators of visual attention, were assessed to evaluate the effectiveness of the game training. Three severe TBI participants were trained in an action game for 10 hours. Saccadic eye movements during a self-paced saccade and an abstract visual search task were investigated during baseline, mid training and post-training. Using Percentage of Non-overlapping Data (PND), analysis showed consistent increase in the rate of the self-paced saccades in participants 1 (PND=80%) and 2 (PND=70%). In abstract search, fixation duration showed a minimally effective decrease for participant 2 (PND= 60%) and a moderately effective reduction in participant 3 (PND= 80%). Search time showed a highly effective reduction in participant 2 (PND = 100%) and moderately effective decrease in participant 3 (PND=70%). Overall, video game training might modify allocation of attention in eye movements. More evidence is required to validate the usefulness of this novel method of the cognitive training

Diagnostic Accuracy of Different Resolutions of Cone Beam Computed Tomography Imaging System for Detection of Vertical Root Fractures In Presence of Casting Posts

Objective: The diagnosis of vertical root fracture (VRF) in endodontically treated teeth is a clinical challenge due to lack of specific clinical and radiographic signs. Although radiographic evaluation such as CBCT is helpful, intracanal posts can produce artifacts and may impair the quality of CBCT scans. This study aimed to compare the diagnostic accuracy of different resolutions of CBCT in detection of VRF in roots with casting post.Methods: Eighty extracted human premolars were under went routine endodontic procedure and cast posts were subsequently prepared. The teeth were randomly divided into two groups. The fracture lines were induced by an Instron machine in test group, while the teeth in control group had no fracture. The teeth were scanned by CBCT with two voxel resolution protocols (0.15mm  and 0.2mm). Three observers assessed the scans for presence of VRF on a 5-point scale. Diagnostic accuracy indices were estimated and the difference were analyzed with the Mann-Whitney test (p<0.05).Results: Probabilistic sensitivity for 0.15mm and 0.2mm resolution was 59.16 (5.2) and 46.66 (16.64), respectively. Furthermore, probabilistic specificity for 0.15mm resolution was 56.16 (15.21) and for 0.2mm was 61.66 (8.77).There were no statistical differences between different resolutions  in all diagnostic values including sensitivity, specificity, positive and negative predictive values (p>0.05).Conclusion: Diagnostic ability of CBCT in presence of casting posts was not influenced by system resolution. According to ALARA principle, 0.2mm voxel resolution protocol is recommended in these cases

The importance of non-technical skills in accounting graduates

The purpose of this study is to look at the quality issue from the perspective of one of the most important customers of higher education institutions-employers that hire the accounting graduates.Specifically, this study determines how well skill requirements match skill preparedness of accounting graduates.Results re­vealed that. five most important non-technical skills required by employers were the ability to perform assigned tasks, having initiative, teamwork, computer literacy, and problem solving.Employers, however; perceived that higher education institutions do not seem to prepare accounting graduates with all the skills required.The majority of employers agree that quality differences exists between accounting graduates ,from public and pri­vate institutions, and accounting graduates with and without professional qualifications.Finally, the study highlights suggestions to improve the quality of accounting graduates, and also recommendations for future research

Clonidine Versus Chloral Hydrate for Recording Sleep EEG in Children

ObjectiveOne of the difficulties for conduct electroencephalography (EEG) in pediatric patient population is that they are not always cooperative during the procedure. Different medications have been used to induce sedation during EEG recording. In order to find a medication with least adverse effects and high efficacy, we aimed to compare clonidine and chloral hydrate as a premedication prior EEG performing in pediatric population. Materials & MethodsA prospective, randomized, single-blinded, controlled trial was carried out over 198 children (9 to 156 months) to investigate the sedative and adverse effects of clonidine and chloral hydrate. Patients, partially sleep-deprived the night before, were randomly divided in two groups of clonidine (100 patients) and chloral hydrate (98 patients), on an alternative day basis.Results The average sleep onset latency was significantly longer in the clonidine group than chloral hydrate group (Mann-Whitney test, p < 0.0001). Sleep duration ranged between 15-150 minutes and it was not significantly different between two groups (Mann-Whitney test p = 0.2). Drowsiness with chloral hydrate terminated faster than with clonidine. Drowsiness after arousal was seen in 58% and 26.1% of patients in the clonidine and chloral hydrate groups respectively that was  significant  (Mann-Whitney test, p = 0.058). EEG results were reported normal in 77 subjects in the chloral hydrate group (77%) and in 69 subjects (69%) in the clonidine group (p = 0.161). Generalized epileptiform discharges  reported significantly  in the clonidine group  (Mann-Whitney test , p = 0.006).ConclusionThe results of this study showed that both chloral hydrate 5% (one ml/kg)and clonidine (4 μg/kg)could be administered as a pre medication agent for EEG recording in children , although drowsiness after arousal of clonidine is greater than chloral hydrate . However, the yield of generalized epileptiform discharges in the clonidine group was more than the chloral hydrate group.

Employers' perception of the quality of accounting graduates in Malaysia

The purpose of this study is to look at the quality issue from the perspective of one of the most important customers of higher education institutions, employers that hire the accounting graduates.Specifically, this study determines how well skill requirements match skill preparedness of accounting graduates.Results revealed that five most important non-technical skills required by employers were the ability to perform assigned tasks, initiative, teamwork, computer literacy, and problem solving. Employers, however,perceived that higher education institutions had failed to prepare accounting graduates with all the skills required. Majority of employers agree that quality differences exists between accounting graduates from public and private institutions, and accounting graduates with and without professional qualifications. Finally, the study highlights suggestion to improve the quality of accounting graduates, and also recommendations for future research

Relationship Between Heavy Metal levels in Seminal Plasma and Sperm Quality in Iranian Men

Introduction: During the last decades, frequent reports on the poor semen quality in humans have raised many researchers' concerns to study the possible impact of lifestyle or environmental factors on semen quality. The debate is continuously growing on the adverse reproductive effects of exposure to heavy and trace metals found in the environment, even at their relatively low levels. Materials and Methods: This study was carried out from July 2018 to February 2019.  A total of 40 men were divided into two groups (idiopathic oligo– and/or asthenozoospermia and normozoospermic men) to determine the correlation between arsenic (As), cadmium (Cd), copper (Cu), and manganese (Mn) levels in the seminal plasma with sperm quality parameters including concentration, total motility, progressive motility, viability, mitochondrial membrane potential (MMP), sperm plasma membrane integrity (SPMI), acrosome integrity (AI) and DNA fragmentation in Iranian men with idiopathic oligo– and/or asthenozoospermia and normozoospermic individuals.  Results: A significant positive or suggestive correlation was found between as concentrations in the seminal plasma and sperm concentration, motility, progressive motility, viability, MMP, SPMI, and DNA fragmentation. Moreover, seminal plasma Cd concentrations were also correlated negatively with sperm viability. We also found a positive correlation between the seminal plasma Mn levels and sperm concentration, motility, progressive motility, morphology, viability, acrosome integrity, and DNA fragmentation. Conclusion: We showed that the levels of As, Cd, and Mn levels in the seminal plasma are associated with the sperm functional parameters. Considering the unpleasant effects of the studied metals on semen quality, it is suggested that long-term contact with these metals be avoided, especially by people at their reproductive age

Health workers readiness and practice in malaria case detection and appropriate treatment: a meta-analysis and meta-regression

BACKGROUND: Health workers (HWs) appropriate malaria case management includes early detection and prompt treatment with appropriate anti-malarial drugs. Subsequently, HWs readiness and practice are considered authentic evidence to measure the health system performance regarding malaria control programme milestones and to issue malaria elimination certification. There is no comprehensive evidence based on meta-analysis, to measure the performance of HWs in case management of malaria. This study aimed to evaluate HWs performance in early malaria case detection (testing) and the appropriate treatment. METHODS: The published literature in English was systematically searched from Medline, Scopus, Embase, and Malaria Journal up to 30th December 2020. The inclusion criteria were any studies that assessed HWs practice in early case detection by malaria testing and appropriate treatment. Eligibility assessment of records was performed independently in a blinded, standardized way by two reviewers. Pooled prevalence estimates were stratified by HWs cadre type. Meta-regression analysis was performed to explore the impact of the appropriateness of the method and risk of bias as potential sources of the heterogeneity in the presence of effective factors. RESULTS: The study pooled data of 9245 HWs obtained from 15 included studies. No study has been found in eliminating settings. The pooled estimate for appropriate malaria treatment and malaria testing were 60%; 95% CI: 53-67% and 57%; 95% CI: 49-65%, respectively. In the final multivariable meta-regression, HWs cadre and numbers, appropriateness of study methods, malaria morbidity and mortality, total admissions of malaria suspected cases, gross domestic product, availability of anti-malarial drugs, and year of the publication were explained 85 and 83% of the total variance between studies and potential sources of the heterogeneity for malaria testing and treating, respectively. CONCLUSION: HWs adherence to appropriate malaria case management guidelines were generally low while no study has been found in eliminating countries. Studies with the inappropriateness methods and risk of bias could be overestimating the actual proportion of malaria appropriate testing and treating. Strategies that focus on improving readiness and early identification of acute febrile diseases especially in the countries that progress to malaria elimination should be highly promoted