Scheduling medical application workloads on virtualized computing systems

This dissertation presents and evaluates a methodology for scheduling medical application workloads in virtualized computing environments. Such environments are being widely adopted by providers of "cloud computing" services. In the context of provisioning resources for medical applications, such environments allow users to deploy applications on distributed computing resources while keeping their data secure. Furthermore, higher level services that further abstract the infrastructure-related issues can be built on top of such infrastructures. For example, a medical imaging service can allow medical professionals to process their data in the cloud, easing them from the burden of having to deploy and manage these resources themselves. In this work, we focus on issues related to scheduling scientific workloads on virtualized environments. We build upon the knowledge base of traditional parallel job scheduling to address the specific case of medical applications while harnessing the benefits afforded by virtualization technology. To this end, we provide the following contributions: (1) An in-depth analysis of the execution characteristics of the target applications when run in virtualized environments. (2) A performance prediction methodology applicable to the target environment. (3) A scheduling algorithm that harnesses application knowledge and virtualization-related benefits to provide strong scheduling performance and quality of service guarantees. In the process of addressing these pertinent issues for our target user base (i.e. medical professionals and researchers), we provide insight that benefits a large community of scientific application users in industry and academia. Our execution time prediction and scheduling methodologies are implemented and evaluated on a real system running popular scientific applications. We find that we are able to predict the execution time of a number of these applications with an average error of 15%. Our scheduling methodology, which is tested with medical image processing workloads, is compared to that of two baseline scheduling solutions and we find that it outperforms them in terms of both the number of jobs processed and resource utilization by 20–30%, without violating any deadlines. We conclude that our solution is a viable approach to supporting the computational needs of medical users, even if the cloud computing paradigm is not widely adopted in its current form.

A Case-Only Genome-wide Association Study of Gender- and Age-specific Risk Markers for Childhood Leukemia

Males and age group 1 to 5 years show a much higher risk for childhood acute lymphoblastic leukemia (ALL). We performed a case-only genome-wide association study (GWAS), using the Illumina Infinium HumanCoreExome Chip, to unmask gender- and age-specific risk variants in 240 non-Hispanic white children with ALL recruited at Texas Children’s Cancer Center, Houston, Texas. Besides statistically most significant results, we also considered results that yielded the highest effect sizes. Existing experimental data and bioinformatic predictions were used to complement results, and to examine the biological significance of statistical results. Our study identified novel risk variants for childhood ALL. The SNP, rs4813720 (RASSF2), showed the statistically most significant gender-specific associations (P < 2 x 10-6). Likewise, rs10505918 (SOX5) yielded the lowest P value (P < 1 x 10-5) for age-specific associations, and also showed the statistically most significant association with age-at-onset (P < 1 x 10-4). Two SNPs, rs12722042 and 12722039, from the HLA-DQA1 region yielded the highest effect sizes (odds ratio (OR) = 15.7; P = 0.002) for gender-specific results, and the SNP, rs17109582 (OR = 12.5; P = 0.006), showed the highest effect size for age-specific results. Sex chromosome variants did not appear to be involved in gender-specific associations. The HLA-DQA1 SNPs belong to DQA1*01:07and confirmed previously reported male-specific association with DQA1*01:07. Twenty one of the SNPs identified as risk markers for gender- or age-specific associations were located in the transcription factor binding sites and 56 SNPs were non-synonymous variants, likely to alter protein function. Although bioinformatic analysis did not implicate a particular mechanism for gender- and age-specific associations, RASSF2 has an estrogen receptor-alpha binding site in its promoter. The unknown mechanisms may be due to lack of interest in gender- and age-specificity in associations. These results provide a foundation for further studies to examine the gender- and age-differential in childhood ALL risk. Following replication and mechanistic studies, risk factors for one gender or age group may have a potential to be used as biomarkers for targeted intervention for prevention and maybe also for treatment.

Development and implementation of a tool to assess the micro/macro elements in an organization

This study examines the congruency of planning between organizational structure and process, through an evaluation and planning model known as the Micro/Macro Dynamic Planning Grid. The model compares day-to-day planning within an organization to planning imposed by organizational administration and accrediting agencies. A survey instrument was developed to assess the micro and macro sociological analysis elements utilized by an organization.^ The Micro/Macro Dynamic Planning Grid consists of four quadrants. Each quadrant contains characteristics that reflect the interaction between the micro and macro elements of planning, objectives and goals within an organization. The Over Macro/Over Micro, Quadrant 1, contains attributes that reflect a tremendous amount of action and ongoing adjustments, typical of an organization undergoing significant changes in either leadership, program and/or structure. Over Macro/Under Micro, Quadrant 2, reflects planning characteristics found in large, bureaucratic systems with little regard given to the workings of their component parts. Under Macro/Under Micro, Quadrant 3, reflects the uncooperative, uncoordinated organization, one that contains a multiplicity of viewpoints, language, objectives and goals. Under Macro/Under Micro, Quadrant 4 represents the worst case scenario for any organization. The attributes of this quadrant are very reactive, chaotic, non-productive and redundant.^ There were three phases to the study: development of the initial instrument, pilot testing the initial instrument and item revision, and administration and assessment of the refined instrument. The survey instrument was found to be valid and reliable for the purposes and audiences herein described.^ In order to expand the applicability of the instrument to other organizational settings, the survey was administered to three professional colleges within a university.^ The first three specific research questions collectively answered, in the affirmative, the basic research question: Can the Micro/Macro Dynamic Planning Grid be applied to an organization through an organizational development tool? The first specific question: Can an instrument be constructed that applies the Micro/Macro Dynamic Planning Grid? The second specific research question: Is the constructed instrument valid and reliable? The third specific research question: Does an instrument that applies the Micro/Macro Dynamic Planning Grid assess congruency of micro and macro planning, goals and objectives within an organization? The fourth specific research question: What are the differences in the responses based on roles and responsibilities within an organization? involved statistical analysis of the response data and comparisons obtained with the demographic data. (Abstract shortened by UMI.) ^

Assessment of the occurrence and potential risks of pharmaceuticals and their metabolites in fish and water using liquid chromatography mass spectrometry

A comprehensive method for the analysis of 11 target pharmaceuticals representing multiple therapeutic classes was developed for biological tissues (fish) and water. Water samples were extracted using solid phase extraction (SPE), while fish tissue homogenates were extracted using accelerated solvent extraction (ASE) followed by mixed-mode cation exchange SPE cleanup and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Among the 11 target pharmaceuticals analyzed, trimethoprim, caffeine, sulfamethoxazole, diphenhydramine, diltiazem, carbamazepine, erythromycin and fluoxetine were consistently detected in reclaimed water. On the other hand, caffeine, diphenhydramine and carbamazepine were consistently detected in fish and surface water samples. In order to understand the uptake and depuration of pharmaceuticals as well as bioconcentration factors (BCFs) under the worst-case conditions, mosquito fish were exposed to reclaimed water under static-renewal for 7 days, followed by a 14-day depuration phase in clean water. Characterization of the exposure media revealed the presence of 26 pharmaceuticals while 5 pharmaceuticals including caffeine, diphenhydramine, diltiazem, carbamazepine, and ibuprofen were present in the organisms as early as 5 h from the start of the exposure. Liquid chromatography ultra-high resolution Orbitrap mass spectrometry was explored as a tool to identify and quantify phase II pharmaceutical metabolites in reclaimed water. The resulting data confirmed the presence of acetyl-sulfamethoxazole and sulfamethoxazole glucuronide in reclaimed water. To my knowledge, this is the first known report of sulfamethoxazole glucuronide surviving intact through wastewater treatment plants and occurring in environmental water samples. Finally, five bioaccumulative pharmaceuticals including caffeine, carbamazepine, diltiazem, diphenhydramine and ibuprofen detected in reclaimed water were investigated regarding the acute and chronic risks to aquatic organisms. The results indicated a low potential risk of carbamazepine even under the worst case exposure scenario. Given the dilution factors that affect environmental releases, the risk of exposure to carbamazepine will be even more reduced.

A novel signal processing method for intraoperative neurophysiological monitoring in spinal surgeries

Intraoperative neurophysiologic monitoring is an integral part of spinal surgeries and involves the recording of somatosensory evoked potentials (SSEP). However, clinical application of IONM still requires anywhere between 200 to 2000 trials to obtain an SSEP signal, which is excessive and introduces a significant delay during surgery to detect a possible neurological damage. The aim of this study is to develop a means to obtain the SSEP using a much less, twelve number of recordings. The preliminary step involved was to distinguish the SSEP with the ongoing brain activity. We first establish that the brain activity is indeed quasi-stationary whereas an SSEP is expected to be identical every time a trial is recorded. An algorithm was developed using Chebychev time windowing for preconditioning of SSEP trials to retain the morphological characteristics of somatosensory evoked potentials (SSEP). This preconditioning was followed by the application of a principal component analysis (PCA)-based algorithm utilizing quasi-stationarity of EEG on 12 preconditioned trials. A unique Walsh transform operation was then used to identify the position of the SSEP event. An alarm is raised when there is a 10% time in latency deviation and/or 50% peak-to-peak amplitude deviation, as per the clinical requirements. The algorithm shows consistency in the results in monitoring SSEP in up to 6-hour surgical procedures even under this significantly reduced number of trials. In this study, the analysis was performed on the data recorded in 29 patients undergoing surgery during which the posterior tibial nerve was stimulated and SSEP response was recorded from scalp. This method is shown empirically to be more clinically viable than present day approaches. In all 29 cases, the algorithm takes 4sec to extract an SSEP signal, as compared to conventional methods, which take several minutes. The monitoring process using the algorithm was successful and proved conclusive under the clinical constraints throughout the different surgical procedures with an accuracy of 91.5%. Higher accuracy and faster execution time, observed in the present study, in determining the SSEP signals provide a much improved and effective neurophysiological monitoring process.

Assessment of the Occurrence and Potential Risks of Pharmaceuticals and their Metabolites in Fish and Water Using Liquid Chromatography Mass Spectrometry

A comprehensive method for the analysis of 11 target pharmaceuticals representing multiple therapeutic classes was developed for biological tissues (fish) and water. Water samples were extracted using solid phase extraction (SPE), while fish tissue homogenates were extracted using accelerated solvent extraction (ASE) followed by mixed-mode cation exchange SPE cleanup and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Among the 11 target pharmaceuticals analyzed, trimethoprim, caffeine, sulfamethoxazole, diphenhydramine, diltiazem, carbamazepine, erythromycin and fluoxetine were consistently detected in reclaimed water. On the other hand, caffeine, diphenhydramine and carbamazepine were consistently detected in fish and surface water samples. In order to understand the uptake and depuration of pharmaceuticals as well as bioconcentration factors (BCFs) under the worst-case conditions, mosquito fish were exposed to reclaimed water under static-renewal for 7 days, followed by a 14-day depuration phase in clean water. Characterization of the exposure media revealed the presence of 26 pharmaceuticals while 5 pharmaceuticals including caffeine, diphenhydramine, diltiazem, carbamazepine, and ibuprofen were present in the organisms as early as 5 h from the start of the exposure. Liquid chromatography ultra-high resolution Orbitrap mass spectrometry was explored as a tool to identify and quantify phase II pharmaceutical metabolites in reclaimed water. The resulting data confirmed the presence of acetyl-sulfamethoxazole and sulfamethoxazole glucuronide in reclaimed water. To my knowledge, this is the first known report of sulfamethoxazole glucuronide surviving intact through wastewater treatment plants and occurring in environmental water samples. Finally, five bioaccumulative pharmaceuticals including caffeine, carbamazepine, diltiazem, diphenhydramine and ibuprofen detected in reclaimed water were investigated regarding the acute and chronic risks to aquatic organisms. The results indicated a low potential risk of carbamazepine even under the worst case exposure scenario. Given the dilution factors that affect environmental releases, the risk of exposure to carbamazepine will be even more reduced.