<p>Dedicated to the memory of Dr. Colin E. Webber</p> / <p>This comparative study of peripheral (p) QCT, high-resolution pQCT (hr-pQCT) and 1.0 Tesla pMRI technologies quantified short-term test-retest reproducibility, validity, one-year detection limit and clinical sensitivity of each modality’s derived bone measures. Select bone outcomes were evaluated from scans performed on Hamiltonian women above 50 years old and externally validated in a population-based cohort. In the local cohort (age: 74 ± 9 years and BMI 27.65 ± 5.74 kg/m²), Tb.Sp measured on pMRI, Ct.Th and vBMD from pQCT showed significant correlations (r²=0.52-0.85) with hr-pQCT, yielding slopes near unity. Bland-Altman analyses revealed significant relationships between pQCT and pMRI bone outcome values (Tb.Th(-), Tb.N(+), BV/TV(-)) and agreement with hr-pQCT. Short-term reproducibility was < 5% for pQCT but only BV/TV was < 5% for pMRI. Co-registration and excluding individuals with fractures mildly reduced precision error and one-year change. In the local cohort, only Ct.Th and cortical vBMD associated with fractures (OR: 1.09-3.28) using hr-pQCT, which was externally validated in the national cohort. Certain trabecular measures on pMRI and pQCT erred towards increased odds for fractures locally. For pQCT, these became significant in the national cohort (OR:1.04-3.81). This Canadian reference dataset for hr-pQCT showed larger Tb.Sp and smaller Tb.N compared to Americans but age-related decline in Ct.Th and BV/TV was faster in Europeans. This study demonstrated validity of pMRI and pQCT-derived volumetric bone outcomes and reasonable short- and long-term precision error for pQCT but not 1.0T pMRI. A single CT slice from pQCT was comparable to 110 slices from hr-pQCT in associations with fractures.</p> / Doctor of Philosophy (Medical Science)

In this study, three different chromatographic column chemistries (C18, Pentafluorophenyl (PFP), Hydrophilic Interaction Chromatography (HILIC)) were compared under optimal conditions to determine which stationary performed best in the separation and detection of a mixture of opioids using LC-MS. Furthermore, these stationary phases were examined in three different column technologies – traditional silica, porous shell, and porous polymer (PRP). The PRP column had the best peak shape for all 13 opioids and dominated for later-eluting compounds. In terms of column reproducibility, the Hamilton C18 column had the lowest %RSD values. The Kinetex HILIC produced the most theoretical plates and best resolution for polar compounds as did the Hamilton C18 for nonpolar compounds. Finally, Kinetex PFP and Hamilton PRP both demonstrated themselves as viable alternatives to the C18 column chemistry for analysis of this drug class.

Catheter-Associated Urinary Tract Infections are considered a clinical indicator of quality of care. A descriptive research study was conducted to identify the strategies used by hospitals to reduce or eliminate CAUTIs. Infection Control Preventionists were surveyed. In a predominately rural southeastern state, this study demonstrated that about 40% of hospitals surveyed are implementing CAUTI prevention processes.

Since its characterization, the definitive shortcoming of the bacterial luciferase (lux) bioluminescent reporter system has been its inability to express at a functional level in the eukaryotic cellular background. While recent developments have allowed for lux function in the lower eukaryote Saccharomyces cerevisiae, they have not provided for autonomous function in higher eukaryotes capable of serving as human biomedical proxies. Here it is reported for the first time that, through a process of poly-bicistronic expression of human codon-optimized lux genes, it is possible to autonomously produce a bioluminescent signal directly from mammalian cells. The low background of the bioluminescent signal, along with its characteristic lack of substrate amendment required for bioluminescent production, makes a mammalian-based lux reporter system ideal for real-time monitoring of cell culture or murine model systems. The delectability of a lux-based system provides for a functionally equivalent process to monitoring firefly luciferase-expressing cells under cell culture or subcutaneous imaging conditions without the well-documented uncertainties stemming from additional substrate introduction. However, the relatively blue-shifted emission wavelength of the lux reporter system, along with its low quantum yield, has been shown to reduce its effectiveness for use during deep tissue imaging of animal subjects. Despite these disadvantages, it has been demonstrated that a human cell line expressing the human codon-optimized lux genes can function as a biosensor for determination of human bioavailability of toxic compounds and that, by regulating the production of the luxC and luxE genes, the lux system can be employed as the first mammalian, real-time, fully autonomous bioreporter. These cell lines provide unique and efficient models for the detection and monitoring of human-relevant compounds of interest. The limiting reagent for bioluminescent production in the mammalian cellular background has been determined to be the cytosolic availability of the FMNH2 co-substrate and, in light of this evidence, directions for future optimization have been characterized and evaluated in respect to their ability to increase bioluminescent yield under these conditions.

Clinicians lack appropriate non-invasive methods to be able to predict, diagnose, and reduce the risk of rejection in the years following kidney transplantation. Protocol biopsies and monitoring of serum creatinine levels are the most common methods of monitoring graft function after transplant; however, they have several negative aspects. Use of traditional factors regarding donors and recipients such as Human Leukocyte Antigen (HLA) DNA typing, pre-transplant anti-HLA antibody levels, and basic demographics (age, ethnicity/race, gender), has proved inadequate for post-transplant graft monitoring past the first few years. We propose that by utilizing immunologic factors available to clinicians across the United States, development of a non-invasive model for predicting renal graft outcome will provide a useful tool for post-transplant patient monitoring. We advocate an expanded model which incorporates both the traditional factors, as well as new factors, which have shown promise in predicting kidney outcome and are widely available for testing using commercial kits. These additional factors include major histocompatibility complex class I chain-related gene A (MICA) typing of donor and recipient, degree of matching for killer cell immunoglobulin-like receptors (KIRs) between donor and recipient, detection of MICA antibodies, and soluble CD30 level (sCD30). This proposed graft-function prediction model is the first to include all of these factors. Using multi-center data from adult recipients of standard-criteria deceased-donor (SCD) kidneys, we were able to construct models, containing the traditional factors only, for prediction of outcome at 1 year and 3 years post-transplant. Using single-center data from adult recipients of standard-criteria deceased-donor kidneys, we developed comparison models containing traditional factors only, as well as, expanded models containing the new suggested variables for prediction of outcome post-transplant. These additional variables, when incorporated into the expanded models provided greater positive predictive values, greater negative predictive values, and lower false negative rates for graft outcome at 1 year and at 3 years post-transplant than the models utilizing traditional factors only. Our results indicate that evaluation of sCD30, MICA and KIR as part of routine protocol testing, is helpful to clinicians for predicting risk of kidney graft rejection.

How is the brain capable of mediating pain relief via the mind alone? Placebo analgesia is just such a case, wherein an inert substance yields relief from a number of pain inducing stimuli. Scholars typically separate several factors thought to contribute to the placebo effect into psychological and neurobiological influences. Psychological mechanisms include expectation and conditioning of analgesic effects, while neurobiological mechanisms implicate the opioidergic descending pain system. The current paper proposes an integrative model in which the rostral anterior cingulate cortex (rACC), implicated in cognitive-affective modulation, receives goal-directed input (i.e., expected pain relief) from the prefrontal cortex. As the rACC processes the cognitive difference between expected and actual pain, it recruits a critical descending pain pathway by means of modulating the periaqueductal gray area (PAG). The PAG is a key relay station that connects to other endogenous subsystems of opioidergic pain relief. Whether the rACC and its connection to the PAG are necessary for the placebo effect is a question future research will have to address.

How is the brain capable of mediating pain relief via the mind alone? Placebo analgesia is just such a case, wherein an inert substance yields relief from a number of pain inducing stimuli. Scholars typically separate several factors thought to contribute to the placebo effect into psychological and neurobiological influences. Psychological mechanisms include expectation and conditioning of analgesic effects, while neurobiological mechanisms implicate the opioidergic descending pain system. The current paper proposes an integrative model in which the rostral anterior cingulate cortex (rACC), implicated in cognitive-affective modulation, receives goal-directed input (i.e., expected pain relief) from the prefrontal cortex. As the rACC processes the cognitive difference between expected and actual pain, it recruits a critical descending pain pathway by means of modulating the periaqueductal gray area (PAG). The PAG is a key relay station that connects to other endogenous subsystems of opioidergic pain relief. Whether the rACC and its connection to the PAG are necessary for the placebo effect is a question future research will have to address.

Play can be beneficial and effective for children experiencing the stress, fears, and anxieties associated with illness or death by expressing their feelings into activity (Brown 2018). It can be difficult for children to verbally communicate complex emotions because they usually are unsure of what words to say to express their emotions. Therapeutic play is a great coping mechanism for coping with death because it allows children to express their emotions through play. Professionals working with children would be better equipped to meet children’s needs with a firmer understanding on the ways in which therapeutic play techniques can be incorporated into their practice. The impact therapeutic play makes can also be beneficial for families as it can help the families understand what the children comprehend which can lead to more efficient communication between members of the family. Professionals aim to assist children in reaching optimal outcomes, which in turn has beneficial impacts for the family overall.

As illness becomes increasingly more common in the United States and across the globe, the need for better and faster medical treatment is greater than ever. The purpose of this work is to evaluate advanced polymers and polymer composites that will provide for increased fluid flow while maintaining outer dimensional, stiffness, and burst resistance characteristics when compared to a currently used material. A polymer configuration consisting of a proprietary formulation that has a durometer approximately 10% higher than the current material with an outer wall thickness of approximately .020" passed a series of tests involving tensile strength, stiffness, flexural fatigue resistance, vacuum lumen collapse resistance and hydraulic burst resistance. This material configuration passed the requirements for applicable test standards and had a tensile strength 13.4% less than the control group, was 52.7% stiffer, did not sustain any noticeable wear or defects during the flexural fatigue test, had a tensile strength 14.8% less that the control group during a post flex fatigue tensile test, did not burst when 150 psi was applied to it for 5 seconds, and is estimated to have a 43% higher flow rate capacity than the current material.

This study correlated the performance accuracy of peripheral blood differentials evaluated by clinical laboratory scientists and clinical laboratory technicians. Fifty-one senior-year students from four clinical laboratory science baccalaureate programs and 37 second-year students from five clinical laboratory technician programs were given 10 peripheral blood differentials to perform. Results were compared to the values assigned by the Rajamaki method of proficiency testing. There was a significant discrepancy in the levels of accuracy between the two cohorts, suggesting that the results of peripheral blood differentials performed by clinical laboratory technicians is suspect. Facilities wishing to maintain or improve the quality of laboratory services should consider allowing only baccalaureate level clinical laboratory scientists to perform peripheral blood differentials.