Thermal-Mechanical Design and Detector Characterization of the Limb Imaging Fourier Transform Spectrometer Experiment

The Limb Imaging Fourier Transform Experiment (LIFE) is a prototype of a satellite remote sensing instrument being developed at the University of Saskatchewan in collaboration with the Canadian Space Agency and ABB Inc. The prototype instrument is designed to take measurements of key atmospheric greenhouse gases on-board a high-altitude balloon gondola, to test the concept and provide insight towards future versions of the instrument. It will take measurements from the stratosphere, providing a vertical profile from the lower stratosphere to the upper troposphere, known as the UTLS region, an important region for understanding climate change. LIFE is conceptually similar to the Gimballed Limb Observer for Radiance Imaging in the Atmosphere (GLORIA), and aims to create a less expensive and smaller instrument to show that a cost-effective infrared Fourier Transform Spectrometer based atmospheric instrument is feasible. This thesis describes two main aspects of the LIFE prototype: The thermal-mechanical design and the characterization of the infrared detector. As a thermal imaging instrument, LIFE has strict thermal requirements and constraints in the harsh high-altitude environment. A thermal-mechanical design is developed and simulated to ensure that all requirements are met and the instrument will operate nominally during its high-altitude balloon flight. The infrared detector must be carefully characterized and optimized for the LIFE application through the altering and optimization of detector settings, to ensure that the measurements taken are of the best possible quality. The instrument successfully flew on its first test flight in Timmins, Ontario in August of 2019. All design requirements were met and the instrument operated nominally, taking numerous successful measurements of the UTLS. The goal of creating a design that would allow the survival and operation of the instrument in a high-altitude environment as well as the goal of optimizing the detector were both completed successfully. Overall, the goal of creating a low cost instrument that allows thermal emission measurements to be taken in the UTLS region was completed, and the knowledge gained from the project can be used to inform future improvements to the LIFE instrument

Patterns of urinary β2-microglobulin excretion by patients treated with aminoglycosides

Patterns of urinary β2-microglobulin excretion in patients treated with aminoglycosides. Aminoglycoside antibiotics are relatively mild nephrotoxins, but their action is site-specific to the proximal tubule. Therefore, use of these drugs presents a unique opportunity to study the temporal relation between the damage to the cells lining the renal proximal tubule and the subsequent rise in the serum creatinine concentration. Our study of 52 aminoglycoside-treated patients included measurements of daily serum creatinine, daily 24-hour urinary β2-microglobulin (β2M) excretion, and determination of aminoglycoside tissue accumulation. An elevation in β2M excretion above the baseline value occurred in 37 of 52 (71%), whereas the serum creatinine concentration rose in only 17 of 52 (33%) of patients. Even fewer patients (10 of 52) demonstrated all three criteria for aminoglycoside nephrotoxicity. These 10 patients had elevated tissue accumulation, evidence of renal tubular damage, and arise in serum creatinine concentration. The increased β2M excretion greater than 50 mg/day preceded the serum creatinine rise by 2 to 7 days. An abnormal baseline β2M was not a risk factor for a subsequent rise in creatinine concentration or vice versa. Although each test is primarily site specific, widespread and severe renal proximal tubular damage, regardless of cause, will eventually lead to an elevation of serum creatinine. Thus, serial monitoring of proximal tubular function with urinary β2M excretion has potential value in the assessment of insults to this site, but cannot be expected to explain all changes in serum creatinine.Modalités de l'excrétion urinaire de β2-microglobulines chez les malades traités par les aminoglycosides. Les aminoglycosides ont une action néphrotoxique de sévérité moyenne spécifiquement localisée au tube proximal. L'emploi de ces drogues offre l'opportunité d'étudier la relation dans le temps entre la lésion des cellules tubulaires proximales et l'élévation consécutive de la créatininémie. L'étude de 52 malades traités par les aminoglycosides a comporté la détermination quotidienne de la créatininémie et de l'excrétion urinaire de β2-microglobuline (β2M) ainsi que la détermination de l'accumulation tissulaire d'aminoglycoside. Une élévation de l'excrétion de β2M au dessus de la valeur basale a été observée chez 37 malades (71%) alors que l'élévation de la créatinine n'est survenue que chez 17 malades (33%). Dix malades seulement ont eu les trois critères de néphrotoxicité par l'aminoglycoside. Ces 10 malades avaient une accumulation tissulaire, des signes de lésions tubulaires et une élévation de la créatinine. Une augmentation de l'excrétion deβ2M, au dessus de 50 mg/24 hr a précédé de 2 à 7 jours l'élévation de la créatininémie. Une excrétion basale anormale de β2M n'est pas un facteur de risque d'élévation ultérieure de la créatininémie, ou réciproquement. Bien que chacun de ces tests soit spécifique d'un site, des lésions tubulaires proximales sévères et étendues doivent déterminer une élévation de la créatinine, quelle que soit leur cause. La surveillance itérative de la fonction tubulaire proximale par la mesure de l'excrétion urinaire de β2M a une valeur potentielle dans l'évaluation des lésions mais ne peut pas expliquer la totalité des modifications de la créatininémie

Pharmacokinetic–pharmacodynamic integration and modelling of oxytetracycline for the calf pathogens Mannheimia haemolytica and Pasteurella multocida

A calf tissue cage model was used to study the pharmacokinetics (PK) and pharmacodynamics (PD) of oxytetracycline in serum, inflamed (exudate) and noninflamed (transudate) tissue cage fluids. After intramuscular administration, the PK was characterized by a long mean residence time of 28.3 hr. Based on minimum inhibitory concentrations (MICs) for six isolates each of Mannheimia haemolytica and Pasteurella multocida, measured in serum, integration of in vivo PK and in vitro PD data established area under serum concentration–time curve (AUC0–∞)/MIC ratios of 30.0 and 24.3 hr for M. haemolytica and P. multocida, respectively. Corresponding AUC0–∞/MIC ratios based on MICs in broth were 656 and 745 hr, respectively. PK-PD modelling of in vitro bacterial time–kill curves for oxytetracycline in serum established mean AUC0–24 hr/MIC ratios for 3log10 decrease in bacterial count of 27.5 hr (M. haemolytica) and 60.9 hr (P. multocida). Monte Carlo simulations predicted target attainment rate (TAR) dosages. Based on the potency of oxytetracycline in serum, the predicted 50% TAR single doses required to achieve a bacteriostatic action covering 48-hr periods were 197 mg/kg (M. haemolytica) and 314 mg/kg (P. multocida), respectively, against susceptible populations. Dosages based on the potency of oxytetracycline in broth were 25- and 27-fold lower (7.8 and 11.5 mg/kg) for M. haemolytica and P. multocida, respectively

Standard PK/PD concepts can be applied to determine a dosage regimen for a macrolide: the case of tulathromycin in the calf

The pharmacokinetic (PK) profile of tulathromycin, administered to calves subcutaneously at the dosage of 2.5 mg/kg, was established in serum, inflamed (exudate), and noninflamed (transudate) fluids in a tissue cage model. The PK profile of tulathromycin was also established in pneumonic calves. For Mannheimia haemolytica and Pasteurella multocida, tulathromycin minimum inhibitory concentrations (MIC) were approximately 50 times lower in calf serum than in Mueller–Hinton broth. The breakpoint value of the PK/pharmacodynamic (PD) index (AUC(0–24 h)/MIC) to achieve a bactericidal effect was estimated from in vitro time‐kill studies to be approximately 24 h for M. haemolytica and P. multocida. A population model was developed from healthy and pneumonic calves and, using Monte Carlo simulations, PK/PD cutoffs required for the development of antimicrobial susceptibility testing (AST) were determined. The population distributions of tulathromycin doses were established by Monte Carlo computation (MCC). The computation predicted a target attainment rate (TAR) for a tulathromycin dosage of 2.5 mg/kg of 66% for M. haemolytica and 87% for P. multocida. The findings indicate that free tulathromycin concentrations in serum suffice to explain the efficacy of single‐dose tulathromycin in clinical use, and that a dosage regimen can be computed for tulathromycin using classical PK/PD concepts

Antibiotic Dosing in Critically Ill Patients Receiving CRRT : Underdosing is Overprevalent

Published CRRT drug dosing algorithms and other dosing guidelines appear to result in underdosed antibiotics, leading to failure to attain pharmacodynamic targets. High mortality rates persist with inadequate antibiotic therapy as the most important risk factor for death. Reasons for unintended antibiotic underdosing in patients receiving CRRT are many. Underdosing may result from lack of the recognition that better hepatic function in AKI patients yields higher nonrenal antibiotic clearance compared to ESRD patients. Other factors include the variability in body size and fluid composition of patients, the serious consequence of delayed achievement of antibiotic pharmacodynamic targets in septic patients, potential subtherapeutic antibiotic concentrations at the infection site, and the influence of RRT intensity on antibiotic concentrations. Too often, clinicians weigh the benefits of overcautious antibiotic dosing to avoid antibiotic toxicity too heavily against the benefits of rapid attainment of therapeutic antibiotic concentrations in critically ill patients receiving CRRT . We urge clinicians to prescribe antibiotics aggressively for these vulnerable patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108650/1/sdi12203.pd