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

Grepafloxacin in Patients with Acute Bacterial Exacerbations of Chronic Bronchitis - a Question of Speed in Bacterial Killing

OBJECTIVE: To characterize the population pharmacokinetics and pharmacodynamics of oral grepafloxacin in patients with acute bacterial exacerbations of chronic bronchitis (ABECB), with particular attention to the speed of bacterial killing. This was possible because the study design incorporated daily cultures of the patients’ sputum

Clinical outcomes in typhoid fever: adverse impact of infection with nalidixic acid-resistant Salmonella typhi

BACKGROUND: Widespread use of fluoroquinolones has resulted in emergence of Salmonella typhi strains with decreased susceptibility to fluoroquinolones. These strains are identifiable by their nalidixic acid-resistance. We studied the impact of infection with nalidixic acid-resistant S. typhi (NARST) on clinical outcomes in patients with bacteriologically-confirmed typhoid fever. METHODS: Clinical and laboratory features, fever clearance time and complications were prospectively studied in patients with blood culture-proven typhoid fever, treated at a tertiary care hospital in north India, during the period from November 2001 to October 2003. Susceptibility to amoxycillin, co-trimoxazole, chloramphenicol, ciprofloxacin and ceftriaxone were tested by disc diffusion method. Minimum inhibitory concentrations (MIC) of ciprofloxacin and ceftriaxone were determined by E-test method. RESULTS: During a two-year period, 60 patients (age [mean ± SD]: 15 ± 9 years; males: 40 [67%]) were studied. All isolates were sensitive to ciprofloxacin and ceftriaxone by disc diffusion and MIC breakpoints. However, 11 patients had clinical failure of fluoroquinolone therapy. Infections with NARST isolates (47 [78%]) were significantly associated with longer duration of fever at presentation (median [IQR] 10 [7-15] vs. 4 [3-6] days; P = 0.000), higher frequency of hepatomegaly (57% vs. 15%; P = 0.021), higher levels of aspartate aminotransferase (121 [66–235] vs. 73 [44–119] IU/L; P = 0.033), and increased MIC of ciprofloxacin (0.37 ± 0.21 vs. 0.17 ± 0.14 μg/mL; P = 0.005), as compared to infections with nalidixic acid-susceptible isolates. All 11 patients with complications were infected with NARST isolates. Total duration of illness was significantly longer in patients who developed complications than in patients who did not (22 [14.8–32] vs. 12 [9.3–20.3] days; P = 0.011). Duration of prior antibiotic intake had a strong positive correlation with the duration of fever at presentation (r = 0.61; P = 0.000) as well as the total duration of illness (r = 0.53; P = 0.000). CONCLUSION: Typhoid fever caused by NARST infection is associated with poor clinical outcomes, probably due to delay in initiating appropriate antibiotic therapy. Fluoroquinolone breakpoints for S. typhi need to be redefined and fluoroquinolones should no longer be used as first-line therapy, if the prevalence of NARST is high

Oseltamivir Is Adequately Absorbed Following Nasogastric Administration to Adult Patients with Severe H5N1 Influenza

In the absence of a parenteral drug, oral oseltamivir is currently recommended by the WHO for treating H5N1 influenza. Whether oseltamivir absorption is adequate in severe influenza is unknown. We measured the steady state, plasma concentrations of nasogastrically administered oseltamivir 150 mg bid and its active metabolite, oseltamivir carboxylate (OC), in three, mechanically ventilated patients with severe H5N1 (male, 30 yrs; pregnant female, 22 yrs) and severe H3N2 (female, 76 yrs). Treatments were started 6, 7 and 8 days after illness onset, respectively. Both females were sampled while on continuous venovenous haemofiltration. Admission and follow up specimens (trachea, nose, throat, rectum, blood) were tested for RNA viral load by reverse transcriptase PCR. In vitro virus susceptibility to OC was measured by a neuraminidase inhibition assay. Admission creatinine clearances were 66 (male, H5N1), 82 (female, H5N1) and 6 (H3N2) ml/min. Corresponding AUC0–12 values (5932, 10,951 and 34,670 ng.h/ml) and trough OC concentrations (376, 575 and 2730 ng/ml) were higher than previously reported in healthy volunteers; the latter exceeded 545 to 3956 fold the H5N1 IC50 (0.69 ng/ml) isolated from the H5N1 infected female. Two patients with follow-up respiratory specimens cleared their viruses after 5 (H5N1 male) and 5 (H3N2 female) days of oseltamivir. Both female patients died of respiratory failure; the male survived. 150 mg bid of oseltamivir was well absorbed and converted extensively to OC. Virus was cleared in two patients but two patients died, suggesting viral efficacy but poor clinical efficacy

Management of intra-abdominal infections : recommendations by the WSES 2016 consensus conference

This paper reports on the consensus conference on the management of intra-abdominal infections (IAIs) which was held on July 23, 2016, in Dublin, Ireland, as a part of the annual World Society of Emergency Surgery (WSES) meeting. This document covers all aspects of the management of IAIs. The Grading of Recommendations Assessment, Development and Evaluation recommendation is used, and this document represents the executive summary of the consensus conference findings.Peer reviewe

Modeling methicillin-resistant Staphylococcus aureus in hospitals: Transmission dynamics, antibiotic usage and its history

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is endemic in many hospital settings, posing substantial threats and economic burdens worldwide. METHODS: We propose mathematical models to investigate the transmission dynamics of MRSA and determine factors that influence the prevalence of MRSA infection when antibiotics are given to patients to treat or prevent infections with either MRSA itself or other bacterial pathogens. RESULTS: Our results suggest that: (i) MRSA always persists in the hospital when colonized and infected patients are admitted; (ii) the longer the duration of treatment of infected patients and the lower the probability of successful treatment will increase the prevalence of MRSA infection; (iii) the longer the duration of contamination of health care workers (HCWs) and the more their contacts with patients may increase the prevalence of MRSA infection; (iv) possible ways to control the prevalence of MRSA infection include treating patients with antibiotic history as quickly and efficiently as possible, screening and isolating colonized and infected patients at admission, and compliance with strict hand-washing rules by HCWs. CONCLUSION: Our modeling studies offer an approach to investigating MRSA infection in hospital settings and the impact of antibiotic history on the incidence of infection. Our findings suggest important influences on the prevalence of MRSA infection which may be useful in designing control policies