217 research outputs found

    Transforming the Professional Flight Program Curriculum: Justification, Process, and Future Development

    Get PDF
    According to the International Civil Aviation Organization (ICAO), by 2036 the aviation sector will need 620,000 new pilots, 125,000 new air traffic controllers, and 1.3 million aircraft maintenance personnel (ICAO, 2018); Pilots seeking a first officer position (a common entry-level position at Part 121 air carriers) are required to possess an Airline Transport Pilot (ATP) Certificate and 1,500 hours of total flight time; There are some exceptions! Support from administration Quantity vs Quality; How can flight faculty improve student learning and job readiness

    River infiltration to a subtropical alluvial aquifer inferred using multiple environmental tracers

    Get PDF
    Chloride (Cl−), stable isotope ratios of water (δ18O and δ2H), sulfur hexafluoride (SF6), tritium (3H), carbon-14 (14C), noble gases (4He, Ne, and Ar), and hydrometry were used to characterize groundwater-surface water interactions, in particular infiltration rates, for the Lower Namoi River (New South Wales, Australia). The study period (four sampling campaigns between November 2009 and November 2011) represented the end of a decade-long drought followed by several high-flow events. The hydrometry showed that the river was generally losing to the alluvium, except when storm-derived floodwaves in the river channel generated bank recharge—discharge cycles. Using 3H/14C-derived estimates of groundwater mean residence time along the transect, infiltration rates ranged from 0.6 to 5 m yr−1. However, when using the peak transition age (a more realistic estimate of travel time in highly dispersive environments), the range in infiltration rate was larger (4–270 m yr−1). Both river water (highest δ2H, δ18O, SF6, 3H, and 14C) and an older groundwater source (lowest δ2H, δ18O, SF6, 3H, 14C, and highest 4He) were found in the riparian zone. This old groundwater end-member may represent leakage from an underlying confined aquifer (Great Artesian Basin). Environmental tracers may be used to estimate infiltration rates in this riparian environment but the presence of multiple sources of water and a high dispersion induced by frequent variations in the water table complicates their interpretation

    Convulsive liability of bupropion hydrochloride metabolites in Swiss albino mice

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>It is known that following chronic dosing with bupropion HCl active metabolites are present in plasma at levels that are several times higher than that of the parent drug, but the possible convulsive effects of the major metabolites are not known.</p> <p>Methods</p> <p>We investigated the convulsive liability and dose-response of the three major bupropion metabolites following intraperitoneal administration of single doses in female Swiss albino mice, namely erythrohydrobupropion HCl, threohydrobupropion HCl, and hydroxybupropion HCl. We compared these to bupropion HCl. The actual doses of the metabolites administered to mice (n = 120; 10 per dose group) were equimolar equivalents of bupropion HCl 25, 50 and 75 mg/kg. Post treatment, all animals were observed continuously for 2 h during which the number, time of onset, duration and intensity of convulsions were recorded. The primary outcome variable was the percentage of mice in each group who had a convulsion at each dose. Other outcome measures were the time to onset of convulsions, mean convulsions per mouse, and the duration and intensity of convulsions.</p> <p>Results</p> <p>All metabolites were associated with a greater percentage of seizures compared to bupropion, but the percentage of convulsions differed between metabolites. Hydroxybupropion HCl treatment induced the largest percentage of convulsing mice (100% at both 50 and 75 mg/kg) followed by threohydrobupropion HCl (50% and 100%), and then erythrohydrobupropion HCl (10% and 90%), compared to bupropion HCl (0% and 10%). Probit analysis also revealed the dose-response curves were significantly different (p < 0.0001) with CD<sub>50 </sub>values of 35, 50, 61 and 82 mg/kg, respectively for the four different treatments. Cox proportional hazards model results showed that bupropion HCl, erythrohydrobupropion HCl, and threohydrobupropion HCl were significantly less likely to induce convulsions within the 2-h post treatment observation period compared to hydroxybupropion HCl. The mean convulsions per mouse also showed the same dose-dependent and metabolite-dependent trends.</p> <p>Conclusion</p> <p>The demonstration of the dose-dependent and metabolite-dependent convulsive effects of bupropion metabolites is a novelty.</p

    Early Antiretroviral Therapy Reduces AIDS Progression/Death in Individuals with Acute Opportunistic Infections: A Multicenter Randomized Strategy Trial

    Get PDF
    Background: Optimal timing of ART initiation for individuals presenting with AIDS-related OIs has not been defined. Methods and Findings: A5164 was a randomized strategy trial of ‘‘early ART’’ - given within 14 days of starting acute OI treatment versus ‘‘deferred ART’’ - given after acute OI treatment is completed. Randomization was stratified by presenting OI and entry CD4 count. The primary week 48 endpoint was 3-level ordered categorical variable: 1. Death/AIDS progression; 2. No progression with incomplete viral suppression (ie HIV viral load (VL) [greater than or equal to] 50 copies/ml); 3. No progression with optimal viral suppression (ie HIV VL <50 copies/ml). Secondary endpoints included: AIDS progression/death; plasma HIV RNA and CD4 responses and safety parameters including IRIS. 282 subjects were evaluable; 141 per arm. Entry OIs included Pneumocytis jirovecii pneumonia 63%, cryptococcal meningitis 12%, and bacterial infections 12%. The early and deferred arms started ART a median of 12 and 45 days after start of OI treatment, respectively. The difference in the primary endpoint did not reach statistical significance: AIDS progression/death was seen in 20 (14%) vs. 34 (24%); whereas no progression but with incomplete viral suppression was seen in 54 (38%) vs. 44 (31%); and no progression with optimal viral suppression in 67 (48%) vs 63 (45%) in the early vs. deferred arm, respectively (p = 0.22). However, the early ART arm had fewer AIDS progression/deaths (OR = 0.51; 95% CI = 0.27–0.94) and a longer time to AIDS progression/death (stratified HR = 0.53; 95% CI = 0.30–0.92). The early ART had shorter time to achieving a CD4 count above 50 cells/mL (p<0.001) and no increase in adverse events. Conclusions: Early ART resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred ART. These results support the early initiation of ART in patients presenting with acute AIDS-related OIs, absent major contraindications

    Sensitization of spinal cord nociceptive neurons with a conjugate of substance P and cholera toxin

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Several investigators have coupled toxins to neuropeptides for the purpose of lesioning specific neurons in the central nervous system. By producing deficits in function these toxin conjugates have yielded valuable information about the role of these cells. In an effort to specifically stimulate cells rather than kill them we have conjugated the neuropeptide substance P to the catalytic subunit of cholera toxin (SP-CTA). This conjugate should be taken up selectively by neurokinin receptor expressing neurons resulting in enhanced adenylate cyclase activity and neuronal firing.</p> <p>Results</p> <p>The conjugate SP-CTA stimulates adenylate cyclase in cultured cells that are transfected with either the NK1 or NK2 receptor, but not the NK3 receptor. We further demonstrate that intrathecal injection of SP-CTA in rats induces the phosphorylation of the transcription factor cyclic AMP response element binding protein (CREB) and also enhances the expression of the immediate early gene c-Fos. Behaviorally, low doses of SP-CTA (1 μg) injected intrathecally produce thermal hyperalgesia. At higher doses (10 μg) peripheral sensitivity is suppressed suggesting that descending inhibitory pathways may be activated by the SP-CTA induced sensitization of spinal cord neurons.</p> <p>Conclusion</p> <p>The finding that stimulation of adenylate cyclase in neurokinin receptor expressing neurons in the spinal cord produces thermal hyperalgesia is consistent with the known actions of these neurons. These data demonstrate that cholera toxin can be targeted to specific cell types by coupling the catalytic subunit to a peptide agonist for a g-protein coupled receptor. Furthermore, these results demonstrate that SP-CTA can be used as a tool to study sensitization of central neurons in vivo in the absence of an injury.</p
    • …
    corecore