PubMed · 14994634
Drawing on different schools of thought, the author illustrates how more unconventional methods can be introduced to stimulate creativity and innovation in product design and engineering.
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John Hockey. Practical creativity.. https://pubmed.ncbi.nlm.nih.gov/14994634/
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This study is demonstrating the scale up of asymmetric microbial Baeyer-Villiger oxidation of racemic bicyclo[3.2.0]hept-2-en-6-one (1) to the kilogram scale using a 50 L bioreactor. The process has been optimized with respect to bottlenecks identified in downscaled experiments. A high productivity was obtained combining a resin-based in situ substrate feeding and product removal methodology (in situ SFPR), a glycerol feed control, and an improved oxygenation device (using a sintered-metal sparger). As expected both regioisomeric lactones [(-)-(1S,5R)-2 and (-)-(1R,5S)-3] were obtained in nearly enantiopure form (ee > 98%) and good yield. This represents the first example of such an asymmetric Baeyer-Villiger biooxidation reaction ever operated at that scale. This novel resin-based in situ SFPR technology therefore clearly opens the way to further (industrial) upscaling of this highly valuable (asymmetric) reaction.
AIM: The energy efficiency of FES-cycling in spinal cord injured subjects is very much lower than that of normal cycling, and efficiency is dependent upon the parameters of muscle stimulation. We investigated measures which can be used to evaluate the effect on cycling performance of changes in stimulation parameters, and which might therefore be used to optimise them. We aimed to determine whether oxygen cost and stimulation cost measurements are sensitive enough to allow discrimination between the efficacy of different activation ranges for stimulation of each muscle group during constant-power cycling. METHODS: We employed a custom FES-cycling ergometer system, with accurate control of cadence and stimulated exercise workrate. Two sets of muscle activation angles ("stimulation patterns"), denoted "P1" and "P2", were applied repeatedly (eight times each) during constant-power cycling, in a repeated measures design with a single paraplegic subject. Pulmonary oxygen uptake was measured in real time and used to determine the oxygen cost of the exercise. A new measure of stimulation cost of the exercise is proposed, which represents the total rate of stimulation charge applied to the stimulated muscle groups during cycling. A number of energy-efficiency measures were also estimated. RESULTS: Average oxygen cost and stimulation cost of P1 were found to be significantly lower than those for P2 (paired t-test, p<0.05): oxygen costs were 0.56+/-0.03l min-1 and 0.61+/-0.04l min-1 (mean+/-S.D.), respectively; stimulation costs were 74.91+/-12.15 mC min-1 and 100.30+/-14.78 mC min-1 (mean+/-S.D.), respectively. Correspondingly, all efficiency estimates for P1 were greater than those for P2. CONCLUSION: Oxygen cost and stimulation cost measures both allow discrimination between the efficacy of different muscle activation patterns during constant-power FES-cycling. However, stimulation cost is more easily determined in real time, and responds more rapidly and with greatly improved signal-to-noise properties than the ventilatory oxygen uptake measurements required for estimation of oxygen cost. These measures may find utility in the adjustment of stimulation patterns for achievement of optimal cycling performance.
Sedation administration and agitation management are fundamental activities in any intensive care unit. A lack of objective measures of agitation and sedation, as well as poor understanding of the underlying dynamics, contribute to inefficient outcomes and expensive healthcare. Recent models of agitation-sedation pharmacodynamics have enhanced understanding of the underlying dynamics and enable development of advanced protocols for semi-automated sedation administration. However, these initial models do not capture all observed dynamics, particularly periods of low sedative infusion. A physiologically representative model that incorporates endogenous agitation reduction (EAR) dynamics is presented and validated using data from 37 critical care patients. High median relative average normalised density (RAND) values of 0.77 and 0.78 support and minimum RAND values of 0.51 and 0.55 for models without and with EAR dynamics respectively show that both models are valid representations of the fundamental agitation-sedation dynamics present in a broad spectrum of intensive care unit (ICU) patients. While the addition of the EAR dynamic increases the ability of the model to capture the observed dynamics of the agitation-sedation system, the improvement is relatively small and the sensitivity of the model to the EAR dynamic is low. Although this may represent a limitation of the model, the inclusion of EAR is shown to be important for accurately capturing periods of low, or no, sedative infusion, such as during weaning prior to extubation.