5-Benzylidene-4-Oxazolidinones Are Synergistic with Antibiotics for the Treatment of Staphylococcus aureus Biofilms

The failure of frontline antibiotics in the clinic is one of the most serious threats to human health and requires a multitude of novel therapeutics and innovative approaches to treatment so as to curtail the growing crisis. In addition to traditional resistance mechanisms resulting in the lack of efficacy of many antibiotics, most chronic and recurring infections are further made tolerant to antibiotic action by the presence of biofilms. Herein, we report an expanded set of 5-benzylidene-4-oxazolidinones that are able to inhibit the formation of Staphylococcus aureus biofilms, disperse preformed biofilms, and, in combination with common antibiotics, are able to significantly reduce the bacterial load in a robust collagen-matrix model of biofilm infection.     

Anti-D in a D-positive renal transplant patient

PURPOSE: We report a case of postoperative reparalysis in the recovery room, following nebulized epinephrine. The patient was pharmacologically reversed with edrophonium after paralysis with rocuronium. CLINICAL FINDINGS: A 12-yr-old girl developed postoperative reparalysis following the intraoperative administration of rocuronium. A total of 0.92 mg.kg-1 rocuronium was administered. After surgery, pharmacological reversal was achieved with 20 mg edrophonium with 0.15 mg atropine sulfate iv 35 min after the last administration of rocuronium. Muscular relaxation was monitored using an ulnar peripheral nerve stimulator (PNS). After reversal, a full train-of-four and sustained tetanus at 50 Hz were present. In the recovery room, following nebulized epinephrine, the patient became apneic. The patient was paralyzed and an ulnar PNS demonstrated only one faint twitch. The paralysis was reversed with 1.5 mg neostigmine with 0.3 mg glycopyrrolate. CONCLUSION: Postoperative reparalysis following rocuronium may be a cause of postoperative respiratory distress. The definitive diagnosis is made using PNS and observing the response to pharmacological reversal. Nebulized epinephrine may have a previously undescribed role in the development of postoperative reparalysis.     

A comparison of leaf-spring with aircushion trailer suspensions in the transport environment

Packaging engineers need to be able to accurately determine the forces present in the shipping environment in order to protect packaged goods. The purpose of this study was to determine the vertical vibration levels measured in three separate truck-trailer suspension systems; conventional leaf-spring, conventional air-ride and damaged air-ride. The main conclusion reached in this study is that the air-ride suspension when maintained gives lower power density (PD) levels on all road surfaces studied. A damaged air-ride suspension and leaf-spring suspension are very similar in response frequencies, although the damaged air-ride produces higher vibration levels at lower frequencies.     

The pharmacokinetics and pharmacodynamics of the oral iron chelator deferiprone (L1) in relation to hemoglobin levels

Recently, we demonstrated that administration of the orally active iron chelating agent deferiprone (1,2-dimethyl-3-hydroxypyrid-4-one (L1)) at 6-hour intervals results in significantly greater urinary iron excretion than that induced during administration of the drug at 12-hour intervals. That study was conducted in thalassemia patients, all of whom had received a packed red cell transfusion of 15 cc/kg. 72 hours prior to evaluation of urinary iron excretion, at a time when endogenous erythropoiesis would be expected to be at its lowest. In clinical practice however, thalassemia patients, suppression of endogenous erythropoiesis is not sustained between transfusions. We set out to determine the influence that administration of deferiprone has on urinary iron excretion at lower hemoglobin concentrations, immediately prior to transfusion. We hypothesized that hemoglobin levels will affect the ability of deferiprone to chelate iron. Ten regularly transfused patients with homozygous beta-thalassemia (HBT) aged mean +/- SD, 20.9 +/- 4.7, range 13 - 27 years, receiving long-term therapy with deferiprone, were treated with deferiprone 75 mg/kg/day, administered every 6 hours (or every 12 hours) for 72 hours immediately prior to a blood transfusion in the first month. One month later each patient received the other of the 2 dosing regimens for 72 hours immediately prior to transfusion. The deferiprone-induced 24-hour urinary iron excretion was similar during both dosing regimens; 0.56 +/- 0.45 mg/kg when L1 was given every 6 hours and 0.48 +/- 0.52 mg/kg when L1 was administered every 12 hours (p = 0.79). However, the calculated 24-hour area under the plasma concentration-time curve (AUC0-24) of deferiprone was significantly lower when deferiprone was administered at 6-hour intervals (6,762.8 +/- 1,601.6 mg*min/l), than that observed when deferiprone was administered every 12 hours (8,250.1 +/- 1,235.7 mg*min/l) (p = 0.04). The pharmacokinetics of deferiprone when administered immediately prior to transfusions are different from those following transfusions. More studies assessing total body iron excretion are needed to determine the contribution of the fecal route in iron excretion.     

Detonation-induced coal gasification

A preliminary experimental and theorotical investigation of the feasibility of detonation-induced pulverized coal gasification is described. The concept envisions a closed annular detonation duct through which a hydrogen/oxygen gasphase detonation propagates continuously. Coal particles injected into the violent and rapidly changing atmosphere produced by the detonation would undergo gasification reactions and be subsequently expelled from the duct. These events would occur in a time period compatible with one revolution of the detonation. A one-dimensional analysis of the response of a single coal particle within the expansion-wave region behind the detonation front is presented. Independent variables include particle diameter, initial H₂/O₂ stoichiometry and expansion wavelength (at the time the particle is overtaken by the detonation front). The most significant result of this analysis is the prediction of relative gas/particle velocities ranging between 125 and 1500m/s, which are sustained throughout particle residence times of 1–15 ms corresponding to 10–1000 μm diameter particles. An experimental facility comprising a 47 m ‘single-shot’ detonation duct that was built for this study is discussed. The duct was 2.54 cm square and was terminated at each end by a 0.36 m diameter × 2.44 m long cylindrical tank which contained helium gas during a test. Sized coal particles were placed at a point within the first 3.7 m length of the duct, and thin brass diaphragms initially separated the duct from the two helium-filled tanks. Detonation was initiated at the duct, end closest to these particles. The diaphragm at that end burst, allowing combustion and gasification products to exhaust into the adjoining tank where they were quenched and decelerated. When the detonation reached the far end of the duct the second diaphragm burst, minimizing wave reflections which would otherwise return to the ‘test section’ end and interfere with the flow field there. After a test the contents of both tanks and the duct were circulated and mixed. A gas sample was then drawn and analysed for yield. Results from preliminary experiments using this facility are presented. Although too few tests were conducted for conclusive observations to be reported, in two experiments yields of CO + CH₄ representing 40 per cent of the total initial carbon content in the coal samples were obtained.     

A decision-making approach to the operation of flexible manufacturing systems

This paper introduces a generic decision-making framework for assigning resources of a manufacturing system to production tasks. Resources are broadly defined production units, such as machines, human operators, or material handling vehicles; and tasks are activities performed by resources. In the specific context of FMS, resources correspond to individual machines; tasks correspond to operations to be performed on parts. The framework assumes a hierarchical structure of the system and calls for the execution of four consecutive steps to make a decision for the assignment of a resource to a task. These steps are 1) establishment of decision-making criteria, 2) formation of alternative assignments, 3) estimation of the consequences of the assignments, and 4) selection of the best alternative assignment. This framework has been applied to an existing FMS as an operational policy that decides what task will be executed on which resource of this FMS. Simulation runs provide some initial results of the application of this policy. It is shown that the policy provides flexibility in terms of system performance and computational effort.     

Behavioral model synthesis with Cones

The Cones synthesis system for automatic generation of VLSI implementations is discussed. Named for the cones in sequential logic, Cones takes behavioral models written in C and produces gate-level implementations in technologies such as standard cells and programmable logic arrays or programmable logic devices. The overall design is produced faster, more efficiently, and with fewer errors. Designers are free to concentrate on functions, instead of on the details of the implementation technology