Triangle-programmed coulometric nanotitrations completed by continuous flow with potentiometric detection

Coulometric nanotitrations were realized in a microchannel system using a continuous-flow titration technique with a triangle current-time profile. Redox and acid-base titrations were carried out on Fe(II) and nitric acid samples, respectively, with the same nanotitrator device. A linear relation between the concentration and the coulometric current transferred to the solution was found. The advantages of this universally applicable nanotitrator are fast response, low sample volume, high sensitivity, and high reproducibility as well as the convenience of handling an automated analyzer of the flow-through type.

Continuous monitoring of bovine spongiform encephalopathy rapid test performance by weak positive tissue controls and quality control charts

Bovine spongiform encephalopathy (BSE) rapid tests and routine BSE-testing laboratories underlie strict regulations for approval. Due to the lack of BSE-positive control samples, however, full assay validation at the level of individual test runs and continuous monitoring of test performance on-site is difficult. Most rapid tests use synthetic prion protein peptides, but it is not known to which extend they reflect the assay performance on field samples, and whether they are sufficient to indicate on-site assay quality problems. To address this question we compared the test scores of the provided kit peptide controls to those of standardized weak BSE-positive tissue samples in individual test runs as well as continuously over time by quality control charts in two widely used BSE rapid tests. Our results reveal only a weak correlation between the weak positive tissue control and the peptide control scores. We identified kit-lot related shifts in the assay performances that were not reflected by the peptide control scores. Vice versa, not all shifts indicated by the peptide control scores indeed reflected a shift in the assay performance. In conclusion these data highlight that the use of the kit peptide controls for continuous quality control purposes may result in unjustified rejection or acceptance of test runs. However, standardized weak positive tissue controls in combination with Shewhart-CUSUM control charts appear to be reliable in continuously monitoring assay performance on-site to identify undesired deviations.

Medetomidine continuous rate intravenous infusion in horses in which surgical anaesthesia is maintained with isoflurane and intravenous infusions of lidocaine and ketamine

OBJECTIVE: To evaluate medetomidine as a continuous rate infusion (CRI) in horses in which anaesthesia is maintained with isoflurane and CRIs of ketamine and lidocaine. STUDY DESIGN: Prospective, randomized, blinded clinical trial. ANIMALS: Forty horses undergoing elective surgery. METHODS: After sedation and induction, anaesthesia was maintained with isoflurane. Mechanical ventilation was employed. All horses received lidocaine (1.5 mg kg(-1) initially, then 2 mg kg(-1) hour(-1)) and ketamine (2 mg kg(-1) hour(-1)), both CRIs reducing to 1.5 mg kg(-1) hour(-1) after 50 minutes. Horses in group MILK received a medetomidine CRI of 3.6 mug kg(-1) hour(-1), reducing after 50 minutes to 2.75 mug kg(-1) hour(-1), and horses in group ILK an equal volume of saline. Mean arterial pressure (MAP) was maintained above 70 mmHg using dobutamine. End-tidal concentration of isoflurane (FE'ISO) was adjusted as necessary to maintain surgical anaesthesia. Group ILK received medetomidine (3 mug kg(-1) ) at the end of the procedure. Recovery was evaluated. Differences between groups were analysed using Mann-Whitney, Chi-Square and anova tests as relevant. Significance was taken as p < 0.05. RESULTS: FE'ISO required to maintain surgical anaesthesia in group MILK decreased with time, becoming significantly less than that in group ILK by 45 minutes. After 60 minutes, median (IQR) FE'ISO in MILK was 0.65 (0.4-1.0) %, and in ILK was 1 (0.62-1.2) %. Physiological parameters did not differ between groups, but group MILK required less dobutamine to support MAP. Total recovery times were similar and recovery quality good in both groups. CONCLUSION AND CLINICAL RELEVANCE: A CRI of medetomidine given to horses which were also receiving CRIs of lidocaine and ketamine reduced the concentration of isoflurane necessary to maintain satisfactory anaesthesia for surgery, and reduced the dobutamine required to maintain MAP. No further sedation was required to provide a calm recovery.

The influence of a continuous rate infusion of dexmedetomidine on the nociceptive withdrawal reflex and temporal summation during isoflurane anaesthesia in dogs

Objective To examine the influence of a low dose dexmedetomidine infusion on the nociceptive withdrawal reflex and temporal summation in dogs during isoflurane anaesthesia. Study design Prospective experimental blinded cross-over study. Animals Eight healthy mixed breed dogs, body weight Mean +/- SD 26.5 +/- 8.4 kg and age 25 +/- 16 months. Methods Anaesthesia was induced with propofol and maintained with isoflurane (Fe'ISO 1.3%) delivered in oxygen and air. After stabilization, baseline recordings (time 0) were obtained, then a dexmedetomidine bolus (1 mug kg(-1) IV) followed by a continuous rate infusion (1 mug kg(-1) hour(-1) ) or saline placebo were administered. At times 10, 30 and 60 minutes after the initial bolus, electrical stimulations of increasing intensity were applied over the lateral plantar digital nerve, and administered both as single and as repeated stimuli. The resulting reflex responses were recorded using electromyography. Data were analysed using a multivariable linear regression model and a Kruskal Wallis test for single stimulation data, and repeated measures anova and paired t-test for repeated stimulation data. Results The AUC for the stimulus-response curves after single stimulation were similar for both treatments at time 0. At times 10, 30 and 60 the AUCs for the stimulus-response curves were significantly lower with dexmedetomidine treatment than with placebo. Temporal summation was evident in both treatments at times 0, 10, 30 and 60 starting from a stimulation intensity of 10 mA. The magnitude of temporal summation was smaller in dexmedetomidine than in placebo treated dogs at time 10, 30 and 60, but not at time 0. Conclusions During isoflurane anaesthesia, low dose dexmedetomidine suppresses the nociceptive reflex responses after single and repeated electrical stimulation. Clinical relevance This experimental study confirms previous reports on its peri-operative efficacy under clinical conditions, and further indicates that dexmedetomidine might reduce the risk of post-operative chronic pain development.

A continuous-time MILP model for short-term scheduling of make-and-pack production processes

In process industries, make-and-pack production is used to produce food and beverages, chemicals, and metal products, among others. This type of production process allows the fabrication of a wide range of products in relatively small amounts using the same equipment. In this article, we consider a real-world production process (cf. Honkomp et al. 2000. The curse of reality – why process scheduling optimization problems are diffcult in practice. Computers & Chemical Engineering, 24, 323–328.) comprising sequence-dependent changeover times, multipurpose storage units with limited capacities, quarantine times, batch splitting, partial equipment connectivity, and transfer times. The planning problem consists of computing a production schedule such that a given demand of packed products is fulfilled, all technological constraints are satisfied, and the production makespan is minimised. None of the models in the literature covers all of the technological constraints that occur in such make-and-pack production processes. To close this gap, we develop an efficient mixed-integer linear programming model that is based on a continuous time domain and general-precedence variables. We propose novel types of symmetry-breaking constraints and a preprocessing procedure to improve the model performance. In an experimental analysis, we show that small- and moderate-sized instances can be solved to optimality within short CPU times.

Effect of Continuous Infusion of Relaxin on Progesterone, Oxytocin, and Relaxin Blood Concentrations and Time of Parturition in Beef Heifers

These studies were designed to determine whether continuous intravenous infusion of increasing dosages of porcine relaxin during late pregnancy in beef heifers would influence circulating blood concentrations of relaxin, progesterone, and oxytocin, and time of onset of parturition. Beef heifers were bred by artificial insemination and, on Day 277, fitted with indwelling jugular cannulas for hormone infusion and blood sampling from Day 277 to 286. Intravenous infusion of purified porcine relaxin (pRLX, 3000 U mg-1) was started in heifers (n = 8) at increasing dosages (200 U h-1 on Days 277 and 278, 300 U h-1 on Days 279 and 280, 500 U h-1 on Day 281, 600 U h-1 on Day 282, and 700 U h-1 on Days 283 to 286). Phosphate buffer saline (PBS, 10 ml h-1) was infused during these same times to control (n = 6) animals. Relaxin treatment steadily increased the circulating plasma concentration of immunoreactive relaxin to more than 120 ng ml-1 compared with less than 0.5 ng ml-1 in PBStreated controls. Relaxin infusion in increasing dosages over the treatment time was associated with a significant decrease (P < 0.01) in plasma progesterone concentration compared with the PBS controls. Plasma levels of oxytocin at 4- hour intervals remained similar (P > 0.05) during the pretreatment period and throughout continuous infusion of pRLX and PBS. Although continuous intravenous infusion of relaxin resulted in a decrease in circulating blood levels of progesterone, it did not significantly reduce the interval between the beginning of pRLX treatment and parturition compared with the PBS-infused control heifers. These results indicate that continuous intravenous infusion of high levels of porcine relaxin resulted in a decrease in progesterone secretion in late pregnant beef heifers.

Combining follow-up and change data is valid in meta-analyses of continuous outcomes: a meta-epidemiological study

OBJECTIVE To investigate whether it is valid to combine follow-up and change data when conducting meta-analyses of continuous outcomes. STUDY DESIGN AND SETTING Meta-epidemiological study of randomized controlled trials in patients with osteoarthritis of the knee/hip, which assessed patient-reported pain. We calculated standardized mean differences (SMDs) based on follow-up and change data, and pooled within-trial differences in SMDs. We also derived pooled SMDs indicating the largest treatment effect within a trial (optimistic selection of SMDs) and derived pooled SMDs from the estimate indicating the smallest treatment effect within a trial (pessimistic selection of SMDs). RESULTS A total of 21 meta-analyses with 189 trials with 292 randomized comparisons in 41,256 patients were included. On average, SMDs were 0.04 standard deviation units more beneficial when follow-up values were used (difference in SMDs: -0.04; 95% confidence interval: -0.13, 0.06; P=0.44). In 13 meta-analyses (62%), there was a relevant difference in clinical and/or significance level between optimistic and pessimistic pooled SMDs. CONCLUSION On average, there is no relevant difference between follow-up and change data SMDs, and combining these estimates in meta-analysis is generally valid. Decision on which type of data to use when both follow-up and change data are available should be prespecified in the meta-analysis protocol.

Self-dual continuous processes

The important application of semi-static hedging in financial markets naturally leads to the notion of conditionally quasi self-dual processes which is, for continuous semimartingales, related to conditional symmetry properties of both their ordinary as well as their stochastic logarithms. We provide a structure result for continuous conditionally quasi self-dual processes. Our main result is to give a characterization of continuous Ocone martingales via a strong version of self-duality.

Implantation of the continuous flow HeartWare(R) left ventricular assist device

Recent outstanding clinical advances with new mechanical circulatory systems have led to additional strategies in the treatment of end-stage heart failure. Heart transplantation can be postponed and for certain patients even replaced by smaller implantable left ventricular assist devices (LVADs). Mechanical support of the failing left ventricle enables appropriate haemodynamic stabilization and recovery of secondary organ failure, often seen in these severely ill patients. These new devices may be of great help to bridge patients until a suitable cardiac allograft is available but are also discussed as definitive treatment for patients who do not qualify for transplantation. Main indications for LVAD implantation are bridge to recovery, bridge to transplantation or destination therapy. An LVAD may be an important tool for patients with an expected prolonged period on the waiting list, for instance those with blood group O or B, with high or low body weight and those with potentially reversible secondary organ failure and pulmonary artery hypertension. However, LVAD implantation means an additional heart operation with inherent perioperative risks and complications during the waiting period. Finally, cardiac transplantation in patients with prior implantation of an LVAD represents a surgical challenge. The care of patients after the implantation of miniaturized LVADs, such as the HeartWare® system, seems to be easier than following pulsatile devices. The explantation of such devices at the time of transplantation is technically more comfortable than after HeartMate II implantation.