Stability of benzylpenicillin during continuous home intravenous therapy

Objectives: The aim of this study was to investigate the temperature profile of home intravenous (iv) antibiotic reservoirs and the stability of 16 megaunits of benzylpenicillin sodium in 120 mL of sodium chloride 0.9% at constant and variable temperatures. Methods: A Tinytag computerized thermometer recorded temperatures every minute in the home iv antibiotic reservoir pouches of nine patients over a 24 h period. Similar bags containing benzylpenicillin sodium (16 megaunits) were maintained either at a constant 36degreesC, 26degreesC or 21-22degreesC or were worn in a pouch by five healthy volunteers for a 24 h period. Other bags were stored at 3-5degreesC for 10 days. The bags were sampled at timed intervals and benzylpenicillin concentrations assayed by HPLC. Results: Median temperatures recorded in the infusion bags worn by the nine patients were in the range 16.7-34.1degreesC. For infusion bags maintained at 36degreesC, 26degreesC and 21-22degreesC, the concentrations of benzylpenicillin dropped below 90% of the initial concentration at a mean time of 5 h 18 min, 12 h 54 min and 13 h 20 min, respectively, whereas for bags worn by the healthy volunteers the mean time for 10% loss of benzylpenicillin was 9 h 20 min. In contrast, at 3-5degreesC, concentrations of benzylpenicillin only dropped below 90% of the initial concentration at 8 days. Conclusions: Significant temperature-dependent degradation of benzylpenicillin occurs during continuous home iv antibiotic programme infusions, which could result in loss of efficacy.

Genetic time-series analysis identifies a major QTL for in vivo alcohol metabolism not predicted by in vitro studies of structural protein polymorphism at the ADH1B or ADH1C loci

After ingestion of a standardized dose of ethanol, alcohol concentrations were assessed, over 3.5 hours from blood (six readings) and breath (10 readings) in a sample of 412 MZ and DZ twins who took part in an Alcohol Challenge Twin Study (ACTS). Nearly all participants were subsequently genotyped on two polymorphic SNPs in the ADH1B and ADH1C loci known to affect in vitro ADH activity. In the DZ pairs, 14 microsatellite markers covering a 20.5 cM region on chromosome 4 that includes the ADH gene family were assessed, Variation in the timed series of autocorrelated blood and breath alcohol readings was studied using a bivariate simplex design. The contribution of a quantitative trait locus (QTL) or QTL's linked to the ADH region was estimated via a mixture of likelihoods weighted by identity-by-descent probabilities. The effects of allelic substitution at the ADH1B and ADH1C loci were estimated in the means part of the model simultaneously with the effects sex and age. There was a major contribution to variance in alcohol metabolism due to a QTL which accounted for about 64% of the additive genetic covariation common to both blood and breath alcohol readings at the first time point. No effects of the ADH1B*47His or ADH1C*349Ile alleles on in vivo metabolism were observed, although these have been shown to have major effects in vitro. This implies that there is a major determinant of variation for in vivo alcohol metabolism in the ADH region that is not accounted for by these polymorphisms. Earlier analyses of these data suggested that alcohol metabolism is related to drinking behavior and imply that this QTL may be protective against alcohol dependence.

Fluid shifts have no influence on ciprofloxacin pharmacokinetics in intensive care patients with intra-abdominal sepsis

This study aimed to investigate whether fluid shifts alter ciprofloxacin pharmacokinetics in critically ill patients over time. Patients >= 18 years, with normal renal function, requiring intensive care treatment and parenteral antibiotics were enrolled. Group A (22 patients) included patients with documented intra-abdominal infections. Group B (18 patients) included patients with severe sepsis from other causes. All patients received intravenous ciprofloxacin 400 mg every 8 h infused over 60 min. Eight timed blood specimens were taken on days 0, 2 and 7. Ciprofloxacin plasma concentrations were determined using high performance liquid chromatography. There were no significant differences between the pharmacokinetics of the two groups or over time. Ciprofloxacin pharmacokinetics in critically ill patients do not change over time, and intra-abdominal sepsis does not alter ciprofloxacin pharmacokinetic parameters to a greater degree than sepsis from other causes in critically ill patients. (c) 2005 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Costs of managing urinary and faecal incontinence in a sub-acute care facility: A "bottom-up" approach

Aims: To measure accurately the direct costs of managing urinary and faecal incontinence in the sub-acute care setting. Materials and Methods: Prospective observational study was undertaken in two sub-acute care units in a metropolitan hospital. A consecutive series of 29 consecutive patients with urinary and/or faecal incontinence, who were in-patients in a geriatric rehabilitation or subacute neurologic unit underwent routine timed voiding protocol, as per usual care. Face-to-face bedside recordings of all incontinence care, with detailed cost analysis, were undertaken. Results: A total of 3,621 occasions of continence care were costed. The median time per 24 hr spent caring for incontinence per patient was 109 min (interquartile range 88-140). Isolated urinary incontinence episodes occurred in 28 patients (96.5%), mixed urinary/faecal incontinence episodes observed in 79.3%, and episodes of pure faecal incontinence were seen in 62%. The median costs of incontinence care in the sub-acute setting was $49AU per 24 hr, the major share ($41) spent on staff wages. The incontinence tasks of toileting assistance, pad changes, bed changes and catheter care were spread evenly across the three 8 hr shifts of duty. Conclusions: As our population demographics include an increasingly greater portion of the elderly, for whom long term institutional care is becoming relatively more scarce, provision of care in the sub-acute unit that may allow rehabilitation and return to home warrants scrutiny. This is the first study that delineates the costs of managing urinary and faecal incontinence in the sub-acute care setting. Such costs are substantial and place a heavy burden upon night-time carets. (C) 2004 Wiley-Liss, Inc.

The effect of depression on balance decline in mature women

Depression has been identified as a risk factor for falls, and a change in balance ability over time has yet to be investigated. This study aimed to identify if, over a 3-year period, balance ability changed in 26 women who were on medication for depression, compared to 26 non-depressed women. The two groups were matched for age, number of co-morbidities, activity level, medications, and height. All participants were simultaneously enrolled in a larger, longitudinal study of ageing. Balance measures included the Functional Reach (FR) test, Lateral Reach (LR) test, Step Test (ST), Timed Up and Go, and the Modified Clinical Test of Sensory Integration and Balance, Unilateral Stance (ULS) and Limit of Stability (LOS) laboratory tests. Results showed a significant difference between the groups on ST, right ULS (eyes closed) and forward end point excursion of the LOS. There was no difference in the number of falls between groups. Analysis of the depressed group alone showed that right FR declined significantly and left and right LR tended towards decline, but not differently between groups. There was no between-group differences for these measures. There was no significant decline in non-depressed women for any measurement. Depressed women have less ability to maintain their balance than non-depressed women, and should be encouraged to participate in appropriate activities known to improve or maintain balance.

A theory for execution-time derivation in real-time programs

We provide an abstract command language for real-time programs and outline how a partial correctness semantics can be used to compute execution times. The notions of a timed command, refinement of a timed command, the command traversal condition, and the worst-case and best-case execution time of a command are formally introduced and investigated with the help of an underlying weakest liberal precondition semantics. The central result is a theory for the computation of worst-case and best-case execution times from the underlying semantics based on supremum and infimum calculations. The framework is applied to the analysis of a message transmitter program and its implementation. (c) 2005 Elsevier B.V. All rights reserved.

Production of triploid Kuruma shrimp, Marsupenaeus (Penaeus) japonicus (Bate) nauplii through inhibition of polar body I, or polar body I and II extrusion using 6-dimethylaminopurine

This study investigated the chromosome ploidy level of Marsupenaeus (Penaeus) japonicus (Bate) non-viable (unhatched) embryos and nauplii after exposure to 6-dimethylaminopurine (6-DMAP), timed to stop either polar body (PB) I, or PBI and II extrusion. Embryos from eight separate families or spawnings were exposed to 150 or 200 mu M 6-DMAP from 1- to 3-min post-spawning detection (psd) for a 4- to 5-min duration (timed to stop PBI extrusion). Separate aliquots of embryos from five of the same spawnings were also exposed to 200 mu M of 6-DMAP from 1- to 3-min psd for a 16-min duration (timed to stop both PBI and II extrusion). For one spawning, a third aliquot of embryos was exposed to 400 p M of 6-DMAP from 1- to 3-min psd for a 16-min duration (timed to stop both PBI and II extrusion). At 18-h psd, non-viable embryo and nauplii samples were taken separately for fluorescent activated cell sorting (FACS). FACS revealed that there were diploids and triploids among all treated non-viable embryos and nauplii. All control non-viable embryos and nauplii were diploid. Percentages of triploid induction for the 4- to 5-min and 16-min durations were not significantly different (P > 0.05). Additionally, no difference was found in the triploidy level of nonviable embryos compared to nauplii in these treatments. The percentage of triploid embryos and nauplii when exposed to 6-DMAP for a 4- to 5-min duration ranged from 29.57% to 99.23% (average 55.28 +/- 5.45%) and from 5.60% to 98.85% (average 46.70 +/- 7.20%), respectively. The percentage of triploid embryos and nauplii when exposed to 6-DMAP for a 16-min duration ranged from 11.71% to 98.96% (average 52.49 +/- 11.00%) and from 47.5% to 99.24% (average 79.38 +/- 5.24%), respectively. To our knowledge, this is the first documentation of successful PBI or PBI and II inhibition in shrimp. This study conclusively shows that treatment of M. japonicus embryos with 6-DMAP at 1- to 3-min pscl for either a 4- to 5-min duration (timed to stop PBl extrusion) or 16-min duration (timed to stop both PBI and II extrusion) results in viable triploid nauplii. (c) 2006 Elsevier B.V. All rights reserved.

Recurrence interval statistics of cellular automaton seismicity models

The recurrence interval statistics for regional seismicity follows a universal distribution function, independent of the tectonic setting or average rate of activity (Corral, 2004). The universal function is a modified gamma distribution with power-law scaling of recurrence intervals shorter than the average rate of activity and exponential decay for larger intervals. We employ the method of Corral (2004) to examine the recurrence statistics of a range of cellular automaton earthquake models. The majority of models has an exponential distribution of recurrence intervals, the same as that of a Poisson process. One model, the Olami-Feder-Christensen automaton, has recurrence statistics consistent with regional seismicity for a certain range of the conservation parameter of that model. For conservation parameters in this range, the event size statistics are also consistent with regional seismicity. Models whose dynamics are dominated by characteristic earthquakes do not appear to display universality of recurrence statistics.

Interference between propagating changes and its effect on system failure

Computer-based, socio-technical systems projects are frequently failures. In particular, computer-based information systems often fail to live up to their promise. Part of the problem lies in the uncertainty of the effect of combining the subsystems that comprise the complete system; i.e. the system's emergent behaviour cannot be predicted from a knowledge of the subsystems. This paper suggests uncertainty management is a fundamental unifying concept in analysis and design of complex systems and goes on to indicate that this is due to the co-evolutionary nature of the requirements and implementation of socio-technical systems. The paper shows a model of the propagation of a system change that indicates that the introduction of two or more changes over time can cause chaotic emergent behaviour.

Simulation of air traffic controllers' behaviour using the operator choice model

The Operator Choice Model (OCM) was developed to model the behaviour of operators attending to complex tasks involving interdependent concurrent activities, such as in Air Traffic Control (ATC). The purpose of the OCM is to provide a flexible framework for modelling and simulation that can be used for quantitative analyses in human reliability assessment, comparison between human computer interaction (HCI) designs, and analysis of operator workload. The OCM virtual operator is essentially a cycle of four processes: Scan Classify Decide Action Perform Action. Once a cycle is complete, the operator will return to the Scan process. It is also possible to truncate a cycle and return to Scan after each of the processes. These processes are described using Continuous Time Probabilistic Automata (CTPA). The details of the probability and timing models are specific to the domain of application, and need to be specified using domain experts. We are building an application of the OCM for use in ATC. In order to develop a realistic model we are calibrating the probability and timing models that comprise each process using experimental data from a series of experiments conducted with student subjects. These experiments have identified the factors that influence perception and decision making in simplified conflict detection and resolution tasks. This paper presents an application of the OCM approach to a simple ATC conflict detection experiment. The aim is to calibrate the OCM so that its behaviour resembles that of the experimental subjects when it is challenged with the same task. Its behaviour should also interpolate when challenged with scenarios similar to those used to calibrate it. The approach illustrated here uses logistic regression to model the classifications made by the subjects. This model is fitted to the calibration data, and provides an extrapolation to classifications in scenarios outside of the calibration data. A simple strategy is used to calibrate the timing component of the model, and the results for reaction times are compared between the OCM and the student subjects. While this approach to timing does not capture the full complexity of the reaction time distribution seen in the data from the student subjects, the mean and the tail of the distributions are similar.

Axiomatisation of an Interval Calculus for Theorem Proving

We provide an axiomatisation of the Timed Interval Calculus, a set-theoretic notation for expressing properties of time intervals. We implement the axiomatisation in the Ergo theorem prover in order to allow the machine-checked proof of laws for reasoning about predicates expressed using interval operators. These laws can be then used in the machine-assisted verification of real-time applications.

Novel ultra-wideband pulse spectrum modulation scheme

Current ultra-wideband communication systems use short narrow timed pulse sequences to transmit information. Some disadvantages of UWB communication systems are its interference of other conventional wireless systems and its reliance on time hopping schemes for multiple access. This paper presents a novel UWB data modulation scheme based on pulse shaping. This modulation scheme adds more flexibility for data modulation in UWB communication systems. The modulation scheme encodes data in both the timing and frequency spectrum of the transmitted pulse. This has the potential to improve data throughput rates and to lower interference between UWB and narrowband systems.

Integrating runtime assertions with dynamic types: Structuring a derivation from an incomputable specification

An inherent incomputability in the specification of a functional language extension that combines assertions with dynamic type checking is isolated in an explicit derivation from mathematical specifications. The combination of types and assertions (into "dynamic assertion-types" - DATs) is a significant issue since, because the two are congruent means for program correctness, benefit arises from their better integration in contrast to the harm resulting from their unnecessary separation. However, projecting the "set membership" view of assertion-checking into dynamic types results in some incomputable combinations. Refinement of the specification of DAT checking into an implementation by rigorous application of mathematical identities becomes feasible through the addition of a "best-approximate" pseudo-equality that isolates the incomputable component of the specification. This formal treatment leads to an improved, more maintainable outcome with further development potential.