A bistable reaction-diffusion system in a stretching flow

We examine the evolution of a bistable reaction in a one-dimensional stretching flow, as a model for chaotic advection. We derive two reduced systems of ordinary differential equations (ODEs) for the dynamics of the governing advection-reaction-diffusion partial differential equations (PDE), for pulse-like and for plateau-like solutions, based on a non-perturbative approach. This reduction allows us to study the dynamics in two cases: first, close to a saddle-node bifurcation at which a pair of nontrivial steady states are born as the dimensionless reaction rate (Damkoehler number) is increased, and, second, for large Damkoehler number, far away from the bifurcation. The main aim is to investigate the initial-value problem and to determine when an initial condition subject to chaotic stirring will decay to zero and when it will give rise to a nonzero final state. Comparisons with full PDE simulations show that the reduced pulse model accurately predicts the threshold amplitude for a pulse initial condition to give rise to a nontrivial final steady state, and that the reduced plateau model gives an accurate picture of the dynamics of the system at large Damkoehler number. Published in Physica D (2006)

Class-D audio amplifiers with negative feedback

There are many different designs for audio amplifiers. Class-D, or switching, amplifiers generate their output signal in the form of a high-frequency square wave of variable duty cycle (ratio of on time to off time). The square-wave nature of the output allows a particularly efficient output stage, with minimal losses. The output is ultimately filtered to remove components of the spectrum above the audio range. Mathematical models are derived here for a variety of related class-D amplifier designs that use negative feedback. These models use an asymptotic expansion in powers of a small parameter related to the ratio of typical audio frequencies to the switching frequency to develop a power series for the output component in the audio spectrum. These models confirm that there is a form of distortion intrinsic to such amplifier designs. The models also explain why two approaches used commercially succeed in largely eliminating this distortion; a new means of overcoming the intrinsic distortion is revealed by the analysis. Copyright (2006) Society for Industrial and Applied Mathematics

Clinical outcome after first and recurrent hemorrhage in patients with untreated brain arteriovenous malformation

Background and Purpose: The morbidity from spontaneous hemorrhage of untreated brain arteriovenous malformations (AVM) is not well described. Methods: The 241 consecutive AVM patients (mean age 3716 years, 52% women) from the prospective Columbia AVM Databank initially presenting with hemorrhage were evaluated using the Rankin Scale (RS) and the National Institute of Health Stroke Scale (NIHSS). From the 241 AVM patients, 29 (12%) had subsequent intracranial hemorrhage during follow-up. For further comparisons, 84 non-AVM patients with intracerebral hemorrhage from the Northern Manhattan Study (NOMAS) served as a control group. Results: In 241 AVM patients presenting with hemorrhage the median RS was 2 and the median NIHSS was 1 (49% RS 0 to 1, 61% NIHSS 2). The median time between hemorrhage and clinical evaluation was 11 days (mean 219 days). Recurrent AVM hemorrhage during follow-up resulted in no significant increase in morbidity (median RS 2, P0.004; median NIHSS 3, P0.322; time between hemorrhage and study evaluation: median 55 days, mean 657 days). Among AVM-hemorrhage subtypes, parenchymatous AVM hemorrhage was associated with higher stroke morbidity (odds ratio, 2.9; 95% CI, 1.5 to 5.8 for NIHSS 2) than nonparenchymatous hemorrhages. Parenchymatous AVM hemorrhage had a significantly better outcome (median NIHSS 1) than non-AVM related hemorrhage (median NIHSS 12; P0.0001). Conclusions: Hemorrhage, either at initial presentation or during follow-up of untreated AVM patients appears to carry

Unruptured arteriovenous malformations of the brain

Unruptured, asymptomatic arteriovenous malformations (AVMs) lurk in the brains of approximately one person in every thousand; their prevalence, based on four studies of magnetic resonance imaging (MRI) of 7,359 people without brain disorders, 1-4 was 0.1 % (95% confidence interval [CI] 0% to 0.2%). Some of these brain AVMs may be discovered if and when they cause intracranial haemorrhage, epileptic seizure(s), headache, or a focal neurological deficit, but many brain AVMs may potentially lie dormant from the cradle to the grave.

Granulocyte-colony-stimulating factor mobilizes bone marrow stem cells in patients with subacute ischemic stroke: the Stem Cell Trial of Recovery EnhanceMent After Stroke (STEMS) Pilot Randomized, Controlled Trial (ISRCTN 16784092)

Background and Purpose - Loss of motor function is common after stroke and leads to significant chronic disability. Stem cells are capable of self-renewal and of differentiating into multiple cell types, including neurones, glia, and vascular cells. We assessed the safety of granulocyte-colony-stimulating factor (G-CSF) after stroke and its effect on circulating CD34 stem cells. Methods - We performed a 2-center, dose-escalation, double-blind, randomized, placebo-controlled pilot trial (ISRCTN 16784092) of G-CSF (6 blocks of 1 to 10 g/kg SC, 1 or 5 daily doses) in 36 patients with recent ischemic stroke. Circulating CD34 stem cells were measured by flow cytometry; blood counts and measures of safety and functional outcome were also monitored. All measures were made blinded to treatment. Results - Thirty-six patients, whose mean SD age was 768 years and of whom 50% were male, were recruited. G-CSF (5 days of 10 g/kg) increased CD34 count in a dose-dependent manner, from 2.5 to 37.7 at day 5 (area under curve, P0.005). A dose-dependent rise in white cell count (P0.001) was also seen. There was no difference between treatment groups in the number of patients with serious adverse events: G-CSF, 7/24 (29%) versus placebo 3/12 (25%), or in their dependence (modified Rankin Scale, median 4, interquartile range, 3 to 5) at 90 days. Conclusions - ”G-CSF is effective at mobilizing bone marrow CD34 stem cells in patients with recent ischemic stroke. Administration is feasible and appears to be safe and well tolerated. The fate of mobilized cells and their effect on functional outcome remain to be determined. (Stroke. 2006;37:2979-2983.)

The Virtual International Stroke Trials Archive

Background and Purpose - Stroke has global importance and it causes an increasing amount of human suffering and economic burden, but its management is far from optimal. The unsuccessful outcome of several research programs highlights the need for reliable data on which to plan future clinical trials. The Virtual International Stroke Trials Archive aims to aid the planning of clinical trials by collating and providing access to a rich resource of patient data to perform exploratory analyses. Methods - Data were contributed by the principal investigators of numerous trials from the past 16 years. These data have been centrally collated and are available for anonymized analysis and hypothesis testing. Results - ”Currently, the Virtual International Stroke Trials Archive contains 21 trials. There are data on 15 000 patients with both ischemic and hemorrhagic stroke. Ages range between 18 and 103 years, with a mean age of 6912 years. Outcome measures include the Barthel Index, Scandinavian Stroke Scale, National Institutes of Health Stroke Scale, Orgogozo Scale, and modified Rankin Scale. Medical history and onset-to-treatment time are readily available, and computed tomography lesion data are available for selected trials. Conclusions - This resource has the potential to influence clinical trial design and implementation through data analyses that inform planning. (Stroke. 2007;38:1905-1910.)

Virtual-Build-to-Order as a Mass Customization Order Fulfilment Model

Virtual-build-to-order (VBTO) is a form of order fulfilment system in which the producer has the ability to search across the entire pipeline of finished stock, products in production and those in the production plan, in order to find the best product for a customer. It is a system design that is attractive to Mass Customizers, such as those in the automotive sector, whose manufacturing lead time exceeds their customers' tolerable waiting times, and for whom the holding of partly-finished stocks at a fixed decoupling point is unattractive or unworkable. This paper describes and develops the operational concepts that underpin VBTO, in particular the concepts of reconfiguration flexibility and customer aversion to waiting. Reconfiguration is the process of changing a product's specification at any point along the order fulfilment pipeline. The extent to which an order fulfilment system is flexible or inflexible reveals itself in the reconfiguration cost curve, of which there are four basic types. The operational features of the generic VBTO system are described and simulation is used to study its behaviour and performance. The concepts of reconfiguration flexibility and floating decoupling point are introduced and discussed.

Fundamental Modes of Operation for Mass Customization

The concept of Mass Customization (MC) - producing customised goods for a mass market - has received considerable attention in the research literature in recent years. However the literature is limited in providing an understanding of the content of MC strategies (the organizational structures, process technologies, etc., that are best in a particular environment) and the process of MC strategies (the sub-strategy that an enterprise should select and how they should go about implementing an MC strategy). In this paper six published classification schemes of relevance to Mass Customization are reviewed. The classification schemes are applied to five case studies of enterprises operating in an MC environment. The limitations of the schemes are analysed and their failure to distinguish key characteristics is highlighted. Analysis of the findings leads to the development of a taxonomy of operational modes for MC. Five fundamental modes of operation for Mass Customization are identified. These modes are described and justified and their application is illustrated by contrasting the information requirements of two modes. The potential of these modes to provide the foundations for detailed configurations models is discussed.

Fundamental behaviour of Virtual-Build-to-Order systems

Virtual-Build-to-Order (VBTO) is an emerging order fulfilment system within the automotive sector that is intended to improve fulfilment performance by taking advantage of integrated information systems. The primary innovation in VBTO systems is the ability to make available all unsold products that are in the production pipeline to all customers. In a conventional system the pipeline is inaccessible and a customer can be fulfilled by a product from stock or having a product Built-to-Order (BTO), whereas in a VBTO system a customer can be fulfilled by a product from stock, by being allocated a product in the pipeline, or by a build-to-order product. Simulation is used to investigate and profile the fundamental behaviour of the basic VBTO system and to compare it to a Conventional system. A predictive relationship is identified, between the proportions of customers fulfilled through each mechanism and the ratio of product variety / pipeline length. The simulations reveal that a VBTO system exhibits inherent behaviour that alters the stock mix and levels, leading to stock levels being higher than in an equivalent conventional system at certain variety / pipeline ratios. The results have implications for the design and management of order fulfilment systems in sectors such as automotive where VBTO is a viable operational model.

Consideration of the relevance of standard quality techniques in Mass Customisation

The business philosophy of Mass Customisation (MC) implies rapid response to customer requests, high efficiency and limited cost overheads of customisation. Furthermore, it also implies the quality benefits of the mass production paradigm are guaranteed. However, traditional quality science in manufacturing is premised on volume production of uniform products rather than of differentiated products associated with MC. This creates quality challenges and raises questions over the suitability of standard quality engineering techniques. From an analysis of relevant MC and quality literature it is argued the aims of MC are aligned with contemporary thinking on quality and that quality concepts provide insights into MC. Quality issues are considered along three dimensions - product development, order fulfilment and customer interaction. The applicability and effectiveness of conventional quality engineering techniques are discussed and a framework is presented which identifies key issues with respect to quality for a spectrum of MC strategies.

Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the developing male Wistar(Han) rat I: no decrease in epididymal sperm count after a single acute dose

It has been reported that fetal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes defects in the male reproductive system of the rat. We set out to replicate and extend these effects using a robust experimental design. Groups of 75 (control vehicle) or 55 (50, 200 or 1000 ng of TCDD kg-1 bodyweight) female Wistar(Han) rats were exposed to TCDD on Gestational Day (GD) 15, then allowed to litter. The high dose group dams showed no sustained weight loss compared to control, but four animals had total litter loss. Pups in the high dose group showed reduced body weight up till day 21, and pups in the medium dose group showed reduced body weight in the first week post partum. Balano-preputial separation (BPS) was significantly delayed in the high dose group male offspring. There were no significant effects of treatment when the offspring were subjected to a functional observational battery, or mated with females to assess reproductive capability. 25 males per group were killed on post natal day (PND) 70, and ~60 animals per group (~30 for the high dose group) on PND120 to assess seminology and other endpoints. At PND120, the two highest dose groups showed a statistically significant elevation of sperm counts, compared to control; however, this effect was small (~30%), within the normal range of sperm counts for this strain of rat, was not reflected in testicular spermatid counts nor PND70 data, and is therefore postulated to have no biological significance. Although there was an increase in the proportion of abnormal sperm at PND70, seminology parameters were otherwise unremarkable. Testis weights in the high dose group were slightly decreased at PND 70 and 120, and at PND120, brain weights were decreased in the high dose group, liver to body weight ratios were increased for all three dose groups, with an increase in inflammatory cell foci in the epididymis in the high dose group. These data show that TCDD is a potent developmental toxin after exposure of the developing fetus, but that acute developmental exposure to TCDD on GD15 caused no decrease in sperm counts.

Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the developing male Wistar(Han) rat II: chronic dosing causes developmental delay

We have investigated whether fetal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes defects in the male reproductive system of the rat, using chronically exposed rats to ensure continuous exposure of the fetus. 5-6 week old rats were exposed to control diet, or diet containing TCDD, to attain an average dose of 2.4, 8 and 46 ng TCDD kg-1 day-1 for twelve weeks, whereupon the rats were mated, and allowed to litter; rats were switched to control diet after parturition. Male offspring were allowed to develop until kills on PND70 (25 per group), or PND120 (all remaining animals). Offspring from the high dose group showed an increase in total litter loss, and the number of animals alive on post-natal day (PND) 4 in the high dose group was ~26% less than control. The high and medium dose offspring showed decreased weights at various ages. Balano-preputial separation was significantly delayed in all three dose groups, compared to control. There were no significant effects of maternal treatment when the offspring were subjected to a functional observational battery, or learning tests, with the exception that the high dose group showed a deficit in motor activity. 20 rats per group were mated to females, and there were no significant effects of maternal treatment on the fertility of these rats, nor on the F1 or F2 sex ratio. Sperm parameters at PND70 and 120 showed no significant effect of maternal treatment, with the exception that there was an increase in the proportion of abnormal sperm in the high dose group at PND70; this is associated with the developmental delay in puberty in this dose group. There were no remarkable findings of maternal treatment on organ weights, with the exception that testis weights were reduced by ~10% at PND70 (but not PND120), and although the experiment was sufficiently powered to detect small changes, ventral prostate weight was not reduced. There were no significant effects of maternal treatment upon histopathological comparison of high dose and control group organs. These data confirm that developmental exposure to TCDD shows no potent effect on adult sperm parameters or accessory sexual organs, but show that delay in BPS occurs after exposure to low doses of TCDD, and this is dependent upon whether TCDD is administered acutely or chronically.

Evaluating Invariances in Document Layout Functions

With the development of variable-data-driven digital presses - where each document printed is potentially unique - there is a need for pre-press optimization to identify material that is invariant from document to document. In this way rasterisation can be confined solely to those areas which change between successive documents thereby alleviating a potential performance bottleneck. Given a template document specified in terms of layout functions, where actual data is bound at the last possible moment before printing, we look at deriving and exploiting the invariant properties of layout functions from their formal specifications. We propose future work on generic extraction of invariance from such properties for certain classes of layout functions.

Amphetamine increases blood pressure and heart rate but has no effect on motor recovery or cerebral haemodynamics in ischaemic stroke: a randomized controlled trial (ISRCTN 36285333)

Amphetamine enhances recovery after experimental ischaemia and has shown promise in small clinical trials when combined with motor or sensory stimulation. Amphetamine, a sympathomimetic, might have haemodynamic effects in stroke patients, although limited data have been published. Subjects were recruited 3-30 days post ischaemic stroke into a phase II randomised (1:1), double blind, placebo-controlled trial. Subjects received dexamphetamine (5mg initially, then 10mg for 10 subsequent doses with 3 or 4 day separations) or placebo in addition to inpatient physiotherapy. Recovery was assessed by motor scales (Fugl-Meyer, FM), and functional scales (Barthel index, BI and modified Rankin score, mRS). Peripheral blood pressure (BP), central haemodynamics and middle cerebral artery blood flow velocity were assessed before, and 90 minutes after, the first 2 doses. 33 subjects were recruited, age 33-88 (mean 71) years, males 52%, 4-30 (median 15) days post stroke to inclusion. 16 patients were randomised to placebo and 17 amphetamine. Amphetamine did not improve motor function at 90 days; mean (standard deviation) FM 37.6 (27.6) vs. control 35.2 (27.8) (p=0.81). Functional outcome (BI, mRS) did not differ between treatment groups. Peripheral and central systolic BP, and heart rate, were 11.2 mmHg (p=0.03), 9.5 mmHg (p=0.04) and 7 beats/minute (p=0.02) higher respectively with amphetamine, compared with control. A non-significant reduction in myocardial perfusion (Buckberg Index) was seen with amphetamine. Other cardiac and cerebral haemodynamics were unaffected. Amphetamine did not improve motor impairment or function after ischaemic stroke but did significantly increase BP and heart rate without altering cerebral haemodynamics.