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.

Beyond the Red Notebook: Essays on Paul Auster (review)

Review of this text edited by Dennis Barone. This article is copyright the Modern Humanities Research Association 1998, and is included in this repository with permission.

Comparing Postcolonial Literatures: Dislocations. (review)

Review of book edited by Ashok Berry and Patricia Murray. Copyright 2002 MHRA, and included in the repository with permission.

'Dis ain't gimme, Florida': Zora Neale Hurston's Their Eyes Were Watching God

Who owns Zora Neale Hurston? That was the question asked in 1990 by Michele Wallace, in an analysis of the ways in which Hurston has been appropriated by later scholars. Wallace's pungent comparison of later critics to so many 'groupies descending on Elvis Presley's estate' in their haste to turn Hurston to their own purposes strikes a cautionary note for any subsequent writer. As she notes, the risk of canonization is that the work will be misused to derail the future of blackwomen in literature and literary criticism. For Wallace, Harold's introduction to his Modern Critical Views anthology of 1986 is a case in point. This article is copyright 2003 MHRA, and is included in this repository with permission.

Napalm and After: The Politics of Grace Paley's Short Fiction

Comparatively few contemporary writers have accompanied American POWs home from Hanoi, been arrested on the White House Lawn, or been dragged off in shackles to serve time in the Greenwich Village Women's House of Detention. Paley's pacifist, socialist politics are also deeply rooted in a family past where memories were still fresh of Tsarist oppression - one uncle shot dead carrying the red flag, and parents who reached America only because the Tsar had a son and amnestied all political prisoners under the age of twenty-one. At this point, Paley's father (imprisoned in Archangel) and her mother (in exile) took their chances (and all their surviving relatives) and very sensibly ran for their lives. Her grandmother recalled family arguments around the table between Paley's father (Socialist), Uncle Grisha (Communist), Aunt Luba (Zionist), and Aunt Mira (also Communist). Paley's own street-wise adolescence involved the usual teenage gang fights, between adherents of the Third and Fourth Internationals. This article is copyright MHRA 2001, and is included in this repository with permission.

Defensive realism and the Concert of Europe

Why do great powers expand? Offensive realist John Mearsheimer claims that states wage an eternal struggle for power, and that those strong enough to seek regional hegemony nearly always do. Mearsheimer's evidence, however, displays a selection bias. Examining four crises between 1814 and 1840, I show that the balance of power restrained Russia, Prussia and France. Yet all three also exercised self-restraint; Russia, in particular, passed up chances to bid for hegemony in 1815 and to topple Ottoman Turkey in 1829. Defensive realism gives a better account of the Concert of Europe, because it combines structural realism with non-realist theories of state preferences.