Design, Science and Conceptual Analysis

Philosophers expend considerable effort on the analysis of concepts, but the value of such work is not widely appreciated. This paper principally analyses some arguments, beliefs, and presuppositions about the nature of design and the relations between design and science common in the literature to illustrate this point, and to contribute to the foundations of design theory.

An introduction to efficiency and productivity analysis

The second edition of An Introduction to Efficiency and Productivity Analysis is designed to be a general introduction for those who wish to study efficiency and productivity analysis. The book provides an accessible, well-written introduction to the four principal methods involved: econometric estimation of average response models; index numbers, data envelopment analysis (DEA); and stochastic frontier analysis (SFA). For each method, a detailed introduction to the basic concepts is presented, numerical examples are provided, and some of the more important extensions to the basic methods are discussed. Of special interest is the systematic use of detailed empirical applications using real-world data throughout the book. In recent years, there have been a number of excellent advance-level books published on performance measurement. This book, however, is the first systematic survey of performance measurement with the express purpose of introducing the field to a wide audience of students, researchers, and practitioners. Indeed, the 2nd Edition maintains its uniqueness: (1) It is a well-written introduction to the field. (2) It outlines, discusses and compares the four principal methods for efficiency and productivity analysis in a well-motivated presentation. (3) It provides detailed advice on computer programs that can be used to implement these performance measurement methods. The book contains computer instructions and output listings for the SHAZAM, LIMDEP, TFPIP, DEAP and FRONTIER computer programs. More extensive listings of data and computer instruction files are available on the book's website: (www.uq.edu.au/economics/cepa/crob2005).

The treatment of tardive dyskinesia: A systematic review and meta-analysis

This systematic review aimed to collate randomized controlled trials (RCTs) of various interventions used to treat tardive dyskinesia (TD) and, where appropriate, to combine the data for mete-analysis, Clinical trials were identified by electronic searches, handsearches and contact with principal investigators. Data were extracted independently by two reviewers, for outcomes related to improvement, deterioration, side-effects and drop out rates. Data were pooled using the Mantel-Haenzel Odds Ratio (fixed effect model). For treatments that had significant effects, the number needed to treat (NNT) was calculated. From 296 controlled clinical trials, data were extracted from 47 trials. For most interventions, we could identify no RCT-derived evidence of efficacy. A meta-analysis showed that baclofen, deanol and diazepam were no more effective than a placebo. Single RCTs demonstrated a lack of evidence of any effect for bromocriptine, ceruletide, clonidine, estrogen, gamma linolenic acid, hydergine, lecithin, lithium, progabide, seligiline and tetrahydroisoxazolopyridinol. The meta-analysis found that five interventions were effective: L-dopa, oxypertine, sodium valproate, tiapride and vitamin E; neuroleptic reduction was marginally significant. Data from single RCTs revealed that insulin, alpha methyl dopa and reserpine were more effective than a placebo. There was a significantly increased risk of adverse events associated with baclofen, deanol, L-dopa, oxypertine and reserpine. Metaanalysis of the impact of placebo (n=485) showed that 37.3% of participants showed an improvement. Interpretation of this systematic review requires caution as the individual trials identified tended to have small sample sizes. For many compounds, data from only one trial were available, and where meta-analyses were possible, these were based on a small number of trials. Despite these concerns, the review facilitated the interpretation of the large and diverse range of treatments used for TD. Clinical recommendations for the treatment of TD are made, based on the availability of RCT-derived evidence, the strength of that evidence and the presence of adverse effects. (C) 1999 Elsevier Science B.V. All rights reserved.

Synthesis, NMR studies and conformational analysis of oxazolidine derivatives of the beta-adrenoreceptor antagonists metoprolol, atenolol and timolol

Formaldehyde-derived oxazolidine derivatives 4-7 of the beta-adrenoreceptor antagonists metoprolol 1, atenolol 2 and timolol 3 have been synthesised. Conformational analysis of 1-3 and the oxazolidine derivatives 4-7 has been performed using H-1 NMR spectroscopy and computational methods. The H-1 NMR studies show that for the aryloxypropanolamine beta-adrenoreceptor antagonists there is a predominance of the conformer in which the amine group is approximately antiperiplanar or trans to the aryloxymethylene group. Both H-1 NMR data and theoretical studies indicate that the oxazolidine derivatives 4-7 and the aryloxypropanolamine beta-adrenoreceptor antagonists 1-3 adopt similar conformations around the beta-amino alcohol moiety. Thus, oxazolidine ring formation does not dramatically alter the preferred conformation adopted by the beta-amino alcohol moiety of 1-3. Oxazolidine derivatives of aryloxypropanolamine beta-adrenoreceptor antagonists may therefore be appropriate as prodrugs, or semi-rigid analogues, when greater lipophilicity is required for drug delivery.

Parallel processing and image analysis in the eyes of mantis shrimps

The compound eyes of mantis shrimps, a group of tropical marine crustaceans, incorporate principles of serial and parallel processing of visual information that may be applicable to artificial imaging systems. Their eyes include numerous specializations for analysis of the spectral and polarizational properties of light, and include more photoreceptor classes for analysis of ultraviolet light, color, and polarization than occur in any other known visual system. This is possible because receptors in different regions of the eye are anatomically diverse and incorporate unusual structural features, such as spectral filters, not seen in other compound eyes. Unlike eyes of most other animals, eyes of mantis shrimps must move to acquire some types of visual information and to integrate color and polarization with spatial vision. Information leaving the retina appears to be processed into numerous parallel data streams leading into the central nervous system, greatly reducing the analytical requirements at higher levels. Many of these unusual features of mantis shrimp vision may inspire new sensor designs for machine vision

Metabolic and kinetic analysis of poly(3-hydroxybutyrate) production by recombinant Escherichia coli

A quantitatively repeatable protocol was developed for poly(3-hydroxybutyrate) (PHB) production by Escherichia coli XL1-Blue (pSYL107). Two constant-glucose fed-batch fermentations of duration 25 h were carried out in a 5-L bioreactor, with the measured oxygen volumetric mass-transfer coefficient (k(L)a) held constant at 1.1 min(-1). All major consumption and production rates were quantified. The intracellular concentration profiles of acetyl-CoA (300 to 600 mug.g RCM-1) and 3-hydroxy-butyryl-CoA (20 to 40 mug.g RCM-1) were measured, which is the first time this has been performed for E. coli during PHB production. The kinetics of PHB production were examined and likely ranges were established for polyhydroxyalkanoate (PHA) enzyme activity and the concentration of pathway metabolites. These measured and estimated values are quite similar to the available literature estimates for the native PHB producer Ralstonia eutropha. Metabolic control analysis performed on the PHB metabolic pathway showed that the PHB flux was highly sensitive to acetyl-CoA/CoA ratio (response coefficient 0.8), total acetyl-CoA + CoA concentration (response coefficient 0.7), and pH (response coefficient -1.25). It was less sensitive (response coefficient 0.25) to NADPH/NADP ratio. NADP(H) concentration (NADPH + NADP) had a negligible effect. No single enzyme had a dominant flux control coefficient under the experimental conditions examined (0.6, 0.25, and 0.15 for 3-ketoacyl-CoA reductase, PHA synthase, and 3-ketothiolase, respectively). In conjunction with metabolic flux analysis, kinetic analysis was used to provide a metabolic explanation for the observed fermentation profile. In particular, the rapid onset of PHB production was shown to be caused by oxygen limitation, which initiated a cascade of secondary metabolic events, including cessation of TCA cycle flux and an increase in acetyl-CoA/CoA ratio. (C) 2001 John Wiley & Sons. Inc. Biotechnol Bioeng 74: 70-80, 2001.

3D reconstruction and quantification of macropores using X-ray computed tomography and image analysis

Axial X-ray Computed tomography (CT) scanning provides a convenient means of recording the three-dimensional form of soil structure. The technique has been used for nearly two decades, but initial development has concentrated on qualitative description of images. More recently, increasing effort has been put into quantifying the geometry and topology of macropores likely to contribute to preferential now in soils. Here we describe a novel technique for tracing connected macropores in the CT scans. After object extraction, three-dimensional mathematical morphological filters are applied to quantify the reconstructed structure. These filters consist of sequences of so-called erosions and/or dilations of a 32-face structuring element to describe object distances and volumes of influence. The tracing and quantification methodologies were tested on a set of undisturbed soil cores collected in a Swiss pre-alpine meadow, where a new earthworm species (Aporrectodea nocturna) was accidentally introduced. Given the reduced number of samples analysed in this study, the results presented only illustrate the potential of the method to reconstruct and quantify macropores. Our results suggest that the introduction of the new species induced very limited chance to the soil structured for example, no difference in total macropore length or mean diameter was observed. However. in the zone colonised by, the new species. individual macropores tended to have a longer average length. be more vertical and be further apart at some depth. Overall, the approach proved well suited to the analysis of the three-dimensional architecture of macropores. It provides a framework for the analysis of complex structures, which are less satisfactorily observed and described using 2D imaging. (C) 2002 Elsevier Science B.V. All rights reserved.

Nonoxynol-9 spermicide for prevention of vaginally acquired HIV and other sexually transmitted infections: systematic review and meta-analysis of randomised controlled trials including more than 5000 women

We aimed to determine the effectiveness of the vaginally administered spermicide nonoxynol-9 (N-9) among women for the prevention of HIV and other sexually transmitted infections (STIs), We did a systematic review of randomised controlled trials, Nine such trials including 5096 women, predominantly sex workers, comparing N-9 with placebo or no treatment, were included. Primary outcomes were new HIV infection, new episodes of various STIs, and genital lesions. Five trials included HIV and nine included STI outcomes, and all but one (2% of the data) contributed to the meta-analysis. Overall, relative risks of HIV infection (1.12, 95% confidence interval 0.88-1.42), gonorrhoea (0.91, 0.67-1.24), chlamyclia (0.88, 0.77-1.01), cervical infection (1.01, 0.84-1-22), trichomoniasis (0.84, 0.69-1.02), bacterial vaginosis (0.88, 0.74-1.04) and candidiasis (0.97, 0.84-1.12) were not significantly different in the N-9 and placebo or no treatment groups. Genital lesions were more common in the N-9 group (1.18, 1.02-1.36). Our review has found no statistically significant reduction in risk of HIV and STIs, and the confidence intervals indicate that any protection that may exist is likely to be very small. There is some evidence of harm through genital lesions. N-9 cannot be recommended for HIV and STI prevention.

The Western Alps from the Jurassic to Oligocene: spatio-temporal constraints and evolutionary reconstructions

Despite extensive research in the last 150 years, the regional tectonic reconstruction of the Western Alps has remained controversial. The curved orogenic belt consists of several ribbon-like continental terranes (Sesia/Austroalpine, Internal Crystalline Massifs, Brianconnais), which are separated by two or more ophiolitic sutures (Piemonte, Valais, Antrona?, Lanzo/ Canavese?). High-pressure (HP) metamorphism of each terrane occurred during distinct orogenic episodes: at similar to65 Ma in the Sesia/Austroalpine, at similar to45 Ma in the Piemonte zone and at similar to35 Ma in the Internal Crystalline Massifs. It is suggested that these events reflect individual accretionary episodes, which together with kinematic indicators and the speed and direction of plate motions, provide constraints for the discussed reconstruction model. The model involves a prolonged orogenic history that took place during relative convergence of Europe and Adria (here considered as a promontory of the African plate). The first accretionary event involved the Sesia/Austroalpine terrane. Final closure of the Piemonte Ocean occurred during the Eocene (similar to45 Ma) and involved ultra-high-pressure (UHP) metamorphism of the Piemonte oceanic crust. Incorporation of the Brianconnais terrane in the accretionary wedge occurred thereafter, possibly during or after subduction of the Valais Ocean in the late Eocene (45-35 Ma). This subduction was terminated at ca. 35 Ma, when the Internal Crystalline Massifs (i.e. the assumed internal parts of the Brianconnais terrane) were buried into great depths and underwent HP and UHP metamorphism. (C) 2004 Elsevier B.V. All rights reserved.

Review of genetic and epigenetic alterations in hepatocarcinogenesis

Hepatocellular carcinoma (HCC) is associated with multiple risk factors and is believed to arise from pre-neoplastic lesions, usually in the background of cirrhosis. However, the genetic and epigenetic events of hepatocarcinogenesis are relatively poorly understood. HCC display gross genomic alterations, including chromosomal instability (CIN), CpG island methylation, DNA rearrangements associated with hepatitis B virus (HBV) DNA integration, DNA hypomethylation and, to a lesser degree, microsatellite instability. Various studies have reported CIN at chromosomal regions, 1p, 4q, 5q, 6q, 8p, 10q, 11p, 16p, 16q, 17p and 22q. Frequent promoter hypermethylation and subsequent loss of protein expression has also been demonstrated in HCC at tumor suppressor gene (TSG), p16, p14, p15, SOCS1, RIZ1, E-cadherin and 14-3-3 sigma. An interesting observation emerging from these studies is the presence of a methylator phenotype in hepatocarcinogenesis, although it does not seem advantageous to have high levels of microsatellite instability. Methylation also appears to be an early event, suggesting that this may precede cirrhosis. However, these genes have been studied in isolation and global studies of methylator phenotype are required to assess the significance of epigenetic silencing in hepatocarcinogenesis. Based on previous data there are obvious fundamental differences in the mechanisms of hepatic carcinogenesis, with at least two distinct mechanisms of malignant transformation in the liver, related to CIN and CpG island methylation. The reason for these differences and the relative importance of these mechanisms are not clear but likely relate to the etiopathogenesis of HCC. Defining these broad mechanisms is a necessary prelude to determine the timing of events in malignant transformation of the liver and to investigate the role of known risk factors for HCC.