Showing papers by "University of Leeds published in 2000"

The Vienna classification of gastrointestinal epithelial neoplasia

Abstract: Background—Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large diVerences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. Aim—To develop common worldwide terminology for gastrointestinal epithelial neoplasia. Methods—Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. Results—The large diVerences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/ dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/ dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). Conclusion—The diVerences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status. (Gut 2000;47:251‐255)

Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies.

Abstract: OBJECTIVE: To examine reproducibility and validity of visual analogue scales (VAS) for measurement of appetite sensations, with and without a diet standardization prior to the test days DESIGN: On two different test days the subjects recorded their appetite sensations before breakfast and every 30 min during the 45 h postprandial period under exactly the same conditions SUBJECTS: 55 healthy men (age 256±06 y, BMI 226±03 kg/m2) MEASUREMENTS: VAS were used to record hunger, satiety, fullness, prospective food consumption, desire to eat something fatty, salty, sweet or savoury, and palatability of the meals Subsequently an ad libitum lunch was served and energy intake was recorded Reproducibility was assessed by the coefficient of repeatability (CR) of fasting, mean 45 h and peak/nadir values RESULTS: CRs (range 20–61 mm) were larger for fasting and peak/nadir values compared with mean 45 h values No parameter seemed to be improved by diet standardization Using a paired design and a study power of 08, a difference of 10 mm on fasting and 5 mm on mean 45 h ratings can be detected with 18 subjects When using desires to eat specific types of food or an unpaired design, more subjects are needed due to considerable variation The best correlations of validity were found between 45 h mean VAS of the appetite parameters and subsequent energy intake (r=±050−053, P<0001) CONCLUSION: VAS scores are reliable for appetite research and do not seem to be influenced by prior diet standardization However, consideration should be given to the specific parameters being measured, their sensitivity and study power

Comparative Genomics of the Eukaryotes

Abstract: A comparative analysis of the genomes of Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae-and the proteins they are predicted to encode-was undertaken in the context of cellular, developmental, and evolutionary processes. The nonredundant protein sets of flies and worms are similar in size and are only twice that of yeast, but different gene families are expanded in each genome, and the multidomain proteins and signaling pathways of the fly and worm are far more complex than those of yeast. The fly has orthologs to 177 of the 289 human disease genes examined and provides the foundation for rapid analysis of some of the basic processes involved in human disease.

Objectivity and reliability in qualitative analysis: Realist, contextualist and radical constructionist epistemologies

Abstract: The effect of the individual analyst on research findings can create a credibility problem for qualitative approaches from the perspective of evaluative criteria utilized in quantitative psychology. This paper explicates the ways in which objectivity and reliability are understood in qualitative analysis conducted from within three distinct epistemological frameworks: realism, contextual constructionism, and radical constructionism. It is argued that quality criteria utilized in quantitative psychology are appropriate to the evaluation of qualitative analysis only to the extent that it is conducted within a naive or scientific realist framework. The discussion is illustrated with reference to the comparison of two independent grounded theory analyses of identical material. An implication of this illustration is to identify the potential to develop a radical constructionist strand of grounded theory.

Four centuries of geomagnetic secular variation from historical records

Abstract: We present a new model of the magnetic › eld at the core{mantle boundary for the interval 1590{1990. The model, called gufm1, is based on a massive new compilation of historical observations of the magnetic › eld. The greater part of the new dataset originates from unpublished observations taken by mariners engaged in merchant and naval shipping. Considerable attention is given to both correction of data for possible mislocation (originating from poor knowledge of longitude) and to proper allocation of error in the data. We adopt a stochastic model for uncorrected positional errors that properly accounts for the nature of the noise process based on a Brownian motion model. The variability of navigational errors as a function of the duration of the voyages that we have analysed is consistent with this model. For the period before 1800, more than 83000 individual observations of magnetic declination were recorded at more than 64000 locations; more than 8000 new observations are for the 17th century alone. The time-dependent › eld model that we construct from the dataset is parametrized spatially in terms of spherical harmonics and temporally in B-splines, using a total of 36512 parameters. The model has improved the resolution of the core › eld, and represents the longest continuous model of the › eld available. However, full exploitation of the database may demand a new modelling methodology.

Genetic compatibility, mate choice and patterns of parentage: invited review.

Abstract: There is growing interest in the possibility that genetic compatibility may drive mate choice, including gamete choice, particularly from the perspective of understanding why females frequently mate with more than one male. Mate choice for compatibility differs from other forms of choice for genetic benefits (such as ‘good genes’) because individuals are expected to differ in their mate preferences, changing the evolutionary dynamics of sexual selection. Recent experiments designed to investigate genetic benefits of polyandry suggest that mate choice on the basis of genetic compatibility may be widespread. However, in most systems the mechanisms responsible for variation in compatibility are unknown. We review potential sources of variation in genetic compatibility and whether there is any evidence for mate choice driven by these factors. Selfish genetic elements appear to have the potential to drive mate compatibility mate choice, though as yet there is only one convincing example. There is abundant evidence for assortative mating between populations in hybrid zones, but very few examples where this is clearly a result of selection against mating with genetically less compatible individuals. There are also numerous cases of inbreeding avoidance, but little evidence that mate choice or differential fertilization success driven by genetic compatibility occurs between unrelated individuals. The exceptions to this are a handful of situations where both the alleles causing incompatibility and the alleles involved in mate choice are located in a chromosome region where recombination is suppressed. As yet there are only a few potential sources of genetic compatibility which have clearly been shown to drive mate choice. This may reflect limitations in the potential for the evolution of mate choice for genetic compatibility within populations, although the most promising sources of such incompatibilities have received relatively little research.

Social cognition models and health behaviour: A structured review

Abstract: A number of social cognition models have been developed to account for socio-demographic variations in health behaviour. This paper distinguishes between: (a) motivational, (b) behavioural enaction, and (c) multi-stage models of health behaviour. The models are evaluated in terms of advancement of existing knowledge and - where appropriate - predictive utility. Common themes that appear within- and between- these categories are discussed, with consideration of ways in which theory may be advanced by future research. Each approach has associated strengths and weaknesses, suggesting that a “consensus” approach to the study of health behaviour may prove fruitful. Identification of the key constructs across different model types would allow coherent integration and promote further understanding of the psycho-social determinants of health behaviour.

Observations and implications of the ultrahigh-energy cosmic rays

Abstract: The authors define ``ultrahigh-energy cosmic rays'' (UHECRs) as those cosmic rays with energies above ${10}^{18}\mathrm{eV}.$ It had been anticipated that there would be a cutoff in the energy spectrum of primary cosmic rays around $6\ifmmode\times\else\texttimes\fi{}{10}^{19}\mathrm{eV}$ induced by the interaction of the particles with the 2.7-K primordial photons. However, recent experimental data have established that particles exist with energies greatly exceeding this. It follows that the sources of such particles are probably nearby, on a cosmological scale. However, although the trajectories of such energetic particles through the galactic and intergalactic magnetic fields may be nearly rectilinear, no astronomical sources have as yet been identified. This is the enigma of the highest-energy cosmic rays. The paper reviews the history of research in this energy regime and critically assesses the observational results on the energy spectrum, arrival directions, and composition of the primary cosmic rays based on observations made by six experiments. The detection methods currently available are described. Special techniques have been developed as particles of ${10}^{20}\mathrm{eV}$ or higher occur at a rate of only about 1 per ${\mathrm{km}}^{2}$ per century. Errors in measurement are given particular attention. The authors also review the theoretical predictions for a number of candidate sources of cosmic rays beyond the predicted cutoff. Finally, the four major projects planned to address the question of the origin of UHECRs are briefly described.

Semi-qualitative Reasoning about Distances: A Preliminary Report

Abstract: We introduce a family of languages intended for representing knowledge and reasoning about metric (and more general distance) spaces. While the simplest language can speak only about distances between individual objects and Boolean relations between sets, the more expressive ones are capable of capturing notions such as 'somewhere in (or somewhere out of) the sphere of a certain radius', 'everywhere in a certain ring', etc. The computational complexity of the satisfiability problem for formulas in our languages ranges from NP-completeness to undecidability and depends on the class of distance spaces in which they are interpreted. Besides the class of all metric spaces, we consider, for example, the spaces R × R and N × N with their natural metrics.

Biological reactions to wear debris in total joint replacement.

Abstract: The vast majority of total hip prostheses currently implanted consist of a hard metal or ceramic femoral head articulating against an ultra-high molecular weight polyethylene (UHMWPE) acetabular cup. Over the last 10 years, evidence has accumulated to show that these prostheses are prone to failure due to late aseptic loosening and few survive beyond 25 years. With an increasing need to implant hip prostheses in the younger, more active patient the need to understand the mechanisms of failure and to develop artificial hip joints using alternative materials have become major issues in the orthopaedic community. This review focuses initially on our current understanding of the biological reactions to UHMWPE prosthetic wear debris in vivo and in vitro since this is believed to be the main cause of late aseptic loosening. While the precise mechanisms of osteolysis induced by UHMWPE wear debris have not been elucidated, the major message to emerge is that it is not the wear volume that determines the biological response to the debris, but the concentration of the wear volume that is within the critical size range (0.2-0.8 micron) for macrophage activation. The review then considers whether the problem of wear-debris-induced osteolysis may be overcome with the use of new generation metal-on-metal or ceramic-on-ceramic prostheses. For metal-on-metal prostheses, the prospects for increasing the osteolysis free life of the implant are good but additional biological problems associated with the nanometre size and reactivity of the wear particles in vivo may emerge. For the ceramic-on-ceramic prostheses, although initial prospects are encouraging, more data are needed on the characteristics of the wear particles generated in vivo before predictions can be made. It is concluded that the pre-clinical testing of any new materials for joint replacement must include an analysis of the wear particle characteristics and their biological reactivity in addition to the usual assessment of wear.

A pooled analysis of magnetic fields and childhood leukaemia.

Abstract: Previous studies have suggested an association between exposure to 50–60 Hz magnetic fields (EMF) and childhood leukaemia. We conducted a pooled analysis based on individual records from nine studies, including the most recent ones. Studies with 24/48-hour magnetic field measurements or calculated magnetic fields were included. We specified which data analyses we planned to do and how to do them before we commenced the work. The use of individual records allowed us to use the same exposure definitions, and the large numbers of subjects enabled more precise estimation of risks at high exposure levels. For the 3203 children with leukaemia and 10 338 control children with estimated residential magnetic field exposures levels < 0.4 μT, we observed risk estimates near the no effect level, while for the 44 children with leukaemia and 62 control children with estimated residential magnetic field exposures ≥ 0.4 μT the estimated summary relative risk was 2.00 (1.27–3.13), P value = 0.002). Adjustment for potential confounding variables did not appreciably change the results. For North American subjects whose residences were in the highest wire code category, the estimated summary relative risk was 1.24 (0.82–1.87). Thus, we found no evidence in the combined data for the existence of the so-called wire-code paradox. In summary, the 99.2% of children residing in homes with exposure levels < 0.4 μT had estimates compatible with no increased risk, while the 0.8% of children with exposures ≥ 0.4 μT had a relative risk estimate of approximately 2, which is unlikely to be due to random variability. The explanation for the elevated risk is unknown, but selection bias may have accounted for some of the increase. © 2000 Cancer Research Campaign

The value of sonography in the detection of bone erosions in patients with rheumatoid arthritis: a comparison with conventional radiography.

Abstract: Objective. The ability to make an early, accurate diagnosis of rheumatoid arthritis (RA) has become increasingly important with the availability of new, expensive, and targeted therapies. However, plain radiography, the traditional method of detecting the characteristic bone erosions and an important adjunct in establishing a diagnosis of RA, is known to be insensitive. This study compared sonography, a modern imaging technique, with conventional radiography for the detection of erosions in the metacarpophalangeal (MCP) joints of patients with RA. Methods. One hundred RA patients (including 40 with early disease) underwent posteroanterior radiography and sonography of the MCP joints of the dominant hand. Twenty asymptomatic control subjects also underwent sonography. Erosion sites were recorded and subsequently compared using each modality. Magnetic resonance imaging (MRI) was performed on the second MCP joint in 25 patients with early RA to confirm the pathologic specificity of sonographic erosions. Intraobserver reliability of sonography readings was assessed using video recordings of 55 MCP joint scans of RA patients, and interobserver reliability was assessed by comparing 160 MCP joint scans performed sequentially by 2 independent observers. Results. Sonography detected 127 definite erosions in 56 of 100 RA patients, compared with radiographic detection of 32 erosions (26 [81%] of which coincided with sonographic erosions) in 17 of 100 patients (P < 0.0001). In early disease, sonography detected 6.5-fold more erosions than did radiography, in 7.5-fold the number of patients. In late disease, these differences were 3.4-fold and 2.7-fold, respectively. On MRI, all sonographic erosions not visible on radiography (n = 12) corresponded by site to MRI abnormalities. The Cohen-kappa values for intra- and interobserver reliability of sonography were 0.75 and 0.76, respectively. Conclusion. Sonography is a reliable technique that detects more erosions than radiography, especially in early RA. Sonographic erosions not seen on radiography corresponded to MRI bone abnormalities. This technology has potential in the management of patients with early RA/inflammatory arthritis and is likely to have major implications for the future practice of rheumatology.

The sinoatrial node, a heterogeneous pacemaker structure.

Abstract: This article focuses on the regional heterogeneity of the mammalian sinoatrial (SA) node in terms of cell morphology, pacemaker activity, action potential configuration and conduction, densities of ionic currents (i(Na), i(Ca,L), i(to), i(K,r), i(K,s) and i(f)), expression of gap junction proteins (Cx40, Cx43 and Cx45), autonomic regulation, and ageing. Experimental studies on the single SA node cell to the whole animal are reviewed. The heterogeneity is considered in terms of the gradient model of the SA node, in which there is gradual change in the intrinsic properties of SA node cells from periphery to centre, and the alternative mosaic model, in which there is a variable mix of atrial and SA node cells from periphery to centre. The heterogeneity is important for the dependable functioning of the SA node as the pacemaker for the heart, because (i) via multiple mechanisms, it allows the SA node to drive the surrounding atrial muscle without being suppressed electrotonically; (ii) via an action potential duration gradient and a conduction block zone, it promotes antegrade propagation of excitation from the SA node to the right atrium and prevents reentry of excitation; and (iii) via pacemaker shift, it allows pacemaking to continue under diverse pathophysiological circumstances.

Proximally Targeted GABAergic Synapses and Gap Junctions Synchronize Cortical Interneurons

Abstract: Networks of GABAergic interneurons are implicated in synchronizing cortical activity at gamma frequencies (30-70 Hz). Here we demonstrate that the combined electrical and GABAergic synaptic coupling of basket cells instantaneously entrained gamma-frequency postsynaptic firing in layers 2/3 of rat somatosensory cortex. This entrainment was mediated by rapid curtailment of gap junctional coupling potentials by GABAA receptor-mediated IPSPs. Electron microscopy revealed spatial proximity of gap junctions and GABAergic synapses on somata and dendrites. Electrical coupling alone entrained postsynaptic firing with a phase lag, whereas unitary GABAergic connections were ineffective in gamma-frequency phasing. These observations demonstrate precise spatiotemporal mechanisms underlying action potential timing in oscillating interneuronal networks.

The use of visual analogue scales to assess motivation to eat in human subjects: a review of their reliability and validity with an evaluation of new hand-held computerized systems for temporal tracking of appetite ratings.

Abstract: This present paper reviews the reliability and validity of visual analogue scales (VAS) in terms of (1) their ability to predict feeding behaviour, (2) their sensitivity to experimental manipulations, and (3) their reproducibility. VAS correlate with, but do not reliably predict, energy intake to the extent that they could be used as a proxy of energy intake. They do predict meal initiation in subjects eating their normal diets in their normal environment. Under laboratory conditions, subjectively rated motivation to eat using VAS is sensitive to experimental manipulations and has been found to be reproducible in relation to those experimental regimens. Other work has found them not to be reproducible in relation to repeated protocols. On balance, it would appear, in as much as it is possible to quantify, that VAS exhibit a good degree of within-subject reliability and validity in that they predict with reasonable certainty, meal initiation and amount eaten, and are sensitive to experimental manipulations. This reliability and validity appears more pronounced under the controlled (but more artificial) conditions of the laboratory where the signal: noise ratio in experiments appears to be elevated relative to real life. It appears that VAS are best used in within-subject, repeated-measures designs where the effect of different treatments can be compared under similar circumstances. They are best used in conjunction with other measures (e.g. feeding behaviour, changes in plasma metabolites) rather than as proxies for these variables. New hand-held electronic appetite rating systems (EARS) have been developed to increase reliability of data capture and decrease investigator workload. Recent studies have compared these with traditional pen and paper (P&P) VAS. The EARS have been found to be sensitive to experimental manipulations and reproducible relative to P&P. However, subjects appear to exhibit a significantly more constrained use of the scale when using the EARS relative to the P&P. For this reason it is recommended that the two techniques are not used interchangeably.

The structure and fluid mechanics of turbidity currents: a review of some recent studies and their geological implications

Abstract: Summary The literature on the structure and behaviour of gravity currents is reviewed, with emphasis on some recent studies, and with particular attention to turbidity currents, though reference is also made to comparable behaviour in pyroclastic flows. Questions of definition are discussed, in particular the distinction between dense currents, which may deposit en masse, and more dilute currents. High-density dispersions may exist as a discrete, independently moving layer beneath a more dilute flow, as the basal part of a continuous density distribution or possibly as a transient depositional layer. Existing theory appears inadequate to explain the behaviour of some high-density dispersions. Surge-type currents are contrasted with quasi-steady currents, which may be generated by a variety of mechanisms including direct feed by rivers in flood. Such fluvially generated currents provide one means of generating currents with reversing buoyancy. Geologically significant turbidity currents are impractical for direct study owing to their large scale and (often) destructive nature. Small-scale laboratory currents offer a wealth of insights into turbidity current behaviour. This paper summarizes recent experimental studies that focus on the physical structure of gravity currents, with emphasis on the velocity and turbulence structure, the vertical density distribution and the stability of stratification. Preliminary quantification of the turbulence structure (including controls on turbulent entrainment, turbulent kinetic energy, Reynolds stresses and turbulence production) has been facilitated by recent technological developments that have allowed the measurement of instantaneous fluctuations in both velocity and concentration. Laboratory models, however, generally involve substantial simplification, and require compromises in some parameters to achieve adequate scaling of the parameters of most interest. Mathematical modelling also provides important insights into turbidity current behaviour. We discuss various approaches to modelling, ranging from simple hydraulic equations to systems of partial differential equations that explicitly treat conservation of momentum, fluid and sediment mass, and turbulent kinetic energy. The application for which the model is designed (i.e. to calculate mean head velocity or to create an instantaneous two-dimensional contour plot of downstream velocity in a current) determines the complexity of the mathematical model required. The behaviour of suspension currents around topography is complex and depends upon the relative height of the topography, and upon the density and velocity structure of the current. Many interactions with topography are well described by the internal Froude number, Fri. Both reflection and deflection of currents may occur on the upstream side of topography, depending upon Fri. On the downstream side of topography, flow separation, lee waves or hydraulic jumps may occur.

CORE: Clinical Outcomes in Routine Evaluation

Abstract: Can different therapists, motivated by different theories and working in different settings, find a single measure - a 'core' - for monitoring their work? This paper introduces the Clinical Outcome...

Self-Concentrations and Effective Glass Transition Temperatures in Polymer Blends

Abstract: In a miscible polymer blend the local environment of a monomer of type A will, on average, be rich in A compared to the bulk composition, φ, and similarly for B; this is a direct consequence of chain connectivity. As a result, the local dynamics of the two chains may exhibit different dependences on temperature and overall composition. By assigning a length scale (or volume) to particular dynamic mode, the relevant “self-concentration” φs can be estimated. For example, we associate the Kuhn length of the chain, lK, with the monomeric friction factor, ζ, and thus the composition and temperature dependences of ζ should be influenced by φs calculated for a volume V ∼ lK3. An effective local composition, φeff, can then be calculated from φs and φ. As lower Tg polymers are generally more flexible, the associated φ s is larger, and the local dynamics in the mixture may be quite similar to the pure material. The higher Tg component, on the other hand, may have a smaller φs, and thus its dynamics in the mixture w...

Red-shifts and red herrings in geographical ecology

Abstract: I draw attention to the need for ecologists to take spatial structure into account more seriously in hypothesis testing. If spatial autocorrelation is ignored, as it usually is, then analyses of ecological patterns in terms of environmental factors can produce very misleading results. This is demonstrated using synthetic but realistic spatial patterns with known spatial properties which are subjected to classical correlation and multiple regression analyses. Correlation between an autocorrelated response variable and each of a set of explanatory variables is strongly biased in favour of those explanatory variables that are highly autocorrelated - the expected magnitude of the correlation coefficient increases with autocorrelation even if the spatial patterns are completely independent. Similarly, multiple regression analysis finds highly autocorrelated explanatory variables “significant” much more frequently than it should. The chances of mistakenly identifying a “significant” slope across an autocorrelated pattern is very high if classical regression is used. Consequently, under these circumstances strongly autocorrelated environmental factors reported in the literature as associated with ecological patterns may not actually be significant. It is likely that these factors wrongly described as important constitute a red-shifted subset of the set of potential explanations, and that more spatially discontinuous factors (those with bluer spectra) are actually relatively more important than their present status suggests. There is much that ecologists can do to improve on this situation. I discuss various approaches to the problem of spatial autocorrelation from the literature and present a randomisation test for the association of two spatial patterns which has advantages over currently available methods.

Effects of parasites on fish behaviour: a review and evolutionary perspective

Abstract: Fish serve as hosts to a range of parasites that are taxonomically diverse and that exhibit a wide variety of life cycle strategies. Whereas many of these parasites are passed directly between ultimate hosts, others need to navigate through a series of intermediate hosts before reaching a host in (or on) which they can attain sexual maturity. The realisation that parasites need not have evolved to minimise their impact on hosts to be successful, and in many cases may even have a requirement for their hosts to be eaten by specific predators to ensure transmission, has renewed interest in the evolutionary basis of infection-associated host behaviour. Fishes have proved popular models for the experimental examination of such hypotheses, and parasitic infections have been demonstrated to have consequences for almost every aspect of fish behaviour. Despite a scarcity of knowledge regarding the mechanistic basis of such behaviour changes in most cases, and an even lower understanding of their ecological consequences, there can be little doubt that infection-associated behaviour changes have the potential to impact severely on the ecology of infected fishes. Changes in foraging efficiency, time budget, habitat selection, competitive ability, predator-prey relationships, swimming performance and sexual behaviour and mate choice have all been associated with – and in some cases been shown to be a result of – parasite infections, and are reviewed here in some detail. Since the behavioural consequences of infections are exposed to evolutionary selection pressures in the same way as are other phenotypic traits, few behavioural changes will be evolutionarily neutral and host behaviour changes that facilitate transmission should be expected. Despite this expectation, we have found little conclusive evidence for the Parasite Increased Trophic Transmission (PITT) hypothesis in fishes, though recent studies suggest it is likely to be an important mechanism. Additionally, since the fitness consequences of the many behavioural changes described have rarely been quantified, their evolutionary and ecological significance is effectively unknown. Potential hosts may also change their behaviour in the presence of infective parasite stages, if they adopt tactics to reduce exposure risk. Such `behavioural resistance', which may take the form of habitat avoidance, prey selectivity or avoidance of infected individuals, can be viewed as behavioural change associated with the threat of being parasitised, and so is included here. Actually harbouring infections may also stimulate fishes to perform certain types of simple or complex behaviours aimed at removing parasites, such as substrate scraping or the visitation of cleaning stations, although the efficacy of the latter as a parasite removal strategy is currently subject to a good deal of debate. The effects parasites have on shoaling behaviour of host fish have attracted a good deal of attention from researchers, and we have provided a case study to summarise the current state of knowledge. Parasites have been shown to affect most of the antipredator effects of shoaling (such as vigilance, co-ordinated evasion and predator confusion) and can also impair an individual's foraging ability. It therefore seems unsurprising that, in a number of species avoidance of parasitised individuals has evolved which may explain the occurrence of parasite-assorted shoals in the field. Parasitised fish are found more often in peripheral shoal positions and show a reduced tendency for shoaling in some fish species. Given the array of host behaviours that may be changed, the fitness consequences of shoal membership for parasitised hosts and their parasites are not always easy to predict, yet an understanding of these is important before we can make predictions regarding the ecological impact of infections on host fish populations. Clearly, there remain many gaps in our knowledge regarding the effects of parasites on the behaviour of host fish. We believe that a much greater understanding of the importance of infection-associated behaviour changes in fish could be gained from high quality research in comparatively few areas. We have completed our review by highlighting the key research topics that we believe should attract new research in this field.

Behavioral Treatment for Chronic Low Back Pain : A Systematic Review Within the Framework of the Cochrane Back Review Group

Abstract: Study Design. A systematic review of randomized controlled trials. Summary of Background Data. The treatment of chronic low back pain is not primarily focused on removing an underlying organic disease but at the reduction of disability through the modification of environmental contingencies and cognitive processes. Behavioral interventions are commonly used in the treatment of chronic (disabling) low back pain. Objectives. To determine whether behavioral therapy is more effective than reference treatments for chronic nonspecific low back pain and which type of behavioral treatment is most effective. Methods. The authors searched the Medline and PsychLit databases and the Cochrane Controlled Trials Register up to April 1999. and Embase up to September 1999. Also screened were references of identified randomized trials and relevant systematic reviews. Methodologic quality assessment and data extraction were performed independently by two reviewers. The magnitude of effect was assessed by computing a pooled effect size for each domain (i.e., behavioral outcomes, overall improvement, back pain-specific and generic functional status, return to work, and pain intensity) using the random effects model. Results. Only six (25%) studies were high quality. There is strong evidence (level 1) that behavioral treatment has a moderate positive effect on pain intensity (pooled effect size 0.62; 95% confidence interval [CI] 0.25, 0.98), and small positive effects on generic functional status (pooled effect size 0.35; 95% CI: 0.04, 0.74) and behavioral outcomes (pooled effect size 0.40; 95% CI: 0.10, 0.70) of patients with chronic low back pain when compared-with waiting-list controls or no treatment. There is moderate evidence (level 2) that a addition of behavioral component to a usual treatment program for chronic low backpain has no positive short-term effect on generic functional status (pooled effect size 0.31; 95% Cl: 0.01, 0.64), pain intensity (pooled effect size 0.03; 95% CI: 0.30, 0.36), and behavioral outcomes (pooled effect size 0.19; 95% CI: 0.08, 0.45). Conclusions. Behavioral treatment seems to be an effective treatment for patients with chronic low back pain,but it is still unknown what type of patients benefitmost from what type of behavioral treatment.

A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis

Abstract: Objective To compare the clinical efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis (RA). Methods In this multicentre, double-blind trial, 999 subjects with active RA were randomized to leflunomide (n = 501; loading dose 100 mg/day for 3 days, maintenance dose 20 mg/day) or methotrexate (n = 498; 10-15 mg/week) for 52 weeks. After 1 yr the subjects could choose to stay for a second year of double-blind treatment. The primary end-points were tender and swollen joint counts and overall physician and patient assessments. Analyses were of the intent-to-treat group. Results After 1 yr, the mean changes in the leflunomide and methotrexate groups, respectively, were -8.3 and -9.7 for tender joint count; -6.8 and -9.0 for swollen joint count; -0.9 and -1.2 for physician global assessment; -0.9 and -1.2 for patient global assessment; -14.4 and -28.2 for erythrocyte sedimentation rate. Improvements seen with methotrexate were significantly greater than those with leflunomide. No further improvement occurred after the second year of treatment and the distinction between the two treatments in terms of tender joint count and patient global assessment was lost. During the first year of treatment, a small and equivalent degree of radiographically assessed disease progression was seen with both drugs. After 2 yr, disease progression was significantly less with methotrexate. The most common treatment-related adverse events in both groups were diarrhoea, nausea, alopecia, rash, headache, and elevated plasma liver enzyme levels. Over 2 yr, 21 subjects receiving methotrexate were withdrawn due to elevated plasma liver enzymes vs eight subjects taking leflunomide. Two drug-related deaths from pulmonary causes were recorded with methotrexate vs no drug-related deaths among the subjects receiving leflunomide. Conclusions Both leflunomide and methotrexate are efficacious for prolonged treatment of RA. At the doses used, some clinical benefit of methotrexate over leflunomide was observed in the first year of treatment. This benefit must be weighed against the potential toxicity of this drug when used without folate supplementation.