A prospective, randomized, pragmatic, health outcomes trial evaluating the incorporation of hylan G-F 20 into the treatment paradigm for patients with knee osteoarthritis (Part 1 of 2): clinical results

Objective: First, to assess the clinical effectiveness of hylan G-F 20 in an appropriate care treatment regimen (as defined by the American College of Rheumatology (ACR) 1995 guidelines) as measured by validated disease-specific outcomes and health-related quality of life endpoints for patients with osteoarthritis (OA) of the knee. Second, to utilize the measures of effectiveness and costs in an economic evaluation (see accompanying manuscript). Design: A total of 255 patients with OA of the knee were enrolled by rheumatologists or orthopedic surgeons into a prospective, randomized, open-label, 1-year, multi-centred trial, conducted in Canada. Patients were randomized to 'Appropriate care with hylan G-F 20' (AC+H) or 'Appropriate care without hylan G-F 20' (AC). Data were collected at clinic visits (baseline, 12 months) and by telephone (1, 2, 4, 6, 8, 10, and 12 months). Results: The AC+H group was superior to the AC group for all primary (% reduction in mean Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale: 38% vs 13%, P=0.0001) and secondary effectiveness outcome measures. These differences were all statistically significant and exceeded the 20% difference between groups seta priori by the investigators as the minimum clinically important difference. Health-related quality of life improvements in the AC+H group were statistically superior for the WOMAC pain, stiffness and physical function (all P

Shock standoff on hypersonic blunt bodies in nonequilibrium gas flows

This paper presents a new theory of hypersonic blunt-nose shock standoff, based on a compressibility coordinate transformation for inviscid flow. It embraces a wide range of nonequilibrium shock-layer chemistry and gas mixtures including ionization and freestream dissociation. An extended binary scaling property of the analysis is also demonstrated. Specific application is made here to the family of arbitrarily diluted dissociating diatomic gases, with parametric study results presented for the scaled shock standoff distance as a function of an appropriate blunt-nose region Damkohler number. Comparisons with other theories and data in the case of nitrogen are also given and discussed.

Macrolides in cystic fibrosis. Is there a role?

A spectrum of anti-inflammatory properties, evidence of anti-infective action against Pseudomonas aeruginosa at sub-inhibitory concentrations and positive clinical experience in patients with diffuse panbronchiolitis, a disease with features in common with cystic fibrosis (CF), has prompted research to evaluate the role of macrolide therapy in patients with CF. Newer macrolides such as azithromycin have the advantage of improved tolerability and a prolonged intracellular half-life requiring an infrequent dosing regimen. Results from initial studies suggest a benefit from several months of macrolide therapy in patients with CF. An improvement in lung function was initially shown in a small open study in children, while maintenance of lung function compared with placebo, reduced acute respiratory exacerbations, and reduced systemic markers of inflammation were demonstrated in a randomized, placebo-controlled study of macrolide therapy in adult patients with CF. Additional controlled studies are required to determine optimal drug, dosage, and duration of therapy, and long-term adverse effects of prolonged therapy with macrolides in patients with CF. The potential, with long-term use, to induce resistance against other bacteria colonizing the upper respiratory tract e.g. pneumococci has not been explored. Measurement of cytokines and inflammatory mediators from the sputum of patients with CF is technically difficult and does not correlate with disease activity. There is a need for easily measurable, reproducible and clinically meaningful end-points for evaluation of new therapies in CF. The choice of appropriate outcome measures, apart from lung function, to monitor disease activity needs careful consideration in clinical trials determining the efficacy of macrolides in patients with CF. Evidence-based recommendations for the use of macrolides in the treatment of CF are not expected for some years although macrolides are already being prescribed for long-term use in some centers. There is a need for further research into mechanisms of anti-inflammatory action of macrolides in the lungs of patients with CF and whether or not such therapy may be beneficial in the long term. Copyright 2002 Adis International

Geographic variation of natural products of tropical nudibranch Asteronotus cespitosus

Extracts of the dorid nudibranch Asteronotus cespitosus from two geographically separate regions of Australia and from the Philippines were compared using thin-layer, high-performance liquid and gas chromatography and H-1 NMR analysis. Halogenated metabolites were detected in all mollusk specimens. The major component detected in digestive tissue of specimens from the Great Barrier Reef in northeastern Australia was 4,6-dibromo2-(2',4'-dibromophenoxy)phenol (1), with minor amounts of 3,5-dibromo-2(3',5'-dibromo-20-methoxyphenoxy)phenol (2). In a specimen collected from northwestern Australia, only 3,5-dibromo-2-(3',5'-dibromo-2'-methoxyphenoxy)phenol was found. The specimen from the Philippines contained 2,3,4,5-tetrabromo-6-(2'-bromophenoxy) phenol (3) together with a novel chlorinated pyrrolidone (4). In addition, the sesquiterpenes dehydroherbadysidolide (5) and spirodysin (6) were detected in the digestive organs and mantle tissue of the nudibranchs from the Great Barrier Reef and from the Philippines, whereas these chemicals were not found in the specimen from northwestern Australia. All of the chemicals (1-3,5, and 6) have previously been isolated from the sponge Dysidea herbacea, as have chlorinated metabolites related to 4. This is the first time the characteristic halogenated metabolites that typify Dysidea herbacea have been reported from a carnivorous mollusk, which implies a dietary origin as opposed to de novo synthesis.

Effectiveness of Three Seed-Trap Designs

Vegetation monitoring is essential to evaluate management and assess condition. However, methods that have been used cannot assess the viability of the community or provide indicators of future condition. Seed traps can be used to measure reproductive potential of a vegetation community via seed rain. This study evaluates three different seed-trap designs and compares their effectiveness in terms of the diversity and abundance of seed captured, the presence of seed-predating insects, cost, manufacturing ease and serviceability. Field trials were conducted in open, grassy woodlands in south-western and south-eastern Queensland. The results showed that the tall funnel-trap design was the least effective, while the wet wind trap and pitfall funnel trap proved more effective. On the basis of the results of this study, further investigations are recommended for testing trap performance in different vegetation communities, seed predation in relation to seed production and variation in seed production over time. Seed traps that monitor seed rain are potentially useful in assessing the health and viability of a vegetation community. Used in conjunction with other monitoring methods, they may offer valuable insights about the dynamics of entire communities and/or individual species, and therefore appropriate management strategies.

Behaviour of the black flying fox Pteropus alecto: 1. An ethogram of behaviour, and preliminary characterisation of mother-infant interactions

The black flying fox Pteropus alecto is one of four species of flying fox found on the Australian mainland. Little information exists about the specific behaviour of this species, and no framework for the study of its behaviour has yet been constructed. In the study reported here, two P alecto colonies were observed at two day roosts in South East Queensland, Australia, between 1998-2000. Observations focused on solitary and social actions in general and on mother-infant interactions in some detail and led to the construction of an ethogram that defines each action structurally and functionally, describing accompanying vocalisations where appropriate. Diurnal activity patterns of P. alecto throughout the year consisted predominantly of roosting, grooming and sleeping, and involved little social activity. Social interactions were largely restricted to the seasonal contexts of the birthing/rearing period of October to March and the subsequent courtship/mating season of February to April. In all, 74 behavioural units were defined with the aim of facilitating further research and the implementation of effective conservation strategies for the species.

Development of axon pathways in the zebrafish central nervous system

The zebrafish has a number of distinct advantages as an experimental model in developmental biology. For example, large numbers of embryos can be generated in each lay, development proceeds rapidly through a very precise temporal staging which exhibits minimal batch-to-batch variability, embryos are transparent and imaging of wholemounts negates the need for tedious histological preparation while preserving three-dimensional spatial relationships. The zebrafish nervous system is proving a convenient model for studies of axon guidance because of its small size and highly stereotypical trajectory of axons. Moreover, a simple scaffold of axon tracts and nerves is established early and provides a template for subsequent development. The ease with which this template can be visualized as well as the ability to spatially resolve individual pioneer axons enables the role of specific cell-cell and molecular interactions to be clearly deciphered. We describe here the morphology and development of the earliest axon pathways in the embryonic zebrafish central nervous system and highlight the major questions that remain to be addressed with regard to axon guidance.

Marine and estuarine reservoir effects in central Queensland, Australia: Determination of Delta R values

As a component of archaeological investigations on the central Queensland coast, a series of five marine shell specimens live-collected between A.D. 1904 and A.D. 1929 and 11 shell/ charcoal paired samples from archaeological contexts were radiocarbon dated to determine local DeltaR values. The object of the study was to assess the potential influence of localized variation in marine reservoir effect in accurately determining the age of marine and estuarine shell from archaeological deposits in the area. Results indicate that the routinely applied DeltaR value of -5 +/- 35 for northeast Australia is erroneously calculated. The determined values suggest a minor revision to Reimer and Reimer's (2000) recommended value for northeast Australia from DeltaR = +11 +/- 5 to + 12 +/- 7, and specifically for central Queensland to DeltaR = +10 +/- 7, for near-shore open marine environments. In contrast, data obtained from estuarine shell/charcoal pairs demonstrate a general lack of consistency, suggesting estuary-specific patterns of variation in terrestrial carbon input and exchange with the open ocean. Preliminary data indicate that in some estuaries, at some time periods, a DeltaR value of more than - 155 +/- 55 may be appropriate, In estuarine contexts in central Queensland, a localized estuary-specific correction factor is recommended to account for geographical and temporal variation in C-14 activity. (C) 2002 Wiley Periodicals.

Role of peripheral afference during acquisition of a complex coordination task

It has long been supposed that the interference observed in certain patterns of coordination is mediated, at least in part, by peripheral afference from the moving limbs. We manipulated the level of afferent input, arising from movement of the opposite limb, during the acquisition of a complex coordination task. Participants learned to generate flexion and extension movements of the right wrist, of 75degrees amplitude, that were a quarter cycle out of phase with a 1-Hz sinusoidal visual reference signal. On separate trials, the left wrist either was at rest, or was moved passively by a torque motor through 50degrees, 75degrees or 100degrees, in synchrony with the reference signal. Five acquisition sessions were conducted on successive days. A retention session was conducted I week later. Performance was initially superior when the opposite limb was moved passively than when it was static. The amplitude and frequency of active movement were lower in the static condition than in the driven conditions and the variation in the relative phase relation across trials was greater than in the driven conditions. In addition, the variability of amplitude, frequency and the relative phase relation during each trial was greater when the opposite limb was static than when driven. Similar effects were expressed in electromyograms. The most marked and consistent differences in the accuracy and consistency of performance (defined in terms of relative phase) were between the static condition and the condition in which the left wrist was moved through 50degrees. These outcomes were exhibited most prominently during initial exposure to the task. Increases in task performance during the acquisition period, as assessed by a number of kinematic variables, were generally well described by power functions. In addition, the recruitment of extensor carpi radialis (ECR), and the degree of co-contraction of flexor carpi radialis and ECR, decreased during acquisition. Our results indicate that, in an appropriate task context, afferent feedback from the opposite limb, even when out of phase with the focal movement, may have a positive influence upon the stability of coordination.

A four-stage index 2 Diagonally Implicit Runge-Kutta method

High index Differential Algebraic Equations (DAEs) force standard numerical methods to lower order. Implicit Runge-Kutta methods such as RADAU5 handle high index problems but their fully implicit structure creates significant overhead costs for large problems. Singly Diagonally Implicit Runge-Kutta (SDIRK) methods offer lower costs for integration. This paper derives a four-stage, index 2 Explicit Singly Diagonally Implicit Runge-Kutta (ESDIRK) method. By introducing an explicit first stage, the method achieves second order stage calculations. After deriving and solving appropriate order conditions., numerical examples are used to test the proposed method using fixed and variable step size implementations. (C) 2001 IMACS. Published by Elsevier Science B.V. All rights reserved.

Axon navigation in the mammalian primary olfactory pathway: Where to next?

The process of establishing long-range neuronal connections can be divided into at least three discrete steps. First, axons need to be stimulated to grow and this growth must be towards appropriate targets. Second, after arriving at their target, axons need to be directed to their topographically appropriate position and in some cases, such as in cortical structures, they must grow radially to reach the correct laminar layer Third, axons then arborize and form synaptic connections with only a defined subpopulation of potential post-synaptic partners. Attempts to understand these mechanisms in the visual system have been ongoing since pioneer studies in the 1940s highlighted the specificity of neuronal connections in the retino-tectal pathway. These classical systems-based approaches culminated in the 1990s with the discovery that Eph-ephrin repulsive interactions were involved in topographical mapping. In marked contrast, it was the cloning of the odorant receptor family that quickly led to a better understanding of axon targeting in the olfactory system. The last 10 years have seen the olfactory pathway rise in prominence as a model system for axon guidance. Once considered to be experimentally intractable, it is now providing a wealth of information on all aspects of axon guidance and targeting with implications not only for our understanding of these mechanisms in the olfactory system but also in other regions of the nervous system.

The benefits of physical activity during pregnancy

The aims of this paper are (1) to comment on the evidence relating to the health risks and benefits of physical activity (PA) for pregnant women and their unborn foetuses, and (2) to discuss the public health benefits of participation in appropriate physical activity during pregnancy. Evidence from recent original research and review papers suggests that there are potential benefits of appropriate PA in terms of maternal weight control and fitness, which are likely to have significant long term public health benefits. Concerns about the potential ill-effects of PA during pregnancy, such as hyperthermia, shortened gestational age and decreased birth weight are not supported by the most recent scientific reviews. The physiological adaptations to exercise during pregnancy appear to protect the foetus from potential harm and, while an upper level of safe activity has not been established, the benefits of continuing to be active during pregnancy appear to outweigh any potential risks. All decisions about participation in physical activity during pregnancy should however be made by women in consultation with their medical advisers.

Dual mode cooling house in the warm humid tropics

Passive techniques as an alternative to artificial cooling can bring important energy, environmental, financial, operational and qualitative benefits. However, regions such as the wet tropics can reach high levels of thermal stress in which passive means alone are unable to provide appropriate thermal comfort standards for some parts of the year. Despite a great accumulation of empirical information on the passive performance of houses for either free-running or conditioned modes, very little work has been done on the thermal performance of buildings that can operate with a mixed-running strategy in warm-humid climates. Buildings with such design features are able to balance the needs for comfort, privacy, and energy efficiency during different periods of the year. As free-running and conditioned modes are believed by many to be 'opposite' approaches, and have been presented as separate strategies, this paper demonstrates that not all parameters are directly opposite and a possible dual-mode integrated operation can be used for warm-humid locations for maximum comfort and minimum energy requirements. For this purpose, simulation runs using ESP-R (University of Strathclyde, ESRU, UK) were based on the climate data of Darwin (Australia) and on the ventilation styles of the house: free running and conditioned. Design features applicable to both, i.e. for a dual mode operation could be identified and the differences between conditioned and free running were demonstrated and proved not to be totally conflicting and therefore suitable for a dual mode operation. Different daily usage profiles (five use patterns were defined), and zoning of sleeping and living areas are presented. The dual mode use patterns compared to the base case house, for all the user possibilities, had improved performances of 17-52%, when compared to the free-running mode and 66-98% when compared to the conditioned mode. Simulation runs using other warm-humid climates (Miami, USA; Sao Luis, Brazil; Kuala Lumpur, Malaysia) were also conducted and compared to the results found for Darwin. (C) 2002 Elsevier Science Ltd. All rights reserved.

Transformation and transposon mutagenesis of Leifsonia xyli subsp. Xyli, causal organism of Ratoon Stunting Discease of sugarcane

Conditions have been developed for genetic transformation and insertional mutagenesis in Leifsonia xyli subsp. xyli (Lxx), the causal organism of ratoon stunting disease (RSD), one of the most damaging and intractable diseases of sugarcane internationally. Transformation frequencies ranged from 1 to 10 colony forming units (CFU)/mug of plasmid DNA using Clavibacter/Escherichia coli shuttle vectors pCG188, pDM302, and pDM306 and ranged from 50 to 500 CFU/mug using cosmid cloning vectors pLAFR3 and pLAFR5-km. The transformation/transposition frequency was 0 to 70 CFU/mug of DNA, using suicide vectors pUCD623 and pSLTP2021 containing transposable elements Tn4431 and Tn5, respectively. It was necessary to grow Lxx in media containing 0.1% glycine for electroporation and to amplify large plasmids in a dam(-)/dcm(-) E. coli strain and purify the DNA by anion exchange. To keep selection pressure at an optimum, the transformants were grown on nitrocellulose filters (0.2-mum pore size) on media containing the appropriate antibiotics. Transposon Tn4431 containing a promoterless lux operon from Vibrio fischeri and a tetracycline-resistance gene was introduced on the suicide vector pUCD623. All but 1% of the putative transposon mutants produce light, indicating transposition into functional Lxx genes. Southern blot analysis of these transformants indicates predominantly single transposon insertions at unique sites. The cosmid cloning vector pLAFR5-km was stably maintained in Lxx. The development of a transformation and transposon mutagenesis system opens the way for molecular analysis of pathogenicity determinants in Lxx.

Molecular engineered porous clays using surfactants

Quaternary ammonium surfactants were used to control the pore structure of bentonite intercalated with a mixed hydro-sol of silicon and titanium. Porous clay heterostructures of alumina and laponite were prepared in the presence of polyethylene oxide (PEO) surfactants. Participation of the surfactants in the synthesis results in significant changes in the structure of porous clay products. Surfactants are involved in different mechanisms, In the case of bentonite, the mean size of the framework pores was directly proportional to the chain length of the quaternary ammonium surfactants. This indicates a molecular templating mechanism, similar to that observed in the synthesis of MCM41. However, in the case of laponite, the size and volume of the mesopores were related to the amount of PEO surfactants used. By using an appropriate surfactant, we can obtain highly porous clays with various pore structures. Introducing surfactants during intercalation is an efficient strategy for the molecular engineering of porous clay adsorbents and catalysts. (C) 2002 Elsevier Science B.V. All rights reserved.