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

The role of handouts, note-taking and overhead transparencies in veterinary science lectures

Objective To study student and staff views of the role and use of handouts, note-taking and overhead transparencies in veterinary science lectures at the University of Queensland Methods The Nominal Group Technique was used to help develop a questionnaire, which was completed by 351 students (a response rate of 84%) and 35 staff (76%) from the 5 years of the veterinary course. The data were analysed using the SAS statistical computer package. Results Staff and students held different views as to the frequency with which handouts should be used, their educational value, and whether they should be complete or partial. Fewer students than staff agreed that handouts discourage further reading in a subject. Almost all staff and students saw the central functions of note-taking to be provision of notes for subsequent revision and encoding information given by the lecturer. More students than staff however, considered that note-taking in lectures interferes with understanding. Staff and students held similar views as to the uses of overheads in lectures. Interestingly however, more staff than students agreed that overheads often contain too much information. Conclusion Both students and staff saw the central role of note-taking as providing a set of good notes for revision. Generally students preferred that this information be provided in the form of partial or complete handouts, while staff preferred students to take notes and to read outside lectures. Surprisingly, more staff than students felt that overhead transparencies often contained too much information. Note-taking, handouts and overhead transparencies need to be linked in a coherent educational strategy to promote effective learning.

A role for the dominant thalamus in language? A linguistic comparison of two cases subsequent to unilateral thalamotomy procedures in the dominant and non-dominant hemispheres

Background: Thalamotomy has been reported to be successful in ameliorating the motor symptoms of tremor and/or rigidity in people with Parkinson's disease (PD), emphasising the bona fide contribution of this subcortical nucleus to the neural circuitry subserving motor function. Despite evidence of parallel yet segregated associative and motor cortico-subcortical-cortical circuits, comparatively few studies have investigated the effects of this procedure on cognitive functions. In particular, research pertaining to the impact of thalamotomy on linguistic processes is fundamentally lacking. Aims: The purpose of this research was to investigate the effects of thalamotomy in the language dominant and non-dominant hemispheres on linguistic functioning, relative to operative theoretical models of subcortical participation in language. This paper compares the linguistic profiles of two males with PD, aged 75 years (10 years of formal education) and 62 years (22 years of formal education), subsequent to unilateral thalamotomy procedures within the language dominant and non-dominant hemispheres, respectively. Methods & Procedures: Comprehensive linguistic profiles comprising general and high-level linguistic abilities in addition to on-line semantic processing skills were compiled up to 1 month prior to surgery and 3 months post-operatively, within perceived on'' periods (i.e., when optimally medicated). Pre- and post-operative language performances were compared within-subjects to a group of 16 non-surgical Parkinson's controls (NSPD) and a group of 16 non-neurologically impaired adults (NC). Outcomes & Results: The findings of this research suggest a laterality effect with regard to the contribution of the thalamus to high-level linguistic abilities and, potentially, the temporal processing of semantic information. This outcome supports the application of high-level linguistic assessments and measures of semantic processing proficiency to the clinical management of individuals with dominant thalamic lesions. Conclusions: The results reported lend support to contemporary theories of dominant thalamic participation in language, serving to further elucidate our current understanding of the role of subcortical structures in mediating linguistic processes, relevant to cortical hemispheric dominance.

Mapping Gray's model of personality onto the Eysenck Personality Profiler (EPP)

The aim of this study was to determine how well Gray's model of personality [Gray, J.A. (1982). The neuropsychology of anxiety: an enquiry into the functions of the septo-hippocampal system. Oxfords: Oxford University Press, Gray, J.A. (1987). The psychology of fear and stress. Cambridge: Cambridge University Press], as measured by the Gray Wilson Personality Questionnaire (GWPQ), can provide a full description of personality as measured by the primary scales of the Eysenck Personality Profiler (EPP) and the type scales of the short version or the EPQ-R. Factor analysis of the GWPQ the Anxiety and linpulsivity scales of the EPP and the Learning Styles Questionnaire (LSQ) showed that the GWPQ seemed to measure general activation and inhibition factors, but not the finer features of Gray's theory. When the GWPQ scales were regressed against each scale of the EPP., it was round that they generally provide only a reasonable explanation of the EPP primary scales. It is concluded that the GWPQ measures general propel-ties of Gray's model, that the linpulsivity and Anxiety scales of the EPP also scent related to the GWPQ scales, and that Gray's model of personality provides only a partial explanation of personality in general. (C) 2002 Published by Elsevier Science Ltd. All rights reserved.

Application of the maximum entropy method to the (2 + 1)D four-fermion model

We investigate spectral functions extracted using the maximum entropy method from correlators measured in lattice simulations of the (2+1)-dimensional four-fermion model. This model is particularly interesting because it has both a chirally broken phase with a rich spectrum of mesonic bound states and a symmetric phase where there are only resonances. In the broken phase we study the elementary fermion, pion, sigma, and massive pseudoscalar meson; our results confirm the Goldstone nature of the π and permit an estimate of the meson binding energy. We have, however, seen no signal of σ→ππ decay as the chiral limit is approached. In the symmetric phase we observe a resonance of nonzero width in qualitative agreement with analytic expectations; in addition the ultraviolet behavior of the spectral functions is consistent with the large nonperturbative anomalous dimension for fermion composite operators expected in this model.

The Three-dimensional Solution Structure of NaD1, a New Floral Defensin from Nicotiana alata and its Application to a Homology Model of the Crop Defense Protein alfAFP

NMR spectroscopy and simulated annealing calculations have been used to determine the three-dimensional structure of NaD1, a novel antifungal and insecticidal protein isolated from the flowers of Nicotiana alata. NaD1 is a basic, cysteine-rich protein of 47 residues and is the first example of a plant defensin from flowers to be characterized structurally. Its three-dimensional structure consists of an a-helix and a triple-stranded anti-parallel beta-sheet that are stabilized by four intramolecular disulfide bonds. NaD1 features all the characteristics of the cysteine-stabilized up motif that has been described for a variety of proteins of differing functions ranging from antibacterial insect defensins and ion channel-perturbing scorpion toxins to an elicitor of the sweet taste response. The protein is biologically active against insect pests, which makes it a potential candidate for use in crop protection. NaD1 shares 31% sequence identity with alfAFP, an antifungal protein from alfalfa that confers resistance to a fungal pathogen in transgenic potatoes. The structure of NaD1 was used to obtain a homology model of alfAFP, since NaD1 has the highest level of sequence identity with alfAFP of any structurally characterized antifungal defensin. The structures of NaD1 and alfAFP were used in conjunction with structure - activity data for the radish defensin Rs-AFP2 to provide an insight into structure-function relationships. In particular, a putative effector site was identified in the structure of NaD1 and in the corresponding homology model of alfAFP. (C) 2002 Elsevier Science Ltd. All rights reserved.

Circular proteins - no end in sight

Circular proteins are a recently discovered phenomenon. They presumably evolved to confer advantages over ancestral linear proteins while maintaining the intrinsic biological functions of those proteins. In general, these advantages include a reduced sensitivity to proteolytic cleavage and enhanced stability. In one remarkable family of circular proteins, the cyclotides, the cyclic backbone is additionally braced by a knotted arrangement of disulfide bonds that confers additional stability and topological complexity upon the family. This article describes the discovery, structure, function and biosynthesis of the currently known circular proteins. The discovery of naturally occurring circular proteins in the past few years has been complemented by new chemical and biochemical methods to make synthetic circular proteins; these are also briefly described.

Identification of the enamelin (g.8344delG) mutation in a new kindred and presentation of a standardized ENAM nomenclature

The amelogenesis imperfectas (Al) area geneticatly heterogeneous group of diseases that result in defective development of tooth enamel. Although X-linked, autosomal. dominant and autosomal. recessive forms of Al have been clinically characterized, only two genes (AMELX and ENAM) have been associated with Al. To date, three enamelin (ENAM) mutations have been identified. These mutations cause phenotypically diverse forms of autosomal. dominant Al. Detailed phenotype-genotype correlations have not been performed for autosomal. dominant Al due to ENAM mutations. We identified a previously unreported kindred segregating for the ENAM mutation, g.8344delG. Light and electron microscopy analyses of unerupted permanent teeth show the enamel is markedly reduced in thickness, Lacks a prismatic structure and has a laminated appearance. Taken together these histological features support the enamelin protein as being critical for the development of a normal. enamel. thickness and that it Likely has a role in regulating c-axis crystallite growth. Because there is growing molecular and phenotypic diversity in the enamelin defects, it is critical to have a nomenclature and numbering system for characterizing these conditions. We present a standardized nomenclature for ENAM mutations that will allow consistent reporting and communication. (C) 2003 Elsevier Science Ltd. All rights reserved.

Mechanism of mitosis-specific activation of MEK1

Activation of cyclin B-Cdc2 is an absolute requirement for entry into mitosis, but other protein kinase pathways that also have mitotic functions are activated during G(2)/M progression. The MAPK cascade has well established roles in entry and exit from mitosis in Xenopus, but relatively little is known about the regulation and function of this pathway in mammalian mitosis. Here we report a detailed analysis of the activity of all components of the Ras/Raf/MEK/ERK pathway in HeLa cells during normal G(2)/M. The focus of this pathway is the dramatic activation of an endomembrane-associated MEK1 without the corresponding activation of the MEK substrate ERK. This is because of the uncoupling of MEK1 activation from ERK activation. The mechanism of this uncoupling involves the cyclin B-Cdc2-dependent proteolytic cleavage of the N-terminal ERK-binding domain of MEK1 and the phosphorylation of Thr(286). These results demonstrate that cyclin B-Cdc2 activity regulates signaling through the MAPK pathway in mitosis.

An EM-based Semi-Parametric Mixture Model Approach to the Regression Analysis of Competing-Risks Data

We consider a mixture model approach to the regression analysis of competing-risks data. Attention is focused on inference concerning the effects of factors on both the probability of occurrence and the hazard rate conditional on each of the failure types. These two quantities are specified in the mixture model using the logistic model and the proportional hazards model, respectively. We propose a semi-parametric mixture method to estimate the logistic and regression coefficients jointly, whereby the component-baseline hazard functions are completely unspecified. Estimation is based on maximum likelihood on the basis of the full likelihood, implemented via an expectation-conditional maximization (ECM) algorithm. Simulation studies are performed to compare the performance of the proposed semi-parametric method with a fully parametric mixture approach. The results show that when the component-baseline hazard is monotonic increasing, the semi-parametric and fully parametric mixture approaches are comparable for mildly and moderately censored samples. When the component-baseline hazard is not monotonic increasing, the semi-parametric method consistently provides less biased estimates than a fully parametric approach and is comparable in efficiency in the estimation of the parameters for all levels of censoring. The methods are illustrated using a real data set of prostate cancer patients treated with different dosages of the drug diethylstilbestrol. Copyright (C) 2003 John Wiley Sons, Ltd.

Dactylomyza gibsoni n.g., n. sp (Digenea: Opecoelidae) from Schuettea woodwardi (Waite) (Monodactylidae) from off Western Australia

An opecoelid digenean, Dactylomyza gibsoni n. g., n. sp. is described and figured from Schuettea woodwardi (Waite), a monodactylid from off the coast of Western Australia. The new genus conforms to the concept of the opecoelid subfamily Opecoelinae. The resemblance of the new genus to three other opecoelid genera, Pseudopecoeloides Yamaguti, 1940, Opecoeloides Odhner, 1928 and Poracanthium Dollfus, 1948, is discussed. Dactylomyza n. g. is distinguished from these morphologically similar worms on the basis of its median genital pore, ventral sucker appendages, uroproct and the absence of an accessory sucker. Pseudopecoeloides equesi Manter, 1947 is transferred to the new genus as Dactylomyza equesi (Manter, 1947) n. comb.

Bartoliella pritchardae n.g., n.sp. (Digenea: Opecoelidae) in Epinephelides armatus (Serranidae) from temperate marine waters of Western Australia

An opecoelid, Bartoliella pritchardae n. g., n. sp., is described from the intestine of Epinephelides armatus from Western Australia. The new genus has been assigned to the subfamily Opecoelininae Gibson & Bray, 1984, bringing the number of genera in the subfamily to two. Although the new genus is similar to Opecoelina Manter, 1934 morphologically, the pedunculate ventral sucker and complete absence of a cirrus-sac necessitate the erection of a new genus. A formal re-definition of the subfamily is given, based on the diagnoses of the genera Opecoelina and Bartoliella n. g.

SOX8 is expressed during testis differentiation in mice and synergizes with SF1 to activate the Amh promoter in vitro

Sox8 is a member of the Sox family of developmental transcription factor genes and is closely related to Sox9, a key gene in the testis determination pathway in mammals. Like Sox9, Sox8 is expressed in the developing mouse testis around the time of sex determination, suggesting that it might play a role in regulating the expression of testis-specific genes. An early step in male sex differentiation is the expression of anti-Mullerian hormone (AMH) in Sertoli cells. Expression of the Amh gene during sex differentiation requires the interaction of several transcription factors, including SF1, SOX9, GATA4, WT1, and DAX1. Here we show that SOX8 may also be involved in regulating the expression of Amh. Expression of Sox8 begins just prior to that of Amh at 12 days post coitum (dpc) in mouse testes and continues beyond 16 dpc in Sertoli cells. In vitro assays showed that SOX8 binds specifically to SOX binding sites within the Amh minimal promoter and, like SOX9, acts synergistically with SF1 through direct protein-protein interaction to enhance Amh expression, albeit at lower levels compared with SOX9. SOX8 and SOX9 appear to have arisen from a common ancestral gene and may have retained some common functions during sexual development. Our data provide the first evidence that SOX8 may partially compensate for the reduced SOX9 activity in campomelic dysplasia and substitute for Sox9 where Sox9 is either not expressed or expressed too late to be involved in sex determination or regulation of Amh expression.