Children with stable asthma have reduced airway matrix metalloproteinase-9 and matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio

Background Childhood asthma is characterized by inflammation of the airways. Structural changes of the airway wall may also be seen in some children early in the course of the disease. Matrix metalloproteinases (MMPs) are key mediators in the metabolism of the extracellular matrix (ECM). Objective To investigate the balance of MMP-8, MMP-9 and tissue inhibitor of metalloproteinases (TIMP)-1 in the airways of children with asthma. Methods One hundred and twenty-four children undergoing elective surgical procedures also underwent non-bronchoscopic bronchoalveolar lavage (BAL). MMP-8, MMP-9 and TIMP-1 were measured by ELISA. Results There was a significant reduction in MMP-9 in atopic asthmatic children (n=31) compared with normal children (n=30) [median difference: 0.57 ng/mL (95% confidence interval: 0.18–1.1 ng/mL)]. The ratio of MMP-9 to TIMP-1 was also reduced in asthmatic children. Levels of all three proteins were significantly correlated to each other and to the relative proportions of particular inflammatory cells in BAL fluid (BALF). Both MMP-8 and MMP-9 were moderately strongly correlated to the percentage neutrophil count (r=0.40 and 0.47, respectively, P

Gaining Access to Data Sources in Statutory Social Work Agencies: The Long and Winding Road

This paper details a researcher's experience of gaining access to three statutory social work agencies in order to conduct a study examining how social workers respond to family support cases and how parents and carers experience the intervention of social workers in these cases. The stages in gaining access are outlined, the gate-keepers involved at each stage are identified and some of the difficulties encountered are highlighted and discussed. The paper concludes that researchers need to give greater priority to access considerations and that social work agencies need to give greater priority to co-operation with researchers.

Computerised Diagnostic Decision Support System for the Classification of Pre-Invasive Cervical Squamous Lesions.

Previous studies have revealed considerable interobserver and intraobserver variation in the histological classification of preinvasive cervical squamous lesions. The aim of the present study was to develop a decision support system (DSS) for the histological interpretation of these lesions. Knowledge and uncertainty were represented in the form of a Bayesian belief network that permitted the storage of diagnostic knowledge and, for a given case, the collection of evidence in a cumulative manner that provided a final probability for the possible diagnostic outcomes. The network comprised 8 diagnostic histological features (evidence nodes) that were each independently linked to the diagnosis (decision node) by a conditional probability matrix. Diagnostic outcomes comprised normal; koilocytosis; and cervical intraepithelial neoplasia (CIN) 1, CIN II, and CIN M. For each evidence feature, a set of images was recorded that represented the full spectrum of change for that feature. The system was designed to be interactive in that the histopathologist was prompted to enter evidence into the network via a specifically designed graphical user interface (i-Path Diagnostics, Belfast, Northern Ireland). Membership functions were used to derive the relative likelihoods for the alternative feature outcomes, the likelihood vector was entered into the network, and the updated diagnostic belief was computed for the diagnostic outcomes and displayed. A cumulative probability graph was generated throughout the diagnostic process and presented on screen. The network was tested on 50 cervical colposcopic biopsy specimens, comprising 10 cases each of normal, koilocytosis, CIN 1, CIN H, and CIN III. These had been preselected by a consultant gynecological pathologist. Using conventional morphological assessment, the cases were classified on 2 separate occasions by 2 consultant and 2 junior pathologists. The cases were also then classified using the DSS on 2 occasions by the 4 pathologists and by 2 medical students with no experience in cervical histology. Interobserver and intraobserver agreement using morphology and using the DSS was calculated with K statistics. Intraobserver reproducibility using conventional unaided diagnosis was reasonably good (kappa range, 0.688 to 0.861), but interobserver agreement was poor (kappa range, 0.347 to 0.747). Using the DSS improved overall reproducibility between individuals. Using the DSS, however, did not enhance the diagnostic performance of junior pathologists when comparing their DSS-based diagnosis against an experienced consultant. However, the generation of a cumulative probability graph also allowed a comparison of individual performance, how individual features were assessed in the same case, and how this contributed to diagnostic disagreement between individuals. Diagnostic features such as nuclear pleomorphism were shown to be particularly problematic and poorly reproducible. DSSs such as this therefore not only have a role to play in enhancing decision making but also in the study of diagnostic protocol, education, self-assessment, and quality control. (C) 2003 Elsevier Inc. All rights reserved.

Self-reported quality of life of 8-12 year old children with cerebral palsy: a cross-sectional European Study

Background

Little is known about the quality of life (QoL) of disabled children. We describe self-reported QoL of children with cerebral palsy, factors that influence it, and how it compares with QoL of the general population.

Methods

1174 children aged 8–12 years were randomly selected from eight population-based registers of children with cerebral palsy in six European countries and 743 (63%) agreed to participate; one further region recruited 75 children from multiple sources. Researchers visited these 818 children. 318 (39%) with severe intellectual impairment could not self-report; 500 (61%) reported their QoL using KIDSCREEN, an instrument with scores in ten domains, each with SD=10. Multivariable regression was used to relate QoL to impairments, pain, and sociodemographic characteristics. Comparisons were made with QoL data from the general population.

Findings

Impairments were not significantly associated with six KIDSCREEN domains. Comparison of least and most able groups showed that severely limited self-mobility was significantly associated with reduced mean score for physical wellbeing (7·6, 95% CI 2·7–12·4); intellectual impairment with reduced mean for moods and emotions (3·7, 1·5–5·9) and autonomy (3·3, 0·9–5·7); and speech difficulties with reduced mean for relationships with parents (4·5, 1·9–7·1). Pain was common and associated with lower QoL on all domains. Impairments and pain explained up to 3% and 7%, respectively, of variation in QoL. Children with cerebral palsy had similar QoL to children in the general population in all domains except schooling, in which evidence was equivocal, and physical wellbeing, in which comparison was not possible.

Interpretation

Parents can be reassured that most children aged 8–12 years with cerebral palsy will have similar QoL to other children. This finding should guide social and educational policy to ensure that disabled children participate fully in society. Because of its association with QoL, children's pain should be carefully assessed.

Mature DC from skin and skin-draining LN retain the ability to acquire and efficiently present targeted antigen.

Skin-draining LN contain several phenotypically distinguishable DC populations, which may be immature or mature. Mature DC are generally considered to have lost the capacity to acquire and present newly encountered Ag. Using antibody-opsonized liposomes as Ag carriers, we show that mature DC purified from skin explants are able to efficiently capture liposomes, process Ag encapsulated within them and activate Ag-specific CD4(+) T cells. Explant DC from mice with Langerhans cells (LC) expressing the primate diphtheria toxin receptor that were exposed to diphtheria toxin in vivo presented Ag as well as explant DC from wild-type mice, indicating that LC are not required and dermal DC are probably responsible for this presentation. We further show that all DC subtypes from LN that capture opsonized Ag are capable of cross-presenting it to CD8(+) T cells. Induction of additional maturation in vivo by LPS or treatment with double-stranded RNA did not alter the Ag presentation capacity of the skin or LN DC subtypes. These results suggest that mature DC present in skin-draining LN may play an important role in the induction of primary and/or secondary immune responses against Ag delivered to the LN that they take up by receptor-mediated endocytosis.

Design of asymmetrical RF and microwave bandpass filters by computer optimization

This paper presents an optimization-based approach to the design of asymmetrical filter structures having the maximum number of return- or insertion-loss ripples in the passband such as those based upon Chebyshev function prototypes. The proposed approach. has the following advantages over the general purpose optimization techniques adopted previously such as: less frequency sampling is required, optimization is carried out with respect to the Chebyshev (or minimax) criterion, the problem of local minima does not arise, and optimization is usually only required for the passband. When implemented around an accurate circuit simulation, the method can be used to include all the effects of discontinuities, junctions, fringing, etc. to reduce the amount of tuning required in the final filter. The design of asymmetrical ridged-waveguide bandpass filters is considered as an example. Measurements on a fabricated filter confirm the accuracy of the design procedure.

Participation of 8-12 year old children with cerebral palsy: a cross-sectional European Survey

Objectives
To evaluate how involvement in life situations (participation) in children with cerebral palsy varies with type and severity of impairment and to investigate geographical variation in participation.

Design
Cross sectional study. Trained interviewers visited parents of children with cerebral palsy; multilevel multivariable regression related participation to impairments, pain, and sociodemographic characteristics.

Setting
Eight European regions with population registers of children with cerebral palsy; one further region recruited children from multiple sources.

Participants
1174 children aged 8-12 with cerebral palsy randomly selected from the population registers, 743 (63%) joined in the study; the further region recruited 75 children.

Main outcome measure
Children’s participation assessed by the Life-H questionnaire covering 10 main areas of daily life. Scoring ignored adaptations or assistance required for participation.

Results
Children with pain and those with more severely impaired walking, fine motor skills, communication, and intellectual abilities had lower participation across most domains. Type of cerebral palsy and problems with feeding and vision were associated with lower participation for specific domains, but the sociodemographic factors examined were not. Impairment and pain accounted for up to a sixth of the variation in participation. Participation on all domains varied substantially between regions: children in east Denmark had consistently higher participation than children in other regions. For most participation domains, about a third of the unexplained variation could be ascribed to variation between regions and about two thirds to variation between individuals.

Conclusions
Participation in children with cerebral palsy should be assessed in clinical practice to guide intervention and assess its effect. Pain should be carefully assessed. Some European countries facilitate participation better than others, implying some countries could make better provision. Legislation and regulation should be directed to ensuring this happens.

Safeguarding: A case for intelligent risk management

‘Risk’ in social work is typically read as risk-of-bads, and specifically extreme bads. This paper develops the implications of the logical objection to attempts to predict low frequency extreme events (such as child homicides). Our argument is that if we focus on these low probability high cost outcomes—these heart wrenching, but unpredictable, tragedies—we take social work away from the good that it can do, leave it open to inappropriate disapprobation, and, in terms of outcomes, do less well by the vulnerable. This point is reinforced by discussion of developments in other academic fields, and by further examination of the logic (and the morality) of protection under uncertainty. We explore the implications for the way social work should be evaluated. A proper academic understanding of risk, and decision making under uncertainty, has, we argue clear practical implications.

Understanding New Product Project Performance

Purpose – The purpose of this paper is to summarize the accumulated body of knowledge on the performance of new product projects and provide directions for further research. Design/methodology/approach – Using a refined classification of antecedents of new product project performance the research results are meta-analyzed in the literature in order to identify the strength and stability of predictor-performance relationships. Findings – The results reveal that 22 variables have a significant relationship with new product project performance, of which only 12 variables have a sizable relationship. In order of importance these factors are the degree of organizational interaction, R&D and marketing interface, general product development proficiency, product advantage, financial/business analysis, technical proficiency, management skill, marketing proficiency, market orientation, technology synergy, project manager competency and launch activities. Of the 34 variables 16 predictors show potential for moderator effects. Research limitations/implications – The validity of the results is constrained by publication bias and heterogeneity of performance measures, and directions for the presentation of data in future empirical publications are provided. Practical implications – This study helps new product project managers in understanding and managing the performance of new product development projects. Originality/value – This paper provides unique insights into the importance of predictors of new product performance at the project level. Furthermore, it identifies which predictor-performance relations are contingent on other factors.

Cement-in-cement revision hip arthroplasty: an analysis of clinical and biomechanical literature

Introduction The number of revision hip arthroplasties is increasing but several aspects of this procedure could be improved. One method of reducing intra-operative complications is the cement-in-cement technique. This procedure entails cementing a smaller femoral prosthesis into the existing stable cement mantle. The aim of this systematic review is to provide a concise overview of the existing historical, operative, biomechanical and clinical literature on the cement-in-cement construct.

Association between participation in life situations of children with cerebral palsy and their physical, social, and attitudinal environment:A cross-sectional multicenter European study

Objective:
To evaluate how participation of children with cerebral palsy (CP) varied with their environment.

Design:
Home visits to children. Administration of Assessment of Life Habits and European Child Environment Questionnaires. Structural equation modeling of putative associations between specific domains of participation and environment, while allowing for severity of child's impairments and pain.

Setting:
European regions with population-based registries of children with CP.

Participants:
Children (n=1174) aged 8 to 12 years were randomly selected from 8 population-based registries of children with CP in 6 European countries. Of these, 743 (63%) agreed to participate; 1 further region recruited 75 children from multiple sources. Thus, there were 818 children in the study.

Interventions:
Not applicable.

Main Outcome Measure:
Participation in life situations.

Results:
For the hypothesized associations, the models confirmed that higher participation was associated with better availability of environmental items. Higher participation in daily activities—mealtimes, health hygiene, personal care, and home life—was significantly associated with a better physical environment at home (P<.01). Mobility was associated with transport and physical environment in the community. Participation in social roles (responsibilities, relationships, recreation) was associated with attitudes of classmates and social support at home. School participation was associated with attitudes of teachers and therapists. Environment explained between 14% and 52% of the variation in participation.

Conclusions:
The findings confirmed the social model of disability. The physical, social, and attitudinal environment of disabled children influences their participation in everyday activities and social roles.