Showing papers by "Maastricht University published in 2010"

An international urogynecological association (IUGA)/international continence society (ICS) joint report on the terminology for female pelvic floor dysfunction

Abstract: Introduction and hypothesis Next to existing terminology of the lower urinary tract, due to its increasing complexity, the terminology for pelvic floor dysfunction in women may be better updated by a female-specific approach and clinically based consensus report. Methods This report combines the input of members of the Standardization and Terminology Committees of two Inter

Susceptibility to Exacerbation in Chronic Obstructive Pulmonary Disease

Abstract: BACKGROUND: Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity. METHODS: We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years. RESULTS: Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count. CONCLUSIONS: Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00292552.)

An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction

Abstract: Next to existing terminology of the lower urinary tract, due to its increasing complexity, the terminology for pelvic floor dysfunction in women may be better updated by a female-specific approach and clinically based consensus report. This report combines the input of members of the Standardization and Terminology Committees of two International Organizations, the International Urogynecological Association (IUGA) and the International Continence Society (ICS), assisted at intervals by many external referees. Appropriate core clinical categories and a subclassification were developed to give an alphanumeric coding to each definition. An extensive process of 15 rounds of internal and external review was developed to exhaustively examine each definition, with decision-making by collective opinion (consensus). A terminology report for female pelvic floor dysfunction, encompassing over 250 separate definitions, has been developed. It is clinically based with the six most common diagnoses defined. Clarity and user-friendliness have been key aims to make it interpretable by practitioners and trainees in all the different specialty groups involved in female pelvic floor dysfunction. Female-specific imaging (ultrasound, radiology, and MRI) has been a major addition while appropriate figures have been included to supplement and help clarify the text. Ongoing review is not only anticipated but will be required to keep the document updated and as widely acceptable as possible. A consensus-based terminology report for female pelvic floor dysfunction has been produced aimed at being a significant aid to clinical practice and a stimulus for research.

Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: 'establishing normal and reference values'.

Abstract: Aims: Carotid-femoral pulse wave velocity (PWV), a direct measure of aortic stiffness, has become increasingly important for total cardiovascular (CV) risk estimation. Its application as a routine tool for clinical patient evaluation has been hampered by the absence of reference values. The aim of the present study is to establish reference and normal values for PWV based on a large European population. Methods and results: We gathered data from 16 867 subjects and patients from 13 different centres across eight European countries, in which PWV and basic clinical parameters were measured. Of these, 11 092 individuals were free from overt CV disease, non-diabetic and untreated by either anti-hypertensive or lipid-lowering drugs and constituted the reference value population, of which the subset with optimal/normal blood pressures (BPs) (n = 1455) is the normal value population. Prior to data pooling, PWV values were converted to a common standard using established conversion formulae. Subjects were categorized by age decade and further subdivided according to BP categories. Pulse wave velocity increased with age and BP category; the increase with age being more pronounced for higher BP categories and the increase with BP being more important for older subjects. The distribution of PWV with age and BP category is described and reference values for PWV are established. Normal values are proposed based on the PWV values observed in the non-hypertensive subpopulation who had no additional CV risk factors. Conclusion: The present study is the first to establish reference and normal values for PWV, combining a sizeable European population after standardizing results for different methods of PWV measurement.

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs

Abstract: Treatment of rheumatoid arthritis (RA) may differ among rheumatologists and currently, clear and consensual international recommendations on RA treatment are not available. In this paper recommendations for the treatment of RA with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects, are described. The recommendations are based on evidence from five systematic literature reviews (SLRs) performed for synthetic DMARDs, biological DMARDs, GCs, treatment strategies and economic issues. The SLR-derived evidence was discussed and summarised as an expert opinion in the course of a Delphi-like process. Levels of evidence, strength of recommendations and levels of agreement were derived. Fifteen recommendations were developed covering an area from general aspects such as remission/low disease activity as treatment aim via the preference for methotrexate monotherapy with or without GCs vis-a-vis combination of synthetic DMARDs to the use of biological agents mainly in patients for whom synthetic DMARDs and tumour necrosis factor inhibitors had failed. Cost effectiveness of the treatments was additionally examined. These recommendations are intended to inform rheumatologists, patients and other stakeholders about a European consensus on the management of RA with DMARDs and GCs as well as strategies to reach optimal outcomes of RA, based on evidence and expert opinion.

Outlier and influence diagnostics for meta‐analysis

Abstract: The presence of outliers and influential cases may affect the validity and robustness of the conclusions from a meta-analysis. While researchers generally agree that it is necessary to examine outlier and influential case diagnostics when conducting a meta-analysis, limited studies have addressed how to obtain such diagnostic measures in the context of a meta-analysis. The present paper extends standard diagnostic procedures developed for linear regression analyses to the meta-analytic fixed- and random/mixed-effects models. Three examples are used to illustrate the usefulness of these procedures in various research settings. Issues related to these diagnostic procedures in meta-analysis are also discussed. Copyright © 2010 John Wiley & Sons, Ltd.

A step-up approach or open necrosectomy for necrotizing pancreatitis

Abstract: Background Necrotizing pancreatitis with infected necrotic tissue is associated with a high rate of complications and death. Standard treatment is open necrosectomy. The outcome may be improved by a minimally invasive step-up approach. Methods In this multicenter study, we randomly assigned 88 patients with necrotizing pancreatitis and suspected or confirmed infected necrotic tissue to undergo primary open necrosectomy or a step-up approach to treatment. The step-up approach consisted of percutaneous drainage followed, if necessary, by minimally invasive retroperitoneal necrosectomy. The primary end point was a composite of major complications (new-onset multiple-organ failure or multiple systemic complications, perforation of a visceral organ or enterocutaneous fistula, or bleeding) or death. Results The primary end point occurred in 31 of 45 patients (69%) assigned to open necrosectomy and in 17 of 43 patients (40%) assigned to the step-up approach (risk ratio with the step-up approach, 0.57; 95% confidence interval, 0.38 to 0.87; P = 0.006). Of the patients assigned to the step-up approach, 35% were treated with percutaneous drainage only. New-onset multiple-organ failure occurred less often in patients assigned to the step-up approach than in those assigned to open necrosectomy (12% vs. 40%, P = 0.002). The rate of death did not differ significantly between groups (19% vs. 16%, P = 0.70). Patients assigned to the step-up approach had a lower rate of incisional hernias (7% vs. 24%, P = 0.03) and new-onset diabetes (16% vs. 38%, P = 0.02). Conclusions A minimally invasive step-up approach, as compared with open necrosectomy, reduced the rate of the composite end point of major complications or death among patients with necrotizing pancreatitis and infected necrotic tissue. (Current Controlled Trials number, ISRCTN13975868.)

Cognitive load theory in health professional education: design principles and strategies

Abstract: CONTEXT Cognitive load theory aims to develop instructional design guidelines based on a model of human cognitive architecture. The architecture assumes a limited working memory and an unlimited long-term memory holding cognitive schemas; expertise exclusively comes from knowledge stored as schemas in long-term memory. Learning is described as the construction and automation of such schemas. Three types of cognitive load are distinguished: intrinsic load is a direct function of the complexity of the performed task and the expertise of the learner; extraneous load is a result of superfluous processes that do not directly contribute to learning, and germane load is caused by learning processes that deal with intrinsic cognitive load. OBJECTIVES This paper discusses design guidelines that will decrease extraneous load, manage intrinsic load and optimise germane load. DISCUSSION Fifteen design guidelines are discussed. Extraneous load can be reduced by the use of goal-free tasks, worked examples and completion tasks, by integrating different sources of information, using multiple modalities, and by reducing redundancy. Intrinsic load can be managed by simple-to-complex ordering of learning tasks and working from low- to high-fidelity environments. Germane load can be optimised by increasing variability over tasks, applying contextual interference, and evoking self-explanation. The guidelines are also related to the expertise reversal effect, indicating that design guidelines for novice learners are different from guidelines for more experienced learners. Thus, well-designed instruction for novice learners is different from instruction for more experienced learners. Applications in health professional education and current research lines are discussed.

Chronic obstructive pulmonary disease phenotypes: the future of COPD.

Abstract: Significant heterogeneity of clinical presentation and disease progression exists within chronic obstructive pulmonary disease (COPD). Although FEV(1) inadequately describes this heterogeneity, a clear alternative has not emerged. The goal of phenotyping is to identify patient groups with unique prognostic or therapeutic characteristics, but significant variation and confusion surrounds use of the term "phenotype" in COPD. Phenotype classically refers to any observable characteristic of an organism, and up until now, multiple disease characteristics have been termed COPD phenotypes. We, however, propose the following variation on this definition: "a single or combination of disease attributes that describe differences between individuals with COPD as they relate to clinically meaningful outcomes (symptoms, exacerbations, response to therapy, rate of disease progression, or death)." This more focused definition allows for classification of patients into distinct prognostic and therapeutic subgroups for both clinical and research purposes. Ideally, individuals sharing a unique phenotype would also ultimately be determined to have a similar underlying biologic or physiologic mechanism(s) to guide the development of therapy where possible. It follows that any proposed phenotype, whether defined by symptoms, radiography, physiology, or cellular or molecular fingerprint will require an iterative validation process in which "candidate" phenotypes are identified before their relevance to clinical outcome is determined. Although this schema represents an ideal construct, we acknowledge any phenotype may be etiologically heterogeneous and that any one individual may manifest multiple phenotypes. We have much yet to learn, but establishing a common language for future research will facilitate our understanding and management of the complexity implicit to this disease.

6th International Consultation on Incontinence. Recommendations of the International Scientific Committee: Evaluation and treatment of urinary incontinence, pelvic organ prolapse and faecal incontinence

Abstract: Scientific report of the proceedings from the 6th International Consultation on Incontinence, (Tokyo 2016).

The Financing of R&D and Innovation

Abstract: Evidence on the “funding gap” for investment innovation is surveyed. The focus is on financial market reasons for underinvestment that exist even when externality-induced underinvestment is absent. We conclude that while small and new innovative firms experience high costs of capital that are only partly mitigated by the presence of venture capital, the evidence for high costs of R&D capital for large firms is mixed. Nevertheless, large established firms do appear to prefer internal funds for financing such investments and they manage their cash flow to ensure this. Evidence shows that there are limits to venture capital as a solution to the funding gap, especially in countries where public equity markets for VC exit are not highly developed. We conclude by suggesting areas for further research.

Appetite control: methodological aspects of the evaluation of foods

Abstract: This report describes a set of scientific procedures used to assess the impact of foods and food ingredients on the expression of appetite (psychological and behavioural). An overarching priority has been to enable potential evaluators of health claims about foods to identify justified claims and to exclude claims that are not supported by scientific evidence for the effect cited. This priority follows precisely from the principles set down in the PASSCLAIM report. The report allows the evaluation of the strength of health claims, about the effects of foods on appetite, which can be sustained on the basis of the commonly used scientific designs and experimental procedures. The report includes different designs for assessing effects on satiation as opposed to satiety, detailed coverage of the extent to which a change in hunger can stand alone as a measure of appetite control and an extensive discussion of the statistical procedures appropriate for handling data in this field of research. Because research in this area is continually evolving, new improved methodologies may emerge over time and will need to be incorporated into the framework. One main objective of the report has been to produce guidance on good practice in carrying out appetite research, and not to set down a series of commandments that must be followed.

Relative Role of Genetic Complement Abnormalities in Sporadic and Familial aHUS and Their Impact on Clinical Phenotype

Abstract: Background and objectives: Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Most childhood cases are caused by Shiga toxin–producing bacteria. The other form, atypical HUS (aHUS), accounts for 10% of cases and has a poor prognosis. Genetic complement abnormalities have been found in aHUS. Design, setting, participants, and measurements: We screened 273 consecutive patients with aHUS for complement abnormalities and studied their role in predicting clinical phenotype and response to treatment. We compared mutation frequencies and localization and clinical outcome in familial (82) and sporadic (191) cases. Results: In >70% of sporadic and familial cases, gene mutations, disease-associated factor H ( CFH ) polymorphisms, or anti-CFH autoantibodies were found. Either mutations or CFH polymorphisms were also found in the majority of patients with secondary aHUS, suggesting a genetic predisposition. Familial cases showed a higher prevalence of mutations in SCR20 of CFH and more severe disease than sporadic cases. Patients with CFH or THBD (thrombomodulin) mutations had the earliest onset and highest mortality. Membrane-cofactor protein ( MCP ) mutations were associated with the best prognosis. Plasma therapy induced remission in 55 to 80% of episodes in patients with CFH , C3, or THBD mutations or autoantibodies, whereas patients with CFI (factor I) mutations were poor responders. aHUS recurred frequently after kidney transplantation except for patients with MCP mutations. Conclusions: Results underline the need of genetic screening for all susceptibility factors as part of clinical management of aHUS and for identification of patients who could safely benefit from kidney transplant.

An evolutionary approach to understanding international business activity: The co-evolution of MNEs and the institutional environment

Abstract: This paper examines the co-evolution of MNE activities and institutions external and internal to the firm. We develop a theoretical framework for this analysis that draws on the more recent writings of Douglass North on institutions as a response to complex forms of uncertainty associated with the rise in global economic interconnectedness, and of Richard Nelson on the co-evolution of technology and institutions. We link historical changes in the character of MNE activities to changes in the institutional environment, and highlight the scope for firm-level creativity and institutional entrepreneurship that may lead to co-evolution with the environment. We argue that the main drivers for institutional entrepreneurship are now found in the increasing autonomy of MNE subsidiaries. Thus MNE agency derives from more decentralized forms of experimentation in international corporate networks, which competence-creating nodes of new initiatives can co-evolve with local institutions. Unlike most other streams of related literature, our approach connects patterns of institutional change in wider business systems with more micro processes of variety generation and experimentation within and across individual firms. This form of co-evolutionary analysis is increasingly important to understanding the interrelationships between MNE activities and public policy.

The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5

Abstract: Tumor hypoxia is a common microenvironmental factor that adversely influences tumor phenotype and treatment response. Cellular adaptation to hypoxia occurs through multiple mechanisms, including activation of the unfolded protein response (UPR). Recent reports have indicated that hypoxia activates a lysosomal degradation pathway known as autophagy, and here we show that the UPR enhances the capacity of hypoxic tumor cells to carry out autophagy, and that this promotes their survival. In several human cancer cell lines, hypoxia increased transcription of the essential autophagy genes microtubule-associated protein 1 light chain 3beta (MAP1LC3B) and autophagy-related gene 5 (ATG5) through the transcription factors ATF4 and CHOP, respectively, which are regulated by PKR-like ER kinase (PERK, also known as EIF2AK3). MAP1LC3B and ATG5 are not required for initiation of autophagy but mediate phagophore expansion and autophagosome formation. We observed that transcriptional induction of MAP1LC3B replenished MAP1LC3B protein that was turned over during extensive hypoxia-induced autophagy. Correspondingly, cells deficient in PERK signaling failed to transcriptionally induce MAP1LC3B and became rapidly depleted of MAP1LC3B protein during hypoxia. Consistent with these data, autophagy and MAP1LC3B induction occurred preferentially in hypoxic regions of human tumor xenografts. Furthermore, pharmacological inhibition of autophagy sensitized human tumor cells to hypoxia, reduced the fraction of viable hypoxic tumor cells, and sensitized xenografted human tumors to irradiation. Our data therefore demonstrate that the UPR is an important mediator of the hypoxic tumor microenvironment and that it contributes to resistance to treatment through its ability to facilitate autophagy.

Circulating MicroRNA-208b and MicroRNA-499 Reflect Myocardial Damage in Cardiovascular Disease

Abstract: Background— Small RNA molecules, called microRNAs, freely circulate in human plasma and correlate with varying pathologies In this study, we explored their diagnostic potential in a selection of prevalent cardiovascular disorders Methods and Results— MicroRNAs were isolated from plasmas from well-characterized patients with varying degrees of cardiac damage: (1) acute myocardial infarction, (2) viral myocarditis, (3) diastolic dysfunction, and (4) acute heart failure Plasma levels of selected microRNAs, including heart-associated (miR-1, -133a, -208b, and -499), fibrosis-associated (miR-21 and miR-29b), and leukocyte-associated (miR-146, -155, and -223) candidates, were subsequently assessed using real-time polymerase chain reaction Strikingly, in plasma from acute myocardial infarction patients, cardiac myocyte–associated miR-208b and -499 were highly elevated, 1600-fold ( P <0005) and 100-fold ( P <00005), respectively, as compared with control subjects Receiver operating characteristic curve analysis revealed an area under the curve of 094 ( P <10−10) for miR-208b and 092 ( P <10−9) for miR-499 Both microRNAs correlated with plasma troponin T, indicating release of microRNAs from injured cardiomyocytes In viral myocarditis, we observed a milder but significant elevation of these microRNAs, 30-fold and 6-fold, respectively Plasma levels of leukocyte-expressed microRNAs were not significantly increased in acute myocardial infarction or viral myocarditis patients, despite elevated white blood cell counts In patients with acute heart failure, only miR-499 was significantly elevated (2-fold), whereas no significant changes in microRNAs studied could be observed in diastolic dysfunction Remarkably, plasma microRNA levels were not affected by a wide range of clinical confounders, including age, sex, body mass index, kidney function, systolic blood pressure, and white blood cell count Conclusions— Cardiac damage initiates the detectable release of cardiomyocyte-specific microRNAs-208b and -499 into the circulation

Unpacking Black Boxes: Mechanisms and Theory Building in Evaluation:

Abstract: There is growing interest in the concept of ‘‘mechanism’’ across many areas of the social sciences. In the field of program and policy evaluation, a number of scholars have also emphasized the importance of causal mechanisms for explaining how and why programs work. However, there appears to be some ambiguity about the meaning and uses of mechanism-based thinking in both the social science and evaluation literature. In this article we attempt to clarify what is meant by mechanisms in the context of program evaluation by identifying three main characteristics of mechanisms and outlining a possible typology of mechanisms. A number of theoretical and practical implications for evaluators are also discussed, along with some precautions to consider when investigating mechanisms that might plausibly account for program outcomes.

Orthographic Depth and Its Impact on Universal Predictors of Reading A Cross-Language Investigation

Abstract: Alphabetic orthographies differ in the transparency of their letter-sound mappings, with English orthography being less transparent than other alphabetic scripts. The outlier status of English has led scientists to question the generality of findings based on English-language studies. We investigated the role of phonological awareness, memory, vocabulary, rapid naming, and nonverbal intelligence in reading performance across five languages lying at differing positions along a transparency continuum (Finnish, Hungarian, Dutch, Portuguese, and French). Results from a sample of 1,265 children in Grade 2 showed that phonological awareness was the main factor associated with reading performance in each language. However, its impact was modulated by the transparency of the orthography, being stronger in less transparent orthographies. The influence of rapid naming was rather weak and limited to reading and decoding speed. Most predictors of reading performance were relatively universal across these alphabetic languages, although their precise weight varied systematically as a function of script transparency.

The BioPAX community standard for pathway data sharing

Abstract: Biological Pathway Exchange (BioPAX) is a standard language to represent biological pathways at the molecular and cellular level and to facilitate the exchange of pathway data. The rapid growth of the volume of pathway data has spurred the development of databases and computational tools to aid interpretation; however, use of these data is hampered by the current fragmentation of pathway information across many databases with incompatible formats. BioPAX, which was created through a community process, solves this problem by making pathway data substantially easier to collect, index, interpret and share. BioPAX can represent metabolic and signaling pathways, molecular and genetic interactions and gene regulation networks. Using BioPAX, millions of interactions, organized into thousands of pathways, from many organisms are available from a growing number of databases. This large amount of pathway data in a computable form will support visualization, analysis and biological discovery.

Myocardial remodeling after infarction: the role of myofibroblasts

Abstract: Myofibroblasts have characteristics of fibroblasts and smooth muscle cells: they produce extracellular matrix and are able to contract. In so doing, they can contribute to tissue replacement and interstitial fibrosis following cardiac injury. The scar formed after myocardial injury is no longer considered to be passive tissue; it is an active playground where myofibroblasts play a role in collagen turnover and scar contraction. Maintaining the extracellular matrix in the scar is essential and can prevent dilatation of the infarct area leading to heart failure. On the other hand, extracellular matrix deposition at sites remote from the infarct area can lead to cardiac stiffness, an inevitable process of myocardial remodeling that occurs in the aftermath of myocardial infarction and constitutes the basis of the development of heart failure. Defining molecular targets on myofibroblasts in conjunction with establishing the feasibility of molecular imaging of these cells might facilitate the early detection and treatment of patients who are at risk of developing heart failure after myocardial infarction.

Revised nomenclature and classification of inherited ichthyoses: Results of the First Ichthyosis Consensus Conference in Sorèze 2009

Abstract: Background Inherited ichthyoses belong to a large, clinically and etiologically heterogeneous group of mendelian disorders of cornification, typically involving the entire integument. Over the recent years, much progress has been made defining their molecular causes. However, there is no internationally accepted classification and terminology. Objective We sought to establish a consensus for the nomenclature and classification of inherited ichthyoses. Methods The classification project started at the First World Conference on Ichthyosis in 2007. A large international network of expert clinicians, skin pathologists, and geneticists entertained an interactive dialogue over 2 years, eventually leading to the First Ichthyosis Consensus Conference held in Soreze, France, on January 23 and 24, 2009, where subcommittees on different issues proposed terminology that was debated until consensus was reached. Results It was agreed that currently the nosology should remain clinically based. "Syndromic" versus "nonsyndromic" forms provide a useful major subdivision. Several clinical terms and controversial disease names have been redefined: eg, the group caused by keratin mutations is referred to by the umbrella term, "keratinopathic ichthyosis"–under which are included epidermolytic ichthyosis, superficial epidermolytic ichthyosis, and ichthyosis Curth-Macklin. "Autosomal recessive congenital ichthyosis" is proposed as an umbrella term for the harlequin ichthyosis, lamellar ichthyosis, and the congenital ichthyosiform erythroderma group. Limitations As more becomes known about these diseases in the future, modifications will be needed. Conclusion We have achieved an international consensus for the classification of inherited ichthyosis that should be useful for all clinicians and can serve as reference point for future research.

Behavioural treatment for chronic low-back pain

Abstract: BACKGROUND: Behavioural treatment, commonly used in the treatment of chronic low-back pain (CLBP), is primarily focused at reducing disability through the modification of environmental contingencies and cognitive processes. In general, three behavioural treatment approaches are distinguished: operant, cognitive and respondent. OBJECTIVES: To determine if behavioural therapy is more effective than reference treatments for CLBP, and which type of behavioural treatment is most effective. SEARCH STRATEGY: We searched the CENTRAL, MEDLINE, EMBASE, and PsycLIT databases up to October 2003. References of identified randomised trials and relevant systematic reviews were screened. SELECTION CRITERIA: Only randomised trials on behavioural treatment for non-specific CLBP were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the methodological quality and extracted the data. The magnitude of effect was assessed by computing a pooled effect size for post-treatment and long-term results for each comparison, for each domain (i.e., behavioural outcomes, overall improvement, back pain specific and generic functional status, return to work, and pain intensity) using the random effects model. MAIN RESULTS: Seven studies (33%) were considered high quality. Comparing behavioural treatment to waiting list control (WLC) revealed strong evidence (4 trials, 134 people) in favour of a combined respondent-cognitive therapy for a medium positive effect on pain, and moderate evidence (2 trials, 39 people) in favour of progressive relaxation for a large positive effect on pain and behavioural outcomes (short-term only). When comparing operant treatment to WLC no significant differences could be detected on general functional status (strong evidence: 2 trials, 87 people) or on behavioural outcomes (moderate evidence; 3 trials, 153 people) (short-term only). There is limited evidence (1 trial, 98 people) that a graded activity program in an industrial setting is more effective than usual care for early return to work and reduced long-term sick leave. There is limited evidence (1 trail, 39 people) that there are no differences between behavioural treatment and exercises. Finally, there is moderate evidence (6 trials, 210 people) that there are no significant differences in short-term and long-term effectiveness when behavioural components are added to usual treatment programs for CLBP (i.e. physiotherapy, back education) on pain, generic functional status and behavioural outcomes. AUTHORS' CONCLUSIONS: Combined respondent-cognitive therapy and progressive relaxation therapy are more effective than WLC on short-term pain relief. However, it is unknown whether these results sustain in the long term. No significant differences could be detected between behavioural treatment and exercise therapy. Whether clinicians should refer patients with CLBP to behavioural treatment programs or to active conservative treatment cannot be concluded from this review.

Customer-to-customer interactions: Broadening the scope of word of mouth research

Abstract: The increasing emphasis on understanding the antecedents and consequences of customer-to-customer (C2C) interactions is one of the essential developments of customer management in recent years. This interest is driven much by new online environments that enable customers to be connected in numerous new ways and also supply researchers’ access to rich C2C data. These developments present an opportunity and a challenge for firms and researchers who need to identify the aspects of C2C research on which to focus, as well as develop research methods that take advantage of these new data. The aim here is to take a broad view of C2C interactions and their effects and to highlight areas of significant research interest in this domain. The authors look at four main areas: the different dimensions of C2C interactions; social system issues related to individuals and to online communities; C2C context issues including product, channel, relational and market characteristics; and the identification, modeling, and assessment of business outcomes of C2C interactions.

The Hofstede model: Applications to global branding and advertising strategy and research

Abstract: Recent years have seen increasing interest in the consequences of culture for global marketing and advertising. Many recent studies point at the necessity of adapting branding and advertising strategies to the culture of the consumer. In order to understand cultural differences, several models have been developed of which the Hofstede model is the most used. This article describes elements of this model that are most relevant to branding and advertising, and reviews studies that have used the model for aspects of international branding and for advertising research. It provides some cautious remarks about applying the model. Suggestions for more cross-cultural research are added.

Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier.

Abstract: Lactobacillus plantarum, a commensal bacterium of humans, has been proposed to enhance the intestinal barrier, which is compromised in a number of intestinal disorders. To study the effect of L. plantarum strain WCFS1 on human barrier function, healthy subjects were administered L. plantarum or placebo in the duodenum for 6 h by means of a feeding catheter. The scaffold protein zonula occludens (ZO)-1 and transmembrane protein occludin were found to be significantly increased in the vicinity of the tight-junction (TJ) structures, which form the paracellular seal between cells of the epithelium. In an in vitro model of the human epithelium, L. plantarum induced translocation of ZO-1 to the TJ region; however, the effects on occludin were minor compared with those seen in vivo. L. plantarum was shown to activate Toll-like receptor 2 (TLR2) signaling, and treatment of Caco-2 monolayers with the TLR2 agonist Pam3-Cys-SK4(PCSK) significantly increased fluorescent staining of occludin in the TJ. Pretreatment of Caco-2 monolayers with L. plantarum or PCSK significantly attenuated the effects of phorbol ester-induced dislocation of ZO-1 and occludin and the associated increase in epithelial permeability. Our results identifying commensal bacterial stimulation of TLR2 in the gut epithelium as a regulator of epithelial integrity have important implications for understanding probiotic mechanisms and the control of intestinal homeostasis.