Evaluation of an education and activation programme to prevent chronic shoulder complaints: design of an RCT [ISRCTN71777817]

BACKGROUND: About half of all newly presented episodes of shoulder complaints (SC) in general practice are reported to last for at least six months. Early interventions aimed at the psychological and social determinants of SC are not common in general practice, although such interventions might prevent the development of chronic SC. The Education and Activation Programme (EAP) consists of an educational part and a time-contingent activation part. The aim of the EAP is to provide patients with the proper cognitions by means of education, and to stimulate adequate behaviour through advice on activities of daily living. DESIGN: The article describes the design of a randomised clinical trial (RCT) to evaluate the effectiveness and cost-effectiveness of an EAP in addition to usual care, compared to usual care only, in the prevention of chronic SC after six months. It also describes the analysis of the cost and effect balance. Patients suffering from SC for less than three months are recruited in general practice and through open recruitment. A trained general practitioner or a trained therapist administers the EAP. Primary outcome measures are patient-perceived recovery, measured by self-assessment on a seven-point scale, and functional limitations in activities of daily living. Questionnaires are used to study baseline measures, prognostic measures, process measures and outcome measures. DISCUSSION: The inclusion of patients in the study lasted until December 31(st )2003. Data collection is to end in June 2004

Effectiveness of behavioural graded activity compared with physiotherapy treatment in chronic neck pain: design of a randomised clinical trial [ISRCTN88733332]

BACKGROUND: Chronic neck pain is a common complaint in the Netherlands with a point prevalence of 14.3%. Patients with chronic neck pain are often referred to a physiotherapist and, although many treatments are available, it remains unclear which type of treatment is to be preferred. The objective of this article is to present the design of a randomised clinical trial, Ephysion, which examines the clinical and cost effectiveness of behavioural graded activity compared with a physiotherapy treatment for patients with chronic non-specific neck pain. METHODS: Eligible patients with non-specific neck pain persisting longer than 3 months will be randomly allocated to either the behavioural graded activity programme or to the physiotherapy treatment. The graded activity programme is based on an operant approach, which uses a time-contingent method to increase the patient's activity level. This treatment is compared with physiotherapy treatment using a pain-contingent method. Primary treatment outcome is the patient's global perceived effect concerning recovery from the complaint. Global perceived effect on daily functioning is also explored as primary outcome to establish the impact of treatment on daily activity. Direct and indirect costs will also be assessed. Secondary outcomes include the patient's main complaints, pain intensity, medical consumption, functional status, quality of life, and psychological variables. Recruitment of patients will take place up to the end of the year 2004 and follow-up measurement will continue until end 2005

Symptom increase following a functional capacity evaluation in patients with chronic low back pain:An explorative study of safety

Introduction: This study was performed to study intensity and duration of symptom increase following an FCE and to explore safety of an FCE. Methods: Included were 92 patients with chronic low back pain (CLBP), mean age 38.5 years, mean self-reported disability 12.5 (Roland Morris Disability Questionnaire). All patients underwent an FCE. Symptom increase was measured with a 2-item questionnaire. Operational definition for safety: no formal complaint filed and symptom increase to occur only temporarily. Results: No formal complaints were filed (n=92). In total, 54 patients returned the questionnaire (59%; 'responders'). Of the responders, 76% reported increased symptom intensity after an FCE, ranging from 'little increase' to 'severe increase'. Symptoms of all responders returned to pre-FCE level. Duration of symptom increase of the responders ranged from 1 day to 3 weeks. Symptom increase resided to pre-FCE level within 1 week in 93% of the responders. Symptom increase was weakly related to self-reported disability (r=0.38, p <0.05). Except for gender, differences between responders and non-responders were non-significant. Conclusion: A temporary increase in symptom intensity following an FCE is common. Within the operational definitions of safety used in this study, assessment of functional capacity of patients with CLBP appears safe

Iterative Evolution of Sympatric Seacow (Dugongidae, Sirenia) Assemblages during the Past ∼26 Million Years

Extant sirenians show allopatric distributions throughout most of their range. However, their fossil record shows evidence of multispecies communities throughout most of the past ∼26 million years, in different oceanic basins. Morphological differences among co-occurring sirenian taxa suggest that resource partitioning played a role in structuring these communities. We examined body size and ecomorphological differences (e.g., rostral deflection and tusk morphology) among sirenian assemblages from the late Oligocene of Florida, early Miocene of India and early Pliocene of Mexico; each with three species of the family Dugongidae. Although overlapping in several ecomorphological traits, each assemblage showed at least one dominant trait in which coexisting species differed. Fossil sirenian occurrences occasionally are monotypic, but the assemblages analyzed herein show iterative evolution of multispecies communities, a phenomenon unparalleled in extant sirenian ecology. As primary consumers of seagrasses, these communities likely had a strong impact on past seagrass ecology and diversity, although the sparse fossil record of seagrasses limits direct comparisons. Nonetheless, our results provide robust support for previous suggestions that some sirenians in these extinct assemblages served as keystone species, controlling the dominance of climax seagrass species, permitting more taxonomically diverse seagrass beds (and sirenian communities) than many of those observed today

Molecular phylogenetics and temporal diversification in the genus Aeromonas based on the sequences of five housekeeping genes

Several approaches have been developed to estimate both the relative and absolute rates of speciation and extinction within clades based on molecular phylogenetic reconstructions of evolutionary relationships, according to an underlying model of diversification. However, the macroevolutionary models established for eukaryotes have scarcely been used with prokaryotes. We have investigated the rate and pattern of cladogenesis in the genus Aeromonas (γ-Proteobacteria, Proteobacteria, Bacteria) using the sequences of five housekeeping genes and an uncorrelated relaxed-clock approach. To our knowledge, until now this analysis has never been applied to all the species described in a bacterial genus and thus opens up the possibility of establishing models of speciation from sequence data commonly used in phylogenetic studies of prokaryotes. Our results suggest that the genus Aeromonas began to diverge between 248 and 266 million years ago, exhibiting a constant divergence rate through the Phanerozoic, which could be described as a pure birth process

Microfluidics: reframing biological enquiry

The underlying physical properties of microfluidic tools have led to new biological insights through the development of microsystems that can manipulate, mimic and measure biology at a resolution that has not been possible with macroscale tools. Microsystems readily handle sub-microlitre volumes, precisely route predictable laminar fluid flows and match both perturbations and measurements to the length scales and timescales of biological systems. The advent of fabrication techniques that do not require highly specialized engineering facilities is fuelling the broad dissemination of microfluidic systems and their adaptation to specific biological questions. We describe how our understanding of molecular and cell biology is being and will continue to be advanced by precision microfluidic approaches and posit that microfluidic tools - in conjunction with advanced imaging, bioinformatics and molecular biology approaches - will transform biology into a precision science

Microfluidic affinity and ChIP-seq analyses converge on a conserved FOXP2-binding motif in chimp and human, which enables the detection of evolutionarily novel targets

The transcription factor forkhead box P2 (FOXP2) is believed to be important in the evolution of human speech. A mutation in its DNA-binding domain causes severe speech impairment. Humans have acquired two coding changes relative to the conserved mammalia

Phosphatase specificity principles uncovered by MRBLE:Dephos and global substrate identification.

Phosphoprotein phosphatases (PPPs) regulate major signaling pathways, but the determinants of phosphatase specificity are poorly understood. This is because methods to investigate this at scale are lacking. Here, we develop a novel in vitro assay, MRBLE:Dephos, that allows multiplexing of dephosphorylation reactions to determine phosphatase preferences. Using MRBLE:Dephos, we establish amino acid preferences of the residues surrounding the dephosphorylation site for PP1 and PP2A-B55, which reveals common and unique preferences. To compare the MRBLE:Dephos results to cellular substrates, we focused on mitotic exit that requires extensive dephosphorylation by PP1 and PP2A-B55. We use specific inhibition of PP1 and PP2A-B55 in mitotic exit lysates coupled with phosphoproteomics to identify more than 2,000 regulated sites. Importantly, the sites dephosphorylated during mitotic exit reveal key signatures that are consistent with MRBLE:Dephos. Furthermore, integration of our phosphoproteomic data with mitotic interactomes of PP1 and PP2A-B55 provides insight into how binding of phosphatases to substrates shapes dephosphorylation. Collectively, we develop novel approaches to investigate protein phosphatases that provide insight into mitotic exit regulation