Biomechanical spinal growth modulation and progressive adolescent scoliosis – a test of the 'vicious cycle' pathogenetic hypothesis: Summary of an electronic focus group debate of the IBSE

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE) introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The text for this debate was written by Dr Ian A Stokes. It evaluates the hypothesis that in progressive scoliosis vertebral body wedging during adolescent growth results from asymmetric muscular loading in a "vicious cycle" (vicious cycle hypothesis of pathogenesis) by affecting vertebral body growth plates (endplate physes). A frontal plane mathematical simulation tested whether the calculated loading asymmetry created by muscles in a scoliotic spine could explain the observed rate of scoliosis increase by measuring the vertebral growth modulation by altered compression. The model deals only with vertebral (not disc) wedging. It assumes that a pre-existing scoliosis curve initiates the mechanically-modulated alteration of vertebral body growth that in turn causes worsening of the scoliosis, while everything else is anatomically and physiologically 'normal' The results provide quantitative data consistent with the vicious cycle hypothesis. Dr Stokes' biomechanical research engenders controversy. A new speculative concept is proposed of vertebral symphyseal dysplasia with implications for Dr Stokes' research and the etiology of AIS. What is not controversial is the need to test this hypothesis using additional factors in his current model and in three-dimensional quantitative models that incorporate intervertebral discs and simulate thoracic as well as lumbar scoliosis. The growth modulation process in the vertebral body can be viewed as one type of the biologic phenomenon of mechanotransduction. In certain connective tissues this involves the effects of mechanical strain on chondrocytic metabolism a possible target for novel therapeutic intervention

Targeting of alpha(v) integrin identifies a core molecular pathway that regulates fibrosis in several organs

Myofibroblasts are the major source of extracellular matrix components that accumulate during tissue fibrosis, and hepatic stellate cells (HSCs) are the major source of myofibroblasts in the liver. To date, robust systems to genetically manipulate these cells have not existed. We report that Pdgfrb-Cre inactivates genes in murine HSCs with high efficiency. We used this system to delete the αv integrin subunit because of the suggested role of multiple αv integrins as central mediators of fibrosis in multiple organs. Depletion of the αv integrin subunit in HSCs protected mice from CCl(4)-induced hepatic fibrosis, whereas global loss of αvβ3, αvβ5 or αvβ6 or conditional loss of αvβ8 on HSCs did not. Pdgfrb-Cre effectively targeted myofibroblasts in multiple organs, and depletion of αv integrins using this system was also protective in models of pulmonary and renal fibrosis. Critically, pharmacological blockade of αv integrins by a novel small molecule (CWHM 12) attenuated both liver and lung fibrosis, even when administered after fibrosis was established. These data identify a core pathway that regulates fibrosis, and suggest that pharmacological targeting of all αv integrins may have clinical utility in the treatment of patients with a broad range of fibrotic diseases

Comparison of radiogrammetrical metacarpal indices in children and reference data from the First Zurich Longitudinal Study

BACKGROUND: A number of radiogrammetrical metacarpal indices are in use, some of which have been adapted for children. OBJECTIVE: The purpose of this study was to compare four known indices-bone mineral density (BMD), relative cortical area, Exton-Smith index, bending breaking resistance index-and the more recently defined pediatric bone index (PBI) according to the two criteria of minimum height dependence and minimum variability in children of equal bone age. MATERIALS AND METHODS: A total of 3,121 left-hand radiographs from 231 healthy Caucasian children ranging in age from 3 to 19 years old were analysed using BoneXpert®, a programme for automatic analysis of hand radiographs and assessment of bone age. RESULTS: Dependence on height for chronological age or bone age and the mean relative standard deviation were lowest in the PBI for both genders pooled. The differences in height dependence were statistically significant and are shown to be clinically relevant. Reference data for PBI are presented. CONCLUSION: PBI may be a better indicator than BMD for bone health in children; however, verification in a clinical group is needed

The definition of placebo in the informed consent forms of clinical trials

Aim: Lack of knowledge concerning the nature of placebo and why it is necessary may influence the participation of patients in clinical trials. The objective of the present study is to review how placebo is described in written information for participants in clinical trials to be evaluated by a Human Research Ethics Committee. Methods: All research protocols submitted for evaluation in a Spanish hospital during 2007–2013 were reviewed. The main characteristics of the studies using a placebo were collected. Three authors read each of them to determine how the term “placebo” was explained and if there was any comment on its efficacy and safety. Results: Two thousand seven-hundred and forty research protocols were evaluated, of which three hundred and fifty-nine used a placebo. Pharmaceutical companies sponsored most placebo-controlled clinical trials (91.9%), and phase III studies were the commonest (59.9%). Oncology (15.0%), cardiology (14.2%), and neurology (13.1%) made the greatest contributions. A review of the informed consent forms showed that placebo was described in a similar manner in most studies: the explanation was limited to between four and eight words. Very few gave information about the risks of its use or adverse reactions from its administration. None of the studies provided details about the placebo effect. And 23 lacked any information about placebo at all. Conclusions: Explanations about placebo in informed consent forms is often scarce, and information about the placebo effect and associated risks are absent. This situation may influence a full understanding of placebo by participants in clinical trials and might reduce their informed decision to participate.The study was supported in part by a grant from Victor Grifols i Lucas Foundation (2010-2011). Astrid Hernández is the recipient of a predoctoral fellowship from the Spanish Agency for International Development Cooperation. No external funding source had any role in the design or interpretation of the data of the stud

An Unsupervised Acoustic Description of Fish Schools and the Seabed in Three Fishing Regions Within the Northern Demersal Scalefish Fishery (NDSF, Western Australia)

Fisheries acoustics is now a standard tool for monitoring marine organisms. Another use of active-acoustics techniques is the potential to qualitatively describe fish school and seafloor characteristics or the distribution of fish density hotspots. Here, we use a geostatistical approach to describe the distribution of acoustic density hotspots within three fishing regions of the Northern Demersal Scalefish Fishery in Western Australia. This revealed a patchy distribution of hotspots within the three regions, covering almost half of the total areas. Energetic, geometric and bathymetric descriptors of acoustically identified fish schools were clustered using robust sparse k-means clustering with a Clest algorithm to determine the ideal number of clusters. Identified clusters were mainly defined by the energetic component of the school. Seabed descriptors considered were depth, roughness, first bottom length, maximum SvSv , kurtosis, skewness and bottom rise time. The ideal number of bottom clusters (maximisation rule with D-Index, Hubert Score and Weighted Sum of Squares), following the majority rule, was three. Cluster 1 (mainly driven by depth) was the sole type present in Region 1, Cluster 2 (mainly driven by roughness and maximum Sv)Sv) dominated Region 3, while Region 2 was split up almost equally between Cluster 2 and 3. Detection of indicator species for the three seabed clusters revealed that the selected clusters could be related to biological information. Goldband snapper and miscellaneous fish were indicators for Cluster 1; Cods, Lethrinids, Red Emperor and other Lutjanids were linked with Cluster 2, while Rankin Cod and Triggerfish were indicators for Cluster 3