Developing, delivering and documenting rehabilitation in a multi-centre randomised controlled surgical trial: experiences from the ProFHER trial

OBJECTIVES: A rigorous approach to developing, delivering and documenting rehabilitation within randomised controlled trials of surgical interventions is required to underpin the generation of reliable and usable evidence. This article describes the key processes used to ensure provision of good quality and comparable rehabilitation to all participants of a multi-centre randomised controlled trial comparing surgery with conservative treatment of proximal humeral fractures in adults. METHODS: These processes included the development of a patient information leaflet on self-care during sling immobilisation, the development of a basic treatment physiotherapy protocol that received input and endorsement by specialist physiotherapists providing patient care, and establishing an expectation for the provision of home exercises. Specially designed forms were also developed to facilitate reliable reporting of the physiotherapy care that patients received. RESULTS: All three initiatives were successfully implemented, alongside the measures to optimise the documentation of physiotherapy. Thus, all participating sites that recruited patients provided the sling immobilisation leaflet, all adhered to the physiotherapy protocol and all provided home exercises. There was exemplary completion of the physiotherapy forms that often reflected a complex patient care pathway. These data demonstrated equal and high access to and implementation of physiotherapy between groups, including the performance of home exercises. CONCLUSION: In order to increase the validity and relevance of the evidence from trials of surgical interventions and meet international reporting standards, careful attention to study design, conduct and reporting of the intrinsic rehabilitation components is required. The involvement of rehabilitation specialists is crucial to achieving this. Cite this article: Bone Joint Res 2014;3:335–40

The In Vivo Wear Resistance of 12 Composite Resins

: The in vivo wear resistance of 12 composite resins were compared with an amalgam control using the Latin Square experimental design. Sixteen edentulous patients wearing specially designed complete dentures formed the experimental population. Materials and Methods : The Michigan Computer Graphics Measurement System was used to digitize the surface of the control and composite resin samples before and after 3-month test periods to obtain wear data. The 12 composite resins selected for this investigation based on their published composite classification types were seven fine particle composites, three blends, and two microfilled composite resins. The Latin Square experimental design was found to be valid with the factor of material being statistically different at the 5% level of significance. Wear was computed as volume loss (mm 3 /mm 2 ), and all of the composites studied had more wear than the amalgam control ( P = .001). Results : After 3 months, the mean (error) of wear of the amalgam was 0.028 (0.006). Means (error) of wear for the 12 composites were ranked from most to least wear by mean wear volume loss. Conclusions : The absence of any relationship between mean wear volume loss and the volume percentage filler was confirmed by the correlation coefficient r = -0.158.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72960/1/j.1532-849X.1992.tb00419.x.pd

Modeling the dynamics of glacial cycles

This article is concerned with the dynamics of glacial cycles observed in the geological record of the Pleistocene Epoch. It focuses on a conceptual model proposed by Maasch and Saltzman [J. Geophys. Res.,95, D2 (1990), pp. 1955-1963], which is based on physical arguments and emphasizes the role of atmospheric CO2 in the generation and persistence of periodic orbits (limit cycles). The model consists of three ordinary differential equations with four parameters for the anomalies of the total global ice mass, the atmospheric CO2 concentration, and the volume of the North Atlantic Deep Water (NADW). In this article, it is shown that a simplified two-dimensional symmetric version displays many of the essential features of the full model, including equilibrium states, limit cycles, their basic bifurcations, and a Bogdanov-Takens point that serves as an organizing center for the local and global dynamics. Also, symmetry breaking splits the Bogdanov-Takens point into two, with different local dynamics in their neighborhoods

Bone marrow mesenchymal stem cells do not enhance intra-synovial tendon healing despite engraftment and homing to niches within the synovium

Intra-synovial tendon injuries display poor healing, which often results in reduced functionality and pain. A lack of effective therapeutic options has led to experimental approaches to augment natural tendon repair with autologous mesenchymal stem cells (MSCs) although the effects of the intra-synovial environment on the distribution, engraftment and functionality of implanted MSCs is not known. This study utilised a novel sheep model which, although in an anatomically different location, more accurately mimics the mechanical and synovial environment of the human rotator cuff, to determine the effects of intra-synovial implantation of MSCs

Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain

The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn^(2+) into the prefrontal cortex indicated that DAT KO mice have a truncated Mn^(2+) distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn^(2+) transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatal-thalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here

Respiratory syncytial virus infection is associated with an altered innate immunity and a heightened pro-inflammatory response in the lungs of preterm lambs

<p>Abstract</p> <p>Introduction</p> <p>Factors explaining the greater susceptibility of preterm infants to severe lower respiratory infections with respiratory syncytial virus (RSV) remain poorly understood. Fetal/newborn lambs are increasingly appreciated as a model to study key elements of RSV infection in newborn infants due to similarities in lung alveolar development, immune response, and susceptibility to RSV. Previously, our laboratory demonstrated that preterm lambs had elevated viral antigen and developed more severe lesions compared to full-term lambs at seven days post-infection. Here, we compared the pathogenesis and immunological response to RSV infection in lungs of preterm and full-term lambs.</p> <p>Methods</p> <p>Lambs were delivered preterm by Caesarian section or full-term by natural birth, then inoculated with bovine RSV (bRSV) via the intratracheal route. Seven days post-infection, lungs were collected for evaluation of cytokine production, histopathology and cellular infiltration.</p> <p>Results</p> <p>Compared to full-term lambs, lungs of preterm lambs had a heightened pro-inflammatory response after infection, with significantly increased MCP-1, MIP-1α, IFN-γ, TNF-α and PD-L1 mRNA. RSV infection in the preterm lung was characterized by increased epithelial thickening and periodic acid-Schiff staining, indicative of glycogen retention. Nitric oxide levels were decreased in lungs of infected preterm lambs compared to full-term lambs, indicating alternative macrophage activation. Although infection induced significant neutrophil recruitment into the lungs of preterm lambs, neutrophils produced less myeloperoxidase than those of full-term lambs, suggesting decreased functional activation.</p> <p>Conclusions</p> <p>Taken together, our data suggest that increased RSV load and inadequate immune response may contribute to the enhanced disease severity observed in the lungs of preterm lambs.</p

The Effect of Adult Aggression on Habitat Selection by Settlers of Two Coral-Dwelling Damselfishes

Coral-reef fishes experience a major challenge when facing settlement in a multi-threat environment, within which, using settlement cues, they need to select a suitable site. Studies in laboratories and artificial setups have shown that the presence of conspecific adults often serves as a positive settlement cue, whose value is explained by the increased survival of juveniles in an already proven fit environment. However, settlement in already inhabited corals may expose the recruits to adult aggression. Daily observations and manipulation experiments were used in the present study, which was conducted in the natural reef. We revealed differential strategies of settlers, which do not necessarily join conspecific adults. Dascyllus aruanus prefer to settle near (not with) their aggressive adults, and to join them only after gaining in size; whereas Dascyllus marginatus settlers in densely populated reefs settle independently of their adult distribution. Our results present different solutions to the challenges faced by fish recruits while selecting their microhabitat, and emphasize the complexity of habitat selection by the naïve settlers. Although laboratory experiments are important to the understanding of fish habitat selection, further studies in natural habitats are essential in order to elucidate the actual patterns of settlement and habitat selection, which are crucial for the survival of coral-reef fish populations

Circumstellar disks and planets. Science cases for next-generation optical/infrared long-baseline interferometers

We present a review of the interplay between the evolution of circumstellar disks and the formation of planets, both from the perspective of theoretical models and dedicated observations. Based on this, we identify and discuss fundamental questions concerning the formation and evolution of circumstellar disks and planets which can be addressed in the near future with optical and infrared long-baseline interferometers. Furthermore, the importance of complementary observations with long-baseline (sub)millimeter interferometers and high-sensitivity infrared observatories is outlined.Comment: 83 pages; Accepted for publication in "Astronomy and Astrophysics Review"; The final publication is available at http://www.springerlink.co

Diagnostic and mechanistic implications of serum free light chains, albumin and alpha-fetoprotein in hepatocellular carcinoma

Background: Mass spectroscopy analysis suggested low serum albumin and high immunoglobulin free light chain (sFLC) levels may have diagnostic value in hepatocellular carcinoma (HCC). Our aims were to apply quantitative assays to confirm these observations, determine their diagnostic utility, and investigate the mechanisms involved. Methods: Albumin, sFLC, routine liver and renal function tests were measured in patients with chronic liver disease with (n=102) and without (n=113) HCC. The discriminant performance was compared with the current standard serological test alpha-fetoprotein (AFP) using receiver operating characteristic (ROC) and area under the curve (AUC) analyses. Results: sFLC and serum albumin were each confirmed to have discriminatory utility in HCC with AUC values of 0.7 and 0.8, respectively. sFLC were strongly correlated with gammaglobulin levels and both these were inversely related to serum albumin levels. The discriminatory utility of sFLC was retained after adjusting for renal and liver function. Conclusions: Serum levels of sFLC and albumin were strongly associated with HCC as predicted by mass spectroscopy. Discrimination of HCC by AFP was improved by the addition of either albumin or sFLC. Larger prospective studies are required to determine how AFP, sFLC and albumin might be combined in a useful diagnostic approach for HCC