Braces optimized with computer-assisted design and simulations are lighter, more comfortable, and more efficient than plaster-cast braces for the treatment of adolescent idiopathic scoliosis

Study Design Feasibility study to compare the effectiveness of 2 brace design and fabrication methods for treatment of adolescent idiopathic scoliosis: a standard plaster-cast method and a computational method combining computer-aided design and fabrication and finite element simulation. Objectives To improve brace design using a new brace design method. Summary of Background Data Initial in-brace correction and patient's compliance to treatment are important factors for brace efficiency. Negative cosmetic appearance and functional discomfort resulting from pressure points, humidity, and restriction of movement can cause poor compliance with the prescribed wearing schedule. Methods A total of 15 consecutive patients with brace prescription were recruited. Two braces were designed and fabricated for each patient: a standard thoracolumbo-sacral orthosis brace fabricated using plaster-cast method and an improved brace for comfort (NewBrace) fabricated using a computational method combining computer-aided design and fabrication software (Rodin4D) and a simulation platform. Three-dimensional reconstructions of the torso and the trunk skeleton were used to create a personalized finite element model, which was used for brace design and predict correction. Simulated pressures on the torso and distance between the brace and patient's skin were used to remove ineffective brace material situated at more than 6 mm from the patient's skin. Biplanar radiographs of the patient wearing each brace were taken to compare their effectiveness. Patients filled out a questionnaire to compare their comfort. Results NewBraces were 61% thinner and had 32% less material than standard braces with equivalent correction. NewBraces were more comfortable (11 of 15 patients) or equivalent to (4 of 15 cases) standard braces. Simulated correction was simulated within 5° compared with in-brace results. Conclusions This study demonstrates the feasibility of designing lighter and more comfortable braces with correction equivalent to standard braces. This design platform has the potential to further improve brace correction efficiency and its compliance

Abundance and Distribution of Enteric Bacteria and Viruses in Coastal and Estuarine Sediments—a Review

The long term survival of fecal indicator organisms (FIOs) and human pathogenic microorganisms in sediments is important from a water quality, human health and ecological perspective. Typically, both bacteria and viruses strongly associate with particulate matter present in freshwater, estuarine and marine environments. This association tends to be stronger in finer textured sediments and is strongly influenced by the type and quantity of clay minerals and organic matter present. Binding to particle surfaces promotes the persistence of bacteria in the environment by offering physical and chemical protection from biotic and abiotic stresses. How bacterial and viral viability and pathogenicity is influenced by surface attachment requires further study. Typically, long-term association with surfaces including sediments induces bacteria to enter a viable-but-non-culturable (VBNC) state. Inherent methodological challenges of quantifying VBNC bacteria may lead to the frequent under-reporting of their abundance in sediments. The implications of this in a quantitative risk assessment context remain unclear. Similarly, sediments can harbor significant amounts of enteric viruses, however, the factors regulating their persistence remains poorly understood. Quantification of viruses in sediment remains problematic due to our poor ability to recover intact viral particles from sediment surfaces (typically <10%), our inability to distinguish between infective and damaged (non-infective) viral particles, aggregation of viral particles, and inhibition during qPCR. This suggests that the true viral titre in sediments may be being vastly underestimated. In turn, this is limiting our ability to understand the fate and transport of viruses in sediments. Model systems (e.g., human cell culture) are also lacking for some key viruses, preventing our ability to evaluate the infectivity of viruses recovered from sediments (e.g., norovirus). The release of particle-bound bacteria and viruses into the water column during sediment resuspension also represents a risk to water quality. In conclusion, our poor process level understanding of viral/bacterial-sediment interactions combined with methodological challenges is limiting the accurate source apportionment and quantitative microbial risk assessment for pathogenic organisms associated with sediments in aquatic environments

Force balance at the magnetopause determined with MMS: Application to flux transfer events

The Magnetospheric Multiscale mission (MMS) consists of four identical spacecraft forming a closely separated (≤10 km) and nearly regular tetrahedron. This configuration enables the decoupling of spatial and temporal variations and allows the calculation of the spatial gradients of plasma and electromagnetic field quantities. We make full use of the well cross‐calibrated MMS magnetometers and fast plasma instruments measurements to calculate both the magnetic and plasma forces in flux transfer events (FTEs) and evaluate the relative contributions of different forces to the magnetopause momentum variation. This analysis demonstrates that some but not all FTEs, consistent with previous studies, are indeed force‐free structures in which the magnetic pressure force balances the magnetic curvature force. Furthermore, we contrast these events with FTE events that have non‐force‐free signatures.Key PointsDemonstrates flux transfer events are not necessarily force freeFinds that in non‐force‐free FTEs, the magnetic force is balanced by the ion pressure gradient force; the electron pressure can be ignoredMinimum variance analysis on the magnetic pressure gradient force gives the best estimate of the axial direction of flux ropesPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135579/1/grl55264_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135579/2/grl55264.pd

Mesenchymal Stem Cell Transition to Tumor-Associated Fibroblasts Contributes to Fibrovascular Network Expansion and Tumor Progression

Tumor associated fibroblasts (TAF), are essential for tumor progression providing both a functional and structural supportive environment. TAF, known as activated fibroblasts, have an established biological impact on tumorigenesis as matrix synthesizing or matrix degrading cells, contractile cells, and even blood vessel associated cells. The production of growth factors, cytokines, chemokines, matrix-degrading enzymes, and immunomodulatory mechanisms by these cells augment tumor progression by providing a suitable environment. There are several suggested origins of the TAF including tissue-resident, circulating, and epithelial-to-mesenchymal-transitioned cells.We provide evidence that TAF are derived from mesenchymal stem cells (MSC) that acquire a TAF phenotype following exposure to or systemic recruitment into adenocarcinoma xenograft models including breast, pancreatic, and ovarian. We define the MSC derived TAF in a xenograft ovarian carcinoma model by the immunohistochemical presence of 1) fibroblast specific protein and fibroblast activated protein; 2) markers phenotypically associated with aggressiveness, including tenascin-c, thrombospondin-1, and stromelysin-1; 3) production of pro-tumorigenic growth factors including hepatocyte growth factor, epidermal growth factor, and interleukin-6; and 4) factors indicative of vascularization, including alpha-smooth muscle actin, desmin, and vascular endothelial growth factor. We demonstrate that under long-term tumor conditioning in vitro, MSC express TAF-like proteins. Additionally, human MSC but not murine MSC stimulated tumor growth primarily through the paracrine production of secreted IL6.Our results suggest the dependence of in vitro Skov-3 tumor cell proliferation is due to the presence of tumor-stimulated MSC secreted IL6. The subsequent TAF phenotype arises from the MSC which ultimately promotes tumor growth through the contribution of microvascularization, stromal networks, and the production of tumor-stimulating paracrine factors

Characterising brown dwarf companions with IRDIS long-slit spectroscopy: HD 1160 B and HD 19467 B

The determination of the fundamental properties (mass, separation, age, gravity and atmospheric properties) of brown dwarf companions allows us to infer crucial informations on their formation and evolution mechanisms. Spectroscopy of substellar companions is available to date only for a limited number of objects (and mostly at very low resolution, R<50) because of technical limitations, i.e., contrast and angular resolution. We present medium resolution (R=350), coronagraphic long-slit spectroscopic observations with SPHERE of two substellar companions, HD 1160 B and HD 19467 B. We found that HD 1160 B has a peculiar spectrum that cannot be fitted by spectra in current spectral libraries. A good fit is possible only considering separately the Y+J and the H spectral band. The spectral type is between M5 and M7. We also estimated a T_eff of 2800-2900 K and a log(g) of 3.5-4.0 dex. The low surface gravity seems to favour young age (10-20 Myr) and low mass (~20 M Jup ) for this object. HD 19467 B is instead a fully evolved object with a T_eff of ~1000 K and log g of ~5.0 dex. Its spectral type is T6+/-1.Comment: 14 pages, 14 Figures. Accepted for publication on MNRA

Nck2 promotes human melanoma cell proliferation, migration and invasion in vitro and primary melanoma-derived tumor growth in vivo

<p>Abstract</p> <p>Background</p> <p>Nck1 and Nck2 adaptor proteins are involved in signaling pathways mediating proliferation, cytoskeleton organization and integrated stress response. Overexpression of Nck1 in fibroblasts has been shown to be oncogenic. Through the years this concept has been challenged and the consensus is now that overexpression of either Nck cooperates with strong oncogenes to transform cells. Therefore, variations in Nck expression levels in transformed cells could endorse cancer progression.</p> <p>Methods</p> <p>Expression of Nck1 and Nck2 proteins in various cancer cell lines at different stages of progression were analyzed by western blots. We created human primary melanoma cell lines overexpressing GFP-Nck2 and investigated their ability to proliferate along with metastatic characteristics such as migration and invasion. By western blot analysis, we compared levels of proteins phosphorylated on tyrosine as well as cadherins and integrins in human melanoma cells overexpressing or not Nck2. Finally, in mice we assessed tumor growth rate of human melanoma cells expressing increasing levels of Nck2.</p> <p>Results</p> <p>We found that expression of Nck2 is consistently increased in various metastatic cancer cell lines compared with primary counterparts. Particularly, we observed significant higher levels of Nck2 protein and mRNA, as opposed to no change in Nck1, in human metastatic melanoma cell lines compared with non-metastatic melanoma and normal melanocytes. We demonstrated the involvement of Nck2 in proliferation, migration and invasion in human melanoma cells. Moreover, we discovered that Nck2 overexpression in human primary melanoma cells correlates with higher levels of proteins phosphorylated on tyrosine residues, assembly of Nck2-dependent pY-proteins-containing molecular complexes and downregulation of cadherins and integrins. Importantly, we uncovered that injection of Nck2-overexpressing human primary melanoma cells into mice increases melanoma-derived tumor growth rate.</p> <p>Conclusions</p> <p>Collectively, our data indicate that Nck2 effectively influences human melanoma phenotype progression. At the molecular level, we propose that Nck2 in human primary melanoma promotes the formation of molecular complexes regulating proliferation and actin cytoskeleton dynamics by modulating kinases or phosphatases activities that results in increased levels of proteins phosphorylated on tyrosine residues. This study provides new insights regarding cancer progression that could impact on the therapeutic strategies targeting cancer.</p

SOSORT 2012 consensus paper: reducing x-ray exposure in pediatric patients with scoliosis

This 2012 Consensus paper reviews the literature on side effects of x-ray exposure in the pediatric population as it relates to scoliosis evaluation and treatment. Alternative methods of spinal assessment and imaging are reviewed, and strategies for reducing the number of radiographs are developed. Using the Delphi technique, SOSORT members developed consensus statements that describe how often radiographs should be taken in each of the pediatric and adolescent sub-populations

Peri-Pubertal Emergence of UNC-5 Homologue Expression by Dopamine Neurons in Rodents

Puberty is a critical period in mesocorticolimbic dopamine (DA) system development, particularly for the medial prefrontal cortex (mPFC) projection which achieves maturity in early adulthood. The guidance cue netrin-1 organizes neuronal networks by attracting or repelling cellular processes through DCC (deleted in colorectal cancer) and UNC-5 homologue (UNC5H) receptors, respectively. We have shown that variations in netrin-1 receptor levels lead to selective reorganization of mPFC DA circuitry, and changes in DA-related behaviors, in transgenic mice and in rats. Significantly, these effects are only observed after puberty, suggesting that netrin-1 mediated effects on DA systems vary across development. Here we report on the normal expression of DCC and UNC5H in the ventral tegmental area (VTA) by DA neurons from embryonic life to adulthood, in both mice and rats. We show a dramatic and enduring pubertal change in the ratio of DCC:UNC5H receptors, reflecting a shift toward predominant UNC5H function. This shift in DCC:UNC5H ratio coincides with the pubertal emergence of UNC5H expression by VTA DA neurons. Although the distribution of DCC and UNC5H by VTA DA neurons changes during puberty, the pattern of netrin-1 immunoreactivity in these cells does not. Together, our findings suggest that DCC:UNC5H ratios in DA neurons at critical periods may have important consequences for the organization and function of mesocorticolimbic DA systems