Clinical study to evaluate the safety and effectiveness of the Aesculap Activ-L™ artificial disc in the treatment of degenerative disc disease

<p>Abstract</p> <p>Background</p> <p>The objective of this clinical study is to evaluate the safety and effectiveness of the Activ-L Artificial Disc for treatment of single-level degenerative disc disease of the lumbar spine in patients who have been unresponsive to at least six months of prior conservative care. The hypothesis of the study is that the Activ-L Disc is non-inferior to the control (the Charité^®Artificial Disc [DePuy Spine] or ProDisc-L^®Total Disc Replacement [Synthes Spine]) with respect to the rate of individual subject success at 24 months. Individual subject success is a composite of effectiveness and safety.</p> <p>Methods/Design</p> <p>The study proposed is a prospective, randomized, single-masked, controlled, multi-center clinical trial consisting of an estimated 414 subjects with single-level DDD of the lumbar spine (L4/L5, or L5/S1) who have failed to improve with conservative treatment for at least six months prior to enrollment. After enrollment, subjects will be randomized in a 2:1 ratio to either the Activ-L Disc (investigational device) or the control (Charité or ProDisc-L). Radiographic endpoints will be evaluated by an independent reviewer at an imaging core laboratory. Each subject will be followed for 5 years post-treatment.</p> <p>Discussion</p> <p>The safety and effectiveness of the Activ-L Artificial Disc for treatment of single-level degenerative disc disease of the lumbar spine will be equivalent to Charité^®Artificial Disc [DePuy Spine] or ProDisc-L^®Total Disc Replacement [Synthes Spine] at 24 months.</p> <p>Trial Registration</p> <p>Current Controlled Trials NCT00589797.</p

Learning Online Smooth Predictors for Realtime Camera Planning using Recurrent Decision Trees

We study the problem of online prediction for realtime camera planning, where the goal is to predict smooth trajectories that correctly track and frame objects of interest (e.g., players in a basketball game). The conventional approach for training predictors does not directly consider temporal consistency, and often produces undesirable jitter. Although post-hoc smoothing (e.g., via a Kalman filter) can mitigate this issue to some degree, it is not ideal due to overly stringent modeling assumptions (e.g., Gaussian noise). We propose a recurrent decision tree framework that can directly incorporate temporal consistency into a data-driven predictor, as well as a learning algorithm that can efficiently learn such temporally smooth models. Our approach does not require any post-processing, making online smooth predictions much easier to generate when the noise model is unknown. We apply our approach to sports broadcasting: given noisy player detections, we learn where the camera should look based on human demonstrations. Our experiments exhibit significant improvements over conventional baselines and showcase the practicality of our approach

Leptin-Receptor-Expressing Mesenchymal Stromal Cells Represent the Main Source of Bone Formed by Adult Bone Marrow

SummaryStudies of the identity and physiological function of mesenchymal stromal cells (MSCs) have been hampered by a lack of markers that permit both prospective identification and fate mapping in vivo. We found that Leptin Receptor (LepR) is a marker that highly enriches bone marrow MSCs. Approximately 0.3% of bone marrow cells were LepR+, 10% of which were CFU-Fs, accounting for 94% of bone marrow CFU-Fs. LepR+ cells formed bone, cartilage, and adipocytes in culture and upon transplantation in vivo. LepR+ cells were Scf-GFP+, Cxcl12-DsRedhigh, and Nestin-GFPlow, markers which also highly enriched CFU-Fs, but negative for Nestin-CreER and NG2-CreER, markers which were unlikely to be found in CFU-Fs. Fate-mapping showed that LepR+ cells arose postnatally and gave rise to most bone and adipocytes formed in adult bone marrow, including bone regenerated after irradiation or fracture. LepR+ cells were quiescent, but they proliferated after injury. Therefore, LepR+ cells are the major source of bone and adipocytes in adult bone marrow

Consumer Preferences for Kiwiberries: Implications of Experimental Auctions

In the current global market, the development of novel products is important for staying competitive. The development of horticultural products often manifests as new cultivars. Gauging consumer interest is an important step in cultivar development because it is a resource-intensive process. The present study used an experimental auction to measure consumers’ willingness to pay (WTP) for novel fruit referred to as kiwiberry (Actinidia arguta and Actinidia kolomikta) and explore consumer segmentation for their preferences. The mean WTP for 6-ounce packages of kiwiberries ranged from $1.63 to$2.19, depending on species and cultivar. Four groups of consumers were identified in relation to their WTP for kiwiberries. Using survey data, socio-demographic variables such as age, education, and neophobic attitudes were significantly different between the mixed kiwiberry price premium and kiwiberry discounting groups. These findings suggest that consumers with variety-seeking tendencies have a WTP for kiwiberries that is comparable to that for other berries. Marketing strategies for these groups are proposed

Nested association mapping of stem rust resistance in wheat using genotyping by sequencing

We combined the recently developed genotyping by sequencing (GBS) method with joint mapping (also known as nested association mapping) to dissect and understand the genetic architecture controlling stem rust resistance in wheat (Triticum aestivum). Ten stem rust resistant wheat varieties were crossed to the susceptible line LMPG-6 to generate F6 recombinant inbred lines. The recombinant inbred line populations were phenotyped in Kenya, South Africa, and St. Paul, Minnesota, USA. By joint mapping of the 10 populations, we identified 59 minor and medium-effect QTL (explained phenotypic variance range of 1%- 20%) on 20 chromosomes that contributed towards adult plant resistance to North American Pgt races as well as the highly virulent Ug99 race group. Fifteen of the 59 QTL were detected in multiple environments. No epistatic relationship was detected among the QTL. While these numerous small- to medium-effect QTL are shared among the families, the founder parents were found to have different allelic effects for the QTL. Fourteen QTL identified by joint mapping were also detected in single-population mapping. As these QTL were mapped using SNP markers with known locations on the physical chromosomes, the genomic regions identified with QTL could be explored more in depth to discover candidate genes for stem rust resistance. The use of GBS-derived de novo SNPs in mapping resistance to stem rust shown in this study could be used as a model to conduct similar markertrait association studies in other plant species.This is an open access article, free of all copiright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

Production, purification and characterization of recombinant, full-length human claudin-1

The transmembrane domain proteins of the claudin superfamily are the major structural components of cellular tight junctions. One family member, claudin-1, also associates with tetraspanin CD81 as part of a receptor complex that is essential for hepatitis C virus (HCV) infection of the liver. To understand the molecular basis of claudin-1/CD81 association we previously produced and purified milligram quantities of functional, full-length CD81, which binds a soluble form of HCV E2 glycoprotein (sE2). Here we report the production, purification and characterization of claudin-1. Both yeast membrane-bound and detergent-extracted, purified claudin-1 were antigenic and recognized by specific antibodies. Analytical ultracentrifugation demonstrated that extraction with n-octyl-ß-d-glucopyranoside yielded monodispersed, dimeric pools of claudin-1 while extraction with profoldin-8 or n-decylphosphocholine yielded a dynamic mixture of claudin-1 oligomers. Neither form bound sE2 in line with literature expectations, while further functional analysis was hampered by the finding that incorporation of claudin-1 into proteoliposomes rendered them intractable to study. Dynamic light scattering demonstrated that claudin-1 oligomers associate with CD81 in vitro in a defined molar ratio of 1:2 and that complex formation was enhanced by the presence of cholesteryl hemisuccinate. Attempts to assay the complex biologically were limited by our finding that claudin-1 affects the properties of proteoliposomes. We conclude that recombinant, correctly-folded, full-length claudin-1 can be produced in yeast membranes, that it can be extracted in different oligomeric forms that do not bind sE2 and that a dynamic preparation can form a specific complex with CD81 in vitro in the absence of any other cellular components. These findings pave the way for the structural characterization of claudin-1 alone and in complex with CD81

Computationally Directed Discovery of MoBi\u3csub\u3e2\u3c/sub\u3e

Incorporating bismuth, the heaviest element stable to radioactive decay, into new materials enables the creation of emergent properties such as permanent magnetism, superconductivity, and nontrivial topology. Understanding the factors that drive Bi reactivity is critical for the realization of these properties. Using pressure as a tunable synthetic vector, we can access unexplored regions of phase space to foster reactivity between elements that do not react under ambient conditions. Furthermore, combining computational and experimental methods for materials discovery at high-pressures provides broader insight into the thermodynamic landscape than can be achieved through experiment alone, informing our understanding of the dominant chemical factors governing structure formation. Herein, we report our combined computational and experimental exploration of the Mo–Bi system, for which no binary intermetallic structures were previously known. Using the ab initio random structure searching (AIRSS) approach, we identified multiple synthetic targets between 0–50 GPa. High-pressure in situ powder X-ray diffraction experiments performed in diamond anvil cells confirmed that Mo–Bi mixtures exhibit rich chemistry upon the application of pressure, including experimental realization of the computationally predicted CuAl2-type MoBi2 structure at 35.8(5) GPa. Electronic structure and phonon dispersion calculations on MoBi2 revealed a correlation between valence electron count and bonding in high-pressure transition metal–Bi structures as well as identified two dynamically stable ambient pressure polymorphs. Our study demonstrates the power of the combined computational–experimental approach in capturing high-pressure reactivity for efficient materials discovery