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Although magnetic resonance imaging (MRI) has been increasingly used as a diagnostic tool for cervical spine injuries in canines, a comprehensive normal MRI anatomy of the canine cervical spine muscles is lacking. Therefore, the purpose of this study was to build a magnetic resonance imaging atlas of the normal cross sectional anatomy of the muscles of the canine cervical spine. MRI scans were performed on a canine cadaver using a combination of T1 and T2-weighted images in the transverse, sagittal and dorsal planes acquired at a slice thickness of 1 mm. Muscle contours were traced manually in each slice, using local osseous structures as reference points for muscle identification. Twenty-two muscles were traced in 401 slices in the cervical region. A three dimensional surface model of all the contoured muscles was created to illustrate the complex geometrical arrangement of canine neck muscles. The cross-sectional area of the muscles was measured at the mid-level of each vertebra. The accuracy of the location of the mapped muscles was verified by comparing the sagittal view of the 3D model of muscles with still photographs obtained from anatomic canine cadaver dissection. We believe that this information will provide a unique and valuable resource for veterinary researchers, clinicians and surgeons who wish to evaluate MRI images of the cervical spine. It will also serve as the foundation for ongoing work to develop a computational model of the canine cervical spine in which anatomical information is combined with electromyographic, kinematic and kinetic data.

Basic science studies remain a critically important part of the knowledge-discovery process in musculoskeletal patient care. This article highlights several of the key advances in orthopaedic basic science over the past year. It should be noted that some topics of tremendous basic science interest, most notably orthopaedic infection and neoplasia, are not covered in detail in this article because they have been the focus of previous Specialty Update articles in The Journal 1 , 2 . ### A Joint as an Organ It is now widely accepted that a joint is best considered an organ, rather than a simple tissue, and that osteoarthritis (OA) represents a spectrum of pathologies affecting several of the core structures that make up the joint. Early understanding of OA focused on the changes that were grossly evident on joint inspection, including cartilage degradation, subchondral bone sclerosis, synovial inflammation, and osteophyte formation. More recently, this picture has been expanded to include the contributions of local changes in peri-articular muscles, nerves, and intra-articular structures such as the fat pad. This expanded understanding of the complexity of joint structure and function3 should facilitate the development of more robust and productive in vitro models for studying joint disease and its management. It will also drive the development of more effective regenerative strategies that target multiple aspects of organ function, rather than focusing on cartilage repair/regeneration alone. ### Posttraumatic OA The majority of preclinical, induced (i.e., nonnatural) models of OA involve the creation of traumatic instability within the joint. Although this may limit the translational relevance of studies performed with these models, particularly with regard to the efficacy of pharmacological or biological therapies, it has facilitated notable recent advances in our understanding of the effects of trauma on function of the joint organ. Blaker et al. reported on the use of mouse models of posttraumatic OA (PTOA) and …

The dynamics of ligand exchange on lanthanide ions is important for catalysis and organic reactions. Recent

A bioactive two-layer coating consisting of hydroxyapatite (HA) and yttria-stabilized zirconia (YSZ) was investigated on cylindrical polyetheretherketone (PEEK) implants using ion beam assisted deposition (IBAD). Post-deposition heat treatments via variable frequency microwave annealing with and without subsequent autoclaving were used to crystallize the as-deposited amorphous HA layer. Microstructural analysis, performed by TEM and EDS, showed that these methods were capable of crystallizing HA coating on PEEK. The in vivo response to cylindrical PEEK samples with and without coating was studied by implanting uncoated PEEK and coated PEEK implants in the lateral femoral condyle of 18 rabbits. Animals were studied in two groups of 9 for observation at 6 or 18weeks post surgery. Micro-CT analysis, histology, and mechanical pull-out tests were performed to determine the effect of the coating on osseointegration. The heat-treated HA/YSZ coatings showed improved implant fixation as well as higher bone regeneration and bone-implant contact area compared to uncoated PEEK. The study offers a novel method to coat PEEK implants with improved osseointegration.

The EuII/III redox couple offers metal-based oxidation-sensing with magnetic resonance imaging making the study of EuII oxidation chemistry important in the design of new probes. Accordingly, we explored oxidation reactions with a set of EuII -containing complexes. Superoxide formation from the reaction between EuII and dioxygen was observed using electron paramagnetic resonance spectroscopy. Additionally, oxidation kinetics of three EuII -containing complexes with bromate and glutathione disulfide at pH values, including 5 and 7, is reported. In the reaction with bromate, the oxidation rate of two of the complexes increased by 7.3 and 6.7 times upon decreasing pH from 7 to 5, but the rate increased by 17 times for a complex containing amide functional groups over the same pH range. The oxidation rate of a fluorobenzo-functionalized cryptate was relatively slow, indicating that the ligand used to impart thermodynamic oxidative stability might also be useful for controlling oxidation kinetics.

Correction for 'Simulations of the water exchange dynamics of lanthanide ions in 1-ethyl-3-methylimidazolium ethyl sulfate ([EMIm][EtSO

The use of animals in research is under increasing scrutiny from the general public, funding agencies, and regulatory authorities. Our ability to continue to perform in-vivo studies in laboratory animals will be critically determined by how researchers respond to this new reality. This Perspectives article summarizes recent and ongoing initiatives within ORS and allied organizations to ensure that musculoskeletal research is performed to the highest ethical standards. It goes on to present an overview of the practical application of the 3Rs (reduction, refinement, and replacement) into experimental design and execution, and discusses recent guidance with regard to improvements in the way in which animal data are reported in publications. The overarching goal of this review is to challenge the status quo, to highlight the absolute interdependence between animal welfare and rigorous science, and to provide practical recommendations and resources to allow clinicians and scientists to optimize the ways in which they undertake preclinical studies involving animals. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:740-751, 2017.

Two new Eu(II)-containing cryptates were prepared with a new nitrogenous cryptand functionalized with three benzo groups. The introduction of three aromatic rings into the ligand backbone imparts lopsided geometrical features on the resulting Eu(II) coordination environments. In both complexes, the interactions between Eu and the amines on the aromatic side of the molecule are weaker than those on the nonaromatic side, resulting in one discrete unit with two distinct faces. One of the new complexes is, to the best of our knowledge, the first direct observation of a bis-aquo Eu(II)-containing cryptate with two nonadjacent inner-sphere water molecules. In addition to solid-phase structure, the electronic UV-visible and emission spectra of the new complexes were studied in acetonitrile. Experimental results show that the decreased Lewis basicity of the aromatic face hypsochromically shifts absorbances and emissions from a structurally related compound without the benzo groups.

This account describes lanthanide coordination chemistry with a focus on the similarities between lanthanide complexes used in catalysis and those used as contrast agents in magnetic resonance imaging.

Summary Objectives: To evaluate the in vitro anti -bacterial activity of a silver-impregnated coating against a biofilm-forming strain of methicillin-resistant Staphylococcus pseud -intermedius (MRSP). Methods: A clinical MRSP isolate sourced from a failed canine knee implant was evaluated for biofilm production and used in the present study. Using a standard test method and a clinically approved titanium substrate, the antimicrobial activity of a novel silver plasma coating was determined at two times: five minutes after inoculation of the specimens (T0) and after 24 hours of incubation (T24). Scanning electron microscopy was used to evaluate the biofilm formation on specimens. Results: The tested clinical MRSP isolate was classified as a strong biofilm producer. The silver coating significantly reduced the MRSP growth more than four log steps compared to the non-coated specimens and showed more than 99.98% reduction in the number of colony forming units after 24 hours. Scanning electron microscopy images revealed that silver-coated surfaces did not manifest detectable biofilm, while biofilm formation was readily observed on the control specimens. Clinical significance: The silver coating exhibited excellent activity against the multi-drug resistant biofilm-forming MRSP isolate. The next stage of this work will involve testing in an animal model of orthopaedic infection. Positive results from animal studies would support the introduction of the silver plasma coating as a new strategy for preventing implant contamination, biofilm formation, and surgical infection in dogs undergoing orthopaedic surgery.Supplementary Material for this paper is available online at: http://dx.doi.org/10.3415/VCOT-15-08-0134

This account describes lanthanide coordination chemistry with a focus on the similarities between lanthanide complexes used in catalysis and those used as contrast agents in magnetic resonance imaging.

Approximately 2 million patients in the United States annually undergo total joint arthroplasty with reaming and placement of intramedullary nails, resulting in extravasation of bone marrow and fat into the circulatory system and potentially causing fat embolism syndrome. Acute and chronic changes in mental status documented after these procedures may be related to embolic events. The Reamer/Irrigator/Aspirator (RIA) device has been shown to decrease intramedullary pressure during reaming. We hypothesized that the use of the RIA in a canine model would reduce the number of microemboli detected in the carotid artery and brain compared with nailing either with or without reaming.Twenty-four large canines underwent unreamed nailing (UR), sequentially reamed nailing (SR), or RIA-reamed nailing (RIA) of bilateral femora (eight dogs per group). During reaming and nailing, the number and size of microemboli transiting the carotid artery were recorded. After euthanasia, the brain was harvested for immunostaining and measurement of microinfarction volumes.Total embolic load passing through the carotid artery was 0.049 cc (UR), 0.045 cc (SR), and 0.013 cc (RIA). The number and size of microemboli in the UR and SR groups were similar; however, the RIA group had significantly fewer larger-sized (200-μm) emboli (p = 0.03). Pathologic examination of the brain confirmed particulate emboli, and histologic analyses demonstrated upregulation of stress-related proteins in all groups, with fewer emboli and less evidence of stress for RIA reaming.RIA reaming decreased microemboli compared with traditional reaming and unreamed nailing, suggesting that intramedullary pressure and heat are important variables. The documented embolic events and brain stress may help to explain subtle neurobehavioral symptoms commonly seen in patients after undergoing long-bone reaming procedures.RIA reaming decreased cranial embolic events and may have an ameliorating effect on postoperative neurologic sequelae.

Reliable methods of imaging myelin are essential to investigate the causes of demyelination and to study drugs that promote remyelination. Myelin-specific compounds can be developed into imaging probes to detect myelin with various imaging techniques. The development of multimodal myelin-specific imaging probes enables the use of orthogonal imaging techniques to accurately visualize myelin content and validate experimental results. Here, we describe the synthesis and application of multimodal myelin-specific imaging agents for light microscopy and magnetic resonance imaging. The imaging agents were synthesized by incorporating the structural features of luxol fast blue MBS, a myelin-specific histological stain, into texaphyrins coordinated to GdIII. These new complexes demonstrated absorption of visible light, emission of near-IR light, and relaxivity values greater than clinically approved contrast agents for magnetic resonance imaging. These properties enable the use of optical imaging and magnetic resonance imaging for visualization of myelin. We performed section- and en block-staining of ex vivo mouse brains to investigate the specificity for myelin of the new compounds. Images obtained from light microscopy and magnetic resonance imaging demonstrate that our complexes are retained in white matter structures and enable detection of myelin.

The influence of albumin on the efficacy of a Eu(2+)-containing complex capable of interacting with human serum albumin (HSA) was investigated at different field strengths (1.4, 3, 7, 9.4, and 11.7 T). Relaxometric measurements indicated that the presence of albumin at higher field strengths (3 T) did not result in an increase in the relaxivity of the Eu(2+) complex, but a relaxation enhancement of 171 ± 11% was observed at 1.4 T. Titration experiments using different percentages (2, 4.5, 6, 10, 15, and 25% w/v) of HSA and variable-temperature (17)O NMR measurements were performed to understand the effect of albumin on the molecular properties of the biphenyl-functionalized Eu(2+) complex that are relevant to magnetic resonance imaging.

This review describes recent research efforts focused on increasing the specificity of contrast agents for proton magnetic resonance imaging (MRI). Contrast agents play an indispensable role in MRI by enhancing the inherent contrast of images; however, the non-specific nature of current clinical contrast agents limits their usefulness. This limitation can be addressed by conjugating contrast agents or contrast-agent-loaded carriers—including polymers, nanoparticles, dendrimers, and liposomes—to molecules that bind to biological sites of interest. An alternative approach to conjugation is synthetically mimicking biological structures with metal complexes that are also contrast agents. In this review, we describe the advantages and limitations of these two targeting strategies with respect to translation from in vitro to in vivo imaging while focusing on advances from the last ten years.

Molecules containing multiple lanthanide ions have unique potential in applications for medical imaging including the areas of magnetic resonance imaging (MRI) and fluoresence imaging. The study of multilanthanide complexes as contrast agents for MRI and as biologically responsive fluorescent probes has resulted in an improved understanding of the structural characteristics that govern the behavior of these complexes. This review will survey the last five years of progress in multinuclear lanthanide complexes with a specific focus on the structural parameters that impact potential medical imaging applications. The patents cited in this review are from the last five years and describe contrast agents that contain multiple lanthanide ions.

The development of efficient methods for the asymmetric Mukaiyama aldol reaction in aqueous solution has received great attention. We have developed a new series of chiral lanthanide-containing complexes that produce Mukaiyama aldol products with outstanding enantioselectivities. In this paper, we describe an optimized ligand synthesis, trends in stereoselectivity that result from changing lanthanide ions, and an exploration of substrate scope that includes aromatic and aliphatic aldehydes and silyl enol ethers derived from aromatic and aliphatic ketones.

Recent advances in the coordination chemistry of Eu(2+) are reviewed. Common synthetic routes for generating discrete Eu(2+)-containing complexes reported since 2000 are summarized, followed by a description of the reactivity of these complexes and their applications in reduction chemistry, polymerization, luminescence, and as contrast agents for magnetic resonance imaging. Rapid development of the coordination chemistry of Eu(2+) has led to an upsurge in the utilization of Eu(2+)-containing complexes in synthetic chemistry, materials science, and medicine.

Cementless fixation for the tibial component in total knee arthroplasty (TKA) remains problematic. Peri-Apatite (PA), a solution-deposited hydroxyapatite, is under investigation as an option for improving the fixation of cementless tibial components. In this study, radiostereometric analysis was used to document implant migration in 48 dogs that underwent TKA with cementless, PA-coated, or cemented tibial components. Migration at 12 weeks was similar in the 2 groups. At 12 months, there was greater migration in the PA-coated group, but the difference between the 2 groups was below the threshold considered clinically significant. In this canine TKA model, cementless fixation with PA performed less well than did cemented fixation, but not to a degree that would make a clinical difference in the short term.

The kinetic stabilities and relaxivities of a series of Eu(2+)-containing cryptates have been investigated. Transmetallation studies that monitored the change in the longitudinal relaxation rate of water protons in the presence of Ca(2+), Mg(2+), and Zn(2+) demonstrated that cryptate structure influences stability, and two of the cryptates studied were inert to transmetallation in the presence of these endogenous ions. The efficacy of these cryptates was determined at different magnetic field strengths, temperatures, and pH values. Cryptate relaxivity was found to be higher at ultra-high field strengths (7 and 9.4 T) relative to clinically relevant field strengths (1.4 and 3 T), but the efficiency of these cryptates decreased as temperature increased. In addition, variation in pH did not yield significant changes in the efficacy of the cryptates. These studies establish a foundation of important properties that are necessary to develop effective positive contrast agents for magnetic resonance imaging from Eu(2+)-containing cryptates.

Background: Unloading treatments for osteoarthritis of the knee, such as valgus braces, have been shown to reduce medial joint-loading and pain. The purpose of this preclinical study was to investigate the tissue response to an extracapsular implantable device (KineSpring System; Moximed, Hayward, California) that is designed to reduce loading across the medial compartment of the knee. Methods: Eleven sheep were implanted with the KineSpring System, consisting of bases secured to the medial femoral and tibial cortices with bone screws and also consisting of a joint-spanning load-absorber composed of a piston and spring assembly inside a polymeric sheath. In nine sheep, titanium alloy washers with either an uncoated or a plasma-sprayed titanium-hydroxyapatite (TPS-HA) coated undersurface were fixed with screws to the contralateral femur and tibia to investigate the effects of surface treatment on extracortical bone apposition. The functionality of the KineSpring System was assessed by fluoroscopy, tissue response was determined by gross and microscopic histology, and implant fixation was determined by radiography, microradiography, and histomorphometry at four, twelve, twenty-six, and fifty-two weeks. Results: The function of the KineSpring System was confirmed in all sheep. Seventeen of eighteen TPS-HA coated bases and thirty-six of thirty-six washers had stable bone fixation; one coated base was loose with evidence of infection. At four weeks, there was an early, expected inflammatory response, but this response resolved by twelve weeks and a pseudosynovial membrane formed around the sheath. Bone apposition increased over time for the TPS-HA coated bases and for uncoated washers (p < 0.05). There was good apposition of the TPS-HA coated washers even at early time points, with no subsequent increase in apposition over time. Conclusions: The KineSpring System demonstrated safety in a simulated use model for periods of up to fifty-two weeks. Screws result in stable implant fixation and TPS-HA coating allows for early and long-lasting cortical bone apposition and integration. Clinical Relevance: This implant warrants further investigation as a means of reducing medial compartment loading and pain in patients with osteoarthritis of the knee.

Extensive periosteal stripping (PS) is a risk factor for post-radiation pathologic fracture following surgery for extremity soft tissue tumors. The purpose of this study was to determine the effects of PS on bone structure and mechanical properties. Thirty-one skeletally mature mice underwent PS, with circumferential removal of periosteum from an 8-mm segment of the mid-diaphysis of the left femur. Thirty-one control mice underwent sham surgery in which the femur was isolated without manipulation of the periosteum. At 2, 6, 12, or 26 weeks following surgery, the left femora were examined by micro-CT to quantify cortical thickness (CtTh), cross-sectional area (CSA), bone volume (BV), and polar moment of inertia (PMI). Three-point mechanical bend testing was performed and peak load, stiffness, and energy to failure were determined. PS resulted in significantly decreased CtTh, CSA, BV, and PMI at all time points. Peak load, stiffness, and energy to failure were significantly reduced at 2, 6, and 12 weeks. There were no significant differences in mechanical properties at 26 weeks. In this mouse model, extensive circumferential PS resulted in sustained changes in bone structure that were still evident after 6 months, accompanied by reductions in bone strength that persisted for at least 3 months.

Graphene's single atomic layer of sp(2) carbon has recently garnered much attention for its potential use in electronic applications. Here, we report a memory application for graphene, which we call graphene flash memory (GFM). GFM has the potential to exceed the performance of current flash memory technology by utilizing the intrinsic properties of graphene, such as high density of states, high work function, and low dimensionality. To this end, we have grown large-area graphene sheets by chemical vapor deposition and integrated them into a floating gate structure. GFM displays a wide memory window of ∼6 V at significantly low program/erase voltages of ±7 V. GFM also shows a long retention time of more than 10 years at room temperature. Additionally, simulations suggest that GFM suffers very little from cell-to-cell interference, potentially enabling scaling down far beyond current state-of-the-art flash memory devices.

Luminescence-decay measurements were studied as a simple and fast technique to determine inner-sphere water coordination numbers of LnIII-based complexes in binary solvent systems that are useful for catalysis. The luminescence-decay rates of EuIII-containing complexes were used to elucidate the coordination environment of EuIII in these solvent systems. Our findings were used to empirically derive easy-to-use equations to determine the average number of inner-sphere water and solvent molecules in binary aqueous solvent systems. The increased knowledge of the inner-sphere coordination environment of catalysts that our equations enable can be used to study lanthanide-catalyzed reactions and new precatalysts.

Objective: To define the kinematic motion patterns of the canine cervical spine, with a particular emphasis on identifying differences between the cranial (C2–C4) and caudal (C5–C7) segments, and to determine the significance of coupled motions (CM) in the canine cervical spine. Study Design: Cadaveric biomechanical study. Sample Population: Cervical spines of 8 Foxhounds. Methods: Spinal specimens were considered free of pathology based on radiographic, computed tomography, and magnetic resonance imaging examinations. All musculature was removed without damaging ligaments or joint capsules. Spines were mounted in a customized pure-moment spine testing jig, and data were collected using an optoelectronic motion capture system. Range of motion, neutral zone and CM in flexion/extension, left/right lateral bending and left/right axial rotation were established. Data were analyzed using mixed-effects maximum likelihood regression models. Results: Total flexion/extension did not change across the 4 levels. There was no difference between flexion and extension, and no CM was identified. Lateral bending was not different across levels, but tended to be greater in the cranial spine. Axial rotation was ∼2.6 times greater in the caudal segments. Lateral bending and axial rotation were coupled. Conclusions: Kinematics of the cranial and caudal cervical spine differed markedly with greater mobility in the caudal cervical spine.

Maintenance ensures the reliability of the equipment to meet operation's demands. Operations ensure the production of sufficient and high quality product. Engineering designs and installs equipment that minimizes risk. Safety ensures that the engineering and administrative controls are in place to minimize that risk. This article presents a concept that combines these reliability and safety efforts, such that the maintenance, operations, engineering and safety groups speak the same language to minimize the overall business risk. This proposed approach combines existing plant reliability efforts with several Process Safety Management elements. The basic steps include identifying safety-critical equipment, ensuring accurate and up-to-date Process Safety Information (PSI), establishing the mechanical integrity (MI) Program, establishing Planned Maintenance (PM) programs, and creating equipment-specific maintenance procedures. The resultant mechanical integrity quality assurance (MI QA) program combines equipment reliability and operational integrity efforts to ensure that the equipment is properly designed (via PSI), fabricated as designed (via PSI and MI), and installed as designed (via Pre-Start-up Safety Reviews). The MI QA program also ensures that the equipment is operated and maintained as designed by trained personnel. Some benefits include being able to: (1) share and document best MI and PM practices between different sites; (2) focus limited PM-related resources on the process safety-critical equipment; and (3) help monitor the essential reliability efforts to ensure continued safe operation. © 2011 American Institute of Chemical Engineers Process Saf Prog, 2011

Objective: To determine whether the fatigue properties of an interlocking nail (ILN) construct are influenced by metaphyseal or diaphyseal location of the locking bolt. Study Design: Ex vivo mechanical investigation. Sample Population: Adult canine femora (n=19 pairs). Methods: Femora were implanted with a 6-mm diameter ILN. In 1 femur, the ILN was locked with a 2.7 mm bolt placed in the diaphysis; the ILN in the contralateral femur was locked with a bolt placed in the metaphysis. Constructs were tested to failure in axial loading (9 pairs) or torsion (10 pairs), with failure defined as displacement>2 mm or a total of 500,000 cycles for axial loading, and rotation>45° for torsional loading. Outcome measures included initial construct stiffness, number of cycles to failure, peak load, and peak torque. After testing, microradiography and histology were used to determine the location and nature of construct failure. Results: Metaphyseal bolts failed at higher axial loads than diaphyseal bolts (P=.03), with bolt failure because of bending at the nail-bolt interface. All of the metaphyseal bolt constructs survived torsional testing whereas 9 of 10 diaphyseal bolt constructs failed catastrophically because of spiral fracture through the adjacent cortical bone. Conclusions: Placement of a locking bolt in metaphyseal bone extends fatigue life under axial loading and decreases the incidence of catastrophic failure under torsional loading.

Background The specific aim of this study was to determine the whether a novel, hydrogel-coated polyester mesh (Scout) can be used to reduce the incidence and severity of adhesion formation in vivo. Methods An established rat model of post-surgical adhesion formation was used in which adhesions are generated through surgical trauma to the surfaces of the cecum and the adjacent abdominal wall. Thirty-seven rats were randomly allocated either to a control group (no intervention; n = 14 rats) or to one of two treatment groups in which the abraded surfaces were separated with either the Scout material (n = 11 rats) or an FDA-approved form of expanded polytetrafluorethylene (PTFE) (PRECLUDE Vessel Guard; n = 12 rats). Animals were euthanized 7 d after surgery and gross necropsy examinations were performed. Mechanical testing was used to measure the strength of any adhesions that were identified, and histology was used to characterize within the adhesion tissue and on the surface(s) of the barrier materials. Results Five animals were excluded because of surgical failure (1 control; 2 PRECLUDE Vessel Guard; 2 Scout). Adhesions were seen in 10 of 13 control animals (77%). There were no adhesions in any of the animals treated with either PRECLUDE Vessel Guard or Scout material. Histology demonstrated mild cellular adhesion to both the PRECLUDE Vessel Guard and the Scout material. Although there was a sub-acute to chronic inflammatory response to the surgical trauma, there was no evidence of delamination, shearing, or degradation of either the Scout material or PRECLUDE Vessel Guard. Conclusions The hydrogel-coated Scout material was as effective as the approved predicate material in this model. Both materials were well tolerated. Further testing of the Scout material is now warranted.

The atomic structure of graphene on polycrystalline copper substrates has been studied using scanning tunneling microscopy. The graphene overlayer maintains a continuous pristine atomic structure over atomically flat planes, monatomic steps, edges, and vertices of the copper surface. We find that facets of different identities are overgrown with graphene's perfect carbon honeycomb lattice. Our observations suggest that growth models including a stagnant catalytic surface do not apply to graphene growth on copper. Contrary to current expectations, these results reveal that the growth of macroscopic pristine graphene is not limited by the underlying copper structure.

Background: Dogs have a high prevalence of disc-associated cervical spinal cord disorders. Despite this, there are no descriptions of the micromorphometry or cellular characteristics of canine cervical intervertebral discs. Hypothesis/Objectives: To compare micromorphometric and cellular characteristics at 4 disc regions (outer annulus [OA], inner annulus [IA], transitional zone [TZ], nucleus pulposus [NP]). We hypothesized that measurements would differ between chondrodystrophic (CH) and nonchondrodystrophic (NCH) dogs. Animals: Six CH dogs and 6 NCH dogs, under 3 years old. Methods: Histologic sections of all cervical discs from each dog were examined. Micromorphometric variables included relative ratio of ventral to dorsal annulus fibrosus (AF), number and mean width of AF fibers, and relative percentage of NP. Cellular variables included cell density, morphology, and grouping. Results: The NP from CH dogs was smaller, more rounded, and more dorsally located compared with that from NCH dogs. The NP occupied a greater proportion of the disc in NCH dogs compared with CH dogs (27.7 versus 15.8%; P < .001). The ratio of ventral to dorsal AF was approximately 3 : 1 in the CH group and 2 : 1 in the NCH group. Cellular variables were region dependent. Cell density was 2.4-fold higher in the OA compared with the NP. Approximately 50 of NP cells and 4.5% of OA cells occurred in groups. Conclusions and Clinical Importance: Micromorphometric variables differed by CH status. Cellular variables differed by disc region. Our findings potentially can explain the high incidence of intervertebral disc extrusions in CH dogs compared with NCH dogs.

Many patients with symptomatic bone metastases receive radiation therapy, even though radiation is known to have potential adverse effects on bone. We hypothesized that the concurrent use of a bisphosphonate drug (zoledronic acid, ZA) or a combination of ZA plus an anabolic agent (parathyroid hormone, PTH) would lead to improvements in the microarchitecture and mechanical properties of irradiated bone. Human breast cancer cells were injected into the distal femur of 56 female nude mice, which were then divided into four groups: no treatment (0 Gy), radiation administered 4 weeks postinjection (20 Gy), radiation plus ZA (12.5 microg/kg weekly from weeks 4 to 12) (20 Gy + ZA), and radiation followed by ZA (25 microg/kg weekly from weeks 4 to 8) and PTH(1-34) (100 microg microg/kg daily from weeks 8 to 12) (20 Gy + ZA + PTH). Left limbs served as normal control bones. Bone loss over the 12-week study was tracked with serial radiography and bone densitometry. At the end of the study, micro-computed tomography and mechanical testing were used to quantify bone microarchitecture and bone strength. Radiation alone failed to prevent tumor-induced decreases in bone mineral density (BMD), trabecular bone volume, and bone strength. Treatment with 20 Gy + ZA or 20 Gy + ZA + PTH as adjuncts to radiation was effective at preserving trabecular bone architecture and bone strength at normal levels. ZA reduced the risk of mechanical fragility following irradiation of a lytic bone lesion. Supplemental use of PTH did not result in further increases in bone strength but was associated with significant increases in BMD and bone mass, suggesting that it may be beneficial in enhancing bone architecture following radiation therapy.

This paper presents an analytical displacements and dispersion relations for optical phonons of a graphene sheet. These results are used to derive the optical deformation potential interactions for graphene as well as to obtain descriptions of the confined optical phonons for graphene.

We report the formation of a nanocomposite comprised of chemically converted graphene and carbon nanotubes. Our solution-based method does not require surfactants, thus preserving the intrinsic electronic and mechanical properties of both components, delivering 240 ohms/square at 86% transmittance. This low-temperature process is completely compatible with flexible substrates and does not require a sophisticated transfer process. We believe that this technology is inexpensive, is massively scalable, and does not suffer from several shortcomings of indium tin oxide. A proof-of-concept application in a polymer solar cell with power conversion efficiency of 0.85% is demonstrated. Preliminary experiments in chemical doping are presented and show that optimization of this material is not limited to improvements in layer morphology.

Introduction Preclinical research is the initial prerequisite to determining the efficacy of an implant for eventual translation into the clinical arena. Once a spinal implant has been validated through benchtop mechanical testing, analytical modeling, and in vitro evaluation, it is often useful to conduct an in vivo study using animal models to assess the interactions of the living tissue environment surrounding the spinal implant. Animal models are often implemented in the assessment of spinal implant behavior to identify potential problems with respect to tissue infiltration and adverse tissue and interface reactions. Biomechanical and biological investigations of the tissue and implant interface, as well as the surrounding supportive tissue structures, can provide early insight into the potential clinical performance once implanted into humans. However, the use of animals for implant evaluation remains controversial due to the varied anatomy, different healing rates, and complicated biomechanical environments. There are numerous challenges that exist with animal models such as determining (1) when an animal study is needed, (2) what the appropriate animal model is, (3) what the appropriate time points and outcome measures are, and (4) what the optimal sample size is. Another challenge for such studies is the need to downsize the spinal implants—a serious issue for some animal models. A panel of eminent experts has been assembled for this symposium to address a number of these issues and challenges with the use of animal models for understanding implant and tissue interface behavior in a living environment. The experts are leaders in their field, and we are fortunate to have them provide insight into these challenges based on their varied experience in this area. We look forward to the readers’ participation and feedback to this symposium.

The electronic properties of graphene, such as high charge carrier concentrations and mobilities, make it a promising candidate for next-generation nanoelectronic devices. In particular, electrons and holes can undergo ballistic transport on the sub-micrometre scale in graphene and do not suffer from the scale limitations of current MOSFET technologies. However, it is still difficult to produce single-layer samples of graphene and bulk processing has not yet been achieved, despite strenuous efforts to develop a scalable production method. Here, we report a versatile solution-based process for the large-scale production of single-layer chemically converted graphene over the entire area of a silicon/SiO(2) wafer. By dispersing graphite oxide paper in pure hydrazine we were able to remove oxygen functionalities and restore the planar geometry of the single sheets. The chemically converted graphene sheets that were produced have the largest area reported to date (up to 20 x 40 microm), making them far easier to process. Field-effect devices have been fabricated by conventional photolithography, displaying currents that are three orders of magnitude higher than previously reported for chemically produced graphene. The size of these sheets enables a wide range of characterization techniques, including optical microscopy, scanning electron microscopy and atomic force microscopy, to be performed on the same specimen.

6 pags, 7 figs, 3 tabs, A dielectric barrier discharge (DBD) technique has been employed to produce uniform atmospheric plasmas of He and N2 gas mixtures in open air in order to functionalize the surface of filtered-arc deposited hydrogen-free diamond-like carbon (DLC) films. XPS measurements were carried out on both untreated and He/N2 DBD plasma-treated DLC surfaces. Chemical states of the C 1s and N 1s peaks were collected and used to characterize the surface bonds. Contact angle measurements were also used to record the short- and long-term variations in wettability of treated and untreated DLC. In addition, cell viability tests were performed to determine the influence of various He/N2 atmospheric plasma treatments on the attachment of osteoblast MC3T3 cells. Current evidence shows the feasibility of atmospheric plasmas in producing long-lasting variations in the surface bonding and surface energy of hydrogen-free DLC and consequently the potential for this technique in the functionalization of DLC-coated devices. © 2008 Elsevier B.V. All rights reserved., Financial support from the Marie Curie Outgoing Fellowship Grant MOIF-CT-2005-02195 is gratefully acknowledged. Work at Lawrence Berkeley National Laboratory was supported by the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. Financial support from the Spanish Ministry of Education under project MAT2004-01451 is also gratefully acknowledged

The goal of this study was to determine whether computer-assisted surgical navigation improves the accuracy of tibial component alignment in canine total knee replacement (TKR).Retrospective radiographic review and prospective ex vivo study.Canine TKR radiographs (n = 17 sets) and canine cadaveric stifles (n = 12).Radiographs from TKR surgical workshops were reviewed to determine the incidence and magnitude of tibial component malalignment. Tibial component alignment was compared after either standard ("surgeon-guided") component placement or computer-assisted ("navigation-guided") placement. Results were compared against the current recommendations of a neutral (0° varus-valgus) ostectomy in the frontal plane and 6° of caudal slope in the sagittal plane. A prospective cadaveric study was then undertaken by performing TKR in 12 canine stifle joints.Malalignment of3° in the frontal and sagittal planes was identified in 12% and 24% of the radiographs from the retrospective review, respectively. Surgical navigation reduced both the mean error (P = .007) and the variability in frontal plane alignment (P .001) as compared with surgeon-guided procedures. The mean error in sagittal plane alignment was not significantly different (P = .321), but variability in alignment was significantly lower when navigation was used (P = .008).Surgical navigation significantly improved accuracy and decreased variability in tibial component alignment in canine TKR. Clinical trials would be required to determine whether these improvements in surgical accuracy lead to better clinical outcomes in terms of joint function and a reduction in long-term implant wear.

To assess technical feasibility and mechanical properties of 3 locking plate designs (Zero-P, Zero-P VA, and Uniplate 2) for use in the canine cervical spine.Prospective ex vivo study.Cadaver cervical spines from skeletally mature large breed dogs (n = 18).Specimens were screened using radiography and allocated into balanced groups based on bone density. Stiffness of intact C4-C5 vertebral motion units was measured in extension, flexion, and lateral bending using nondestructive 4-point bend testing. Uniplate 2 was then implanted at C4-C5 and mechanical testing was repeated. Mechanical test data were compared against those from 6 spines implanted with monocortical screws, an allograft ring spacer, and PMMA.The Zero-P and Zero-P VA systems could not be surgically implanted due to anatomical constraints in the vertebral column sizes of the canine cervical spines used in this study. Fixation with Uniplate 2 or with screws/PMMA significantly increased stiffness of the C4-C5 vertebral motion units compared to unaltered specimens (P .001) in extension. Stiffness of the titanium screw/PMMA fixation was significantly greater than the Uniplate 2 construct in extension. Flexion and lateral bending could not be evaluated in 3 of 6 specimens in the Uniplate 2 group due to failure at the bone/implant interface during extension testing.Fixation with Uniplate 2 was biomechanically inferior to screws/PMMA. Particularly concerning was the incidence of vertebral fracture after several testing cycles. Based on our results, Zero-P, Zero-P VA, and Uniplate 2 cannot be recommended for use in dogs requiring cervical fusion.

OBJECTIVE To characterize and compare gait variables in Doberman Pinschers with and without cervical spondylomyelopathy (CSM). ANIMALS 18 Doberman Pinschers (9 clinically normal dogs and 9 CSM-affected dogs). PROCEDURES A neurologic examination was performed on all dogs. The diagnosis of CSM was confirmed with MRI. Temporospatial and kinetic gait variables were measured by use of a pressure-sensitive walkway. Temporospatial variables evaluated included stance phase duration, swing phase duration, gait cycle duration, stride length, and gait velocity. Kinetic variables evaluated included peak vertical force and vertical impulse. Random-effects linear regression was used to determine the difference between CSM-affected and clinically normal dogs for each of the 7 variables. RESULTS Values for temporospatial variables were significantly smaller in the thoracic limbs of CSM-affected dogs, compared with values for the thoracic limbs of clinically normal dogs. For the kinetic variables, peak vertical force was significantly higher in the thoracic limbs than the pelvic limbs for all dogs. Vertical impulse values were higher in the thoracic limbs than the pelvic limbs. There were significant differences in mean vertical impulse between the thoracic and pelvic limbs for both groups. CONCLUSIONS AND CLINICAL RELEVANCE In this study, significant differences in temporospatial variables were identified between the thoracic limbs of clinically normal and CSM-affected dogs, with the values being smaller for the CSM-affected dogs than for the clinically normal dogs. A pressure-sensitive walkway may provide a valid, practical option for rapid, objective assessment of gait and response to treatment in dogs with CSM.

The Eu(II) ion rivals Gd(III) in its ability to enhance contrast in magnetic resonance imaging. However, all reported Eu(II)-based complexes have been studied in vitro largely because the tendency of Eu(II) to oxidize to Eu(III) has been viewed as a major obstacle to in vivo imaging. Herein, we present solid- and solution-phase characterization of a Eu(II)-containing cryptate and the first in vivo use of Eu(II) to provide contrast enhancement. The results indicate that between one and two water molecules are coordinated to the Eu(II) core upon dissolution. We also demonstrate that Eu(II)-based contrast enhancement can be observed for hours in a mouse.

Polyether ether ketone (PEEK) is a highly heat-resistant thermoplastic with excellent strength and elastic modulus similar to human bone, making it an attractive material for orthopedic implants. However, the hydrophobic surface of PEEK implants induces fibrous encapsulation which is unfavorable for stable implant anchorage. In this study, PEEK was coated via ion-beam-assisted deposition (IBAD) using a two-layer design of yttria-stabilized zirconia (YSZ) as a heat-protection layer, and hydroxyapatite (HA) as a top layer to improve osseointegration. Microstructural analysis of the coatings showed a dense, uniform columnar grain structure in the YSZ layer and no delamination from the substrate. The HA layer was found to be amorphous and free of porosities in its as-deposited state. Subsequent heat treatment via microwave energy followed by autoclaving crystallized the HA layer, confirmed by SEM and XRD analysis. An in vitro study using MC3T3 preosteoblast cells showed improved bioactivity in heat-treated sample groups. Cell proliferation, differentiation, and mineralization were analyzed by MTT assay and DNA content, osteocalcin expression, and Alizarin Red S (AR-S) content, respectively. Initial cell growth was increased, and osteogenic maturation and mineralization were accelerated most on coatings that underwent a combined microwave and autoclave heat treatment process as compared to uncoated PEEK and amorphous HA surfaces. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 560-567, 2017.

Ewing's sarcoma of bone is a primary childhood malignancy of bone that is treated with X-radiation therapy in combination with surgical excision and chemotherapy. To better study Ewing's sarcoma of bone we developed a novel model of primary Ewing's sarcoma of bone and then treated animals with X-radiation therapy. We identified that uncontrolled tumor resulted in lytic bone destruction while X-radiation therapy decreased lytic bone destruction and increased limb-length asymmetry, a common, crippling complication of X-radiation therapy. Osteoclasts were indentified adjacent to the tumor, however, we were unable to detect RANK-ligand in the Ewing's tumor cells in vitro, which lead us to investigate alternate mechanisms for osteoclast formation. Ewing's sarcoma tumor cells and archival Ewing's sarcoma of bone tumor biopsy samples were shown to express MCSF, which could promote osteoclast formation. Increased monocyte numbers were detected in peripheral blood and spleen in animals with untreated Ewing's sarcoma tumor while monocyte number in animals treated with x-radiation had normal numbers of monocytes. Our data suggest that our Ewing's sarcoma of bone model will be useful in the study Ewing's sarcoma tumor progression in parallel with the effects of chemotherapy and X-radiation therapy.

In magnetic resonance imaging, contrast agents are molecules that increase the contrast-to-noise ratio of non-invasively acquired images. The information gained from magnetic resonance imaging can be increased using responsive contrast agents that undergo chemical changes, and consequently changes to contrast enhancement, for example in response to specific biomarkers that are indicative of diseases. A major limitation with modern responsive contrast agents is concentration-dependence that requires the concentration of contrast agent to be known: an extremely challenging task in vivo. Here, we review advances in several strategies aimed at overcoming the concentration-dependent nature of responsive contrast agents.

The negative irradiation complications of growth loss leading to limb length asymmetry and pathological fracture incurred following radiation therapy in pediatric patients has led to a renewed interest in understanding the specific effects of irradiation on the growth plate and the surrounding bone. In the present report, we examined the radiation therapy effects on primary rat growth cartilage chondrocytes in order to determine the chondrocyte radiosensitivity relative to other bone cell constituents and tumor cells, the postirradiation temporal progression of radiation-induced alterations in chondrocyte function, and the time course for the functional restoration of chondrocyte pathways that drive the eventual recovery in growth function. We employed an in vitro primary rat costochondral growth cartilage cell culture model system to evaluate the radiation therapy effects on proliferative chondrocytes using serial radiation doses (0-20 Gy) that are well within the clinically relevant range. Following irradiation, all of the following occurred in a dose-dependent manner: proliferation decreased, cytotoxicity increased, several markers of apoptosis increased, markers of radiation-induced cellular differentiation increased, and cell synthetic activity was disturbed. Alterations in proliferation, cell death, and induction of apoptosis are likely due to a transient radiation-induced derangement of the parathyroid hormone-related protein-Indian hedgehog proliferation-maturation pathway. Alterations in cellular differentiation and cell synthetic activity are novel observations for chondrocytes. Further, these results correspond very well to our previous work in an in vivo Sprague-Dawley rat model, making this model particularly relevant to researching the radiation therapy effects on longitudinal growth.

Pathological fracture is a devastating complication of osteolytic bone metastases. The progression of osteolysis and its effect on bone fracture risk are poorly understood. The goal of this study was to determine the temporal changes in bone strength following tumor inoculation in a preclinical model of tumor osteolysis. In addition, a predictive model was developed between non-invasive radiographic measures and bone strength. The right femora of female nude mice were injected with breast cancer cells; the left limb served as a sham-operated control. Radiographs and DEXA scans were obtained at the time of surgery and at 3, 6, and 9 weeks. Groups of mice were euthanized at each time point for mechanical assessment. Micro-CT analysis was performed on a sub-set of mice with advanced state disease to quantify bone loss. Radiographs documented an increase in tumor osteolysis over time, with 58% of the mice showing signs of osteolysis at 3 weeks, 75% at 6 weeks, and 81% at 9 weeks. BMD measurements revealed a 21.6% increase from baseline in the controls whereas tumor-injected femora failed to increase in BMD over the same time course. Tumor-bearing limbs exhibited statistically significant decreases in torque at failure (86%), energy to failure (88%), and initial stiffness (94%) compared to the controls. Both lysis scores and BMD measurements proved to be modest predictors of mechanical strength, accounting for approximately 73% and 41% of variation in torque at failure, respectively. Micro-CT analysis revealed decreases in both total bone volume in the distal femur (31%) and metaphyseal fractional trabecular bone (89%). We have shown that non-invasive radiographic techniques provide a useful tool for monitoring the progression of tumor osteolysis and for predicting the mechanical strength of tumor-bearing bones in this model. By integrating non-invasive measures of tumor osteolysis and fracture risk, we have validated a clinically relevant platform for evaluating new therapeutic approaches for preserving and/or restoring bone affected by metastatic disease.

Bone metastasis is a common untreatable complication associated with prostate cancer. Metastatic cells seed in skeletal sites under active turnover containing dense marrow cellularity. We hypothesized that differences in these skeletal-specific processes are among the critical factors that facilitate the preferential localization of metastatic prostate cancer in bone. To test this, athymic mice were administered PTH to induce bone turnover and increase marrow cellularity daily 1 wk before and after intracardiac inoculation of luciferase-tagged PC-3 cells. Tumor localization was monitored by bioluminescence imaging weekly for 5 wk. At the time of tumor inoculation, PTH-treated mice demonstrated significant increases in serum levels of bone turnover markers such as osteocalcin and tartrate-resistant acid phosphatase 5b and in the number of tartrate-resistant acid phosphatase-positive osteoclasts per millimeter of bone when compared with the other groups. Likewise, PTH treatment stimulated a qualitative increase in marrow cellular proliferation as determined by 5-bromo-2'-deoxyuridine immunostaining. Skeletal metastases formed in the hind limb and craniofacial regions of young mice with no difference between groups. In adult mice, however, bioluminescent signals in the hind limb and craniofacial regions were 3-fold higher in PTH-treated mice vs. controls. Fluorochrome labeling revealed increased bone formation activity in trabecular bone adjacent to tumors. When zoledronic acid, a nitrogen-containing bisphosphonate that inhibits osteoclast-mediated bone resorption, was administered concurrently with PTH, a significant reduction in the incidence of bone tumors was observed. Overall, these studies provide new evidence that skeletal sites rich in marrow cellularity under active turnover offer a more congenial microenvironment to facilitate cancer localization in the skeleton.

At therapeutic levels in pediatric patients, radiation causes damage to the growth plate and contributes to growth deformity and fractures. The purpose of this project was to examine the effects of x-ray irradiation on regional bone mineral density (BMD) and osteoclast histology of rat bone with and without radioprotectant amifostine (AMF) pretreatment. Seventy-two weanling rats had their right knee irradiated with single fraction 17.5 Gy, whereas the left leg was used as an internal control. Twelve animals were euthanized at each of 6 time periods (0.5-6 wk) after irradiation, half having received 100 mg/kg amifostine. BMD (g/cm3) was determined for both the right and left femurs using peripheral quantitative computed tomography (CT) (pQCT). Tibial sections were stained for osteoclasts/chondroclasts with tartrate-resistant acid phosphatase. Statistically significant increases in BMD within the radiation field were seen in the treatment groups' right irradiated legs over the control unirradiated left legs at all time points from 0.5 through 6 weeks. Anatomically, a peak in BMD occurs in the region immediately adjacent to the chondro-osseous junction at 2 weeks after irradiation and then moves proximally within the adjacent metaphysis after 3 weeks. Corresponding to these findings, histologically a 2-week nadir occurs after irradiation in osteoclasts/chondroclast numbers adjacent to the chondro-osseous junction with a 71.9% decrease compared with controls (p

We report a kinetic study of the water exchange on lanthanide ions in water/[1-ethyl-3-methylimidazolium][trifluoromethylsufate] (water/[EMIm][OTf]). The results from 17O-NMR measurements show that the water-exchange rates in water/[EMIm][OTf] increase with decreasing size of the lanthanide ions. This trend for water-exchange is similar to the previously reported trend in water/1-ethyl-3-methylimidazolium ethyl sulfate (water/[EMIm][EtSO4]) but opposite to that in water. To gain atomic-level insight into these water-exchange reactions, molecular dynamics simulations for lanthanide ions in water/[EMIm][OTf] have been performed using the atomic-multipole-optimized-energetics-for-biomolecular-application polarizable force field. Our molecular dynamics simulations reproduce the experimental water-exchange rates in terms of the trend and provide possible explanations for the observed experimental behavior. The smaller lanthanide ions in water/[EMIm][OTf] undergo faster water exchange because the smaller lantha...