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Purpose Partial meniscectomy is a common orthopedic procedure intended to improve knee pain and function in patients with irreparable meniscal tears. However, 6–25% of partial meniscectomy patients experience persistent knee pain after surgery. In this randomized controlled trial (RCT) involving subjects with knee pain following partial meniscectomy, it was hypothesized that treatment with a synthetic medial meniscus replacement (MMR) implant provides significantly greater improvements in knee pain and function compared to non-surgical care alone. Methods In this prospective, multicenter RCT, subjects with persistent knee pain following one or more previous partial meniscectomies were randomized to receive either MMR or non-surgical care. This analysis evaluated the 1-year outcomes of this 2-year clinical trial. Patient-reported knee pain, function, and quality of life were measured using nine separate patient-reported outcomes. The primary outcomes were the pain subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS) and the average of all five KOOS subscales (KOOS Overall). Treatment cessation was defined as permanent device removal in the MMR group and any surgical procedure to the index knee in the non-surgical care group. Results Treated subjects had a median age of 52 years old (range 30–69 years) and one or more previous partial meniscectomies at a median of 34 months (range 5–430 months) before trial entry. Among 127 subjects treated with either MMR (n = 61) or non-surgical care (n = 66), 11 withdrew from the trial or were lost to follow-up (MMR, n = 0; non-surgical care, n = 11). The magnitude of improvement from baseline to 1 year was significantly greater in subjects who received MMR in both primary outcomes of KOOS Pain (P = 0.013) and KOOS Overall (P = 0.027). Treatment cessation was reported in 14.5% of non-surgical care subjects and only 4.9% of MMR subjects (n.s.). Conclusion Treatment with the synthetic MMR implant resulted in significantly greater improvements in knee pain, function, and quality of life at 1 year of follow-up compared to treatment with non-surgical care alone. Level of evidence I.

Aurora kinases play a key role in mitotic progression. Over-expression of Aurora kinases is found in several human cancers and correlated with histological malignancy and clinical outcomes. Therefore, Aurora kinase inhibitors should be useful in the treatment of cancers. Cell-based screening methods have an advantage over biochemical approaches because hits can be optimized to inhibit targets in the proper intracellular context. We developed a novel Aurora kinase inhibitor R763/AS703569 using an image-based phenotypic screen. The anti-proliferative effect was examined in a panel of tumor cell lines and primary cells. The efficacy was determined in a broad panel of xenograft models. R763/AS703569 inhibits Aurora kinases, along with a limited number of other kinases including FMS-related tyrosine kinase 3 (FLT3), and has potent anti-proliferative activity against many cell types accompanying unique phenotypic changes such as enlarged cell size, endoreduplication and apoptosis. The endoreduplication cycle induced by R763/AS703569 was irreversible even after the compound was withdrawn from the culture. Oral administration of R763/AS703569 demonstrated marked inhibition of tumor growth in xenograft models of pancreatic, breast, colon, ovarian, and lung tumors and leukemia. An acute myeloid leukemia cell line MV4-11, which carries a FLT3 internal tandem duplication mutation, is particularly sensitive to R763/AS703569 in vivo. R763/AS703569 is a potent inhibitor of Aurora kinases and exhibited significant anti-proliferative activity against a wide range of tumor cells both in vitro and in vivo. Inhibition of Aurora kinases has the potential to be a new addition to the treatment of cancers.

High-resolution transmission electron microscopy studies of hydrothermally derived platelike lead titanate nanoparticles reveal that below a critical size of approximately 70 nm, the single ferroelectric domain polarization axis reorients from perpendicular to parallel to the plate. We suggest that during particle growth, ions in the hydrothermal processing medium compensate for the ferroelectric depolarization energy. When the processing medium is removed by washing and drying, single domain nanoparticles minimize their depolarization energy by c-axis flipping.

Preferred orientation in textured ceramics is often assessed by comparing the relative intensities of x-ray diffraction reflections to those of a randomly oriented ceramic using the Lotgering degree of orientation (f). However, this paper provides evidence that indiscriminate assessments of f can be misleading. Using measured intensities of a modestly textured tape cast bismuth titanate (Na0.5Bi4.5Ti4O15) ceramic, calculated f values vary from 7.4 to 73.2% depending on the reflections included in the calculation. The texture is also quantified by calculating the orientation distribution function (ODF) using measured pole figures. A model is then presented that demonstrates f is nonlinear with the multiple of preferred (00l)-orientations, the standard unit of the 00l pole figure.

Polycrystalline BaxSr(1−x)TiO3 (BST) thin films were processed on Pt-coated glass substrates at temperatures below 100 °C by reacting TiO2 films in alkaline solutions containing Ba2+ and/or Sr2+. The TiO2 was deposited by spin-casting a titanium metalorganic precursor onto Pt-coated glass substrates, followed by pyrolysis in air at 400 °C. Film stoichiometry deviated from the initial solution composition, with a preferred incorporation of Sr2+ into the perovskite lattice. The BST thin films had dielectric constants ranging from 100 to 185 and dielectric loss values below 0.25. Capacitance–voltage and current–voltage relationships were examined to determine the effect of phase stoichiometry and processing route on dielectric properties.

Metalorganic liquid precursors were used to examine the effects of processing atmosphere on texture development in oriented Pb(Zr0.60Ti0.40)O3 thin films. After removal of organic ligands via pyrolysis, the films were heated at 25 °C/min in a 5% H2/Ar atmosphere until a switching temperature, after which the atmosphere was switched to pure oxygen. The films were heated to a maximum temperature of 650 °C with switching temperatures ranging from 450 to 600 °C. The degree of (111) orientation in the lead zirconate titanate (PZT) films increased with increasing switching temperature, resulting in highly textured (111) PZT films. These results suggest that atmosphere control plays a significant role in texture development during rapid thermal processing.

Successful application of sol-gel, metalorganic decomposition, or hydrothermal routes to ceramic thin films depends on the mechanical integrity of the precursor film. Above a critical thickness, a precursor film will crack or decohere from the substrate during drying. The cracking and thickness of thin metalorganic precursor films were simultaneously observed during drying using a standard optical microscope. Isochromatic color fringes produced by interference of reflected white light were used to monitor film thickness. The critical film thickness was determined by the color fringe corresponding to the thickness at which propagating cracks terminated. As a demonstration of the technique, the critical thickness of titanium di(isopropoxide) bis(ethyl acetoacetate) films was measured, showing increased critical thickness with the addition of small amounts of an elastomeric polymer.

Leg pain in athletes has many aetiologies. The clinician must strive to specifically define the clinical problem in order to administer the appropriate treatment for the athlete’s condition. Clinical conditions in the leg causing symptoms in athletes include chronic exertional compartment syndrome (CECC), tendinitis, medial tibial stress syndrome, stress fractures, fascial defects, musculotendinous junction disruptions (tennis leg), popliteal artery entrapment syndrome, effort-induced venous thrombosis and nerve entrapment. Appropriate diagnostic studies are needed to allow accurate diagnosis. A work-up might include radiographs, bone scans and compartment pressure measurement. Many of these conditions relate to overuse and training errors. Conservative measures including rest, activity modification and rehabilitation will permit a gradual return to participation in sports. Some problems, such as CECC, popliteal artery entrapment syndrome and nerve entrapment may require surgical intervention to allow the resolution of symptoms. Clinicians should be familiar with the range of problems causing leg pain in order to prescribe specific treatment for each athlete.

Bone substitutes are often required to replace damaged tissue due to injuries, diseases and genetic malformations. Traditional bone substitutes, such as autografts, allografts, xenografts and metal implants, are far from ideal as each have their own specific problems and limitations. Bone tissue engineering offers a promising opportunity for bone regeneration in a natural way. However, currently the scientific challenges of bone tissue engineering lie in the development of suitable scaffold materials that can improve bone cell adhesion, proliferation and differentiation. The design of nanophase titania/polymer composites offers an exciting approach to combine the advantages of a degradable polymer with nano-size ceramic grains that optimize biological properties for bone regeneration. Importantly, nanophase titania mimics the size scale of constituent components of bone since bone itself is a nanostructured composite composed of nanometer hydroxyapatite crystals well-dispersed in a mostly collagen matrix. Previous studies have shown significant improvement in protein adsorption, osteoblast (bone-forming cell) adhesion and long-term functions on nano-grain ceramic materials compared to traditional micron-grain ceramic materials. This study used nanometer grain size titania dispersed in a model polymer (PLGA or poly-lactic-co-glycolic acid) matrix by using various sonication powers to increase osteoblast adhesion. The surface characteristics of the composites, such as topography, titania surface area coverage and surface roughness, were studied by scanning electron microscopy and atomic force microscopy. Of all the composites formulated in this study, osteoblast adhesion was the greatest on nanophase titania/PLGA (30/70 wt.%) sonicated at 118.75 for 10 minutes; this composite was the closest in terms of nanometer surface roughness compared to bone of all the composites formulated. In this manner, this study suggests that nanophase titania sonicated in PLGA under these conditions should be further studied for orthopedic applications.

Much work is needed in the design of more effective bone tissue engineering materials to induce the growth of normal bone tissue. Nanotechnology offers exciting alternatives to traditional bone implants since bone itself is a nanostructured material composed of nanofibered hydroxyapatite well-dispersed in a mostly collagen matrix. For this purpose, poly-lactic-co-glycolic acid (PLGA) was dissolved in chloroform and nanometer grain size titania was dispersed by various sonication powers from 0 W to 166 W. Previous results demonstrated that the dispersion of titania in PLGA was enhanced by increasing the intensity of sonication and that greater osteoblast (bone-forming cells) adhesion correlated with improved nanophase titania dispersion in PLGA. However, adhesion of osteoblasts to material surfaces, alone, is not adequate to determine long-term functions of implant materials. For this reason, and as a next step to determine the efficacy of nanocomposites in bone applications, subsequent functions of osteoblasts on nanophase titania/PLGA composites were investigated in vitro in this study. For the first time, results correlated better osteoblast long-term functions, specifically the deposition of calcium-containing mineral, with improved nanophase titania dispersions in PLGA.In this manner, the present study demonstrated that PLGA composites with well-dispersed nanophase titania can improve osteoblast functions necessary for the further investigation of these materials in orthopedic applications.

Plasma spray deposition of hydroxyapatite (HA) onto a titanium implant involves high temperatures that may alter HA crystallinity and induce cracks in the coating. For this reason, the objective of this study was to design a novel HA coating material and method. Titanium was coated with HA, titania, and Poly (dl-lactic-glycolic acid) (PLGA) using sol-gel processing. The biocompatibility of the HA coating in the present study was compared to that of a plasmasprayed HA coating. Results of this study showed that osteoblast adhesion was promoted more in the HA coating proposed in this study than on the plasma-sprayed HA coating. In addition, hydrothermal treatment of the coating appeared to improve the biocompatibility of the HA coating. Since osteoblast adhesion is a necessary requirement for increased bonding of an implant to juxtaposed bone, these results support that hydrothermally sol-gel processed HA may be an optimal implant coating material and method.

Nanocrystalline lead titanate was synthesized by reacting nanocrystalline titanium oxide in aqueous solutions of potassium hydroxide and lead acetate at 200 degrees C. X-ray diffraction (XRD) and TEM studies suggest that the initial KOH concentration influenced the nucleation and growth behavior of the lead titanate nanoparticles. Powders were processed in aqueous solutions containing 0.10 M lead acetate and a Pb:Ti ratio of 1, with varying concentrations of KOH. Powders processed in 0.01 M KOH were composed of irregularly shaped particles with 50-100 nm in size, processing in 0.10 M KOH produced particles with finger-like morphology and broader particle size distribution, and processing in 1.0 M KOH resulted in anisometric plates with (001) facets, and 100-200 nm in size. XRD studies have shown systematic variations in the position and symmetry of reflections with a l component as a function of particle size. This indicates that the c/a ratio of lead titanate increases with decreasing nanoparticle size

Polarization versus applied field (P-E) hysteresis loop measurements on Pb(Zr,Ti)O3 (PZT) thin films were performed using a controlled-atmosphere probe station. Measurements were made using two different capacitor configurations, each producing differing results. The capacitor configurations included using either the typical arrangement of two top electrodes (planar) or an arrangement using contacts to the top and the bottom electrodes (sandwich). The films included PZT films deposited using pulsed laser deposition (PLD) and commercially-available rfsputtered PZT thin films. Qualitatively similar results were obtained for both types of films. For both PLD and Ramtron PZT films, translation of ferroelectric hysteresis loops along the polarization axis was observed for sandwich capacitors. The magnitude of this voltage was strongly dependent on the partial pressure of oxygen at room temperature. Translations were not observed for the same films using the planar capacitor configuration. However, for both sandwich and planar configurations, the thin film capacitance was sensitive to changes in pO2.

The influence of Pb/Ti ratio on the particle size of hydrothermally derived lead titanate (PbTiO3) powders was investigated. Phase pure PbTiO3 powder was synthesized by reacting nanocrystalline TiC2 powder in a 1 m KOH solution for 15 h at 200°C with Pb/Ti ratios of 1 and 5. Faceted platelet particles with a low aspect ratio were formed in solutions with Pb/Ti ratios of 1 and 5. The observed particle size of PbTiO3 was 200 nm and larger when Pb/Ti = 1, while 50 - 100 nm sized particles formed when Pb/Ti = 5. In support of TEM observations, the BET specific surface area data increased from 4.4 m2/g to 7.3 m2/g as the Pb/Ti ratio was increased from I to 5. PbTiO3 particle size was controlled by either inhibiting or promoting dissolution-precipitation. Dissolution-precipitation in a high pH solution was inhibited by maintaining an excess of Pb ions in solution and it was promoted when input concentrations of Pb and Ti were equivalent.

Composite BaTiO3/polymer films (in-situ growth of BaTiO3 particles in a polymer matrix. A solution of a polybutadiene/polystyrene triblock copolymer and titanium diisoproxide bis(ethlyacetoacetate) dissolved in toluene was cast onto a Ag-coated substrate. Subsequent hydrothermal treatment of the films in 1.0 M Ba(OH)2 solutions at 80° C resulted in the nucleation and growth of BaTiO3 within the polymer matrix. The volume fraction/connectivity of BaTiO3 was controlled by varying the relative amounts of titanium precursor and polymer in solution. Growth of BaTiO3 within the polymer was examined by infrared spectroscopy and electron microscopy. The dielectric constant of the composite films increased with BaTiO3 content.

PZT thin films with the composition Pb(Zr0.6Ti0 4)O3 were processed via metallo-organic decomposition (MOD) with {111} and {100} orientations. Ferroelectric measurements showed that the {111} and {100} oriented films had remanent polarizations of 19.5 μC/cm2 and 16 μC/cm2, respectively. Both x-ray pole figure analysis and the Harris texture index were used to quantify the degree of {100}, {110}, and {111} orientation in each film, with reasonable agreement between the two methods. The {100} oriented thin film was determined to be 582 times random for the Harris technique versus 522 times random for pole figure analysis, while the {111} oriented film was 41 times random for the Harris technique and 81 times random for pole figure analysis. The axisymmetric texture of the films allow 2-D pole figure analysis to provide a quantitative characterization of film texture.

BaxSr1-xTiO3 (BST) thin films and powders were processed below 100°C by hydrolyzing Ti metal-organic precursors and TiO2 powder in alkaline Ba/Sr containing aqueous solutions. Film and powder stoichiometries were examined by x-ray diffraction (XRD), and powder stoichiometries were measured by wavelength dispersive spectroscopy (WDS). Both XRD and WDS results showed that Sr cations were more readily incorporated in BST than Ba cations. A thermodynamic model is introduced to predict BST stoichiometry for pH and solution composition. The model is demonstrated for carbonates that also form hydrothermally with Ba and Sr in solid solution, showing good agreement with experimentally measured stoichiometries and confirming a higher reactivity of the Sr cation.

Current metal/metal oxide patterning techniques typically involve photolithography, an expensive, time-consuming process, and/or a vacuum system, which also adds significantly to the cost. In this study, fabrication of metal oxide upper electrodes for Pb(ZrxTi1-x)O3 (PZT) memories by metallorganic decomposition (MOD) was coupled with laser beam patterning. Metal oxide organic precursors were treated with an absorption-enhancing dye and were spun on to ferroelectric PZT films followed by selective area laser beam exposure. This technique was employed to pattern RuO2 and (La,Sr)CoO3 electrodes. A variety of patterns (dot, line, and circular) were prepared which demonstrates the suitability of laser patterning for a variety of applications. The minimum power density required to generate a continuous conductive oxide pattern was found to be approximately 2.5 kW/cm2 at a scan speed of 25 mm/min. Resistivity values for the patterned lines were 660 Ω-cm for RuO2 and 59 mΩ-cm for LSCO.

In the conclusion to this multi-part article I first review the discussions carried out around the six essential questions in psychiatric diagnosis – the position taken by Allen Frances on each question, the commentaries on the respective question along with Frances’ responses to the commentaries, and my own view of the multiple discussions. In this review I emphasize that the core question is the first – what is the nature of psychiatric illness – and that in some manner all further questions follow from the first. Following this review I attempt to move the discussion forward, addressing the first question from the perspectives of natural kind analysis and complexity analysis. This reflection leads toward a view of psychiatric disorders – and future nosologies – as far more complex and uncertain than we have imagined.

In face of the multiple controversies surrounding the DSM process in general and the development of DSM-5 in particular, we have organized a discussion around what we consider six essential questions in further work on the DSM. The six questions involve: 1) the nature of a mental disorder; 2) the definition of mental disorder; 3) the issue of whether, in the current state of psychiatric science, DSM-5 should assume a cautious, conservative posture or an assertive, transformative posture; 4) the role of pragmatic considerations in the construction of DSM-5; 5) the issue of utility of the DSM – whether DSM-III and IV have been designed more for clinicians or researchers, and how this conflict should be dealt with in the new manual; and 6) the possibility and advisability, given all the problems with DSM-III and IV, of designing a different diagnostic system. Part I of this article took up the first two questions. Part II will take up the second two questions. Question 3 deals with the question as to whether DSM-V should assume a conservative or assertive posture in making changes from DSM-IV. That question in turn breaks down into discussion of diagnoses that depend on, and aim toward, empirical, scientific validation, and diagnoses that are more value-laden and less amenable to scientific validation. Question 4 takes up the role of pragmatic consideration in a psychiatric nosology, whether the purely empirical considerations need to be tempered by considerations of practical consequence. As in Part 1 of this article, the general introduction, as well as the introductions and conclusions for the specific questions, are written by James Phillips, and the responses to commentaries are written by Allen Frances.

Hydrothermally derived films of BaTiCO3 were fabricated by reacting thin layers of titanium organometallic liquid precursors in aqueous solutions containing Ba(OH)2 and having a high pH. Cubic submicron polycrystalline films of BaTiCO3 (thickness = 1 μm) were formed at 70°C. Low concentrations of block copolymers of polybutadiene and polystyrene were incorporated into the liquid precursor to prevent precursor film cracking. Higher polymer concentrations allowed fabrication of polymer/ceramic composite films by virtue of the low temperature used in hydrothermal processing.