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The aim of this article was to study clinical and radiographic outcomes following treatment of bone healing disorders with a novel osteoinductive system that utilizes poly (ethyl acrylate), fibronectin and an ultra-low concentration of recombinant human bone morphogenetic protein-2. A case series of nine dogs and two cats were treated, and clinical records and radiographs were reviewed. Radiographs were scored by two blinded observers using the modified Radiographic Union Score for Tibial Fractures. Long-term follow-up was obtained using the Canine Orthopaedic Index and Feline Musculoskeletal Pain Index. Follow-up data were available for 11 treatments (10 cases). Complications: three minor, three major, one catastrophic (non-union requiring amputation). Lameness median 320 (range: 42–1,082) days postoperatively: ‘sound’ (three cases), ‘subtle’ (two), ‘mild’ (three), ‘moderate’ (one), and ‘non-weightbearing’ (one). The attending clinician judged 9 of 11 treatments achieved radiographic union; modified Radiographic Union Score for Tibial Fractures observers 1 and 2 agreed with the clinician in 8/9 and 5/9 treatments respectively. Long-term Canine Orthopaedic Index scores for five dogs median 650 (range: 544–1,724) days postoperatively: 15/64 (median) for four dogs with acceptable outcomes, 30/64 in one dog with a poor outcome. Feline Musculoskeletal Pain Index scores for two cats 433 and 751 days postoperatively: 48/60 and 60/60. Eight of 10 cases were sound or showed subtle or mild lameness in the short- or long-term, and radiographic union occurred in the majority of treatments.

Understanding atypical forms of diabetes may lead to personalized treatment regimens and discovery of novel pathophysiologic mechanisms of diabetes. We aimed to create a high-throughput method for identifying patients with atypical diabetes in large electronic health record (EHR) databases and validate this method in the Mass General Brigham (MGB) Biobank. Patients with likely type 2 diabetes (T2D) were identified using a validated machine-learning (ML) algorithm. “Typical” T2D was filtered out through a “base algorithm” that excluded individuals with body mass index (BMI) ever >30 kg/m2, HDL values ever < 50 mg/dL, and triglycerides ever >150 mg/dL. To remove people with typical type 1 diabetes (T1D) , we tested six additional “branch algorithms,” relying on clinical characteristics, including autoantibodies, medication usage, and T1D diagnosis determined by ML algorithm, resulting in six overlapping cohorts. Charts were then manually reviewed, and diabetes type was classified by two endocrinologists into one of three categories: atypical, not atypical, and indeterminate due to missing information. We identified 1potentially atypical cases, of whom 16 individuals were confirmed to have atypical diabetes after expert review, across the six branch algorithms. The branch algorithm which excluded T1D by removing patients who had ever used outpatient insulin had the highest percentage yield (13 of 27; 48.2%) of atypical diabetes . The 16 atypical cases had significantly lower BMI and higher HDL compared to an unselected group of individuals with T1D or T2D diagnosis by ML algorithm. Compared to the ML T1D group, the atypical group had a significantly higher T2D polygenic score and lower hemoglobin A1c. In summary, we designed an algorithm to identify individuals with atypical diabetes within an EHR database with up to 48% yield which may shed light on the heterogeneity of T2D and help generate cohorts of atypical cases for studies, such as the Rare and Atypical Diabetes Network (RADIANT) . Disclosure V.Chen: Other Relationship; Draeger. S.Cromer: Other Relationship; Johnson & Johnson Medical Devices Companies, Research Support; National Institute of Diabetes and Digestive and Kidney Diseases. C.Han: None. W.G.Marshall: None. S.Emongo: None. T.Majarian: Employee; Vertex Pharmaceuticals Incorporated. J.C.Florez: Consultant; AstraZeneca, Goldfinch Bio, Inc., Other Relationship; AstraZeneca, Merck & Co., Inc., Novo Nordisk. J.M.Mercader: None. M.Udler: None.

High-pressure studies have been performed on the e-form of the powerful explosive CL-20. Hydrostatic compression over the pressure range 0–12 GPa has been monitored using synchrotron X-ray powder d...

We have determined the high pressure structure of perdeuterated ethanol by using neutron powder diffraction in the pressure region ∼2.5–4.0 GPa and compare it to that previously measured by single-crystal X-ray diffraction and the one suggested by ab initio structure calculations. In contrast to previous X-ray single-crystal studies, we see no evidence for a disordered proton around the hydroxyl group, but confirm the monoclinic symmetry in the measured pressure region. We also present the compression behaviour of the unit cell in this pressure range.

We report a pressure-induced transition to a new crystalline phase of biurea (C2D6N4O2). Neutron-powder diffraction and Raman spectra, measured up to 3.89 GPa reveal this transition to be isosymmetric, where substantial intramolecular reorientation leads to an abrupt decrease in unit cell volume at ∼0.6 GPa and an increase in some intermolecular contact distances. DFT and vibrational energy calculations suggest that the ambient pressure phase is stabilised by zero point energy and entropy, until the pressure–volume–driven transition at 0.6 GPa.

The crystal structure of the complex formed between acetone and bromine has been determined between 14 K and 200 K. The structure exhibits negative 2D thermal expansion at low temperature and colossal thermal expansion in the perpendicular dimension. At low temperature the C[double bond{,} length as m-dash]O bond is significantly longer than that observed in free acetone.

This study details the structural characterization of glycolide-h4 as a function of pressure to 6 GPa using neutron powder diffraction on the PEARL instrument at ISIS Neutron and Muon source. Glycolide-h4, rather than its deuterated isotopologue, was used in this study due to the difficulty of deuteration. The low background afforded by zirconia-toughened alumina anvils nevertheless enabled the collection of data suitable for structural analysis to be obtained to a pressure of 5 GPa. Glycolide-h4 undergoes a reconstructive phase transition at 0.15 GPa to a previously identified form (II), which is stable to 6 GPa.

Neutron powder diffraction has been used to determine accurate molecular structures and thermal expansion properties for the complexes formed between by iodine and bromine with 1{,}4 dioxane. The marked anisotropy in the magnitudes of the principal axes of the thermal expansion tensor for both compounds can be associated with the different intermolecular forces present{,} with the smallest values being associated with the halogen bonds formed between oxygen and the diatomic halogen molecules. The smallest thermal expansion coefficient of the 1{,}4 dioxane iodine complex is smaller than the corresponding coefficient in the corresponding bromine complex reflecting the stronger halogen bond formed between iodine and oxygen when compared to that formed between oxygen and bromine.

Neutron powder diffraction has been used to observe the changes in hydrogen bonding that occur as a function of temperature in ND4IO3 and, thus, determine the structural features that occur during the low-temperature (103 K) phase transition. It is shown that in the deuterated material the change is not a phase change per se but rather a structural reorganization in which the hydrogen bonding becomes firmly locked in at the phase transition temperature, and stays in this configuration upon further cooling to 4.2 K. In addition, both the differences and changes in the axial thermal expansion coefficients in the region 100–290 K can be explained by the changes involving both the hydrogen bonding and the secondary I...O halogen bonds.

The structure of the complex formed between trimethylamine and iodine monochloride had been redetermined by a combination of neutron powder diffraction and X-ray single crystal diffraction techniques. The structure determined using NPD shows that the geometry of the trimethylamine moiety resembles that in trimethylammonium cations rather than in the free trimethylamine molecule. The structure shows the presence of weak C–D⋯Cl hydrogen bonds, The I–Cl bond length is in agreement with that derived from an analysis of the pKb values of a series of nitrogen bases and previously determined structures containing N⋯ICl fragments.

The PEARL instrument at ISIS has been designed for, and dedicated to, in situ studies of materials at high pressure, using the Paris–Edinburgh press. In recent years, upgrades to the instrument have led to improvements in data quality and the range of achievable pressures and temperatures; currently 0.5–28 GPa and 80–1400 K. This paper describes the technical characteristics of the instrument, its current capabilities, and gives a brief overview of the science that has been performed, using representative examples.

The crystal structure of l-threonine has been studied to a maximum pressure of 22.3 GPa using single-crystal X-ray and neutron powder diffraction. The data have been interpreted in the light of previous Raman spectroscopic data by Holanda et al. (J. Mol. Struct. (2015), 1092, 160-165) in which it is suggested that three phase transitions occur at ca. 2 GPa, between 8.2 and 9.2 GPa and between 14.0 and 15.5 GPa. In the first two of these transitions the crystal retains its P212121 symmetry, in the third, although the unit cell dimensions are similar either side of the transition, the space group symmetry drops to P21. The ambient pressure form is labelled phase I, with the successive high-pressure forms designated I′, II and III, respectively. Phases I and I′ are very similar, the transition being manifested by a slight rotation of the carboxylate group. Phase II, which was found to form between 8.5 and 9.2 GPa, follows the gradual transformation of a long-range electrostatic contact becoming a hydrogen bond between 2.0 and 8.5 GPa, so that the transformation reflects a change in the way the structure accommodates compression rather than a gross change of structure. Phase III, which was found to form above 18.2 GPa in this work, is characterised by the bifurcation of a hydroxyl group in half of the molecules in the unit cell. Density functional theory (DFT) geometry optimisations were used to validate high-pressure structural models and PIXEL crystal lattice and intermolecular interaction energies are used to explain phase stabilities in terms of the intermolecular interactions.

This work reports the hydrostatic compression of the perdeuterated α-form of FOX-7 using neutron powder diffraction to follow the structural changes up to 4.58 GPa at room temperature. The equation of state for the hydrostatic compression of the α-form over the range 0–4.14 GPa has been determined, and a phase transition was observed over the pressure range 3.63–4.24 GPa. On the basis of dispersion-corrected density functional theory (DFT-D) calculations performed on the γ-form over a range of pressures, the high-pressure form observed in the neutron diffraction experiments can unambiguously be identified as being different from the γ-form and should therefore be denoted as the e-form. Based on similarities between the simulated and experimental powder diffraction patterns of the γ- and e-forms, it is suggested that the e-form adopts a planar, layered structure. The structural responses to pressure of the α-form observed experimentally are reproduced by DFT-D calculations, but in-depth analysis of the bon...

The high-pressure structural behaviour of phosphoric acid is described. A compression study of the monoclinic phase, using neutron powder diffraction and X-ray single-crystal diffraction, shows that it converts to a previously unobserved orthorhombic phase on decompression. Compression of this new phase is reported up to 6.3 GPa. The orthorhombic phase is found to be more efficiently packed, with reduced void space, resulting in a larger bulk modulus. Molecule–molecule interaction energies reveal a more extensive network of increased attractive forces in the orthorhombic form relative to the monoclinic form, suggesting greater thermodynamic stability.

The fluoroperovskite phase RbCaF3 has been investigated using high-pressure neutron powder diffraction in the pressure range ~0–7.9 GPa at room temperature. It has been found to undergo a first-order high-pressure structural phase transition at ~2.8 GPa from the cubic aristotype phase to a hettotype phase in the tetragonal space group I4/mcm. This transition, which also occurs at ~200 K at ambient pressure, is characterised by a linear phase boundary and a Clapeyron slope of 2.96 × 10−5 GPa K−1, which is in excellent agreement with earlier, low-pressure EPR investigations. The bulk modulus of the high-pressure phase (49.1 GPa) is very close to that determined for the low-pressure phase (50.0 GPa), and both are comparable with those determined for the aristotype phases of CsCdF3, TlCdF3, RbCdF3, and KCaF3. The evolution of the order parameter with pressure is consistent with recent modifications to Landau theory and, in conjunction with polynomial approximations to the pressure dependence of the lattice parameters, permits the pressure variation of the bond lengths and angles to be predicted. On entering the high-pressure phase, the Rb–F bond lengths decrease from their extrapolated values based on a third-order Birch–Murnaghan fit to the aristotype equation of state. By contrast, the Ca–F bond lengths behave atypically by exhibiting an increase from their extrapolated magnitudes, resulting in the volume and the effective bulk modulus of the CaF6 octahedron being larger than the cubic phase. The bulk moduli for the two component polyhedra in the tetragonal phase are comparable with those determined for the constituent binary fluorides, RbF and CaF2.

The equation of state and the crystal structure of the gillespite-structured phase Ba 0.5 Sr 0.5 CuSi 4 O 10 have been determined at seventeen pressures, ambient to 6.5 GPa, using powder neutron diffraction. At ~4.45 GPa, a structural phase transition is observed from the low-pressure structure, in space group P 4/ ncc , to a high-pressure structure in space group P 42 1 2. No experimental evidence was found for the presence of weak superlattice reflections with wave vector (2π/3 a , 2π/3 a , 0) that have recently been observed in the high-pressure, single-crystal X-ray diffraction patterns of the isostructural compounds BaCuSi 4 O 10 and BaCrSi 4 O 10 , and it should be noted that the possibility remains that the crystal structure reported here may represent the average of a similar commensurately ordered phase. The isothermal bulk modulus of the low-pressure phase, determined using a third-order Birch-Murnaghan equation of state, is 81.6(8) GPa with an initial pressure derivative of −3.3(3). The bulk modulus of the high-pressure phase was found to be smaller, estimated as 59.4 GPa. The phase transition appears to be driven by the need to relax the strong over-bonding of the alkaline-earth site, but apparently not that associated with the square-planar copper sites, which remain significantly over-bonded in the high-pressure phase. The phase transition equates to the loss of the centres of symmetry in the low-pressure phase, and results in marked differences in the tilting of the symmetry-independent Si 2 O 7 polyhedral groups, and in the aplanarity of the associated bonded CuO 4 square-planar groups. From the limited data that exists on isostructural compounds of gillespite, the low-pressure structure appears to be unstable at volume reductions of 4–6 %, however the structure of the high-pressure phase seems to depend on whether or not the cation in the square-planar site is a Jahn-Teller ion.

The crystal structures of the simple monoclinic halogen-bonded complexes pyridine–ICl and pyridine–IBr have been redetermined using modern X-ray and neutron diffraction techniques. The representation quadric surfaces for the thermal expansion tensor have been found to consist of a hyperboloid of one sheet. Negative thermal expansion occurs parallel to the crystallographic b axis, whilst there is colossal thermal expansion in a direction approximately parallel to the a* direction. These effects arise because of a decrease in the strength of an already weak C–H⋯X (X = Br, Cl) hydrogen bond with increasing temperature. The decrease in strength of the hydrogen bonding originates because of the reduction in the strength of the halogen bond formed between the nitrogen atom and the IX moiety with increasing temperature. Thus since at 298 K the I–X bonds are shorter than at 110 K, there will be a smaller partial negative charge on the X halogen at 298 K, leading to a weaker C–H⋯X hydrogen bond.

Two crystalline phases of aniline have been investigated by a combination of single crystal X-ray diffraction data on aniline-h7 and neutron powder diffraction data on aniline-d7. Phase-I, which is formed on cooling the liquid at ambient pressure, is monoclinic (P21Ic). Orthorhombic (Pna21) phase-II was crystallised at 0.84 GPa at room temperature and structurally characterised at pressures up to 7.3 GPa. The strongest intermolecular interactions in both structures are NH···π contacts and NH···N H-bonds. These interactions occur within layers in both phases, and the phases differ in the way the layers are stacked. The structures of both phases have been obtained under two sets of identical conditions, at 0.84 GPa and 0.35 GPa and studied at room temperature by neutron powder and X-ray single-crystal diffraction. At 0.84 GPa phase-II is the thermodynamically stable form because it has a lower molar volume than phase-I, but as the pressure is reduced the volume of phase-I becomes less than that of phase-II, and at 0.35 GPa phase-II partially transformed into phase-I. PIXEL calculations indicate that the intermolecular interaction energy for pairs of molecules connected by H-bonds is -9 to -16 kJ mol-1 in phase-I and II at 0.84 GPa, but one of these becomes destabilising in phase-II at 7.3 GPa, with an energy of +1 kJ mol-1, making it similar to several compressed CH center···π contacts. The results demonstrate how the hierarchy of intermolecular interaction energies can be manipulated with pressure, driving a H-bond beyond its ambient-pressure distance limit into repulsive region of its potential, and trapping it within a compressed crystal structure.

Neutron powder diffraction data have been collected from deuterated ice VI (space groupP42/nmc,Z= 10) at 76 state points in its field of thermodynamic stability above 150 K (approximately 0.6

While the correlation of atherosclerotic plaque locations with local wall shear stress magnitude has been evaluated previously by other investigators in both right (RCA) and left coronary arteries (LCA), the relative performance of average wall shear stress (AWSS), average wall shear stress gradient (AWSSG), oscillatory shear index (OSI) and relative residence time (RRT) as indicators of potential atherosclerotic plaque locations has not been studied for the LCA. Here we determine the performance of said wall shear parameters in the LCA for the prediction of plaque development locations and compare these results to those previously found in the RCA.We obtained 30 patient-specific geometries (mean age 67.1 (± 9.2) years, all with stable angina) of the LCA using dual-source computed tomography and virtually removed any plaque present. We then performed computational fluid dynamics simulations to calculate the wall shear parameters.For the 96 total plaques, AWSS had a higher sensitivity for the prediction of plaque locations (86 ± 25%) than AWSSG (65 ± 37%, p0.05), OSI (67 ± 32%, p0.01) or RRT (48 ± 38%, p0.001). RRT had a higher PPV (49 ± 36%) than AWSS (31 ± 20%, p0.05) or AWSSG (16 ± 12%, p0.001). Segment 5 of the LCA presented with overall low values for sensitivity and PPV. Parameter performance in the remainder of the LCA was comparable to that in the RCA.AWSS features remarkably high sensitivity, but does not reach the PPV of RRT. This may indicate that while low wall shear stress is necessary for plaque formation, its presence alone is not sufficient to predict future plaque locations. Time dependent factors have to be taken into account as well.

The thermoelastic properties of a sample of chalcopyrite from the Palabora mine, South Africa, have been investigated in the temperature range 4.2 – 330 K at ambient pressure, and between 0.22 and 6.81 GPa at ambient temperature. Magnetization measurements indicated a transition to a second antiferromagnetically ordered phase in the region of 53 K; however, all attempts to characterize this magnetic phase by introducing an ordered moment onto the copper site were unsuccessful owing to the small magnitude of the refined magnetic moment. In agreement with other low-temperature crystallographic measurements made on non-antiferromagnetically ordered adamantine-structured semiconducting materials (group IV; I–VII, II–VI, III–V, I–III–VI2, II–IV–V2 compounds), chalcopyrite exhibits negative linear and volumetric thermal expansion over a significant temperature interval. Calculation of the speeds of sound for a number of high-symmetry wave vectors is consistent with Blackman’s model for negative thermal expansion. The unit-cell volume and isochoric heat-capacity have been fitted assuming a two-term Debye internal energy function, with consistent values being found for the two characteristic temperatures. The temperature dependence of the thermodynamic Gruneisen parameter shows a deep minimum of ~−3 at T/θ ~0.55 (θ is the Debye temperature at 0 K) and a high-temperature limit of ~0.7; these results are the first demonstration that a chalcopyrite-structured phase behaves in the characteristic manner of the simpler adamantine-structured semiconducting materials. No systematic variation in either the nuclear nor the magnetic structure was found between 4.2 and 330 K, and the vibrational Debye temperatures derived by fitting the temperature dependence of the isotropic atomic displacement parameters show no relationship to features in the phonon density of states function. The bulk modulus of chalcopyrite is 77(2) GPa, in good agreement with that determined by ab initio calculations and a recent X-ray-diffraction study, and its pressure derivative is 2.0(6). At high pressure, chalcopyrite remains antiferromagnetically ordered until 6.7(2) GPa, at which point a transition to an amorphous phase is observed. Slow decompression of this phase leads to only a limited recovery of the crystalline phase.

In article number 1800361, Matthew J. Dalby, Manuel Salmeron‐Sanchez, and co‐workers coat structural material, e.g., particles or scaffolds, with a bioactive synthetic material that organizes fibronectin to present BMP‐2 with high efficiency. This is used as a novel regenerative approach to heal critical‐sized bone defects. Simultaneous integrin and growth factor receptor synergistic signaling drives stem cell differentiation leading to bone regeneration in the first veterinary patient.

The phase diagram of the energetic material hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) has been explored using X-ray and neutron diffraction from ambient pressure to 8 GPa. Two phases of RDX have been structurally characterized. The high-pressure γ-polymorph exists above 4 GPa while the metastable β-polymorph has been isolated from the high boiling point solvent nitrobenzene. Interestingly, neutron diffraction measurements at high pressures and high temperatures show that the β-polymorph isolated under ambient conditions is not the same polymorph as can be accessed at high pressures and temperatures.

We have employed a combination of powder neutron diffraction and single-crystal synchrotron X-ray diffraction to characterize the pressure-induced phase transitions that occur in the perovskite-type relaxor ferroelectric PbSc0.5Ta0.5O3 (PST) and Pb0.78Ba0.22Sc0.5Ta0.5O3 (PST-Ba). At ambient pressure the symmetry of the average structure for both compounds is Fm\bar{3}m as a result of partial ordering of the Sc and Ta cations on the octahedral sites. At pressures above the phase transition both the neutron and X-ray diffraction patterns exhibit an increase in the intensities of h,k,l = all odd reflections and no appearance of additional Bragg reflections. Synchrotron single-crystal X-ray diffraction data show that the intensity of hhh peaks, h = 2n + 1, does not change with pressure. This indicates that the structural distortion arising from the phase transition has a glide-plane pseudo-symmetry along the 〈111〉 cubic directions. Rietveld refinement to the neutron powder data shows that the high-pressure phase has either R\bar{3}c or R\bar{3} symmetry, depending on whether the presence of 1:1 octahedral cation ordering is neglected or taken into account, and comprises octahedral tilts of the type a − a − a − that continuously evolve with pressure. The cubic-to-rhombohedral transition is also marked by a large increase in the anisotropy of the displacement ellipsoids of the Pb cations, indicating larger displacements of Pb cations along the rhombohedral threefold axis rather than within the perpendicular plane. For PST the anisotropy of the Pb displacement parameters decreases at approximately 3 GPa above the phase-transition pressure. For both PST and PST-Ba the average magnitudes of Pb-cation displacements expressed in terms of isotropic displacement ellipsoids gradually decrease over the entire pressure range from ambient to 7.35 GPa.

Objective: To describe the novel use of circular external skeletal fixation (CESF) for repair of bilateral fractures of the caudal aspect of the mandibles. Study Design: Clinical report. Animals: A 5-month-old female Newfoundland. Methods: A 2-ring CESF was used to immobilize the mandible relative to the maxillae. Results: Anatomic dental occlusion and reduction of the right hemimandible were achieved with mild malalignment of the left hemimandible. Fracture healing occurred within 20 days. Transient epistaxis and reduced temporomandibular joint range of motion occurred at the time of fixator removal but normal use of the mandible was reported 6 months postoperatively. Conclusions: CESF effectively immobilized the mandible permitting rapid fracture healing with minimal morbidity. Clinical Relevance: Maxillomandibular CESF may represent a simple, effective option for the management of challenging fractures involving the caudal aspect of the mandible.

This article reviews how the advances in the techniques for the collection and analysis of high-pressure X-ray and neutron diffraction data, augmented by spectroscopic data, now permit the accurate determination of the full crystal structure of energetic materials under extreme conditions. Using these methods, the crystal structure of the high-pressure γ-form of RDX (1,3,5-trinitrohexahydro-s-triazine) has been determined–the first case of a high-pressure structure of an energetic material. In addition, the crystal structure of the highly metastable β-form has been determined and, contrary to the previous reports, has been shown to be different from the form obtained at elevated temperatures and pressures.

Gene therapy is an attractive method for the treatment of cardiovascular disease. However, using current strategies, induction of gene expression at therapeutic levels is often inefficient. In this study, we demonstrate a novel electroporation method to enhance delivery of a plasmid expressing an angiogenic growth factor (vascular endothelial growth factor, i.e. VEGF), which previously documented to stimulate revascularization in coronary artery disease. DNA expression plasmids were delivered in vivo to the porcine heart with or without co-administered electroporation in order to determine the potential effect of electrically mediated delivery. The results demonstrated that plasmid delivery through electroporation significantly increased cardiac expression of VEGF compared to injection of plasmid alone. This is the first report demonstrating successful intracardiac delivery, through in vivo electroporation, of a protein expressing plasmid in a large animal.

The results are described of a series of neutron powder diffraction experiments over the pressure and temperature ranges 0

SummaryObesity is an increasingly important health problem for both man and dog. Osteoarthritis (OA) is a significant cause of pain and disability in both species. A link between obesity and OA has been established in man, though the exact mechanism of the relationship remains to be fully elucidated – current research supports both biomechanical and biochemical theories. There is good evidence (class I*) to support weight loss as an effective treatment for human knee OA. In the dog, the relationship is just beginning to be investigated. The results of one study in dogs (class IV evidence*) suggest that preventing the development of overweightness and obesity reduces the prevalence of hip dysplasia and OA of the hip and other joints. Three other studies (class III and IV evidence*) support weight loss as an effective treatment for OA in affected over-weight and obese dogs. Further research could yield greater understanding of the pathophysiology of this relationship, perhaps identifying novel therapeutic targets. Confirmation and better understanding of the positive effect of treating and preventing obesity on symptoms and prevalence of OA is likely to be valuable in the campaign against canine obesity.

An important intermediate phase in the crystallization of aqueous solutions of sodium sulfate is the highly metastable sodium sulfate heptahydrate (Na(2)SO(4).7H(2)O). This has been structurally characterized for the first time by in situ single crystal X-ray diffraction. The crystal structure shows that each sodium cation is octahedrally coordinated to water molecules, with a slight distortion due to one of the water molecules being disordered. The hydrated sodium cations are hydrogen-bonded to form a three-dimensional bonded network, which is markedly different from the architecture of one-dimensional bonded chains observed in sodium sulfate decahydrate (mirabilite). This major structural difference explains the reconstructive nature of the transformation observed between the heptahydrate and mirabilite. High-pressure crystallization of a 3.41 mol/kg water aqueous solution of sodium sulfate at 1.54 GPa in a diamond-anvil cell resulted in the formation of a previously unknown sodium sulfate hydrate, which we have determined by single crystal X-ray diffraction methods to be an octahydrate, Na(2)SO(4).8H(2)O. In this structure the sulfate ions are coordinated directly to sodium ions. This resembles anhydrous sodium sulfate (thenardite) but contrasts with the heptahydrate and decahydrate in which the sodium ions are coordinated exclusively by water molecules. This observation demonstrates how the delicate balance of inter- and intramolecular bonds in the crystal structure can be significantly altered by the application of pressure.

Two high-pressure polymorphs of sulfuric acid monohydrate (oxonium hydrogensulfate) have been obtained at ambient temperature by crystallisation at high pressure from the liquid at 1.3 GPa (form III) and by direct compression of the ambient-pressure form I first to 1.26 GPa (form II) and then to 1.72 GPa (form III). The structure of form III was solved by single crystal X-ray diffraction and this structure was used as the basis for the refinement of hydrogen positions using high-pressure neutron powder diffraction data. Form III crystallises in the orthorhombic crystal system at 1.97 GPa, and features parallel chains of hydrogensulfate ions linked by oxonium ions to form a three-dimensional hydrogen-bonded network. On further compression to 3.05 GPa, the direction of maximum compressibility is found to be along the a-axis and is associated with the shortening of a hydrogen bond between a hydrogensulfate ion and an oxonium ion. The structure of form II remains elusive although at ambient temperature it is stable (or metastable) at pressures as low as 0.42 GPa, perhaps indicating that it could be recoverable to ambient-pressure at low temperature.

The crystal structure of deuterated topaz [topaz-OD; Al2SiO4(OD)2], synthesized at 10 GPa and 800 °C, has been determined using neutron powder diffraction at pressures up to 7.5 GPa. The linear axial compressibilities obtained from regressions of the lattice constants vs. pressure are βa = 1.87(1) × 10 –3 GPa –1 , βb = 1.71(1) × 10 –3 GPa –1 , and βc = 2.73(1) × 10 –3 GPa –1 . The occupancy of the D1 site was found to be greater than that of D2, as shown independently using neutron diffraction and infrared spectra at ambient conditions. A bifurcated hydrogen bond involving the D1 site, O4-D1···O2 and O4D1···O3, and a trifurcated hydrogen bond involving D2 site, O4-D2···O1, O4-D2···O2, and O4-D2···O4 are proposed for hydrogen-bond donor and acceptor pairs in addition to those reported previously. The observed pressure dependences of the hydrogen-bonding geometry show that these donor and acceptor pairs are classifiable into two types of interaction: (1) those that strengthen as a function of pressure (O4-D1···O3, O4-D2···O2, and O4-D2···O4) and (2) those that weaken (O4-D1···O1 and O4-D2···O1). These results also demonstrate that the reason for the contrasting behavior of the ν(OH) between F-rich natural topaz and topaz-OH are both the cooperative effect, O4-D2···O4-D1···O3, and the increasing Al-O4 distance.

The structure of CaIrO 3 ( Cmcm ) has been refined at high pressure and at low temperature using time-of-flight neutron powder diffraction data. Evidence supporting deviation from space group Cmcm to Cmc 2 1 is inconclusive. As CaIrO 3 ( Cmcm ) unit-cell volume changes, refinements indicate deformation of cation-centered coordination polyhedra, rather than tilting. Structure models demonstrate Ca 2+ -centered polyhedra are an order of magnitude more compressible than Ir 4+ -centered octahedra. Bond valence sums show significant chemical strain (over-bonding) of calcium and oxygen at ambient conditions. Implications for structure change in MgSiO 3 post-perovskite are discussed and a method for predicting the Clapeyron slope between perovskite and post-perovskite phases is proposed based on extrapolation of the volume-ratio between cation-centered polyhedra.

The crystal structure of the high-pressure phase of potassium hydrogen carbonate, here termed KHCO 3 form III, has been solved using single-crystal X-ray diffraction techniques. It adopts triclinic P 1 symmetry and is formed on direct compression of the monoclinic ambient-pressure phase (kalicinite, form I) via a first-order phase transition at 3.2 GPa (Δ V / V ~4%). We have also used time-of-flight high-pressure neutron powder-diffraction to determine the structural changes in KDCO 3 of the form I and III polymorphs to 8.3 GPa. This study indicates that the transition appears to be in response to pronounced displacements of the K + cations and the cooperative tilting of the (DCO 3 − ) 2 dimers. The O···O hydrogen bond distance shows a monotonic compression over the entire pressure range studied with no obvious discontinuity at the phase transition. However, the O-D···O bond angle appears to exhibit an abrupt ~4° decrease across the I–III phase transition with a concomitant change in its pressure dependence. Birch Murnaghan fits to the equation of state data above and below the transition indicate that form III [B 0 = 26.5(2.8) GPa, B′ = 5.2(6)] is marginally less compressible than form I [B 0 = 22.7(8) GPa, B′ = 4.1(5)].

We have investigated the P-T phase diagram of ammonia dihydrate (ADH), ND3 center dot 2D(2)O, using powder neutron diffraction methods over the range 0-9 GPa, 170-300 K. In addition to the ambient pressure phase, ADH I, we have identified three high-pressure phases, ADH II, III, and IV, each of which has been reproduced in at least three separate experiments. Another, apparently body-centred-cubic, phase of ADH has been observed on a single occasion above 6 GPa at 170 K. The existence of a dehydration boundary has been confirmed where, upon compression or warming, ADH IV decomposes to a high-pressure ice phase (ice VII or VIII) and a high-pressure phase of ammonia monohydrate (AMH V or VI).

This article shows that pressure can be a low-intensity route to the synthesis of polymethacrylic acid. The exploration of perdeuterated methacrylic acid at high pressure using neutron diffraction reveals that methacrylic acid exhibits two polymorphic phase transformations at relatively low pressures. The first is observed at 0.39 GPa, where both phases were observed simultaneously and confirm our previous observations. This transition is followed by a second transition at 1.2 GPa to a new polymorph that is characterized for the first time. On increasing pressure, the diffraction pattern of phase III deteriorates significantly. On decompression phase III persists to 0.54 GPa before transformation to the ambient pressure phase. There is significant loss of signal after decompression, signifying that there has been a loss of material through polymerization. The orientation of the molecules in phase III provides insight into the possible polymerization reaction.

The crystal structures of amino acids, which are composed of molecules in their zwitterionic tautomers, are usually interpreted in terms of strong NH…O hydrogen bond formation between the ammonium and carboxylate groups, supported by weaker dispersion or CH…O interactions. This view of the factors which promote thermodynamic stability in the crystalline amino acids has been re-examined in two phases of glycine, the trigonal γ-form, which is the thermodynamically most stable form under ambient conditions, and the ε-form, which is generated from γ-glycine at high pressure. A combination of Hirshfeld surface analysis, periodic DFT, PIXEL and symmetry-adapted perturbation theory calculations indicates that the conventional interpretation of intermolecular interactions in crystalline amino acids phases fails to recognise the over-whelming significance of Coulombic attraction and repulsion. There are no intermolecular interactions in either phase that can plausibly be described as dispersion-based. The interaction energies of molecules connected by so-called CH…O H-bonds are far in excess of accepted values for such interactions. Of the 14 closest intermolecular contacts in both phases, six have destabilizing interaction energies: in γ-glycine a hydrogen bond with ‘text-book’ NH…O contact geometry is part of a destabilising molecule-molecule interaction. The relative stabilities of the phases are best understood not in terms of a series of stabilising atom-atom contacts, but rather as a balance between efficient filling of space in the high-pressure ε-phase, and more weakly repulsive electrostatic whole-molecule interactions in the γ-phase.

Background The response of molecular crystal structures to changes in externally applied conditions such as temperature and pressure are the result of a complex balance between strong intramolecular bonding, medium strength intermolecular interactions such as hydrogen bonds, and weaker intermolecular van der Waals contacts. At high pressure the additional thermodynamic requirement to fill space efficiently becomes increasingly important. Results The crystal structure of piperidine-d11 has been determined at 2 K and at room temperature at pressures between 0.22 and 1.09 GPa. Unit cell dimensions have been determined between 2 and 255 K, and at pressures up to 2.77 GPa at room temperature. All measurements were made using neutron powder diffraction. The crystal structure features chains of molecules formed by NH…N H-bonds with van der Waals interactions between the chains. Although the H-bonds are the strongest intermolecular contacts, the majority of the sublimation enthalpy may be ascribed to weaker but more numerous van der Waals interactions. Conclusions Analysis of the thermal expansion data in the light of phonon frequencies determined in periodic DFT calculations indicates that the expansion at very low temperature is governed by external lattice modes, but above 100 K the influence of intramolecular ring-flexing modes also becomes significant. The principal directions of thermal expansion are determined by the sensitivity of different van der Waals interactions to changes in distance. The principal values of the strain developed on application of pressure are similarly oriented to those determined in the variable-temperature study, but more isotropic because of the need to minimise volume by filling interstitial voids at elevated pressure.

The room-temperature high-pressure behaviour of PbWO4 and BaWO4 scheelites (I41/a, Z = 4) has been studied with synchrotron angle-dispersive x-ray powder diffraction in a diamond anvil cell and time-of-flight neutron powder diffraction in a large-volume Paris–Edinburgh cell. Full profile Rietveld refinements of the neutron data provide evidence for distinct compressibility mechanisms in these materials. The distortion in the anionic array from the ideal fluorite packing in BaWO4 increases upon compression while it decreases in PbWO4.

The structural properties under hydrostatic pressure up to 3 GPa of the layered rare earth carbide halide superconductor Y2C2I2 are studied by neutron powder diffraction at room temperature. The compressibilities are anisotropic, such that the compressibility perpendicular to the layers is approximately twice as large as within the layers. The atomic positional parameters determined from the powder diffraction patterns as a function of pressure were used as the basis for highly resolved electronic structure calculations. These reveal the electronic density of states at EF to increase with pressure. As is shown quantitatively, this effect outweighs the pressure induced lattice stiffening effects and is responsible for the pressure induced increase and saturation of Tc towards 2 GPa.

The sequence of ferroelectric phase transitions (Pm3̅m—P4mm—Amm2) in BaTiO3 has been studied as a function of temperature (298 K–130 K) at a fixed pressure (3.2 GPa). The same sequence of transitions is observed as for ambient pressures, but the transition temperatures are reduced. The spontaneous strains of the non-cubic phases are determined. Whilst the structure of the tetragonal phase at high pressure is qualitatively similar to the ambient structure, both the spontaneous strain and the Ti displacement are smaller in the high pressure structure than the ambient structure.

Time-of-s ight neutron powder data and synchrotron infrared absorption spectra were collected for katoite hydrogarnet [Ca3Al2(O4D4)3] at pressures to 9.4 and 9.8 GPa, respectively. The phase transition from space group Ia3d to I4 3d was observed in the neutron spectrum at ∼7.5 GPa, as indicated by the presence of two weak res ections (730 and 530) that violate the hkl conditions (hk0, h ≠ 2n) imposed by the a-glide operation. However, attempts to reÞ ne the high-pressure structure in space group I4 3d did not signiÞ cantly improve the Þ t and produced a chemically unreasonable O-D bond length at the second D position. Structure reÞ nements in Ia3d indicate that (1) the O-D bond length, corrected for the effects of thermal motion, remains essentially constant (∼0.95 A) with increasing pressure; (2) hydrogen bond lengths shorten with increasing pressure; however, the variation in O-D⋅⋅⋅O angles indicates a preferential strengthening of H bonds; and (3) the compression mechanism is characterized by bond shortening rather than bond bending. The new results are in excellent agreement with both high-pressure X-ray diffraction experiments and ab initio calculations, and illustrate the need to eliminate peak broadening in high-pressure neutron powder experiments. IR spectra collected for the same sample showed discontinuities in both O-H and O-D vibrational frequencies at ∼5 GPa, suggesting that deuteration does not signiÞ cantly affect the pressure of the transition. The higher pressure observed for the transition in the neutron data is probably due to lower signal-to-noise levels, which mask the weaker, symmetry-forbidden res ections at lower pressure.

Although the application of high pressure to organic compounds may favour thermodynamically the adoption of a new polymorphic form, for compounds with high melting points there is often a substantial kinetic barrier to be overcome before the molecules can rearrange. Hence pressure-induced phase changes are often very slow or may not occur at all. We have overcome this problem by growing single crystals from solution at high pressure. Using this technique we have prepared and structurally characterised for the first time a new polymorph of acetamide and a sesquihydrate of parabanic acid. We also report the results of a high-pressure powder neutron diffraction study on parabanic acid-d 2 , which show that up to a pressure of 2.1 GPa direct compression does not induce a phase transition although several intermolecular interactions are substantially altered.

The structure of CrF3 has been studied in the pressure range from ambient to 9.12 GPa by time-of-flight neutron powder diffraction. Rietveld refinements of the crystal structure were performed in the space group R\overline 3 c for all the recorded data sets. It was found that volume reduction is achieved through rotation of the CrF6 octahedra and that the Cr—F—Cr bond angle decreases from 144.80 (7) to 133.9 (4)° within the investigated pressure range. Furthermore, a small octahedral strain was found to develop during compression. The octahedral strain reflects an elongation of the CrF6 octahedra along the c-axis direction. The zero-pressure bulk modulus B o and its pressure derivative B_o^{\prime} were determined to be B o = 29.2 (4) GPa and B^{\prime}_o = 10.1 (3).

The structure of ReO3has been studied over the pressure range from 1.27 to 8.01 GPa by neutron powder time-of-flight diffraction as well as by X-ray diffraction up to 41 GPa using Fluorinert as the pressure-transmitting medium. The cubic Im\bar{3} phase was found to be stable in the pressure range 0.5 to 13.2 GPa and to be highly compressible with a zero-pressure bulk modulus ofBo= 43 (1) GPa. The neutron data were used in least-squares refinements, showing that the ReO6octahedra remain almost undistorted, while the Re—O—Re bond angle decreases from 166.5 (1) to 146.4 (3)° within the investigated pressure range of 1.27 to 8.01 GPa. The compression mechanism is also described in terms of sphere-packing models of the oxygen anions.

The temperature-dependence of the cation distribution in synthetic spinel (MgAl 2 O 4 ) was investigated using in situ time-of-flight neutron powder diffraction at ISIS, the pulsed-neutron source at the Rutherford Appleton Laboratory. Neutron diffraction patterns of stoichiometric MgAl 2 O 4 were collected on heating from room temperature to ∼1600 K at pressures of ∼2.6 GPa. The cation distribution was determined directly from site occupancies obtained by Rietveld refinement. The equilibrium non-convergent ordering was analyzed using the O’Neill-Navrotsky (1983) thermodynamic model, which fits the observed behavior well over the temperature range of the measurements. Fitting the data between 790 and 1600 K yields α = 31(6) kJ/mol and β = −20(13) kJ/mol in the expression for the free energy of ordering. The high-pressure temperature-dependent behavior, as compared to equivalent ambient-pressure behavior, demonstrates that disordering occurs to a much greater extent in MgAl 2 O 4 at high pressure and that pressure favors disordering toward the inverse structure.

Pure lead phosphate, Pb3(PO4)2, undergoes a phase transition from C2/c to R\bar 3m symmetry at a pressure of approximately 1.8 GPa and room temperature. Single-crystal X-ray diffraction measurements of the unit-cell parameters of a sample doped with 1.6% Ba2+ for the Pb2+ indicates that the doping reduces the transition pressure by approximately 0.1 GPa. The structural evolution of both samples through the phase transition has been determined by Rietveld refinement of neutron powder diffraction data collected to pressures of 6.3 and 3.3 GPa, respectively. There is no evidence for any significant change in the local structure at the phase transition at high pressures; the structure of the R\bar 3m phase at pressures just above the phase transition includes disordered positions for several atoms. The observation of diffuse scattering from the R\bar 3m phase at high pressure by single-crystal X-ray diffraction suggests that the disorder is static and arises from the presence of several orientations of the ordered microdomains of the monoclinic local structure. The macroscopic transition from monoclinic to trigonal symmetry therefore appears to correspond to the pressure at which the coherency strains between the locally monoclinic microdomains are sufficient to create a dimensionally trigonal lattice within which local displacements of atoms are still significant. A further pressure increase then decreases the magnitude of these displacements until at 3.5 GPa or higher they are not detectable by our current experimental probes, and the structure appears to have true local and global trigonal symmetry.