Decoupling Carrier Concentration and Electron-Phonon Coupling in Oxide Heterostructures Observed with Resonant Inelastic X-Ray Scattering.

We report the observation of multiple phonon satellite features in ultrathin superlattices of the form nSrIrO_{3}/mSrTiO_{3} using resonant inelastic x-ray scattering (RIXS). As the values of n and m vary, the energy loss spectra show a systematic evolution in the relative intensity of the phonon satellites. Using a closed-form solution for the RIXS cross section, we extract the variation in the electron-phonon coupling strength as a function of n and m. Combined with the negligible carrier doping into the SrTiO_{3} layers, these results indicate that the tuning of the electron-phonon coupling can be effectively decoupled from doping. This work both showcases a feasible method to extract the electron-phonon coupling in superlattices and unveils a potential route for tuning this coupling, which is often associated with superconductivity in SrTiO_{3}-based systems.

Doping Evolution of Magnetic Order and Magnetic Excitations in (Sr_{1-x}La_{x})_{3}Ir_{2}O_{7}.

We use resonant elastic and inelastic x-ray scattering at the Ir-L_{3} edge to study the doping-dependent magnetic order, magnetic excitations, and spin-orbit excitons in the electron-doped bilayer iridate (Sr_{1-x}La_{x})_{3}Ir_{2}O_{7} (0≤x≤0.065). With increasing doping x, the three-dimensional long range antiferromagnetic order is gradually suppressed and evolves into a three-dimensional short range order across the insulator-to-metal transition from x=0 to 0.05, followed by a transition to two-dimensional short range order between x=0.05 and 0.065. Because of the interactions between the J_{eff}=1/2 pseudospins and the emergent itinerant electrons, magnetic excitations undergo damping, anisotropic softening, and gap collapse, accompanied by weakly doping-dependent spin-orbit excitons. Therefore, we conclude that electron doping suppresses the magnetic anisotropy and interlayer couplings and drives (Sr_{1-x}La_{x})_{3}Ir_{2}O_{7} into a correlated metallic state with two-dimensional short range antiferromagnetic order. Strong antiferromagnetic fluctuations of the J_{eff}=1/2 moments persist deep in this correlated metallic state, with the magnon gap strongly suppressed.

Rapid relief of acute sore throat with AMC/DCBA throat lozenges: randomised controlled trial.

AIM: As antibiotics are generally not recommended for the treatment of acute sore throat, the availability of clinically efficacious, over-the-counter (OTC) treatment alternatives is becoming increasingly important. This study was designed to determine the analgesic properties of amylmetacresol and 2,4-dichlorobenzyl alcohol (AMC/DCBA) throat lozenges (Strepsils) in the relief of acute sore throat caused by upper respiratory tract infections. METHODS: Patients (n = 310) were randomly assigned to receive AMC/DCBA throat lozenges (n = 155) or non-medicated placebo lozenges (n = 155). After baseline assessments, patients completed three rating assessments at 10 timepoints from 5 to 20 min after first dose. Subsequent lozenges were taken as required, and assessments were made at the end of Day 1, 24 h after first dose, and at the end of Days 2 and 3. Analgesic properties were assessed by comparing severity of throat soreness and sore throat relief ratings. Difficulty in swallowing and functional impairment scores were also assessed. RESULTS: Amylmetacresol/DCBA throat lozenges reduced throat soreness at 5 min after first dose, which persisted for 2 h and was significantly different vs. non-medicated lozenges at all assessment timepoints for the duration of the 3-day study. Similar significant effects were observed with sore throat relief, easing of difficulty with swallowing and functional impairment scores. There were no differences in adverse events reported between treatment groups. CONCLUSION: Amylmetacresol/DCBA throat lozenges provide rapid analgesic effects that last for 2 h, providing ongoing relief long after the lozenge has dissolved. The superior analgesic effects and improvements in functional impairment scores observed with AMC/DCBA throat lozenges translate into pain relief benefits that are clinically meaningful and are thus a suitable OTC treatment option for patients in the self-management of acute sore throat.

Strain-engineering Mott-insulating La2CuO4.

The transition temperature Tc of unconventional superconductivity is often tunable. For a monolayer of FeSe, for example, the sweet spot is uniquely bound to titanium-oxide substrates. By contrast for La2-xSrxCuO4 thin films, such substrates are sub-optimal and the highest Tc is instead obtained using LaSrAlO4. An outstanding challenge is thus to understand the optimal conditions for superconductivity in thin films: which microscopic parameters drive the change in Tc and how can we tune them? Here we demonstrate, by a combination of x-ray absorption and resonant inelastic x-ray scattering spectroscopy, how the Coulomb and magnetic-exchange interaction of La2CuO4 thin films can be enhanced by compressive strain. Our experiments and theoretical calculations establish that the substrate producing the largest Tc under doping also generates the largest nearest neighbour hopping integral, Coulomb and magnetic-exchange interaction. We hence suggest optimising the parent Mott state as a strategy for enhancing the superconducting transition temperature in cuprates.

The internal pressure and stress environment of the scoliotic intervertebral disc--a review.

The aetiology, in terms of both initiation and progression, of the deformity in idiopathic scoliosis is at present unclear. Even in neuromuscular cases, the mechanisms underlying progression are not fully elucidated. It is thought, however, that asymmetrical loading is involved in the progression of the disease, with evidence mainly from animal studies and modelling. There is, however, very little direct information as to the origin or mechanism of action of these forces in the scoliotic spine. This review describes the concept of intervertebral disc pressure or stress and examines possible measurement techniques. The biological and mechanical consequences of abnormalities in these parameters are described. Future possible studies and their clinical significance are also briefly discussed. Techniques of pressure measurement have culminated in the development of 'pressure profilometry', which provides stress profiles across the disc in mutually perpendicular axes. A hydrated intervertebral disc exhibits mainly hydrostatic behaviour. However, in pathological states such as degeneration and scoliosis, non-hydrostatic behaviour predominates and annular peaks of stress occur. Recent studies have shown that, in scoliosis, high hydrostatic pressures are seen with asymmetrical stresses from concave to convex sides. These abnormalities could influence both disc and endplate cellular activity directly, causing asymmetrical growth and matrix changes. In addition, disc cells could be influenced via nutritional changes consequent to end-plate calcification. Evidence suggests that the stress environment of the scoliotic disc is abnormal, probably generated by high and asymmetrical loading of non-muscular origin. If present in the scoliotic spine during daily activities, this could generate a positive feedback of cellular changes, resulting in curve progression. Future advances in understanding may rely on the development of computer models owing to the difficulties of in-vivo invasive measurements.

The effect of leg fracture level and vehicle front-end geometry on pedestrian knee injury and response.

In this study a MADYMO (mathematical dynamic modelling) model has been used to identify the influence of leg fracture on the injuries sustained by the pedestrian during front end impact with a vehicle. A factorial study of a MADYMO pedestrian and vehicle model are used to investigate the effect of different leg fracture tolerances, geometry, and vehicle compliance on the criteria measured in the European Enhanced Vehicle-safety Committee (EEVC) pedestrian safety tests. These criteria include knee bending, knee shear response, and lower leg bone (tibia) acceleration. The main study examines the spread of typical values of lower limb tolerance based on reported literature and contrasts the response of weaker, low-strength bones, normal tolerance, and limbs which do not fracture. Results show that knee bending angles and therefore ligament strains are significantly increased when fracture does not occur, and are decreased in bones exhibiting a low-strength response. Bone fracture tolerance is shown to be a significant parameter influencing knee bending. The parameters are compared to show that knee shear is significantly influenced by vehicle bumper compliance and that both criteria are heavily influenced by bumper height. Vehicles with more aggressive geometry, higher bumpers, and larger bumper lead were considered for comparative purposes.

Pulmonary hypertension from prominent vascular involvement in diffuse amyloidosis.

Pulmonary arterial hypertension was found in a patient with myeloma who had a diffuse lung lesion. Echocardiographic and hemodynamic data from pulmonary arterial catheterization demonstrated relatively well-preserved left ventricular function. The diagnosis of diffuse pulmonary amyloidosis was established by open lung biopsy, which revealed severe diffuse vascular deposition of amyloid with mild involvement of the alveolar septa. Pulmonary arterial hypertension secondary to vascular deposition of amyloid in the lungs is rare. This case corroborates the clinicopathologic relationship.

A one-dimensional theoretical prediction of the effect of reduced end-plate permeability on the mechanics of the intervertebral disc.

The permeability of the cartilage end-plate (CEP) may play an important role in intervertebral disc (IVD) degeneration by controlling the convective and diffusive transport of metabolites into the nucleus pulposus. A one-dimensional poroelastic model was used to predict the effect of a CEP of lower permeability than the disc tissue on the convective transfer into and out of the IVD. With decreasing CEP permeability, associated with degeneration, the model predicted that the change in disc height with time became more linear; the disc could not rehydrate as quickly; and internal fluid movement was slowed. This study has shown that CEP permeability will only markedly have an effect on fluid movement, and hence convective nutrition, if the permeability of the CEP is reduced to less than that of the disc tissue.

Rigid-body modelling of shaken baby syndrome.

Recent reassessment of the literature on the shaken baby syndrome (SBS) has revealed a lack of scientific evidence and understanding of all aspects of the syndrome. In particular, studies have been unable to clarify the mechanisms of injury, indicating that impact, rather than shaking alone, is necessary to cause the type of brain damage observed. Rigid-body modelling (RBM) was used to investigate the effect of neck stiffness on head motion and head-torso impacts as a possible mechanism of injury. Realistic shaking data obtained from an anthropometric test dummy (ATD) was used to simulate shaking. In each study injury levels for concussion were exceeded, though impact-type characteristics were required to do so in the neck stiffness study. Levels for the type of injury associated with the syndrome were not exceeded. It is unlikely that further gross biomechanical investigation of the syndrome will be able to significantly contribute to the understanding of SBS. Current injury criteria are based on high-energy, single-impact studies. Since this is not the type of loading in SBS it is suggested that their application here is inappropriate and that future studies should focus on injury mechanisms in low-energy cyclic loading.

Effects of hydrostatic pressure on matrix synthesis in different regions of the intervertebral disk.

The intervertebral disk is routinely subjected to compressive loads that alter with posture and muscle activity and can produce pressures > 2 MPa in human lumbar disks in vivo (A. Nachemson and G. Elfstrom. Scand. J. Rehabil. Med. 2, Suppl. 1:1-40, 1979; A. Nachemson and J. M. Morris. J. Bone Jt. Surg. Am. Vol. 46A: 1077-1092, 1964). We measured the effect of load on hydrostatic pressures in bovine caudal disks. With increase in applied load, pressure increased linearly in the nucleus and inner annulus. The resting pressure measured after slaughter (0.19 +/- 0.05 MPa) and the pressure at failure (34 MPa, estimated from the vertebrae/disk segment failure load of 7,430 +/- 590 N) define the limits that can occur in vivo. Because hydrostatic pressure influences matrix synthesis in articular cartilage, we have examined the effects of pressures in the range 1-10 MPa applied for 20 s or 2 h on proteoglycan synthesis in bovine caudal and human lumbar intervertebral disks in vitro. In the nucleus pulposus and inner annulus of bovine disks, application of hydrostatic pressure in the range of 1-7.5 MPa for only 20 s stimulated matrix synthesis over the following 2 h at atmospheric pressure. The maximum stimulation in the bovine disks was seen in the inner annulus after application of 2.5 MPa, where proteoglycan synthesis rates doubled. Exposure to 2.5 MPa also stimulated synthesis in the nucleus pulposus of human disks taken at surgery, whereas 7.5 MPa inhibited synthesis in five out of six specimens. With 2-h continuous exposure to the same levels of pressure, no stimulation was seen in the nucleus of bovine disks, and significant stimulation was only observed at 5.0 MPa in the inner annulus. Exposure to 10 MPa for either 20 s or 2 h inhibited proteoglycan synthesis in these regions of the disks. In contrast, in the outer annulus, where loading does not lead to a rise in hydrostatic pressure in vivo, there was no significant response to hydrostatic pressure over the range of 1-10 MPa in bovine or human disks.

Hepatic metastatic thymoma and myasthenia gravis twenty-two years after the apparent cure of an invasive thymoma. A case report and review of the literature.

We report the case of a 62-year-old woman who presented in myasthenic crisis 22 years after radiation- and chemotherapy of an invasive thymoma which occurred during pregnancy. There was no evidence of recurrence of the thymoma at its original site, but an isolated hepatic metastasis was discovered. Biopsy of the mass revealed a spindle cell thymoma, whereas the original histology was that of a mixed round and spindle cell thymoma with moderate lymphocytic infiltration. The patient expired in spite of treatment with steroids, pyridostigmine bromide and plasma exchange on the one hand and cyclophosphamide with adriamycin on the other. To our knowledge, 22 years is the longest reported interval for the appearance of metastatic thymoma and myasthenia gravis after the diagnosis and apparent cure of a primary thymoma. This is also the only reported case of thymoma occurring during pregnancy but not associated with a rapidly fatal outcome.

Psychiatric status, somatisation, and health care utilization of frequent attenders at the emergency department: a comparison with routine attenders.

Seventy-seven frequent attenders at an emergency department (ED) in an inner-city hospital in the UK (defined as seven or more visits in the previous 12 months) were compared with 182 patients who were attending the same department on a routine basis. Patients completed the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and the Short Form (SF)-36. Information was obtained on 64% of the frequent attenders and 45% underwent a detailed psychiatric assessment. Of the frequent attenders, 45% had psychiatric disorder and 49% had some form of an alcohol-related disorder. Compared with routine attenders, frequent attenders reported lower health status, had more psychiatric disorder (odds ratio: OR=8.2, 95% confidence interval: CI=3.8--18.1), had more general hospital admissions (OR=19.9, 95% CI=8.3--47.8), more psychiatric admissions (OR=167.5, 95% CI=9.5--2959.0), and more GP visits (95% CI for difference=-10.2 to -5.7). There was no evidence that frequent attenders had more somatisation than routine attenders. Specific treatment and management strategies need to be developed for this group of patients, although a substantial proportion may be difficult to engage in the treatment process.

An analytical model of intervertebral disc mechanics.

The intervertebral disc is a complex mechanical structure, and it is important to understand the loading of specific structures which might cause damage leading to failure or mechanical impairment. At present it is only possible to model such internal loadings owing to the extreme technical difficulties involved in experimental measurement. The simple analytical model described in this paper makes exact predictions of the loads carried by fibres and also their path within the annulus fibrosus, without pre-defining the fibre configuration. The disc is modelled as an axially symmetric structure comprising a fluid filled centre, retained by a thin, doubly curved, fibre-reinforced membrane under tensile stress. The annulus is taken to consist of two lamellae reinforced by oppositely oriented collagen fibres that are free to follow paths defined by one of two geometrical rules. The predictive power and possible uses of the model are illustrated using boundary conditions experimentally determined from a typical young disc. The model was used to calculate the shape of the membrane surface, fibre path, volume of disc, area of annulus, length of fibre bundle and tension at a point along length of fibre. Equatorial fibre angle could be approximately predicted (to about 5 degrees), since there was only a small range of valid solutions to the model. The predicted surface profiles, fibre loads and angles were found to be in reasonable agreement with published experimental studies. Two examples of how the static model might be used to calculate changes in disc morphology and loading are included to demonstrate how a wide range of experimental data and theoretical behavior might be incorporated. This analytical model is important since it enables exact solutions to be calculated for the forces acting at any point along a fibre, their paths and also the surface geometry, from a small number of physical measurements without the need to estimate the mechanical properties of individual areas of the disc. It facilitates the prediction of the behaviour of the disc under varying load by providing a framework that can be further developed using a wide range and combination of experimental conditions and theoretical relationships.

Musculoskeletal motion flow fields using hierarchical variable-sized block matching in ultrasonographic video sequences.

We examine tissue deformations using non-invasive dynamic musculoskeletal ultrasonograhy, and quantify its performance on controlled in vitro gold standard (groundtruth) sequences followed by clinical in vivo data. The proposed approach employs a two-dimensional variable-sized block matching algorithm with a hierarchical full search. We extend this process by refining displacements to sub-pixel accuracy. We show by application that this technique yields quantitatively reliable results.

Knoop microhardness anisotropy of the ovine radius.

The Knoop indenter has been used to characterise fully the Knoop microhardness (H(K)) anisotropy of compact bone. 2120 indentations were performed on mature ovine radii and a linear relationship was found between H(K) and the angle between the major diagonal of the indenter and the lamella boundaries (p<<0.001). H(K) increased significantly with ash fraction (p<0.001), but decreased with atmospheric vapour pressure (p<0.05). A significant interaction was found between ash fraction and atmospheric vapour pressure (p<0.01). H(K) significantly varied with indentation position along the diaphysis and around the cortex (both p<<0.001), however radial variation in H(K) was not statistically significant. The variation of ash fraction showed similar trends. These data show that H(K) varies similarly to Vickers microhardness, but in addition, can provide clear information on the anisotropy of Haversian bone without the need for excising many different indentation planes. A large number of indentations are required to obtain low type I and type II errors in the statistical analysis.

The internal mechanics of the intervertebral disc under cyclic loading.

The mechanics of the intervertebral disc (IVD) under cyclic loading are investigated via a one-dimensional poroelastic model and experiment. The poroelastic model, based on that of Biot (J. Appl. Phys. 12 (1941) 155; J. Appl. Mech. 23 (1956) 91), includes a power-law relation between porosity and permeability, and a linear relation between the osmotic potential and solidity. The model was fitted to experimental data of the unconfined IVD undergoing 5 cyclic loads of 20 min compression by an applied stress of 1MPa, followed by 40 min expansion. To obtain a good agreement between experiment and theory, the initial elastic deformation of the IVD, possibly associated with the bulging of the IVD into the vertebral bodies or laterally, was removed from the experimental data. Many combinations of the permeability-porosity relationship with the initial osmotic potential (pi(i)) were investigated, and the best-fit parameters for the aggregate modulus (H(A)) and initial permeability (k(i)) were determined. The values of H(A) and k(i) were compared to literature values, and agreed well especially in the context of the adopted high-stress testing regime, and the strain related permeability in the model.

Microhardness anisotropy of lamellar bone.

The Knoop microhardness test has been utilised to observe in-plane microhardness anisotropy of rat tibiae. The elongated rhombohedral geometry of the Knoop indenter enables the Knoop microhardness (HK) to be calculated for a given indenter orientation. Two indenter orientations were used: the major axis of the indenter was aligned along the length of, and across the mid-sagittal section. The statistical analysis demonstrated that the variation in HK was primarily due to the orientation of the Knoop indenter (p < 0.001). HK was consistently greater when the indenter was aligned with the major diagonal radial on the mid-sagittal section.

High-frequency ultrasound imaging of the intervertebral disc.

In vitro investigation of the detailed structure of the intervertebral disc has been reliant upon microdissection and histological techniques. However, these techniques are laborious and destructive; the latter aspect is important because it precludes repetitive testing of the disc during in vitro experimentation. The aim of the present study was to investigate the potential of using scanning acoustic microscopy (SAM) to image the detailed structure of the intact disc. A mechanically scanned 46-MHz transducer operating in pulse-echo mode was used to obtain images of porcine coccygeal and lumbar discs; scanned regions-of-interest (ROIs) were marked using permanent dye and small surface cuts, respectively. SAM images were compared with corresponding images obtained using conventional histological techniques. The annulus fibrosus was characterised by alternate light and dark bands; the former represent the boundary between adjacent lamellae. Lamellar discontinuities and pathologic abnormalities were observed in specimens. SAM is a novel, nondestructive method for detailed visualisation of the internal structure of the disc in vitro.

Intervertebral disc structure: observation by a novel use of ultrasound imaging.

The internal structure of intervertebral discs is clinically important in the management of back pain. No current routine imaging modality is able to image disc structure satisfactorily. The aim of this work was to investigate and validate ultrasound imaging so that it might be applied to assessment of structural integrity and degree of degeneration. The optimum imaging technique was determined using a 3.5 MHz probe in one female subject. The applicability of this technique to investigate disc structure in the entire thoracolumbar spine was further investigated in 13 subjects. The optimum disc imaging technique was found to be a posterolateral approach, 1 to 2 cm lateral of the dorsal midline, that revealed structure within the disc not apparent using other approaches. It was demonstrated that posterolateral imaging introduces a smaller reproducibility error in measurements of linear dimensions close to the disc. It is possible to observe internal structure within the disc between T11 and L3 in at least 54% of individuals.