Elastic strain-induced amorphization in high-entropy alloys.

Elastic stability is the basis for understanding structural responses to external stimuli in crystalline solids, including melting, incipient plasticity and fracture. In this work, elastic stability is investigated in a series of high-entropy alloys (HEAs) using in situ mechanical tests and atomic-resolution characterization in transmission electron microscopy. Under tensile loading, the HEA lattices are observed to undergo a sudden loss of ordering as the elastic strain reached ∽ 10%. Such elastic strain-induced amorphization stands in intrinsic contrast to previously reported dislocation-mediated elastic instability and defect accumulation-mediated amorphization, introducing a form of elastic instability. Together with the first principle calculations and atomic-resolution chemical mapping, we identify that the elastic strain-induced amorphization is closely related to the depressed dislocation nucleation due to the local atomic environment inhomogeneity of HEAs. Our findings provide insights for the understanding of the fundamental nature of physical mechanical phenomena like elastic instability and incipient plasticity.

Electrically reversible cracks in an intermetallic film controlled by an electric field.

Cracks in solid-state materials are typically irreversible. Here we report electrically reversible opening and closing of nanoscale cracks in an intermetallic thin film grown on a ferroelectric substrate driven by a small electric field (~0.83 kV/cm). Accordingly, a nonvolatile colossal electroresistance on-off ratio of more than 108 is measured across the cracks in the intermetallic film at room temperature. Cracks are easily formed with low-frequency voltage cycling and remain stable when the device is operated at high frequency, which offers intriguing potential for next-generation high-frequency memory applications. Moreover, endurance testing demonstrates that the opening and closing of such cracks can reach over 107 cycles under 10-µs pulses, without catastrophic failure of the film.

Multiscale structure and damage tolerance of coconut shells.

We investigated the endocarp of the fruit of Cocos nucifera (i.e., the inner coconut shell), examining the structure across multiple length scales through advanced characterization techniques and in situ testing of mechanical properties. Like many biological materials, the coconut shell possesses a hierarchical structure with distinct features at different length scales that depend on orientation and age. Aged coconut was found to have a significantly stronger (ultimate tensile strength, UTS = 48.5MPa), stiffer (Young's modulus, E = 1.92GPa), and tougher (fracture resistance (R-curve) peak of KJ = 3.2MPa m1/2) endocarp than the younger fruit for loading in the latitudinal orientation. While the mechanical properties of coconut shell were observed to improve with age, they also become more anisotropic: the young coconut shell had the same strength (17MPa) and modulus (0.64GPa) values and similar R-curves for both longitudinal and latitudinal loading configurations, whereas the old coconut had 82% higher strength for loading in the latitudinal orientation, and >50% higher crack growth toughness for cracking on the latitudinal plane. Structural aspects affecting the mechanical properties across multiple length scales with aging were identified as improved load transfer to the cellulose crystalline nanostructure (identified by synchrotron x-ray diffraction) and sclerification of the endocarp, the latter of which included closing of the cell lumens and lignification of the cell walls. The structural changes gave a denser and mechanically superior micro and nanostructure to the old coconut shell. Additionally, the development of anisotropy was attributed to the formation of an anisotropic open channel structure throughout the shell of the old coconut that affected both crack initiation during uniaxial tensile tests and the toughening mechanisms of crack trapping and deflection during crack propagation.

Giant panda׳s tooth enamel: Structure, mechanical behavior and toughening mechanisms under indentation.

The giant panda׳s teeth possess remarkable load-bearing capacity and damage resistance for masticating bamboos. In this study, the hierarchical structure and mechanical behavior of the giant panda׳s tooth enamel were investigated under indentation. The effects of loading orientation and location on mechanical properties of the enamel were clarified and the evolution of damage in the enamel under increasing load evaluated. The nature of the damage, both at and beneath the indentation surfaces, and the underlying toughening mechanisms were explored. Indentation cracks invariably were seen to propagate along the internal interfaces, specifically the sheaths between enamel rods, and multiple extrinsic toughening mechanisms, e.g., crack deflection/twisting and uncracked-ligament bridging, were active to shield the tips of cracks from the applied stress. The giant panda׳s tooth enamel is analogous to human enamel in its mechanical properties, yet it has superior hardness and Young׳s modulus but inferior toughness as compared to the bamboo that pandas primarily feed on, highlighting the critical roles of the integration of underlying tissues in the entire tooth and the highly hydrated state of bamboo foods. Our objective is that this study can aid the understanding of the structure-mechanical property relations in the tooth enamel of mammals and further provide some insight on the food habits of the giant pandas.

Sclerostin-antibody treatment of glucocorticoid-induced osteoporosis maintained bone mass and strength.

UNLABELLED: This study was to determine if antibody against sclerostin (Scl-Ab) could prevent glucocorticoid (GC)-induced osteoporosis in mice. We found that Scl-Ab prevented GC-induced reduction in bone mass and bone strength and that the anabolic effects of Scl-Ab might be partially achieved through the preservation of osteoblast activity through autophagy. INTRODUCTION: Glucocorticoids (GCs) inhibit bone formation by altering osteoblast and osteocyte cell activity and lifespan. A monoclonal antibody against sclerostin, Scl-Ab, increased bone mass in both preclinical animal and clinical studies in subjects with low bone mass. The objectives of this study were to determine if treatment with the Scl-Ab could prevent loss of bone mass and strength in a mouse model of GC excess and to elucidate if Scl-Ab modulated bone cell activity through autophagy. METHODS: We generated reporter mice that globally expressed dsRed fused to LC3, a protein marker for autophagosomes, and evaluated the dose-dependent effects of GCs (0, 0.8, 2.8, and 4 mg/kg/day) and Scl-Ab on autophagic osteoblasts, bone mass, and bone strength. RESULTS: GC treatment at 2.8 and 4 mg/kg/day of methylprednisolone significantly lowered trabecular bone volume (Tb-BV/TV) at the lumbar vertebrae and distal femurs, cortical bone mass at the mid-shaft femur (FS), and cortical bone strength compared to placebo (PL). In mice treated with GC and Scl-Ab, Tb-BV/TV increased by 60-125 %, apparent bone strength of the lumbar vertebrae by 30-70 %, FS-BV by 10-18 %, and FS-apparent strength by 13-15 %, as compared to GC vehicle-treated mice. GC treatment at 4 mg/kg/day reduced the number of autophagic osteoblasts by 70 % on the vertebral trabecular bone surface compared to the placebo group (PL, GC 0 mg), and GC + Scl-Ab treatment. CONCLUSIONS: Treatment with Scl-Ab prevented GC-induced reduction in both trabecular and cortical bone mass and strength and appeared to maintain osteoblast activity through autophagy.

Growth inhibition and altered gene transcript levels in earthworms (Eisenia fetida) exposed to 2,2',4,4'-tetrabromodiphenyl ether.

The toxic effects of the ubiquitous pollutant 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) on the earthworm Eisenia fetida were assessed by determining growth-inhibition and gene transcript levels of superoxide dismutase (SOD), catalase (CAT), glutathione transferase (GST), and transcriptional changes of the stress-response gene (heat-shock protein 70 [Hsp70]). Somatic growth and growth-inhibition rates in all BDE-47-treated groups were significantly different from those of the controls. The SOD gene transcripts were upregulated at all exposure doses and reached the maximum at the concentration of 400 mg/kg dry weight (dw) (3.84-fold, P < 0.01), which protected earthworms from oxidative stresses. However, downregulation of CAT and Hsp70 was present in all exposure doses and reached to the minimum at concentrations of 400 mg/kg dw (0.07-fold, P < 0.01 and 0.06-fold, P < 0.01, respectively). Upregulation of GST gene transcript level presented significant changes at concentrations of 10 (2.69-fold, P < 0.05) and 100 mg/kg dw (2.55-fold, P < 0.05). SOD maintained a dynamic balance to upregulate SOD expression to eliminate superoxide radicals in all dosage treatments, but downregulation of CAT decreased the ability to eliminate hydrogen peroxide. These changes could result in biochemical and physiological disturbances in earthworms.

Breakdown of food waste by anaerobic fermentation and non-oxygen producing photosynthesis using a photosynthetic bacterium.

Large volumes of food waste are produced by restaurants, hotels, etc generating problems in its collection, processing and disposal. Disposal as garbage increases the organic matter in landfills and leachates. The photosynthetic bacterium Rhodopseudomonas palustris (CGA 009) easily broke down food waste. R. palustris produces H2 under anaerobic conditions and digests a very wide range of organic compounds. R. palustris reduced BOD by ≈70% and COD by ≈33%, starch, ammonia, nitrate, was removed but had little effect on reducing sugar or the total phosphorus, lipid, protein, total solid in a 7-day incubation. R. palustris produced a maximum of 80ml H2/g COD/day. A two-stage anaerobic digestion using yeast as the first stage, followed by a R. palustris digestion was tested but production of H2 was low.

Effects of sequential osteoporosis treatments on trabecular bone in adult rats with low bone mass.

UNLABELLED: We used an osteopenic adult ovariectomized (OVX) rat model to evaluate various sequential treatments for osteoporosis, using FDA-approved agents with complementary tissue-level mechanisms of action. Sequential treatment for 3 months each with alendronate (Aln), followed by PTH, followed by resumption of Aln, created the highest trabecular bone mass, best microarchitecture, and highest bone strength. INTRODUCTION: Individual agents used to treat human osteoporosis reduce fracture risk by ∼ 50-60%. As agents that act with complementary mechanisms are available, sequential therapies that mix antiresorptive and anabolic agents could improve fracture risk reduction, when compared with monotherapies. METHODS: We evaluated bone mass, bone microarchitecture, and bone strength in adult OVX, osteopenic rats, during different sequences of vehicle (Veh), parathyroid hormone (PTH), Aln, or raloxifene (Ral) in three 90-day treatment periods, over 9 months. Differences among groups were evaluated. The interrelationships of bone mass and microarchitecture endpoints and their relationship to bone strength were studied. RESULTS: Estrogen deficiency caused bone loss. OVX rats treated with Aln monotherapy had significantly better bone mass, microarchitecture, and bone strength than untreated OVX rats. Rats treated with an Aln drug holiday had bone mass and microarchitecture similar to the Aln monotherapy group but with significantly lower bone strength. PTH-treated rats had markedly higher bone endpoints, but all were lost after PTH withdrawal without follow-up treatment. Rats treated with PTH followed by Aln had better bone endpoints than those treated with Aln monotherapy, PTH monotherapy, or an Aln holiday. Rats treated initially with Aln or Ral, then switched to PTH, also had better bone endpoints, than monotherapy treatment. Rats treated with Aln, then PTH, and returned to Aln had the highest values for all endpoints. CONCLUSION: Our data indicate that antiresorptive therapy can be coupled with an anabolic agent, to produce and maintain better bone mass, microarchitecture, and strength than can be achieved with any monotherapy.

How tough is brittle bone? Investigating osteogenesis imperfecta in mouse bone.

The multiscale hierarchical structure of bone is naturally optimized to resist fractures. In osteogenesis imperfecta, or brittle bone disease, genetic mutations affect the quality and/or quantity of collagen, dramatically increasing bone fracture risk. Here we reveal how the collagen defect results in bone fragility in a mouse model of osteogenesis imperfecta (oim), which has homotrimeric α1(I) collagen. At the molecular level, we attribute the loss in toughness to a decrease in the stabilizing enzymatic cross-links and an increase in nonenzymatic cross-links, which may break prematurely, inhibiting plasticity. At the tissue level, high vascular canal density reduces the stable crack growth, and extensive woven bone limits the crack-deflection toughening during crack growth. This demonstrates how modifications at the bone molecular level have ramifications at larger length scales affecting the overall mechanical integrity of the bone; thus, treatment strategies have to address multiscale properties in order to regain bone toughness. In this regard, findings from the heterozygous oim bone, where defective as well as normal collagen are present, suggest that increasing the quantity of healthy collagen in these bones helps to recover toughness at the multiple length scales.

Assessment of the use of sediment fences for control of erosion and sediment phosphorus loss after potato harvesting on sloping land.

In humid temperate areas, after harvest of potatoes, it is difficult to prevent soil erosion and diffuse pollution. In some autumn weather conditions, in-field mitigation such as cultivation or sowing are not possible, while edge of field measures can be costly and inflexible. We have assessed the potential of modified sediment fences, widely used on building sites, for erosion mitigation post-harvest of potato crops. Field scale assessments were conducted on fields in the Lunan catchment, eastern Scotland. Sediment retention was estimated by two methods: a topographic survey method using a hand held Real Time Kinematic Global Positioning System (RTK-GPS), and direct measurement of sediment depth using a graduated cane. In the 2010/11 trial the main fence comprised 70 m of entrenched fine mesh (0.25 mm) and coarser mesh (4mm) fabric pinned to a contour fence near the base of the field. This retained an estimated 50.9 m(3) (80.2 tonnes) of sediment, with weighted mean total P (TP) content of 0.09 % in the<2mm soil fraction. In the 2011/12 trial, the main 146 m fence was of intermediate mesh size (1.2mm). The fence was partitioned into nine upslope plots, with 3 replicates of each of 3 cultivation methods: T1 (full grubbing--a light, tined cultivator), T2 (partial grubbing) and T3 (no grubbing). Average plot slopes ranged from 9.9 to 11.0 %. The amounts of TP accumulating as sediment at the fences were: 9.3 (sd = 7.8), 11.8 (sd = 10.2) and 25.7 (sd = 5.8)kg P/ha of upslope plot for the T1, T2 and T3 treatments respectively.

Reprint of: Assessment of the use of sediment fences for control of erosion and sediment phosphorus loss after potato harvesting on sloping land.

In humid temperate areas, after harvest of potatoes, it is difficult to prevent soil erosion and diffuse pollution. In some autumn weather conditions, in-field mitigation such as cultivation or sowing are not possible, while edge of field measures can be costly and inflexible. We have assessed the potential of modified sediment fences, widely used on building sites, for erosion mitigation post-harvest of potato crops. Field scale assessments were conducted on fields in the Lunan catchment, eastern Scotland. Sediment retention was estimated by two methods: a topographic survey method using a hand held Real Time Kinematic Global Positioning System (RTK-GPS), and direct measurement of sediment depth using a graduated cane. In the 2010/11 trial the main fence comprised 70 m of entrenched fine mesh (0.25 mm) and coarser mesh (4mm) fabric pinned to a contour fence near the base of the field. This retained an estimated 50.9 m(3) (80.2 tonnes) of sediment, with weighted mean total P (TP) content of 0.09 % in the<2mm soil fraction. In the 2011/12 trial, the main 146 m fence was of intermediate mesh size (1.2mm). The fence was partitioned into nine upslope plots, with 3 replicates of each of 3 cultivation methods: T1 (full grubbing--a light, tined cultivator), T2 (partial grubbing) and T3 (no grubbing). Average plot slopes ranged from 9.9 to 11.0 %. The amounts of TP accumulating as sediment at the fences were: 9.3 (sd=7.8), 11.8 (sd=10.2) and 25.7 (sd=5.8)kg P/ha of upslope plot for the T1, T2 and T3 treatments respectively.

The nitric oxide redox sibling nitroxyl partially circumvents impairment of platelet nitric oxide responsiveness.

Impaired platelet responsiveness to nitric oxide (NO resistance) is a common characteristic of many cardiovascular disease states and represents an independent risk factor for cardiac events and mortality. NO resistance reflects both scavenging of NO by superoxide (O2(-)), and impairment of the NO receptor, soluble guanylate cyclase (sGC). There is thus an urgent need for circumvention of NO resistance in order to improve clinical outcomes. Nitroxyl (HNO), like NO, produces vasodilator and anti-aggregatory effects, largely via sGC activation, but is not inactivated by O2(-). We tested the hypothesis that HNO circumvents NO resistance in human platelets. In 57 subjects with or without ischemic heart disease, platelet responses to the HNO donor isopropylamine NONOate (IPA/NO) and the NO donor sodium nitroprusside (SNP) were compared. While SNP (10µM) induced 29±3% (p<0.001) inhibition of platelet aggregation, IPA/NO (10µM) caused 75±4% inhibition (p<0.001). In NO-resistant subjects (n=28), the IPA/NO:SNP response ratio was markedly increased (p<0.01), consistent with partial circumvention of NO resistance. Similarly, cGMP accumulation in platelets was greater (p<0.001) with IPA/NO than with SNP stimulation. The NO scavenger carboxy-PTIO (CPTIO, 200µM) inhibited SNP and IPA/NO responses by 92±7% and 17±4% respectively (p<0.001 for differential inhibition), suggesting that effects of IPA/NO are only partially NO-mediated. ODQ (10µM) inhibited IPA/NO responses by 36±8% (p<0.001), consistent with a contribution of sGC/haem to IPA/NO inhibition of aggregation. There was no significant relationship between whole blood ROS content and IPA/NO responses. Thus the HNO donor IPA/NO substantially circumvents platelet NO resistance while acting, at least partially, as a haem-mediated sGC activator.

Proposed pathogenesis for atypical femoral fractures: lessons from materials research.

Atypical femoral fractures (AFFs) have been well defined clinically and epidemiologically. Less clear are the underlying mechanisms responsible. This commentary points out the likely sources of decreased resistance to fracture using lessons from bone material studies and biomechanics. We hypothesize that the key element in the cascade of events leading to failure of the largest and strongest bone in the human body is long-term suppression of normal bone turnover caused by exposure to potent anti-remodeling agents, most notably the bisphosphonates (BPs). Suppressed bone turnover produces changes in bone that alter its material quality and these changes could lead to adverse effects on its mechanical function. At the submicroscopic [<1 µm] level of collagen fibrils, suppression of bone turnover allows continued addition of non-enzymatic cross links that can reduce collagen's plasticity and this in turn contributes to reduced bone toughness. Further, adverse changes in hydroxyapatite crystalline structure and composition can occur, perhaps increasing collagen's brittleness. At the microscopic level [~1-500 µm] of the bone-matrix structure, suppressed bone turnover allows full mineralization of cortical bone osteons and results in a microstructure of bone that is more homogeneous. Both brittleness and loss of heterogeneity allow greater progression of microscopic cracks that can occur with usual physical activity; in crack mechanical terms, normal mechanisms that dissipate crack tip growth energy are greatly reduced and crack progression is less impeded. Further, the targeted repair of cracks by newly activated BMUs appears to be preferentially suppressed by BPs. We further hypothesize that it is not necessary to have accumulation of many cracks to produce an AFF, just one that progresses - one that is not stopped by bone's several protective mechanisms and is allowed to penetrate through a homogeneous environment. The remarkable straight transverse fracture line is an indicator of the slow progression of a "mother crack" and the failure of usual mechanisms to bridge or deflect the crack. Research in AFF mechanisms has been focused at the organ level, describing the clinical presentation and radiologic appearance. Although today we have not yet connected all the dots in the pathophysiology of BP-induced AFF, recent advances in measuring bone mechanical qualities at the submicroscopic and tissue levels allow us to explain how spontaneous catastrophic failure of the femur can occur.

Biobased plastics in a bioeconomy.

Bioeconomy plans include a biobased industries sector in which some oil-derived plastics and chemicals are replaced by new or equivalent products derived, at least partially, from biomass. Some of these biobased products are here today, but to fulfil their societal potential, greater attention is required to promote awareness, and to improve their market share while making valuable contributions to climate change mitigation.

Changes to the cell, tissue and architecture levels in cranial suture synostosis reveal a problem of timing in bone development.

Premature fusion of cranial sutures is a common problem with an incidence of 3-5 per 10,000 live births. Despite progress in understanding molecular/genetic factors affecting suture function, the complex process of premature fusion is still poorly understood. In the present study, corresponding excised segments of nine patent and nine prematurely fused sagittal sutures from infants (age range 3-7 months) with a special emphasis on their hierarchical structural configuration were compared. Cell, tissue and architecture characteristics were analysed by transmitted and polarised light microscopy, 2D-histomorphometry, backscattered electron microscopy and energy-dispersive-x-ray analyses. Apart from wider sutural gaps, patent sutures showed histologically increased new bone formation compared to reduced new bone formation and osseous edges with a more mature structure in the fused portions of the sutures. This pattern was accompanied by a lower osteocyte lacunar density and a higher number of evenly mineralised osteons, reflecting pronounced lamellar bone characteristics along the prematurely fused sutures. In contrast, increases in osteocyte lacunar number and size accompanied by mineralisation heterogeneity and randomly oriented collagen fibres predominantly signified woven bone characteristics in patent, still growing suture segments. The already established woven-to-lamellar bone transition provides evidence of advanced bone development in synostotic sutures. Since structural and compositional features of prematurely fused sutures did not show signs of pathological/defective ossification processes, this supports the theory of a normal ossification process in suture synostosis - just locally commencing too early. These histomorphological findings may provide the basis for a better understanding of the pathomechanism of craniosynostosis, and for future strategies to predict suture fusion and to determine surgical intervention.

Enhanced phosphoinositide 3-kinase(p110α) activity prevents diabetes-induced cardiomyopathy and superoxide generation in a mouse model of diabetes.

AIMS/HYPOTHESIS: Diabetic cardiomyopathy is characterised by diastolic dysfunction, oxidative stress, fibrosis, apoptosis and pathological cardiomyocyte hypertrophy. Phosphoinositide 3-kinase (PI3K)(p110α) is a cardioprotective kinase, but its role in the diabetic heart is unknown. The aim of this study was to assess whether PI3K(p110α) plays a critical role in the induction of diabetic cardiomyopathy, and whether increasing PI3K(p110α) activity in the heart can prevent the development of cardiac dysfunction in a setting of diabetes. METHODS: Type 1 diabetes was induced with streptozotocin in adult male cardiac-specific transgenic mice with increased PI3K(p110α) activity (constitutively active PI3K [p110α], caPI3K] or decreased PI3K(p110α) activity (dominant-negative PI3K [p110α], dnPI3K) and non-transgenic (Ntg) mice for 12 weeks. Cardiac function, histological and molecular analyses were performed. RESULTS: Diabetic Ntg mice displayed diastolic dysfunction and increased cardiomyocyte size, expression of atrial and B-type natriuretic peptides (Anp, Bnp), fibrosis and apoptosis, as well as increased superoxide generation and increased protein kinase C ß2 (PKCß2), p22 ( phox ) and apoptosis signal-regulating kinase 1 (Ask1) expression. Diabetic dnPI3K mice displayed an exaggerated cardiomyopathy phenotype compared with diabetic Ntg mice. In contrast, diabetic caPI3K mice were protected against diastolic dysfunction, pathological cardiomyocyte hypertrophy, fibrosis and apoptosis. Protection in diabetic caPI3K mice was associated with attenuation of left ventricular superoxide generation, attenuated Anp, Bnp, PKCß2, Ask1 and p22 ( phox ) expression, and elevated AKT. Further, in cardiomyocyte-like cells, increased PI3K(p110α) activity suppressed high glucose-induced superoxide generation and enhanced mitochondrial function. CONCLUSIONS/INTERPRETATION: These results demonstrate that reduced PI3K activity accelerates the development of diabetic cardiomyopathy, and that enhanced PI3K(p110α) activity can prevent adverse cardiac remodelling and dysfunction in a setting of diabetes.

Mo-Si-B alloys for ultrahigh-temperature structural applications.

A continuing quest in science is the development of materials capable of operating structurally at ever-increasing temperatures. Indeed, the development of gas-turbine engines for aircraft/aerospace, which has had a seminal impact on our ability to travel, has been controlled by the availability of materials capable of withstanding the higher-temperature hostile environments encountered in these engines. Nickel-base superalloys, particularly as single crystals, represent a crowning achievement here as they can operate in the combustors at ~1100 °C, with hot spots of ~1200 °C. As this represents ~90% of their melting temperature, if higher-temperature engines are ever to be a reality, alternative materials must be utilized. One such class of materials is Mo-Si-B alloys; they have higher density but could operate several hundred degrees hotter. Here we describe the processing and structure versus mechanical properties of Mo-Si-B alloys and further document ways to optimize their nano/microstructures to achieve an appropriate balance of properties to realistically compete with Ni-alloys for elevated-temperature structural applications.

High-intensity focused ultrasound treatment of liver tumours: post-treatment MRI correlates well with intra-operative estimates of treatment volume.

OBJECTIVES: To assess the safety and feasibility of high-intensity focused ultrasound (HIFU) ablation of liver tumours and to determine whether post-operative MRI correlates with intra-operative imaging. METHODS: 31 patients were recruited into two ethically approved clinical trials (median age 64; mean BMI 26 kg m(-2)). Patients with liver tumours (primary or metastatic) underwent a single HIFU treatment monitored using intra-operative B-mode ultrasound. Follow-up consisted of radiology and histology (surgical trial) or radiology alone (radiology trial). Radiological follow-up was digital subtraction contrast-enhanced MRI. RESULTS: Treatment according to protocol was possible in 30 of 31 patients. One treatment was abandoned because of equipment failure. Transient pain and superficial skin burns were seen in 81% (25/31) and 39% (12/31) of patients, respectively. One moderate skin burn occurred. One patient died prior to radiological follow-up. Radiological evidence of ablation was seen in 93% (27/29) of patients. Ablation accuracy was good in 89% (24/27) of patients. In three patients the zone of ablation lay ≤2 mm outside the tumour. The median cross-sectional area (CSA) of the zone of ablation was 5.0 and 5.1 cm(2) using intra-operative and post-operative imaging, respectively. The mean MRI:B-mode CSA ratio was 1.57 [95% confidence interval (CI)=0.57-2.71]. There was positive correlation between MRI and B-mode CSA (Spearman's r=0.48; 95% CI 0.11-0.73; p=0.011) and the slope of linear regression was significantly non-zero (1.23; 95% CI=0.68-1.77; p<0.0001). CONCLUSIONS: HIFU ablation of liver tumours is safe and feasible. HIFU treatment is accurate, and intra-operative assessment of treatment provides an accurate measure of the zone of ablation and correlates well with MRI follow-up.

Coenzyme Q10 attenuates diastolic dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis in the db/db mouse model of type 2 diabetes.

AIMS/HYPOTHESIS: An increase in the production of reactive oxygen species is commonly thought to contribute to the development of diabetic cardiomyopathy. This study aimed to assess whether administration of the antioxidant coenzyme Q(10) would protect the diabetic heart against dysfunction and remodelling, using the db/db mouse model of type 2 diabetes. Furthermore, we aimed to compare the efficacy of coenzyme Q(10) to that of the ACE inhibitor ramipril. METHODS: Six-week-old non-diabetic db/+ mice and diabetic db/db mice received either normal drinking water or water supplemented with coenzyme Q(10) for 10 weeks. Endpoint cardiac function was assessed by echocardiography and catheterisation. Ventricular tissue was collected for histology, gene expression and protein analysis. RESULTS: Untreated db/db diabetic mice exhibited hyperglycaemia, accompanied by diastolic dysfunction and adverse structural remodelling, including cardiomyocyte hypertrophy, myocardial fibrosis and increased apoptosis. Systemic lipid peroxidation and myocardial superoxide generation were also elevated in db/db mice. Coenzyme Q(10) and ramipril treatment reduced superoxide generation, ameliorated diastolic dysfunction and reduced cardiomyocyte hypertrophy and fibrosis in db/db mice. Phosphorylation of Akt, although depressed in untreated db/db mice, was restored with coenzyme Q(10) administration. We postulate that preservation of cardioprotective Akt signalling may be a mechanism by which coenzyme Q(10)-treated db/db mice are protected from pathological cardiac hypertrophy. CONCLUSIONS/INTERPRETATION: These data demonstrate that coenzyme Q(10) attenuates oxidative stress and left ventricular diastolic dysfunction and remodelling in the diabetic heart. Addition of coenzyme Q(10) to the current therapy used in diabetic patients with diastolic dysfunction warrants further investigation.

Impact of thermomechanical texture on the superelastic response of Nitinol implants.

The phenomenon of superelasticity in near-equiatomic NiTi, which originates from a first-order martensitic phase transition, is exploited in an increasing number of biomedical devices, most importantly endovascular stents. These stents are often manufactured from microtubing, which is shown to be highly textured crystallographically. Synchrotron X-ray microdiffraction provided microstructural, phase, and strain analysis from Nitinol tube sections that were deformed in situ along longitudinal, circumferential, and transverse orientations. We show that the large variation in the superelastic response of NiTi in these three tube directions is strongly influenced by the path that the martensitic transformation follows through the microstructure. Specifically, in severely worked NiTi, bands of [100] grains occur whose orientation deviates markedly from the surrounding matrix; these bands have an unusually large impact on the initiation and the propagation of martensite, and hence on the mechanical response. Understanding the impact of these local microstructural effects on global mechanical response, as shown here, leads to a much fuller understanding of the causes of deviation of the mechanical response from predictions and unforeseen fracture in NiTi biomedical devices.