Understanding the crystallographic and nanomechanical properties of bryozoans.

This study examines how microscale differences in skeletal ultrastructure affect the crystallographic and nanomechanical properties of two related bryozoan species: (i) Hornera currieae, which is found at relatively quiescent depths of c. 1000 m, and (ii) Hornera robusta, which lives at depths of 50-400 m where it is exposed to currents and storm waves. Microstructural and Electron Backscatter Diffraction (EBSD) observations show that in both species the secondary walls are composed of low-Mg calcite crystallites that grow with their c-axes perpendicular to the wall. Branches in H. currieae develop a strong preferred orientation of the calcite c-axes, while in H. robusta the c-axes are more scattered. Microstructural observations suggest that the degree of scattering is controlled by the underlying morphology of the skeletons: in H. currieae the laminated branch walls are smooth and relatively uninterrupted, whereas the wall architecture of H. robusta is modified by numerous deflections, forming pustules and ridges associated with microscopic tubules. Modelling of the Young's modulus and measurements of nanoindentation hardness indicate that the observed scattering of the crystallite c-axes affects the elastic modulus and nanohardness of the branches, and therefore controls the mechanical properties of the skeletal walls. At relatively high pressure in deep waters, the anisotropic skeletal architecture of H. currieae is aimed at concentrating elasticity normal to the skeleton wall. In comparison, in the relatively shallow and active hydrographic regime of the continental shelf, the elastically isotropic skeleton of H. robusta is designed to increase protection from external predators and stronger omni-directional currents.

Making EBSD on water ice routine.

Electron backscatter diffraction (EBSD) on ice is a decade old. We have built upon previous work to select and develop methods of sample preparation and analysis that give >90% success rate in obtaining high-quality EBSD maps, for the whole surface area (potentially) of low porosity (<15%) water ice samples, including very fine-grained (<10 µm) and very large (up to 70 mm by 30 mm) samples. We present and explain two new methods of removing frost and providing a damage-free surface for EBSD: pressure cycle sublimation and 'ironing'. In general, the pressure cycle sublimation method is preferred as it is easier, faster and does not generate significant artefacts. We measure the thermal effects of sample preparation, transfer and storage procedures and model the likelihood of these modifying sample microstructures. We show results from laboratory ice samples, with a wide range of microstructures, to illustrate effectiveness and limitations of EBSD on ice and its potential applications. The methods we present can be implemented, with a modest investment, on any scanning electron microscope system with EBSD, a cryostage and a variable pressure capability.

Cost savings with a new screening algorithm for pulmonary arterial hypertension in systemic sclerosis.

BACKGROUND: Screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) is now standard care in this disease. The existing Australian Scleroderma Interest Group algorithm (ASIGSTANDARD ) is based on transthoracic echocardiography (TTE) and pulmonary function tests (PFT). Recently, ASIG has derived and validated a new screening algorithm (ASIGPROPOSED ) that incorporates N-terminal pro-B-type natriuretic peptide level together with PFT in order to decrease reliance on TTE, which has some limitations. Right heart catheterisation (RHC) remains the gold standard for the diagnosis of PAH in patients who screen 'positive'. AIM: To compare the cost of PAH screening in SSc with ASIGSTANDARD and ASIGPROPOSED algorithms. METHODS: We applied both ASIGSTANDARD and ASIGPROPOSED algorithms to 643 screen-naïve SSc patients from the Australian Scleroderma Cohort Study (ASCS), assuming a PAH prevalence of 10%. We compared the costs of screening, the number of TTE required and both the total number of RHC required and the number of RHC needed to diagnose one case of PAH, and costs, according to each algorithm. We then extrapolated the costs to the estimated total Australian SSc population. RESULTS: In screen-naïve patients from the ASCS, ASIGPROPOSED resulted in 64% fewer TTE and 10% fewer RHC compared with ASIGSTANDARD , with $1936 (15%) saved for each case of PAH diagnosed. When the costs were extrapolated to the entire Australian SSc population, there was an estimated screening cost saving of $946 000 per annum with ASIGPROPOSED , with a cost saving of $851 400 in each subsequent year of screening. CONCLUSIONS: ASIGPROPOSED substantially reduces the number of TTE and RHC required and results in substantial cost savings in SSc-PAH screening compared with ASIGSTANDARD .

Reversed scan direction reduces electron beam damage in EBSD maps.

The deleterious effects of electron beam damage on high-resolution electron backscatter diffraction (EBSD) maps of undeformed quartz are significantly reduced by scanning in the direction opposite to that dictated by widely used EBSD acquisition software. Higher quality electron backscatter patterns are produced when the electron beam moves progressively down the sample (the apparent 'up' direction in the resulting maps) for all step sizes where beam damage affects EBSD map quality (≤ ∼0.4 µm in this study). The relative improvement associated with downward scanning increases as step size is reduced. A comparison of high-resolution maps made in experimentally deformed quartz demonstrates that downward scanning reduces by a factor of ∼2 the lower limit in step size relative to maps scanned in the conventional direction. The electron beam damages quartz at its point of entry, forming ∼0.1-µm diameter bumps visible in Scanning electron microscope (SEM) images. Downward scanning produces better results because it minimizes the flux of electrons through these loci of damaged crystal.

The association of antiphospholipid antibodies with cardiopulmonary manifestations of systemic sclerosis.

OBJECTIVES: To determine the prevalence and correlates of antiphospholipid antibodies (APLA) in systemic sclerosis (SSc). METHODS: Nine hundred and forty SSc patients were tested for APLA using an ELISA assay at recruitment. Clinical manifestations were defined as present, if ever present from SSc diagnosis. Logistic regression analysis was used to determine the associations of APLA. RESULTS: One or more types of APLA were present in 226 (24.0%) patients. Anticardiolipin (ACA) IgG (ACA-IgG) antibodies were associated with right heart catheter-diagnosed pulmonary arterial hypertension (PAH), with higher titres corresponding with a higher likelihood of PAH (moderate titre (20-39 U/ml) ACA-IgG odds ratio [OR] 1.70, 95% CI: 1.01-2.93, p=0.047; high titre (>40 U/ml) ACA-IgG OR 4.60, 95% CI:1.02-20.8, p=0.047). Both ACA-IgM (OR 2.04, 95% CI: 1.4-3.0, p<0.0001) and ACA-IgG (OR 1.84, 95% CI: 1.2-2.8, p=0.005) were associated with interstitial lung disease (ILD). Increasing ACA-IgM and IgG titres were associated with increased likelihood of ILD. ACA-IgG was a marker of coexistent pulmonary hypertension and ILD (ILD-PH) (OR 2.10, 95% CI: 1.1-4.2, p=0.036). We also found an association between ACA-IgG and digital ulcers (OR 1.76, 95% CI: 1.16-2.67, p=0.008) and ACA-IgM and Raynaud's phenomenon (OR 2.39, 95% CI: 1.08-5.27, p=0.031). There was no association between APLA and SSc disease subtype, peak skin score, presence of other autoantibodies, mortality or other disease manifestations. CONCLUSIONS: The association of APLA with PAH, ILD, ILD-PH, Raynaud's phenomenon and digital ulcers suggests that endothelial abnormalities and small vessel thrombosis may be important in the pathogenesis of these disease features.

Microstructural analysis of Co-Cr dental alloy at the metal-porcelain interface: a pilot study.

OBJECTIVE: The purpose of the study was to observe whether conventional porcelain firings had an effect on the underlying microstructure of cobalt-chromium alloys used in porcelain-fused-to-metal systems. METHODS: One as cast (non-veneered) and two porcelain veneered Co-Cr specimens layered with and without tungsten(W)-metal conditioner were manufactured and analysed. Electron backscatter diffraction was used to determine the crystal structures and grain size across the porcelain-fused-to-metal interface. RESULTS: No difference was found in the microstructure of the alloy in both with and without W-metal conditioner. For the porcelain fired specimens, disparately sized granular structures were observed adjacent to the metal-porcelain interfaces compared to the bulk of the metal. Ellipsoid shaped grains at the alloy surface ranged between 1-11 µm in diameter and averaged 2.70 µm (SD: 2.17 µm) for the specimen layered with W-metal conditioner and 2.86 µm (SD: 1.85 µm) for the specimen layered without W-metal conditioner. Grains located in the bulk were > 200 µm with dendritic-like features. The depth of the fine grain structure adjacent to the surface had an average depth of 15 µm. The crystal structure of the surface layer was found to be predominantly hexagonal close-packed whereas the underlying bulk was a mixture of both face-centered cubic and hexagonal close-packed phases. For the as cast specimen, similar large grains of over 200 µm was observed but exhibited no dendritic like features. In addition, no fine grains were observed at the surface region of the as cast alloy. CONCLUSION: Conventional porcelain firings altered the interfacial and bulk microstructure of the alloy while the presence of the W-metal conditioner had no influence on the underlying alloy microstructure.

Should patients with systemic sclerosis-related pulmonary arterial hypertension be anticoagulated?

Pulmonary arterial hypertension (PAH) is a major cause of mortality in scleroderma and despite 'advanced' therapies confers a median survival of less than 5 years. Anticoagulation in systemic sclerosis-related PAH (SSc-PAH) is currently one of the most contentious issues in the management of patients with connective tissue disease. While some studies have shown a survival benefit with warfarin therapy in this disease, others have not. Accordingly, a state of clinical equipoise exists in relation to anticoagulation in SSc-PAH. With an over fivefold reduction in mortality demonstrated in some observational studies, the issue of anticoagulation in SSc-PAH demands resolution through a well-designed randomised controlled trial.

Most individuals with treated blood pressures above target receive only one or two antihypertensive drug classes.

BACKGROUND: A significant proportion of individuals taking antihypertensive therapies fail to achieve blood pressures <140/90 mmHg. In order to develop strategies for improved treatment of blood pressure, we examined the association of blood pressure control with antihypertensive therapies and clinical and lifestyle factors in a cohort of adults at increased cardiovascular risk. METHODS: A cross-sectional study of 3994 adults from Melbourne and Shepparton, Australia enrolled in the SCReening Evaluation of the Evolution of New Heart Failure (SCREEN-HF) study. Inclusion criteria were age ≥60 years with one or more of self-reported ischaemic or other heart disease, atrial fibrillation, cerebrovascular disease, renal impairment or treatment for hypertension or diabetes for ≥2 years. Exclusion criteria were known heart failure or cardiac abnormality on echocardiography or other imaging. The main outcome measures were the proportion of participants receiving antihypertensive therapy with blood pressures ≥140/90 mmHg and the association of blood pressure control with antihypertensive therapies and clinical and lifestyle factors. RESULTS: Of 3623 participants (1975 men and 1648 women) receiving antihypertensive therapy, 1867 (52%) had blood pressures ≥140/90 mmHg. Of these 1867 participants, 1483 (79%) were receiving only one or two antihypertensive drug classes. Blood pressures ≥140/90 mmHg were associated with increased age, male sex, waist circumference and log amino-terminal-pro-B-type natriuretic peptide levels. CONCLUSIONS: Most individuals with treated blood pressures above target receive only one or two antihypertensive drug classes. Prescribing additional antihypertensive drug classes and lifestyle modification may improve blood pressure control in this population of individuals at increased cardiovascular risk.

Early identification of asymptomatic subjects at increased risk of heart failure and cardiovascular events: progress and future directions.

Increasing evidence for a latent, preclinical phase of cardiac pathology prior to the development of symptomatic heart failure has fuelled interest in the potential of developing a screening program for early disease detection and intervention. Cardiac biomarkers have shown promise in identifying subjects with significant left ventricular dysfunction and more recently to assist in cardiovascular risk stratification. However, a number of questions remain regarding the use of these biomarkers for screening purposes. In particular, appropriate cut-off levels and adjustment for individual patient characteristics still need to be established and further cost-effectiveness studies are required before screening programs can be undertaken. Given the enormous and increasing burden of cardiac failure worldwide, the potential of these biomarkers to identify those at greatest risk of the condition, either alone or as part of a hybrid screening strategy is of great interest to the cardiology community. The aim of this review is to outline evidence behind the argument for screening, discuss the remaining barriers to its development and implementation and highlight potential areas for future research.

Acute rheumatic fever and rheumatic heart disease--priorities in prevention, diagnosis and management. A report of the CSANZ Indigenous Cardiovascular Health Conference, Alice Springs 2011.

Three priority areas in the prevention, diagnosis and management of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) were identified and discussed in detail: 1. Echocardiography and screening/diagnosis of RHD ­ Given the existing uncertainty it remains premature to advocate for or to incorporate echocardiographic screening for RHD into Australian clinical practice. Further research is currently being undertaken to evaluate the potential for echocardiography screening. 2. Secondary prophylaxis ­ Secondary prophylaxis (long acting benzathine penicillin injections) must be seen as a priority. Systems-based approaches are necessary with a focus on the development and evaluation of primary health care-based or led strategies incorporating effective health information management systems. Better/novel systems of delivery of prophylactic medications should be investigated. 3. Management of advanced RHD ­ National centres of excellence for the diagnosis, assessment and surgical management of RHD are required. Early referral for surgical input is necessary with multidisciplinary care and team-based decision making that includes patient, family, and local health providers. There is a need for a national RHD surgical register and research strategy for the assessment, intervention and long-term outcome of surgery and other interventions for RHD.

Clinical risk prediction model for 30-day all-cause re-hospitalisation or mortality in patients hospitalised with heart failure.

BACKGROUND: This study aimed to develop a risk prediction model (AUS-HF model) for 30-day all-cause re-hospitalisation or death among patients admitted with acute heart failure (HF) to inform follow-up after hospitalisation. The model uses routinely collected measures at point of care. METHODS: We analyzed pooled individual-level data from two cohort studies on acute HF patients followed for 30-days after discharge in 17 hospitals in Victoria, Australia (2014-2017). A set of 58 candidate predictors, commonly recorded in electronic medical records (EMR) including demographic, medical and social measures were considered. We used backward stepwise selection and LASSO for model development, bootstrap for internal validation, C-statistic for discrimination, and calibration slopes and plots for model calibration. RESULTS: The analysis included 1380 patients, 42.1% female, median age 78.7 years (interquartile range = 16.2), 60.0% experienced previous hospitalisation for HF and 333 (24.1%) were re-hospitalised or died within 30 days post-discharge. The final risk model included 10 variables (admission: eGFR, and prescription of anticoagulants and thiazide diuretics; discharge: length of stay>3 days, systolic BP, heart rate, sodium level (<135 mmol/L), >10 prescribed medications, prescription of angiotensin converting enzyme inhibitors or angiotensin receptor blockers, and anticoagulants prescription. The discrimination of the model was moderate (C-statistic = 0.684, 95%CI 0.653, 0.716; optimism estimate = 0.062) with good calibration. CONCLUSIONS: The AUS-HF model incorporating routinely collected point-of-care data from EMRs enables real-time risk estimation and can be easily implemented by clinicians. It can predict with moderate accuracy risk of 30-day hospitalisation or mortality and inform decisions around the intensity of follow-up after hospital discharge.

Increased tissue kallikrein levels in type 2 diabetes.

AIMS/HYPOTHESIS: We measured components of the kallikrein- kinin system in human type 2 diabetes mellitus and the effects of statin therapy on the circulating kallikrein-kinin system. METHODS: Circulating levels of bradykinin and kallidin peptides, and high and low molecular weight kininogens, as well as plasma and tissue kallikrein, and kallistatin were measured in non-diabetic and diabetic patients before coronary artery bypass graft surgery. Tissue kallikrein levels in atrial tissue were examined by immunohistochemistry and atrial tissue kallikrein mRNA quantified. RESULTS: Plasma levels of tissue kallikrein were approximately 62% higher in diabetic than in non-diabetic patients (p=0.001), whereas no differences were seen in circulating levels of bradykinin and kallidin peptides, and high and low molecular weight kininogens, or in plasma kallikrein or kallistatin. Immunohistochemistry revealed a twofold increase in tissue kallikrein levels in atrial myocytes (p= 0.015), while tissue kallikrein mRNA levels were increased eightfold in atrial tissue of diabetic patients (p=0.014). Statin therapy did not change any variables of the circulating kallikrein-kinin system. Neither aspirin, calcium antagonists, beta blockers or long-acting nitrate therapies influenced any kallikrein-kinin system variable. CONCLUSIONS/INTERPRETATION: Tissue kallikrein levels are increased in type 2 diabetes, whereas statin therapy does not modify the circulating kallikrein-kinin system. Cardiac tissue kallikrein may play a greater cardioprotective role in type 2 diabetic than in non-diabetic patients and contribute to the benefits of ACE inhibitor therapy in type 2 diabetic patients. However, our findings do not support a role for the kallikrein-kinin system in mediating the effects of statin therapy on endothelial function.

Evidence for sediment eruption on deep sea floor, gulf of Mexico.

A large crater has been discovered on the sea floor, Gulf of Mexico, in a water depth of 2176 meters. Deep-tow high-resolution imagery shows that the crater is cut into a low hill surrounded by near-surface concentric faults. Approximately 2 million cubic meters of ejected sediment forms a peripheral debris field. The low hill and faults may be related to mud diapirism or intrusion of gas hydrates into near-surface sediments. A recent eruption evacuated sediments from the crater, apparently because of release of overpressured petrogenic gas.

Antiquity of the continental slope along the middle-atlantic margin of the United States.

A detailed high-resolution geophysical study of part of the continental slope along the mid-Atlantic margin of the United States indicates that it is an ancient, relict landscape largely unmodified by modern slope processes. The slope morphology is heavily influenced by bedrock outcrops, including joints and bedding planes, rather than by any single degradational process. A pelagic drape averaging 3 to 5 meters in thickness blankets the slope. Carbon-14 dates from eight drop cores show that the drape was deposited in late Pleistocene and Holocene times. The Holocene part of the drape, comprising the uppermost 1 meter, was deposited at a continuous rate of 10 centimeters per 1000 years. Most features on the slope predate the drape cover.

Turbidity current activity in a british columbia fjord.

A year-long monitoring program within an elongated channel-fan system in Bute Inlet of British Columbia, Canada, detected active sand-transporting turbidity currents. Measurements of bottom velocities and sediment collected in traps, as well as damage to moorings and equipment, captured the signatures of frequent energetic events. Maximum calculated velocities achieved were 335 centimeters per second, with flow thicknesses of more than 30 meters. Coarse sand was transported at least 6 to 7.5 meters above the sea floor. Turbidity currents flowed a minimum distance of 25.9 kilometers, but possibly as far as 40 to 50 kilometers, over bottom slopes of generally less than 1 degrees.

Crystallographic preferred orientation (CPO) of gypsum measured by electron backscatter diffraction (EBSD).

An investigation by electron backscatter diffraction on gypsum shows that this technique can be used to study the microstructures and crystallographic preferred orientation of gypsum. Presented here are the methods, verification tests and data obtained from a naturally deformed sample of gypsum-rich rock. The electron backscatter diffraction data show the sample has a strong crystallographic preferred orientation.

The Weighted Burgers Vector: a new quantity for constraining dislocation densities and types using electron backscatter diffraction on 2D sections through crystalline materials.

The Weighted Burgers Vector (WBV) is defined here as the sum, over all types of dislocations, of [(density of intersections of dislocation lines with a map) x (Burgers vector)]. Here we show that it can be calculated, for any crystal system, solely from orientation gradients in a map view, unlike the full dislocation density tensor, which requires gradients in the third dimension. No assumption is made about gradients in the third dimension and they may be non-zero. The only assumption involved is that elastic strains are small so the lattice distortion is entirely due to dislocations. Orientation gradients can be estimated from gridded orientation measurements obtained by EBSD mapping, so the WBV can be calculated as a vector field on an EBSD map. The magnitude of the WBV gives a lower bound on the magnitude of the dislocation density tensor when that magnitude is defined in a coordinate invariant way. The direction of the WBV can constrain the types of Burgers vectors of geometrically necessary dislocations present in the microstructure, most clearly when it is broken down in terms of lattice vectors. The WBV has three advantages over other measures of local lattice distortion: it is a vector and hence carries more information than a scalar quantity, it has an explicit mathematical link to the individual Burgers vectors of dislocations and, since it is derived via tensor calculus, it is not dependent on the map coordinate system. If a sub-grain wall is included in the WBV calculation, the magnitude of the WBV becomes dependent on the step size but its direction still carries information on the Burgers vectors in the wall. The net Burgers vector content of dislocations intersecting an area of a map can be simply calculated by an integration round the edge of that area, a method which is fast and complements point-by-point WBV calculations.

Functional, structural and molecular aspects of diastolic heart failure in the diabetic (mRen-2)27 rat.

OBJECTIVE: Diabetic cardiomyopathy is an increasingly recognized cause of cardiac failure despite preserved left ventricular systolic function. Given the over-expression of angiotensin II in human diabetic cardiomyopathy, we hypothesized that combining hyperglycaemia with an enhanced tissue renin-angiotensin system would lead to the development of diastolic dysfunction with adverse remodeling in a rodent model. METHODS: Homozygous (mRen-2)27 rats and non-transgenic Sprague Dawley (SD) rats were randomized to receive streptozotocin (diabetic) or vehicle (non-diabetic) and followed for 6 weeks. Prior to tissue collection, animals underwent pressure-volume loop acquisition. RESULTS: Diabetic Ren-2 rats developed impairment of both active and passive phases of diastole, accompanied by reductions in SERCA-2a ATPase and phospholamban along with activation of the fetal gene program. Structural features of diabetic cardiomyopathy in the Ren-2 rat included interstitial fibrosis, cardiac myocyte hypertrophy and apoptosis in conjunction with increased activity of transforming growth factor-beta (p<0.01 compared with non-diabetic Ren-2 rats for all parameters). No significant functional or structural derangements were observed in non-transgenic, SD diabetic rats. CONCLUSION: These findings indicate that the combination of enhanced tissue renin-angiotensin system and hyperglycaemia lead to the development of diabetic cardiomyopathy. Fibrosis, and myocyte hypertrophy, a prominent feature of this model, may be a consequence of activation of the pro-sclerotic cytokine, transforming growth factor-beta, by the diabetic state.