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In this paper, the Ti6Al4V alloy surface was modified via ceramic conversion treatment (CCT) with or without a pre-deposited silver layer. After characterizing the surface morphologies, microstructure and phase constituents of the ceramic oxide layer formed at 620 °C, we investigated the surface hardness and the cross-sectional nano-hardness profile under the oxide layer. The static load-bearing capacity of the oxide layers was examined by applying discrete loads via a Vickers indenter and observing the indentations. A scratch test was used to evaluate the load-bearing capacity and the adhesion/cohesion of the oxide layers. The wettability of the surface changed due to the incorporation of silver and the change of surface morphology. Reciprocating friction and wear test was used to assess the tribological properties. Small and dispersed silver nanoparticles and clusters were found in the oxide layer of the Ag pre-deposited Ti6Al4V samples, and they had much better tribological properties in terms of reduced coefficient of friction and wear volume. With the assistance of silver, the efficiency of the CCT was significantly improved. [ABSTRACT FROM AUTHOR]

To quantify the frequency and clinical implications of systemic sclerosis (SSc)-associated left ventricular function (LV) impairment. Australian Scleroderma Cohort Study participants meeting ACR/EULAR criteria for SSc with ≥1 echocardiographic LVEF measurement were included. Overt LV dysfunction was indicated by reduced LV ejection fraction (LVEF) and subclinical LV dysfunction was measured using impaired LV global longitudinal strain (LV-GLS>-16 %). Those with secondary causes of LV dysfunction (myocardial ischaemia, valvulopathy and pulmonary arterial hypertension) were excluded. Chi-squared tests, two-sample t -tests or Wilcoxon rank-sum tests were used for between-group comparison as appropriate. Generalised estimating equations(GEE) were used to model longitudinal data. Kaplan-Meier and Cox proportional hazard models were used for survival analyses. Of 1141 participants with no co-morbid cardiac disease, 2.4 % ever recorded a LVEF<50 %, while only 0.6 % ever recorded a LVEF≤40 %. LV-GLS data were available for 90 % of participants at one centre (n = 218). Impaired LV-GLS was detected in 21 % despite LVEF≥50 %. Those with a LVEF<50 % were more frequently male (p = 0.01) with dcSSc (p < 0.01), higher inflammatory markers (p < 0.02) and skeletal muscle disease (p < 0.05). In multivariable analyses, recording a LVEF<50 % was associated with increased mortality (HR2.3, 95 %CI1.0–4.8, p = 0.04). Impaired LV-GLS was also associated with poorer survival in univariable analyses (HR3.4, 95 %CI1.0–11.8, p = 0.05). Those with a LVEF<50 % more frequently recorded WHO Class III/IV dyspnoea (OR3.5, 95 %CI1.6–7.7, p < 0.01), with shorter six-minute walk distance (p = 0.01), higher Health Assessment Questionnaire-Disability Index scores (p < 0.01) and lower Short Form-36 Physical Component Summary scores (p = 0.02). Increased dyspnoea (WHO Class III/IV dyspnoea; OR3.6, 95 %CI1.4–9.2, p < 0.01) was also seen in those with impaired LV-GLS. Both overt and subclinical SSc-associated LV dysfunction are associated with worse survival and impaired physical function. The frequency of abnormal LV-GLS in those with consistently normal LVEF suggests an under-appreciated burden of subtle LV systolic dysfunction in SSc that has a significant impact on patient symptomatology. [Display omitted] [ABSTRACT FROM AUTHOR]

The negative effects of warming temperatures on coral physiology are well-documented. However, research increasingly suggests that these effects are variable and that the degree to which corals are impacted by higher temperatures are dependent on a range of environmental and physiological variables. In tropical corals, which live near their upper thermal limits, these disparities have led to significant differences in bleaching and other negative health effects even over relatively small spatial scales. However, the response of temperate corals across small spatial scales is less well understood despite their occurrence in areas with larger temperature ranges than their tropical counterpart. To determine whether responses to thermal stress (27.4 versus 29 °C) differed in a common temperate coral species across a small geographic area, as has been documented in tropical corals, we evaluated coral growth and photosynthetic efficiency (Fv/Fm) of the coral Oculina arbuscula over the course of eight weeks when grown at differing temperatures. When measured as buoyant mass (calcification), growth of O. arbuscula did not differ as a function of temperature or site of collection. In contrast, when measured as change in tissue mass or total wet mass, elevated temperature suppressed growth. Change in total wet mass also varied significantly by collection site, corals from some sites experiencing little if any growth and those from other sites experiencing negative growth. Photosynthetic efficiency (Fv/Fm) was significantly lower at 29 °C than at 27.4 °C. Analyses of symbionts showed that sequence variants related to the genus Breviolum made up ∼98% of all Symbiondiniaceae across all sites and temperature treatments with one variant (100% sequence identity to Breviolum psygmophilum) being 91% of the total community. Only one Symbiodiniaceae, with a 99.28% sequence identity to Breviolum psygmophilum , differed significantly as a function of temperature. It also comprised only 1–3% of the community. Bacterial microbiome variance increased during our experiment, but there were no significant effects of temperature or collection site. For O. arbuscula from these collection sites, location did not impact the coral's ability to withstand the effects of temperature stress. • Elevated temperatures suppress tissue growth of Oculina arbuscula. • Higher temperature lowered Symbiodiniaceae photosynthetic efficiency of O. arbuscula. • Temperature had minimal effects on composition of coral microbiomes. [ABSTRACT FROM AUTHOR]

We aimed to quantify the burden of exercise intolerance in systemic sclerosis (SSc) and explore the disease features that contribute to impaired exercise capacity (measured as peak oxygen uptake, peak VO 2) to provide novel mechanistic insights into the causes of physical disability in SSc. Thirty-three SSc patients with no history of cardiac disease and no active myositis underwent cardiac and skeletal muscle MRI, transthoracic echocardiography, pulmonary function tests and cardiopulmonary exercise testing (CPET). CPET results were compared to an age-, sex-, and weight-matched controls with no overt cardiopulmonary disease. Native T1 and T2-mapping sequences were used to quantify diffuse fibroinflammatory myocardial disease and qualitative assessment of skeletal muscle oedema was performed. The associations between parameters of cardiorespiratory function and skeletal muscle abnormalities and peak VO 2 were evaluated with linear regression analysis. Exercise capacity was markedly impaired in SSc and significantly reduced when compared to control subjects (percent predicted peak VO 2 : 70% vs 98%, p < 0⋅01). Diffuse myocardial fibroinflammatory disease (p < 0⋅01) and skeletal muscle oedema (p = 0⋅01) were significantly associated with reduced exercise capacity. There was no association between impaired exercise capacity and left ventricular ejection fraction. SSc is associated with marked functional impairment that is not explained by commonly used parameters of cardiac function such as left ventricular ejection fraction. Rather, only more sensitive measures of organ involvement are associated with impaired exercise tolerance. Our results show diffuse interstitial changes of the myocardium and skeletal muscle affect oxygen uptake and are important contributors to functional limitation in SSc. [ABSTRACT FROM AUTHOR]

This paper describes a parsimonious methodology employed by the World Bank for estimating potential output using the production function method. Despite the necessity of strong assumptions, sensitivity analysis suggests the reported estimates for 159 countries are robust to alternative specifications. Moreover, for the majority of countries estimated output gaps are positively correlated with inflation acceleration and negatively correlated with current account balances. An examination of estimated output gaps and post-crisis economic developments in several middle-income countries suggest that the methods can play a useful role in guiding macroeconomic policy. [ABSTRACT FROM AUTHOR]

Abstract: Angelman syndrome (AS) is a severe neurodevelopmental disorder associated with disruption of maternally inherited UBE3A (ubiquitin protein ligase E3A) expression. At the present time, there is no effective treatment for AS. Mouse lines with loss of maternal Ube3a (Ube3a m−/p+ ) recapitulate multiple aspects of the clinical AS profile, including impaired motor coordination, learning deficits, and seizures. Thus, these genetic mouse models could serve as behavioral screens for preclinical efficacy testing, a critical component of drug discovery for AS intervention. However, the severity and consistency of abnormal phenotypes reported in Ube3a m−/p+ mice can vary, dependent upon age and background strain, which is problematic for the detection of beneficial drug effects. As part of an ongoing AS drug discovery initiative, we characterized Ube3a m−/p+ mice on either a 129S7/SvEvBrd-Hprt b-m2 (129) or C57BL/6J (B6) background across a range of functional domains and ages to identify reproducible and sufficiently large phenotypes suitable for screening therapeutic compounds. The results from the study showed that Ube3a m−/p+ mice have significant deficits in acquisition and reversal learning in the Morris water maze. The findings also demonstrated that Ube3a m−/p+ mice exhibit motor impairment in a rotarod task, hypoactivity, reduced rearing and marble-burying, and deficient fear conditioning. Overall, these profiles of abnormal phenotypes can provide behavioral targets for evaluating effects of novel therapeutic strategies relevant to AS. [Copyright &y& Elsevier]

The metabotropic glutamate receptors (mGluRs) are evolutionarily conserved from nematodes to vertebrates. The Caenorhabditis elegans ( C. elegans ) genome contains three mGluR genes referred to as mgl-1, mgl-2, and mgl-3. The aim of this study was to characterize the pharmacological profiles of orthosteric and allosteric mGluR ligands on mgl-2. A phylogenetic analysis revealed that mgl-2 is closely associated with the mammalian Group 1 mGluRs (mGluR1 and mGluR5) and is distinct from Group 2 and 3 mGluRs. The ligand binding domain of mgl-2 displayed higher homology to the rat Group 1 mGluRs binding domains compared to the level of homology in the heptahelical transmembrane domain regions. We found that, when transiently expressed in human embryonic kidney 293 cells, mgl-2 can be activated by glutamate and couples to human G-proteins to induce the release of intracellular calcium. Dose–response analyses revealed that mgl-2 has approximately a 15–20-fold lower affinity for glutamate and quisqualate compared to rat mGluR5. In contrast to orthosteric agonists, Group 1 negative allosteric modulators that target the transmembrane domain were ineffective at mgl-2. Surprisingly, CDPPB, an mGluR5 positive allosteric modulator, potentiated glutamate mediated activation of mgl-2, although MPEP and fenobam, two mGluR5 antagonists that share similar binding residues with CDPPB were ineffective at mgl-2. These findings indicate that selective pressures on mGluR protein structures have resulted in conservation of the glutamate binding site, whereas the allosteric modulator sites have been subjected to greater divergent evolutionary changes. [ABSTRACT FROM AUTHOR]

Abstract: We present a case of an intermediate right coronary artery lesion with a fractional flow reserve (FFR) of 0.93 despite a myocardial perfusion scan demonstrating reversible ischemia in the inferior wall. An assessment of microvascular resistance was performed using the index of microcirculatory resistance (IMR). This was consistent with elevated resistance and may explain the discordance between the high FFR result, the positive perfusion study, and the lesion appearance on angiography. FFR assumes stable and minimal resistance at hyperemia; however, there may be situations where this does not occur, contributing to discrepant values. An understanding of the underlying physiological principles that underpin FFR is required for all physicians using this increasingly utilized technique. [Copyright &y& Elsevier]

To establish a gold standard for the information given to patients about the risks associated with third molar extractions, we surveyed 79 oral and maxillofacial surgeons (OMFS) to find out what information they gave to patients during the consent process. We also surveyed 62 medicolegal solicitors to find out what information they thought patients should be given before the procedure, and in what form. A total of 20/76 OMFS (26%) used a two-stage process to obtain consent; 13 (17%) included paraesthesia on the consent form and also gave out an information leaflet. All the lawyers agreed that patients should give their consent in writing and thought that the risk of paraesthesia should be included on the form. Three-quarters thought that they should also be given an information leaflet that includes paraesthesia. We encourage surgeons to do this as part of the two-stage consent process. [ABSTRACT FROM AUTHOR]

Objectives: We sought to establish the relationship between invasive measures of diastolic function and untwisting parameters measured with speckle tracking imaging. Background: Left ventricular (LV) diastolic function is determined by early diastolic relaxation (which creates suction gradients for LV filling) and myocardial stiffness. Assessment of LV torsion has shown that untwisting begins before aortic valve closure and, in animals, might be an important component of normal diastolic filling. Studies in human subjects using indirect indexes derived from right heart catheterization have suggested a relationship between τ and measures of untwisting, but the relationship between directly measured diastolic function indexes with micromanometer catheters and untwisting parameters has not been established in human subjects. Methods: Simultaneous Millar micromanometer LV pressure and echocardiographic assessment was performed on 18 patients (10 male, mean age 66 years) with normal systolic function and a spectrum of diastolic function. Invasive rate of the rise of LV pressure, dp/dt minimum and τ were recorded as measures of active relaxation, and the LV minimum diastolic pressure was recorded as an index of diastolic suction. The LV stiffness constant and functional chamber stiffness were estimated from hybrid pressure-volume loops. Echocardiographic speckle tracking imaging was used to quantify torsion. Results: As relaxation was impaired, (prolonged τ) untwisting was delayed (r = 0.35, p < 0.01). There were nonsignificant associations between reduced untwisting and longer values of τ and lower dp/dt minimum. Reduction in the extent of untwisting before mitral valve opening was associated with increased LV minimum diastolic pressure (r = −0.30, p < 0.034). No relation was observed between the LV stiffness constant (β: r = 0.11, p = NS) or the functional LV chamber stiffness (b: r = 0.11, p = NS) and untwisting. Conclusions: Untwisting parameters are related to invasive indexes of LV relaxation and suction but not to LV stiffness. These data suggest that untwisting is an important component of early diastolic LV filling but not later diastolic events. [Copyright &y& Elsevier]

Background: Pain management is critical to the management of patients in the emergency department (ED). The clinical decision-making process for prescribing medications is complicated by its subjective nature. Historically, racial and ethnic minority groups and women have not had their pain managed as aggressively as White and male patients.Objective: The objective of this study was to determine whether race and biological sex affect the pain management process by means of evaluating data from a large hospital system with diverse patient demographic characteristics.Methods: This was a retrospective study of adult patients who presented an ED within the hospital system and were discharged from the ED with a diagnosis of undifferentiated abdominal pain during a single year. Patient pain was classified as mild, moderate, or severe, and patients were further stratified by race, ethnicity, sex, and insurance status. Pain management was assessed by narcotic vs non-narcotic administration.Results: A total of 32,676 patients were included in the study. Narcotic administration was more likely in White patients with undifferentiated abdominal pain (22%) compared with Black patients (12%; adjusted odds ratio 0.50; 95% CI 0.46-0.54). This persists across patient-reported pain scores. In addition, women (16.99%) were prescribed narcotics less often than men (19.41%; p < 0.0001).Conclusions: Although differences in pain management practices have been explored previously, this study provided a large, updated, multifacility assessment that confirmed that race- and sex-based differences in pain management persist, specifically in the decision to treat with narcotics. Further investigation is warranted to determine the root causes of these differences. [ABSTRACT FROM AUTHOR]

While exploring water soluble rhodamine based fluorescent polymeric systems for biological imaging applications we came across new rhodamine derivatives that possess interesting optical properties. We report the synthesis of three different 2',7'-diphenylated rhodamine derivatives (1-3) with distinct photophysical properties. The three rhodamine derivatives differ by the number of methyl groups present on the nitrogens and their absorption maxima are red-shifted on increased methylation. We observed an unusual inertness of these compounds toward traditional DCC-DMAP esterification conditions, which we attribute to the ease of lactonization in the presence of even minute amounts of the nucleophile/base DMAP (pKa=9.2). Synthesis of acrylate esters was successfully accomplished using MSNT (1-(Mesitylene-2-sulfonyl)-3-nitro-1,2,4-triazole) coupling conditions using a much milder nucleophile/base, for example, N-methyl imidazole (pKa=6.95). [ABSTRACT FROM AUTHOR]

Background: Legionnaires' disease is under-diagnosed because of inconsistent use of diagnostic tests and uncertainty about whom to test. We assessed the increase in case detection following large-scale introduction of routine PCR testing of respiratory specimens in New Zealand.Methods: LegiNZ was a national surveillance study done over 1-year in which active case-finding was used to maximise the identification of cases of Legionnaires' disease in hospitals. Respiratory specimens from patients of any age with pneumonia, who could provide an eligible lower respiratory specimen, admitted to one of 20 participating hospitals, covering a catchment area of 96% of New Zealand's population, were routinely tested for legionella by PCR. Additional cases of Legionnaires' disease in hospital were identified through mandatory notification.Findings: Between May 21, 2015, and May 20, 2016, 5622 eligible specimens from 4862 patients were tested by PCR. From these, 197 cases of Legionnaires' disease were detected. An additional 41 cases were identified from notification data, giving 238 cases requiring hospitalisation. The overall incidence of Legionnaires' disease cases in hospital in the study area was 5·4 per 100 000 people per year, and Legionella longbeachae was the predominant cause, found in 150 (63%) of 238 cases.Interpretation: The rate of notified disease during the study period was three-times the average over the preceding 3 years. Active case-finding through systematic PCR testing better clarified the regional epidemiology of Legionnaires' disease and uncovered an otherwise hidden burden of disease. These data inform local Legionnaires' disease testing strategies, allow targeted antibiotic therapy, and help identify outbreaks and effective prevention strategies. The same approach might have similar benefits if applied elsewhere in the world.Funding: Health Research Council of New Zealand. [ABSTRACT FROM AUTHOR]

Background: In this prospective study, we compared the invasive measures of microvascular function in two subsets: patients with pharmacoinvasive thrombolysis for STEMI, and patients undergoing percutaneous coronary intervention (PCI) for NSTEMI.Methods: The study consisted of 17 patients with STEMI referred for cardiac catheterisation post thrombolysis, and 20 patients with NSTEMI. Coronary physiological indexes were measured in each patient before and after PCI.Results: The median pre-PCI index of microcirculatory function (IMR) at baseline was significantly higher in the STEMI group than the NSTEMI group (26 units vs. 15 units, p = 0.02). Following PCI, IMR decreased in both groups (STEMI 20 units vs. NSTEMI 14 units, p = 0.10). There was an inverse correlation between post PCI IMR and left ventricular ejection fraction (LVEF) (r = -0.52, p = 0.001). Furthermore, post PCI IMR was an independent predictor of index admission LVEF in the total population (β = -0.388, p = 0.02).Conclusion: Invasive measures of microvascular function are inferior in a pharmacoinvasive STEMI group compared to a clinically stable NSTEMI group. In the STEMI population, the IMR following coronary intervention appears to predict LVEF. [ABSTRACT FROM AUTHOR]

The physicochemical design and synthesis of effective cancer-directed and particle-based nanotherapeutic imaging agents remains a challenging task. Of critical importance is the ability to demonstrate maximum delivery, retention, and treatment efficacy for platforms designed to deposit their cargo at sites of disease without attendant dose-limiting toxicity. In this work, we describe dual-modality nanoparticle drug conjugates (NDCs) which utilize protease sensitive linkers to attached drug compounds and imaging labels to a clinically translated class of ultrasmall silica nanoparticle (C′ dots). We describe the synthesis and characterization of these linker-drug constructs. Linkers incorporating dipeptide enzyme substrates are attached to analogs of a prototypical epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), through a cleavable amide bond or para -aminobenzyloxycarbonyl (PABC) group. These constructs are conjugated onto C′ dots leading to the desired NDCs. These NDCs exhibit fast and predictable release kinetics in the presence of model proteases, and are stable in various biological media. Finally, in vitro assays show NDCs to be highly active in reducing phosphorylated EGFR levels in H1650 cells, a human tumor-derived cell line. The data suggests that NDCs exhibit desirable properties that warrant further development toward oncological therapy. [ABSTRACT FROM AUTHOR]

Background: We undertook a prospective study to assess the impact of routine incorporation of right atrial pressure into the calculation of FFR in a real world elective PCI cohort. Methods: 42 patients with stenoses in 2 separate epicardial vessels at coronary angiography were studied. Using a temperature and pressure sensing guidewire (TPSG) FFR and FFRRAP were performed in the target vessel pre and post PCI and in a non-target vessel. FFR was defined as Pd/Pa, FFRRAP as Pd-Pv/Pa-Pv where Pv was right atrial pressure and Pd/Pa were the hyperemic distal and proximal arterial pressures respectively. Results: Mean RAP was 9.1±0.7mmHg. Mean FFR was significantly lower when RAP was included in the calculation (FFRRAP 0.77±0.19 vs. FFR 0.80±0.16, p<0.001). In the target vessel pre PCI, incorporating RAP into the calculation of FFR resulted in a significant difference in the FFR value (FFR Pre-PCI 0.69 ±0.02 vs. FFRRAP Pre-PCI 0.63±0.03, p<0.0001). 21 patients had an FFR ≤0.8 in the group. If right atrial pressure were utilized to calculate FFR prior to PCI, an additional 9 patients would have been re-categorised to an FFR ≤0.8. Following PCI, mean FFR was lower when RAP was incorporated (Post PCI FFRRAP 0.93±0.05 vs. Post PCI FFR 0.95±0.06, p<0.001). Conclusion: Incorporation of right atrial pressure into the calculation of FFR significantly alters FFR values and may potentially reclassify lesions below ischaemic thresholds. [ABSTRACT FROM AUTHOR]

Abstract: Assessment of the left ventricular pressure measured across an aortic valve prosthesis is occasionally necessary when noninvasive imaging and Doppler echocardiographic data are inconclusive or differ from the clinical findings for specific scenarios, such as diagnosing constrictive or restrictive physiology. We present a case in which we safely and effectively replicate the previous successful application of a PressureWire in diagnosing constrictive pericarditis in a patient with a bileafltet mechanical aortic and mitral valves. [Copyright &y& Elsevier]

Abstract: This study reports changes in coal-mine drainage constituent concentrations through an anaerobic SO4-reducing bioreactor monitored over a 3-a period. The purpose of the study was to identify and monitor over time the biogeochemical mechanisms that control the attenuation of toxic compounds in the mine drainage. This information is needed to investigate bioreactor performance and longevity. The water treated at the case example site, the Tab-Simco Mine, was highly acidic with an average pH of 2.9, a net acidity of 1674mg/L CaCO3 equivalent-CCE, and high levels of dissolved , Al, Fe and Mn. The results of this study indicated that the treatment system increased the pH of the acid mine drainage (AMD) to 6.2 and decreased the median acidity to 22.7mg/LCCE, from 2981 to 1750mg/L, Fe from 450.6 to 1.76mg/L, Al from 113 to 0.42mg/L, and Mn from 36.4 to 23.3mg/L. Geochemical modeling indicates that the bioreactor discharge is saturated with respect to the minerals alunite, gibbsite, siderite, rhodochrosite, jarosite, and Fe hydroxide precipitates. The observed trends also include seasonal variations in reduction and a general decline in the amount of alkalinity produced. The average δ 34S value of the in the untreated AMD was+7.3‰. In the bioreactor, δ 34S value of increased from an average of+6.9‰ to+9.2‰, suggesting the presence of bacterial SO4 reduction processes. Preliminary results of a bacterial community analysis show that DNA sequences corresponding to bacteria capable of SO4 reduction were present in the bioreactor outflow sample. However, these sequences were outnumbered by sequences similar to bacteria capable of reoxdizing reduced sulfur species. This study illustrates the dynamic nature of metal removal in SO4-reducing bioreactor-based treatment systems. [Copyright &y& Elsevier]