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BACKGROUND: Individually, noninvasive ventilation (NIV) and helium-oxygen gas mixtures (heliox) diminish ventilatory workload and improve exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). NIV in combination with heliox may have additive effects on exercise tolerance in severe COPD. METHODS: We assessed the safety, tolerability, and efficacy of heliox and NIV during exercise in patients with severe COPD. SETTING: Pulmonary rehabilitation facility in an academic tertiary-care medical center. PROTOCOL: Twelve patients with severe COPD were enrolled. Using a sequential randomized placebo-controlled crossover study design, the patients performed 4 separate constant-work stationary bicycle cardiopulmonary exercise studies at 80% of maximal workload during application of sham NIV, NIV, 60:40 heliox with sham NIV, and 60:40 heliox with NIV. Tolerability, safety, and exercise duration as determined by constant-work cardiopulmonary exercise test were the primary outcome measures. Secondary outcome measures at peak exercise and iso-time included rate of perceived exertion, dyspnea, leg pain, heart rate, respiratory rate, systolic and diastolic blood pressure, tympanic temperature, and oxyhemoglobin saturation. RESULTS: No adverse effects occurred during or after application of NIV, heliox, or NIV with heliox. Exercise duration using heliox with NIV was significantly longer than both heliox (P = .01) and NIV (P = .007), but not placebo (P = .09). Relative to placebo, all treatment arms permitted lower respiratory rates at peak exercise. Heliox, with or without NIV, was associated with significant improvements in oxyhemoglobin saturation at peak exercise, relative to placebo or NIV alone. CONCLUSIONS: The adjunctive use of NIV with heliox during exercise proved both safe and tolerable in patients with severe COPD. The lack of demonstrable efficacy to any of the treatment arms relative to placebo (P = .09) may be the result of the small sample size (ie, type 2 error)-a conclusion emphasized by the large standard deviations and differences in treatment group variances in exercise duration alone. [ABSTRACT FROM AUTHOR]

Recently researchers in the family therapy field have encouraged a focus on aspects of therapy common across all models that are important to therapeutic change. The purpose of this study was to build on the 'common factors' literature by exploring clients' perspectives of what was useful to their therapeutic experience. Quantitative and qualitative measures were used to collect data from 41 clients who participated in therapy at a university-based family therapy clinic. Quantitative results indicated that therapeutic relationship, client motivation, extratherapeutic factors, and hope and expectancy accounted for 49% of the variance of clients' perception of change and 73% of the variance of clients' perceptions of therapy helpfulness. Qualitative results indicated the therapeutic relationship to be the most helpful aspect of clients' therapeutic experience. [ABSTRACT FROM AUTHOR]

Stent implantation in the rabbit aorta has been shown to increase vessel wall compliance at the inflow to the stent, but it is uncertain whether similar effects might be seen in the coronary arteries of humans and whether this would have any significant clinical consequences. First, we measured vessel compliance (systolic lumen area--diastolic lumen area/pulse pressure) before, immediately after, and at the 6-month follow-up visit at a site 5 mm upstream of the proximal edge of an implanted coronary stent in patients undergoing coronary intervention using motorized pull-back intravascular ultrasound recordings. Compliance in the upstream segment increased significantly immediately after stenting (before 7.13 +/- 1.49 vs after 10.73 +/- 1.36 mm2/mm Hg, p = 0.03), an effect that was unchanged at 6 months of follow-up (11.84 +/- 2.11 mm2/mm Hg, p = 0.08 vs before stenting). Second, we examined the site of plaque rupture in all patients presenting with an acute coronary syndrome in whom the culprit lesion was in a vessel that had had a stent implanted >12 months previously (n = 31). Plaque rupture was statistically more likely at the inflow to the stent (n = 22) than at other sites within the culprit vessel (n = 9, p <0.01). We conclude that stenting causes an increase in vessel compliance immediately proximal to the stent, and that when a vessel has been previously stented, plaque rupture is most likely to occur at the stent inflow site. [ABSTRACT FROM AUTHOR]

X-ray Diffraction Computed Tomography (XRD-CT) represents a cutting-edge method for non-destructive material analysis, offering the unique capability of providing molecular-level information with spatial resolution. In this study, we have applied XRD-CT to investigate pharmaceutically relevant tablets that have been subjected to a range of compression pressures typical in tablet manufacturing. By employing XRD-CT to pharmaceutical tablets, we reveal material changes without tablet destruction, thereby avoiding potential phase transformations during sample preparation that could lead to errors in the interpretation of the processes that have occurred. Utilizing a pressure-sensitive marker, glycolide, we have tracked changes within tablet structures induced by compression, pinpointing locations where glycolide undergoes pressure-induced transformation. Additionally, we conducted a follow-up study with analysis one month later, observing an in-situ hydrolysis reaction of glycolide within the tablets. Through the complementary use of electron diffraction, we have elucidated the structure of the hydrolysis product, further enhancing our understanding of temporal changes in the tablets., (© 2024 Wiley‐VCH GmbH.)

Septal artery perforations are an uncommon complication of percutaneous coronary intervention. Unlike epicardial vessels, septal perforations do not result in pericardial effusions but rather produce septal haematomas. While most can be managed expectantly, a small proportion requires active management to prevent rapid haematoma expansion resulting in compromise of right ventricular filling and 'dry tamponade'. We present two cases of septal artery perforation during percutaneous coronary intervention and propose a management approach that takes into account the unique haemodynamic consequences of this complication., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to disclose., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Numerous guidelines on the diagnosis and management of hypertrophic cardiomyopathy (HCM) have been published, by learned societies, over the past decade. Although helpful they are often long and less adapted to nonexperts. This writing panel was challenged to produce a document that grew as much from years of practical experience as it did from the peer-reviewed literature. As such, rather than produce yet another set of guidelines, we aim herein to deliver a concentrate of our own experiential learning and distill for the reader the essence of effective and appropriate HCM care. This Clinical Practice Update on HCM is therefore aimed at general cardiologists and other cardiovascular practitioners rather than for HCM specialists. We set the stage with a description of the condition and its clinical presentation, discuss the central importance of "obstruction" and how to look for it, review the role of cardiac magnetic resonance imaging, reflect on the appropriate use of genetic testing, review the treatment options for symptomatic HCM-crucially including cardiac myosin inhibitors, and deal concisely with practical issues surrounding risk assessment for sudden cardiac death, and management of the end-stage HCM patient. Uniquely, we have captured the pediatric experience on our panel to discuss appropriate differences in the management of younger patients with HCM. We ask the reader to remember that this document represents expert consensus opinion rather than dogma and to use their best judgement when dealing with the HCM patient in front of them., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The management of diabetes mellitus and its resultant end organ dysfunction represents a major challenge to global health-care systems. Diabetic cardiac and kidney disease commonly co-occur and are significant contributors to the morbidity and mortality of patients with diabetes, carrying a poor prognosis. The tight link of these parallel end organ manifestations suggests a deeper common underlying pathology. Here, we outline the mechanistic link between diabetic cardiac and kidney disease, providing evidence for the role of endothelial dysfunction in both processes and the potential for cellular therapy to correct these disorders. Specifically, we review the preclinical and clinical evidence for endothelial progenitor cell therapy in cardiac, kidney, and cardio-renal disease applications. Finally, we outline novel approaches to endothelial progenitor cell therapy through cell enhancement and the use of extracellular vesicles, discussing published and future work., (© The Author(s) 2024. Published by Oxford University Press.)

Pharmaceutical cocrystals use common robust hydrogen bonding synthons to create novel materials with different physicochemical properties. In this systematic study of a series of cocrystals, we explore the effect of high pressure on one of these commonly used motifs, the acid-pyridine motif, to assess the commonality of behaviour under extreme conditions. We have surveyed five pyridine dicarboxylic acid systems using both synchrotron and neutron diffraction methods to elucidate the changes in structure. We observe that the hydrogen bonding in these systems compress at a similar rate despite the changes to the molecular make-up of the solids and that on compression the changes in structure are indicative that the layers move along the major slip planes in the structure. We have observed two phase transitions to new forms of the pyrazine:malonic acid system, one for each stoichiometric ratio. This study demonstrates that the combination of two complementary diffraction approaches is key to understanding polymorphic behaviour at high pressure., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Iain D H Oswald reports financial support was provided by Engineering and Physical Sciences Research Council. Iain D H Oswald reports financial support was provided by Science and Technology Facilities Council. Iain D H Oswald reports a relationship with Science and Technology Facilities Council that includes: board membership, consulting or advisory, and travel reimbursement., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

We present an extensive exploration of the solid-form landscape of chlorpropamide (CPA) using a combined experimental-computational approach at the frontiers of both fields. We have obtained new conformational polymorphs of CPA, placing them into context with known forms using flexible-molecule crystal structure prediction. We highlight the formation of a new polymorph (ζ-CPA) via spray-drying experiments despite its notable metastability (14 kJ/mol) relative to the thermodynamic α-form, and we identify and resolve the ball-milled η-form isolated in 2019. Additionally, we employ impurity- and gel-assisted crystallization to control polymorphism and the formation of novel multicomponent forms. We, thus, demonstrate the power of this collaborative screening approach to observe, rationalize, and control the formation of new metastable forms., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Postsynthetic modification of metal-organic frameworks (MOFs) has proven to be a hugely powerful tool to tune physical properties and introduce functionality, by exploiting reactive sites on both the MOF linkers and their inorganic secondary building units (SBUs), and so has facilitated a wide range of applications. Studies into the reactivity of MOF SBUs have focussed solely on removal of neutral coordinating solvents, or direct exchange of linkers such as carboxylates, despite the prevalence of ancillary charge-balancing oxide and hydroxide ligands found in many SBUs. Herein, we show that the μ 2 -OH ligands in the MIL-53 topology Sc MOF, GUF-1, are labile, and can be substituted for μ 2 -OCH 3 units through reaction with pore-bound methanol molecules in a very rare example of pressure-induced postsynthetic modification. Using comprehensive solid-state NMR spectroscopic analysis, we show an order of magnitude increase in this cluster anion substitution process after exposing bulk samples suspended in methanol to a pressure of 0.8 GPa in a large volume press. Additionally, single crystals compressed in diamond anvil cells with methanol as the pressure-transmitting medium have enabled full structural characterisation of the process across a range of pressures, leading to a quantitative single-crystal to single-crystal conversion at 4.98 GPa. This unexpected SBU reactivity - in this case chemisorption of methanol - has implications across a range of MOF chemistry, from activation of small molecules for heterogeneous catalysis to chemical stability, and we expect cluster anion substitution to be developed into a highly convenient novel method for modifying the internal pore surface and chemistry of a range of porous materials., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

Understanding the solvation and desolvation of pharmaceutical materials is an important part of materials discovery and development. In situ structural data are vital to understand the changes to crystal form that may occur in the system. In this study, the isolation and characterization of seven solvates of the L-type calcium channel antagonist, nifedipine, is described using variable-temperature powder X-ray diffraction so that the structural evolution as a function of temperature can be followed. The solvates reported herein can be split into those that are structurally similar to the previously reported dimethyl sulfoxide (DMSO) and dioxane solvates and those that have a novel packing arrangement. Of particular note is the solvate with tetrahydrofuran (THF) which has a hydrogen-bonding motif between the nifedipine molecules very similar to that of metastable β-nifedipine. In addition to variable-temperature X-ray diffraction, the stability of the solid forms was assessed using differential scanning calorimetry and thermogravimetric analysis and indicates that in all cases desolvation results in the thermodynamically stable α-polymorph of nifedipine even with the THF solvate. From the diffraction data the pathway of desolvation during heating of the DMF solvate showed conversion to another likely 1:1 polymorph before desolvation to α-nifedipine. The desolvation of this material indicated a two-stage process; first the initial loss of 90% of the solvent before the last 10% is lost on melting. The methanol solvate shows interesting negative thermal expansion on heating, which is rarely reported in organic materials, but this behaviour can be linked back to the winerack-type hydrogen-bonding pattern of the nifedipine molecules., (open access.)

Adjuvants are essential components of subunit vaccines added to enhance immune responses to antigens through immunomodulation. Very few adjuvants have been approved for human use by regulatory agencies due to safety concerns. Current subunit vaccine adjuvants approved for human use are very effective in promoting humoral immune responses but are less effective at promoting T-cell immunity. In this study, we evaluated a novel pure enantio-specific cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (R-DOTAP) as an immunomodulator for subunit vaccines capable of inducing both humoral- and cellular-mediated immunity. Using recombinant protein antigens derived from SARS-CoV2 spike or novel computationally optimized broadly reactive influenza antigen (COBRA) proteins, we demonstrated that R-DOTAP nanoparticles promoted strong cellular- and antibody-mediated immune responses in both monovalent and bivalent vaccines. R-DOTAP-based vaccines induced antigen-specific and polyfunctional CD8 + and CD4 + effector T cells and memory T cells, respectively. Antibody responses induced by R-DOTAP showed a balanced Th1/Th2 type immunity, neutralizing activity and protection of mice from challenge with live SARS-CoV2 or influenza viruses. R-DOTAP also facilitated significant dose sparing of the vaccine antigens. These studies demonstrate that R-DOTAP is an excellent immune stimulator for the production of next-generation subunit vaccines containing multiple recombinant proteins.

Purpose: This study aimed to investigate hamstring architectural, strength, and morphological adaptations after an eccentric or isometric hip extension exercise intervention., Methods: Twenty-four recreationally active males performed either an eccentric ( n = 12) or an isometric hip extension ( n = 12) exercise intervention, twice per week for 6 wk, followed by a 4-wk detraining period. Biceps femoris long head (BFlh) architecture was assessed pre-intervention, mid-intervention, post-intervention, and post-detraining via two-dimensional ultrasound. Strength was assessed pre-intervention, post-intervention, and post-detraining during an isokinetic knee flexion, an isometric hip extension, a Nordic hamstring exercise, and a single-leg hamstring bridge repetition to fatigue test. Hamstring muscle morphology was assessed via magnetic resonance imaging before strength testing sessions., Results: The eccentric hip extension exercise intervention significantly lengthened BFlh fascicles (+19.7%, P < 0.001, d = 1.57), increased eccentric knee flexion torque (ECC 60°·s -1 , +12%, P < 0.005, d = 0.66; ECC 180°·s -1 , +8.3%, P < 0.05, d = 0.41), and increased BFlh (+13.3%, P < 0.001, d = 1.96) and semimembranosus (SM) muscle volume (+12.5%, P < 0.001, d = 2.25). After 4 wk of detraining, BFlh fascicles were significantly shortened in the eccentric group (-14.8%, P < 0.005, d = -1.25), whereas eccentric knee flexion torque and BFlh and SM volumes were unchanged. The isometric hip extension exercise intervention significantly increased isometric knee flexion torque (+10.4%, P < 0.05, d = 0.54), isometric hip extension force (+12.4%, P < 0.05, d = 0.41), and semitendinosus volume (+15%, P = 0.054, d = 1.57). All other outcome measures saw no significant changes. After 4 wk of detraining, no significant changes to any variables were observed in the isometric group., Conclusions: The eccentric but not isometric hip extension exercise intervention significantly increased BFlh fascicle length. Both exercise interventions demonstrated contraction mode-specific increases in strength. However, the eccentric hip extension exercise intervention resulted in preferential hypertrophy of BFlh and SM, and the isometric hip extension exercise intervention led to selective hypertrophy of semitendinosus., (Copyright © 2022 by the American College of Sports Medicine.)

Background: Treating known risk factors for coronary artery disease (CAD) has substantially reduced CAD morbidity and mortality. However, a significant burden of CAD remains unexplained. Immunoglobulin E sensitization to mammalian oligosaccharide galactose-α-1,3-galactose (α-Gal) was recently associated with CAD in a small observational study. We sought to confirm that α-Gal sensitization is associated with CAD burden, in particular noncalcified plaque. Additionally, we sort to assess whether that α-Gal sensitization is associated with ST-segment-elevated myocardial infarction (STEMI) Methods: We performed a cross-sectional analysis of participants enrolled in the BioHEART cohort study. We measured α-Gal specific-immunoglobulin E antibodies in serum of 1056 patients referred for CT coronary angiography for suspected CAD and 100 selected patients presenting with STEMI, enriched for patients without standard modifiable risk factors. CT coronary angiograms were assessed using coronary artery calcium scores and segmental plaque scores., Results: α-Gal sensitization was associated with presence of noncalcified plaque (odds ratio, 1.62 [95% CI, 1.04-2.53], P =0.03) and obstructive CAD (odds ratio, 2.05 [95% CI, 1.29-3.25], P =0.002), independent of age, sex, and traditional risk factors. The α-Gal sensitization rate was 12.8-fold higher in patients with STEMI compared with matched healthy controls and 2.2-fold higher in the patients with STEMI compared with matched stable CAD patients (17% versus 1.3%, P =0.01 and 20% versus 9%, P =0.03, respectively)., Conclusions: α-Gal sensitization is independently associated with noncalcified plaque burden and obstructive CAD and occurs at higher frequency in patients with STEMI than those with stable or no CAD. These findings may have implications for individuals exposed to ticks, as well as public health policy. Registration: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12618001322224.

Dynamic organic crystals have come to the fore as potential lightweight alternatives to inorganic actuators providing high weight-to-force ratios. We have observed pressure-induced superelastic behaviour in Form I of isonicotinamide. The reversible single-crystal to single-crystal transformation exhibited by the system is an important component for functioning actuators. Crucially, our observations have enabled us to propose a mechanism for the molecular movement supported by Pixel energy calculations, that may pave the way for the future design and development of functioning dynamic crystals.

Comprehensive and meaningful policy analysis in the field of physical activity is difficult, not least because of the variable influence of other policy domains. However, in 2011 a Policy Assessment Tool (PAT) was developed by members of the WHO European Network for the Promotion of Health-Enhancing Physical Activity (HEPA Europe) and tested in several different countries. In 2014, Wales joined a global initiative, active healthy kids (AHK) Global Alliance, that supported the development of country level 'Report Cards' scoring a range of indicators that influence physical activity amongst children and young people, one of which was labelled 'Government Strategies and Investments'. For the first two Report Cards this indicator and its associated 'score' was informed subjectively by expert consensus. In 2018, it was decided to utilize the Policy Audit Tool Version 2 (PAT v2) developed by HEPA Europe to aid analysis and to develop and test a scoring rubric aligned to the tool. The subsequent process indicated that the tool could be applied and translated into a 'grade' that could be used in conjunction with the other indicators of the AHK Report Card to generate overall Report Card grades. The use of both the HEPA PAT v2 and the scoring rubric offers an opportunity to provide greater consistency and potential for developing both comparative and trend data when assessing policy impact on physical activity in children and young people. These tools should be utilized by the AHK Global Alliance in future Report Cards., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To assess the prognostic implications of the degree of coronary collaterals on outcomes in patients with a CTO., Background: Coronary chronic total occlusions (CTO) are identified frequently in patients undergoing coronary angiography and have been associated with poorer prognosis. Whether the degree of coronary collaterals, the hallmark of CTOs impacts prognosis, is unknown., Methods: A search of EMBASE, MEDLINE, and Cochrane Library was conducted to identify studies reporting on coronary collaterals and risk of all-cause mortality, acute myocardial infarction (AMI) and successful percutaneous coronary intervention (PCI). Patients with Rentrop grade 0 or 1 collaterals were defined as poor collaterals, while Rentrop grade 2 or 3 were defined as robust collaterals., Results: Twelve studies with a total of 3,369 were included. Patients with robust collaterals did not have lower rates of AMI (OR: 0.89, 95%CI: 0.39-2.04) or lower rates of all-cause mortality (OR: 0.81, 95% CI: 0.42-1.58), however were more likely to have successful PCI (OR: 4.04, 95%CI: 1.10-14.85)., Conclusion: The presence of robust collaterals is not associated with lower rates of AMI or mortality, but does increase the likelihood of successful CTO PCI. These results have importance implications with respect to the indications for CTO PCI as well as selecting appropriate patients to undergo the procedure., (© 2020 Wiley Periodicals LLC.)

Progress is reported in analytical in situ environmental scanning transmission electron microscopy (ESTEM) for visualizing and analysing in real-time dynamic gas-solid catalyst reactions at the single-atom level under controlled reaction conditions of gas environment and temperature. The recent development of the ESTEM advances the capability of the established ETEM with the detection of fundamental single atoms, and the associated atomic structure of selected solid-state heterogeneous catalysts, in catalytic reactions in their working state. The new data provide improved understanding of dynamic atomic processes and reaction mechanisms, in activity and deactivation, at the fundamental level; and in the chemistry underpinning important technological processes. The benefits of atomic resolution-E(S)TEM to science and technology include new knowledge leading to improved technological processes, reductions in energy requirements and better management of environmental waste. This article is part of a discussion meeting issue 'Dynamic in situ microscopy relating structure and function'.

Agricultural development has resulted in the degradation of freshwater ecosystems worldwide. Two key stressors impacting streams and rivers draining agricultural catchments are deposited fine sediment (e.g. due to erosion) and reduced flows (e.g. due to water abstraction, dams, or climate change). Past studies have identified fine sediment as a 'master stressor' in streams, but the effects of different sediment grain sizes in combination with reduced flow velocity are poorly understood. We manipulated deposited fine sediment (no added sediment; silt: 0-0.125 mm; fine sand: 0.125-0.250 mm; coarse sand: 1-2 mm) and flow velocity (fast: 26.5 cm/s; medium: 13.9 cm/s; slow: 0.0 cm/s) simultaneously in 60 outdoor stream mesocosms. We determined the individual and combined effects of these stressors on the benthic, drifting, and emerging stream macroinvertebrate communities. Both fine sediment and reduced flow velocity had pervasive detrimental impacts on stream invertebrate communities. Negative effects of sediment were worse at the smaller two grain sizes for some responses (abundance of Chironomidae, Copepoda, Psilochorema spp.); however, for several sediment-sensitive common taxa or community-level invertebrate metrics, effects were negative regardless of grain size. Although their combined effects were mainly additive, sediment impacts were worsened by reduced flow velocities in several cases. Our findings imply that (a) especially for sediment-sensitive species, all fine sediment <2 mm has profound negative effects, (b) sediment grain size matters for some invertebrate taxa, where severity of impacts increased as particle size decreased, and (c) negative effects of sedimentation can become worse when combined with reduced flow velocity., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Many heterogeneous chemical reactions involve gases catalyzed over solid surfaces at elevated temperatures and play a critical role in the production of energy, healthcare, pollution control, industrial products, and food. These catalytic reactions take place at the atomic level, with active structures forming under reaction conditions. A fundamental understanding of catalysis at the single atom resolution is therefore a major advance in a rational framework upon which future catalytic processes can be built. Visualization and analysis of gas-catalyst chemical reactions at the atomic level under controlled reaction conditions are key to understanding the catalyst structural evolution and atomic scale reaction mechanisms crucial to the performance and the development of improved catalysts and chemical processes. Increasingly, dynamic single atoms and atom clusters are believed to lead to enhanced catalyst performance, but despite considerable efforts, reaction mechanisms at the single atom level under reaction conditions of gas and temperature are not well understood. The development of the atomic lattice resolution environmental transmission electron microscope (ETEM) by the authors is widely used to visualize gas-solid catalyst reactions at this atomic level. It has recently been advanced to the environmental scanning TEM (ESTEM) with single atom resolution and full analytical capabilities. The ESTEM employs high-angle annular dark-field imaging where intensity is approximately proportional to the square of the atomic number ( Z ). In this Account, we highlight the ESTEM development also introduced by the authors for real time in situ studies to reliably discern metal atoms on lighter supports in gas and high temperature environments, evolving oxide/metal interfaces, and atomic level reaction mechanisms in heterogeneous catalysts more generally and informatively, with utilizing the wider body of literature. The highlights include platinum/carbon systems of interest in fuel cells to meet energy demands and reduce environmental pollution, in reduction/oxidation (redox) mechanisms of copper and nickel nanoparticles extensively employed in catalysis, electronics, and sensors, and in the activation of supported cobalt catalysts in Fischer-Tropsch (FT) synthesis to produce fuels. By following the dynamic reduction process at operating temperature, we investigate Pt atom migrations from irregular nanoparticles in a carbon supported platinum catalyst and the resulting faceting. We outline the factors that govern the mechanism involved, with the discovery of single atom interactions which indicate that a primary role of the nanoparticles is to act as reservoirs of low coordination atoms and clusters. This has important implications in supported nanoparticle catalysis and nanoparticle science. In copper and nickel systems, we track the oxidation front at the atomic level as it proceeds across a nanoparticle, by directly monitoring Z -contrast changes with time and temperature. Regeneration of deactivated catalysts is key to prolong catalyst life. We discuss and review analyses of dynamic redox cycles for the redispersion of nickel nanoparticles with single atom resolution. In the FT process, pretreatment of practical cobalt/silica catalysts reveals higher low-coordination Co 0 active sites for CO adsorption. Collectively, the ESTEM findings generate structural insights into catalyst dynamics important in the development of efficient catalysts and processes.

Aims: Recent reports have shown a high incidence of silent left ventricular apical ballooning (LVAB) in the intensive care unit (ICU) setting with potential implications for safe use of inotropes and vasopressors. We examined the incidence, predictors, and associated outcomes of LVAB in patients in a contemporary tertiary Australian ICU., Methods and Results: In a prospective cohort study, patients were screened within 24 h of admission to the ICU and enrolled if they were deemed critically unwell based on mechanical ventilation, administration of >5 mg/min of noradrenaline, or need for renal replacement therapy. Exclusion criteria were a primary diagnosis of Takotsubo cardiomyopathy, admission to ICU after cardiac surgery, or with acute myocardial infarction or heart failure. Echocardiography was performed, and the presence/absence of LVAB was documented. A total of 116 patients were enrolled of whom four had LVAB (3.5%, 95% confidence interval 0.9-8.6%). Female sex was the only baseline demographic or clinical characteristic associated with incident LVAB. Medical history, ICU admission indication, and choice of inotropes were not associated with increased risk. Patients with LVAB had no deaths and had similar lengths of ICU and hospital stay compared with patients with no LVAB., Conclusions: The incidence of silent LVAB suggestive of TC was substantially lower in this study than recently reported in other international ICU settings. We did not observe a suggestion of worse outcomes. A larger, multi-centre study, prospectively screening for LVAB may help understand any variation between centres and regions, with important implications for ICU management., (© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

A coronary chronic total occlusion (CTO) is a common finding during coronary angiography and is associated with increased mortality and poorer cardiovascular prognosis. Technological developments in percutaneous strategies for revascularisation have resulted in increased interest in this area. However, until recently, there has been a paucity of robust scientific randomised data comparing the efficacy of medical management with percutaneous strategies. Both observational data, and to a lesser extent, randomised data, suggest that CTO percutaneous coronary intervention (PCI) should be considered in symptomatic patients. However, in the absence of any randomised data, CTO PCI should not be performed for prognostic benefit. Ongoing trials are needed to confirm these findings as well as to identify the optimal timing and strategy of such interventions., (Copyright © 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Concurrent coronary artery disease in a vessel remote from a chronic total occlusion (CTO) is common and presents a management dilemma. While the use of adjunctive coronary physiology to guide revascularization is now commonplace in the catheterization laboratory, the presence of a CTO provides a unique and specific situation whereby the physiological assessment is more complex and relies on theoretical assumptions. Broadly, the physiological assessment of a CTO relies on assessing the function and regression of collaterals, the assessment of the microcirculation, the impact of collateral steal as well as assessing the severity of a lesion in the donor vessel (the vessel supplying the majority of collaterals to the CTO). Recent studies have shown that physiological assessment of the donor vessel in the setting of a CTO may overestimate the severity of stenosis, and that after revascularization of a CTO, the index of ischemia may increase, potentially altering the need for revascularization. In this review article, we present the current literature on physiological assessment of patients with a CTO, management recommendations and identify areas for ongoing research.

Atomic-scale relaxations of platinum nanoparticles (Pt NPs) for fuel-cell catalysts are evaluated by spherical-aberration corrected environmental transmission electron microscopy (ETEM) under reference high-vacuum and N 2 atmospheres, and then under reactive H 2 , CO and O 2 atmospheres, combined with ex situ durability test using an electrochemical half-cell. In high-vacuum, increasing roughness due to continuous relaxation of surface-adsorbed Pt atoms is quantified in real-space. Under H 2 and N 2 atmospheres at a critical partial pressure of 1 × 10 -2 Pa the stability of the surface facets is for the first time found to be improved. The adsorption behaviour of CO molecules is investigated using experimentally measured Pt-Pt bond lengths on the topmost surface layer of Pt NPs. The deactivation of Pt NPs in the anode environment of a proton-exchange-membrane fuel-cell is demonstrated at the atomic-scale in the ETEM, and the transformation of NPs into disordered nanoclusters is systematically quantified using the partial size distribution of Pt atomic clusters under controlled heating experiments at 423, 573 and 723 K.

Purpose: Patients with Alzheimer's Disease (AD) exhibit decreased retinal blood flow and vessel density (VD). However, it is not known whether these changes are also present in individuals with early AD (eAD) or amnestic type mild cognitive impairment (aMCI), an enriched pre-AD population with a higher risk for progressing to dementia. We performed a prospective case-control clinical study to investigate whether optical coherence tomography angiography (OCTA) parameters in the macula and disc are altered in those with aMCI and eAD., Methods: This is a single center study of 32 participants. Individuals with aMCI/eAD (n = 16) were 1:1 matched to cognitively normal controls (n = 16). We evaluated OCTA images of the parafoveal superficial capillary plexus (SCP) and two vascular layers in the peripapillary region, the radial peripapillary capillary (RPC) and superficial vascular complex (SVC). Outcome vascular and structural parameters included VD, vessel length density (VLD), adjusted flow index (AFI) and structural retinal nerve fiber layer (RNFL) thickness. We compared these parameters between the two groups and examined the correlation between OCTA parameters and cognitive performance on the Montreal Cognitive Assessment (MoCA)., Results: Cognitively impaired participants demonstrated statistically significant decrease in parafoveal SCP VD and AFI as compared to controls, but no statistically significant difference in peripapillary parameters. Furthermore, we found a significant positive correlation between MoCA scores for the entire study cohort and both the parafoveal SCP VD and peripapillary RPC VLD., Conclusion: OCTA shows significant decline in parafoveal flow and VD in individuals with early cognitive impairment related to AD, suggesting that these parameters could have potential utility as early disease biomarkers. In contrast, the presence of larger vascular channels in the peripapillary region may have obscured subtle capillary changes in that region. Overall, the correlation between vascular OCTA parameters and cognitive performance supports further OCTA studies in this population., Competing Interests: The authors have declared that no competing interests exist.

Coronary chronic total occlusions (CTO) occur when there is complete, or near complete occlusion of a vessel, angiographically appreciated by the presence of a collateral circulation with late filling of the occluded vessel. With restoration of anterograde blood flow there is alteration in vascular wall stress which may influence distal vessel size. We sought to determine if the distal vessel size changes following revascularization of the CTO. We retrospectively reviewed patients who underwent successful CTO revascularization and who subsequently underwent repeat angiography. We measured the size of the vessel proximal and distal to the stented segment to assess for change in luminal diameter. Thirty-seven successful CTO revascularization procedures were reviewed. The mean age was 70.3, with 81% male. The most commonly revascularised artery was the right coronary artery (RCA). The median time between angiograms was 194 days. The indexed luminal diameter distal to the stented segment had a greater increase in size compared to the proximal segment (31.1 vs 4.8%, p < 0.0001). The increase in distal vessel was seen in both RCA (34.5 vs 8%, p < 0.001) and non-RCA (28.7 vs 1.9%, p < 0.001). The distal vessel had a more marked increase in distal luminal diameter if there was no resting hypokinesis in the territory supplied by the CTO (35.6 vs 15.0%, p < 0.01). The luminal diameter distal to a revascularized CTO has a greater increase in size compared to the proximal vessel and persists over time. This may have implications on determining stent sizing during CTO procedures as well as determining suitable vessels for attempted revascularization.

The capacity of stem and progenitor cells to stimulate cardiac regeneration has been studied for almost 20 years, with very promising preclinical data and mixed clinical results. Several cell types have been studied, identified by their cell surface markers, differentiation capacity and their secreted growth factors. Bone marrow derived mesenchymal stem cells (MSCs) have been found to have potent regenerative capacity, through multiple mechanisms, including mesoderm lineage differentiation, immunomodulation, and paracrine stimulation. MSCs also secrete exosomes and microvesicles, which themselves contain potent angiogenic cytokines or mRNA molecules with effects on their local milieu. This concise review summarizes the mechanisms of MSC-based cardiac regeneration and highlighting results from molecular and preclinical studies. We also discuss clinical trial results to date, and ongoing studies. Furthermore, we discuss novel approaches for the enhancement of MSC based cardiac regeneration, such as genetic modification. Stem Cells Translational Medicine 2018;7:543-550., (© 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Reduction reactions in practical bimetallic platinum-cobalt electrode catalyst precursors containing platinum, cobalt and cobalt oxides in hydrogen at 200, 450 and 700 °C for 6 h have been studied in situ using an aberration corrected environmental (scanning) transmission electron microscope (AC E(S)TEM). Little difference was observed in reduction at 200 °C but during and after reduction at 450 °C, small nanoparticles less than 3 nm in diameter with tetragonal PtCo structures were observed and limited Pt 3 Co ordering could be seen on the surfaces of larger nanoparticles. During and after reduction at 700 °C, fully ordered Pt 3 Co and PtCo nanoparticles larger than 4 nm were produced and the average nanoparticle size almost trebled relative to the fresh precursor. After reduction at 450 and 700 °C, most nanoparticles were disordered platinum/cobalt alloys with fcc structure. After reduction at 700 °C many of the smallest nanoparticles disappeared suggesting Ostwald ripening had occurred. Mechanisms concerning the thermal transformation of mixed cobalt and platinum species are discussed, offering new insights into the creation of bimetallic platinum-cobalt nanoparticles in fuel cell catalysts., (© 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.)

The integration of inflammatory signals is paramount in controlling the intensity and duration of immune responses. Eicosanoids, particularly PGE 2 , are critical molecules in the initiation and resolution of inflammation and in the transition from innate to acquired immune responses. Microsomal PGE synthase 1 (mPGES1) is an integral membrane enzyme whose regulated expression controls PGE 2 levels and is highly expressed at sites of inflammation. PGE 2 is also associated with modulation of autoimmunity through altering the IL-23/IL-17 axis and regulatory T cell (Treg) development. During a type II collagen-CFA immunization response, lack of mPGES1 impaired the numbers of CD4 + regulatory (Treg) and Th17 cells in the draining lymph nodes. Ag-experienced mPGES1 -/- CD4 + cells showed impaired IL-17A, IFN-γ, and IL-6 production when rechallenged ex vivo with their cognate Ag compared with their wild-type counterparts. Additionally, production of PGE 2 by cocultured APCs synergized with that of Ag-experienced CD4 + T cells, with mPGES1 competence in the APC compartment enhancing CD4 + IL-17A and IFN-γ responses. However, in contrast with CD4 + cells that were Ag primed in vivo, exogenous PGE 2 inhibited proliferation and skewed IL-17A to IFN-γ production under Th17 polarization of naive T cells in vitro. We conclude that mPGES1 is necessary in vivo to mount optimal Treg and Th17 responses during an Ag-driven primary immune response. Furthermore, we uncover a coordination of autocrine and paracrine mPGES1-driven PGE 2 production that impacts effector T cell IL-17A and IFN-γ responses., (Copyright © 2018 by The American Association of Immunologists, Inc.)

Purpose: Chemoresistant ovarian cancers grow in suspension within the ascites fluid. To screen the effect of chemotherapeutics and biologics on resistant ovarian cancers with a personalized basis, we developed a 3D hanging drop spheroid platform. Experimental Design: We initiated spheroids with primary aldehyde dehydrogenase-positive (ALDH + ) CD133 + ovarian cancer stem cells (OvCSC) from different patient samples and demonstrated that stem cell progeny from harvested spheroids was similar to the primary tumor. OvCSC spheroids were utilized to initiate tumors in immunodeficient mice. Drug responses to cisplatin and ALDH-targeting compound or JAK2 inhibitor determined whether the OvCSC population within the spheroids could be targeted. Cells that escaped therapy were isolated and used to initiate new spheroids and model tumor reemergence in a personalized manner. Results: OvCSC spheroids from different patients exhibited varying and personalized responses to chemotherapeutics. Xenografts were established from OvCSC spheroids, even with a single spheroid. Distinct responses to therapy were observed in distinct primary tumor xenografts similar to those observed in spheroids. Spheroids resistant to cisplatin/ALDH inhibitor therapy had persistent, albeit lower ALDH expression and complete loss of CD133 expression, whereas those resistant to cisplatin/JAK2 inhibitor therapy were enriched for ALDH + cells. Conclusions: Our 3D hanging drop suspension platform can be used to propagate primary OvCSCs that represent individual patient tumors effectively by differentiating in vitro and initiating tumors in mice. Therefore, our platform can be used to study cancer stem cell biology and model tumor reemergence to identify new targeted therapeutics from an effective personalized medicine standpoint. Clin Cancer Res; 23(22); 6934-45. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Aims Identification and management of the Standard Modifiable Cardiovascular Risk Factors (SMuRFs; hypercholesterolaemia, hypertension, diabetes and smoking) has substantially improved cardiovascular disease outcomes. However, cardiovascular disease remains the leading cause of death worldwide. Suspecting an evolving pattern of risk factor profiles in the ST elevation myocardial infarction (STEMI) population with the improvements in primary care, we hypothesized that the proportion of 'SMuRFless' STEMI patients may have increased. Methods/results We performed a single centre retrospective study of consecutive STEMI patients presenting from January 2006 to December 2014. Over the study period 132/695 (25%) STEMI patients had 0 SMuRFs, a proportion that did not significantly change with age, gender or family history. The proportion of STEMI patients who were SMuRFless in 2006 was 11%, which increased to 27% by 2014 (odds ratio 1.12 per year, 95% confidence interval: 1.04-1.22). The proportion of patients with hypercholesterolaemia decreased (odds ratio 0.92, 95% confidence interval 0.86-0.98), as did the proportion of current smokers (odds ratio 0.93, 95% confidence interval 0.86-0.99), with no significant change in the proportion of patients with diabetes and hypertension. SMuRF status was not associated with extent of coronary disease; in-hospital outcomes, or discharge prescribing patterns. Conclusion The proportion of STEMI patients with STEMI poorly explained by SMuRFs is high, and is significantly increasing. This highlights the need for bold approaches to discover new mechanisms and markers for early identification of these patients, as well as to understand the outcomes and develop new targeted therapies.

In a seminal report on laser-induced nucleation in aqueous supersaturated solutions (Phys. Rev. Lett., 1996, 77, 3475) it was noted that needle-shaped crystals of urea were aligned with the direction of the electric field of the linearly polarized laser pulse. The results gave rise to a new mechanism for control of crystal nucleation involving alignment of solute molecules (optical Kerr effect) now commonly known as non-photochemical laser-induced nucleation (NPLIN). Recent theoretical and experimental work has cast doubts on the optical Kerr effect mechanism. In the present letter we present results from digital imaging of urea-crystal growth immediately following laser-induced nucleation. Analysis of the data shows no statistically significant correlation between crystal angle and direction of linear polarization. The results overturn a long-held result that has shaped theoretical and experimental studies of NPLIN.

Understanding the oxidation and reduction mechanisms of catalytically active transition metal nanoparticles is important to improve their application in a variety of chemical processes. In nanocatalysis the nanoparticles can undergo oxidation or reduction in situ, and thus the redox species are not what are observed before and after reactions. We have used the novel environmental scanning transmission electron microscope (ESTEM) with 0.1 nm resolution in systematic studies of complex dynamic oxidation and reduction mechanisms of copper nanoparticles. The oxidation of copper has previously been reported to be dependent on its crystallography and its interaction with the substrate. By following the dynamic oxidation process in situ in real time with high-angle annular dark-field imaging in the ESTEM, we use conditions ideal to track the oxidation front as it progresses across a copper nanoparticle by following the changes in the atomic number (Z) contrast with time. The oxidation occurs via the nucleation of the oxide phase (Cu 2 O) from one area of the nanoparticle which then progresses unidirectionally across the particle, with the Cu-to-Cu 2 O interface having a relationship of Cu{111}//Cu 2 O{111}. The oxidation kinetics are related to the temperature and oxygen pressure. When the process is reversed in hydrogen, the reduction process is observed to be similar to the oxidation, with the same crystallographic relationship between the two phases. The dynamic observations provide unique insights into redox mechanisms which are important to understanding and controlling the oxidation and reduction of copper-based nanoparticles.

A 72-year-old woman presented with acute coronary syndrome. There was diffuse coronary ectasia and severe stenosis in the proximal left anterior descending artery consistent with coronary vasculitis. Despite treatment with high-dose immunosuppression, she underwent percutaneous coronary intervention for refractory angina., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Multicellular tumor spheroids are powerful in vitro models to perform preclinical chemosensitivity assays. We compare different methodologies to generate tumor spheroids in terms of resultant spheroid morphology, cellular arrangement and chemosensitivity. We used two cancer cell lines (MCF7 and OVCAR8) to generate spheroids using i) hanging drop array plates; ii) liquid overlay on ultra-low attachment plates; iii) liquid overlay on ultra-low attachment plates with rotating mixing (nutator plates). Analysis of spheroid morphometry indicated that cellular compaction was increased in spheroids generated on nutator and hanging drop array plates. Collagen staining also indicated higher compaction and remodeling in tumor spheroids on nutator and hanging drop arrays compared to conventional liquid overlay. Consequently, spheroids generated on nutator or hanging drop plates had increased chemoresistance to cisplatin treatment (20-60% viability) compared to spheroids on ultra low attachment plates (10-20% viability). Lastly, we used a mathematical model to demonstrate minimal changes in oxygen and cisplatin diffusion within experimentally generated spheroids. Our results demonstrate that in vitro methods of tumor spheroid generation result in varied cellular arrangement and chemosensitivity.

Objectives: Assess the effect of aspiration thrombectomy on diagnosis and management of embolic acute myocardial infarction., Background: Discrimination of embolic acute myocardial infarction from atherosclerotic plaque rupture/erosion prompts oral anticoagulation treatment of source of embolus, as well as avoiding unnecessary stenting and dual antiplatelet therapy. However, detection is difficult without aspiration., Methods: We compared rates of diagnosis of embolic infarction for 2.5 years prior to (pre-RAT) and 2.5 years post routine aspiration thrombectomy (post-RAT). Baseline demographics, outcomes, and treatment strategies were also compared between the embolic infarction and atherosclerotic infarction., Results: Diagnosed embolic infarction rose from 1.2% in the pre-RAT era to 2.8% in the post-RAT period (P < 0.05). In addition, more successful removal of thrombus by aspiration led to less stenting (20% vs. 55% P < 0.05) in the post-RAT period thus avoiding the hazards of "triple therapy." Embolic infarction was more frequently associated with atrial fibrillation (55% vs. 8%), had higher mortality (17% vs. 4%), and had higher rates of embolic stroke (13% vs. 0.3%) when compared with atherosclerotic MI (all P < 0.05)., Conclusions: Routine aspiration thrombectomy more readily identifies embolic infarction allowing more specific therapy and avoidance of stenting and triple anticoagulant therapy., (© 2015 Wiley Periodicals, Inc.)

Background: Ovarian cancer grows and metastasizes from multicellular spheroidal aggregates within the ascites fluid. Multicellular tumor spheroids are therefore physiologically significant 3D in vitro models for ovarian cancer research. Conventional hanging drop cultures require high starting cell numbers, and are tedious for long-term maintenance. In this study, we generate stable, uniform multicellular spheroids using very small number of ovarian cancer cells in a novel 384 well hanging drop array platform., Methods: We used novel tumor spheroid platform and two ovarian cancer cell lines (A2780 and OVCAR3) to demonstrate the stable incorporation of as few as 10 cells into a single spheroid., Results: Spheroids had uniform geometry, with projected areas (42.60×10(3)μm-475.22×10(3)μm(2) for A2780 spheroids and 37.24×10(3)μm(2)-281.01×10(3)μm(2) for OVCAR3 spheroids) that varied as a function of the initial cell seeding density. Phalloidin and nuclear stains indicated cells formed tightly packed spheroids with demarcated boundaries and cell-cell interaction within spheroids. Cells within spheroids demonstrated over 85% viability. 3D tumor spheroids demonstrated greater resistance (70-80% viability) to cisplatin chemotherapy compared to 2D cultures (30-50% viability)., Conclusions: Ovarian cancer spheroids can be generated from limited cell numbers in high throughput 384 well plates with high viability. Spheroids demonstrate therapeutic resistance relative to cells in traditional 2D culture. Stable incorporation of low cell numbers is advantageous when translating this research to rare patient-derived cells. This system can be used to understand ovarian cancer spheroid biology, as well as carry out preclinical drug sensitivity assays., (Copyright © 2015 Elsevier Inc. All rights reserved.)

A detailed experimental study of laser-induced nucleation (LIN) of carbon dioxide (CO2) gas bubbles is presented. Water and aqueous sucrose solutions supersaturated with CO2 were exposed to single nanosecond pulses (5 ns, 532 nm, 2.4-14.5 MW cm(-2)) and femtosecond pulses (110 fs, 800 nm, 0.028-11 GW cm(-2)) of laser light. No bubbles were observed with the femtosecond pulses, even at high peak power densities (11 GW cm(-2)). For the nanosecond pulses, the number of bubbles produced per pulse showed a quadratic dependence on laser power, with a distinct power threshold below which no bubbles were observed. The number of bubbles observed increases linearly with sucrose concentration. It was found that filtering of solutions reduces the number of bubbles significantly. Although the femtosecond pulses have higher peak power densities than the nanosecond pulses, they have lower energy densities per pulse. A simple model for LIN of CO2 is presented, based on heating of nanoparticles to produce vapor bubbles that must expand to reach a critical bubble radius to continue growth. The results suggest that non-photochemical laser-induced nucleation of crystals could also be caused by heating of nanoparticles.

The gas injection line of the latest spherical aberration-corrected environmental transmission electron microscope has been modified for achieving real-time/atomic-scale observations in moisturised gas atmospheres for the first time. The newly developed Wet-TEM system is applied to platinum carbon electrode catalysts to investigate the effect of water molecules on the platinum/carbon interface during deactivation processes such as sintering and corrosion. Dynamic in situ movies obtained in dry and 24% moisturised nitrogen environments visualize the rapid rotation, migration and agglomeration of platinum nanoparticles due to the physical adsorption of water and the hydroxylation of the carbon surface. The origin of the long-interconnected aggregation of platinum nanoparticles was discovered to be a major deactivation process in addition to conventional carbon corrosion.