Role of PI3K in myocardial ischaemic preconditioning: mapping pro-survival cascades at the trigger phase and at reperfusion

The Reperfusion Injury Salvage Kinase (RISK) pathway is considered the main pro-survival kinase cascade mediating the ischaemic preconditioning (IPC) cardioprotective effect. To assess the role of PI3K-Akt, its negative regulator PTEN and other pro-survival proteins such as ERK and STAT3 in the context of IPC, C57BL/6 mouse hearts were retrogradely perfused in a Langendorff system and subjected to 4 cycles of 5 min. ischaemia and 5 min. reperfusion prior to 35 min. of global ischaemia and 120 min. of reperfusion. Wortmannin, a PI3K inhibitor, was administered either at the stabilization period or during reperfusion. Infarct size was assessed using triphenyl tetrazolium staining, and phosphorylation levels of Akt, PTEN, ERK, GSK3β and STAT3 were evaluated using Western blot analyses. IPC reduced infarct size in hearts subjected to lethal ischaemia and reperfusion, but this effect was lost in the presence of Wortmannin, whether it was present only during preconditioning or only during early reperfusion. IPC increased the levels of Akt phosphorylation during both phases and this effect was fully abrogated by PI3K, whilst its downstream GSK3β was phosphorylated only during the trigger phase after IPC. Both PTEN and STAT3 were phosphorylated during both phases after IPC, but this was PI3K independent. IPC increases ERK phosphorylation during both phases, being only PI3K-dependent during the IPC phase. In conclusion, PI3K-Akt plays a major role in IPC-induced cardioprotection. However, PTEN, ERK and STAT3 are also phosphorylated by IPC through a PI3K-independent pathway, suggesting that cardioprotection is mediated through more than one cell signalling cascade

Validity of acute cardiovascular outcome diagnoses in European electronic health records: a systematic review protocol

INTRODUCTION: Cardiovascular diseases (CVDs) are among the leading causes of death globally. Electronic health records (EHRs) provide a rich data source for research on CVD risk factors, treatments and outcomes. Researchers must be confident in the validity of diagnoses in EHRs, particularly when diagnosis definitions and use of EHRs change over time. Our systematic review provides an up-to-date appraisal of the validity of stroke, acute coronary syndrome (ACS) and heart failure (HF) diagnoses in European primary and secondary care EHRs. METHODS AND ANALYSIS: We will systematically review the published and grey literature to identify studies validating diagnoses of stroke, ACS and HF in European EHRs. MEDLINE, EMBASE, SCOPUS, Web of Science, Cochrane Library, OpenGrey and EThOS will be searched from the dates of inception to April 2019. A prespecified search strategy of subject headings and free-text terms in the title and abstract will be used. Two reviewers will independently screen titles and abstracts to identify eligible studies, followed by full-text review. We require studies to compare clinical codes with a suitable reference standard. Additionally, at least one validation measure (sensitivity, specificity, positive predictive value or negative predictive value) or raw data, for the calculation of a validation measure, is necessary. We will then extract data from the eligible studies using standardised tables and assess risk of bias in individual studies using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Data will be synthesised into a narrative format and heterogeneity assessed. Meta-analysis will be considered when a sufficient number of homogeneous studies are available. The overall quality of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation tool. ETHICS AND DISSEMINATION: This is a systematic review, so it does not require ethical approval. Our results will be submitted for peer-review publication. PROSPERO REGISTRATION NUMBER: CRD42019123898

Operator theory and function theory in Drury-Arveson space and its quotients

The Drury-Arveson space $H^2_d$, also known as symmetric Fock space or the $d$-shift space, is a Hilbert function space that has a natural $d$-tuple of operators acting on it, which gives it the structure of a Hilbert module. This survey aims to introduce the Drury-Arveson space, to give a panoramic view of the main operator theoretic and function theoretic aspects of this space, and to describe the universal role that it plays in multivariable operator theory and in Pick interpolation theory.Comment: Final version (to appear in Handbook of Operator Theory); 42 page

Dual mechanism model for fluid particle breakup in the entire turbulent spectrum

This work provides an in-depth understanding of different breakup mechanisms for fluid particles in turbulent flows. All the disruptive and cohesive stresses are considered for the entire turbulent energy spectrum and their contributions to the breakup are evaluated. A new modeling framework is presented that bridges across turbulent subranges. The model entails different mechanisms for breakup by abandoning the classical limitation of inertial models. The predictions are validated with experiments encompassing both breakup regimes for droplets stabilized by internal viscosity and interfacial tension down to the micrometer length scale, which covers both the inertial and dissipation subranges. The model performance ensures the reliability of the framework, which involves different mechanisms. It retains the breakup rate for inertial models, improves the predictions for the transition region from inertia to dissipation, and bridges seamlessly to Kolmogorov-sized droplets

Cardiovascular disease in women: Implications for improving health outcomes

Objective: To collate data on women and cardiovascular disease in Australia and globally to inform public health campaigns and health care interventions. Design: Literature review. Results: •Women with acute coronary syndromes show consistently poorer outcomes than men, independent of comorbidity and management, despite less anatomical obstruction of coronary arteries and relatively preserved left ventricular function. Higher mortality and complication rates are best documented amongst younger women and those with ST-segment-elevation myocardial infarction.•Sex differences in atherogenesis and cardiovascular adaptation have been hypothesised, but not proven.•Atrial fibrillation carries a relatively greater risk of stroke in women than in men, and anticoagulation therapy is associated with higher risk of bleeding complications.•The degree of risk conferred by single cardiovascular risk factors and combinations of risk factors may differ between the sexes, and marked postmenopausal changes are seen in some risk factors.•Sociocultural factors, delays in seeking care and differences in self-management behaviours may contribute to poorer outcomes in women.•Differences in clinical management for women, including higher rates of misdiagnosis and less aggressive treatment, have been reported, but there is a lack of evidence to determine their effects on outcomes, especially in angina.•Although enrolment of women in randomised clinical trials has increased since the 1970s, women remain underrepresented in cardiovascular clinical trials. Conclusions: Improvement in the prevention and management of CVD in women will require a deeper understanding of women's needs by the community, health care professionals, researchers and government. © 2011 Royal College of Nursing, Australia

Fair scans of the seesaw. Consequences for predictions on LFV processes

Usual analyses based on scans of the seesaw parameter-space can be biassed since they do not cover in a fair way the complete parameter-space. More precisely, we show that in the common "R-parametrization", many acceptable R-matrices, compatible with the perturbativity of Yukawa couplings, are normally disregarded from the beginning, which produces biasses in the results. We give a straightforward procedure to scan the space of complex R-matrices in a complete way, giving a very simple rule to incorporate the perturbativity requirement as a condition for the entries of the R-matrix, something not considered before. As a relevant application of this, we show that the extended believe that BR(mu --> e, gamma) in supersymmetric seesaw models depends strongly on the value of theta_13 is an "optical effect" produced by such biassed scans, and does not hold after a careful analytical and numerical study. When the complete scan is done, BR(mu --> e, gamma) gets very insensitive to theta_13. Moreover, the values of the branching ratio are typically larger than those quoted in the literature, due to the large number of acceptable points in the parameter-space which were not considered before. Including (unflavoured) leptogenesis does not introduce any further dependence on theta_13, although decreases the typical value of BR(mu --> e, gamma).Comment: 22 pages, 5 figure

Eta Carinae -- Physics of the Inner Ejecta

Eta Carinae's inner ejecta are dominated observationally by the bright Weigelt blobs and their famously rich spectra of nebular emission and absorption lines. They are dense (n_e ~ 10^7 to 10^8 cm^-3), warm (T_e ~ 6000 to 7000 K) and slow moving (~40 km/s) condensations of mostly neutral (H^0) gas. Located within 1000 AU of the central star, they contain heavily CNO-processed material that was ejected from the star about a century ago. Outside the blobs, the inner ejecta include absorption-line clouds with similar conditions, plus emission-line gas that has generally lower densities and a wider range of speeds (reaching a few hundred km/s) compared to the blobs. The blobs appear to contain a negligible amount of dust and have a nearly dust-free view of the central source, but our view across the inner ejecta is severely affected by uncertain amounts of dust having a patchy distribution in the foreground. Emission lines from the inner ejecta are powered by photoionization and fluorescent processes. The variable nature of this emission, occurring in a 5.54 yr event cycle, requires specific changes to the incident flux that hold important clues to the nature of the central object.Comment: This is Chapter 5 in a book entitled: Eta Carinae and the Supernova Impostors, Kris Davidson and Roberta M. Humphreys, editors Springe