Isolated human pulmonary artery structure and function pre‐ and post‐cardiopulmonary bypass surgery

Background: Pulmonary dysfunction is a known complication after cardiac surgery using cardiopulmonary bypass, ranging from subclinical functional changes to prolonged postoperative ventilation, acute lung injury, and acute respiratory distress syndrome. Whether human pulmonary arterial function is compromised is unknown. The aim of the present study was to compare the structure and function of isolated and cannulated human pulmonary arteries obtained from lung biopsies after the chest was opened (pre–cardiopulmonary bypass) to those obtained at the end of cardiopulmonary bypass (post–cardiopulmonary bypass) from patients undergoing coronary artery bypass graft surgery. Methods and Results: Pre‐ and post–cardiopulmonary bypass lung biopsies were received from 12 patients undergoing elective surgery. Intralobular small arteries were dissected, cannulated, pressurized, and imaged using confocal microscopy. Functionally, the thromboxane mimetic U46619 produced concentration‐dependent vasoconstriction in 100% and 75% of pre‐ and post–cardiopulmonary bypass arteries, respectively. The endothelium‐dependent agonist bradykinin stimulated vasodilation in 45% and 33% of arteries pre‐ and post–cardiopulmonary bypass, respectively. Structurally, in most arteries smooth muscle cells aligned circumferentially; live cell viability revealed that although 100% of smooth muscle and 90% of endothelial cells from pre–cardiopulmonary bypass biopsies had intact membranes and were considered viable, only 60% and 58%, respectively, were viable from post–cardiopulmonary bypass biopsies. Conclusions: We successfully investigated isolated pulmonary artery structure and function in fresh lung biopsies from patients undergoing heart surgery. Pulmonary artery contractile tone and endothelium‐dependent dilation were significantly reduced in post–cardiopulmonary bypass biopsies. The decreased functional responses were associated with reduced cell viability. Clinical Trial Registration: URL: http://www.isrctn.com/ISRCTN34428459. Unique identifier: ISRCTN 34428459.</p

Correlates of Omani adults' physical inactivity and sitting time

Objective: To inform public health approaches for chronic disease prevention, the present study identified sociodemographic, anthropometric and behavioural correlates of work, transport and leisure physical inactivity and sitting time among adults in Oman

Bimetallic Pt(II)-bipyridyl-diacetylide/Ln(III) tris-diketonate adducts based on a combination of coordinate bonding and hydrogen bonding between the metal fragments: syntheses, structures and photophysical properties

The luminescent Pt(II) complex [Pt(4,4'-Bu-t(2)-bipy){CC-(5-pyrimidinyl)}(2)] (1) was prepared by coupling of [Pt(4,4'-Bu-t(2)-bipy)Cl-2] with 5-ethynyl-pyrimidine, and contains two pyrimidinyl units pendant from a Pt(H) bipyridyl diacetylide core; it shows luminescence at 520 nm which is typical of Pt(II) luminophores of this type. Reaction with [Ln(hfac)(3)(H2O)(2)] (hfac = anion of hexafluoroacetylacetone) affords as crystalline solids the compounds [1 center dot {Ln(hfac)(3)(H2O)}{Ln(hfac)(3)(H2O)(2)}] (Ln = Nd, Gd, Er, Yb), in which the {Ln(hfac)(3)(H2O)} unit is coordinated to one pyrimidine ring via an N atom, whereas the {Ln(hfac)(3)(H2O)(2)} unit is associated with two N atoms, one from each pyrimidine ring of 1, via N center dot center dot center dot HOH hydrogen-bonding interactions involving the coordinated water ligands on the lanthanide centre. Solution spectroscopic studies show that the luminescence of 1 is partly quenched on addition of [Ln(hfac)(3)(H2O)(2)] (Ln = Er, Nd) by formation of Pt(II)/Ln(III) adducts in which Pt(II)-> Ln(III) photoinduced energy-transfer occurs to the low-lying f-f levels of the Ln(Ill) centre. Significant quenching occurs with both Er(Ill) and Nd(III) because both have several f-f states which match well the (MLCT)-M-3 emission energy of 1. Time-resolved luminescence studies show that Pt(II)-Er(III) energy-transfer (7.0 x 10(7) M-1) is around three times faster than Pt(II)-> Nd(III) energy-transfer (approximate to 2 x 10(7) M-1) over the same distance because the luminescence spectrum of l overlaps better with the absorption spectrum of Er(111) than with Nd(III). In contrast Yb(111) causes no significant quenching of 1 because it has only a single f-f excited level which is a poor energy match for the Pt(II)-based excited state

Understanding the Basis for Down Syndrome Phenotypes

Down syndrome is a collection of features that are caused by trisomy for human Chromosome 21. While elevated transcript levels of the more than 350 genes on the chromosome are primarily responsible, it is likely that multiple genetic mechanisms underlie the numerous ways in which development and function diverge in individuals with trisomy 21 compared to euploid individuals. We consider genotype–phenotype interactions with the goal of producing working concepts that will be useful for approaches to ameliorate the effects of trisomy

CD74-dependent Deregulation of the Tumor Suppressor Scribble in Human Epithelial and Breast Cancer Cells

The γ subunit of the major histocompatibility complex (MHC) class II complex, CD74, is overexpressed in a significant proportion of metastatic breast tumors, but the mechanistic foundation and biologic significance of this phenomenon are not fully understood. Here, we show that when CD74 is overexpressed in human cancer and noncancerous epithelial cells, it interacts and interferes with the function of Scribble, a product of a well-known tumor suppressor gene. Furthermore, using epithelial cell lines expressing CD74 under the control of tetracycline-inducible promoter and quantitative high-resolution mass spectrometry, we demonstrate that, as a result of CD74 overexpression, the phosphorylation pattern of the C-terminal part of Scribble undergoes specific changes. This is accompanied with a translocation of the protein from the sites of cell-to-cell contacts at the plasma membrane to the cytoplasm, which is likely to effectively enhance the motility and invasiveness of the cancer cells. © 2013 Neoplasia Press, Inc. All rights reserved

Low-frequency ventilation during cardiopulmonary bypass for lung protection:A randomized controlled trial

OBJECTIVE: Pulmonary dysfunction is a common complication in patients undergoing heart surgery. Current clinical practice does not include any specific strategy for lung protection. To compare the anti-inflammatory effects of low-frequency ventilation (LFV), as measured by nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) p65 pathway activation, for the entire cardiopulmonary bypass (CPB) vs both lungs left collapsed in patients undergoing coronary artery bypass grafting (CABG). METHODS: Two groups parallel randomized controlled trial. The primary outcome was inflammation measured by NF-κB p65 activation in pre- and post-CPB lung biopsies. Secondary outcomes were additional inflammatory markers in both biopsy tissue and blood. RESULTS: Thirty-seven patients were randomly allocated to LFV (18) and to both lungs left collapsed (19). The mean concentration of NF-κB p65 in the biopsies before chest closure (adjusted for pre-CPB concentration) was higher in the LFV group compared to both lungs left collapsed group but this was not significant (0.102, 95% confidence interval, -0.022 to 0.226, P = 0.104). There were no significant differences between groups in the other inflammatory markers measured in tissue and blood. CONCLUSIONS: In patients undergoing elective CABG, the use of LFV during CPB when compared to both lungs left collapsed does not seem to reduce inflammation in lung biopsies and blood

Refinement-based verification of sequential implementations of Stateflow charts

Simulink/Stateflow charts are widely used in industry for the specification of control systems, which are often safety-critical. This suggests a need for a formal treatment of such models. In previous work, we have proposed a technique for automatic generation of formal models of Stateflow blocks to support refinement-based reasoning. In this article, we present a refinement strategy that supports the verification of automatically generated sequential C implementations of Stateflow charts. In particular, we discuss how this strategy can be specialised to take advantage of architectural features in order to allow a higher level of automation.Comment: In Proceedings Refine 2011, arXiv:1106.348

Exploring the role of socioeconomic status and psychological characteristics on talent development in an English soccer academy

This is the final version. Available on open access from Routledge via the DOI in this recordSocial factors and psychological characteristics can influence participation and development in talent pathways. However, the interaction between these two factors is relatively unknown. The aim of this study was to investigate the implications of socioeconomic status and psychological characteristics in English academy soccer players (n=58; aged 11 to 16 years). To assess socioeconomic status, participants' home postcodes were coded according to each individual's social classification and credit rating, applying the UK General Registrar Classification system and CameoTM geodemographic database, respectively. Participants also completed the six factor Psychological Characteristics for Developing Excellence Questionnaire (PCDEQ). A classification of 'higher-potentials' (n=19) and 'lower-potentials' (n=19) were applied through coach potential rankings. Data were standardised using z-scores to eliminate age bias and data were analysed using independent sample t-tests. Results showed that higher-potentials derived from families with significantly lower social classifications (p=0.014) and reported higher levels for PCDEQ Factor 3 (coping with performance and developmental pressures) (p=0.007) compared to lower-potentials. This study can be used to support the impetus for researchers and practitioners to consider the role of social factors and psychological characteristics when developing sporting talent. For example, facilitating player-centred development within an academy and, where necessary, providing individuals with additional support

Reconstructing institutional complexity in practice: A relational model of institutional work and complexity

This article develops a relational model of institutional work and complexity. This model advances current institutional debates on institutional complexity and institutional work in three ways. First, it provides a relational and dynamic perspective on institutional complexity by explaining how constellations of logics - and their degree of internal contradiction - are constructed rather than given. Second, it refines our current understanding of agency, intentionality and effort in institutional work by demonstrating how different dimensions of agency interact dynamically in the institutional work of reconstructing institutional complexity. Third, it situates institutional work in the everyday practice of individuals coping with the institutional complexities of their work. In doing so, it reconnects the construction of institutionally complex settings to the actions and interactions of the individuals who inhabit them

Work-Life Balance Starts with Proper Deadlines and Exemplary Agencies

Diversity, equity and inclusion (DEI) programs can only be implemented successfully if proper work-life balance is possible in Heliophysics (and in STEM field in general). One of the core issues stems from the culture of "work-above-life" associated with mission concepts, development, and implementation but also the expectations that seem to originate from numerous announcements from NASA (and other agencies). The benefits of work-life balance are well documented; however, the entire system surrounding research in Heliophysics hinders or discourages proper work-life balance. For example, there does not seem to be attention paid by NASA Headquarters (HQ) on the timing of their announcements regarding how it will be perceived by researchers, and how the timing may promote a culture where work trumps personal life. The same is true for remarks by NASA HQ program officers during panels or informal discussions, where seemingly innocuous comments may give a perception that work is expected after "normal" work hours. In addition, we are calling for work-life balance plans and implementation to be one of the criteria used for down-selection and confirmation of missions (Key Decision Points: KDP-B, KDP-C).Comment: White paper submitted to the Decadal Survey for Solar and Space Physics (Heliophysics) 2024-2033; 6 page