Optimising approximate entropy for assessing cardiac dyssynchrony with radionuclide ventriculography

Left ventricular dyssynchrony can be assessed with phase parameters from radionuclide ventriculography (RNVG), including approximate entropy (ApEn). The input values used to calculate ApEn will affect the results significantly, so it is essential to optimise ApEn for the application. However to date, no optimisation for ApEn applied to images has been published. In this paper, generated data were used to simulate patient phase images, allowing the input parameters for ApEn to be tested and optimised in a controlled environment. Clinical images were then used to confirm that the selected parameters were appropriate. The results demonstrate the effect of input parameters for ApEn and the most appropriate use with RNVG phase images. This work demonstrates the importance of optimisation and standardisation when using ApEn as a measure of dyssynchrony

Fate of transition metals during passive carbonation of ultramafic mine tailings via air capture with potential for metal resource recovery

Mineral carbonation in ultramafic mine tailings is generally accepted to be a safe and long term means of trapping and storing CO2 within the structures of minerals, but it poses the risk of releasing potentially hazardous metal contaminants from mineral wastes into the environment. Stockpiles of reactive, finely pulverised ultramafic mine tailings are ideal natural laboratories for the observation and promotion of the carbonation of Mg-silicate and Mg-hydroxide waste minerals via reaction with atmospheric or industrial CO2. However, ultramafic mine tailings commonly contain first-row transition metals (e.g., Cr, Co, Cu, Ni) in potentially toxic concentrations within the crystal structures of Mg-silicates, sulphides, and oxides. These transition metals are likely to be mobilised by mineral carbonation reactions, which require mineral dissolution to supply cations for reaction with carbon. At Woodsreef Chrysotile Mine, New South Wales, Australia, transition metals (i.e., Fe, Cr, Ni, Mn, Co, Cu) are most concentrated within minor oxides (magnetite and chromite) and trace alloys (awaruite, Ni2-3Fe and wairauite, CoFe) in serpentine tailings, however, mobilisation of transition metals appears to occur predominantly during dissolution of serpentine and brucite, which are more abundant and reactive phases, respectively. Here, we present new synchrotron X-ray fluorescence mapping data that provide insights into the mobility of first-row transition metals (Fe, Cr, Ni, Mn, Co, Cu) during weathering and carbonation of ultramafic mine tailings collected from the Woodsreef Chrysotile Mine. These data indicate that the recently precipitated carbonate minerals, hydromagnesite [Mg5(CO3)4(OH)2·4H2O] and pyroaurite [Mg6Fe2(CO3)(OH)16·4H2O] sequester trace metals from the tailings at concentrations of 10 s–100 s of ppm, most likely via substitution for Mg or Fe within their crystal structures, or by the physical trapping of small (μm-scale) transition-metal-rich grains (i.e., magnetite, chromite, awaruite), which are stabilised within alkaline carbonate cements. Trace transition metals are present at relatively high concentrations in the bulk tailings (i.e., ∼0.3 wt.% NiO and Cr2O3) and they are largely retained within the unaltered mineral assemblage. The weathering products that occur at the surface of the tailings and form a cement between grains of partially dissolved gangue minerals immobilise transition metals on spatial scales of micrometres and at comparable concentrations to those observed in the unaltered tailings. The end result is that trace metals are not present at detectable levels within mine pit waters. Our observations of metal mobility during passive carbonation suggest that mineral products of accelerated carbonation treatments are likely to sequester trace metals. Thus, accelerated carbonation is unlikely to pose an environmental risk in the form of metalliferous drainage so long as the neutralisation potential of the tailings is not exceeded. Understanding both trace transition metal geochemistry and mineralogy within materials targeted for mineral carbonation could allow optimisation of treatment processes and design for recovery of valuable metals. In ex situ reactors employing acid pre-treatments, trace metals mobilised from reactive phases such as serpentine and brucite could potentially be recovered using pH-swing methods, while recalcitrant metal-rich accessory minerals, including magnetite, awaruite and chromite, could be recovered from treated residue material by conventional mineral separation processes. Recovery of valuable metals (i.e., Ni, Cr and Co) as by-products of accelerated mineral carbonation technologies could also provide an important economic incentive to support broader adoption of this technology

Radionuclide ventriculography phase analysis for risk stratification of patients undergoing cardiotoxic cancer therapy

Background: Accurate diagnostic tools to identify patients at risk of cancer therapy-related cardiac dysfunction (CTRCD) are critical. For patients undergoing cardiotoxic cancer therapy, ejection fraction assessment using radionuclide ventriculography (RNVG) is commonly used for serial assessment of left ventricular (LV) function. Methods: In this retrospective study, approximate entropy (ApEn), synchrony, entropy, and standard deviation from the phase histogram (phase SD) were investigated as potential early markers of LV dysfunction to predict CTRCD. These phase parameters were calculated from the baseline RNVG phase image for 177 breast cancer patients before commencing cardiotoxic therapy. Results: Of the 177 patients, 11 had a decline in left ventricular ejection fraction (LVEF) of over 10% to an LVEF below 50% after treatment had commenced. This patient group had a significantly higher ApEn at baseline to those who maintained a normal LVEF throughout treatment. Of the parameters investigated, ApEn was superior for predicting the risk of CTRCD. Combining ApEn with the baseline LVEF further improved the discrimination between the groups. Conclusions: The results suggest that RNVG phase analysis using approximate entropy may aid in the detection of sub-clinical LV contraction abnormalities, not detectable by baseline LVEF measurement, predicting a subsequent decline in LVEF

Developing and pre-testing a decision board to facilitate informed choice about delivery approach in uncomplicated pregnancy

<p>Abstract</p> <p>Background</p> <p>The rate of caesarean sections is increasing worldwide, yet medical literature informing women with uncomplicated pregnancies about relative risks and benefits of elective caesarean section (CS) compared with vaginal delivery (VD) remains scarce. A decision board may address this gap, providing systematic evidence-based information so that patients can more fully understand their treatment options. The objective of our study was to design and pre-test a decision board to guide clinical discussions and enhance informed decision-making related to delivery approach (CS or VD) in uncomplicated pregnancy.</p> <p>Methods</p> <p>Development of the decision board involved two preliminary studies to determine women's preferred mode of risk presentation and a systematic literature review for the most comprehensive presentation of medical risks at the time (VD and CS). Forty women were recruited to pre-test the tool. Eligible subjects were of childbearing age (18-40 years) but were not pregnant in order to avoid raising the expectation among pregnant women that CS was a universally available birth option. Women selected their preferred delivery approach and completed the Decisional Conflict Scale to measure decisional uncertainty before and after reviewing the decision board. They also answered open-ended questions reflecting what they had learned, whether or not the information had helped them to choose between birth methods, and additional information that should be included. Descriptive statistics were used to analyse sample characteristics and women's choice of delivery approach pre/post decision board. Change in decisional conflict was measured using Wilcoxon's sign rank test for each of the three subscales.</p> <p>Results</p> <p>The majority of women reported that they had learned something new (n = 37, 92%) and that the tool had helped them make a hypothetical choice between delivery approaches (n = 34, 85%). Women wanted more information about neonatal risks and personal experiences. Decisional uncertainty decreased (p < 0.001) and perceived effectiveness of decisions increased (p < 0.001) post-intervention.</p> <p>Conclusion</p> <p>Non-pregnant women of childbearing age were positive about the decision board and stated their hypothetical delivery choices were informed by risk presentation, but wanted additional information about benefits and experiences. This study represents a preliminary but integral step towards ensuring women considering delivery approaches in uncomplicated pregnancies are fully informed.</p

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Cation Exchange in Smectites as a New Approach to Mineral Carbonation

Mineral carbonation of alkaline mine residues is a carbon dioxide removal (CDR) strategy that can be employed by the mining industry. Here, we describe the mineralogy and reactivity of processed kimberlites and kimberlite ore from Venetia (South Africa) and Gahcho Kué (Canada) diamond mines, which are smectite-rich (2.3–44.1 wt.%). Whereas, serpentines, olivines, hydrotalcites and brucite have been traditionally used for mineral carbonation, little is known about the reactivity of smectites to CO2. The smectite from both mines is distributed as a fine-matrix and is saponite, Mx/mm+Mg3(AlxSi4−x)O10(OH)2·nH2O, where the layer charge deficiency is balanced by labile, hydrated interlayer cations (Mm+). A positive correlation between cation exchange capacity and saponite content indicates that smectite is the most reactive phase within these ultramafic rocks and that it can be used as a source of labile Mg2+ and Ca2+ for carbonation reactions. Our work shows that smectites provide the fast reactivity of kimberlite to CO2 in the absence of the highly reactive mineral brucite [Mg(OH)2]. It opens up the possibility of using other, previously inaccessible rock types for mineral carbonation including tailings from smectite-rich sediment-hosted metal deposits and oil sands tailings. We present a decision tree for accelerated mineral carbonation at mines based on this revised understanding of mineralogical controls on carbonation potential

The sensorium at work: the sensory phenomenology of the working body

The sociology of the body and the sociology of work and occupations have both neglected to some extent the study of the ‘working body’ in paid employment, particularly with regard to empirical research into the sensory aspects of working practices. This gap is perhaps surprising given how strongly the sensory dimension features in much of working life. This article is very much a first step in calling for a more phenomenological, embodied and ‘fleshy’ perspective on the body in employment, and examines some of the theoretical and conceptual resources available to researchers wishing to focus on the lived working-body experiences of the sensorium. We also consider some possible representational forms for a more evocative, phenomenologically-inspired portrayal of sensory, lived-working-body experiences, and offer suggestions for future avenues of research

Listeriolysin O Is Strongly Immunogenic Independently of Its Cytotoxic Activity

The presentation of microbial protein antigens by Major Histocompatibility Complex (MHC) molecules is essential for the development of acquired immunity to infections. However, most biochemical studies of antigen processing and presentation deal with a few relatively inert non-microbial model antigens. The bacterial pore-forming toxin listeriolysin O (LLO) is paradoxical in that it is cytotoxic at nanomolar concentrations as well as being the source of dominant CD4 and CD8 T cell epitopes following infection with Listeria monocytogenes. Here, we examined the relationship of LLO toxicity to its antigenicity and immunogenicity. LLO offered to antigen presenting cells (APC) as a soluble protein, was presented to CD4 T cells at picomolar to femtomolar concentrations- doses 3000–7000-fold lower than free peptide. This presentation required a dose of LLO below the cytotoxic level. Mutations of two key tryptophan residues reduced LLO toxicity by 10–100-fold but had no effect on its presentation to CD4 T cells. Thus there was a clear dissociation between the cytotoxic properties of LLO and its very high antigenicity. Presentation of LLO to CD8 T cells was not as robust as that seen in CD4 T cells, but still occurred in the nanomolar range. APC rapidly bound and internalized LLO, then disrupted endosomal compartments within 4 hours of treatment, allowing endosomal contents to access the cytosol. LLO was also immunogenic after in vivo administration into mice. Our results demonstrate the strength of LLO as an immunogen to both CD4 and CD8 T cells

Characterization of the Tomato ARF Gene Family Uncovers a Multi-Levels Post-Transcriptional Regulation Including Alternative Splicing

Background: The phytohormone auxin is involved in a wide range of developmental processes and auxin signaling is known to modulate the expression of target genes via two types of transcriptional regulators, namely, Aux/IAA and Auxin Response Factors (ARF). ARFs play a major role in transcriptional activation or repression through direct binding to the promoter of auxin-responsive genes. The present study aims at gaining better insight on distinctive structural and functional features among ARF proteins. Results: Building on the most updated tomato (Solanum lycopersicon) reference genome sequence, a comprehensive set of ARF genes was identified, extending the total number of family members to 22. Upon correction of structural annotation inconsistencies, renaming the tomato ARF family members provided a consensus nomenclature for all ARF genes across plant species. In silico search predicted the presence of putative target site for small interfering RNAs within twelve Sl-ARFs while sequence analysis of the 59-leader sequences revealed the presence of potential small uORF regulatory elements. Functional characterization carried out by transactivation assay partitioned tomato ARFs into repressors and activators of auxin-dependent gene transcription. Expression studies identified tomato ARFs potentially involved in the fruit set process. Genome-wide expression profiling using RNA-seq revealed that at least one third of the gene family members display alternative splicing mode of regulation during the flower to fruit transition. Moreover, the regulation of several tomato ARF genes by both ethylene and auxin, suggests their potential contribution to the convergence mechanism between the signaling pathways of these two hormones. Conclusion: All together, the data bring new insight on the complexity of the expression control of Sl-ARF genes at the transcriptional and post-transcriptional levels supporting the hypothesis that these transcriptional mediators might represent one of the main components that enable auxin to regulate a wide range of physiological processes in a highly specific and coordinated manner