The interfacial structure of polymeric surfactant stabilised air-in-water foams

Small-angle neutron scattering was used to probe the interfacial structure of nitrogen-in-water foams created using a series of tri-block polymeric surfactants of the poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (EOx–POy–EOx) range, from which the nature of the polymeric interface could be characterised. The data follow a pronounced Q−4 decay, along with a number of inflexions and weak but well-defined peaks. These characteristics were well-described by a model embodying paracrystalline stacks of adsorbed polymer layers, whose formation is induced by the presence of the air–water interface, adsorbed at the flat air–water (film lamellae) interface. A minimum of approximately five paracrystalline polymer layers of thickness of the order of 85–160 Å, interspersed with somewhat thicker (400 Å) films of continuous aqueous phase were found to best fit the data. The thickness of the layer (L) was shown to follow a relationship predicted by anchor block dominated polymer adsorption theories from non-selective solvents, L EO1PO1/3. The insight gained from these studies should permit a more rational design of polymeric stabilisers for hydrophilic polyurethane foams

Caveolae protect endothelial cells from membrane rupture during increased cardiac output.

Caveolae are strikingly abundant in endothelial cells, yet the physiological functions of caveolae in endothelium and other tissues remain incompletely understood. Previous studies suggest a mechanoprotective role, but whether this is relevant under the mechanical forces experienced by endothelial cells in vivo is unclear. In this study we have sought to determine whether endothelial caveolae disassemble under increased hemodynamic forces, and whether caveolae help prevent acute rupture of the plasma membrane under these conditions. Experiments in cultured cells established biochemical assays for disassembly of caveolar protein complexes, and assays for acute loss of plasma membrane integrity. In vivo, we demonstrate that caveolae in endothelial cells of the lung and cardiac muscle disassemble in response to acute increases in cardiac output. Electron microscopy and two-photon imaging reveal that the plasma membrane of microvascular endothelial cells in caveolin 1(-/-) mice is much more susceptible to acute rupture when cardiac output is increased. These data imply that mechanoprotection through disassembly of caveolae is important for endothelial function in vivo

Beyond BRAFV600: Clinical Mutation Panel Testing by Next-Generation Sequencing in Advanced Melanoma

The management of melanoma has evolved owing to improved understanding of its molecular drivers. To augment the current understanding of the prevalence, patterns, and associations of mutations in this disease, the results of clinical testing of 699 advanced melanoma patients using a pan-cancer next-generation sequencing (NGS) panel of hotspot regions in 46 genes were reviewed. Mutations were identified in 43 of the 46 genes on the panel. The most common mutations were BRAFV600 (36%), NRAS (21%), TP53 (16%), BRAFNon-V600 (6%), and KIT (4%). Approximately one-third of melanomas had >1 mutation detected, and the number of mutations per tumor was associated with melanoma subtype. Concurrent TP53 mutations were the most frequent events in tumors with BRAFV600and NRAS mutations. Melanomas with BRAFNon-V600mutations frequently harbored concurrent NRAS mutations (18%), which were rare in tumors with BRAFV600 mutations (1.6%). The prevalence of BRAFV600 and KIT mutations were significantly associated with melanoma subtypes, and BRAFV600 and TP53 mutations were significantly associated with cutaneous primary tumor location. Multiple potential therapeutic targets were identified in metastatic unknown primary and cutaneous melanomas that lacked BRAFV600and NRAS mutations. These results enrich our understanding of the patterns and clinical associations of oncogenic mutations in melanoma

The influence of visual flow and perceptual load on locomotion speed

Visual flow is used to perceive and regulate movement speed during locomotion. We assessed the extent to which variation in flow from the ground plane, arising from static visual textures, influences locomotion speed under conditions of concurrent perceptual load. In two experiments, participants walked over a 12-m projected walkway that consisted of stripes that were oriented orthogonal to the walking direction. In the critical conditions, the frequency of the stripes increased or decreased. We observed small, but consistent effects on walking speed, so that participants were walking slower when the frequency increased compared to when the frequency decreased. This basic effect suggests that participants interpreted the change in visual flow in these conditions as at least partly due to a change in their own movement speed, and counteracted such a change by speeding up or slowing down. Critically, these effects were magnified under conditions of low perceptual load and a locus of attention near the ground plane. Our findings suggest that the contribution of vision in the control of ongoing locomotion is relatively fluid and dependent on ongoing perceptual (and perhaps more generally cognitive) task demands

The Sodium/Proton Exchanger NHE8 Regulates Late Endosomal Morphology and Function

The pH and lumenal environment of intracellular organelles is considered essential for protein sorting and trafficking through the cell. We provide the first evidence that a mammalian sodium (potassium)/proton exchanger, NHE8, plays a key role in the control of protein trafficking and endosome morphology

Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (>= 65 years; estimated glomerular filtration rate <= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off <= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Modelling of transport in highly heterogeneous porous media, with application to the flushing of waste

This thesis is concerned with predicting the fate of contaminants using tracer and contaminant flushing datasets in otherwise poorly characterised heterogeneous media. A deductive approach towards constraining prediction uncertainty is adopted, by narrowing a 'pool' of plausible process models and associated parameter sets. Mathematical comparison of simple transport models is used to allow enhanced diagnosis. Transport models are put into a framework. Then they are compared using commonly used measures of breakthrough curves (least squares fitting, method of moments and late-time concentration gradients). Experimental data and models for transport in waste are then reviewed using this framework. Two new tracer datasets, at laboratory and lysimeter scales, are analysed and modelled. Strong evidence is shown of 'dual-porosity' diffusive exchange effects being an important component in transport in municipal solid waste. However, it is not possible to discriminate between contributions to dispersion through advective and diffusive effects. Approaches to enhance the diagnostic capability of future waste experiments are developed. One possible 'entrant' to the 'pool' of models is examined: a stochastic channel network model. Histograms of nodes and average heads are evaluated at different distances from a range of boundary conditions for large ensembles revealing key insights into network flow behaviour near different types of boundary. Key properties of the network are related to typical continuum analyses, including dimensionality of flow and genesis of apparent 'skins' near boundaries. 'Classical' percolation networks (with zero spatial correlation) are also analysed, revealing new insights into their network properties within finite boundaries. In summary, progress towards predicting the fate of contaminants in highly heterogeneous systems is made through a thorough delineation of the behaviour of simple models in tandem with adoption of a fertile approach to adding new conceptual models. The increased rigorousness of using multiple diagnostic criteria in conjunction with adopting a philosophy of working with multiple working hypotheses is commended as a methodology that provides a sound basis from which to employ multiple-model uncertainty analysis for predictive purposes in the future.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Evaluating landfill aftercare strategies: a life cycle assessment approach

This study investigates the potential impacts caused by the loss of active environmental control measures during the aftercare period of landfill management. A combined mechanistic solute flow model and life cycle assessment (LCA) approach was used to evaluate the potential impacts of leachate emissions over a 10,000 year time horizon. A continuum of control loss possibilities occurring at different times and for different durations were investigated for four different basic aftercare scenarios, including a typical aftercare scenario involving a low permeability cap and three accelerated aftercare scenarios involving higher initial infiltration rates. Assuming a ‘best case’ where control is never lost, the largest potential impacts resulted from the typical aftercare scenario. The maximum difference between potential impacts from the ‘best case’ and the ‘worst case’, where control fails at the earliest possible point and is never reinstated, was only a fourfold increase. This highlights potential deficiencies in standard life cycle impact assessment practice, which are discussed. Nevertheless, the results show how the influence of active control loss on the potential impacts of landfilling varies considerably depending on the aftercare strategy used and highlight the importance that leachate treatment efficiencies have upon impact

Mechanistic flow modelling and LCA results in support of Evaluating landfill aftercare strategies: a life cycle assessment approach

Dataset supporting: Turner, David, Beaven, Richard and Woodman, Nicholas (2016) Evaluating landfill aftercare strategies: a life cycle assessment approach. Waste Management The zip file contains three Excel spreadsheet files. &quot;Mechanistic flow modelling and LCA results.xlsx&quot; contains results of the 4 different scenarios modeled, organized by 1) pathway 2) impact category and 3) by species. The remaining two spreadsheet files contain the results of two different sensitivity analyses.</span