Very high pressure liquid chromatography using fully porous particles: Quantitative analysis of fast gradient separations without post-run times

Using a column packed with fully porous particles, four methods for controlling the flow rates at which gradient elution runs are conducted in very high pressure liquid chromatography (VHPLC) were tested to determine whether reproducible thermal conditions could be achieved, such that subsequent analyses would proceed at nearly the same initial temperature. In VHPLC high flow rates are achieved, producing fast analyses but requiring high inlet pressures. The combination of high flow rates and high inlet pressures generates local heat, leading to temperature changes in the column. Usually in this case a post-run time is input into the analytical method to allow the return of the column temperature to its initial state. An alternative strategy involves operating the column without a post-run equilibration period and maintaining constant temperature variations for subsequent analysis after conducting one or a few separations to bring the column to a reproducible starting temperature. A liquid chromatography instrument equipped with a pressure controller was used to perform constant pressure and constant flow rate VHPLC separations. Six replicate gradient separations of a nine component mixture consisting of acetophenone, propiophenone, butyrophenone, valerophenone, hexanophenone, heptanophenone, octanophenone, benzophenone, and acetanilide dissolved in water/acetonitrile (65:35, v/v) were performed under various experimental conditions: constant flow rate, two sets of constant pressure, and constant pressure operation with a programmed flow rate. The relative standard deviations of the response factors for all the analytes are lower than 5% across the methods. Programming the flow rate to maintain a fairly constant pressure instead of using instrument controlled constant pressure improves the reproducibility of the retention times by a factor of 5, when plotting the chromatograms in time.

Application of the gradient boosted method in randomised clinical trials: participant variables that contribute to depression treatment efficacy of duloxetine, SSRIs or placebo

Randomised, placebo-controlled trials of treatments for depression typically collect outcomes data but traditionally only analyse data to demonstrate efficacy and safety. Additional post-hoc statistical techniques may reveal important insights about treatment variables useful when considering inter-individual differences amongst depressed patients. This paper aims to examine the Gradient Boosted Model (GBM), a statistical technique that uses regression tree analyses and can be applied to clinical trial data to identify and measure variables that may influence treatment outcomes.

The social gradient of fractures at any skeletal site in men and women: data from the Geelong Osteoporosis Study Fracture Grid.

Age-specific and age-standardized associations between socioeconomic status (SES) and fractures in adults showed a social gradient of fracture, irrespective of fracture site. Compared to the highest SES, males in the lowest SES group had a sixfold increased odds for any fracture, whilst females had a twofold increased odds.

Frequency-domain beamformers using conjugate gradient techniques for speech enhancement

A multiple-iteration constrained conjugate gradient (MICCG) algorithm and a single-iteration constrained conjugate gradient (SICCG) algorithm are proposed to realize the widely used frequency-domain minimum-variance-distortionless-response (MVDR) beamformers and the resulting algorithms are applied to speech enhancement. The algorithms are derived based on the Lagrange method and the conjugate gradient techniques. The implementations of the algorithms avoid any form of explicit or implicit autocorrelation matrix inversion. Theoretical analysis establishes formal convergence of the algorithms. Specifically, the MICCG algorithm is developed based on a block adaptation approach and it generates a finite sequence of estimates that converge to the MVDR solution. For limited data records, the estimates of the MICCG algorithm are better than the conventional estimators and equivalent to the auxiliary vector algorithms. The SICCG algorithm is developed based on a continuous adaptation approach with a sample-by-sample updating procedure and the estimates asymptotically converge to the MVDR solution. An illustrative example using synthetic data from a uniform linear array is studied and an evaluation on real data recorded by an acoustic vector sensor array is demonstrated. Performance of the MICCG algorithm and the SICCG algorithm are compared with the state-of-the-art approaches.

Utilization of organic matter by invertebrates along an estuarine gradient in an intermittently open estuary

In intermittently open estuaries, the sources of organic matter sustaining benthic invertebrates are likely to vary seasonally, particularly between periods of connection and disconnection with the ocean and higher and lower freshwater flows. This study investigated the contribution of allochthonous and autochthonous primary production to the diet of representative invertebrate species using stable isotope analysis (SIA) during the austral summer and winter (2008, 2009) in an intermittently open estuary on the south-eastern coast of Australia. As the study was conducted towards the end of a prolonged period of drought, a reduced influence of freshwater/terrestrial organic matter was expected. Sampling was conducted along an estuarine gradient, including upper, middle and lower reaches and showed that the majority of assimilated organic matter was derived from autochthonous estuarine food sources. Additionally, there was an input of allochthonous organic matter, which varied along the length of the estuary, indicated by distinct longitudinal trends in carbon and nitrogen stable isotope signatures along the estuarine gradient. Marine seaweed contributed to invertebrate diets in the lower reaches of the estuary, while freshwater/terrestrial organic matter had increased influence in the upper reaches. Suspension-feeding invertebrates derived large parts of their diet from freshwater/terrestrial material, despite flows being greatly reduced in comparison with non-drought years.

Gradient structure produced by three roll planetary milling: numerical simulation and microstructural observations

In this study a gradient grain structure was produced by processing rod billets through three roll planetary milling (also known as PSW process). This kind of gradient structure is reported to provide an excellent combination of strength and ductility owing to an ultrafine-grained surface layer and a coarse-grained interior of the billet. Specifically, copper rod samples were subjected to up to six passes of PSW at room temperature. To study the evolution of the microstructure during the deformation, microhardness measurements and Electron Backscatter Diffraction (EBSD) analysis were performed after one, three and six passes. Additionally, the distributions of the equivalent stress during PSW and the equivalent strain after processing were studied by finite element analysis using the commercial software QFORM. The results showed the efficacy of PSW as a means of imparting a gradient ultrafine-grained structure to copper rods. A good correlation between the simulated equivalent strain distribution and the measured microhardness distribution was demonstrated.

DNA methylation and the social gradient of osteoporotic fracture: a conceptual model

INTRODUCTION: Although there is a documented social gradient for osteoporosis, the underlying mechanism(s) for that gradient remain unknown. We propose a conceptual model based upon the allostatic load theory, to suggest how DNA methylation (DNAm) might underpin the social gradient in osteoporosis and fracture. We hypothesise that social disadvantage is associated with priming of inflammatory pathways mediated by epigenetic modification that leads to an enhanced state of inflammatory reactivity and oxidative stress, and thus places socially disadvantaged individuals at greater risk of osteoporotic fracture. METHODS/RESULTS: Based on a review of the literature, we present a conceptual model in which social disadvantage increases stress throughout the lifespan, and engenders a proinflammatory epigenetic signature, leading to a heightened inflammatory state that increases risk for osteoporotic fracture in disadvantaged groups that are chronically stressed. CONCLUSIONS: Our model proposes that, in addition to the direct biological effects exerted on bone by factors such as physical activity and nutrition, the recognised socially patterned risk factors for osteoporosis also act via epigenetic-mediated dysregulation of inflammation. DNAm is a dynamic modulator of gene expression with considerable relevance to the field of osteoporosis. Elucidating the extent to which this epigenetic mechanism transduces the psycho-social environment to increase the risk of osteoporotic fracture may yield novel entry points for intervention that can be used to reduce individual and population-wide risks for osteoporotic fracture. Specifically, an epigenetic evidence-base may strengthen the importance of lifestyle modification and stress reduction programs, and help to reduce health inequities across social groups. MINI ABSTRACT: Our conceptual model proposes how DNA methylation might underpin the social gradient in osteoporotic fracture. We suggest that social disadvantage is associated with priming of inflammatory signalling pathways, which is mediated by epigenetic modifications, leading to a chronically heightened inflammatory state that places disadvantaged individuals at greater risk of osteoporosis.

The microbiome: a biological mechanism underpinning the social gradient of musculoskeletal conditions?

We read with interest the article by Steves et al, published in J Bone Miner Res, 2016; 31(2):261-269 (1). The authors review available evidence and suggest that the modifiable nature of the gut microbiome (GM) provides a potential therapeutic target to intervene in musculoskeletal conditions of aging.