Development of an R script for simple lipidomic and metabolomic data analysis

Background: Metabolomic and lipidomic studies generate vast quantities of data that are often analysed in a closed software environment with little to no access to the underlying algorithms. As a result, data processed via different software pipelines yield different results thus leading to a widespread problem of low reproducibility within these fields. To address this problem, we are developing LipidAnalyst; an R based lipidomics software pipeline. As a part of this project, we are creating a simple statistical analysis and graphing module in R to generate accurate, reproducible, high-resolution figures. Methods: R scripts were developed under version 3.5.3 with the capability to undertake statistical analyses (e.g. ANOVA) and post-hoc tests (e.g. Tukey). Additional code plotted resultant information as high resolution violin and box plots that depicted statistical significance. Thereafter, lipidomic and metabolomic data were analysed by this code and compared against commercial software and Metaboanalyst, a primary software used in metabolomic and lipidomic research. Results: Code generated in house demonstrated the same results as those generated using commercial software (e.g. JMP 14.0 Pro) but were different from results obtained by using the MetaboAnalyst pipeline. Conclusions: This study demonstrated the prevalent danger of using closed-source software pipelines for the analysis of lipidomic and metabolomic data without validating the analysis outcomes via open-source software. Open source software such as LipidAnalyst, that has also been independently validated using multiple data sets, can then be published with the results to enable transparency of data analysis and improve the replicability of results across different labs.https://scholarscompass.vcu.edu/gradposters/1092/thumbnail.jp

Lyapunov Exponent Pairing for a Thermostatted Hard-Sphere Gas under Shear in the Thermodynamic Limit

We demonstrate why for a sheared gas of hard spheres, described by the SLLOD equations with an iso-kinetic Gaussian thermostat in between collisions, deviations of the conjugate pairing rule for the Lyapunov spectrum are to be expected, employing a previous result that for a large number of particles $N$, the iso-kinetic Gaussian thermostat is equivalent to a constant friction thermostat, up to $1/\sqrt{N}$ fluctuations. We also show that these deviations are at most of the order of the fourth power in the shear rate.Comment: 4 pages, to appear in Rapid Comm., Phys. Rev.

“I need somebody who knows about feet” a qualitative study investigating the lived experiences of conservative treatment for patients with posterior tibial tendon dysfunction

Background: Posterior tibial tendon dysfunction is a disabling, chronic, progressive tendon condition that detrimentally affects foot, ankle and lower limb function. Research suggests that posterior tibial tendon dysfunction is poorly recognised and difficult to treat. When posterior tibial tendon dysfunction is diagnosed, the clinician is faced with a weak evidence base and guidelines for the common conservative treatments to guide their management. Moreover, there are no current evidence-based guidelines for the conservative management of posterior tibial tendon dysfunction. Emerging research suggests that posterior tibial tendon dysfunction not only has a physical impact on the patient, but it also has psychosocial impact on quality of life. Conservative treatments for posterior tibial tendon dysfunction are generally undertaken during early management. The most common are foot orthoses, exercises, bracing, lifestyle changes and injections. Quantitative evidence supporting conservative treatments for posterior tibial tendon dysfunction in relation to function, pain and patient reported outcome measures are reported in the literature. There is a paucity of qualitative research investigating the psychosocial impact of the common treatments for posterior tibial tendon dysfunction. Interpretative phenomenology is concerned with lived experience which is involves the detailed exploration of experience which is embedded within the social and temporal contexts of the lifeworld of the person. The aim of study research is to investigate the lived experience of conservative treatments for patients who have posterior tibial tendon dysfunction using Interpretative Phenomenological Analysis. Methods: Five participants with posterior tibial tendon dysfunction were purposively recruited from a private podiatry practice and semi-structured interviews were conducted to examine their lived experiences of treatment for posterior tibial tendon dysfunction. The data for this study was collected and analysed using Interpretative Phenomenological Analysis. Results: This research identified three superordinate themes which influenced the lived experience of treatment for these patients (i) adverse experience during the patient journey (ii) treatment burden, and (iii) negative self-concept. Conclusion: This study highlights some of what is anecdotally known about the lived experience of treatment for patients with posterior tibial tendon dysfunction, but has never been studied in a qualitative, methodological manner. This study addresses the gap in the qualitative literature. It reveals novel aspects of the lived experience throughout the patient journey, the detrimental impact of treatment burden, loss and negative self-concept. This evidence is important because it highlights the need for a greater understanding of the psychological and social factors that can influence the lived experience of treatment for this group of patients

A systematically coarse-grained model for DNA, and its predictions for persistence length, stacking, twist, and chirality

We introduce a coarse-grained model of DNA with bases modeled as rigid-body ellipsoids to capture their anisotropic stereochemistry. Interaction potentials are all physicochemical and generated from all-atom simulation/parameterization with minimal phenomenology. Persistence length, degree of stacking, and twist are studied by molecular dynamics simulation as functions of temperature, salt concentration, sequence, interaction potential strength, and local position along the chain, for both single- and double-stranded DNA where appropriate. The model of DNA shows several phase transitions and crossover regimes in addition to dehybridization, including unstacking, untwisting, and collapse which affect mechanical properties such as rigidity and persistence length. The model also exhibits chirality with a stable right-handed and metastable left-handed helix.Comment: 30 pages, 20 figures, Supplementary Material available at http://www.physics.ubc.ca/~steve/publications.htm

The impact of intolerance of uncertainty and cognitive behavioural instructions on safety learning

Background Difficulty updating threat associations to safe associations has been observed in individuals who score high in self-reported Intolerance of Uncertainty (IU). Here we sought to determine whether an instruction based on fundamental principles of Cognitive Behavioural Therapy could promote safety learning in individuals with higher levels of IU, whilst controlling for self-reported trait anxiety (STICSA). Methods We measured skin conductance response, pupil dilation and expectancy ratings during an associative threat learning task in which participants either received a cognitive behavioural instruction or no instruction prior to threat extinction (n = 92). Results Analyses revealed that both self-reported IU and STICSA similarly predicted differences in skin conductance response. Only individuals with lower IU/STICSA in the cognitive behavioural instruction condition displayed successful safety learning via skin conductance response. Conclusions These initial results provide some insight into how simple cognitive behavioural instructions combined with exposure are applied differently in individuals with varying levels of self-reported anxiety. The results further our understanding of the role of basic cognitive behavioural principles and self-reported anxiety in safety learning

Fluctuation formula for nonreversible dynamics in the thermostated Lorentz gas

We investigate numerically the validity of the Gallavotti-Cohen fluctuation formula in the two and three dimensional periodic Lorentz gas subjected to constant electric and magnetic fields and thermostated by the Gaussian isokinetic thermostat. The magnetic field breaks the time reversal symmetry, and by choosing its orientation with respect to the lattice one can have either a generalized reversing symmetry or no reversibility at all. Our results indicate that the scaling property described by the fluctuation formula may be approximately valid for large fluctuations even in the absence of reversibility.Comment: 6 pages, 6 figure

Master equation approach to the conjugate pairing rule of Lyapunov spectra for many-particle thermostatted systems

The master equation approach to Lyapunov spectra for many-particle systems is applied to non-equilibrium thermostatted systems to discuss the conjugate pairing rule. We consider iso-kinetic thermostatted systems with a shear flow sustained by an external restriction, in which particle interactions are expressed as a Gaussian white randomness. Positive Lyapunov exponents are calculated by using the Fokker-Planck equation to describe the tangent vector dynamics. We introduce another Fokker-Planck equation to describe the time-reversed tangent vector dynamics, which allows us to calculate the negative Lyapunov exponents. Using the Lyapunov exponents provided by these two Fokker-Planck equations we show the conjugate pairing rule is satisfied for thermostatted systems with a shear flow in the thermodynamic limit. We also give an explicit form to connect the Lyapunov exponents with the time-correlation of the interaction matrix in a thermostatted system with a color field.Comment: 10 page

Lyapunov instability for a periodic Lorentz gas thermostated by deterministic scattering

In recent work a deterministic and time-reversible boundary thermostat called thermostating by deterministic scattering has been introduced for the periodic Lorentz gas [Phys. Rev. Lett. {\bf 84}, 4268 (2000)]. Here we assess the nonlinear properties of this new dynamical system by numerically calculating its Lyapunov exponents. Based on a revised method for computing Lyapunov exponents, which employs periodic orthonormalization with a constraint, we present results for the Lyapunov exponents and related quantities in equilibrium and nonequilibrium. Finally, we check whether we obtain the same relations between quantities characterizing the microscopic chaotic dynamics and quantities characterizing macroscopic transport as obtained for conventional deterministic and time-reversible bulk thermostats.Comment: 18 pages (revtex), 7 figures (postscript

The detection of tethered and rising bubbles using multiple acoustic techniques

There exists a range of acoustic techniques for characterizing bubble populations within liquids. Each technique has limitations, and complete characterization of a population requires the sequential or simultaneous use of several, so that the limitations of each find compensation in the others. Here, nine techniques are deployed using one experimental rig, and compared to determine how accurately and rapidly they can characterize given bubble populations. These are, specifically (i) two stationary bubbles attached to a wire; and (ii) injected, rising bubble

What do I do now? Intolerance of uncertainty is associated with discrete patterns of anticipatory physiological responding to different contexts

Heightened physiological responses to uncertainty are a common hallmark of anxiety disorders. Many separate studies have examined the relationship between individual differences in intolerance of uncertainty (IU) and physiological responses to uncertainty during different contexts. Despite this there is a scarcity of research examining the extent to which individual differences in IU are related to shared or discrete patterns of anticipatory physiological responding across different contexts. Anticipatory physiological responses to uncertainty were assessed in three different contexts (associative threat learning and extinction, threat uncertainty, decision-making) within the same sample (n = 45). During these tasks, behavioural responses (i.e. reaction times, choices), skin conductance and corrugator supercilli activity were recorded. In addition, self-reported IU and trait anxiety were measured. IU was related to both skin conductance and corrugator supercilii activity for the associative threat learning and extinction context, and decision-making context. However, trait anxiety was related to corrugator supercilii activity during the threat uncertainty context. Ultimately, this research helps us further tease apart the role of IU on different aspects of anticipation (i.e. valence and arousal) across contexts, which will be relevant for future IU-related models of psychopathology