Regular Grids: An Irregular Approach to the 3D Modelling Pipeline

The 3D modelling pipeline covers the process by which a physical object is scanned to create a set of points that lay on its surface. These data are then cleaned to remove outliers or noise, and the points are reconstructed into a digital representation of the original object. The aim of this thesis is to present novel grid-based methods and provide several case studies of areas in the 3D modelling pipeline in which they may be effectively put to use. The first is a demonstration of how using a grid can allow a significant reduction in memory required to perform the reconstruction. The second is the detection of surface features (ridges, peaks, troughs, etc.) during the surface reconstruction process. The third contribution is the alignment of two meshes with zero prior knowledge. This is particularly suited to aligning two related, but not identical, models. The final contribution is the comparison of two similar meshes with support for both qualitative and quantitative outputs

Mesh Alignment using Grid based PCA

We present an algorithm for mesh alignment by performing Principal Components Analysis (PCA) on a set of nodes of a regular 3D grid. The use of a 3D lattice external to both inputs increases the robustness of PCA, particularly when dealing with meshes of different and possibly uneven vertex density. The proposed algorithm was tested on meshes that have undergone standard mesh processing operations such as smoothing, simplification and remeshing. In several cases the results indicate an improved robustness compared to performing PCA directly on mesh vertices

Intercomparison of Multiple UV-LIF Spectrometers using the Aerosol Challenge Simulator

Measurements of primary biological aerosol particles (PBAPs) have been conducted worldwide using ultraviolet light-induced fluorescence (UV-LIF) spectrometers. However, how these instruments detect and respond to known biological and non-biological particles, and how they compare, remains uncertain due to limited laboratory intercomparisons. Using the Defence Science and Technology Laboratory, Aerosol Challenge Simulator (ACS), controlled concentrations of biological and non-biological aerosol particles, singly or as mixtures, were produced for testing and intercomparison of multiple versions of the Wideband Integrated Bioaerosol Spectrometer (WIBS) and Multiparameter Bioaerosol Spectrometer (MBS). Although the results suggest some challenges in discriminating biological particle types across different versions of the same UV-LIF instrument, a difference in fluorescence intensity between the non-biological and biological samples could be identified for most instruments. While lower concentrations of fluorescent particles were detected by the MBS, the MBS demonstrates the potential to discriminate between pollen and other biological particles. This study presents the first published technical summary and use of the ACS for instrument intercomparisons. Within this work a clear overview of the data pre-processing is also presented, and documentation of instrument version/model numbers is suggested to assess potential instrument variations between different versions of the same instrument. Further laboratory studies sampling different particle types are suggested before use in quantifying impact on ambient classification.Peer reviewe

Viloxazine, a Non-stimulant Norepinephrine Reuptake Inhibitor, for the Treatment of Attention Deficit Hyperactivity Disorder: A 3 Year Update.

Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in childhood. Current treatment options for ADHD include pharmacological treatment (stimulants, non-stimulants, anti-depressants, anti-psychotics), psychological treatment (behavioral therapy with or without parent training, cognitive training, neurofeedback), and complementary and alternative therapies (vitamin supplementation, exercise). Central nervous system (CNS) stimulants are the primary pharmacological therapy used in treatment; however, these stimulant drugs carry a high potential for abuse and severe psychological/physical dependence. Viloxazine, a non-stimulant medication without evidence of drug dependence, is a selective norepinephrine reuptake inhibitor that has historically been prescribed as an anti-depressant medication. The extended-release (ER) form was approved by the US Food and Drug Administration (FDA) in April 2021 for the treatment of ADHD in pediatric patients aged 6-17 years. Phase 2 and 3 randomized control trials have demonstrated significant efficacy of viloxazine in improving ADHD symptoms versus placebo. Related to its long-standing use as an antidepressant, the safety profile and pharmacokinetics of viloxazine are well understood. Viloxazine appears to be a suitable alternative to current standard-of-care pharmacotherapy for ADHD, but the further investigation remains to be done in comparing its efficacy to that of current treatments

Abnormal mitochondrial L-arginine transport contributes to the pathogenesis of heart failure and rexoygenation injury

Impaired mitochondrial function is fundamental feature of heart failure (HF) and myocardial ischemia. In addition to the effects of heightened oxidative stress, altered nitric oxide (NO) metabolism, generated by a mitochondrial NO synthase, has also been proposed to impact upon mitochondrial function. However, the mechanism responsible for arginine transport into mitochondria and the effect of HF on such a process is unknown. We therefore aimed to characterize mitochondrial L-arginine transport and to investigate the hypothesis that impaired mitochondrial L-arginine transport plays a key role in the pathogenesis of heart failure and myocardial injury

Detection of Airborne Biological Particles in Indoor Air Using a Real-Time Advanced Morphological Parameter UV-LIF Spectrometer and Gradient Boosting Ensemble Decision Tree Classifiers

We present results from a study evaluating the utility of supervised machine learning to classify single particle ultraviolet laser-induced fluorescence (UV-LIF) signatures to investigate airborne primary biological aerosol particle (PBAP) concentrations in a busy, multifunctional building using a Multiparameter Bioaerosol Spectrometer. First we introduce and demonstrate a gradient boosting ensemble decision tree algorithm’s ability to accurately classify laboratory generated PBAP samples into broad taxonomic classes with a high level of accuracy. We then develop a framework to appraise the classification accuracy and performance using the Hellinger distance metric to compare product parameter probability density function similarity; this framework showed that key training classes were sufficiently different in terms of particle fluorescence and morphology to facilitate classification. We also demonstrate the utility of including advanced morphological parameters to minimise inter-class conflation and improve classification confidence, where relying on the fluorescent spectra alone would likely result in misattribution. Finally, we apply these methods to ambient data collected within a large multi-functional building where ambient bacterial- and fungal-like classes were identified to display trends corresponding to human activity; fungal-like classes displayed a consistent diurnal trend with a maximum at midday and hourly peaks correlating to movements within the building; bacteria-like aerosol displayed complex, episodic events during opening hours. All PBAP classes fell to low baseline concentrations when the building was unoccupied overnight and at weekendsPeer reviewe

Oral activated charcoal prevents experimental cerebral malaria in mice and in a randomized controlled clinical trial in man did not interfere with the pharmacokinetics of parenteral artesunate.

BACKGROUND: Safe, cheap and effective adjunct therapies preventing the development of, or reducing the mortality from, severe malaria could have considerable and rapid public health impact. Oral activated charcoal (oAC) is a safe and well tolerated treatment for acute poisoning, more recently shown to have significant immunomodulatory effects in man. In preparation for possible efficacy trials in human malaria, we sought to determine whether oAC would i) reduce mortality due to experimental cerebral malaria (ECM) in mice, ii) modulate immune and inflammatory responses associated with ECM, and iii) affect the pharmacokinetics of parenteral artesunate in human volunteers. METHODS/PRINCIPAL FINDINGS: We found that oAC provided significant protection against P. berghei ANKA-induced ECM, increasing overall survival time compared to untreated mice (p<0.0001; hazard ratio 16.4; 95% CI 6.73 to 40.1). Protection from ECM by oAC was associated with reduced numbers of splenic TNF(+) CD4(+) T cells and multifunctional IFNgamma(+)TNF(+) CD4(+) and CD8(+) T cells. Furthermore, we identified a whole blood gene expression signature (68 genes) associated with protection from ECM. To evaluate whether oAC might affect current best available anti-malarial treatment, we conducted a randomized controlled open label trial in 52 human volunteers (ISRCTN NR. 64793756), administering artesunate (AS) in the presence or absence of oAC. We demonstrated that co-administration of oAC was safe and well-tolerated. In the 26 subjects further analyzed, we found no interference with the pharmacokinetics of parenteral AS or its pharmacologically active metabolite dihydroartemisinin. CONCLUSIONS/SIGNIFICANCE: oAC protects against ECM in mice, and does not interfere with the pharmacokinetics of parenteral artesunate. If future studies succeed in establishing the efficacy of oAC in human malaria, then the characteristics of being inexpensive, well-tolerated at high doses and requiring no sophisticated storage would make oAC a relevant candidate for adjunct therapy to reduce mortality from severe malaria, or for immediate treatment of suspected severe malaria in a rural setting. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN64793756

Bayes Wars Redivivus - An Exchange

An electronic exchange among 10 evidence scholars that began with a discussion of the restyled Federal Rules and grew into a significant restatement of debates in evidentiary scholarship over the last 50 years, touching on relevance, probative value, inference, Bayesianism and the foundations of evidence, with an introduction by Michael Risinger

CXCR4 Antagonism attenuates the development of diabetic cardiac fibrosis

Heart failure (HF) is an increasingly recognized complication of diabetes. Cardiac fibrosis is an important causative mechanism of HF associated with diabetes. Recent data indicate that inflammation may be particularly important in the pathogenesis of cardiovascular fibrosis. We sought to determine the mechanism by which cardiac fibrosis develops and to specifically investigate the role of the CXCR4 axis in this process. Animals with type I diabetes (streptozotocin treated mice) or type II diabetes (Israeli Sand-rats) and controls were randomized to treatment with a CXCR4 antagonist, candesartan or vehicle control. Additional groups of mice also underwent bone marrow transplantation (GFP+ donor marrow) to investigate the potential role of bone marrow derived cell mobilization in the pathogenesis of cardiac fibrosis. Both type I and II models of diabetes were accompanied by the development of significant cardiac fibrosis. CXCR4 antagonism markedly reduced cardiac fibrosis in both models of diabetes, similar in magnitude to that seen with candesartan. In contrast to candesartan, the anti-fibrotic actions of CXCR4 antagonism occurred in a blood pressure independent manner. Whilst the induction of diabetes did not increase the overall myocardial burden of GFP+ cells, it was accompanied by an increase in GFP+ cells expressing the fibroblast marker alpha-smooth muscle actin and this was attenuated by CXCR4 antagonism. CXCR4 antagonism was also accompanied by increased levels of circulating regulatory T cells. Taken together the current data indicate that pharmacological inhibition of CXCR4 significantly reduces diabetes induced cardiac fibrosis, providing a potentially important therapeutic approach

On the alleged simplicity of impure proof

Roughly, a proof of a theorem, is “pure” if it draws only on what is “close” or “intrinsic” to that theorem. Mathematicians employ a variety of terms to identify pure proofs, saying that a pure proof is one that avoids what is “extrinsic,” “extraneous,” “distant,” “remote,” “alien,” or “foreign” to the problem or theorem under investigation. In the background of these attributions is the view that there is a distance measure (or a variety of such measures) between mathematical statements and proofs. Mathematicians have paid little attention to specifying such distance measures precisely because in practice certain methods of proof have seemed self- evidently impure by design: think for instance of analytic geometry and analytic number theory. By contrast, mathematicians have paid considerable attention to whether such impurities are a good thing or to be avoided, and some have claimed that they are valuable because generally impure proofs are simpler than pure proofs. This article is an investigation of this claim, formulated more precisely by proof- theoretic means. After assembling evidence from proof theory that may be thought to support this claim, we will argue that on the contrary this evidence does not support the claim