A virtual element method for transversely isotropic elasticity

This work studies the approximation of plane problems concerning transversely isotropic elasticity, using a low-order virtual element method (VEM). The VEM is an alternative finite element method characterised by complete freedom in determining element geometries that are otherwise polygonal in two dimensions, or polyhedral in three. Transversely isotropic materials are characterised by an axis of symmetry perpendicular to a plane of isotropy, and have applications ranging from fibre reinforcement to biological materials. The governing equations of the transversely isotropic elasticity problem are derived and a virtual element formulation of the problem is presented along with a sample implementation of the method. This work focuses on the treatment of near-incompressibility and near-inextensibility. These are explored both for homogeneous problems, in which the plane of isotropy is fixed; and non-homogeneous problems, in which the fibre directions defining the plane of isotropy vary with position. In the latter case various options are explored for approximating the non-homogeneous terms at an element level. The VEM approximations are shown through a range of numerical examples to be robust and locking-free, for a selection of element geometries, and fibre directions corresponding to mild and strong inhomogeneity

A virtual element method for hyperelasticity

This thesis studies the approximation of plane problems of hyperelasticity, using a loworder virtual element method (VEM). The VEM is an extension of the finite element method (FEM). It is characterised by considerable freedom with regard to element geometry, permitting arbitrary polygonal and polyhedral elements in two and three dimensions respectively. Furthermore, the local basis functions are not known explicitly on elements and take the simple form of piecewise-linear Lagrangian functions on element boundaries. All integrations are performed on element edges. The VEM formulation typically involves a consistency term, computed via a projection, and a stabilization term, which must be approximated. Problems concerning isotropic and transversely isotropic hyperelastic material models are considered. Examples of transversely isotropic materials, which are characterised by an axis of symmetry normal to a plane of isotropy, range from simple fibre-reinforced materials to biological tissues. To date, in the context of hyperelasticity, investigation of the performance of VEM has primarily focused on problems involving the isotropic neo-Hookean material model. Furthermore, there has been limited investigation into the behaviour of the VEM in the nearly incompressible and nearly inextensible limits. In this thesis a VEM formulation with a novel approach to the construction of the stabilization term is formulated and implemented for problems involving isotropic and transversely isotropic hyperelastic materials. The governing equations of hyperelasticity are derived and various isotropic and transversely isotropic constitutive models are presented. This is followed by presentation of the virtual element formulation of the hyperelastic problem and a possible approach to its practical implementation. Through a range of numerical examples, the VEM with the proposed stabilization term is found to exhibit robust and accurate behaviour for a variety of mesh types, including those comprising highly non-convex element geometries, and for problems involving severe deformations. Furthermore, the versatility of the proposed VEM formulation is demonstrated through its application to a range of popular isotropic and transversely isotropic material models for a wide variety of material parameters. Through this investigation the VEM is found to exhibit locking-free behaviour in the limiting cases of near-incompressibility and near-inextensibility, both separately and combined

On mesh coarsening procedures for the virtual element method

In the context of adaptive remeshing, the virtual element method provides significant advantages over the finite element method. The attractive features of the virtual element method, such as the permission of arbitrary element geometries, and the seamless permission of 'hanging' nodes, have inspired many works concerning error estimation and adaptivity. However, these works have primarily focused on adaptive refinement techniques with little attention paid to adaptive coarsening (i.e. de-refinement) techniques that are required for the development of fully adaptive remeshing procedures. In this work novel indicators are proposed for the identification of patches/clusters of elements to be coarsened, along with a novel procedure to perform the coarsening. The indicators are computed over prospective patches of elements rather than on individual elements to identify the most suitable combinations of elements to coarsen. The coarsening procedure is robust and suitable for meshes of structured and unstructured/Voronoi elements. Numerical results demonstrate the high degree of efficacy of the proposed coarsening procedures and sensible mesh evolution during the coarsening process. It is demonstrated that critical mesh geometries, such as non-convex corners and holes, are preserved during coarsening, and that meshes remain fine in regions of interest to engineers, such as near singularities

Mulch and groundcover effects on soil temperature and moisture, surface reflectance, grapevine water potential, and vineyard weed management

The objectives of this research were to identify alternatives to glyphosate for intra- row (under-trellis) vineyard floor management and to evaluate the potential for intra- row and inter-row (alleyway) groundcovers to reduce vegetative vigor of `Marquette\u27 grapevines (Vitis spp.) in a southeast Nebraska vineyard. The experiment was a randomized factorial design with five intra-row treatments (crushed glass mulch [CG], distillers\u27 grain mulch [DG], creeping red fescue [CRF], non-sprayed control [NSC], and glyphosate [GLY]) and three inter-row treatments (creeping red fescue [CRF], Kentucky bluegrass [KB], and resident vegetation [RV]). Treatments were established in 2010-2011 and measurements were conducted during 2012 and 2013 on 5- and 6-year- old vines. Soil temperatures were mostly higher under mulches and lower under intra- row groundcovers, compared to GLY. Weed cover in CG, DG, and CRF treatments was the same or less than GLY. At most sampling dates, inter-row soil moisture was lowest under KB. Intra-row soil moisture was highest under DG mulch and lowest under CRF and NSC; CG had the same or lower soil moisture than GLY. Surprisingly, we did not detect differences in mid-day photosynthetically active radiation (PAR) reflectance, despite visual differences among the intra-row treatments. Mid-day vine water potential did not differ among treatments. We concluded it is not necessary to maintain a bare soil strip under established vines in this region, where soil fertility and moisture are non-limiting

Rapid inactivation and sample preparation for SARS-CoV-2 PCR-based diagnostics using TNA-Cifer Reagent E

RT-qPCR remains a key diagnostic methodology for COVID-19/SARS-CoV-2. Typically, nasal or saliva swabs from patients are placed in virus transport media (VTM), RNA is extracted at the pathology laboratory, and viral RNA is measured using RT-qPCR. In this study, we describe the use of TNA-Cifer Reagent E in a pre-clinical evaluation study to inactivate SARS-CoV-2 as well as prepare samples for RT-qPCR. Adding 1 part TNA-Cifer Reagent E to 5 parts medium containing SARS-CoV-2 for 10 min at room temperature inactivated the virus and permitted RT-qPCR detection. TNA-Cifer Reagent E was compared with established column-based RNA extraction and purification methodology using a panel of human clinical nasal swab samples (n = 61), with TNA-Cifer Reagent E showing high specificity (100%) and sensitivity (97.37%). Mixtures of SARS-CoV-2 virus and TNA-Cifer Reagent E could be stored for 3 days at room temperature or for 2 weeks at 4°C without the loss of RT-qPCR detection sensitivity. The detection sensitivity was preserved when TNA-Cifer Reagent E was used in conjunction with a range of VTM for saliva samples but only PBS (Gibco) and Amies Orange for nasal samples. Thus, TNA-Cifer Reagent E improves safety by rapidly inactivating the virus during sample processing, potentially providing a safe means for molecular SARS-CoV-2 testing outside traditional laboratory settings. The reagent also eliminates the need for column-based and/or automated viral RNA extraction/purification processes, thereby providing cost savings for equipment and reagents, as well as reducing processing and handling times

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

AfriBooms: An Online Treebank for Afrikaans

Compared to well-resourced languages such as English and Dutch, natural language processing (NLP) tools for Afrikaans are still not abundant. In the context of the AfriBooms project, KU Leuven and the North-West University collaborated to develop a first, small treebank, a dependency parser, and an easy to use online linguistic search engine for Afrikaans for use by researchers and students in the humanities and social sciences. The search tool is based on a similar development for Dutch, i.e. GrETEL, a user-friendly search engine which allows users to query a treebank by means of a natural language example instead of a formal search instruction.status: publishe