Computing bounds for linear functionals of exact weak solutions to Poisson's equation

We present a method for Poisson’s equation that computes guaranteed upper and lower bounds for the values of piecewise-polynomial linear functional outputs of the exact weak solution of the infinite-dimensional continuum problem with piecewise-polynomial forcing. The method results from exploiting the Lagrangian saddle point property engendered by recasting the output problem as a constrained minimization problem. Localization is achieved by Lagrangian relaxation and the bounds are computed by appeal to a local dual problem. The proposed method computes approximate Lagrange multipliers using traditional finite element approximations to calculate a primal and an adjoint solution along with well known hybridization techniques to calculate interelement continuity multipliers. The computed bounds hold uniformly for any level of refinement, and in the asymptotic convergence regime of the finite element method, the bound gap decreases at twice the rate of the energy norm measure of the error in the finite element solution. Given a finite element solution and its output adjoint solution, the method can be used to provide a certificate of precision for the output with an asymptotic complexity that is linear in the number of elements in the finite element discretization. The elemental contributions to the bound gap are always positive and hence lend themselves to be used as adaptive indicators, as we demonstrate with a numerical example

The Role of Texture, Cracks, and Fractures in Highly Anisotropic Shales

Organic shales generally have low permeability unless fractures are present. However, how gas, oil, and water flows into these fractures remains enigmatic. The alignment of clay minerals and the alignment of fractures and cracks are effective means to produce seismic anisotropy. Thus, the detection and characterization of this anisotropy can be used to infer details about lithology, rock fabric, and fracture and crack properties within the subsurface. We present a study characterizing anisotropy using S wave splitting from microseismic sources in a highly anisotropic shale. We observe very strong anisotropy (up to 30%) with predominantly VTI (vertical transverse isotropy) symmetry, but with evidence of an HTI (horizontal transverse isotropy) overprint due to a NE striking vertical fracture set parallel to the maximum horizontal compressive stress. We observe clear evidence of a shear wave triplication due to anisotropy, which to our knowledge is one of only a very few observations of such triplications in field‐scale data. We use modal proportions of minerals derived from X‐ray fluorescence data combined with realistic textures to estimate the contribution of intrinsic anisotropy as well as possible contributions of horizontally aligned cracks. We find that aligned clays can explain much of the observed anisotropy and that any cracks contributing to the vertical transverse isotropy (VTI) must have a low ratio of normal to tangential compliance (ZN/ZT), typical of isolated cracks with low hydraulic connectivity. Subhorizontal cracks have also been observed in the reservoir, and we propose that their reactivation during hydraulic fracturing may be an important mechanism to facilitate gas flow

Etiology of Persistent Microalbuminuria in Nigeria (P_MICRO study): Protocol and study design

BACKGROUND: Microalbuminuria is an independent risk factor for cardiovascular and kidney disease and a predictor of end organ damage, both in the general population and in persons with HIV (PWH). Microalbuminuria is also an important risk factor for mortality in PWH treated with antiretroviral therapy (ART). In the ongoing Renal Risk Reduction (R3) study in Nigeria, we identified a high prevalence of microalbuminuria confirmed by two measurements 4-8 weeks apart in ART-experienced, virologically suppressed PWH. Although Stage 1 or 2 hypertension and exposure to potentially nephrotoxic antiretroviral medications were common in R3 participants, other traditional risk factors for albuminuria and kidney disease, including diabetes, APOL1 high-risk genotype, and smoking were rare. Co-infection with endemic pathogens may also be significant contributors to albuminuria, but co-infections were not evaluated in the R3 study population. METHODS: In Aim 1, we will cross-sectionally compare the prevalence of albuminuria and established kidney disease risk factors in a cohort of PWH to age- and sex-matched HIV-negative adults presenting for routine care at the Aminu Kano Teaching Hospital in Kano, Nigeria. We will leverage stored specimens from 2500 R3 participants and enroll an additional 500 PLWH recently initiated on ART (≤ 24 months) and 750 age- and sex-matched HIV-negative adults to determine the contribution of HIV, hypertension, and other comorbid medical conditions to prevalent albuminuria. In Aim 2, we will follow a cohort of 1000 HIV-positive, ART-treated and 500 HIV-negative normoalbuminuric adults for 30 months to evaluate the incidence and predictors of albuminuria. DISCUSSION: The findings from this study will support the development of interventions to prevent or address microalbuminuria in PWH to reduce kidney and cardiovascular morbidity and mortality. Such interventions might include more intensive monitoring and treatment of traditional risk factors, the provision of renin-angiotensin aldosterone system or sodium-glucose cotransporter-2 inhibitors, consideration of changes in ART regimen, and screening and treatment for relevant co-infections

Computing Bounds for Linear Functionals of Exact Weak Solutions to Poisson’s Equation

We present a method for Poisson’s equation that computes guaranteed upper and lower bounds for the values of linear functional outputs of the exact weak solution of the infinite dimensional continuum problem using traditional finite element approximations. The guarantee holds uniformly for any level of refinement, not just in the asymptotic limit of refinement. Given a finite element solution and its output adjoint solution, the method can be used to provide a certificate of precision for the output with an asymptotic complexity which is linear in the number of elements in the finite element discretization.Singapore-MIT Alliance (SMA

The design and development of a multicentric protocol to investigate the impact of adjunctive doxycycline on the management of peripheral lymphoedema caused by lymphatic filariasis and podoconiosis

BACKGROUND: As new lymphatic filariasis infections are eliminated through mass chemotherapy, previously affected individuals are left with the sequellae, especially chronic progressive lymphoedema. Currently this is managed by careful attention to limb hygiene to prevent infection. Studies over the past 15 years have suggested that the incorporation of doxycycline treatment may arrest or even reverse progression of lymphoedema. Most of this work has been observational or based on small studies, and if this intervention is effective, studies need to be conducted on a larger scale and under diverse geographical and social conditions before it can be incorporated into treatment policy. METHODS/DESIGN: The double-blind, placebo-controlled study was designed to investigate the impact of six weeks treatment with doxycycline added to standard limb hygiene on early stage filarial lymphoedema in five sites in Africa and the Indian subcontinent. One site in Cameroon is selected for studying lymphoedema in podoconiosis. Each site was individually powered with the potential to undertake a meta-analysis on completion. Evaluation methods followed those used in Ghana in 2012 with additions resulting from advances in technology. The details of the core protocol and how it was varied to take account of differing situations at each of the sites are provided. The study will enrol up to 1800 patients and will complete in mid-2021. CONCLUSIONS: This paper provides details of what challenges were faced during its development and discusses the issues and how they were resolved. In particular, the reasons for inclusion of new technology and the problems encountered with the supply of drugs for the studies are described in detail. By making these details available, it is hoped that the study protocol will help others interested in improving treatment for filarial lymphoedema in the design of future studies. Trial registration India: Clintrials.gov. NCT02929121 registered 10 Oct 2016: https://clinicaltrials.gov/ct2/show/NCT02929121 Mali: Clintrials.gov. NCT02927496 registered 7 Oct 2016: https://clinicaltrials.gov/ct2/show/NCT0292749 Sri Lanka: Clintrials.gov. NCT02929134 registered 10 Oct 2016: https://clinicaltrials.gov/ct2/show/NCT02929134 Ghana: ISRCTN. 14042737 registered 10 July 2017: https://doi.org/10.1186/ISRCTN14042737 Tanzania: ISRCTN. 65756724 registered 21 July 2017: https://doi.org/10.1186/ISRCTN65756724 Cameroon: ISRCTN. 1181662 registered 25 July 2017: https://doi.org/10.1186/ISRCTN11881662

Modelling the spread of American foulbrood in honeybees

We investigate the spread of American foulbrood (AFB), a disease caused by the bacterium Paenibacillus larvae, that affects bees and can be extremely damaging to beehives. Our dataset comes from an inspection period carried out during an AFB epidemic of honeybee colonies on the island of Jersey during the summer of 2010. The data include the number of hives of honeybees, location and owner of honeybee apiaries across the island. We use a spatial SIR model with an underlying owner network to simulate the epidemic and characterize the epidemic using a Markov chain Monte Carlo (MCMC) scheme to determine model parameters and infection times (including undetected ‘occult’ infections). Likely methods of infection spread can be inferred from the analysis, with both distance- and owner-based transmissions being found to contribute to the spread of AFB. The results of the MCMC are corroborated by simulating the epidemic using a stochastic SIR model, resulting in aggregate levels of infection that are comparable to the data. We use this stochastic SIR model to simulate the impact of different control strategies on controlling the epidemic. It is found that earlier inspections result in smaller epidemics and a higher likelihood of AFB extinction

Brown adipose tissue activation as measured by infrared thermography by mild anticipatory psychological stress in lean healthy females

Brown adipose tissue (BAT) has been implicated in the pathogenesis of obesity, type 2 diabetes and the metabolic syndrome and is a potential therapeutic target. Brown adipose tissue can have a significant impact on energy balance and glucose homeostasis through the action of uncoupling protein 1, dissipating chemical energy as heat following neuroendocrine stimulation. We hypothesized that psychological stress, which is known to promote cortisol secretion, would simultaneously activate BAT at thermoneutrality. Brown adipose tissue activity was measured using infrared thermography to determine changes in the temperature of the skin overlying supraclavicular BAT (TSCR). A mild psychological stress was induced in five healthy, lean, female, Caucasian volunteers using a short mental arithmetic (MA) test. The TSCR was compared with a repeated assessment, in which the MA test was replaced with a period of relaxation. Although MA did not elicit an acute stress response, anticipation of MA testing led to an increase in salivary cortisol, indicative of an anticipatory stress response, that was associated with a trend towards higher absolute and relative TSCR. A positive correlation between TSCR and cortisol was found during the anticipatory phase, a relationship that was enhanced by increased cortisol linked to MA. Our findings suggest that subtle changes in the level of psychological stress can stimulate BAT, findings that may account for the high variability and inconsistency in reported BAT prevalence and activity measured by other modalities. Consistent assessment of this uniquely metabolic tissue is fundamental to the discovery of potential therapeutic strategies against metabolic disease