Uniting mathematics and biology for control of visceral leishmaniasis

The neglected tropical disease (NTD) visceral leishmaniasis (VL) has been targeted by the WHO for elimination as a public health problem on the Indian subcontinent by 2017 or earlier. To date there is a surprising scarcity of mathematical models capable of capturing VL disease dynamics, which are widely considered central to planning and assessing the efficacy of interventions. The few models that have been developed are examined, highlighting the necessity for better data to parameterise and fit these and future models. In particular, the characterisation and infectiousness of the different disease stages will be crucial to elimination. Modelling can then assist in establishing whether, when, and how the WHO VL elimination targets can be met

Experimental study into the behaviour of profiled composite walls under combined axial and thermal loadings

Profiled composite walls (PCWs) are regularly used in construction because they provide enhanced ductility, shear resistance and damage tolerance when compared to traditional reinforced concrete walls. Although much research has been conducted to understand the structural performance of PCWs at ambient temperature, studies into their performance at high temperatures remain limited. In this work, a comprehensive set of experiments has been conducted to investigate the performance of PCWs at both ambient and elevated temperatures. A heat source comprising of radiant burners and 1MN MTS machine were employed to deliver known and actively controlled thermal and structural boundary conditions on the PCW samples. The experiments were conducted to understand the effects of an incident heat flux when combined with loads. The results from this study have shown that (i) the axial load capacity of PCWs decreases as the temperature increases; (ii) the PCWs tends to exhibit ductile failure modes when cold but brittle failure at high temperature; (iii) due to thermal bowing, the failure plane of the PCWs subjected to one-side heating shifts closer to the heating source; and (iv) applying a load in an eccentric manner can compensate for the effect of temperature gradient

Iron Oxide Nanoparticles: Tunable Size Synthesis and Analysis in Terms of the Core–Shell Structure and Mixed Coercive Model

Iron oxide nanoparticles (NPs) are currently a very active research field. To date, a comprehensive study of iron oxide NPs is still lacking not only on the size dependence of structural phases but also in the use of an appropriate model. Herein, we report on a systematic study of the structural and magnetic properties of iron oxide NPs prepared by a co-precipitation method followed by hydrothermal treatment. X-ray diffraction and transmission electron microscopy reveal that the NPs have an inverse spinel structure of iron oxide phase (Fe3O4) with average crystallite sizes (DXRD) of 6–19 nm, while grain sizes (DTEM) are of 7–23 nm. In addition, the larger the particle size, the closer the experimental lattice constant value is to that of the magnetite structure. Magnetic field-dependent magnetization data and analysis show that the effective anisotropy constants of the Fe3O4 NPs are about five times larger than that of their bulk counterpart. Particle size (D) dependence of the magnetization and the non-saturating behavior observed in applied fields up to 50 kOe are discussed using the core–shell structure model. We find that with decreasing D, while the calculated thickness of the shell of disordered spins (t ∼ 0.3 nm) remains almost unchanged, the specific surface areas Sa increases significantly, thus reducing the magnetization of the NPs. We also probe the coercivity of the NPs by using the mixed coercive Kneller and Luborsky model. The calculated results indicate that the coercivity rises monotonously with the particle size, and are well matched with the experimental ones

Variations in visceral leishmaniasis burden, mortality and the pathway to care within Bihar, India

BACKGROUND: Visceral leishmaniasis (VL) has been targeted by the WHO for elimination as a public health problem (< 1 case/10,000 people/year) in the Indian sub-continent (ISC) by 2020. Bihar State in India, which accounts for the majority of cases in the ISC, remains a major target for this elimination effort. However, there is considerable spatial, temporal and sub-population variation in occurrence of the disease and the pathway to care, which is largely unexplored and a threat to achieving the target. METHODS: Data from 6081 suspected VL patients who reported being clinically diagnosed during 2012-2013 across eight districts in Bihar were analysed. Graphical comparisons and Chi-square tests were used to determine differences in the burden of identified cases by season, district, age and sex. Log-linear regression models were fitted to onset (of symptoms)-to-diagnosis and onset-to-treatment waiting times to estimate their associations with age, sex, district and various socio-economic factors (SEFs). Logistic regression models were used to identify factors associated with mortality. RESULTS: Comparisons of VL caseloads suggested an annual cycle peaking in January-March. A 17-fold variation in the burden of identified cases across districts and under-representation of young children (0-5 years) relative to age-specific populations in Bihar were observed. Women accounted for a significantly lower proportion of the reported cases than men (41 vs 59%, P < 0.0001). Age, district of residence, house wall materials, caste, treatment cost, travelling for diagnosis and the number of treatments for symptoms before diagnosis were identified as correlates of waiting times. Mortality was associated with age, district of residence, onset-to-treatment waiting time, treatment duration, cattle ownership and cost of diagnosis. CONCLUSIONS: The distribution of VL in Bihar is highly heterogeneous, and reported caseloads and associated mortality vary significantly across different districts, posing different challenges to the elimination campaign. Socio-economic factors are important correlates of these differences, suggesting that elimination will require tailoring to population and sub-population circumstances

Processes at the margins of supraglacial debris cover:Quantifying dirty ice ablation and debris redistribution

Current glacier ablation models have difficulty simulating the high‐melt transition zone between clean and debris‐covered ice. In this zone, thin debris cover is thought to increase ablation compared to clean ice, but often this cover is patchy rather than continuous. There is a need to understand ablation and debris dynamics in this transition zone to improve the accuracy of ablation models and the predictions of future debris cover extent. To quantify the ablation of partially debris‐covered ice (or ‘dirty ice’), a high‐resolution, spatially‐continuous ablation map was created from repeat unmanned aerial systems (UAS) surveys, corrected for glacier flow in a novel way using on‐glacier ablation stakes. Surprisingly, ablation is similar (range ~5 mm w.e. per day) across a wide range of percentage debris covers (~30‐80%) due to the opposing effects of a positive correlation between percentage debris cover and clast size, countered by a negative correlation with albedo. Once debris cover becomes continuous, ablation is significantly reduced (by 61.6% compared to a partial debris cover), and there is some evidence that the cleanest ice (<~15% debris cover) has a lower ablation than dirty ice (by 3.7%). High‐resolution feature tracking of clast movement revealed a strong modal clast velocity where debris was continuous, indicating that debris moves by creep down moraine slopes, in turn promoting debris cover growth at the slope toe. However, not all slope margins gain debris due to the removal of clasts by supraglacial streams. Clast velocities in the dirty ice area were twice as fast than clasts within the continuously debris‐covered area, as clasts moved by sliding off their boulder tables. These new quantitative insights into the interplay between debris cover characteristics and ablation can be used to improve the treatment of dirty ice in ablation models, in turn improving estimates of glacial meltwater production

Determination of Clinical Outcome in Mitral Regurgitation With Cardiovascular Magnetic Resonance Quantification

Background—Surgery for severe mitral regurgitation is indicated if symptoms or left ventricular dilation or dysfunction occur. However, prognosis is already reduced by this stage, and earlier surgery on asymptomatic patients has been advocated if valve repair is likely, but identifying suitable patients for early surgery is difficult. Quantifying the regurgitation may help, but evidence for its link with outcome is limited. Cardiovascular magnetic resonance (CMR) can accurately quantify mitral regurgitation, and we examined whether this was associated with the future need for surgery. Methods and Results—One hundred nine asymptomatic patients with echocardiographic moderate or severe mitral regurgitation had baseline CMR scans and were followed up for up to 8 years (mean, 2.5±1.9 years). CMR quantification accurately identified patients who progressed to symptoms or other indications for surgery: 91% of subjects with regurgitant volume ≤55 mL survived to 5 years without surgery compared with only 21% with regurgitant volume >55 mL (P40%. CMR-derived end-diastolic volume index showed a weaker association with outcome (proportions surviving without surgery at 5 years, 90% for left ventricular end-diastolic volume index <100 mL/m2 versus 48% for ≥100 mL/m2) and added little to the discriminatory power of regurgitant fraction/volume alone. Conclusions—CMR quantification of mitral regurgitation was associated with the development of symptoms or other indications for surgery and showed better discriminatory ability than the reference-standard CMR-derived ventricular volumes. CMR may be able to identify appropriate patients for early surgery, with the potential to change clinical practice, although the clinical benefits of early surgery require confirmation in a clinical trial

Connected healthcare: Improving patient care using digital health technologies

Now more than ever, traditional healthcare models are being overhauled with digital technologies of Healthcare 4.0 being increasingly adopted. Worldwide, digital devices are improving every stage of the patient care pathway. For one, sensors are being used to monitor patient metrics 24/7, permitting swift diagnosis and interventions. At the treatment stage, 3D printers are currently being investigated for the concept of personalised medicine by allowing patients access to on-demand, customisable therapeutics. Robots are also being explored for treatment, by empowering precision surgery or targeted drug delivery. Within medical logistics, drones are being leveraged to deliver critical treatments to remote areas, collect samples, and even provide emergency aid. To enable seamless integration within healthcare, the Internet of Things technology is being exploited to form closed-loop systems that remotely communicate with one another. This review outlines the most promising healthcare technologies and devices, their strengths, drawbacks, and scopes for clinical adoption

Temperatures in Pigs During 3 T MRI Temperatures, Heart Rates, and Breathing Rates of Pigs During RF Power Deposition in a 3 T (128 MHz) Body Coil

Exposure to radiofrequency (RF) power deposition during magnetic resonance imaging (MRI) induces elevated body-tissue temperatures and may cause changes in heart and breathing rates, disturbing thermoregulation. Eleven temperature sensors were placed in muscle tissue and one sensor in the rectum (measured in 10 cm depth) of 20 free-breathing anesthetized pigs to verify temperature curves during RF exposure. Tissue temperatures and heart and breathing rates were measured before, during, and after RF exposure. Pigs were placed into a 60-cm diameter whole-body resonator of a 3 T MRI system. Nineteen anesthetized pigs were divided into four RF exposure groups: sham (0 W/kg), low-exposure (2.7 W/kg, mean exposure time 56 min), moderate-exposure (4.8 W/kg, mean exposure time 31 min), and high-exposure (4.4 W/kg, mean exposure time 61 min). One pig was exposed to a whole-body specific absorption rate (wbSAR) of 11.4 W/kg (extreme-exposure). Hotspot temperatures, measured by sensor 2, increased by mean 5.0 ± 0.9°C, min 3.9; max 6.3 (low), 7.0 ± 2.3°C, min 4.6; max 9.9 (moderate), and 9.2 ± 4.4°C, min 6.1, max 17.9 (high) compared with 0.3 ± 0.3°C in the sham-exposure group (min 0.1, max 0.6). Four time-temperature curves were identified: sinusoidal, parabolic, plateau, and linear. These curve shapes did not correlate with RF intensity, rectal temperature, breathing rate, or heart rate. In all pigs, rectal temperatures increased (2.1 ± 0.9°C) during and even after RF exposure, while hotspot temperatures decreased after exposure. When rectal temperature increased by 1°C, hotspot temperature increased up to 42.8°C within 37 min (low-exposure) or up to 43.8°C within 24 min (high-exposure). Global wbSAR did not correlate with maximum hotspot. Bioelectromagnetics. 2021;42:37–50

Cluster randomised trial and development of a sandfly sex pheromone lure to reduce Leishmania infantum infection

Introduction: Vector control tools are needed to combat leishmaniasis. A semi-synthetic version of a Lutzomyia longipalpis aggregation/sex pheromone (9-methlygermacrene-B) has been developed, and shown efficacy to attract sandflies in the lab and to chicken sheds in the field. Here, we present results from a cluster-randomised trial performed in Brazil where we test the efficacy of the pheromone deployed with insecticide, a novel lure-and-kill intervention, to reduce leishmaniasis transmission to the canine reservoir. Aim: Investigate the efficacy of sandfly sex pheromone baited + insecticide treated chicken roosts to reduce transmission of Leishmania infantum among the reservoir population (dogs). Methods: We conducted a cluster-randomised trial across 42 communities in Brazil. Pheromone lures plus insecticide were applied in 14 communities, and outcomes compared to that of 28 other communities that received either a placebo (sham lure + insecticide) or deltamethrin-impregnated collars fitted to dogs. We quantify the primary intervention effects by comparison of the number of uninfected dogs that seroconverted in each arm over the course of the 2-year trial. Results: A reduction in canine incidence is attributed to the pheromone + insecticide intervention, which is consistent across the levels of hierarchical analysis, though the errors are broad. The performance of the pheromone followed similar patterns as the collar arm which significantly reduced seroconversion incidence. Conclusion: These data represent the first trial of a synthetic vector pheromone applied in public health control, and the first cluster-randomised trial of dog collars in Brazil. Both methods show potential for the control of zoonotic visceral leishmaniasis in the Americas; developments of the pheromone lure-and-kill strategy are underway