New approaches to measuring anthelminthic drug efficacy: parasitological responses of childhood schistosome infections to treatment with praziquantel

By 2020, the global health community aims to control and eliminate human helminthiases, including schistosomiasis in selected African countries, principally by preventive chemotherapy (PCT) through mass drug administration (MDA) of anthelminthics. Quantitative monitoring of anthelminthic responses is crucial for promptly detecting changes in efficacy, potentially indicative of emerging drug resistance. Statistical models offer a powerful means to delineate and compare efficacy among individuals, among groups of individuals and among populations.; We illustrate a variety of statistical frameworks that offer different levels of inference by analysing data from nine previous studies on egg counts collected from African children before and after administration of praziquantel.; We quantify responses to praziquantel as egg reduction rates (ERRs), using different frameworks to estimate ERRs among population strata, as average responses, and within strata, as individual responses. We compare our model-based average ERRs to corresponding model-free estimates, using as reference the World Health Organization (WHO) 90 % threshold of optimal efficacy. We estimate distributions of individual responses and summarize the variation among these responses as the fraction of ERRs falling below the WHO threshold.; Generic models for evaluating responses to anthelminthics deepen our understanding of variation among populations, sub-populations and individuals. We discuss the future application of statistical modelling approaches for monitoring and evaluation of PCT programmes targeting human helminthiases in the context of the WHO 2020 control and elimination goals

The Role of Structural Flexibility in Plasmon Driven Coupling Reactions Kinetic Limitations in the Dimerization of Nitro Benzenes

Abstract The plasmon-driven dimerization of 4-nitrothiophenol (4NTP) to 4-4′-dimercaptoazobenzene (DMAB) is a testbed for understanding bimolecular photoreactions enhanced by nanoscale metals, in particular, regarding the relevance of electron transfer and heat transfer from the metal to the molecule. By adding a methylene group between the thiol bond and the nitrophenyl, structural flexibility is added to the reactant molecule. Time-resolved surface-enhanced Raman-spectroscopy proves that this (4-nitrobenzyl)mercaptan (4NBM) molecule has a larger dimerization rate and dimerization yield than 4NTP and higher selectivity toward dimerization. X-ray photoelectron spectroscopy and density functional theory calculations show that the electron transfer prefers activation of 4NTP over 4NBM. It is concluded that the rate limiting step of this plasmonic reaction is the dimerization step, which is dramatically enhanced by the additional flexibility of the reactant. This study may serve as an example for using nanoscale metals to simultaneously provide charge carriers for bond activation and localized heat for driving bimolecular reaction steps. The molecular structure of reactants can be tuned to control the reaction kinetics

Identifying and evaluating field indicators of urogenital schistosomiasis-related morbidity in preschool-aged children

BACKGROUND:Several studies have been conducted quantifying the impact of schistosome infections on health and development in school-aged children. In contrast, relatively little is known about morbidity levels in preschool-aged children (≤ 5 years) who have been neglected in terms of schistosome research and control. The aim of this study was to compare the utility of available point-of-care (POC) morbidity diagnostic tools in preschool versus primary school-aged children (6-10 years) and determine markers which can be used in the field to identify and quantify Schistosoma haematobium-related morbidity. METHODS/PRINCIPAL FINDINGS:A comparative cross-sectional study was conducted to evaluate the performance of currently available POC morbidity diagnostic tools on Zimbabwean children aged 1-5 years (n=104) and 6-10 years (n=194). Morbidity was determined using the POC diagnostics questionnaire-based reporting of haematuria and dysuria, clinical examination, urinalysis by dipsticks, and urine albumin-to-creatinine ratio (UACR). Attributable fractions were used to quantify the proportion of morbidity attributable to S. haematobium infection. Based on results of attributable fractions, UACR was identified as the most reliable tool for detecting schistosome-related morbidity, followed by dipsticks, visual urine inspection, questionnaires, and lastly clinical examination. The results of urine dipstick attributes showed that proteinuria and microhaematuria accounted for most differences between schistosome egg-positive and negative children (T=-50.1; p<0.001). These observations were consistent in preschool vs. primary school-aged children. CONCLUSIONS/SIGNIFICANCE:Preschool-aged children in endemic areas can be effectively screened for schistosome-related morbidity using the same currently available diagnostic tools applicable to older children. UACR for detecting albuminuria is recommended as the best choice for rapid assessment of morbidity attributed to S. haematobium infection in children in the field. The use of dipstick microhaematuria and proteinuria as additional indicators of schistosome-related morbidity would improve the estimation of disease burden in young children

Ultrafast dynamics in plasmon exciton core shell systems the role of heat

Strong coupling between plasmons and excitons gives rise to new hybrid polariton states with potential applications in various fields. Despite a plethora of research on plasmon exciton systems, their transient behaviour is not yet fully understood. Besides Rabi oscillations in the first few femtoseconds after optical excitation, coupled systems show interesting non linear features on the picosecond time scale. Here, we conclusively show that the source of these features is heat that is generated inside the particles. Until now, this hypothesis was only based on phenomenological arguments. We investigate the role of heat by recording the transient spectra of plasmon exciton core shell nanoparticles with excitation off the polariton resonance. We present analytical simulations that precisely recreate the measurements solely by assuming an initial temperature rise of the electron gas inside the particles. The simulations combine established strategies for describing uncoupled plasmonic particles with a recently published model for static spectra. The simulations are consistent for various excitation powers, confirming that heating of the particles is indeed the root of the changes in the transient signal

Optical Spectra of Plasmon Exciton Core Shell Nanoparticles A Heuristic Quantum Approach

Light matter coupling in plasmonic nanocavities has been widely studied in the past years. Yet, for core shell particles, popular electromagnetic models that use the classical Lorentz oscillator to describe the shell predict extinction spectra with three maxima, if the plasmon and the shell absorption are in resonance. In contrast, experiments exhibit only two peaks, as also expected from simple quantum models of hybrid states. In order to reconcile the convenient and widely used classical electromagnetic description with experimental data, we connect it to the quantum world by conceiving a heuristic quantum model. Our model is based on the permittivity of a two level system in a classical electric field derived from the optical Bloch equations. The light matter coupling is included via the collective vacuum Rabi frequency amp; 937;0. Using our model, we obtain excellent agreement with a series of experimental extinction spectra of particles with various coupling strengths due to a systematic size variation. The suppression of the third maximum, which mainly stems from the absorption in the shell, can be interpreted as a vacuum induced power broadening, which may occur in lossy plasmonic cavities below the strong coupling regim

Signatures of strong coupling on nanoparticles Revealing absorption anticrossing by tuning the dielectric environment

Strongly coupled plasmon-exciton systems offer promising applications in nanooptics. The classification of the coupling regime is currently debated both from experimental and theoretical perspectives. We present a method to unambiguously identify strong coupling in plasmon-exciton core-shell nanoparticles by measuring true absorption spectra of the system. We investigate the coupling of excitons in J-aggregates to the localized surface plasmon polaritons on gold nanospheres and nanorods by fine-tuning the plasmon resonance via layer-by-layer deposition of polyelectrolytes. While both structures show a characteristic anticrossing in extinction and scattering experiments, the careful assessment of the systems' light absorption reveals that strong coupling of the plasmon to the exciton is only present in the nanorod system. In a phenomenological model of two classical coupled oscillators, intermediate coupling strengths split up only the resonance frequency of the light-driven oscillator, while the other one still dissipates energy at its original frequency. Only in the strong-coupling limit, both oscillators split up the frequencies at which they dissipate energy, qualitatively explaining our experimental finding