Accelerated development of malaria monoclonal antibodies

L9LS, a potent and safe antimalarial monoclonal antibody, demonstrated 88% protective efficacy against infection in a phase 1 trial in healthy adults.(1) These promising results are the first of many to usher in a potential new era of malaria prevention

Proton induced K-shell ionization cross sections for a wide range of elements (4 ≤ Z ≤ 92) within ECPSSR theory and updated experimental data

AbstractWithin the individual treatment of the elements from beryllium (4Be) to uranium (92U), the experimental databases are normalized to their corresponding values of the ECPSSR model to deduce the semi-empirical cross sections. These databases rely on the different compilations available in the literature and on the other data extracted from papers published from 1953 till 2010. In the present paper, a fourth order polynomial was used to fit very well the existing normalized database of K-shell ionization cross sections by proton. These procedures generate a new set of parameters for the sake of the quick calculation of the semi-empirical cross sections. A comparison is made between the deduced results and those obtained by using the ECPSSR model where a remarkable discrepancy is observed at low-proton velocity regime especially for the lightest elements

Accelerating towards P. vivax elimination with a novel serological test-and-treat strategy: a modelling case study in Brazil

BACKGROUND: Plasmodium vivax malaria is challenging to control and eliminate. Treatment with radical cure drugs fails to target the hidden asymptomatic and hypnozoite reservoirs in populations. PvSeroTAT, a novel serological test-and-treat intervention using a serological diagnostic to screen hypnozoite carriers for radical cure eligibility and treatment, could accelerate P. vivax elimination. METHODS: Using a previously developed mathematical model of P. vivax transmission adapted to the Brazilian context as a case study for implementation, we evaluate the public health impact of various deployment strategies of PvSeroTAT as a mass campaign. We compare relative reductions in prevalence, cases averted, glucose-6-phosphate dehydrogenase (G6PD) tests, and treatment doses of PvSeroTAT campaigns to strengthened case management alone or mass drug administration (MDA) campaigns across different settings. FINDINGS: Deploying a single round of PvSeroTAT with 80% coverage to treat cases with a high efficacy radical cure regimen with primaquine is predicted to reduce point population prevalence by 22.5% [95% UI: 20.2%-24.8%] in a peri-urban setting with high transmission and by 25.2% [95% UI: 9.6%-42.2%] in an occupational setting with moderate transmission. In the latter example, while a single PvSeroTAT achieves 9.2% less impact on prevalence and averts 300 less cases per 100,000 than a single MDA (25.2% [95% UI: 9.6%-42.2%] point prevalence reduction versus 34.4% [95% UI: 24.9%-44%]), PvSeroTAT requires 4.6 times less radical cure treatments and G6PD tests. Layering strengthened case management and deploying four rounds of PvSeroTAT six months apart is predicted to reduce point prevalence by a mean of 74.1% [95% UI: 61.3%-86.3%] or more in low transmission settings with less than 10 cases per 1000 population. INTERPRETATION: Modelling predicts that mass campaigns with PvSeroTAT are predicted to reduce P. vivax parasite prevalence across a range of transmission settings and require fewer resources than MDA. In combination with strengthened case management, mass campaigns of serological test-and-treat interventions can accelerate towards P. vivax elimination. FUNDING: This project was funded in part by the Bill and Melinda Gates Foundation and the National Health and Medical Research Council

Modelling to inform next-generation medical interventions for malaria prevention and treatment

Global progress against malaria has stagnated and novel medical interventions to prevent malaria are needed to fill gaps in existing tools and improve protection against infection and disease. Candidate selection for next-generation interventions should be supported by the best available evidence. Target product profiles and preferred product characteristics play a key role in setting selection criteria requirements and early endorsement by health authorities. While clinical evidence and expert opinion often inform product development decisions, integrating modelling evidence early and iteratively into this process provides an opportunity to link product characteristics with expected public health outcomes. Population models of malaria transmission can provide a better understanding of which, and at what magnitude, key intervention characteristics drive public health impact, and provide quantitative evidence to support selection of use-cases, transmission settings, and deployment strategies. We describe how modelling evidence can guide and accelerate development of new malaria vaccines, monoclonal antibodies, and chemoprevention

Coincidence Angular Correlation in Electron Impact Single or Double Ionisation of Atoms and Molecules

Experimental results obtained with our multi-parameter multi-coincidence spectrometer are presented for the (e,3e) double ionisation of Ar and (e,2e) single ionisation of small molecules. The (e,3e) measurements are discussed in terms of competition between the two double ionisation processes present under the chosen kinematics, and qualitative conclusions are given. The results for the ionisation of H2 and the outer orbital of N2 are compared with the predictions of the most elaborate available theoretical models for description of the molecular ionisation process. Overall reasonable agreement is observed and tentative interpretations for the discrepancies are discussed

Hafnium to thorium M-shell X-ray production cross sections by proton impact

Theoretical M-shell X-ray production cross sections have been calculated within the ECPSSR model. The semi-empirical cross sections are then deduced by fitting the available experimental data normalized to their corresponding theoretical values for elements with 72 ≤ Z ≤ 90 by proton in the energy range 0.1–4.0 MeV. Also, an analytical formula has been used to calculate the empirical X-ray production cross sections by direct fitting of the same experimental data, which are found to be universal, both for individual and collective fits. On the other hand, based on the individual fitting which gives the reliable cross sections, we attempt to deduce another new empirical cross sections by assuming that the ratio empirical to ECPSSR of the cross sections is roughly the same for all elements. In addition, our results are presented for selected heavy elements, namely 74W, 79Au and 83Bi, being the most extensively studied. Finally, a comparison is made between the different procedures followed here and the experimental data. Keywords: M-shell X-ray production cross sections, ECPSSR theory, Semi-empirical and empirical cross section

New procedure calculation of photon-induced Kβ/Kα intensity ratios for elements 16S to 92U

In this paper, the measured Kβ/Kα intensity ratio values published in the literature from 1980 to 2011 have been reported. The weighted- and unweighted-mean values of the experimental data were fitted by the analytical function to deduce new semiempirical and empirical intensity ratios in the atomic range of 16 ≤ Z ≤ 92. The semi-empirical intensity ratios were then deduced by fitting the experimental data normalized to their corresponding theoretical values and the experimental data were directly fitted to deduce the empirical ones. The results were compared with the other theoretical and experimental values reported in the literature

Investigation of the (e,2e) single ionisation of He and Ar at large energy loss and close to minimum momentum transfer

International audienc

Empirical L Shell Fluorescence Yields for Elements with 40 ≤ Z ≤ 92

Based on the fact that ratio of ionization to X-ray production cross-sections are independent of the excitation energy of projectile for a given target, we have deduced a new values of L shell average fluorescence yield from existing experimental compilation (till 2014) for a wide range of elements (40 ≤ Z ≤ 92) by proton impact (up to 10.0 MeV) of ionization and X-ray production cross-sections which are found to be universal when plotted as a function of the scaled velocity of projectile. The obtained empirical cross-sections are found reliable and then exploited to derive new values of average fluorescence yield. The obtained values are compared with earlier theoretical and experimental results and an agreement is observed for all elements