Contributors to the June Issue/Notes

Notes by Henry S. Romano, William C. Malone, Joseph F. Rudd, Leonard D. Bodkin, James D. Sullivan, Robert J. Callahan, Jr., William Meehan, Alphonse Spahn, Robert E. Sullivan, John F. Power, Francis J. Paulson, John Merryman, J. Barrett Guthrie, Robert T. Fanning, Robert T. Stewart, and R. L. Miller

Contributors to the June Issue/Notes

Notes by Henry S. Romano, William C. Malone, Joseph F. Rudd, Leonard D. Bodkin, James D. Sullivan, Robert J. Callahan, Jr., William Meehan, Alphonse Spahn, Robert E. Sullivan, John F. Power, Francis J. Paulson, John Merryman, J. Barrett Guthrie, Robert T. Fanning, Robert T. Stewart, and R. L. Miller

Toward in vivo detection of hydrogen peroxide with ultrasound molecular imaging

We present a new class of ultrasound molecular imaging agents that extend upon the design of micromotors that are designed to move through fluids by catalyzing hydrogen peroxide (H_2O_2) and propelling forward by escaping oxygen microbubbles. Micromotor converters require 62 mm of H_2O_2 to move – 1000-fold higher than is expected in vivo. Here, we aim to prove that ultrasound can detect the expelled microbubbles, to determine the minimum H_2O_2 concentration needed for microbubble detection, explore alternate designs to detect the H_2O_2 produced by activated neutrophils and perform preliminary in vivo testing. Oxygen microbubbles were detected by ultrasound at 2.5 mm H_2O_2. Best results were achieved with a 400–500 nm spherical design with alternating surface coatings of catalase and PSS over a silica core. The lowest detection limit of 10–100 μm was achieved when assays were done in plasma. Using this design, we detected the H2O2 produced by freshly isolated PMA-activated neutrophils allowing their distinction from naïve neutrophils. Finally, we were also able to show that direct injection of these nanospheres into an abscess in vivo enhanced ultrasound signal only when they contained catalase, and only when injected into an abscess, likely because of the elevated levels of H_2O_2 produced by inflammatory mediators

Antimicrobial utilization research and activities in Botswana, the past, present and the future

A number of activities are ongoing to reduce AMR in Botswana by improving antimicrobial utilization across all sectors. However, there is a need to share experiences. With the objective of sharing these, the second one day symposium was held in the University of Botswana in October 2018 involving both private and public hospitals. In Lenmed Bokamoso hospital, ESKAPE organisms were associated with 50-90% of clinical infections; however, there was no correlation between healthcare associated infections (HAIs) and admission swab positivity with ESKAPE or ESBL isolates. Hang times, the time between a prescription and IV administration, were also discussed. At Nyangabwe Hospital, the prevalence of HAIs was 13.54%, 48.9% were laboratory confirmed of which 8.5% were blood stream infections (BSIs). The prevalence of different bacteria causing neonatal BSIs was also investigated. At Princess Marina Hospital, positive cultures were seen in 22.4% of blood cultures with contaminants comprising the majority. Several activities are ongoing in Botswana across sectors as a result of the findings and will be periodically reported to further improve antibiotic utilization

The HANDE-QMC Project: Open-Source Stochastic Quantum Chemistry from the Ground State Up.

Building on the success of Quantum Monte Carlo techniques such as diffusion Monte Carlo, alternative stochastic approaches to solve electronic structure problems have emerged over the past decade. The full configuration interaction quantum Monte Carlo (FCIQMC) method allows one to systematically approach the exact solution of such problems, for cases where very high accuracy is desired. The introduction of FCIQMC has subsequently led to the development of coupled cluster Monte Carlo (CCMC) and density matrix quantum Monte Carlo (DMQMC), allowing stochastic sampling of the coupled cluster wave function and the exact thermal density matrix, respectively. In this Article, we describe the HANDE-QMC code, an open-source implementation of FCIQMC, CCMC and DMQMC, including initiator and semistochastic adaptations. We describe our code and demonstrate its use on three example systems; a molecule (nitric oxide), a model solid (the uniform electron gas), and a real solid (diamond). An illustrative tutorial is also included

Recommendations for selecting drug-drug interactions for clinical decision support

To recommend principles for including drug-drug interactions (DDIs) in clinical decision support

Comparison of artemether-lumefantrine and chloroquine with and without primaquine for the treatment of Plasmodium vivax infection in Ethiopia: A randomized controlled trial

Background: Recent efforts in malaria control have resulted in great gains in reducing the burden of Plasmodium falciparum, but P. vivax has been more refractory. Its ability to form dormant liver stages confounds control and elimination efforts. To compare the efficacy and safety of primaquine regimens for radical cure, we undertook a randomized controlled trial in Ethiopia. Methods and findings: Patients with normal glucose-6-phosphate dehydrogenase status with symptomatic P. vivax mono-infection were enrolled and randomly assigned to receive either chloroquine (CQ) or artemether-lumefantrine (AL), alone or in combination with 14 d of semi-supervised primaquine (PQ) (3.5 mg/kg total). A total of 398 patients (n = 104 in the CQ arm, n = 100 in the AL arm, n = 102 in the CQ+PQ arm, and n = 92 in the AL+PQ arm) were followed for 1 y, and recurrent episodes were treated with the same treatment allocated at enrolment. The primary endpoints were the risk of P. vivax recurrence at day 28 and at day 42. The risk of recurrent P. vivax infection at day 28 was 4.0% (95% CI 1.5%–10.4%) after CQ treatment and 0% (95% CI 0%–4.0%) after CQ+PQ. The corresponding risks were 12.0% (95% CI 6.8%–20.6%) following AL alone and 2.3% (95% CI 0.6%–9.0%) following AL+PQ. On day 42, the risk was 18.7% (95% CI 12.2%–28.0%) after CQ, 1.2% (95% CI 0.2%–8.0%) after CQ+PQ, 29.9% (95% CI 21.6%–40.5%) after AL, and 5.9% (95% CI 2.4%–13.5%) after AL+PQ (overall p < 0.001). In those not prescribed PQ, the risk of recurrence by day 42 appeared greater following AL treatment than CQ treatment (HR = 1.8 [95% CI 1.0–3.2]; p = 0.059). At the end of follow-up, the incidence rate of P. vivax was 2.2 episodes/person-year for patients treated with CQ compared to 0.4 for patients treated with CQ+PQ (rate ratio: 5.1 [95% CI 2.9–9.1]; p < 0.001) and 2.3 episodes/person-year for AL compared to 0.5 for AL+PQ (rate ratio: 6.4 [95% CI 3.6–11.3]; p < 0.001). There was no difference in the occurrence of adverse events between treatment arms. The main limitations of the study were the early termination of the trial and the omission of haemoglobin measurement after day 42, resulting in an inability to estimate the cumulative risk of anaemia. Conclusions: Despite evidence of CQ-resistant P. vivax, the risk of recurrence in this study was greater following treatment with AL unless it was combined with a supervised course of PQ. PQ combined with either CQ or AL was well tolerated and reduced recurrence of vivax malaria by 5-fold at 1 y

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal