Mass campaigns with antimalarial drugs: a modelling comparison of artemether-lumefantrine and DHA-piperaquine with and without primaquine as tools for malaria control and elimination

Antimalarial drugs are a powerful tool for malaria control and elimination. Artemisinin-based combination therapies (ACTs) can reduce transmission when widely distributed in a campaign setting. Modelling mass antimalarial campaigns can elucidate how to most effectively deploy drug-based interventions and quantitatively compare the effects of cure, prophylaxis, and transmission-blocking in suppressing parasite prevalence. A previously established agent-based model that includes innate and adaptive immunity was used to simulate malaria infections and transmission. Pharmacokinetics of artemether, lumefantrine, dihydroartemisinin, piperaquine, and primaquine were modelled with a double-exponential distribution-elimination model including weight-dependent parameters and age-dependent dosing. Drug killing of asexual parasites and gametocytes was calibrated to clinical data. Mass distribution of ACTs and primaquine was simulated with seasonal mosquito dynamics at a range of transmission intensities. A single mass campaign with antimalarial drugs is insufficient to permanently reduce malaria prevalence when transmission is high. Current diagnostics are insufficiently sensitive to accurately identify asymptomatic infections, and mass-screen-and-treat campaigns are much less efficacious than mass drug administrations. Improving campaign coverage leads to decreased prevalence one month after the end of the campaign, while increasing compliance lengthens the duration of protection against reinfection. Use of a long-lasting prophylactic as part of a mass drug administration regimen confers the most benefit under conditions of high transmission and moderately high coverage. Addition of primaquine can reduce prevalence but exerts its largest effect when coupled with a long-lasting prophylactic.Comment: 14 pages, 5 figure

HMC algorithm with multiple time scale integration and mass preconditioning

We describe a new HMC algorithm variant we have recently introduced and extend the published results by preliminary results of a simulation with a pseudo scalar mass value of about 300 MeV. This new run confirms our expectation that simulations with such pseudo scalar mass values become feasible and affordable with our HMC variant. In addition we discuss simulations from hot and cold starts at a pseudo scalar mass value of about 300 MeV, which we performed in order to test for possible meta-stabilities.Comment: 6 pages, Talk presented at Lattice 2005 (machines and algorithms

Mapping Structural Knowledge of Scientific Creationism to Direct Information and Object Structure Design in Planning Textbooks and Educational Materials

A worldview, such as that defined by Institute for Creation Research tenets of scientific creationism, is a cognitive structure or schemata that impacts human information processing and learning. Cognitive research indicates that there is not a physical referent for such structural knowledge in the human brain. But planners and writers of educational materials view structural knowledge or worldview as a useful metaphor for describing how the human brain constructs or structures knowledge. Research indicates that structural knowledge is tied to memory processes, problem solving, learning, and knowledge acquisition. This paper focuses on the use of mapping techniques to plan and design instructional experiences for materials or programs intended to advance learners’ development of structural knowledge (worldview) presented in the Institute for Creation Research tenets for scientific creationism

Learning and Study Strategies as they Relate to Success in an Open-Entry/Open-Exit College Developmental Reading Course

This study examines whether student interviews, students\u27 responses on the Learning and Study Styles Inventory (LASSI), or both, could be useful for sorting students who are likely to succeed from those students who are less likely to succeed in an open-entry/open-exit college reading skills course at a small, rural Michigan community college. The study combined qualitative data in the form of student interviews and quantitative data that consisted of LASSI scores from 41 students. The qualitative part of the study employed a constant comparative method to analyze data from five semi-structured interviews.The quantitative part of the study computed Pearson r correlations for each of LASSI\u27s 10 subscales and the LASSI total score with success in the reading course. ANOVA was used on all scores that correlated at a significance level equal to or below .05 level to determine if results were affected by gender or age. The qualitative part of the study revealed several factors that appear to distinguish course completers from non-completers. Successful completers reported that they were self-disciplined and sought help when needed. Non-completers described themselves as procrastinators who lacked self-discipline and had not sought help. Past experience in a self-paced course and having had a choice of course format also related to success. The quantitative part of the study found that the LASSI total score and seven of the subscale scores correlated at a significance level equal to or below the .05 level. The LASSI total score exhibited the strongest correlation; the subscale scores Motivation, Concentration, Selecting Main Ideas, Time Management, Self-Testing, Test Strategies, and Information Processing also had significant correlations. Recommendations include providing courses in both traditional and open-entry/open-exit formats, allowing for student choice , and screening with the LASSI and/or using careful advising to assure optimal student placement

Optimal population-level infection detection strategies for malaria control and elimination in a spatial model of malaria transmission

Mass campaigns with antimalarial drugs are potentially a powerful tool for local elimination of malaria, yet current diagnostic technologies are insufficiently sensitive to identify all individuals who harbor infections. At the same time, overtreatment of uninfected individuals increases the risk of accelerating emergence of drug resistance and losing community acceptance. Local heterogeneity in transmission intensity may allow campaign strategies that respond to index cases to successfully target subpatent infections while simultaneously limiting overtreatment. While selective targeting of hotspots of transmission has been proposed as a strategy for malaria control, such targeting has not been tested in the context of malaria elimination. Using household locations, demographics, and prevalence data from a survey of four health facility catchment areas in southern Zambia and an agent-based model of malaria transmission and immunity acquisition, a transmission intensity was fit to each household based on neighborhood age-dependent malaria prevalence. A set of individual infection trajectories was constructed for every household in each catchment area, accounting for heterogeneous exposure and immunity. Various campaign strategies (mass drug administration, mass screen and treat, focal mass drug administration, snowball reactive case detection, pooled sampling, and a hypothetical serological diagnostic) were simulated and evaluated for performance at finding infections, minimizing overtreatment, reducing clinical case counts, and interrupting transmission. For malaria control, presumptive treatment leads to substantial overtreatment without additional morbidity reduction under all but the highest transmission conditions. Selective targeting of hotspots with drug campaigns is an ineffective tool for elimination due to limited sensitivity of available field diagnostics

Verifying continuous variable entanglement of intense light pulses

Three different methods have been discussed to verify continuous variable entanglement of intense light beams. We demonstrate all three methods using the same set--up to facilitate the comparison. The non--linearity used to generate entanglement is the Kerr--effect in optical fibres. Due to the brightness of the entangled pulses, standard homodyne detection is not an appropriate tool for the verification. However, we show that by using large asymmetric interferometers on each beam individually, two non-commuting variables can be accessed and the presence of entanglement verified via joint measurements on the two beams. Alternatively, we witness entanglement by combining the two beams on a beam splitter that yields certain linear combinations of quadrature amplitudes which suffice to prove the presence of entanglement.Comment: 11 pages, 7 figures, to appear in Phys. Rev.

Untangling the Recombination Line Emission from HII Regions with Multiple Velocity Components

HII regions are the ionized spheres surrounding high-mass stars. They are ideal targets for tracing Galactic structure because they are predominantly found in spiral arms and have high luminosities at infrared and radio wavelengths. In the Green Bank Telescope HII Region Discovery Survey (GBT HRDS) we found that >30% of first Galactic quadrant HII regions have multiple hydrogen radio recombination line (RRL) velocities, which makes determining their Galactic locations and physical properties impossible. Here we make additional GBT RRL observations to determine the discrete HII region velocity for all 117 multiple-velocity sources within 18deg. < l < 65deg. The multiple-velocity sources are concentrated in the zone 22deg. < l < 32deg., coinciding with the largest regions of massive star formation, which implies that the diffuse emission is caused by leaked ionizing photons. We combine our observations with analyses of the electron temperature, molecular gas, and carbon recombination lines to determine the source velocities for 103 discrete H II regions (88% of the sample). With the source velocities known, we resolve the kinematic distance ambiguity for 47 regions, and thus determine their heliocentric distances.Comment: 44 pages, 5 figures, 16 pages of tables; Accepted by ApJ

Malaria elimination campaigns in the Lake Kariba region of Zambia: a spatial dynamical model

Background As more regions approach malaria elimination, understanding how different interventions interact to reduce transmission becomes critical. The Lake Kariba area of Southern Province, Zambia, is part of a multi-country elimination effort and presents a particular challenge as it is an interconnected region of variable transmission intensities. Methods In 2012-13, six rounds of mass-screen-and-treat drug campaigns were carried out in the Lake Kariba region. A spatial dynamical model of malaria transmission in the Lake Kariba area, with transmission and climate modeled at the village scale, was calibrated to the 2012-13 prevalence survey data, with case management rates, insecticide-treated net usage, and drug campaign coverage informed by surveillance. The model was used to simulate the effect of various interventions implemented in 2014-22 on reducing regional transmission, achieving elimination by 2022, and maintaining elimination through 2028. Findings The model captured the spatio-temporal trends of decline and rebound in malaria prevalence in 2012-13 at the village scale. Simulations predicted that elimination required repeated mass drug administrations coupled with simultaneous increase in net usage. Drug campaigns targeted only at high-burden areas were as successful as campaigns covering the entire region. Interpretation Elimination in the Lake Kariba region is possible through coordinating mass drug campaigns with high-coverage vector control. Targeting regional hotspots is a viable alternative to global campaigns when human migration within an interconnected area is responsible for maintaining transmission in low-burden areas

The overlap operator as a continued fraction

We use a continued fraction expansion of the sign-function in order to obtain a five dimensional formulation of the overlap lattice Dirac operator. Within this formulation the inverse of the overlap operator can be calculated by a single Krylov space method where nested conjugate gradient procedures are avoided. We show that the five dimensional linear system can be made well conditioned using equivalence transformations on the continued fractions. This is of significant importance when dynamical overlap fermions are simulated.Comment: 3 pages, 1 figure, talk presented by U. Wenger at Lattice2001(chiral