Search

A search for time-directional coincidences of ultra-high-energy (UHE) photons above 10 EeV with gravitational wave (GW) events from the LIGO/Virgo runs O1 to O3 is conducted with the Pierre Auger Observatory. Due to the distinctive properties of photon interactions and to the background expected from hadronic showers, a subset of the most interesting GW events is selected based on their localization quality and distance. Time periods of 1000 s around and 1 day after the GW events are analyzed. No coincidences are observed. Upper limits on the UHE photon fluence from a GW event are derived that are typically at ∼7 MeV cm ^−2 (time period 1000 s) and ∼35 MeV cm ^−2 (time period 1 day). Due to the proximity of the binary neutron star merger GW170817, the energy of the source transferred into UHE photons above 40 EeV is constrained to be less than 20% of its total GW energy. These are the first limits on UHE photons from GW sources.

Planetary nebula (PN) surveys in systems beyond ∼10 Mpc often find high-excitation, point-like sources with [O iii ] λ 5007 fluxes greater than the apparent bright-end cutoff of the planetary nebula luminosity function (PNLF). Here we identify PN superpositions as one likely cause for the phenomenon and describe the proper procedures for deriving PNLF distances when object blends are a possibility. We apply our technique to two objects: a model Virgo-distance elliptical galaxy observed through a narrowband interference filter, and the Fornax lenticular galaxy NGC 1380 surveyed with the MUSE integral-field unit spectrograph. Our analyses show that even when the most likely distance to a galaxy is unaffected by the possible presence of PN superpositions, the resultant value will still be biased toward too small a distance due to the asymmetrical nature of the error bars. We discuss the future of the PNLF in an era where current ground-based instrumentation can push the technique to distances beyond ∼35 Mpc.

A catalog containing details of the highest-energy cosmic rays recorded through the detection of extensive air showers at the Pierre Auger Observatory is presented with the aim of opening the data to detailed examination. Descriptions of the 100 showers created by the highest-energy particles recorded between 2004 January 1 and 2020 December 31 are given for cosmic rays that have energies in the range 78–166 EeV. Details are also given on a further nine very energetic events that have been used in the calibration procedure adopted to determine the energy of each primary. A sky plot of the arrival directions of the most energetic particles is shown. No interpretations of the data are offered.

Realistic mappings of genes to morphology are inherently multivariate on both sides of the equation. The importance of coordinated gene effects on morphological phenotypes is clear from the intertwining of gene actions in signaling pathways, gene regulatory networks, and developmental processes underlying the development of shape and size. Yet, current approaches tend to focus on identifying and localizing the effects of individual genes and rarely leverage the information content of high-dimensional phenotypes. Here, we explicitly model the joint effects of biologically coherent collections of genes on a multivariate trait – craniofacial shape – in a sample of n = 1145 mice from the Diversity Outbred (DO) experimental line. We use biological process Gene Ontology (GO) annotations to select skeletal and facial development gene sets and solve for the axis of shape variation that maximally covaries with gene set marker variation. We use our process-centered, multivariate genotype-phenotype (process MGP) approach to determine the overall contributions to craniofacial variation of genes involved in relevant processes and how variation in different processes corresponds to multivariate axes of shape variation. Further, we compare the directions of effect in phenotype space of mutations to the primary axis of shape variation associated with broader pathways within which they are thought to function. Finally, we leverage the relationship between mutational and pathway-level effects to predict phenotypic effects beyond craniofacial shape in specific mutants. We also introduce an online application that provides users the means to customize their own process-centered craniofacial shape analyses in the DO. The process-centered approach is generally applicable to any continuously varying phenotype and thus has wide-reaching implications for complex trait genetics.

Introduction: The United States Centers for Disease Control and Prevention (CDC), through U.S. President's Emergency Plan for AIDS Relief (PEPFAR), supports a third of all people receiving HIV care globally. CDC works with local partners to improve methods to find, treat, and prevent HIV and tuberculosis. However, a shortage of trained medical professionals has impeded efforts to control the HIV epidemic in Sub-Saharan Africa and Asia. The Project Extension for Community Healthcare Outcomes (ECHOTM) model expands capacity to manage complex diseases, share knowledge, disseminate best practices, and build communities of practice. This manuscript describes a practical protocol for an evaluation framework and toolkit to assess ECHO implementation.Methods and Analysis: This mixed methods, developmental evaluation design uses an appreciative inquiry approach, and includes a survey, focus group discussion, semi-structured key informant interviews, and readiness assessments. In addition, ECHO session content will be objectively reviewed for accuracy, content validity, delivery, appropriateness, and consistency with current guidelines. Finally, we offer a mechanism to triangulate data sources to assess acceptability and feasibility of the evaluation framework and compendium of monitoring and evaluation tools.Expected impact of the study on public health: This protocol offers a unique approach to engage diverse group of stakeholders using an appreciative inquiry process to co-create a comprehensive evaluation framework and a compendium of assessment tools. This evaluation framework utilizes mixed methods (quantitative and qualitative data collection tools), was pilot tested in Tanzania, and has the potential for contextualized use in other countries who plan to evaluate their Project ECHO implementation.

In this erratum, we clarify the details of the comparison of

In this article, we report on the latest investigations and achievements in proton beam shaping with our laser-driven ion beamline at GSI Helmholtzzentrum für Schwerionenforschung GmbH. This beamline was realized within the framework of the Laser Ion Generation, Handling, and Transport (LIGHT) collaboration to study the combination of laser-driven ion beams with conventional accelerator components. At its current state, the ions are accelerated by the high-power laser PHELIX via target normal sheath acceleration, and two pulsed high-magnetic solenoids are used for energy selection, transport, and transverse focusing. In between the two solenoids, there is a rf cavity that gives the LIGHT beamline the capability to longitudinally manipulate and temporally compress ion bunches to sub-nanosecond durations. To get optimal results, the rf cavity has to be synchronized with the PHELIX laser and therefore a reliable measurement of the temporal ion beam profile is necessary. In the past, these measurements showed unexpected correlations between the temporal beam profile and the phase as well as the electric field strength of the cavity. In this article, we present a numerical simulation of the beam transport through the LIGHT beamline which explains this behavior by a beam filamentation. We also report on our latest experimental campaigns, in which we combined transverse and longitudinal focusing for the first time. This led to proton bunches with a peak intensity of (3.28±0.24)×10^{8} protons/(ns mm^{2}) at a central energy of (7.72±0.14) MeV. The intensity refers to a circle with a diameter of (1.38±0.02) mm that encloses 50% of the protons in the focal spot at the end of the beamline. The temporal bunch width at this position was (742±40) ps (FWHM).

Background: People with schizophrenia are more likely to develop cannabis use disorder (CUD) and experience worse outcomes with use. Yet as cannabis is legalized for medical and recreational use, there is interest in its therapeutic potential.Objectives: To conduct a systematic review summarizing the design and results of controlled trials using defined doses of THC and CBD in schizophrenia.Method: A keyword search of eight online literature databases identified 11 eligible reports.Results: One placebo controlled trial (13 stable patients without CUD) found that intravenous THC increased psychosis and worsened learning/recall. Two reports of a functional magnetic resonance (fMRI) study of smoked or oral THC in 12 abstinent patients with schizophrenia and CUD found no change in symptoms and cognition, and an amelioration of impaired resting state brain function in areas implicated in reward function and the default mode network. One 4 week trial in acutely psychotic inpatients without CUD (mean age 30 y) found 800 mg CBD to be similarly efficacious to amisupride in improving psychosis and cognition. Two 6 week studies of CBD augmentation of antipsychotics in stable outpatients reported mixed results: CBD 600 mg was not more effective than placebo; CBD 1,000 mg reduced symptoms in a sample that did not exclude cannabis use and CUD. A brain fMRI and proton magnetic resonance spectroscopy study of single dose CBD in a sample that did not exclude CUD and cannabis use found that CBD improved symptoms and brain function during a learning/recall task and was associated with increased hippocampal glutamate.Discussion: There is substantial heterogeneity across studies in dose, method of drug delivery, length of treatment, patient age, whether patients with cannabis use/CUD were included or excluded, and whether patients were using antipsychotic medication.Conclusion: There is insufficient evidence for an effect of THC or CBD on symptoms, cognition, and neuroimaging measures of brain function in schizophrenia. At this time, research does not support recommending medical cannabis (THC or CBD) for treating patients with schizophrenia. Further research should examine THC and CBD in schizophrenia with and without comorbid CUD and consider the role of CBD in mitigating symptom exacerbation from THC.

Abstract Background Diabetes mellitus is a chronic disease that impacts an increasing percentage of people each year. Among its comorbidities, diabetics are two to four times more likely to develop cardiovascular diseases. While HbA1c remains the primary diagnostic for diabetics, its ability to predict long-term, health outcomes across diverse demographics, ethnic groups, and at a personalized level are limited. The purpose of this study was to provide a model for precision medicine through the implementation of machine-learning algorithms using multiple cardiac biomarkers as a means for predicting diabetes mellitus development. Methods Right atrial appendages from 50 patients, 30 non-diabetic and 20 type 2 diabetic, were procured from the WVU Ruby Memorial Hospital. Machine-learning was applied to physiological, biochemical, and sequencing data for each patient. Supervised learning implementing SHapley Additive exPlanations (SHAP) allowed binary (no diabetes or type 2 diabetes) and multiple classification (no diabetes, prediabetes, and type 2 diabetes) of the patient cohort with and without the inclusion of HbA1c levels. Findings were validated through Logistic Regression (LR), Linear Discriminant Analysis (LDA), Gaussian Naïve Bayes (NB), Support Vector Machine (SVM), and Classification and Regression Tree (CART) models with tenfold cross validation. Results Total nuclear methylation and hydroxymethylation were highly correlated to diabetic status, with nuclear methylation and mitochondrial electron transport chain (ETC) activities achieving superior testing accuracies in the predictive model (~ 84% testing, binary). Mitochondrial DNA SNPs found in the D-Loop region (SNP-73G, -16126C, and -16362C) were highly associated with diabetes mellitus. The CpG island of transcription factor A, mitochondrial (TFAM) revealed CpG24 (chr10:58385262, P = 0.003) and CpG29 (chr10:58385324, P = 0.001) as markers correlating with diabetic progression. When combining the most predictive factors from each set, total nuclear methylation and CpG24 methylation were the best diagnostic measures in both binary and multiple classification sets. Conclusions Using machine-learning, we were able to identify novel as well as the most relevant biomarkers associated with type 2 diabetes mellitus by integrating physiological, biochemical, and sequencing datasets. Ultimately, this approach may be used as a guideline for future investigations into disease pathogenesis and novel biomarker discovery.

Abstract Measurements of the $$\pi ^\pm $$ π± , $$K^\pm $$ K± , and proton double differential yields emitted from the surface of the 90-$$\hbox {cm}$$ cm -long carbon target (T2K replica) were performed for the incoming $$31\,$$ 31 $$\hbox {GeV}\!/\!c$$ GeV/c protons with the NA61/SHINE spectrometer at the CERN SPS using data collected during 2010 run. The double differential $$\pi ^\pm $$ π± yields were measured with increased precision compared to the previously published NA61/SHINE results, while the $$K^\pm $$ K± and proton yields were obtained for the first time. A strategy for dealing with the dependence of the results on the incoming proton beam profile is proposed. The purpose of these measurements is to reduce significantly the (anti)neutrino flux uncertainty in the T2K long-baseline neutrino experiment by constraining the production of (anti)neutrino ancestors coming from the T2K target.

Examination of speech datasets for detecting dementia, collected via various speech tasks, has revealed links between speech and cognitive abilities. However, the speech dataset available for this research is extremely limited because the collection process of speech and baseline data from patients with dementia in clinical settings is expensive. In this paper, we study the spontaneous speech dataset from a recent ADReSS challenge, a Cookie Theft Picture (CTP) dataset with balanced groups of participants in age, gender, and cognitive status. We explore state-of-the-art deep transfer learning techniques from image, audio, speech, and language domains. We envision that one advantage of transfer learning is to eliminate the design of handcrafted features based on the tasks and datasets. Transfer learning further mitigates the limited dementia-relevant speech data problem by inheriting knowledge from similar but much larger datasets. Specifically, we built a variety of transfer learning models using commonly employed MobileNet (image), YAMNet (audio), Mockingjay (speech), and BERT (text) models. Results indicated that the transfer learning models of text data showed significantly better performance than those of audio data. Performance gains of the text models may be due to the high similarity between the pre-training text dataset and the CTP text dataset. Our multi-modal transfer learning introduced a slight improvement in accuracy, demonstrating that audio and text data provide limited complementary information. Multi-task transfer learning resulted in limited improvements in classification and a negative impact in regression. By analyzing the meaning behind the Alzheimer's disease (AD)/non-AD labels and Mini-Mental State Examination (MMSE) scores, we observed that the inconsistency between labels and scores could limit the performance of the multi-task learning, especially when the outputs of the single-task models are highly consistent with the corresponding labels/scores. In sum, we conducted a large comparative analysis of varying transfer learning models focusing less on model customization but more on pre-trained models and pre-training datasets. We revealed insightful relations among models, data types, and data labels in this research area.

Pediatric obstructive sleep apnea (OSA), a relatively common sleep-related breathing disorder affecting ∼1-5% of children, is often caused by anatomical obstruction and/or collapse of the nasal and/or pharyngeal airways. The resulting sleep disruption and intermittent hypoxia lead to various systemic morbidities. Predicting the development of OSA from craniofacial features alone is currently not possible, and controversy remains as to whether upper-airway obstruction facilitates reduced midfacial growth or vice versa. Currently, there is no rodent model that recapitulates both the development of craniofacial abnormalities and upper-airway obstruction to address these questions. Here, we describe that mice with a neural crest-specific deletion of Bmp7 (Bmp7ncko) present with a shorter, more acute-angled cranial base, midfacial hypoplasia, nasal septum deviation, turbinate swelling and branching defects, and nasal airway obstruction. Interestingly, several of these craniofacial features develop after birth during periods of rapid midfacial growth and precede the development of an upper-airway obstruction. We identified that, in this rodent model, no single feature appeared to predict upper-airway obstruction, but the sum of those features resulted in reduced breathing frequency, apneas and overall reduced oxygen consumption. Metabolomics analysis of serum from peripheral blood identified increased levels of hydroxyproline, a metabolite upregulated under hypoxic conditions. As this model recapitulates many features observed in OSA, it offers unique opportunities for studying how upper-airway obstruction affects breathing physiology and leads to systemic morbidities. This article has an associated First Person interview with the first author of the paper.

Cancer stem cells (CSCs) have been identified in many cancer types including primary head and neck cutaneous squamous cell carcinoma (HNcSCC). This study aimed to identify and characterize CSCs in metastatic HNcSCC (mHNcSCC). Immunohistochemical staining performed on mHNcSCC samples from 15 patients demonstrated expression of the induced pluripotent stem cell (iPSC) markers OCT4, SOX2, NANOG, KLF4, and c-MYC in all 15 samples. In situ hybridization and RT-qPCR performed on four of these mHNcSCC tissue samples confirmed transcript expression of all five iPSC markers. Immunofluorescence staining performed on three of these mHNcSCC samples demonstrated expression of c-MYC on cells within the tumor nests (TNs) and the peri-tumoral stroma (PTS) that also expressed KLF4. OCT4 was expressed on the SOX2+/NANOG+/KLF4+ cells within the TNs, and the SOX2+/NANOG+/KLF4+ cells within the PTS. RT-qPCR demonstrated transcript expression of all five iPSC markers in all three mHNcSCC-derived primary cell lines, except for SOX2 in one cell line. Western blotting showed the presence of SOX2, KLF4, and c-MYC but not OCT4 and NANOG in the three mHNcSCC-derived primary cell lines. All three cell lines formed tumorspheres, at the first passage. We demonstrated an OCT4+/NANOG+/SOX2+/KLF4+/c-MYC+ CSC subpopulation and an OCT4+/NANOG-/SOX2+/KLF4+/c-MYC+ subpopulation within the TNs, and an OCT4+/NANOG+/SOX2+/KLF4+/c-MYC+ subpopulation within the PTS of mHNcSCC.

Investigating the molecular basis for tooth shape variation provides an important glimpse into the evolution of tooth function. We recently showed that loss of mesenchymal BMP7 is sufficient to alter morphology and function of the toothrow. Here we report on the underlying mechanism. Expression of mesenchymal Bmp7 is observed at sites where mineralization is initiated, in tooth cusps of developing molars. Neural crest-specific deletion of Bmp7 (Bmp7ncko) resulted in a complete lack of dentin/enamel formation at birth, the time when mineralization is normally initiated in the upper molars, similar to what was observed in Bmp2ncko mice. Unlike loss of Bmp2, loss of Bmp7 did not affect odontoblast polarization and did not significantly alter the levels of pSmad1/5/8, but almost completely abolished canonical Wnt signaling in (pre)-ameloblasts. Tooth mineralization resumed with a 48-h delay allowing for additional mesenchymal proliferation. Enamel volume was still reduced at P4 and P8, but was comparable in erupted teeth, which were broader and had altered cusp shapes. Tooth eruption was also delayed. Overall, enamel appeared inconspicuous, although some structural changes along with reduced mineral density could be observed. Loss of Bmp7 led to an increase in mesenchymal Bmp6 suggesting an interplay between Bmp6 and Bmp7 in the regulation of mineralization initiation. Our findings show that regulation of the onset of tooth mineralization is a hitherto unsuspected mechanism controlling tooth shape variation. Initiation of tooth mineralization is regulated by a complex epithelial-mesenchymal Bmp/Wnt-signaling network to which Bmp7 contributes. This network is separate and independent of the Bmp2-signaling network regulating odontoblast cell polarization. From an evolutionary perspective, addition of Bmp7 as initiator of tooth mineralization might be akin to an upgrade of an existing computer operating system. While not essential, it provides obviously sufficient advantage warranting its evolutionary incorporation.

Wnt signaling has been implicated as a driver of prostate cancer-related osteoblast differentiation, and previous studies have linked modifications in Wnt function with the induction of tumor metastasis. A unique aspect of prostate cancer bone metastases in mouse models is their relative predilection to the hindlimb (femur) compared to the forelimb (humerus). Comparative gene expression profiling was performed within the humerus and femur from non–tumor-bearing mice to evaluate differences in the microenvironments of these locations. This revealed the relative overexpression of the Wnt signaling inhibitors WIF1 and SOST in the humerus compared to the femur, with increased WNT5A expression in femur bone marrow, suggesting a coordinated upregulation of Wnt signals within the femur compared to the humerus. Conditioned medium (CM) from bone marrow stromal cells (HS-5 cells) was used to mimic the bone marrow microenvironment, which strongly promoted prostate cancer cell invasion (3.3-fold increase in PC3 cells, P

Abstract Elves are a class of transient luminous events, with a radial extent typically greater than 250 km, that occur in the lower ionosphere above strong electrical storms. We report the observation of 1,598 elves, from 2014 to 2016, recorded with unprecedented time resolution (100 ns) using the fluorescence detector (FD) of the Pierre Auger Cosmic‐Ray Observatory. The Auger Observatory is located in the Mendoza province of Argentina with a viewing footprint for elve observations of 3·106 km 2, reaching areas above the Pacific and Atlantic Oceans, as well as the Córdoba region, which is known for severe convective thunderstorms. Primarily designed for ultrahigh energy cosmic‐ray observations, the Auger FD turns out to be very sensitive to the ultraviolet emission in elves. The detector features modified Schmidt optics with large apertures resulting in a field of view that spans the horizon, and year‐round operation on dark nights with low moonlight background, when the local weather is favorable. The measured light profiles of 18% of the elve events have more than one peak, compatible with intracloud activity. Within the 3‐year sample, 72% of the elves correlate with the far‐field radiation measurements of the World Wide Lightning Location Network. The Auger Observatory plans to continue operations until at least 2025, including elve observations and analysis. To the best of our knowledge, this observatory is the only facility on Earth that measures elves with year‐round operation and full horizon coverage.

Over the last three decades corals have declined precipitously in the Florida Keys. Their population decline has prompted restoration effort. Yet, little effort has been invested in understanding the contemporary niche spaces of coral species, which could assist in prioritizing conservation habitats. We sought to predict the probability of occurrence of 23 coral species, including the critically endangered Acropora cervicornis, using observations at 985 sites from 2011-2015. We ran boosted regression trees to evaluate the relationship between the presence of these corals and eight potential environmental predictors: (i) bathymetry (m), (ii) mean of daily sea surface temperature (SST) (°C), (iii) variance of SST (°C), (iv) range of SST (°C), (v) chlorophyll-a concentration (mg m3), (vi) turbidity (m-1), (vii) wave energy (kJ m-2), and (viii) distance from coast (km). The Marquesas and the lower and upper Florida Keys were predicted to support the most suitable habitats for the 23 coral species examined. A. cervicornis had one of the smallest areas of suitable habitat, which was limited to the lower and upper Florida Keys, the Dry Tortugas, and nearshore Broward-Miami reefs. The best environmental predictors of site occupancy of A. cervicornis were SST range (4-5°C) and turbidity (K490 between 0.15-0.25 m-1). Historically A. cervicornis was reported in clear oligotrophic waters, although the present results find the coral species surviving in nearshore turbid conditions. Nearshore, turbid reefs may shade corals during high-temperature events, and therefore nearshore reefs in south Florida may become important refuges for corals as the ocean temperatures continue to increase.

Abstract The ‘KASCADE Cosmic ray Data Centre’ is a web portal (https://kcdc.ikp.kit.edu), where the data of the astroparticle physics experiment KASCADE-Grande are made available for the interested public. The KASCADE experiment was a large-area detector for the measurement of high-energy cosmic rays via the detection of extensive air showers. The multi-detector installations KASCADE and its extension KASCADE-Grande stopped the active data acquisition in 2013 after more than 20 years of data taking. In several updates since our first release in 2013 with KCDC we provide the public measured and reconstructed parameters of more than 433 million air showers. In addition, KCDC provides meta data information and documentation to enable a user outside the community of experts to perform their own data analysis. Simulation data from three different high energy interaction models have been made available as well as a compilation of measured and published spectra from various experiments. In addition, detailed educational examples shall encourage high-school students and early stage researchers to learn about astroparticle physics, cosmic radiation as well as the handling of Big Data and about the sustainable and public provision of scientific data.

Abstract Background Artemisinin-based combinations differ in their impact on gametocyte prevalence and density. This study assessed female and male gametocyte dynamics after treating children with uncomplicated Plasmodium falciparum malaria with either pyronaridine–artesunate (PA) or artemether–lumefantrine (AL). Methods Kenyan children with uncomplicated Plasmodium falciparum malaria were included and randomly assigned to PA or AL treatment. Filter paper blood samples were collected as a source of RNA for quantitative reverse-transcription PCR (qRT-PCR) and nucleic acid sequence based amplification (QT-NASBA) to detect female gametocytes (targeting Pfs25 mRNA). Male gametocytes were detected by qRT-PCR (targeting PfMGET mRNA). Duration of gametocyte carriage, the female and male gametocyte response and the agreement between qRT-PCR and QT-NASBA were determined. Results The mean duration of female gametocyte carriage was significantly longer for PA (4.9 days) than for AL (3.8 days) as estimated by QT-NASBA (P = 0.036), but this difference was less clear when determined by Pfs25 qRT-PCR (4.5 days for PA and 3.7 for AL, P = 0.166). qRT-PCR based female gametocyte prevalence decreased from 100% (75/75) at baseline to 6.06% (4/66) at day 14 in the AL group and from 97.7% (83/85) to 13.9% (11/79) in the PA group. Male gametocyte prevalence decreased from 41.3% (31/75) at baseline to 19.7% (13/66) at day 14 in the AL group and from 35.3% (30/85) to 22.8% (18/79) in the PA group. There was good agreement between Pfs25 qRT-PCR and QT-NASBA female gametocyte prevalence (0.85, 95% CI 0.82–0.87). Conclusions This study indicates that female gametocyte clearance may be slightly faster after AL compared to PA. Male gametocytes showed similar post-treatment clearance between study arms. Future studies should further address potential differences between the post-treatment transmission potential after PA compared to AL. Trial registration This study is registered at clinicaltrials.gov under NCT02411994. Registration date: 8 April 2015. https://clinicaltrials.gov/ct2/show/NCT02411994?term=pyronaridine-artesunate&cond=Malaria&cntry=KE&rank=1

Abstract Background Pyronaridine–artesunate is a novel artemisinin-based combination therapy. The efficacy and safety of pyronaridine–artesunate were compared with artemether–lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in children. Methods This phase III open-label randomized controlled non-inferiority trial was conducted in Western Kenya. Children aged 6 months to ≤ 12 years with a bodyweight > 5 kg and microscopically confirmed P. falciparum malaria were randomly assigned in a 1:1 ratio to orally receive pyronaridine–artesunate or artemether–lumefantrine, dosed according to bodyweight, for 3 days. Results Of 197 participants, 101 received pyronaridine–artesunate and 96 received artemether–lumefantrine. The day-28 adequate clinical and parasitological response in the per-protocol population, PCR-corrected for reinfections, was 98.9% (93/94, 95% CI 94.2–99.8) for pyronaridine–artesunate and 96.4% (81/84, 95% CI 90.0–98.8) for artemether–lumefantrine. Pyronaridine–artesunate was found to be non-inferior to artemether–lumefantrine: the treatment difference was 2.5% (95% CI − 2.8 to 9.0). Adverse events occurred in 41.6% (42/101) and 34.4% (33/96) of patients in the pyronaridine–artesunate group and the artemether–lumefantrine group, respectively. No participants were found to have alanine or aspartate aminotransferase levels > 3 times the upper limit of normal. Conclusions Pyronaridine–artesunate was well tolerated, efficacious and non-inferior to artemether–lumefantrine for the treatment of uncomplicated P. falciparum malaria in Kenyan children. Results are in line with previous reports and inclusion of pyronaridine–artesunate in paediatric malaria treatment programmes should be considered. This study is registered at clinicaltrials.gov under NCT02411994. Registration date: 8 April 2015. https://clinicaltrials.gov/ct2/show/NCT02411994?term=pyronaridine–artesunate&cond=Malaria&cntry=KE&rank=1

Efficient energy transport by laser-driven relativistic electron beams is crucial in many applications including inertial confinement fusion, and particle acceleration. Here the authors demonstrate relativistic electron beam guiding in dense plasma with an externally imposed high magnetic field.