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BACKGROUND: TB preventive treatment (TPT) prevents the development of TB disease in individuals at risk of progression from infection to disease. However, implementation of TPT for children is poor in most high-burden settings. The long duration and pill burden of the 6-month once-daily isoniazid regimen (6H) pose significant barriers to completion. We aimed to understand children’s, caregivers’, and healthcare providers’ experiences of the 12-week once-weekly rifapentine and isoniazid (3HP) regimen using a dispersible tablet formulation in South Africa. METHODS: Serial, in-depth qualitative interviews with 20 child-caregiver dyads, including 5 children living with HIV (CLWH) and 9 healthcare providers across two study sites implementing a pharmacokinetic and safety trial of 3HP, were analysed deductively. RESULTS: Of those with experience using both 3HP and 6H, caregivers and healthcare providers preferred 3HP, and study participants reported that the 3HP formulation was more palatable and easier to prepare and administer. Caregivers and healthcare providers were concerned about optimally integrating 3HP into routine care, primarily due to its once-weekly administration. Children with HIV preferred the once-daily 6H regimen for its ease of use with their daily antiretroviral therapy. CONCLUSIONS: 3HP reduced the administration burden for children and their caregivers. Once weekly, 3HP dosing will require education and adherence support to ensure completion.

BACKGROUND: Chest X-ray (CXR) interpretation is challenging for the diagnosis of paediatric TB. We assessed the performance of a three half-day CXR training module for healthcare workers (HCWs) at low healthcare levels in six high TB incidence countries. METHODS: Within the TB-Speed Decentralization Study, we developed a three half-day training course to identify normal CXR, CXR of good quality and identify six TB-suggestive features. We performed a pre–post training assessment on a pre-defined set of 20 CXR readings. We compared the proportion of correctly interpreted CXRs and the median reading score before and after the training using the McNemar test and a linear mixed model. RESULTS: Of 191 HCWs, 43 (23%) were physicians, 103 (54%) nurses, 18 (9.4%) radiology technicians and 12 (6.3%) other professionals. Of 2,840 CXRs with both assessment, respectively 1,843 (64.9%) and 2,277 (80.2%) were correctly interpreted during pre-training and post-training (P < 0.001). The median reading score improved significantly from 13/20 to 16/20 after the training, after adjusting by country, facility and profession (adjusted β = 3.31, 95% CI 2.44–4.47). CONCLUSION: Despite some limitations of the course assessment that did not include abnormal non-TB suggestive CXR, study findings suggest that a short CXR training course could improve HCWs’ interpretation skills in diagnosing paediatric TB.

BACKGROUND: We evaluated the palatability and acceptability of a 100 mg dispersible and a non-dispersible 250 mg levofloxacin (LVX) tablet formulation in children. METHODS: Perform was a randomised, open-label, cross-over trial of the relative bioavailability of LVX dispersible vs. crushed non-dispersible tablets in children aged

Abstract The North Atlantic Storm Track acts as a conveyor belt for extratropical cyclones that frequently deliver high winds and rainfall to northwest European shelf seas. Storms are primarily considered detrimental to shelf sea stratification due to wind-driven mixing countering thermal buoyancy, but their impact on shelf scale stratification cycles remains poorly understood. Here, we show that storms trigger stratification through enhanced surface buoyancy from rainfall. A multidecadal model confirms that rainfall contributed to triggering seasonal stratification 88% of the time from 1982 to 2015. Stratification could be further modulated by large-scale climate oscillations, such as the Atlantic Multidecadal Variability (AMV), with stratification onset dates being twice as variable during a positive AMV phase than a negative one. Further insights into how changing storm activity will impact shelf seas are discussed beyond the current view of increasing wind-driven mixing, with significant implications for marine productivity and ecosystem function.

Abstract Background The enteral route is commonly utilised to support the nutritional requirements of critically ill patients. However, there is paucity of data guiding clinicians regarding the appropriate method of delivering the prescribed dose. Continuous enteral feeding is commonly used; however, a bolus or intermittent method of administration may provide several advantages such as minimising interruptions. The purpose of this meta-analysis is to compare a continuous versus an intermittent or bolus enteral nutrition administration method. Methods A systematic review and meta-analysis were performed with studies identified from the PubMed, EMBASE, Cochrane Library and Web of Science databases. Studies were included if they compared a continuous with either an intermittent or bolus administration method of enteral nutrition in adult patients admitted to the intensive care unit. Study quality was assessed using the PEDro and Newcastle–Ottawa scoring systems. Review Manager was used for performing the random-effects meta-analysis on the outcomes of mortality, constipation, diarrhoea, increased gastric residuals, pneumonia, and bacterial colonisation. Results A total of 5546 articles were identified, and 133 were included for full text review. Fourteen were included in the final analysis. There was an increased risk of constipation with patients receiving continuous enteral nutrition (relative risk 2.24, 95% confidence interval 1.01–4.97, p = 0.05). No difference was identified in other outcome measures. No appreciable bias was identified. Conclusion The current meta-analysis has not identified any clinically relevant difference in most outcome measures relevant to the care of critically ill patients. However, there is a paucity of high-quality randomised controlled clinical trials to guide this decision. Therefore, clinicians may consider either dosing regimen in the context of the patient’s care requirements.

The continental shelf seas are important at a global scale for ecosystem services. These highly dynamic regions are under a wide range of stresses, and as such future management requires appropriate monitoring measures. A key metric to understanding and predicting future change are the rates of biological production. We present here the use of an autonomous underwater glider with an oxygen (O2) and a wet-chemical microfluidic total oxidised nitrogen (NOx-=NO3-+NO2-) sensor during a spring bloom as part of a 2019 pilot autonomous shelf sea monitoring study. We find exceptionally high rates of net community production using both O2 and NOx- water column inventory changes, corrected for air–sea gas exchange in case of O2. We compare these rates with 2007 and 2008 mooring observations finding similar rates of NOx- consumption. With these complementary methods we determine the O2:N amount ratio of the newly produced organic matter (7.8 ± 0.4) and the overall O2:N ratio for the total water column (5.7 ± 0.4). The former is close to the canonical Redfield O2:N ratio of 8.6 ± 1.0, whereas the latter may be explained by a combination of new organic matter production and preferential remineralisation of more reduced organic matter at a higher O2:N ratio below the euphotic zone.

The availability of multiple gene sequences, and in particular full genome sequence data, for microbial strains has changed how taxonomists delineate subspecies belonging to the Archaea and Bacteria. Well-defined phylogenetic lineages that share higher genome similarity values compared to the widely used species thresholds are often described as subspecies, despite clear evidence of genetic isolation between them. These well-defined lineages, reflecting notable genetic isolation of the core genome represent more recently evolved, unique and sui generis evolutionary units. Because they bear all of the hallmarks of species, most contemporary subspecies likely represent species in their own right. Although there is considerable value in defining intraspecies variation (e.g., pathovar, serovar and symbiovar), the discriminating properties of such units are mostly encoded on accessory subgenomic compartments. We therefore argue that the taxonomic category of subspecies has become irrelevant and propose that its use should be discontinued. This will minimize inconsistencies related to the subjective nature of species-subspecies distinctions. Formal recognition of biologically relevant variation within species based on the accessory genome information will have practical significance in fields such as clinical, industrial and agricultural microbiology.

Abstract Background The presentation of pulmonary tuberculosis (PTB) in young children is often clinically indistinguishable from other common respiratory illnesses, which are frequently infections of viral aetiology. As little is known about the role of viruses in children with PTB, we investigated the prevalence of respiratory viruses in children with suspected PTB at presentation and follow-up. Methods In an observational cohort study, children

Since January 1, 2001, the only acceptable nomenclatural type for species under the International Code of Nomenclature of Prokaryotes (ICNP) has been pure cultures. Here, we argue that this requirement is discordant with the more inclusive nature of nomenclatural types accepted under other codes of nomenclature and posit that the unique rigidity of the ICNP has failed to serve the broad research community and has stifled progress. This case is based on the axiom that many archaea and bacteria are interdependent in nature and therefore difficult, if not impossible, to grow, preserve, and distribute as pure cultures. As such, a large proportion of Earth's biodiversity cannot be named under the current system, which limits our ability to communicate about microbial diversity within and beyond the microbiology research community. Genome sequence data are now encouraged for valid publication of new taxa in microbial systematics journals, and metagenome-assembled genomes and single cell-amplified genomes are being generated rapidly from every biome on Earth. Thus, genome sequences are available for both cultivated and uncultivated microorganisms and can readily serve as a new category of nomenclatural type, allowing for a unified nomenclature for all archaea and bacteria, whether or not they are available as pure cultures. Ideally this would be under a single code of nomenclature but, as we review here, the newly established SeqCode will operate in parallel with the ICNP as a first step toward this goal.

Abstract The Muon Ionization Cooling Experiment (MICE) collaboration seeks to demonstrate the feasibility of ionization cooling, the technique by which it is proposed to cool the muon beam at a future neutrino factory or muon collider. The emittance is measured from an ensemble of muons assembled from those that pass through the experiment. A pure muon ensemble is selected using a particle-identification system that can reject efficiently both pions and electrons. The position and momentum of each muon are measured using a high-precision scintillating-fibre tracker in a 4 T solenoidal magnetic field. This paper presents the techniques used to reconstruct the phase-space distributions in the upstream tracking detector and reports the first particle-by-particle measurement of the emittance of the MICE Muon Beam as a function of muon-beam momentum.

The ability to make measurements of phosphate (PO43–) concentrations at temporal and spatial scales beyond those offered by shipboard observations offers new opportunities for investigations of the marine phosphorus cycle. We here report the first in situ PO43– dataset from an underwater glider (Kongsberg Seaglider) equipped with a PO43– Lab-on-Chip (LoC) analyser. Over 44 days, a 120 km transect was conducted in the northern North Sea during late summer (August and September). Surface depletion of PO43– (

Ionization cooling is the preferred method for producing bright muon beams. This cooling technique requires the operation of normal conducting, radio-frequency (rf) accelerating cavities within the multi-tesla fields of dc solenoid magnets. Under these conditions, cavities exhibit increased susceptibility to rf breakdown, which can damage cooling channel components and imposes limits on channel length and transmission efficiency. We report, for the first time, stable high-vacuum, normal-conducting cavity operation at gradients of 50 MV/m in an external magnetic field of three tesla, through the use of beryllium cavity elements. This eliminates a significant technical risk that has previously been inherent in ionization cooling channel designs.

The capability of accelerating electron bunches at high repetition rate is one of the key performance criteria for all high average power particle accelerator applications. High gradient laser-driven acceleration holds the potential for greatly reducing size and costs of future machines, but typically requires very high peak laser powers. On the other hand, MHz pulse trains of TW-class laser beams are much beyond the state of the art, so that laser recycling and recirculation is a necessary step to bridge that gap. In this experiment we demonstrate for the first time an inverse free electron laser accelerator (IFEL) operating within an active optical cavity showing the ability to laser-accelerate electron bunch trains in burst mode at >20 MHz repetition rate. The experimental setup, synchronization challenges and acceleration results are presented. It is found that careful control of the dispersive properties of the cavity is required in order to sustain high accelerating gradients over many passes in the laser pulse train.

Exchangeable organic carbon (OC) dynamics and CO2 fluxes in the Antarctic Peninsula during austral summer were highly variable, but the region appeared to be a net sink for OC and nearly in balance for CO2. Surface exchangeable dissolved organic carbon (EDOC) measurements had a 43 ± 3 (standard error, hereafter SE) μmol C L−1 overall mean and represented around 66% of surface non-purgeable dissolved organic carbon (DOC) in Antarctic waters, while the mean concentration of the gaseous fraction of organic carbon (GOC H–1) was 46 ± 3 SE μmol C L−1. There was a tendency towards low fugacity of dissolved CO2 (fCO2-w) in waters with high chlorophyll a (Chl a) content and high fCO2-w in areas with high krill densities. However, such relationships were not found for EDOC. The depth profiles of EDOC were also quite variable and occasionally followed Chl a profiles. The diel cycles of EDOC showed two distinct peaks, in the middle of the day and the middle of the short austral dark period, concurrent with solar radiation maxima and krill night migration patterns. However, no evident diel pattern for GOC H–1 or CO2 was observed. The pool of exchangeable OC is an important and active compartment of the carbon budget surrounding the Antarctic Peninsula and adds to previous studies highlighting its importance in the redistribution of carbon in marine environments.

Using layer transfer and wafer bonding followed by epitaxial regrowth, we design, realize, and characterize a novel generation of Germanium-on-Glass (GoG) near-infrared light sensors. In particular, we demonstrate GoG p-n junction photodetectors and GoG solar cells. In terms of performance, GoG junctions compare well with Germanium (Ge) structures on either Ge or Si. The photodiodes show a minimum dark current density of 50 μA/cm2 at 1 V reverse voltage and a maximum sensitivity of 280 mA/W at 1.55 μm and 5 V bias; the solar cells exhibit conversion efficiencies as high as 2.41% and fill factors of 53%, similar to structures grown on crystalline Ge substrates.

Los mapas de distribución son herramientas clave para la gestión medioambiental y los análisis biogeográficos. Pero el éxito en las predicciones de distribución espacial es limitado cuando se dispone de datos imprecisos de la presencia/ausencia. Tanto falsas ausencias como falsas presencias pueden estar relacionadas con desviaciones locales del equilibrio (por ejemplo, extinciones temporales o colonizaciones no exitosas). Además, las falsas ausencias pueden surgir de un esfuerzo de muestreo limitado. Aquí se explora una estrategia analítica para obtener información adicional sobre el patron de presencia/ausencia de una especie diana a partir de la presencia/ausencia de otras especies en la comunidad. La logica es simple: la especie diana debería tener una mayor probabilidad de presencia en un punto si una muestra de este punto es faunísticamente muy similar a las muestras de otros puntos donde la especie ha sido detectada. Por tanto, primeros se modela la presencia/ausencia de la especie diana en función de la similaridad faunística entre puntos. En segundo lugar, los datos observados para la especie diana son reajustados en función de la probabilidad esperada de presencia: las presencias observadas en puntos con probabilidad de presencia muy baja son interpretadas como presencias inestables, y recodificadas como ausencias. De manera similar, las ausencias en puntos con probabilidad de presencia muy elevada son interpretadas como falsas ausencias, y recodificadas como presencias. En el caso experimental estudiado, el procedimiento de recodificación esta basado en los datos de presencia/ausencia de 174 especies, abarcando un abanico taxonómico muy amplio (caracoles terrestres, coleópteros, arañas e isópodos). El mapa de distribución de celdas de 1 km2 del coleóptero endémico Phylan semicostatus es modelado a partir de estos datos. El mapa de distribución es elaborado a partir de cuatro variables medioambientales, usando una estrategia analítica basada en algoritmos genéticos (GARP). Los mapas obtenidos con los datos recodificados parecen ser mas estables y menos susceptibles de fallar en sus predicciones que los mapas elaborados directamente con los datos originales.

Muon beams of low emittance provide the basis for the intense, well-characterized neutrino beams necessary to elucidate the physics of flavor at a neutrino factory and to provide lepton-antilepton collisions at energies of up to several TeV at a muon collider. The international Muon Ionization Cooling Experiment (MICE) aims to demonstrate ionization cooling, the technique by which it is proposed to reduce the phase-space volume occupied by the muon beam at such facilities. In an ionization-cooling channel, the muon beam passes through a material in which it loses energy. The energy lost is then replaced using rf cavities. The combined effect of energy loss and reacceleration is to reduce the transverse emittance of the beam (transverse cooling). A major revision of the scope of the project was carried out over the summer of 2014. The revised experiment can deliver a demonstration of ionization cooling. The design of the cooling demonstration experiment will be described together with its predicted cooling performance.

Low emittance tuning at the Cornell Electron Storage Ring (CESR) test accelerator depends on precision measurement of vertical dispersion and transverse coupling. The CESR beam position monitors (BPMs) consist of four button electrodes, instrumented with electronics that allow acquisition of turn-by-turn data. The response to the beam will vary among the four electrodes due to differences in electronic gain and/or misalignment. This variation in the response of the BPM electrodes will couple real horizontal offset to apparent vertical position, and introduce spurious measurements of coupling and vertical dispersion. To alleviate this systematic effect, a beam based technique to measure the relative response of the four electrodes has been developed. With typical CESR parameters, simulations show that turn-by-turn BPM data can be used to determine electrode gains to within ∼0.1%.

A relatively new technique for measuring the electron cloud density in storage rings has been developed and successfully demonstrated [S. De Santis, J. M. Byrd, F. Caspers, A. Krasnykh, T. Kroyer, M. T. F. Pivi, and K. G. Sonnad, Phys. Rev. Lett. 100, 094801 (2008).PRLTAO0031-900710.1103/PhysRevLett.100.094801]. We present the experimental results of a systematic application of this technique at the Cornell Electron Storage Ring Test Accelerator. The technique is based on the phase modulation of the TE mode transmitted in a synchrotron beam pipe caused by the periodic variation of the density of electron plasma. Because of the relatively simple hardware requirements, this method has become increasingly popular and has been since successfully implemented in several machines. While the principles of this technique are straightforward, quantitative derivation of the electron cloud density from the measurement requires consideration of several effects, which we address in detail.