Cause-specific mortality of children younger than 5 years in communities receiving biannual mass azithromycin treatment in Niger: verbal autopsy results from a cluster-randomised controlled trial.

BACKGROUND: The Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) trial found that biannual mass distribution of azithromycin to children younger than 5 years in Niger reduced the primary outcome of all-cause mortality by 18%. We aimed to determine the causes of mortality among deceased children using verbal autopsy. METHODS: In this 2-year cluster-randomised controlled trial, 594 community clusters in Niger were randomly allocated (1:1 ratio) to receive biannual mass distributions of either oral azithromycin (approximately 20 mg per kg of bodyweight) or placebo targeted to children aged 1-59 months. Participants, study investigators, and field workers were masked to treatment allocation. Between Nov 23, 2014, and July 31, 2017, 3615 child deaths were recorded by use of biannual house-to-house censuses, and verbal autopsies were done between May 26, 2015, and May 17, 2018, to identify cause of death. Cause-specific mortality, as assessed by verbal autopsy, was a prespecified secondary outcome. This trial is completed and is registered with ClinicalTrials.gov, NCT02047981. FINDINGS: Between Nov 23, 2014, and July 31, 2017, 303 communities (n=40 375 children at baseline) in Niger received mass azithromycin and 291 communities (n=35 747 children at baseline) received placebo. Treatment coverage was 90·3% (SD 10·6) in the azithromycin group and 90·4% (10·1) in the placebo group. No communities were lost to follow-up. In total, 1727 child deaths in the azithromycin group and 1888 child deaths in the placebo group were reported from the population censuses. Of these, the cause of death for 1566 (90·7%) children in the azithromycin group and 1735 (91·9%) children in the placebo group were ascertained by verbal autopsy interviews. In the azithromycin group, 437 (27·9%) deaths were due to malaria, 252 (16·1%) deaths were due to pneumonia, and 234 (14·9%) deaths were due to diarrhoea. In the placebo group, 493 (28·4%) deaths were due to malaria, 275 (15·9%) deaths were due to pneumonia, and 251 (14·5%) deaths were due to diarrhoea. Relative to communities that received placebo, child mortality in communities that received azithromycin was lower for malaria (incidence rate ratio 0·78, 95% CI 0·66-0·92; p=0·0029), dysentery (0·65, 0·44-0·94; p=0·025), meningitis (0·67, 0·46-0·97; p=0·036), and pneumonia (0·83, 0·68-1·00; p=0·051). The distribution of causes of death did not differ significantly between the two study groups (p=0·98). INTERPRETATION: Mass azithromycin distribution resulted in approximately a third fewer deaths in children aged 1-59 months due to meningitis and dysentery, and a fifth fewer deaths due to malaria and pneumonia. The lack of difference in the distribution of causes of death between the azithromycin and placebo groups could be attributable to the broad spectrum of azithromycin activity and the study setting, in which most childhood deaths were due to infections. FUNDING: Bill & Melinda Gates Foundation

Superconducting single photon detectors integrated with diamond nanophotonic circuits

Photonic quantum technologies promise to repeat the success of integrated nanophotonic circuits in non-classical applications. Using linear optical elements, quantum optical computations can be performed with integrated optical circuits and thus allow for overcoming existing limitations in terms of scalability. Besides passive optical devices for realizing photonic quantum gates, active elements such as single photon sources and single photon detectors are essential ingredients for future optical quantum circuits. Material systems which allow for the monolithic integration of all components are particularly attractive, including III-V semiconductors, silicon and also diamond. Here we demonstrate nanophotonic integrated circuits made from high quality polycrystalline diamond thin films in combination with on-chip single photon detectors. Using superconducting nanowires coupled evanescently to travelling waves we achieve high detection efficiencies up to 66 % combined with low dark count rates and timing resolution of 190 ps. Our devices are fully scalable and hold promise for functional diamond photonic quantum devices.Comment: 28 pages, 5 figure

Chemical mechanical polishing of thin film diamond

The demonstration that Nanocrystalline Diamond (NCD) can retain the superior Young's modulus (1100 GPa) of single crystal diamond twinned with its ability to be grown at low temperatures (<450 C) has driven a revival into the growth and applications of NCD thin films. However, owing to the competitive growth of crystals the resulting film has a roughness that evolves with film thickness, preventing NCD films from reaching their full potential in devices where a smooth film is required. To reduce this roughness, films have been polished using Chemical Mechanical Polishing (CMP). A Logitech Tribo CMP tool equipped with a polyurethane/polyester polishing cloth and an alkaline colloidal silica polishing fluid has been used to polish NCD films. The resulting films have been characterised with Atomic Force Microscopy, Scanning Electron Microscopy and X-ray Photoelectron Spectroscopy. Root mean square roughness values have been reduced from 18.3 nm to 1.7 nm over 25 μm2, with roughness values as low as 0.42 nm over ∼0.25 μm2. A polishing mechanism of wet oxidation of the surface, attachment of silica particles and subsequent shearing away of carbon has also been proposed. © 2013 Elsevier Ltd. All rights reserved

Surface zeta potential and diamond seeding on gallium nitride films

With the high breakdown voltage and current handling ability of GaN, AlGaN/GaN on SiC HEMT structures are the current benchmark for high-power, high-frequency applications[1]. However, in such devices the GaN epilayer and particularly the SiC substrate, with thermal conductivity of around 400 W/mK, limit the heat extraction leading to de-rating of the maximum power dissipation[2]. Through replacement of the substrate and capping of the transistor channel with diamond of thermal conductivity of up to 2000 W/mK, large decreases in the thermal resistance should therefore be achievable allowing full utilisation of the properties of GaN based devices[3]. The growth of pinhole free, thin film diamond on non-diamond substrates requires the use of a nucleation enhancement step. One of the most commonly used techniques involves seeding the substrate with nanodiamond particles, resulting in high nucleation densities of the order of 1011 cm-2[4]. As attachment of the particle to the substrate is dependent on both the zeta potential of the surface and the particles, it is essential to measure the zeta potential of the surface and tailor the surface groups of the seeds to reach such nucleation densities. In the present study we have measured the surface zeta potential of the GaN surface. Using such knowledge, diamond films have been successfully grown atop GaN on sapphire wafers, without the addition of a thermally resistant intermediate dielectric layer to aid growth as used within previous studies[1]. Films were grown at 850 °C, under 5% methane admixture (CH4/H2) conditions to a thickness of ~150 nm, as judged by in-situ laser interferometry. SEM characterization of the resulting samples revealed continuous films over the 15 by 15 mm samples, free of pinholes, and highly crystalline. The dataset contains 7 files. The txt file is the raw data for pH vs zeta potential for both faces of GaN ( Ga- and N- face). The AFM dataset is in a folder named AFM and the data for each sample namely, Ga-face unseeded, N- face unseeded, G-face seeded with H-terminated diamond, N-face seeded with H-terminated diamond, Ga-face seeded with O-terminated diamond and N-face seeded with O-terminated diamond are in their respective folders. Any AFM analyesis software like WSXM can be used to open and analyse the data. References 1. J. W. Pomeroy, M. Bernardoni, D. C. Dumka, D. M. Fanning and M. Kuball, Applied Physics Letters 104 (8), 083513 (2014). 2. J. Pomeroy, M. Bernardoni, A. Sarua, A. Manoi, D. C. Dumka, D. M. Fanning and M. Kuball, presented at the 2013 IEEE Compound Semiconductor Integrated Circuit Symposium (CSICS), 2013 (unpublished). 3. O. A. Williams, Diamond and Related Materials 20 (5-6), 621-640 (2011). Oliver A. Williams, Olivier Douhéret, Michael Daenen, Ken Haenen, Eiji Ōsawa, Makoto Takahashi, Chemical Physics Letters 445, 255 (2007

Longer-Term Assessment of Azithromycin for Reducing Childhood Mortality in Africa

BackgroundThe MORDOR I trial (Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance) showed that in Niger, mass administration of azithromycin twice a year for 2 years resulted in 18% lower postneonatal childhood mortality than administration of placebo. Whether this benefit could increase with each administration or wane owing to antibiotic resistance was unknown.MethodsIn the Niger component of the MORDOR I trial, we randomly assigned 594 communities to four twice-yearly distributions of either azithromycin or placebo to children 1 to 59 months of age. In MORDOR II, all these communities received two additional open-label azithromycin distributions. All-cause mortality was assessed twice yearly by census workers who were unaware of participants' original assignments.ResultsIn the MORDOR II trial, the mean (±SD) azithromycin coverage was 91.3±7.2% in the communities that received twice-yearly azithromycin for the first time (i.e., had received placebo for 2 years in MORDOR I) and 92.0±6.6% in communities that received azithromycin for the third year (i.e., had received azithromycin for 2 years in MORDOR I). In MORDOR II, mortality was 24.0 per 1000 person-years (95% confidence interval [CI], 22.1 to 26.3) in communities that had originally received placebo in the first year and 23.3 per 1000 person-years (95% CI, 21.4 to 25.5) in those that had originally received azithromycin in the first year, with no significant difference between groups (P = 0.55). In communities that had originally received placebo, mortality decreased by 13.3% (95% CI, 5.8 to 20.2) when the communities received azithromycin (P = 0.007). In communities that had originally received azithromycin and continued receiving it for an additional year, the difference in mortality between the third year and the first 2 years was not significant (-3.6%; 95% CI, -12.3 to 4.5; P = 0.50).ConclusionsWe found no evidence that the effect of mass administration of azithromycin on childhood mortality in Niger waned in the third year of treatment. Childhood mortality decreased when communities that had originally received placebo received azithromycin. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT02047981.)