Paediatric multiple sclerosis and antibody-associated demyelination: clinical, imaging, and biological considerations for diagnosis and care

The field of acquired CNS neuroimmune demyelination in children is transforming. Progress in assay development, refinement of diagnostic criteria, increased biological insights provided by advanced neuroimaging techniques, and high-level evidence for the therapeutic efficacy of biological agents are redefining diagnosis and care. Three distinct neuroimmune conditions-multiple sclerosis, myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder (AQP4-NMOSD)-can now be distinguished, with evidence from humans and animal models supporting distinct pathobiological disease mechanisms. The development of highly effective therapies for adult-onset multiple sclerosis and AQP4-NMOSD that suppress relapse rate by more than 90% has motivated advocacy for trials in children. However, doing clinical trials is challenging because of the rarity of these conditions in the paediatric age group, necessitating new approaches to trial design, including age-based trajectory modelling based on phase 3 studies in adults. Despite these limitations, the future for children and adolescents living with multiple sclerosis, MOGAD, or AQP4-NMOSD is far brighter than in years past, and will be brighter still if successful therapies to promote remyelination, enhance neuroprotection, and remediate cognitive deficits can be further accelerated

Broadband characterisation of in-duct acoustic sources using an equivalent source approach

This paper is concerned with the development of an experimental method capable of independently characterising low Mach number, in-duct fluid machines, such as pumps, fans, etc. The aim is to propose and test a source characterisation method that is suitable for acoustic simulation and the construction Virtual Acoustic Prototypes. Such a requirement demands that the source characterisation be (a) independent, so that components can be virtually (re)combined within different assemblies and (b) valid over a wide frequency range so as to enable the output of a virtual assembly to be auralised. In this regard, standard methods based on sound power are not suitable. An equivalent source approach is proposed, based on a two-stage measurement procedure in which source strengths are obtained by solving an inverse problem. The experimental application of the procedure is illustrated as part of a case study where a high speed compressor unit is independently characterised and the resulting source data used to predict the operational response in a new assembly. Three frequency ranges are identified based on plane wave, modal and statistical behavior within the duct. The same measured data is used within each regime but subject to different processing according to different assumptions. Predictions are shown to be in good agreement with the directly measured response over a broad frequency range (100 Hz–10 kHz)

Rituximab monitoring and redosing in pediatric neuromyelitis optica spectrum disorder.

Abstract OBJECTIVE: To study rituximab in pediatric neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD) and the relationship between rituximab, B cell repopulation, and relapses in order to improve rituximab monitoring and redosing. METHODS: Multicenter retrospective study of 16 children with NMO/NMOSD receiving 652 rituximab courses. According to CD19 counts, events during rituximab were categorized as "repopulation," "depletion," or "depletion failure" relapses (repopulation threshold CD19 6510 7 10(6) cells/L). RESULTS: The 16 patients (14 girls; mean age 9.6 years, range 1.8-15.3) had a mean of 6.1 events (range 1-11) during a mean follow-up of 6.1 years (range 1.6-13.6) and received a total of 76 rituximab courses (mean 4.7, range 2-9) in 42.6-year cohort treatment. Before rituximab, 62.5% had received azathioprine, mycophenolate mofetil, or cyclophosphamide. Mean time from rituximab to last documented B cell depletion and first repopulation was 4.5 and 6.8 months, respectively, with large interpatient variability. Earliest repopulations occurred with the lowest doses. Significant reduction between pre- and post-rituximab annualized relapse rate (ARR) was observed (p = 0.003). During rituximab, 6 patients were relapse-free, although 21 relapses occurred in 10 patients, including 13 "repopulation," 3 "depletion," and 4 "depletion failure" relapses. Of the 13 "repopulation" relapses, 4 had CD19 10-50 7 10(6) cells/L, 10 had inadequate monitoring ( 641 CD19 in the 4 months before relapses), and 5 had delayed redosing after repopulation detection. CONCLUSION: Rituximab is effective in relapse prevention, but B cell repopulation creates a risk of relapse. Redosing before B cell repopulation could reduce the relapse risk further. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that rituximab significantly reduces ARR in pediatric NMO/NMOSD. This study also demonstrates a relationship between B cell repopulation and relapses

(+)-Hexacyclinol

A sample of the title compound [systematic name: (1aS,2aS,3S,5aS,6aS,7R,7aS,7bS,8R,8aS,10R)-7-hydr­oxy-3-(1-meth­oxy-1-methyl­ethyl)-10-(2-methyl-1-propen­yl)-1a,5a,6a,7,7a,7b,8,8a-octa­hydro-2H-8,2a-(epoxy­methano)phenanthro[2,3-b:6,7-b′]bis­oxirene-2,5(3H)-dione], C23H28O7, was generated by enanti­oselective synthesis. There are three mol­ecules of the compound in the crystallographic asymmetric unit. Hydrogen bonding between alcohol H atoms and keto groups of adjacent mol­ecules appears to stabilize the structure. The compound is enanti­omerically pure but the absolute configuration could not be determined directly in this study. Accordingly, the illustrated configuration was assigned on the basis of the nature of the chiral nonracemic precursor used in the synthesis

Podoconiosis and soil-transmitted helminths (STHs): double burden of neglected tropical diseases in Wolaita zone, rural southern Ethiopia

Background Both podoconiosis and soil-transmitted helminth (STH) infections occur among barefoot people in areas of extreme poverty; however, their co-morbidity has not previously been investigated. We explored the overlap of STH infection and podoconiosis in Southern Ethiopia and quantified their separate and combined effects on prevalent anemia and hemoglobin levels in podoconiosis patients and health controls from the same area. Methods and Principal Findings A two-part comparative cross-sectional study was conducted in Wolaita zone, southern Ethiopia. Data were collected from adult patients presenting with clinically confirmed podoconiosis, and unmatched adult neighborhood controls living in the same administrative area. Information on demographic and selected lifestyle factors was collected using interviewer-administered questionnaires. Stool samples were collected and examined qualitatively using the modified formalin-ether sedimentation method. Hemoglobin level was determined using two different methods: hemoglobinometer and automated hematology analyzer. A total of 913 study subjects (677 podoconiosis patients and 236 controls) participated. The prevalence of any STH infection was 47.6% among patients and 33.1% among controls (p<0.001). The prevalence of both hookworm and Trichuris trichiura infections was significantly higher in podoconiosis patients than in controls (AOR 1.74, 95% CI 1.25 to2.42, AOR 6.53, 95% CI 2.34 to 18.22, respectively). Not wearing shoes and being a farmer remained significant independent predictors of infection with any STH. There was a significant interaction between STH infection and podoconiosis on reduction of hemoglobin level (interaction p value = 0.002). Conclusions Prevalence of any STH and hookworm infection was higher among podoconiosis patients than among controls. A significant reduction in hemoglobin level was observed among podoconiosis patients co-infected with hookworm and ‘non-hookworm STH’. Promotion of consistent shoe-wearing practices may have double advantages in controlling both podoconiosis and hookworm infection in the study area

Dual-satellite (Sentinel-2 and Landsat 8) remote sensing of supraglacial lakes in Greenland

Remote sensing is commonly used to monitor supraglacial lakes on the Greenland Ice Sheet (GrIS); however, most satellite records must trade off higher spatial resolution for higher temporal resolution (e.g. MODIS) or vice versa (e.g. Landsat). Here, we overcome this issue by developing and applying a dual-sensor method that can monitor changes to lake areas and volumes at high spatial resolution (10–30&thinsp;m) with a frequent revisit time ( ∼ 3 days). We achieve this by mosaicking imagery from the Landsat 8 Operational Land Imager (OLI) with imagery from the recently launched Sentinel-2 Multispectral Instrument (MSI) for a  ∼ 12&thinsp;000&thinsp;km2 area of West Greenland in the 2016 melt season. First, we validate a physically based method for calculating lake depths with Sentinel-2 by comparing measurements against those derived from the available contemporaneous Landsat 8 imagery; we find close correspondence between the two sets of values (R2 = 0.841; RMSE&thinsp; = &thinsp;0.555&thinsp;m). This provides us with the methodological basis for automatically calculating lake areas, depths, and volumes from all available Landsat 8 and Sentinel-2 images. These automatic methods are incorporated into an algorithm for Fully Automated Supraglacial lake Tracking at Enhanced Resolution (FASTER). The FASTER algorithm produces time series showing lake evolution during the 2016 melt season, including automated rapid ( ≤ 4 day) lake-drainage identification. With the dual Sentinel-2–Landsat 8 record, we identify 184 rapidly draining lakes, many more than identified with either imagery collection alone (93 with Sentinel-2; 66 with Landsat 8), due to their inferior temporal resolution, or would be possible with MODIS, due to its omission of small lakes  &lt; 0.125&thinsp;km2. Finally, we estimate the water volumes drained into the GrIS during rapid-lake-drainage events and, by analysing downscaled regional climate-model (RACMO2.3p2) run-off data, the water quantity that enters the GrIS via the moulins opened by such events. We find that during the lake-drainage events alone, the water drained by small lakes ( &lt; 0.125&thinsp;km2) is only 5.1&thinsp;% of the total water volume drained by all lakes. However, considering the total water volume entering the GrIS after lake drainage, the moulins opened by small lakes deliver 61.5&thinsp;% of the total water volume delivered via the moulins opened by large and small lakes; this is because there are more small lakes, allowing more moulins to open, and because small lakes are found at lower elevations than large lakes, where run-off is higher. These findings suggest that small lakes should be included in future remote-sensing and modelling work.</p

Diagnosis of childhood tuberculosis and host RNA expression in Africa

Improved diagnostic tests for tuberculosis in children are needed. We hypothesized that transcriptional signatures of host blood could be used to distinguish tuberculosis from other diseases in African children who either were or were not infected with the human immunodeficiency virus (HIV

The Antarctic Peninsula Under a 1.5 degrees C Global Warming Scenario

Warming of the Antarctic Peninsula in the latter half of the twentieth century was greater than any other terrestrial environment in the Southern Hemisphere, and clear cryospheric and biological consequences have been observed. Under a global 1.5°C scenario, warming in the Antarctic Peninsula is likely to increase the number of days above 0°C, with up to 130 of such days each year in the northern Peninsula. Ocean turbulence will increase, making the circumpolar deep water (CDW) both warmer and shallower, delivering heat to the sea surface and to coastal margins. Thinning and recession of marine margins of glaciers and ice caps is expected to accelerate to terrestrial limits, increasing iceberg production, after which glacier retreat may slow on land. Ice shelves will experience continued increase in meltwater production and consequent structural change, but not imminent regional collapses. Marine biota can respond in multiple ways to climatic changes, with effects complicated by past resource extraction activities. Southward distribution shifts have been observed in multiple taxa during the last century and these are likely to continue. Exposed (ice free) terrestrial areas will expand, providing new habitats for native and non-native organisms, but with a potential loss of genetic diversity. While native terrestrial biota are likely to benefit from modest warming, the greatest threat to native biodiversity is from non-native terrestrial species

Optoelectronics with electrically tunable PN diodes in a monolayer dichalcogenide

One of the most fundamental devices for electronics and optoelectronics is the PN junction, which provides the functional element of diodes, bipolar transistors, photodetectors, LEDs, and solar cells, among many other devices. In conventional PN junctions, the adjacent p- and n-type regions of a semiconductor are formed by chemical doping. Materials with ambipolar conductance, however, allow for PN junctions to be configured and modified by electrostatic gating. This electrical control enables a single device to have multiple functionalities. Here we report ambipolar monolayer WSe2 devices in which two local gates are used to define a PN junction exclusively within the sheet of WSe2. With these electrically tunable PN junctions, we demonstrate both PN and NP diodes with ideality factors better than 2. Under excitation with light, the diodes show photodetection responsivity of 210 mA/W and photovoltaic power generation with a peak external quantum efficiency of 0.2%, promising numbers for a nearly transparent monolayer sheet in a lateral device geometry. Finally, we demonstrate a light-emitting diode based on monolayer WSe2. These devices provide a fundamental building block for ubiquitous, ultra-thin, flexible, and nearly transparent optoelectronic and electronic applications based on ambipolar dichalcogenide materials.Comment: 14 pages, 4 figure