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

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

Automatic Quantum Error Correction

Criteria are given by which dissipative evolution can transfer populations and coherences between quantum subspaces, without a loss of coherence. This results in a form of quantum error correction that is implemented by the joint evolution of a system and a cold bath. It requires no external intervention and, in principal, no ancilla. An example of a system that protects a qubit against spin-flip errors is proposed. It consists of three spin 1/2 magnetic particles and three modes of a resonator. The qubit is the triple quantum coherence of the spins, and the photons act as ancilla.Comment: 16 pages 12 fig LaTex uses multicol, graphicx expanded version of letter submitted to Phys Rev Let

The BMV experiment : a novel apparatus to study the propagation of light in a transverse magnetic field

In this paper, we describe in detail the BMV (Bir\'efringence Magn\'etique du Vide) experiment, a novel apparatus to study the propagation of light in a transverse magnetic field. It is based on a very high finesse Fabry-Perot cavity and on pulsed magnets specially designed for this purpose. We justify our technical choices and we present the current status and perspectives.Comment: To be published in the European Physical Journal

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

Meltwater produced by wind–albedo interaction stored in an East Antarctic ice shelf

Surface melt and subsequent firn air depletion can ultimately lead to disintegration of Antarctic ice shelves1,2 causing grounded glaciers to accelerate3 and sea level to rise. In the Antarctic Peninsula, foehn winds enhance melting near the grounding line4, which in the recent past has led to the disintegration of the most northerly ice shelves5,6. Here, we provide observational and model evidence that this process also occurs over an East Antarctic ice shelf, where meltwaterinduced firn air depletion is found in the grounding zone. Unlike the Antarctic Peninsula, where foehn events originate from episodic interaction of the circumpolar westerlies with the topography, in coastal East Antarctica high temperatures are caused by persistent katabatic winds originating from the ice sheet’s interior. Katabatic winds warm and mix the air as it flows downward and cause widespread snow erosion, explaining >3 K higher near-surface temperatures in summer and surface melt doubling in the grounding zone compared with its surroundings. Additionally, these winds expose blue ice and firn with lower surface albedo, further enhancing melt. The in situ observation of supraglacial flow and englacial storage of meltwater suggests that ice-shelf grounding zones in East Antarctica, like their Antarctic Peninsula counterparts, are vulnerable to hydrofracturing7

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

Treatment Approaches for MOG-Ab-Associated Demyelination in Children

Purpose of review The purpose of this review is to summarize current understanding regarding the treatment of myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated demyelination in children. Emphasis is placed on the unique obstacles we face when predicting the risk of relapse and the important implications of such challenges when planning treatment protocols. Recent findings MOG-Abs are consistently identified in a range of acquired demyelinating syndromes (ADS) in adults and children with a clinical phenotype distinct of MS and AQP4-Ab neuromyelitis optica spectrum disorder. Although initially thought to be associated with a benign disease, recent reports of children who are treatment-resistant and developed progressive disability over time raise important questions about how children with relapsing MOG-Ab disease should be managed. Summary MOG-Abs are common in children with ADS with both monophasic and relapsing disease courses. Treatment of patients with MOG-Ab-associated demyelination includes management of acute relapses and chronic immunotherapy for those with relapsing disease. Emerging consensus supports distinction of treatment strategies from those typically used for relapsing remitting MS, and several groups debate whether to follow treatment protocols akin to those for AQP4-Ab NMOSD. A key challenge remains predicting the severity of the disease at onset. Collaborative international consensus to derive shared clinical evaluative platforms standardized biological and neuroimaging protocols which can be used clinically, and partnered research programs are required to advance personalized treatment for children with MOG-Ab-associated demyelination

Formation of pedestalled, relict lakes on the McMurdo Ice Shelf, Antarctica

ABSTRACTSurface debris covers much of the western portion of the McMurdo Ice Shelf and has a strong influence on the local surface albedo and energy balance. Differential ablation between debris-covered and debris-free areas creates an unusual heterogeneous surface of topographically low, high-ablation, and topographically raised (‘pedestalled’), low-ablation areas. Analysis of Landsat and MODIS satellite imagery from 1999 to 2018, alongside field observations from the 2016/2017 austral summer, shows that pedestalled relict lakes (‘pedestals’) form when an active surface meltwater lake that develops in the summer, freezes-over in winter, resulting in the lake-bottom debris being masked by a high-albedo, superimposed, ice surface. If this ice surface fails to melt during a subsequent melt season, it experiences reduced surface ablation relative to the surrounding debris-covered areas of the ice shelf. We propose that this differential ablation, and resultant hydrostatic and flexural readjustments of the ice shelf, causes the former supraglacial lake surface to become increasingly pedestalled above the lower topography of the surrounding ice shelf. Consequently, meltwater streams cannot flow onto these pedestalled features, and instead divert around them. We suggest that the development of pedestals has a significant influence on the surface-energy balance, hydrology and flexure of the ice shelf.Ia

Pediatric multiple sclerosis: update on diagnostic criteria, imaging, histopathology and treatment choices

Pediatric multiple sclerosis (MS) represents less than 5% of the MS population, but patients with pediatric-onset disease reach permanent disability at a younger age than adult onset patients. Accurate diagnosis at presentation and optimal long-term treatment is vital to mitigate ongoing neuroinflammation and irreversible neurodegeneration. However, it may be difficult to early differentiate pediatric MS from acute disseminated encephalomyelitis (ADEM) and neuromyelitis optica spectrum disorders (NMOSD) as they often have atypical presentation that differs from that of adult-onset MS. The purpose of this review is to summarize the updated views on diagnostic criteria, imaging, histopathology and treatment choices