Epidemiology of neuromyelitis optica spectrum disorder and its prevalence and incidence worldwide

Neuromyelitis optica spectrum disorder (NMOSD) is an uncommon inflammatory disease of the central nervous system, manifesting clinically as optic neuritis, myelitis, and certain brain and brainstem syndromes. Cases clinically diagnosed as NMOSD may include aquaporin 4 (AQP4)-antibody-seropositive autoimmune astrocytopathic disease, myelin oligodendrocyte glycoprotein (MOG)-antibody-seropositive inflammatory demyelinating disease, and double-seronegative disease. AQP4-antibody disease has a high female-to-male ratio (up to 9:1), and its mean age at onset of ~40 years is later than that seen in multiple sclerosis. For MOG-antibody disease, its gender ratio is closer to 1:1, and it is more common in children than in adults. Its clinical phenotypes differ but overlap with those of AQP4-antibody disease and include acute disseminated encephalomyelitis, brainstem and cerebral cortical encephalitis, as well as optic neuritis and myelitis. Double-seronegative disease requires further research and clarification. Population-based studies over the past two decades report the prevalence and incidence of NMOSD in different populations worldwide. One relevant finding is the varying prevalence observed in different racial groups. Consistently, the prevalence of NMOSD among Whites is ~1/100,000 population, with an annual incidence of <1/million population. Among East Asians, the prevalence is higher, at ~3.5/100,000 population, while the prevalence in Blacks may be up to 10/100,000 population. For MOG-antibody disease, hospital-based studies largely do not observe any significant racial preponderance so far. This disorder comprises a significant proportion of NMOSD cases that are AQP4-antibody-seronegative. A recent Dutch nationwide study reported the annual incidence of MOG-antibody disease as 1.6/million population (adult: 1.3/million, children: 3.1/million). Clinical and radiological differences between AQP4-antibody and MOG-antibody associated diseases have led to interest in the revisions of NMOSD definition and expanded stratification based on detection of a specific autoantibody biomarker. More population-based studies in different geographical regions and racial groups will be useful to further inform the prevalence and incidence of NMOSD and their antibody-specific subgroups. Accessibility to AQP4-antibody and MOG-antibody testing, which is limited in many centers, is a challenge to overcome. Environmental and genetic studies will be useful accompaniments to identify other potential pathogenetic factors and specific biomarkers in NMOSD

Projected WIMP sensitivity of the LUX-ZEPLIN dark matter experiment

LUX-ZEPLIN (LZ) is a next-generation dark matter direct detection experiment that will operate 4850 feet underground at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, USA. Using a two-phase xenon detector with an active mass of 7 tonnes, LZ will search primarily for low-energy interactions with weakly interacting massive particles (WIMPs), which are hypothesized to make up the dark matter in our galactic halo. In this paper, the projected WIMP sensitivity of LZ is presented based on the latest background estimates and simulations of the detector. For a 1000 live day run using a 5.6-tonne fiducial mass, LZ is projected to exclude at 90% confidence level spin-independent WIMP-nucleon cross sections above 1.4 × 10-48cm2 for a 40 GeV/c2 mass WIMP. Additionally, a 5σ discovery potential is projected, reaching cross sections below the exclusion limits of recent experiments. For spin-dependent WIMP-neutron(-proton) scattering, a sensitivity of 2.3 × 10−43 cm2 (7.1 × 10−42 cm2) for a 40 GeV/c2 mass WIMP is expected. With underground installation well underway, LZ is on track for commissioning at SURF in 2020

Measurement of the gamma ray background in the Davis Cavern at the Sanford Underground Research Facility

Deep underground environments are ideal for low background searches due to the attenuation of cosmic rays by passage through the earth. However, they are affected by backgrounds from γ-rays emitted by 40K and the 238U and 232Th decay chains in the surrounding rock. The LUX-ZEPLIN (LZ) experiment will search for dark matter particle interactions with a liquid xenon TPC located within the Davis campus at the Sanford Underground Research Facility, Lead, South Dakota, at the 4,850-foot level. In order to characterise the cavern background, in-situ γ-ray measurements were taken with a sodium iodide detector in various locations and with lead shielding. The integral count rates (0--3300~keV) varied from 596~Hz to 1355~Hz for unshielded measurements, corresponding to a total flux in the cavern of 1.9±0.4~γ cm−2s−1. The resulting activity in the walls of the cavern can be characterised as 220±60~Bq/kg of 40K, 29±15~Bq/kg of 238U, and 13±3~Bq/kg of 232Th

Sex ratio and age of onset in AQP4 antibody-associated NMOSD: a review and meta-analysis

BACKGROUND: Aquaporin-4 (AQP4) antibody-associated neuromyelitis optica spectrum disorder (NMOSD) is an antibody-mediated inflammatory disease of the central nervous system. We have undertaken a systematic review and meta-analysis to ascertain the sex ratio and mean age of onset for AQP4 antibody associated NMOSD. We have also explored factors that impact on these demographic data. METHODS: A systematic search of databases was conducted according to the PRISMA guidelines. Articles reporting sex distribution and age of onset for AQP4 antibody-associated NMSOD were reviewed. An initially inclusive approach involving exploration with regression meta-analysis was followed by an analysis of just AQP4 antibody positive cases. RESULTS: A total of 528 articles were screened to yield 89 articles covering 19,415 individuals from 88 population samples. The female:male sex ratio was significantly influenced by the proportion of AQP4 antibody positive cases in the samples studied (p < 0.001). For AQP4 antibody-positive cases the overall estimate of the sex ratio was 8.89 (95% CI 7.78-10.15). For paediatric populations the estimate was 5.68 (95% CI 4.01-8.03) and for late-onset cases, it was 5.48 (95% CI 4.10-7.33). The mean age of onset was significantly associated with the mean life expectancy of the population sampled (p < 0.001). The mean age of onset for AQP4 antibody-positive cases in long-lived populations was 41.7 years versus 33.3 years in the remainder. CONCLUSIONS: The female:male sex ratio and the mean age of onset of AQP4 antibody-associated NMOSD are significantly higher than MS. The sex ratio increases with the proportion of cases that are positive for AQP4 antibodies and the mean age of onset increases with population life expectancy

Diagnosis and classification of optic neuritis

There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals with multiple sclerosis, neuromyelitis optica spectrum disorder, or myelin oligodendrocyte glycoprotein antibody-associated disease. Epidemiological data show that, cumulatively, optic neuritis is most frequently caused by many conditions other than multiple sclerosis. Worldwide, the cause and management of optic neuritis varies with geographical location, treatment availability, and ethnic background. We have developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups. Our diagnostic criteria are based on clinical features that permit a diagnosis of possible optic neuritis; further paraclinical tests, utilising brain, orbital, and retinal imaging, together with antibody and other protein biomarker data, can lead to a diagnosis of definite optic neuritis. Paraclinical tests can also be applied retrospectively on stored samples and historical brain or retinal scans, which will be useful for future validation studies. Our criteria have the potential to reduce the risk of misdiagnosis, provide information on optic neuritis disease course that can guide future treatment trial design, and enable physicians to judge the likelihood of a need for long-term pharmacological management, which might differ according to optic neuritis subgroups

An Ultrahigh-energy γ\gamma-ray Bubble Powered by a Super PeVatron

International audienceWe report the detection of a $\gamma$-ray bubble spanning at least 100$\rm deg^2$ in ultra high energy (UHE) up to a few PeV in the direction of the star-forming region Cygnus X, implying the presence Super PeVatron(s) accelerating protons to at least 10 PeV. A log-parabola form with the photon index $\Gamma (E) = (2.71 \pm 0.02) + (0.11 \pm 0.02) \times \log_{10} (E/10 \ {\rm TeV})$ is found fitting the gamma-ray energy spectrum of the bubble well. UHE sources, `hot spots' correlated with very massive molecular clouds, and a quasi-spherical amorphous $\gamma$-ray emitter with a sharp central brightening are observed in the bubble. In the core of $\sim 0.5^{\circ}$, spatially associating with a region containing massive OB association (Cygnus OB2) and a microquasar (Cygnus X-3), as well as previously reported multi-TeV sources, an enhanced concentration of UHE $\gamma$-rays are observed with 2 photons at energies above 1 PeV. The general feature of the bubble, the morphology and the energy spectrum, are reasonably reproduced by the assumption of a particle accelerator in the core, continuously injecting protons into the ambient medium

LHAASO-KM2A detector simulation using Geant4

International audienceKM2A is one of the main sub-arrays of LHAASO, working on gamma ray astronomy and cosmic ray physics at energies above 10 TeV. Detector simulation is the important foundation for estimating detector performance and data analysis. It is a big challenge to simulate the KM2A detector in the framework of Geant4 due to the need to track numerous photons from a large number of detector units (>6000) with large altitude difference (30 m) and huge coverage (1.3 km^2). In this paper, the design of the KM2A simulation code G4KM2A based on Geant4 is introduced. The process of G4KM2A is optimized mainly in memory consumption to avoid memory overffow. Some simpliffcations are used to signiffcantly speed up the execution of G4KM2A. The running time is reduced by at least 30 times compared to full detector simulation. The particle distributions and the core/angle resolution comparison between simulation and experimental data of the full KM2A array are also presented, which show good agreement

Constraints on Ultra Heavy Dark Matter Properties from Dwarf Spheroidal Galaxies with LHAASO Observations

International audienceIn this work we try to search for signals generated by ultra-heavy dark matter at the Large High Altitude Air Shower Observatory (LHAASO) data. We look for possible gamma-ray by dark matter annihilation or decay from 16 dwarf spheroidal galaxies in the field of view of LHAASO. Dwarf spheroidal galaxies are among the most promising targets for indirect detection of dark matter which have low fluxes of astrophysical $\gamma$-ray background while large amount of dark matter. By analyzing more than 700 days observational data at LHAASO, no significant dark matter signal from 1 TeV to 1 EeV is detected. Accordingly we derive the most stringent constraints on the ultra-heavy dark matter annihilation cross-section up to EeV. The constraints on the lifetime of dark matter in decay mode are also derived

Pointing calibration of LHAASO-WFCTA telescopes using bright stars

International audienceOne of the main scientific objectives of the Large High Altitude Air Shower Observatory (LHAASO) is to perform accurate measurements of the energy spectra for different cosmic ray masses, from a few TeV to 100 PeV. As one of the main sub-arrays of LHAASO, the Wide Field-of-View Cherenkov Telescope Array (WFCTA), which consists of 18 telescopes, can help in achieving this goal. The pointing accuracy of each telescope is crucial for reconstructing energy and determining mass-sensitive parameters. In this study, a method for absolute pointing calibration using ultraviolet bright stars was established. The proposed method can achieve a pointing accuracy of approximately 0.02° by using more than five stars. When more stars are used in the telescope’s field of view, the accuracy of the pointing calibration can be improved, e.g, a pointing accuracy of 0.01° can be achieved when using more than 15 stars. A high-precision inclinometer with a monitor resolution of 0.003° was installed on the camera to monitor the zenith direction of the telescope at every second. After calibration using bright stars, the absolute pointing accuracy of the inclinometer was 0.02°. •Method for absolute pointing calibration using ultraviolet bright stars established.•A pointing accuracy of ∼0.02°can be achieved using more than five stars.•A pointing accuracy of 0.01°can be achieved when using more than 15 stars•Accuracy of the pointing calibration increases with number of bright stars

Measurement of ultra-high-energy diffuse gamma-ray emission of the Galactic plane from 10 TeV to 1 PeV with LHAASO-KM2A

International audienceThe diffuse Galactic $\gamma$-ray emission, mainly produced via interactions between cosmic rays and the diffuse interstellar medium, is a very important probe of the distribution, propagation, and interaction of cosmic rays in the Milky Way. In this work we report the measurements of diffuse $\gamma$-rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner ($15^{\circ}10$~TeV). The energy spectrum in the inner Galaxy regions can be described by a power-law function with an index of $-2.99\pm0.04$, which is different from the curved spectrum as expected from hadronic interactions between locally measured cosmic rays and the line-of-sight integrated gas content. Furthermore, the measured flux is higher by a factor of $\sim3$ than the prediction. A similar spectrum with an index of $-2.99\pm0.07$ is found in the outer Galaxy region, and the absolute flux for $10\lesssim E\lesssim60$ TeV is again higher than the prediction for hadronic cosmic ray interactions. The latitude distributions of the diffuse emission are consistent with the gas distribution, while the longitude distributions show slight deviation from the gas distribution. The LHAASO measurements imply that either additional emission sources exist or cosmic ray intensities have spatial variations