Clinical and genetic evaluation of 23 children with infantile onset epileptic encephalopathy

Free Paper Presentation: FP5BACKGROUND: Infantile epileptic encephalopathies (IEE) are a group of conditions in which cognitive, sensory, and/or motor functions deteriorate as a consequence of epileptic activities, which consist of frequent seizures and/or major interictal paroxysmal activity. There are various causes of IEE and they may occur at any age. METHODS: We reviewed patients in the Department of Paediatrics and Adolescent Medicine of the University of Hong Kong, Queen Mary Hospital and Duchess of Kent Children’s Hospital with the clinical …published_or_final_versio

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Clinical Characteristics and Transmission of COVID-19 in Children and Youths During 3 Waves of Outbreaks in Hong Kong

IMPORTANCE: Schools were closed intermittently across Hong Kong to control the COVID-19 outbreak, which led to significant physical and psychosocial problems among children and youths. OBJECTIVE: To compare the clinical characteristics and sources of infection among children and youths with COVID-19 during the 3 waves of outbreaks in Hong Kong in 2020. DESIGN, SETTING AND PARTICIPANTS: This cross-sectional study involved children and youths aged 18 years or younger with COVID-19 in the 3 waves of outbreaks from January 23 through December 2, 2020. Data were analyzed from December 2020 through January 2021. MAIN OUTCOMES AND MEASURES: Demographic characteristics, travel and contact histories, lengths of hospital stay, and symptoms were captured through the central electronic database. Individuals who were infected without recent international travel were defined as having domestic infections. RESULTS: Among 397 children and youths confirmed with COVID-19 infections, the mean (SD) age was 9.95 (5.34) years, 220 individuals (55.4%) were male, and 154 individuals (38.8%) were asymptomatic. There were significantly more individuals who were infected without symptoms in the second wave (59 of 118 individuals [50.0%]) and third wave (94 of 265 individuals [35.5%]) than in the first wave (1 of 14 individuals [7.1%]) (P = .001). Significantly fewer individuals who were infected in the second and third waves, compared with the first wave, had fever (first wave: 10 individuals [71.4%]; second wave: 22 individuals [18.5%]; third wave: 98 individuals [37.0%]; P < .001) or cough (first wave: 6 individuals [42.9%]; second wave: 15 individuals [12.7%]; third wave: 52 individuals [19.6%]; P = .02). Among all individuals, 394 individuals (99.2%) had mild illness. One patient developed chilblains (ie, COVID toes), 1 patient developed multisystem inflammatory syndrome in children, and 1 patient developed post–COVID-19 autoimmune hemolytic anemia. In all 3 waves, 204 patients with COVID-19 (51.4%) had domestic infections. Among these individuals, 186 (91.2%) reported having a contact history with another individual with COVID-19, of which most (183 individuals [90.0%]) were family members. In the third wave, 18 individuals with domestic infections had unknown contact histories. Three schoolmates were confirmed with COVID-19 on the same day and were reported to be close contacts. CONCLUSIONS AND RELEVANCE: his cross-sectional study found that nearly all children and youths with COVID-19 in Hong Kong had mild illness. These findings suggest that household transmission was the main source of infection for children and youths with domestic infections and that the risk of being infected at school was small

Arrival Directions of Cosmic Rays above 32 EeV from Phase One of the Pierre Auger Observatory

A promising energy range to look for angular correlations between cosmic rays of extragalactic origin and their sources is at the highest energies, above a few tens of EeV (1 EeV equivalent to 10^(18) eV). Despite the flux of these particles being extremely low, the area of similar to 3000 km^(2) covered at the Pierre Auger Observatory, and the 17 yr data-taking period of the Phase 1 of its operations, have enabled us to measure the arrival directions of more than 2600 ultra-high-energy cosmic rays above 32 EeV. We publish this data set, the largest available at such energies from an integrated exposure of 122,000 km^(2) sr yr, and search it for anisotropies over the 3.4 pi steradians covered with the Observatory. Evidence for a deviation in excess of isotropy at intermediate angular scales, with similar to 15 degrees Gaussian spread or similar to 25 degrees top-hat radius, is obtained at the 4 sigma significance level for cosmic-ray energies above similar to 40 EeV

Searches for Ultra-High-Energy Photons at the Pierre Auger Observatory

The Pierre Auger Observatory, which is the largest air-shower experiment in the world, offers unprecedented exposure to neutral particles at the highest energies. Since the start of data collection more than 18 years ago, various searches for ultra-high-energy (UHE, E greater than or similar to 10^(17) eV) photons have been performed, either for a diffuse flux of UHE photons, for point sources of UHE photons or for UHE photons associated with transient events such as gravitational wave events. In the present paper, we summarize these searches and review the current results obtained using the wealth of data collected by the Pierre Auger Observatory

Search for Ultra-high-energy Photons from Gravitational Wave Sources with the Pierre Auger Observatory

A search for time-directional coincidences of ultra-high-energy (UHE) photons above 10 EeV with gravitational wave (GW) events from the LIGO/Virgo runs O1 to O3 is conducted with the Pierre Auger Observatory. Due to the distinctive properties of photon interactions and to the background expected from hadronic showers, a subset of the most interesting GW events is selected based on their localization quality and distance. Time periods of 1000 s around and 1 day after the GW events are analyzed. No coincidences are observed. Upper limits on the UHE photon fluence from a GW event are derived that are typically at &amp; SIM;7 MeV cm(-2) (time period 1000 s) and &amp; SIM;35 MeV cm(-2) (time period 1 day). Due to the proximity of the binary neutron star merger GW170817, the energy of the source transferred into UHE photons above 40 EeV is constrained to be less than 20% of its total GW energy. These are the first limits on UHE photons from GW sources

High sensitivity and specificity in proposed clinical diagnostic criteria for anti‐N‐methyl‐D‐aspartate receptor encephalitis

Aim: To determine the validity of the proposed clinical diagnostic criteria for anti‐N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis in paediatric patients. / Method: The diagnostic criteria for anti‐NMDAR encephalitis proposed by Graus et al. (2016) use clinical features and conventional investigations to facilitate early immunotherapy before antibody status is available. The criteria are satisfied if patients develop four out of six symptom groups within 3 months, together with at least one abnormal investigation (electroencephalography/cerebrospinal fluid) and reasonable exclusion of other disorders. We evaluated the validity of the criteria using a retrospective cohort of paediatric patients with encephalitis. Twenty‐nine patients with anti‐NMDAR encephalitis and 74 comparison children with encephalitis were included. / Results: As expected, the percentage of patients with anti‐NMDAR encephalitis who fulfilled the clinical criteria increased over time. During the hospital inpatient admission, most patients (26/29, 90%) with anti‐NMDAR encephalitis fulfilled the criteria, significantly more than the comparison group (3/74, 4%) (p<0.001). The median time of fulfilling the criteria in patients with anti‐NMDAR encephalitis was 2 weeks from first symptom onset (range 1–6). The sensitivity of the criteria was 90% (95% confidence interval 73–98) and the specificity was 96% (95% confidence interval 89–99). / Interpretation: The proposed diagnostic criteria for anti‐NMDAR encephalitis have good sensitivity and specificity. Incomplete criteria do not exclude the diagnosis. / What this paper adds: The proposed clinical diagnostic criteria for anti‐N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis by Graus et al. (2016) have high sensitivity and specificity in paediatric patients. The median time of fulfilling the criteria in patients with anti‐NMDAR was 2 weeks from first symptom onset

Critical windows for nutritional interventions against stunting.

An analysis of early growth patterns in children from 54 resource-poor countries in Africa and Southeast Asia shows a rapid falloff in the height-for-age z score during the first 2 y of life and no recovery until ≥5 y of age. This finding has focused attention on the period -9 to 24 mo as a window of opportunity for interventions against stunting and has garnered considerable political backing for investment targeted at the first 1000 d. These important initiatives should not be undermined, but the objective of this study was to counteract the growing impression that interventions outside of this period cannot be effective. We illustrate our arguments using longitudinal data from the Consortium of Health Oriented Research in Transitioning collaboration (Brazil, Guatemala, India, Philippines, and South Africa) and our own cross-sectional and longitudinal growth data from rural Gambia. We show that substantial height catch-up occurs between 24 mo and midchildhood and again between midchildhood and adulthood, even in the absence of any interventions. Longitudinal growth data from rural Gambia also illustrate that an extended pubertal growth phase allows very considerable height recovery, especially in girls during adolescence. In light of the critical importance of maternal stature to her children's health, our arguments are a reminder of the importance of the more comprehensive UNICEF/Sub-Committee on Nutrition Through the Life-Cycle approach. In particular, we argue that adolescence represents an additional window of opportunity during which substantial life cycle and intergenerational effects can be accrued. The regulation of such growth is complex and may be affected by nutritional interventions imposed many years previously