[1] This paper evaluates the use of field data on the spatial variability of snow water equivalent (SWE) to guide the design of distributed snow models. An extensive reanalysis of results from previous field studies in different snow environments around the world is presented, followed by an analysis of field data on spatial variability of snow collected in the headwaters of the Jollie River basin, a rugged mountain catchment in the Southern Alps of New Zealand. In addition, area-averaged simulations of SWE based on different types of spatial discretization are evaluated. Spatial variability of SWE is shaped by a range of different processes that occur across a hierarchy of spatial scales. Spatial variability at the watershed-scale is shaped by variability in near-surface meteorological fields (e.g., elevation gradients in temperature) and, provided suitable meteorological data is available, can be explicitly resolved by spatial interpolation/extrapolation. On the other hand, spatial variability of SWE at the hillslope-scale is governed by processes such as drifting, sloughing of snow off steep slopes, trapping of snow by shrubs, and the nonuniform unloading of snow by the forest canopy, which are more difficult to resolve explicitly. Subgrid probability distributions are often capable of representing the aggregate-impact of unresolved processes at the hillslope-scale, though they may not adequately capture the effects of elevation gradients. While the best modeling strategy is case-specific, the analysis in this paper provides guidance on both the suitability of several common snow modeling approaches and on the choice of parameter values in subgrid probability distributions.

The sensitivity of glaciers to climatic change is key information in assessing the response and sea-level implications of projected future warming. New Zealand glaciers are important globally as an example of how maritime glaciers will contribute to sea-level rise. A spatially distributed energy-balance model is applied to Brewster Glacier, New Zealand, in order to calculate glacier mass balance, run-off and sensitivity to climate change. The model successfully simulates four annual mass-balance cycles. Close to half (52%) of the energy available for melt on the glacier is supplied by turbulent heat fluxes, with radiation less important, except during the winter. Model sensitivity to temperature change is one of the largest reported on Earth, at −2.0 m w.e. a−1 °C−1. In contrast, a 50% change in precipitation is required to offset the mass-balance change resulting from a 1 °C temperature change. Meltwater runoff sensitivity is also very high, increasing 60% with a 1°C warming. The extreme sensitivity of mass balance to temperature change suggests that significant ice loss will occur with even moderate climate warming.

ObjectiveTo report the clinical and investigative features of children with a clinical diagnosis of probable autoimmune encephalopathy, both with and without antibodies to central nervous system antigens.MethodPatients with encephalopathy plus one or more of neuropsychiatric symptoms, seizures, movement disorder or cognitive dysfunction, were identified from 111 paediatric serum samples referred from five tertiary paediatric neurology centres to Oxford for antibody testing in 2007–2010. A blinded clinical review panel identified 48 patients with a diagnosis of probable autoimmune encephalitis whose features are described. All samples were tested/retested for antibodies to N-methyl-D-aspartate receptor (NMDAR), VGKC-complex, LGI1, CASPR2 and contactin-2, GlyR, D1R, D2R, AMPAR, GABA(B)R and glutamic acid decarboxylase.ResultsSeizures (83%), behavioural change (63%), confusion (50%), movement disorder (38%) and hallucinations (25%) were common. 52% required intensive care support for seizure control or profound encephalopathy. An acute infective organism (15%) or abnormal cerebrospinal fluid (32%), EEG (70%) or MRI (37%) abnormalities were found. One 14-year-old girl had an ovarian teratoma. Serum antibodies were detected in 21/48 (44%) patients: NMDAR 13/48 (27%), VGKC-complex 7/48(15%) and GlyR 1/48(2%). Antibody negative patients shared similar clinical features to those who had specific antibodies detected. 18/34 patients (52%) who received immunotherapy made a complete recovery compared to 4/14 (28%) who were not treated; reductions in modified Rankin Scale for children scores were more common following immunotherapies. Antibody status did not appear to influence the treatment effect.ConclusionsOur study outlines the common clinical and paraclinical features of children and adolescents with probable autoimmune encephalopathies. These patients, irrespective of positivity for the known antibody targets, appeared to benefit from immunotherapies and further antibody targets may be defined in the future.

More than 98% of Duchenne muscular dystrophy (DMD) mutations result in the premature termination of the dystrophin open reading frame at various points over its 11-kb length. Despite this wide variation in coding potential (0%-98.6% of the full-length protein), the truncating mutations are associated with a surprisingly uniform severity of phenotype. This uniformity is probably attributable to ablation of the message by nonsense-mediated decay (NMD). The rare truncating mutations that occur near the 3' end of the dystrophin gene (beyond exon 70) can however result in extremely variable phenotypes (both intra- and inter-familially). We suggest that all proteins encoded by such mutant genes are capable in principle of rescuing the DMD phenotype but that NMD abrogates the opportunity to effect this rescue. The observed variability may therefore reflect an underlying variation in the efficiency of NMD between individuals. We discuss this hypothesis with particular reference to a well-characterised Becker muscular dystrophy patient with a frameshift mutation, where expression of a truncated dystrophin rescues the muscular but not mental phenotype.

Objective: We aimed to describe the extent of neurodevelopmental impairments and identify the genetic etiologies in a large cohort of patients with epilepsy with myoclonic atonic seizures (MAE). Methods: We deeply phenotyped MAE patients for epilepsy features, intellectual disability, autism spectrum disorder, and attention-deficit/hyperactivity disorder using standardized neuropsychological instruments. We performed exome analysis (whole exome sequencing) filtered on epilepsy and neuropsychiatric gene sets to identify genetic etiologies. Results: We analyzed 101 patients with MAE (70% male). The median age of seizure onset was 34 months (range = 6-72 months). The main seizure types were myoclonic atonic or atonic in 100%, generalized tonic-clonic in 72%, myoclonic in 69%, absence in 60%, and tonic seizures in 19% of patients. We observed intellectual disability in 62% of patients, with extremely low adaptive behavioral scores in 69%. In addition, 24% exhibited symptoms of autism and 37% exhibited attention-deficit/hyperactivity symptoms. We discovered pathogenic variants in 12 (14%) of 85 patients, including five previously published patients. These were pathogenic genetic variants in SYNGAP1 (n = 3), KIAA2022 (n = 2), and SLC6A1 (n = 2), as well as KCNA2, SCN2A, STX1B, KCNB1, and MECP2 (n = 1 each). We also identified three new candidate genes, ASH1L, CHD4, and SMARCA2 in one patient each. Significance: MAE is associated with significant neurodevelopmental impairment.MAE is genetically heterogeneous, and we identified a pathogenic genetic etiology in 14% of this cohort by exome analysis. These findings suggest that MAE is a manifestation of several etiologies rather than a discrete syndromic entity. K E Y W O R D S Doose syndrome, epilepsy/seizures, genetics, myoclonic astatic epilepsy SUPPORTING INFORMATION Additional supporting information may be found online in the Supporting Information section. How to cite this article: Tang S, Addis L, Smith A, et al; EuroEPINOMICS-RES Consortium. Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures. Epilepsia. 2020;61:995-1007. https://