Eukaryotic translation elongation factor 2 (eEF2), encoded by the gene EEF2, is an essential factor involved in the elongation phase of protein translation. A specific heterozygous missense variant (p.P596H) in EEF2 was originally identified in association with autosomal dominant adult-onset spinocerebellar ataxia-26 (SCA26). More recently, additional heterozygous missense variants in this gene have been described to cause a novel, childhood-onset neurodevelopmental disorder with benign external hydrocephalus. Herein, we report two unrelated individuals with a similar gene-disease correlation to support this latter observation. Patient 1 is a 7-year-old male with a previously reported, de novo missense variant (p.V28M) who has motor and speech delay, autism spectrum disorder, failure to thrive with relative macrocephaly, unilateral microphthalmia with coloboma and eczema. Patient 2 is a 4-year-old female with a novel de novo nonsense variant (p.Q145X) with motor and speech delay, hypotonia, macrocephaly with benign ventricular enlargement, and keratosis pilaris. These additional cases help to further expand the genotypic and phenotypic spectrum of this newly described EEF2-related neurodevelopmental syndrome.

Multidecadal "megadroughts" were a notable feature of the climate of the American Southwest over the Common era, yet we still lack a comprehensive theory for what caused these megadroughts and why they curiously only occurred before about 1600 CE. Here, we use the Paleo Hydrodynamics Data Assimilation product, in conjunction with radiative forcing estimates, to demonstrate that megadroughts in the American Southwest were driven by unusually frequent and cold central tropical Pacific sea surface temperature (SST) excursions in conjunction with anomalously warm Atlantic SSTs and a locally positive radiative forcing. This assessment of past megadroughts provides the first comprehensive theory for the causes of megadroughts and their clustering particularly during the Medieval era. This work also provides the first paleoclimatic support for the prediction that the risk of American Southwest megadroughts will markedly increase with global warming.

Abstract: This study develops a reconstruction of the frequency of extreme cold‐season precipitation and the occurrence of landfalling atmospheric river (AR) storm tracks across the southwestern Unites States using a network of tree ring chronologies and the Living Blended Drought Atlas (LBDA), a 500‐year tree ring based reconstruction of the summer Palmer Drought Severity Index. The first two rotated empirical orthogonal functions of the LBDA across the Southwest are shown to relate well to previously identified patterns of regional AR activity. Accordingly, the rotated empirical orthogonal functions also record patterns of extreme precipitation associated with those ARs, albeit with some uncertainty introduced by nonextreme precipitation. A network of chronologies sensitive to cold‐season precipitation is then used to reconstruct the occurrence of landfalling ARs and extreme precipitation along the southern Californian coast, demonstrating for the first time the feasibility of reconstructing AR landfalls and extreme events in the Southwest based on spatial patterns in a network of dendroclimatic proxies.

A suite of climate data sets and multiple representations of atmospheric moisture demand are used to calculate many estimates of the self-calibrated Palmer Drought Severity Index, a proxy for near-surface soil moisture, across California from 1901 to 2014 at high spatial resolution. Based on the ensemble of calculations, California drought conditions were record breaking in 2014, but probably not record breaking in 2012-2014, contrary to prior findings. Regionally, the 2012-2014 drought was record breaking in the agriculturally important southern Central Valley and highly populated coastal areas. Contributions of individual climate variables to recent drought are also examined, including the temperature component associated with anthropogenic warming. Precipitation is the primary driver of drought variability but anthropogenic warming is estimated to have accounted for 8-27% of the observed drought anomaly in 2012-2014 and 5-18% in 2014. Although natural variability dominates, anthropogenic warming has substantially increased the overall likelihood of extreme California droughts.

The tree-ring-based North American Drought Atlas (NADA), Monsoon Asia Drought Atlas (MADA), and Old World Drought Atlas (OWDA) collectively yield a near-hemispheric gridded reconstruction of hydroclimate variability over the last millennium. To test the robustness of the large-scale representation of hydroclimate variability across the drought atlases, the joint expression of seasonal climate variability and teleconnections in the NADA, MADA, and OWDA are compared against two global, observation-based PDSI products. Predominantly positive (negative) correlations are determined between seasonal precipitation (surface air temperature) and collocated tree-ring-based PDSI, with average Pearson's correlation coefficients increasing in magnitude from boreal winter to summer. For precipitation, these correlations tend to be stronger in the boreal winter and summer when calculated for the observed PDSI record, while remaining similar for temperature. Notwithstanding these differences, the drought atlases robustly express teleconnection patterns associated with the El Niño-Southern Oscillation (ENSO), North Atlantic Oscillation (NAO), Pacific Decadal Oscillation (PDO), and Atlantic Multidecadal Oscillation (AMO). These expressions exist in the drought atlas estimates of boreal summer PDSI despite the fact that these modes of climate variability are dominant in boreal winter, with the exception of the Atlantic Multidecadal Oscillation. ENSO and NAO teleconnection patterns in the drought atlases are particularly consistent with their well-known dominant expressions in boreal winter and over the OWDA domain, respectively. Collectively, our findings confirm that the joint Northern Hemisphere drought atlases robustly reflect large-scale patterns of hydroclimate variability on seasonal to multidecadal timescales over the 20^th century and are likely to provide similarly robust estimates of hydroclimate variability prior to the existence of widespread instrumental data.

Severe and persistent 21st-century drought in southwestern North America (SWNA) motivates comparisons to medieval megadroughts and questions about the role of anthropogenic climate change. We use hydrological modeling and new 1200-year tree-ring reconstructions of summer soil moisture to demonstrate that the 2000-2018 SWNA drought was the second driest 19-year period since 800 CE, exceeded only by a late-1500s megadrought. The megadrought-like trajectory of 2000-2018 soil moisture was driven by natural variability superimposed on drying due to anthropogenic warming. Anthropogenic trends in temperature, relative humidity, and precipitation estimated from 31 climate models account for 47% (model interquartiles of 35 to 105%) of the 2000-2018 drought severity, pushing an otherwise moderate drought onto a trajectory comparable to the worst SWNA megadroughts since 800 CE.