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Predictability on seasonal time scales over the North Atlantic-Europe region is assessed using a seasonal prediction system based on an initialized version of the Max Planck Institute Earth System Model (MPI-ESM). For this region, two of the dominant predictors on seasonal time scales are El Niño-Southern Oscillation (ENSO) and sudden stratospheric warming (SSW) events. Multiple studies have shown a potential for improved North Atlantic predictability for either predictor. Their respective influences are however difficult to disentangle, since the stratosphere is itself impacted by ENSO. Both El Niño and SSW events correspond to a negative signature of the North Atlantic Oscillation (NAO), which has a major influence on European weather. This study explores the impact on Europe by separating the stratospheric pathway of the El Niño teleconnection. In the seasonal prediction system, the evolution of El Niño events is well captured for lead times of up to 6 months, and stratospheric variability is reproduced with a realistic frequency of SSW events. The model reproduces the El Niño teleconnection through the stratosphere, involving a deepened Aleutian low connected to a warm anomaly in the northern winter stratosphere. The stratospheric anomaly signal then propagates downward into the troposphere through the winter season. Predictability of 500-hPa geopotential height over Europe at lead times of up to 4 months is shown to be increased only for El Niño events that exhibit SSW events, and it is shown that the characteristic negative NAO signal is only obtained for winters also containing major SSW events for both the model and the reanalysis data. [ABSTRACT FROM AUTHOR]

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons that results in progressive weakness and death from respiratory failure, commonly within about 3 years. Previous studies have shown association of a locus on chromosome 9p with ALS and linkage with ALS-frontotemporal dementia. We aimed to test whether this genomic region is also associated with ALS in an independent set of UK samples, and to identify risk factors associated with ALS in a further genome-wide association study that combined data from the independent analysis with those from other countries.Methods: We collected samples from patients with sporadic ALS from 20 UK hospitals and obtained UK control samples from the control groups of the Depression Case Control study, the Bipolar Affective Case Control Study, and the British 1958 birth cohort DNA collection. Genotyping of DNA in this independent analysis was done with Illumina HumanHap550 BeadChips. We then undertook a joint genome-wide analysis that combined data from the independent set with published data from the UK, USA, Netherlands, Ireland, Italy, France, Sweden, and Belgium. The threshold for significance was p=0·05 in the independent analysis, because we were interested in replicating a small number of previously reported associations, whereas the Bonferroni-corrected threshold for significance in the joint analysis was p=2·20×10(-7)Findings: After quality control, samples were available from 599 patients and 4144 control individuals in the independent set. In this analysis, two single nucleotide polymorphisms in a locus on chromosome 9p21.2 were associated with ALS: rs3849942 (p=2·22×10(-6); odds ratio [OR] 1·39, 95% CI 1·21-1·59) and rs2814707 (p=3·32×10(-6); 1·38, 1·20-1·58). In the joint analysis, which included samples from 4312 patients with ALS and 8425 control individuals, rs3849942 (p=4·64×10(-10); OR 1·22, 95% CI 1·15-1·30) and rs2814707 (p=4·72×10(-10); 1·22, 1·15-1·30) were associated with ALS.Interpretation: We have found strong evidence of a genetic association of two single nucleotide polymorphisms on chromosome 9 with sporadic ALS, in line with findings from previous independent GWAS of ALS and linkage studies of ALS-frontotemporal dementia. Our findings together with these earlier findings suggest that genetic variation at this locus on chromosome 9 causes sporadic ALS and familial ALS-frontotemporal dementia. Resequencing studies and then functional analysis should be done to identify the defective gene. [ABSTRACT FROM AUTHOR]