BACKGROUND Genetic variants of the prion protein gene (PRNP) strongly determine susceptibility to prion diseases. All tested patients with definite variant Creutzfeldt-Jakob disease (vCJD) are homozygous for methionine at a common polymorphism at codon 129. A further genetic polymorphism at codon 219, a common variant in several Asian populations, is considered protective against sporadic CJD. OBJECTIVE To report a finding of heterozygosity at codon 219 in 2 patients with vCJD. DESIGN Case reports. SETTING MRC (Medical Research Council) Prion Unit and Department of Neurodegenerative Disease, University College London Institute of Neurology, and National Prion Clinic, National Hospital for Neurology and Neurosurgery. Patients Two patients with clinical and investigation findings consistent with the diagnoses of probable vCJD. MAIN OUTCOME MEASURES Clinical and genetic findings. RESULTS A 34-year-old man had a 15-month history of behavioral change progressing to ataxia, dysarthria, involuntary choreiform movements, and severe cognitive impairment. Cerebrospinal fluid analysis was positive for 14-3-3 protein, electroencephalography showed generalized slowing, and magnetic resonance imaging revealed thalamic high signal bilaterally, typical of vCJD. A 31-year-old woman had a 16-month history of cognitive decline, ataxia, involuntary choreiform movements, and myoclonic jerks. Magnetic resonance imaging showed bilateral pulvinar high signal. The diagnosis was confirmed by a tonsillar biopsy demonstrating abnormal prion protein deposition in a typical pattern for vCJD. PRNP sequencing showed a methionine homozygous codon 129 genotype and an E219K polymorphism in both patients. CONCLUSIONS The E219K polymorphism is neutral or may even confer susceptibility to vCJD. The observations are interpretable in the context of the conformational selection model of prion replication. A barrier to prion disease transmission depends on the degree to which permitted pathologic conformations of the prion protein overlap between the inoculum and the host.

We discuss the formation and evolution of transient coherent excitonic states induced by ultrashort laser irradiation of metal surfaces supporting the surface and image potential bands (typically the low index surfaces of Cu and Ag). These states, which evolve into the image potential states in the course of screening of primary optically excited electron–hole pair, may play the role of early intermediate states in pump–probe spectroscopies of surfaces (e.g. two‐photon‐photoemission or sum‐frequency generation) if the formation of image charge density proceeds on the time scale of the order of or longer than the pump–probe pulse duration and delay. In this regime a pump–probe experiment may yield information on the characteristics of such states rather than the states in relaxed image potential bands. Time scales of the various stages of these processes are estimated using an exactly solvable model of surface screening.