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On 6 and 9 August 1945, the two atomic bombs codenamed ‘Little Boy’ and ‘Fat Man’ were dropped on the Japanese industrial cities of Hiroshima and Nagasaki. Their explosions represented both a fi ttingly devastating fi nal chapter to the all-encompassing world war of the preceding years and the opening salvo of what would become decades of nuclear uncertainty. Less than a decade earlier, on 26 April 1937, one of the fi rst comprehensive aerial bombings of any defenceless civilian population befell the historic town of Guernica in Spain’s Basque region during the Spanish Civil War. The number of people killed in the bombing of Guernica was placed at 1,645 by the Basque government, though modern fi gures suggest that between 153 and 400 civilians died. By contrast, at least 148,000 people were killed in the Japanese bombings before the effects of the spread of radiation are taken into account as recalled by Catherine Jolivette (218). That this short period of time saw such an escalation in the means of mass destruction is a mark of the events of the years that bridged the gap. But the atom bomb’s realization was only the most devastating and concrete example of the potential of nuclear power. Its development was a consequence of a longer history of advances in the fi elds of molecular and theoretical physics that were believed to be leading the way towards a better understanding of, and appreciation for, the physical world. That scientifi c ambition found its corollary in Britain after 1945 as the circumstances of war set the ground for the Labour Party to implement a wave of social reforms geared towards ‘building a better world’ from its ruins: the engines of what would become known as the Welfare State. Yet the continuing effects of austerity and the gradual decline into Cold War similarly undermined such efforts. This overlapping sense of hope and despair is mirrored in the artistic output of the years that span these two points, stretching before and beyond in either direction. As Carol Jacobi writes in her essay in British Art in the Nuclear Age concerned with the relation of artistic production in the early post-war years to the cultures of crisis and community engendered by the experience of war

Botulinum toxin type A (Dysport) has been shown in European studies to be a safe and effective treatment for cervical dystonia. This multicenter, double-blind, randomized, controlled trial assessed the safety and efficacy of Dysport in cervical dystonia patients in the United States. Eighty patients were randomly assigned to receive one treatment with Dysport (500 units) or placebo. Participants were followed up for 4 to 20 weeks, until they needed further treatment. They were assessed at baseline and weeks 2, 4, 8, 12, 16, and 20 after treatment. Dysport was significantly more efficacious than placebo at weeks 4, 8, and 12 as assessed by the Toronto Western Spasmodic Torticollis Rating Scale (10-point vs. 3.8-point reduction in total score, respectively, at week 4; P < or = 0.013). Of participants in the Dysport group, 38% showed positive treatment response, compared to 16% in the placebo group (95% confidence interval, 0.02-0.41). The median duration of response to Dysport was 18.5 weeks. Side effects were generally similar in the two treatment groups; only blurred vision and weakness occurred significantly more often with Dysport. No participants in the Dysport group converted from negative to positive antibodies after treatment. These results confirm previous reports that Dysport (500 units) is safe, effective, and well-tolerated in patients with cervical dystonia.

Mutations in LRRK2 were first reported as causing Parkinson's disease (PD) in late 2004. Since then, approximately a dozen LRRK2 substitutions have been identified that are believed to be pathogenic mutations. The substitution of adenine for guanine at nucleotide 4541 (4541G>A) in LRRK2 was recently reported. This substitution resulted in the replacement of an arginine at position 1514 with a glutamine (R1514Q). Although this substitution was not found in a large cohort of controls, its pathogenicity could not be verified. We have now genotyped the R1514Q substitution in a sample of 954 PD patients from 429 multiplex PD families. This substitution was identified in 1.8% of the PD patients; however, the majority of the PD sibships segregating this substitution were discordant for this putative mutation. In addition, the R1514Q substitution was detected in 1.4% of neurologically evaluated, control individuals. These data suggest that the R1514Q variant is not a pathogenic LRRK2 mutation. We believe it is imperative that the causative nature of any newly identified genetic variant be determined before it is included in any panel for diagnostic testing.

Stereotactic posteroventral pallidotomy can improve motor performance in Parkinson's disease. Interruption of inhibitory pallidal projections to ventrolateral thalamus, components of a cortical-basal ganglia motor loop allows for this clinical benefit. We hypothesized that pallidotomy would lead to increased movement related activity in motor cortical areas receiving projections from ventrolateral thalamus. This was tested in 6 Parkinson's disease patients who underwent stereotactic posteroventral pallidotomy. Each patient was imaged with positron emission tomography (PET) measures of regional cerebral blood flow (rCBF) during performance of a simple prehension task and at rest. Scans were acquired before and 17 weeks after surgery. After pallidotomy, movement-related changes of rCBF increased significantly in both the supplementary motor area (SMA) and premotor cortex but not in primary motor cortex. The results demonstrate the importance of pallidothalamic circuitry for regulating volitional movements and confirm that disruption of inhibitory input to the ventrolateral thalamus can augment movement-related activity in motor association areas.

Structural equation modeling was used to examine functional interactions between cortical and subcortical motor areas in Parkinson's disease patients and normal subjects. Neuronal activity was defined by positron emission tomography (PET) imaging of regional cerebral blood flow (rCBF) during performance of movement and control tasks. Patients were scanned before and 8-12 weeks after stereotactic unilateral left posterovental globus pallidotomy. Pallidotomy attenuates basal ganglion inhibition of thalamocortical neurons involved in motor control and reduces the severity of bradykinesia in Parkinson's disease patients. It was hypothesized that with surgery there would be a similar alteration in thalamocortical interactions as measured with PET rCBF. A path analysis model of cortical and basal ganglia circuitry (defined by anatomic and electrophysiologic connectivity) was used to estimate unidirectional path coefficients describing the magnitude of region to region interactions. The resultant interactions defined a composite task-and disease-specific functional network of connectivity. After pallidotomy, there were significant reductions in the strength of interactions between the globus pallidus projection to thalamus, and the thalamus, projection to mesial frontal motor areas, consistent with the presumed physiologic interactions of these areas. This modeling approach can identify regional interactions that are not always apparent in categorical comparisons of inmaging data. ©1994 Wiley-Liss, Inc.