A common framework for approaches to extreme event attribution

The extent to which a given extreme weather or climate event is attributable to anthropogenic climate change is a question of considerable public interest. From a scientific perspective, the question can be framed in various ways, and the answer depends very much on the framing. One such framing is a risk-based approach, which answers the question probabilistically, in terms of a change in likelihood of a class of event similar to the one in question, and natural variability is treated as noise. A rather different framing is a storyline approach, which examines the role of the various factors contributing to the event as it unfolded, including the anomalous aspects of natural variability, and answers the question deterministically. It is argued that these two apparently irreconcilable approaches can be viewed within a common framework, where the most useful level of conditioning will depend on the question being asked and the uncertainties involved.

Genetic and phenotypic characterization of complex hereditary spastic paraplegia

The hereditary spastic paraplegias are a heterogeneous group of degenerative disorders that are clinically classified as either pure with predominant lower limb spasticity, or complex where spastic paraplegia is complicated with additional neurological features, and are inherited in autosomal dominant, autosomal recessive or X-linked patterns. Genetic defects have been identified in over 40 different genes, with more than 70 loci in total. Complex recessive spastic paraplegias have in the past been frequently associated with mutations in SPG11 (spatacsin), ZFYVE26/SPG15, SPG7 (paraplegin) and a handful of other rare genes, but many cases remain genetically undefined. The overlap with other neurodegenerative disorders has been implied in a small number of reports, but not in larger disease series. This deficiency has been largely due to the lack of suitable high throughput techniques to investigate the genetic basis of disease, but the recent availability of next generation sequencing can facilitate the identification of disease- causing mutations even in extremely heterogeneous disorders. We investigated a series of 97 index cases with complex spastic paraplegia referred to a tertiary referral neurology centre in London for diagnosis or management. The mean age of onset was 16 years (range 3 to 39). The SPG11 gene was first analysed, revealing homozygous or compound heterozygous mutations in 30/97 (30.9%) of probands, the largest SPG11 series reported to date, and by far the most common cause of complex spastic paraplegia in the UK, with severe and progressive clinical features and other neurological manifestations, linked with magnetic resonance imaging defects. Given the high frequency of SPG11 mutations, we studied the autophagic response to starvation in eight affected SPG11 cases and control fibroblast cell lines, but in our restricted study we did not observe correlations between disease status and autophagic or lysosomal markers. In the remaining cases, next generation sequencing was carried out revealing variants in a number of other known complex spastic paraplegia genes, including five in SPG7 (5/97), four in FA2H (also known as SPG35) (4/97) and two in ZFYVE26/SPG15. Variants were identified in genes usually associated with pure spastic paraplegia and also in the Parkinson’s disease-associated gene ATP13A2, neuronal ceroid lipofuscinosis gene TPP1 and the hereditary motor and sensory neuropathy DNMT1 gene, highlighting the genetic heterogeneity of spastic paraplegia. No plausible genetic cause was identified in 51% of probands, likely indicating the existence of as yet unidentified genes.

Reflections on the concept of the common good from an economic perspective

The chapter considers how the common good can be implemented when opinions differ within society about the nature of the common good. It explains how economic analysis can shed light on efficient conflict-management in these circumstances. The chapter argues, more generally, that virtue theorists make too little use of economics because they have an unduly restricted view of the nature and scope of the discipline

Treason, felony and Lollardy: a common petition in the hand of Richard Osbarn, Clerk of the Chamber of the Guildhall 1400–c. 1437

This article examines a common petition presented in the English parliament of 1425 requesting that those imprisoned for long periods for the crimes of treason, felony and Lollardy might be brought to trial. On the basis of palaeographical and orthographical evidence, this petition is demonstrated to be written by Richard Osbarn, clerk of the chamber of the London Guildhall between 1400 and 1437. The implications of this discovery throw new light on the way petitions were formulated, suggesting that the scribes of petitions played a greater role than previously thought, and in some cases identified with the complaint itself.