Speech, truth and liberty: Bentham to John Stuart Mill

Bentham’s Utilitarianism transforms earlier free speech doctrine in the service of the pursuit of truth and the control of government, preserving the distinction between statements of opinion and of fact and awarding the latter a lesser degree of protection. The work of James Mill and the early writings of John Stuart Mill retain this distinction, but their accounts are weighed down by the problems of a direct Utilitarian approach, in their consequentialist balancing of different values against each other, and in their dependence on a majoritarian epistemology and their commitment to a naive progressive optimism. Mill goes on in On Liberty to address and resolve these problems on the basis of a new justification for free speech as free deliberative thought. I argue that, contrary to most interpretations, his new justification leaves untouched the basic distinction between absolutely protected expressions of opinion and only functionally and contingently protected assertions of fact, leaving room for restrictions on factual statements, especially when untrue

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

The method of bookkeeping, deduced from clear principles

James Dodson FRS devised a new way of teaching double entry bookkeeping based on deductive logic, and he employed this method of scientific analysis to require recognition of assets and changes in their value in the absence of prior market transactions. This paper is designed to advance knowledge of accounting history by demonstrating diversity in the history of accounting thought and by revealing how it can be influenced by new ways of thinking gaining credence within the wider contemporary environment. Understanding of the history of double entry bookkeeping is broadened and deepened by locating Dodson’s treatise within the context of the scientific revolution; a time when complete obedience to the scriptures and classical authorities came under challenge from the systematic pursuit of knowledge based on reasoning, critical questioning, and the establishment of clear relationships between cause and effect