L.F. Marsigli (1658-1730): Early Contributions to Marine Science and Hydrography

During a career as a military engineer working in and around the Danube basin, Marsigli's wide-ranging scientific investigations provided him with a method when in 1706 he settled on the southern coast of France. His maritime studies led him to compose a treatise on the sea bed and its waters, followed by a lengthy section on corals and other lithophytes, which he misguidedly believed to be plants. Published as Histoire physique de Ia mer (1725), the issue in 1999 of the original text with English translation support the modern view of his priority in describing the physical aspects of this zone and confirm his title as 'Father of Oceanography'.Durante su carrera de ingeniero militar, trabajando en y alrededor de la cuenca del Danubio, las investigaciones cientrficas de gran alcance de Marsigli le proporcionaron un metoda cuando, en 1706, se instalo en la costa meridional de Francia. Sus estudios marittimos le llevaron a redactar un tratado sobre el fondo del mary sus aguas, seguido de una larga seccion sobre los carafes y otros litofitos, que confundio con plantas. Publicado como "Histoire physique de la mer" (1725), el ejemplar de 1999 del texto original con la traduccion inglesa documentan la vision moderna de su prioridad al describir los aspectos fisicos de esta zona y confirmar su titulo de 'Padre de la Oceanografia '.Les investigations scientifiques de grande envergure rea/isees par L.F. Marsigli, tout au long de sa carriere d'ingenieur militaire dans le bassin du Danube lui permirent d'acquerir une methode lorsqu 'en 1706 if s 'etablit sur Ia cote meridionale de la France. Ses etudes maritimes le conduisirent a rediger un traite sur le fond marin et ses eaux, suivi d 'une longue section sur les coraux et autres lithophytes, qu 'il prenait a tort pour des plantes. La publication du texte original de "le Histoire physique de la mer " (1725) en 1999, accompagne de la traduction en anglais, confirme la vision moderne de la priorite qu'il accordait a la description des aspects physiques de cette zone et vient conforter son appellation de " Pere de l'oceanographie "

London and beyond: essays in honour of Derek Keene

This volume contains selected papers from a major conference held in October 2008 to celebrate the 20th anniversary of the setting up of the Centre for Metropolitan History at the IHR, and the contribution of Professor Derek Keene to the Centre, the IHR and the wider world of scholarship. 'One of the pioneer volumes in the handsomely produced new Institute of Historical Research Conference series, this book serves as a fitting tribute to one of the most influential urban historians of our time.' - Ian Archer, Urban History, May 2013

Patents and Industrialisation. An Historical Overview of the British Case, 1624-1907

A Report to the Strategic Advisory Board on Intellectual Property Policy (SABIP), U

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities

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 development of instruments and apparatus for physical oceanography 1800-1914.

Early attempts to formulate a science of the sea were stimulated by the scientific revolution of the 17th century, but were far ahead of the technical capabilities and achieved little as instruments produced were unsuited to use within all but the shallowest waters. During the first half of the 19th century impetus was given by the Navy's specific demand for oceanographic information as part of their search for a Northwest Passage through Arctic waters. Despite the provision of ships and crews together with many newly-devised instruments the observations were recognised to be unsatisfactory. In the second half of the 19th century telegraph companies commenced laying submarine cables across the seas. Under commercial pressure they drew on newly -developed materials and techniques and the steam engine in order to construct and use the first efficient deep-sea sounders and samplers. Later in the same century marine zoologists obtained the backing of scientific societies and the Admiralty, which enabled them to develop waterbottles and thermometers suitable for deep sea work. They were thereby enabled to elucidate the structure of various water-masses within the body of the ocean. This work culminated in a series of long transoceanic research cruises. Commercial demands came to the fore again in the attempt to halt the decline in the fisheries of the North Atlantic and adjacent seas. Thermometers, waterbottles and current meters were designed to record the fine detail of water quality and movement so that the slight but important variations occurring seasonally and annually could be accurately registered. International cooperation and standardization of instruments was recognised as an important factor. Details of apparatus are scattered throughout a wide range of literature, often not that in which the scientific results are discussed