Hugh Llewellyn Keenleyside: Commissioner of the Northwest Territories, 1947-1950

In March 1947, Hugh Keenleyside was recalled from his posting as Ambassador to Mexico and appointed Commissioner of the Northwest Territories and Deputy Minister of Mines and Resources, positions he held until October 1950. His credentials were unusual and his tenure short, but within three and a half years, the former diplomat transformed the somewhat laissez-faire style of northern government into one of active intervention supported by major financial investment. ... Hugh Keenleyside's accomplishments as Commissioner of the Northwest Territories cannot be fully understood without recognizing that he had failed to meet his own expectations and ambitious objectives. Yet regardless of resistance and criticism from his more conservative colleagues and political masters, the determined reformer dramatically changed the direction of government policies to end the period of "benign neglect" and mark the beginning of heavy financial investment and government intervention into almost every aspect of northern affairs. ..

Why The St. Roch? Why The Northwest Passage? Why 1940? New Answers To Old Questions

For almost half a century, the reasons behind orders sending the RCMP schooner St. Roch through the Northwest Passage during the Second World War have puzzled historians and other scholars. True, there were rumors of a defence-related mission, but there was no hard evidence, no tangible proof. Nor did the captain, Sgt. Henry Larsen, provide many clues other than "Canada was at war and the government had realized the need to demonstrate the country's sovereignty over the Arctic islands" ... a statement not verified in official documents. Then unexpectedly last year, during research on Canadian wartime relations with Greenland, two memos were found in RCMP archival files that directly linked the voyage of the St. Roch to a government plan to defend and occupy the island in the spring of 1940 .... Although these memos might appear to contradict Larsen's own explanation, careful study of the documents and related circumstances suggests that the reference to sovereignty in the autobiography published posthumously could also be defined in very broad terms to include security considerations. Omission of any reference to the initial motive behind the orders was entirely in keeping with his responsibility as a member of the Royal Canadian Mounted Police to maintain a confidence in the national interest. Today, the rationale for that secrecy is no longer valid, and the once-secret documents explaining the circumstances and events are now accessible to the public. Perhaps it was a stroke of fate that his information should come to light during the 50th-anniversary celebrations of the venerable ship's historic voyage through the Northwest Passage. Along with pride of achievement is now added new pride of a greater purpose. ..

Attachment Matters for All - An Attachment Mapping Exercise for Children's Services in Scotland

As part of the first phase of the Looked After Strategic Implementation Group (LACSIG), the Scottish Children’s Reporter Administration (SCRA) undertook research into care and permanence planning for younger children in care.1 They focused on 100 children all aged under four years old when they first came to the attention of services and examined how long it took from that point to achieve permanence. For over 90% of children this process took longer than two years and more than half had still not achieved a permanent placement four years after first contact with services. Several children had also experienced multiple placements, with transitions between carers often occurring at critical developmental points. The research highlighted the negative impact on long-term outcomes of such continued disruption of children’s attachments

Attachment Matters for All : Executive Summary

In 2011 the Scottish Children’s Reporter Administration (SCRA) published research into care and permanence planning for looked after children. This identified long delays in achieving permanence, multiple placements and the adverse effects of these on children’s attachments. Potential long-term effects on individuals of poor attachment experiences in infancy and childhood include an increased risk of violent and anti-social behaviour, mental and physical health difficulties and a reduced capacity to parent their own children. Attachment-informed practice can ameliorate the long-term effects of early adversity. The Scottish Government responded to the SCRA research by commissioning the Centre for Excellence for Looked After Children in Scotland (CELCIS) and Scottish Attachment in Action (SAIA) to map attachment training and attachment-focused practice in Scotland

Oncogene expression from extrachromosomal DNA is driven by copy number amplification and does not require spatial clustering in glioblastoma stem cells

Extrachromosomal DNA (ecDNA) are frequently observed in human cancers and are responsible for high levels of oncogene expression. In glioblastoma (GBM), ecDNA copy number correlates with poor prognosis. It is hypothesized that their copy number, size, and chromatin accessibility facilitate clustering of ecDNA and colocalization with transcriptional hubs, and that this underpins their elevated transcriptional activity. Here, we use super-resolution imaging and quantitative image analysis to evaluate GBM stem cells harbouring distinct ecDNA species (EGFR, CDK4, PDGFRA). We find no evidence that ecDNA routinely cluster with one another or closely interact with transcriptional hubs. Cells with EGFR-containing ecDNA have increased EGFR transcriptional output, but transcription per gene copy is similar in ecDNA compared to the endogenous chromosomal locus. These data suggest that it is the increased copy number of oncogene-harbouring ecDNA that primarily drives high levels of oncogene transcription, rather than specific interactions of ecDNA with each other or with high concentrations of the transcriptional machinery

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)