The glacial geomorphology of the western cordilleran ice sheet and Ahklun ice cap, Southern Alaska

During the late Wisconsinan, Southern Alaska was covered by two large ice masses; the western arm of the Cordilleran Ice Sheet and the Ahklun Mountains Ice Cap. Compared to the other ice sheets that existed during this period (e.g. the British-Irish, Laurentide and Fennoscandian ice sheets), little is known about the geomorphology they left behind. This limits our understanding of their flow pattern and retreat. Here we present systematic mapping of the glacial geomorphology of the two ice masses which existed in Southern Alaska. Due to spatially variable data availability, mapping was conducted using digital elevation models and satellite images of varying resolutions. Offshore, we map the glacial geomorphology using available bathymetric data. For the first time, we document >5000 subglacial lineations, recording ice flow direction. The distribution of moraines is presented, as well as features related to glacial meltwater drainage patterns (eskers and meltwater channels). Prominent troughs were also mapped on Alaska's continental shelf. This map provides the data required for a glacial inversion of these palaeo-ice masses

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

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 glacial geomorphology of the western cordilleran ice sheet and Ahklun ice cap, Southern Alaska

<p>During the late Wisconsinan, Southern Alaska was covered by two large ice masses; the western arm of the Cordilleran Ice Sheet and the Ahklun Mountains Ice Cap. Compared to the other ice sheets that existed during this period (e.g. the British-Irish, Laurentide and Fennoscandian ice sheets), little is known about the geomorphology they left behind. This limits our understanding of their flow pattern and retreat. Here we present systematic mapping of the glacial geomorphology of the two ice masses which existed in Southern Alaska. Due to spatially variable data availability, mapping was conducted using digital elevation models and satellite images of varying resolutions. Offshore, we map the glacial geomorphology using available bathymetric data. For the first time, we document >5000 subglacial lineations, recording ice flow direction. The distribution of moraines is presented, as well as features related to glacial meltwater drainage patterns (eskers and meltwater channels). Prominent troughs were also mapped on Alaska's continental shelf. This map provides the data required for a glacial inversion of these palaeo-ice masses.</p

Marking out the pitch: a historiography and taxonomy of football fiction

Football, or soccer as it is more commonly referred to in Australia and the US, is arguably the world’s most popular sport. It generates a proportionate volume of related writing. Within this landscape, works of novel-length fiction are seemingly rare. This paper establishes and maps a substantial body of football fiction works, explores elements and qualities exhibited individually and collectively. In bringing together current, limited surveys of the field, it presents the first rigorous definition of football fiction and captures the first historiography of the corpus. Drawing on distant reading methods developed in conjunction with closer textual analyses, the historiography and subsequent taxonomy represent the first articulation of relationships across the body of work, identify growth areas and establish a number of movements and trends. In advancing the understanding of football fiction as a collective body, the paper lays foundations for further research and consideration of the works in generic terms