Digital Preservation Maturity, Resourcing, Policy and Strategy Survey (2018) - Selected Anonymised Raw Data
Contributors: Langley, Somaya, Pretlove, Lee
... The Digital Preservation at Oxford and Cambridge (DPOC) project and the Digital Preservation Coalition (DPC) developed a survey aimed at gathering basic data about digital preservation activities in organisations. The survey was run from April to May 2018 and gathered information about digital preservation maturity levels, staffing resources, and the policy and strategy landscapes of institutions currently doing or considering digital preservation activities. This is the raw anonymised dataset associated with this survey. For further information on the DPOC project, see: http://www.dpoc.ac.uk/
The use of PrP transgenic Drosophila to replace and reduce vertebrate hosts in the bioassay of mammalian prion infectivity [version 1; referees: 2 approved]
Contributors: Thackray, Alana Maureen, Andréoletti, O, Bujdoso, Raymond
... Prion diseases are fatal neurodegenerative conditions of humans and vertebrate species. The transmissible prion agent is a novel infectious particle composed principally of PrP Sc, an abnormal isomer of the normal host protein PrP C. The only reliable method to detect mammalian prion infectivity is by bioassay, invariably in a vertebrate host. The current prion bioassays typically involve intracerebral or peripheral inoculation of test material into the experimental host and subsequent euthanasia when clinical signs of terminal prion disease become evident. It may be months or years before the onset of clinical disease becomes evident and a pre-determined clinical end-point is reached. Consequently, bioassay of prion infectivity in vertebrate species is cumbersome, time consuming, expensive, and increasingly open to ethical debate because these animals are subjected to terminal neurodegenerative disease. Prions are a significant risk to public health through the potential for zoonotic transmission of animal prion diseases. Attention has focussed on the measurement of prion infectivity in different tissues and blood from prion-infected individuals in order to determine the distribution of infectious prions in diseased hosts. New animal models are required in order to replace or reduce, where possible, the dependency on the use of vertebrate species, including the 'gold standard' mouse prion bioassay, to assess prion infectivity levels. Here we highlight the development of a Drosophila-based prion bioassay, a highly sensitive and rapid invertebrate animal system that can efficiently detect mammalian prions. This novel invertebrate model system will be of considerable interest to biologists who perform prion bioassays as it will promote reduction and replacement in the number of sentient animals currently used for this purpose. This article is a composite of previous methods that provides an overview of the methodology of the model and discusses the experimental data to promote its viability for use instead of more sentient hosts.
The effects of gestational diabetes mellitus on fetal growth and neonatal birth measures in an African cohort.
Contributors: Macaulay, S, Munthali, RJ, Dunger, David Brian, Norris, SA
... AIM: Fetal exposure to gestational diabetes mellitus (GDM) is said to alter fetal growth and increase the risk of macrosomia. However, little research on GDM exists in African populations. This study aimed to assess longitudinal fetal growth and neonatal birth measures among Black African babies exposed to GDM. METHODS: Pregnant women (Soweto, South Africa) enrolled into a cohort study were followed up with repeated fetal ultrasounds. At 24-28 weeks' gestation a 2-h 75 g oral glucose tolerance test was performed and GDM was diagnosed using the World Health Organization's 2013 criteria. Neonatal birth measures were assessed. RESULTS: The study involved 741 women; 83 (11.2%) with GDM and 658 (88.8%) without. A total of 4040 fetal ultrasounds were performed. GDM exposure was associated with an increase in fetal growth measures, especially abdominal circumference, which was already seen at 16-18 weeks' gestation. Male fetuses in particular, showed a significant association between GDM exposure and increased abdominal circumference (P = 0.009). Most women with GDM (66.3%) received management; all received diet therapy and 32.7% were prescribed medication. There was no difference in birth measures between the GDM-exposed and unexposed neonates. CONCLUSION: Repeated ultrasound measures identified the effects of GDM as early as 16-18 weeks' gestation, well before a diagnosis of GDM would usually be made. Sex differences in fetal growth were observed, with GDM-exposed male fetuses being more affected with larger abdominal circumferences than females. A low rate of macrosomia was observed compared with historical GDM populations.
Contributors: Greaves, JS, Scaife, AMM, Frayer, DT, Green, David Alan, Mason, BS, Smith, AMS
... Several interstellar environments produce 'anomalous microwave emission' (AME), with brightness peaks at tens-of-gigahertz frequencies. The emission's origins are uncertain -- rapidly spinning nanoparticles could emit electric-dipole radiation, but the polycyclic aromatic hydrocarbons that have been proposed as the carrier are now found not to correlate with Galactic AME signals. The difficulty is in identifying co-spatial sources over long lines of sight. Here we identify AME in three proto-planetary discs. These are the only known systems that host hydrogenated nanodiamonds, in contrast to the very common detection of polycyclic aromatic hydrocarbons. Using spectroscopy, the nanodiamonds are located close to the host stars, at physically well-constrained temperatures. Developing disc models, we reproduce the emission with diamonds 0.75--1.1 nm in radius, holding <= 1-2% of the carbon budget. Ratios of microwave emission to stellar luminosity are approximately constant, allowing nanodiamonds to be ubiquitous but emitting below detection thresholds in many star systems. This result is compatible with the findings with similar-sized diamonds found within Solar System meteorites. As nanodiamond spectral absorption is seen in interstellar sightlines, these particles are also a candidate for generating galaxy-scale AME.
Contributors: Hughes, Laura Elizabeth, Rittman, Timothy, Robbins, Trevor, Rowe, James Benedict
... The distribution of pathology in frontotemporal dementia is anatomically selective, to distinct cortical regions and with differential neurodegeneration across the cortical layers. The cytoarchitecture and connectivity of cortical laminae preferentially supports frequency-specific oscillations and hierarchical information transfer between brain regions. We therefore predicted that in frontotemporal dementia, core functional deficits such as disinhibition would be associated with differences in the frequency spectrum and altered cross-frequency coupling between frontal cortical regions. We examined this hypothesis using a “Go-NoGo” response inhibition paradigm with eighteen patients with behavioural variant frontotemporal dementia and 20 healthy aged-matched during magnetoencephalography. During Go and NoGo trials, beta desynchronisation was severely attenuated in patients. Beta power was associated with increased impulsivity, as measured by the Cambridge Behavioural Inventory, a carer based questionnaire of changes in everyday behaviour. To quantify the changes in cross-frequency coupling in the frontal lobe, we used Dynamic Causal Modeling to test a family of hierarchical casual models, which included the inferior frontal gyrus, pre-supplementary motor area (preSMA) and primary motor cortex. This analysis revealed evidence for cross-frequency coupling in a fully connected network in both groups. However, in the patient group, we identified a significant loss of reciprocal connectivity of the inferior frontal gyrus, particularly for interactions in the gamma band and for theta to alpha coupling. Importantly, although prefrontal coupling was diminished, gamma connectivity between preSMA and motor cortex was enhanced in patients. We propose that the disruption of behavioural control arises from reduced frequency-specific connectivity of the prefrontal cortex, together with a hyper-synchronous reorganisation of connectivity among preSMA and motor regions. These results are supported by preclinical evidence of the selectivity of frontotemporal lobar degeneration on oscillatory dynamics, and provide a clinically relevant yet precise neurophysiological signature of behavioural control as a potential pharmacological target for early phase experimental medicines studies.
Contributors: Abbott, BP, Abbott, R, Abbott, TD, Acernese, F, Ackley, K, Adams, C, Adams, T, Addesso, P, Adhikari, RX, Adya, VB
... On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40 8 8-+ Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 M. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One-Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient's position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta.
Contributors: Matthews, Alexander, Ghahramani, Zoubin
... Dropout, a stochastic regularisation technique for training of neural networks, has recently been reinterpreted as a specific type of approximate inference algorithm for Bayesian neural networks. The main contribution of the reinterpretation is in providing a theoretical framework useful for analysing and extending the algorithm. We show that the proposed framework suffers from several issues; from undefined or pathological behaviour of the true posterior related to use of improper priors, to an ill-defined variational objective due to singularity of the approximating distribution relative to the true posterior. Our analysis of the improper log uniform prior used in variational Gaussian dropout suggests the pathologies are generally irredeemable, and that the algorithm still works only because the variational formulation annuls some of the pathologies. To address the singularity issue, we proffer Quasi-KL (QKL) divergence, a new approximate inference objective for approximation of high-dimensional distributions. We show that motivations for variational Bernoulli dropout based on discretisation and noise have QKL as a limit. Properties of QKL are studied both theoretically and on a simple practical example which shows that the QKL-optimal approximation of a full rank Gaussian with a degenerate one naturally leads to the Principal Component Analysis solution.
Contributors: Wen, Tanya, Duncan, John, Mitchell, Daniel
... The multiple-demand (MD) network is sensitive to many aspects of task difficulty, including such factors as rule complexity, memory load, attentional switching and inhibition. Many accounts link MD activity to top-down task control, raising the question of response when performance is limited by the quality of sensory input, and indeed, some prior results suggest little effect of sensory manipulations. Here we examined judgments of motion direction, manipulating difficulty by either motion coherence or salience of irrelevant dots. We manipulated each difficulty type across six levels, from very easy to very hard, and additionally manipulated whether difficulty level was blocked, and thus known in advance, or randomized. Despite the very large manipulations employed, difficulty had little effect on MD activity, especially for the coherence manipulation. Contrasting with these small or absent effects, we observed the usual increase of MD activity The multiple-demand (MD) network is sensitive to many aspects of task difficulty, including such factors as rule complexity, memory load, attentional switching and inhibition. Many accounts link MD activity to top-down task control, raising the question of response when performance is limited by the quality of sensory input, and indeed, some prior results suggest little effect of sensory manipulations. Here we examined judgments of motion direction, manipulating difficulty by either motion coherence or salience of irrelevant dots. We manipulated each difficulty type across six levels, from very easy to very hard, and additionally manipulated whether difficulty level was blocked, and thus known in advance, or randomized. Despite the very large manipulations employed, difficulty had little effect on MD activity, especially for the coherence manipulation. Contrasting with these small or absent effects, we observed the usual increase of MD activity with increased rule complexity. We suggest that, for simple sensory discriminations, it may be impossible to compensate for reduced stimulus information by increased top-down control.
Contributors: Lee, Lana, Huq, Tahmida, Driscoll, Judith Louise, Hoye, Robert
... Bismuth-based compounds have recently gained interest as solar absorbers with the potential to have low toxicity, be efficient in devices, and be processable using facile methods. We review recent theoretical and experimental investigations into bismuth- based compounds, which shape our understanding of their photovoltaic potential, with particular focus on their defect-tolerance. We also review the processing methods that have been used to control the structural and optoelectronic properties of single crystals and thin films. Additionally, we discuss the key factors limiting their device perfor- mance, as well as the future steps needed to ultimately realize these new materials for commercial applications.
Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.
Contributors: Davies, Gail, Lam, Max, Harris, Sarah E, Trampush, Joey W, Luciano, Michelle, Hill, W David, Hagenaars, Saskia P, Ritchie, Stuart J, Marioni, Riccardo E, Fawns-Ritchie, Chloe
... General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.