Insensitivity to loss predicts apathy in Huntington's disease

Background Apathy is a deficit in goal‐directed behavior that significantly affects quality of life and function. It is common in Huntington's disease and other disorders affecting corticostriatal pathways. Deficits in processing of reward, altered effort, and executive dysfunction are associated with apathy in other disorders, but the cognitive processes leading to apathy in Huntington's disease remain largely unknown. A previously reported deficit in learning from losses in Huntington's disease raises the possibility of a hitherto unrecognized mechanism leading to apathy. This study's objective was to delineate the cognitive processes associated with apathy in HD. Methods We tested 51 Huntington's disease participants and 26 controls on a battery of novel and established measures to assess the contribution to apathy in Huntington's disease of executive function, reward value, reward‐effort calculations, instrumental learning, and response to reward and loss. Results Huntington's disase participants had deficits in instrumental learning with impaired response to loss, but no evidence to suggest altered reward‐related behavior or effort. We also saw an executive dysfunction contribution to apathy in Huntington's disease. Discussion We report the novel finding that apathy in Huntington's disease is associated with blunted responses to losses and impaired instrumental learning. This association is consistent with the known early degeneration of the indirect pathway and amygdala involvement in apathy in Huntington's disease, but is previously unreported in any disorder. In keeping with the comparative preservation of the ventral striatum and orbitofrontal cortex in Huntington's disease, reward valuation and reward‐effort calculations did not contribute to apathy

Strain-dependent and distinctive T-cell responses to HIV antigens following immunisation of mice with differing chimpanzee adenovirus vaccine vectors

In vivo vaccination studies are conventionally conducted in a single mouse strain with results, only reflecting responses to a single immunogenetic background. We decided to examine the immune response to an HIV transgene (gag, pol and nef fusion protein) in 3 strains of mice (CBA, C57BL/6 and BALB/c) to determine the spectrum of responses and in addition to determine whether the serotype of the adenoviral vector used (ChAd3 and ChAd63) impacted the outcome of response. Our results demonstrated that all three strains of mice responded to the transgene and that the magnitude of responses were different between the strains. The C57BL/6 strain showed the lowest range of responses compared to the other strains and, very few responses were seen to the same peptide pool in all three strains of mice. In CBA and BALB/c mice there were significant differences in IFNγ production dependent on the adenoviral vector used. Our results suggest that employing a single strain of mouse may underestimate the efficacy and efficiency of vaccine products

New Perspectives on Glacial Geomorphology in Earth's Deep Time Record

International audienceThe deep time (pre-Quaternary) glacial record is an important means to understand the growth, development, and recession of the global cryosphere on very long timescales (10 6-10 8 Myr). Sedimentological description and interpretation of outcrops has traditionally played an important role. Whilst such data remain vital, new insights are now possible thanks to freely accessible aerial and satellite imagery, the widespread availability and affordability of Uncrewed Aerial Vehicles, and accessibility to 3D rendering software. In this paper, we showcase examples of glaciated landscapes from the Cryogenian, Ediacaran, Late Ordovician and Late Carboniferous where this approach is revolutionizing our understanding of deep time glaciation. Although some problems cannot be overcome (erosion or dissolution of the evidence), robust interpretations in terms of the evolving subglacial environment can be made. Citing examples from Australia (Cryogenian), China (Ediacaran), North and South Africa (Late Ordovician, Late Carboniferous), and Namibia (Late Carboniferous), we illustrate how the power of glacial geomorphology can be harnessed to interpret Earth's ancient glacial record

The climatic significance of Late Ordovician-early Silurian black

The Ordovician-Silurian transition (455-430 Ma) is characterized by repeated climatic perturbations, concomitant with major changes in the global oceanic redox state best exemplified by the periodic deposition of black shales. The relationship between the climatic evolution and the oceanic redox cycles, however, remains largely debated. Here, using an ocean-atmosphere general circulation model accounting for ocean biogeochemistry (MITgcm), we investigate the mechanisms responsible for the burial of organic carbon immediately before, during and right after the latest Ordovician Hirnantian (445-444 Ma) glacial peak. Our results are compared with recent sedimentological and geochemical data. We show that the late Katian time slice (445 Ma), typified by the deposition of black shales at tropical latitudes, represents an unperturbed oceanic state, with regional organic carbon burial driven by the surface primary productivity. During the Hirnantian, our experiments predict a global oxygenation event, in agreement with the disappearance of the black shales in the sedimentary record. This suggests that deep-water burial of organic matter may not be a tenable triggering factor for the positive carbon excursion reported at that time. Our simulations indicate that the perturbation of the ocean circulation induced by the release of freshwater, in the context of the post-Hirnantian deglaciation, does not sustain over sufficiently long geological periods to cause the Rhuddanian (444 Ma) oceanic anoxic event. Input of nutrients to the ocean, through increased continental weathering and the leaching of newly-exposed glaciogenic sediments, may instead constitute the dominant control on the spread of anoxia in the early Silurian

Conceptualising sustainability in UK urban Regeneration: a discursive Formation

Despite the wide usage and popular appeal of the concept of sustainability in UK policy, it does not appear to have challenged the status quo in urban regeneration because policy is not leading in its conceptualisation and therefore implementation. This paper investigates how sustainability has been conceptualised in a case-based research study of the regeneration of Eastside in Birmingham, UK, through policy and other documents, and finds that conceptualisations of sustainability are fundamentally limited. The conceptualisation of sustainability operating within urban regeneration schemes should powerfully shape how they make manifest (or do not) the principles of sustainable development. Documents guide, but people implement regeneration—and the disparate conceptualisations of stakeholders demonstrate even less coherence than policy. The actions towards achieving sustainability have become a policy ‘fix’ in Eastside: a necessary feature of urban policy discourse that is limited to solutions within market-based constraints

Orbitally forced ice sheet fluctuations during the Marinoan Snowball Earth glaciation

Two global glaciations occurred during the Neoproterozoic. Snowball Earth theory posits that these were terminated after millions of years of frigidity when initial warming from rising atmospheric CO2 concentrations was amplified by the reduction of ice cover and hence a reduction in planetary albedo. This scenario implies that most of the geological record of ice cover was deposited in a brief period of melt-back. However, deposits in low palaeo-latitudes show evidence of glacial–interglacial cycles. Here we analyse the sedimentology and oxygen and sulphur isotopic signatures of Marinoan Snowball glaciation deposits from Svalbard, in the Norwegian High Arctic. The deposits preserve a record of oscillations in glacier extent and hydrologic conditions under uniformly high atmospheric CO2 concentrations. We use simulations from a coupled three-dimensional ice sheet and atmospheric general circulation model to show that such oscillations can be explained by orbital forcing in the late stages of a Snowball glaciation. The simulations suggest that while atmospheric CO2 concentrations were rising, but not yet at the threshold required for complete melt-back, the ice sheets would have been sensitive to orbital forcing. We conclude that a similar dynamic can potentially explain the complex successions observed at other localities

A clinical and cost effectiveness trial of a parent group intervention to manage challenging restricted and repetitive behaviours in young children with autism spectrum disorder: study protocol for a randomized controlled trial

Background Restricted and repetitive behaviours vary greatly across the autism spectrum, and although not all are problematic some can cause distress and interfere with learning and social opportunities. We have, alongside parents, developed a parent group based intervention for families of young children with autism, which aims to offer support to parents and carers; helping them to recognise, understand and learn how to respond to their child’s challenging restricted repetitive behaviours. Methods The study is a clinical and cost-effectiveness, multi-site randomised controlled trial of the Managing Repetitive Behaviours (MRB) parent group intervention versus a psychoeducation parent group Learning About Autism (LAA) (n = 250; 125 intervention/125 psychoeducation; ~ 83/site) for parents of young children aged 3–9 years 11 months with a diagnosis of autism. All analyses will be done under intention-to-treat principle. The primary outcome at 24 weeks will use generalised estimating equation (GEE) to compare proportion of children with improved RRB between the MRB group and the LAA group. The GEE model will account for the clustering of children by parent groups using exchangeable working correlation. All secondary outcomes will be analysed in a similar way using appropriate distribution and link function. The economic evaluation will be conducted from the perspective of both NHS costs and family access to local community services. A ‘within trial’ cost-effectiveness analysis with results reported as the incremental cost per additional child achieving at least the target improvement in CGI-I scale at 24 weeks. Discussion This is an efficacy trial to investigate the clinical and cost-effectiveness of a parent group based intervention designed to help parents understand and manage their child’s challenging RRB. If found to be effective, this intervention has the potential to improve the well-being of children and their families, reduce parental stress, greatly enhance community participation and potential for learning, and improve longer-term outcomes. Trial registration Trial ID: ISRCTN15550611 Date registered: 07/08/2018. Sponsor and Monitor: Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust R&D Manager Lyndsey Dixon, Address: St Nicholas Hospital, Jubliee Road, Gosforth, Newcastle upon Tyne NE3 3XT, [email protected], Tel: 0191 246 722

Bedforms and sedimentary structures related to supercritical flows in glacigenic settings

Upper-flow-regime bedforms, including upper-stage-plane beds, antidunes, chutes-and-pools and cyclic steps, are ubiquitous in glacigenic depositional environments characterized by abundant meltwater discharge and sediment supply. In this study, the depositional record of Froude near-critical and supercritical flows in glacigenic settings is reviewed, and similarities and differences between different depositional environments are discussed. Upper-flow-regime bedforms may occur in subglacial, subaerial and subaqueous environments, recording deposition by free-surface flows and submerged density flows. Although individual bedform types are generally not indicative of any specific depositional environment, some observed trends are similar to those documented in non-glacigenic settings. Important parameters for bedform evolution that differ between depositional environments include flow confinement, bed slope, aggradation rate and grain size. Cyclic-step deposits are more common in confined settings, like channels or incised valleys, or steep slopes of coarse-grained deltas. Antidune deposits prevail in unconfined settings and on more gentle slopes, like glacifluvial fans, sand-rich delta slopes or subaqueous (ice-contact) fans. At low aggradation rates, only the basal portions of bedforms are preserved, such as scour fills related to the hydraulic-jump zone of cyclic steps or antidune-wave breaking, which are common in glacifluvial systems and during glacial lake-outburst floods and (related) lake-level falls. Higher aggradation rates result in increased preservation potential, possibly leading to the preservation of complete bedforms. Such conditions are met in sediment-laden jökulhlaups and subaqueous proglacial environments characterized by expanding density flows. Coarser-grained sediment leads to steeper bedform profiles and highly scoured facies architectures, while finer-grained deposits display less steep bedform architectures. Such differences are in part related to stronger flows, faster settling of coarse clasts, and more rapid breaking of antidune waves or hydraulic-jump formation over hydraulically rough beds. © 2020 The Authors. Sedimentology published by John Wiley & Sons Ltd on behalf of International Association of Sedimentologist