Editorial: Quaternary revolutions

PublishedEditorialJournalEditorialThe QRA@50 meeting was organized by a team of people including the editors, John Catt, Catherine Souch, Tom Hill, Danni Pearce and a team of postgraduates and staff from the Royal Geographical Society-Institute of British Geographers (RGS-IBG). It was made possible by support from a number of sponsors, including RGS-IBG, van Walt, Beta Analytic Ltd, the Natural History Museum, Wiley-Blackwell and C3W (Climate Change Consortium of Wales). We would like to thank the reviewers of all the papers for their comments and suggested improvements to the papers

Ranking the Predictive Power of Clinical and Biological Features Associated With Disease Progression in Huntington's Disease

Huntington’s disease (HD) is characterised by a triad of cognitive, behavioural, and motor symptoms which lead to functional decline and loss of independence. With potential disease-modifying therapies in development, there is interest in accurately measuring HD progression and characterising prognostic variables to improve efficiency of clinical trials. Using the large, prospective Enroll-HD cohort, we investigated the relative contribution and ranking of potential prognostic variables in patients with manifest HD. A random forest regression model was trained to predict change of clinical outcomes based on the variables, which were ranked based on their contribution to the prediction. The highest-ranked variables included novel predictors of progression—being accompanied at clinical visit, cognitive impairment, age at diagnosis and tetrabenazine or antipsychotics use—in addition to established predictors, cytosine adenine guanine (CAG) repeat length and CAG-age product. The novel prognostic variables improved the ability of the model to predict clinical outcomes and may be candidates for statistical control in HD clinical studies

Deglacial to postglacial palaeoenvironments of the Celtic Sea: Lacustrine conditions versus a continuous marine sequence

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Recent work on the last glaciation of the British Isles has led to an improved understanding of the nature and timing of the retreat of the British-Irish Ice Sheet (BIIS) from its southern maximum (Isles of Scilly), northwards into the Celtic and Irish seas. However, the nature of the deglacial environments across the Celtic Sea shelf, the extent of subaerial exposure and the existence (or otherwise) of a contiguous terrestrial linkage between Britain and Ireland following ice retreat remains ambiguous. Multiproxy research, based on analysis of 12 BGS vibrocores from the Celtic Deep Basin (CDB), seeks to address these issues. CDB cores exhibit a shell-rich upward fining sequence of Holocene marine sand above an erosional contact cut in laminated muds with infrequent lonestones. Molluscs, in situ Foraminifera and marine diatoms are absent from the basal muds, but rare damaged freshwater diatoms and foraminiferal linings occur. Dinoflagellate cysts and other non-pollen palynomorphs evidence diverse, environmentally incompatible floras with temperate, boreal and Arctic glaciomarine taxa co-occurring. Such multiproxy records can be interpreted as representing a retreating ice margin, with reworking of marine sediments into a lacustrine basin. Equally, the same record may be interpreted as recording similar conditions within a semi-enclosed marine embayment dominated by meltwater export and deposition of reworked microfossils. As assemblages from these cores contrast markedly with proven glaciomarine sequences from outside the CDB, a glaciolacustrine interpretation is favoured for the laminated sequence, truncated by a Late Weichselian transgressive sequence fining upwards into fully marine conditions. Reworked rare intertidal molluscs from immediately above the regional unconformity provide a minimum date c.13.9cal. ka BP for commencement of widespread marine erosion. Although suggestive of glaciolacustrine conditions, the exact nature and timing of laminated sediment deposition within the CDB, and the implications this has on (pen)insularity of Ireland following deglaciation, remain elusive. © 2013 The Boreas Collegium.Funded by NERC PhD research studentship grant. Grant Number: GT04/97/289/ES; two NSERC-funded radiocarbon allocations. Grant Numbers: 746/0898, 814/0999; MacEwan Universit

Plasmodium falciparum (Haemosporodia: Plasmodiidae) and O'nyong-nyong virus development in a transgenic Anopheles gambiae (Diptera: Culicidae) strain

Transgenic Anopheles gambiae Giles (Diptera: Culicidae) mosquitoes have been developed that confer sexual sterility on males that carry a transgene encoding a protein which cuts ribosomal DNA. A relevant risk concern with transgenic mosquitoes is that their capacity to transmit known pathogens could be greater than the unmodified form. In this study, the ability to develop two human pathogens in these transgenic mosquitoes carrying a homing endonuclease which is expressed in the testes was compared with its nontransgenic siblings. Infections were performed with Plasmodium falciparum (Welch) and o'nyong-nyong virus (ONNV) and the results between the transgenic and nontransgenic sibling females were compared. There was no difference observed with ONNV isolate SG650 in intrathoracic infections or the 50% oral infectious dose measured at 14 d postinfection or in mean body titers. Some significant differences were observed for leg titers at the medium and highest doses for those individuals in which virus titer could be detected. No consistent difference was observed between the transgenic and nontransgenic comparator females in their ability to develop P. falciparum NF54 strain parasites. This particular transgene caused no significant effect in the ability of mosquitoes to become infected by these two pathogens in this genetic background. These results are discussed in the context of risk to human health if these transgenic individuals were present in the environment

Measuring compensation in neurodegeneration using MRI

PURPOSE OF REVIEW: Despite signs of cortical and subcortical loss, patients with prodromal and early-stage neurodegenerative disease are able to perform at a level comparable to the normal population. It is presumed that the onset of compensatory processes, that is changes in brain activation within a function-specific network or in the recruitment of a region outside of the task-network, underlies this maintenance of normal performance. However, in most studies to date, increased brain activity is not correlated with indices of both disease and performance and what appears to be compensation could simply be a symptom of neurodegeneration. RECENT FINDINGS: MRI studies have explored compensation in neurodegenerative disease, claiming that compensation is evident across a number of disorders, including Alzheimer's and Parkinson's disease, but generally always in early stages; after this point, compensation is generally no longer able to operate under the severe burden of disease. However, none of these studies explicitly adopted a particular model of compensation. Thus, we also discuss our recent attempts to operationalize compensation for empirical testing. SUMMARY: There is clear evidence of compensatory processes in the early stages of neurodegenerative disease. However, for a more complete understanding, this requires more explicit empirical modelling

Multimodal characterization of the visual network in Huntington's disease gene carriers

Objective A sensorimotor network structural phenotype predicted motor task performance in a previous study in Huntington’s disease (HD) gene carriers. We investigated in the visual network whether structure – function – behaviour relationship patterns, and the effects of the HD mutation, extended beyond the sensorimotor network. Methods We used multimodal visual network MRI structural measures (cortical thickness and white matter connectivity), plus visual evoked potentials and task performance (Map Search; Symbol Digit Modalities Test) in healthy controls and HD gene carriers. Results Using principal component (PC) analysis, we identified a structure – function relationship common to both groups. PC scores differed between groups indicating white matter disorganization (higher RD, lower FA) and slower, and more disperse, VEP signal transmission (higher VEP P100 latency and lower VEP P100 amplitude) in HD than controls while task performance was similar. Conclusions HD may be associated with reduced white matter organization and efficient visual network function but normal task performance. Significance These findings indicate that structure – function relationships in the visual network, and the effects of the HD mutation, share some commonalities with those in the sensorimotor network. However, implications for task performance differ between the two networks suggesting the influence of network specific factors

Huntington disease: natural history, biomarkers and prospects for therapeutics

Huntington disease (HD) can be seen as a model neurodegenerative disorder, in that it is caused by a single genetic mutation and is amenable to predictive genetic testing, with estimation of years to predicted onset, enabling the entire range of disease natural history to be studied. Structural neuroimaging biomarkers show that progressive regional brain atrophy begins many years before the emergence of diagnosable signs and symptoms of HD, and continues steadily during the symptomatic or 'manifest' period. The continued development of functional, neurochemical and other biomarkers raises hopes that these biomarkers might be useful for future trials of disease-modifying therapeutics to delay the onset and slow the progression of HD. Such advances could herald a new era of personalized preventive therapeutics. We describe the natural history of HD, including the timing of emergence of motor, cognitive and emotional impairments, and the techniques that are used to assess these features. Building on this information, we review recent progress in the development of biomarkers for HD, and potential future roles of these biomarkers in clinical trials

Use of a trabecular metal implant in ankle arthrodesis after failed total ankle replacement: A short-term follow-up of 13 patients

Patients and methods 13 patients with a migrated or loose total ankle implant underwent arthrodesis with the use of a retrograde intramedullary nail through a trabecular metal Tibial Cone. The mean follow-up time was 1.4 (0.6-3.4) years. Results At the last examination, 7 patients were pain-free, while 5 had some residual pain but were satisfied with the procedure. 1 patient was dissatisfied and experienced pain and swelling when walking. The implant-bone interfaces showed no radiographic zones or gaps in any patient, indicating union. Interpretation The method is a new way of simplifying and overcoming some of the problems of performing arthrodesis after failed total ankle replacement