The Walbottle coin hoard of 1879: re-examination and reassessment

This article reappraises the Walbottle (Throckley) hoard of late third-century Roman coins. The complicated biography of the hoard since its discovery in 1879 is described, followed by a summary of the re-identified coins and a discussion of the dating of the hoard. The results of a ground-breaking metallurgical study of a sample of the Walbottle coins are also presented, emphasising the on-going value of antiquarian finds when subjected to careful re-evaluation and analysis

Validation of a commercially available indirect assay for SARS-CoV-2 neutralising antibodies using a pseudotyped virus assay.

Objectives To assess whether a commercially available CE-IVD, ELISA-based surrogate neutralisation assay (cPass, Genscript) provides a genuine measure of SARS-CoV-2 neutralisation by human sera, and further to establish whether measuring responses against the RBD of S was a diagnostically useful proxy for responses against the whole S protein. Methods Serum samples from 30 patients were assayed for anti-NP responses, for ‘neutralisation’ by the surrogate neutralisation assay and for neutralisation by SARS-CoV-2 S pseudotyped virus assays utilising two target cell lines. Correlation between assays was measured using linear regression. Results The responses observed within the surrogate neutralisation assay demonstrated an extremely strong, highly significant positive correlation with those observed in both pseudotyped virus assays. Conclusions The tested ELISA-based surrogate assay provides an immunologically useful measure of functional immune responses in a much quicker and highly automatable fashion. It also reinforces that detection of anti-RBD neutralising antibodies alone is a powerful measure of the capacity to neutralise viral infection

The effect of intervertebral cartilage on neutral posture and range of motion in the necks of sauropod dinosaurs

The necks of sauropod dinosaurs were a key factor in their evolution. The habitual posture and range of motion of these necks has been controversial, and computer-aided studies have argued for an obligatory sub-horizontal pose. However, such studies are compromised by their failure to take into account the important role of intervertebral cartilage. This cartilage takes very different forms in different animals. Mammals and crocodilians have intervertebral discs, while birds have synovial joints in their necks. The form and thickness of cartilage varies significantly even among closely related taxa. We cannot yet tell whether the neck joints of sauropods more closely resembled those of birds or mammals. Inspection of CT scans showed cartilage:bone ratios of 4.5% for Sauroposeidon and about 20% and 15% for two juvenile Apatosaurus individuals. In extant animals, this ratio varied from 2.59% for the rhea to 24% for a juvenile giraffe. It is not yet possible to disentangle ontogenetic and taxonomic signals, but mammal cartilage is generally three times as thick as that of birds. Our most detailed work, on a turkey, yielded a cartilage:bone ratio of 4.56%. Articular cartilage also added 11% to the length of the turkey's zygapophyseal facets. Simple image manipulation suggests that incorporating 4.56% of neck cartilage into an intervertebral joint of a turkey raises neutral posture by 15°. If this were also true of sauropods, the true neutral pose of the neck would be much higher than has been depicted. An additional 11% of zygapophyseal facet length translates to 11% more range of motion at each joint. More precise quantitative results must await detailed modelling. In summary, including cartilage in our models of sauropod necks shows that they were longer, more elevated and more flexible than previously recognised

Persistent fluctuations in stride intervals under fractal auditory stimulation

Copyright @ 2014 Marmelat et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Stride sequences of healthy gait are characterized by persistent long-range correlations, which become anti-persistent in the presence of an isochronous metronome. The latter phenomenon is of particular interest because auditory cueing is generally considered to reduce stride variability and may hence be beneficial for stabilizing gait. Complex systems tend to match their correlation structure when synchronizing. In gait training, can one capitalize on this tendency by using a fractal metronome rather than an isochronous one? We examined whether auditory cues with fractal variations in inter-beat intervals yield similar fractal inter-stride interval variability as isochronous auditory cueing in two complementary experiments. In Experiment 1, participants walked on a treadmill while being paced by either an isochronous or a fractal metronome with different variation strengths between beats in order to test whether participants managed to synchronize with a fractal metronome and to determine the necessary amount of variability for participants to switch from anti-persistent to persistent inter-stride intervals. Participants did synchronize with the metronome despite its fractal randomness. The corresponding coefficient of variation of inter-beat intervals was fixed in Experiment 2, in which participants walked on a treadmill while being paced by non-isochronous metronomes with different scaling exponents. As expected, inter-stride intervals showed persistent correlations similar to self-paced walking only when cueing contained persistent correlations. Our results open up a new window to optimize rhythmic auditory cueing for gait stabilization by integrating fractal fluctuations in the inter-beat intervals.Commission of the European Community and the Netherlands Organisation for Scientific Research

Task-Related Effects on the Temporal and Spatial Dynamics of Resting-State Functional Connectivity in the Default Network

Recent evidence points to two potentially fundamental aspects of the default network (DN), which have been relatively understudied. One is the temporal nature of the functional interactions among nodes of the network in the resting-state, usually assumed to be static. The second is possible influences of previous brain states on the spatial patterns (i.e., the brain regions involved) of functional connectivity (FC) in the DN at rest. The goal of the current study was to investigate modulations in both the spatial and temporal domains. We compared the resting-state FC of the DN in two runs that were separated by a 45 minute interval containing cognitive task execution. We used partial least squares (PLS), which allowed us to identify FC spatiotemporal patterns in the two runs and to determine differences between them. Our results revealed two primary modes of FC, assessed using a posterior cingulate seed – a robust correlation among DN regions that is stable both spatially and temporally, and a second pattern that is reduced in spatial extent and more variable temporally after cognitive tasks, showing switching between connectivity with certain DN regions and connectivity with other areas, including some task-related regions. Therefore, the DN seems to exhibit two simultaneous FC dynamics at rest. The first is spatially invariant and insensitive to previous brain states, suggesting that the DN maintains some temporally stable functional connections. The second dynamic is more variable and is seen more strongly when the resting-state follows a period of task execution, suggesting an after-effect of the cognitive activity engaged during task that carries over into resting-state periods

Is there loss or qualitative changes in the expression of thyroid peroxidase protein in thyroid epithelial cancer?

There is disagreement concerning the expression of thyroid peroxidase (TPO) in thyroid cancer, some studies finding qualitative as well as quantitative differences compared to normal tissue. To investigate TPO protein expression and its antigenic properties, TPO was captured from a solubilizate of thyroid microsomes by a panel of murine anti-TPO monoclonal antibodies and detected with a panel of anti-human TPO IgGκ Fab. TPO protein expression in 30 samples of malignant thyroid tissue was compared with TPO from adjacent normal tissues. Virtual absence of TPO expression was observed in 8 cases. In the remaining 22 malignant thyroid tumours the TPO protein level varied considerably from normal to nearly absent when compared to normal thyroid tissue or tissues from patients with Graves' disease (range less than 0.5 to more than 12.5 μg mg−1 of protein). When expressed TPO displayed similar epitopes, to that of TPO from Graves' disease tissue. The results obtained by the TPO capturing method were confirmed by SDS-PAGE and Western blot analysis with both microsomes and their solubilizates. The present results show that in about two-thirds of differentiated thyroid carcinomas, TPO protein is expressed, albeit to a more variable extent than normal; when present, TPO in malignant tissues is immunologically normal. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Identification of plasma proteins relating to brain neurodegeneration and vascular pathology in cognitively normal individuals

This project was funded by DPUK through MRC (grant no. MR/L023784/2) and the UK Medical Research Council Award to the University of Oxford (grant no. MC_PC_17215). L.S is funded by the Virtual Brain Cloud from European comission (grant no. H2020-SC1-DTH-2018-1). C.R.B is funded by National Institutes of Health (NIH) research grant R01AG054628. S.R.C is funded by National Institutes of Health (NIH) research grant (R01AG054628), Medical Research Council (MR/R024065/1), Age UK and Economic and Social Research Council. R.E.M. was supported by Alzheimer's Research UK major project grant ARUKPG2017B-10. C.H was supported by an MRC Human Genetics Unit programme grant “Quantitative traits in health and disease” (U.MC_UU_00007/10). H.C.W received funding from Wellcome Trust. J.W is funded by TauRx pharmaceuticals Ltd and received Educational grant from Biogen paid to Alzheimer Scotland/Brain Health Scotland. G.W received GRAMPIAN UNIVERSITY HOSPITALS NHS TRUST, Scottish Government—Chief Scientist Office, ROLAND SUTTON ACADEMIC TRUST, Medical Research Scotland, Sutton Academic Trust and ROLAND SUTTON ACADEMIC TRUST. J.M.W received Wellcome Trust Strategic Award, MRC UK Dementia Research Institute and MRC project grants, Fondation Leducq, Stroke Association, British Heart Foundation, Alzheimer Society, and the European Union H2020 PHC-03-15 SVDs@Target grant (666881). D.S received MRC (MR/S010351/1), MRC (MR/W002388/1) and MRC (MR/W002566/1). A.M is supported by the Wellcome Trust (104036/Z/14/Z, 216767/Z/19/Z, 220857/Z/20/Z) and UKRI MRC (MC_PC_17209, MR/S035818/1). This work is part of a project that has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 847776. In addition, A.M has received grant support from The Sackler Trust, outside of the work presented. N.B received grant to institution from GSK as part of GSK/Oxford FxG initiative. A.N.H received John Black Charitable Fund-Rosetrees, H2020 funding from European Comission-Project Virtual Brain Cloud, AI for the Discovery of new therapies in Parkinson's (A2926), Rising Start Initiative—stage 2, Brain-Gut Microbiome (Call: PAR-18-296; Award ID: 1U19AG063744-01), Gut-liver-brain biochemical axis in Alzheimer's disease (5RF1AG057452-01), Virtual Brain Cloud (Call: H2020-SC1-DTH- 2018-1; Grant agreement ID: 826421). Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006) and is currently supported by the Wellcome Trust (216767/Z/19/Z). Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Edinburgh Clinical Research Facility, University of Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” [STRADL] Reference 104036/Z/14/Z). We are grateful to all the families who took part; the general practitioners and the Scottish School of Primary Care for their help in recruiting them; and the whole Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, health-care assistants, and nurses.Peer reviewedPublisher PD

Qualia: The Geometry of Integrated Information

According to the integrated information theory, the quantity of consciousness is the amount of integrated information generated by a complex of elements, and the quality of experience is specified by the informational relationships it generates. This paper outlines a framework for characterizing the informational relationships generated by such systems. Qualia space (Q) is a space having an axis for each possible state (activity pattern) of a complex. Within Q, each submechanism specifies a point corresponding to a repertoire of system states. Arrows between repertoires in Q define informational relationships. Together, these arrows specify a quale—a shape that completely and univocally characterizes the quality of a conscious experience. Φ— the height of this shape—is the quantity of consciousness associated with the experience. Entanglement measures how irreducible informational relationships are to their component relationships, specifying concepts and modes. Several corollaries follow from these premises. The quale is determined by both the mechanism and state of the system. Thus, two different systems having identical activity patterns may generate different qualia. Conversely, the same quale may be generated by two systems that differ in both activity and connectivity. Both active and inactive elements specify a quale, but elements that are inactivated do not. Also, the activation of an element affects experience by changing the shape of the quale. The subdivision of experience into modalities and submodalities corresponds to subshapes in Q. In principle, different aspects of experience may be classified as different shapes in Q, and the similarity between experiences reduces to similarities between shapes. Finally, specific qualities, such as the “redness” of red, while generated by a local mechanism, cannot be reduced to it, but require considering the entire quale. Ultimately, the present framework may offer a principled way for translating qualitative properties of experience into mathematics