Quasi-diffusion magnetic resonance imaging (QDI): A fast, high b-value diffusion imaging technique.

To enable application of non-Gaussian diffusion magnetic resonance imaging (dMRI) techniques in large-scale clinical trials and facilitate translation to clinical practice there is a requirement for fast, high contrast, techniques that are sensitive to changes in tissue structure which provide diagnostic signatures at the early stages of disease. Here we describe a new way to compress the acquisition of multi-shell b-value diffusion data, Quasi-Diffusion MRI (QDI), which provides a probe of subvoxel tissue complexity using short acquisition times (1-4 min). We also describe a coherent framework for multi-directional diffusion gradient acquisition and data processing that allows computation of rotationally invariant quasi-diffusion tensor imaging (QDTI) maps. QDI is a quantitative technique that is based on a special case of the Continuous Time Random Walk model of diffusion dynamics and assumes the presence of non-Gaussian diffusion properties within tissue microstructure. QDI parameterises the diffusion signal attenuation according to the rate of decay (i.e. diffusion coefficient, D in mm2 s-1) and the shape of the power law tail (i.e. the fractional exponent, α). QDI provides analogous tissue contrast to Diffusional Kurtosis Imaging (DKI) by calculation of normalised entropy of the parameterised diffusion signal decay curve, Hn, but does so without the limitations of a maximum b-value. We show that QDI generates images with superior tissue contrast to conventional diffusion imaging within clinically acceptable acquisition times of between 84 and 228 s. We show that QDI provides clinically meaningful images in cerebral small vessel disease and brain tumour case studies. Our initial findings suggest that QDI may be added to routine conventional dMRI acquisitions allowing simple application in clinical trials and translation to the clinical arena

Nonlinear damping in mechanical resonators based on graphene and carbon nanotubes

Carbon nanotubes and graphene allow fabricating outstanding nanomechanical resonators. They hold promise for various scientific and technological applications, including sensing of mass, force, and charge, as well as the study of quantum phenomena at the mesoscopic scale. Here, we have discovered that the dynamics of nanotube and graphene resonators is in fact highly exotic. We propose an unprecedented scenario where mechanical dissipation is entirely determined by nonlinear damping. As a striking consequence, the quality factor Q strongly depends on the amplitude of the motion. This scenario is radically different from that of other resonators, whose dissipation is dominated by a linear damping term. We believe that the difference stems from the reduced dimensionality of carbon nanotubes and graphene. Besides, we exploit the nonlinear nature of the damping to improve the figure of merit of nanotube/graphene resonators.Comment: main text with 4 figures, supplementary informatio

Spatial constancy of attention across eye movements is mediated by the presence of visual objects

Recent studies have shown that attentional facilitation lingers at the retinotopic coordinates of a previously attended position after an eye movement. These results are intriguing, because the retinotopic location becomes behaviorally irrelevant once the eyes have moved. Critically, in these studies participants were asked to maintain attention on a blank location of the screen. In the present study, we examined whether the continuing presence of a visual object at the cued location could affect the allocation of attention across eye movements. We used a trans-saccadic cueing paradigm in which the relevant positions could be defined or not by visual objects (simple square outlines). We find an attentional benefit at the spatiotopic location of the cue only when the object (the placeholder) has been continuously present at that location. We conclude that the presence of an object at the attended location is a critical factor for the maintenance of spatial constancy of attention across eye movements, a finding that helps to reconcile previous conflicting results

Analysis of host responses to Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africa.

BACKGROUND: Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas. METHODS: We analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens. RESULTS: There was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST(-) and TST(+) contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST(+) contacts (LTBI) compared to TB and TST(-) contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen. CONCLUSIONS: Our multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may be useful for vaccine efficacy trials

Multi-centre reproducibility of diffusion MRI parameters for clinical sequences in the brain.

The purpose of this work was to assess the reproducibility of diffusion imaging, and in particular the apparent diffusion coefficient (ADC), intra-voxel incoherent motion (IVIM) parameters and diffusion tensor imaging (DTI) parameters, across multiple centres using clinically available protocols with limited harmonization between sequences. An ice-water phantom and nine healthy volunteers were scanned across fives centres on eight scanners (four Siemens 1.5T, four Philips 3T). The mean ADC, IVIM parameters (diffusion coefficient D and perfusion fraction f) and DTI parameters (mean diffusivity MD and fractional anisotropy FA), were measured in grey matter, white matter and specific brain sub-regions. A mixed effect model was used to measure the intra- and inter-scanner coefficient of variation (CV) for each of the five parameters. ADC, D, MD and FA had a good intra- and inter-scanner reproducibility in both grey and white matter, with a CV ranging between 1% and 7.4%; mean 2.6%. Other brain regions also showed high levels of reproducibility except for small structures such as the choroid plexus. The IVIM parameter f had a higher intra-scanner CV of 8.4% and inter-scanner CV of 24.8%. No major difference in the inter-scanner CV for ADC, D, MD and FA was observed when analysing the 1.5T and 3T scanners separately. ADC, D, MD and FA all showed good intra-scanner reproducibility, with the inter-scanner reproducibility being comparable or faring slightly worse, suggesting that using data from multiple scanners does not have an adverse effect compared with using data from the same scanner. The IVIM parameter f had a poorer inter-scanner CV when scanners of different field strengths were combined, and the parameter was also affected by the scan acquisition resolution. This study shows that the majority of diffusion MRI derived parameters are robust across 1.5T and 3T scanners and suitable for use in multi-centre clinical studies and trials

Criminal and Noncriminal Psychopathy: The Devil is in the Detail

Brooks, NS ORCiD: 0000-0003-1784-099XPsychopathy is prevalent and problematic in criminal populations, but is also found to be present in noncriminal populations. In 1992, Robert Hare declared that psychopaths may also “be found in the boardroom”, which has since been followed by an interest in the issue of noncriminal, or even successful, psychopathy. In this chapter, the paradox of criminal and noncriminal psychopathy is discussed with specific attention given to the similarities and differences that account for psychopathic personality across contexts. That psychopathy is a condition typified by a constellation of traits and behaviours requires wider research across diverse populations, and thus the streams of research related to criminal and noncriminal psychopathy are presented and the implications of these contrasting streams are explored

Computational Modeling of PI3K/AKT and MAPK Signaling Pathways in Melanoma Cancer

Background Malignant melanoma is an aggressive tumor of the skin and seems to be resistant to current therapeutic approaches. Melanocytic transformation is thought to occur by sequential accumulation of genetic and molecular alterations able to activate the Ras/Raf/MEK/ERK (MAPK) and/or the PI3K/AKT (AKT) signalling pathways. Specifically, mutations of B-RAF activate MAPK pathway resulting in cell cycle progression and apoptosis prevention. According to these findings, MAPK and AKT pathways may represent promising therapeutic targets for an otherwise devastating disease. Result Here we show a computational model able to simulate the main biochemical and metabolic interactions in the PI3K/AKT and MAPK pathways potentially involved in melanoma development. Overall, this computational approach may accelerate the drug discovery process and encourages the identification of novel pathway activators with consequent development of novel antioncogenic compounds to overcome tumor cell resistance to conventional therapeutic agents. The source code of the various versions of the model are available as S1 Archive

Buber, educational technology, and the expansion of dialogic space

Buber’s distinction between the ‘I-It’ mode and the ‘I-Thou’ mode is seminal for dialogic education. While Buber introduces the idea of dialogic space, an idea which has proved useful for the analysis of dialogic education with technology, his account fails to engage adequately with the role of technology. This paper offers an introduction to the significance of the I-It/I-Thou duality of technology in relation to opening dialogic space. This is followed by a short schematic history of educational technology which reveals the role technology plays, not only in opening dialogic space, but also in expanding dialogic space. The expansion of dialogic space is an expansion of what it means to be ‘us’ as dialogic engagement facilitates the incorporation, into our shared sense of identity, of aspects of reality that are initially experienced as alien or ‘other’. Augmenting Buber with an alternative understanding of dialogic space enables us to see how dialogue mediated by technology, as well as dialogue with monologised fragments of technology (robots), can, through education, lead to an expansion of what it means to be human

Modelling the public health impact of male circumcision for HIV prevention in high prevalence areas in Africa

Background: Recent clinical trials in Africa, in combination with several observational epidemiological studies, have provided evidence that male circumcision can reduce HIV female-to-male transmission risk by 60% or more. However, the public health impact of large-scale male circumcision programs for HIV prevention is unclear. Methods: Two mathematical models were examined to explore this issue: a random mixing model and a compartmental model that distinguishes risk groups associated with sex work. In the compartmental model, two scenarios were developed, one calculating HIV transmission and prevalence in a context similar to the country of Botswana, and one similar to Nyanza Province, in western Kenya. Results: In both models, male circumcision programs resulted in large and sustained declines in HIV prevalence over time among both men and women. Men benefited somewhat more than women, but prevalence among women was also reduced substantially. With 80% male circumcision uptake, the reductions in prevalence ranged from 45% to 67% in the two "countries", and with 50% uptake, from 25% to 41%. It would take over a decade for the intervention to reach its full effect. Conclusion: Large-scale uptake of male circumcision services in African countries with high HIV prevalence, and where male circumcision is not now routinely practised, could lead to substantial reductions in HIV transmission and prevalence over time among both men and women

Stormwater harvesting from landscaped areas:effect of herbicide application on water quality and usage

The suitability of stormwater harvested from pervious pavement system (PPS) structures for reuse purposes was investigated in conditions where glyphosate-containing herbicides (GCH) are applied as part of PPS maintenance procedure. The experiment was based on the four-layered design previously described as detailed in CIRIA C582. Results indicated that the highest sodium absorption ratio (SAR) of 1.6 recorded in this study, was less than that at which loss of permeability begins to occur as well as deterioration of matrix structure. Furthermore, the maximum electrical conductivity (ECw) of 2990 μS cm−1, recorded for 7200 mg L−1 concentration (GCH) was slightly below the unstable classification range at which salinity problems related to water quality occur such that salts accumulate in the root zone to the extent that crop yields are adversely affected. However, GCH concentration of 720 mg L−1 was within ‘permissible’ range while that of 72 mg L−1 was within ‘excellent’ range. Current study raises some environmental concerns owing to the overall impact that GCH at concentrations above 72 mg L−1 exerts on the net performance of the organic decomposers, heavy metal and hydrocarbon release from the system and thus, should be further investigated. However, effluent from all the test models including those dosed with high GCH concentration of 7200 mg L−1 do not pose any threat in terms of infiltration or deterioration associated with salinity although, there are indications that high dosage of the herbicide could lead to an elevated electrical conductivity of the recycled water.<br/