Characterisation of a single photon counting pixel system for imaging of low-contrast objects

In the framework of the Medipix collaboration the PCC, a single photon counting pixel chip, has been developed with the aim of improving the contrast resolution in medical imaging applications. The PCC consists of a matrix of 64x64 square pixels with 170 mm side length, each pixel comprising a 15 bit counter and a pulse height discriminator. The chip has been bump bonded to equally segmented 200 mm thick SI-LEC GaAs detectors showing a very high absorption energy for X-rays used in diagnostics. An absolute calibration of the system with a radioactive source and a synchrotron beam are described resulting in the value of the test input capacitance of ~24.7 fF. Using this value a full characterisation of the system from electrical measurements is presented. The entire system can reach a minimum threshold of ~2100 e- with ~250e- rms noise. One of the characteristics of the PCC is the possibility to adjust the thresholds of all pixels on a pixel-by-pixel basis with 3-bit precision. The threshold distribution after adjustment is ~120 e- rms. The spatial resolution of the system has been measured to be 3.61p/mm. A comparison of a tooth image taken with the PCC and with a screen-CDD system demonstrates its imaging capabilities

Are prices of new dwellings different? A spectral analysis of UK property vintages

The work makes two contributions to Hui’s (2011) dynamic house price classification. First, a house price ripple in cycles from Modern to Older dwellings is revealed and, second, as New housing is shown to have lower volatility than the other two. Using spectral analysis, it is argued that there is a 7½-year repeat buyer-second-hand cycle and a five year, first time buyer-New housing cycle, common to three house price vintages. These cycles reinforce each other every fifteen years, which corresponds with a Minsky super-cycle in housing finance. The equity of the owner-occupier is fortified by higher house prices whereas new builds extract embedded equity from the market. Government should support builders and facilitate access to market to first time buyers and through programmes like Help-to-Buy 1. However, to address the greater price instability that should follow, Government should impose a capital gains tax on the house seller

Methanol Accelerates DMPC Flip-Flop and Transfer: A SANS Study on Lipid Dynamics

© 2019 Biophysical Society Methanol is a common solubilizing agent used to study transmembrane proteins/peptides in biological and synthetic membranes. Using small angle neutron scattering and a strategic contrast-matching scheme, we show that methanol has a major impact on lipid dynamics. Under increasing methanol concentrations, isotopically distinct 1,2-dimyristoyl-sn-glycero-3-phosphocholine large unilamellar vesicle populations exhibit increased mixing. Specifically, 1,2-dimyristoyl-sn-glycero-3-phosphocholine transfer and flip-flop kinetics display linear and exponential rate enhancements, respectively. Ultimately, methanol is capable of influencing the structure-function relationship associated with bilayer composition (e.g., lipid asymmetry). The use of methanol as a carrier solvent, despite better simulating some biological conditions (e.g., antimicrobial attack), can help misconstrue lipid scrambling as the action of proteins or peptides, when in actuality it is a combination of solvent and biological agent. As bilayer compositional stability is crucial to cell survival and protein reconstitution, these results highlight the importance of methanol, and solvents in general, in biomembrane and proteolipid studies

The Quenching of Isopropyl Group Rotation in Van Der Waals Molecular Solids

X-ray diffraction experiments are employed to determine the molecular and crystal structure of 3-isopropylchrysene. Based on this structure, electronic structure calculations are employed to calculate methyl group and isopropyl group rotational barriers in a central molecule of a ten-molecule cluster. The two slightly inequivalent methyl group barriers are found to be 12 and 15 kJ mol(-1) and the isopropyl group barrier is found to be about 240 kJ mol(-1), meaning that isopropyl group rotation is completely quenched in the solid state. For comparison, electronic structure calculations are also performed in the isolated molecule, determining both the structure and the rotational barriers, which are determined to be 15 kJ mol(-1) for both the isopropyl group and the two equivalent methyl groups. These calculations are compared with, and are consistent with, previously published NMR (1)H spin-lattice relaxation experiments where it was found that the barrier for methyl group rotation was 11 +/- 1 kJ mol(-1) and that the barrier for isopropyl group rotation was infinite on the solid state NMR time scale

THE EUROPEAN PROJECT "VERSUS+ / HERITAGE FOR PEOPLE". OBJECTIVES AND METHODOLOGY

Abstract. The project "VerSus+ / Heritage for PEOPLE", founded by the European Commission as part of the Creative Europe Culture Programme (Ref. 607593-CREA-1-2019-1-ES-CULT-COOP1) during the period 2019–2023, focuses on the transmission of knowledge to all branches of society and the general public. Its aim is to raise awareness on what constitutes the basis for the conservation of the tangible and intangible heritage as well as for a more sustainable contemporary architecture. This in-depth transmission of the lessons from vernacular heritage to future society is to be carried out in specific defined contexts, such as islands and archipelagos (geographically limited territories that are accessible to collaborators and administrative, technical and social agents), where vernacular heritage is under pressure, subjected to the transformations of contemporary life, particularly mass tourism. These pilot experiences should serve as a real testing ground for the implementation of actions for social participation, dissemination, education, communication, and promotion in different contexts and through different media. This project aims to reach out to society in order to showcase the sustainable qualities of the examples identified, through the establishment of an operative approach that can be adjusted to different contexts. The experiences on each island are expected to have repercussions throughout the region and, in turn, throughout the country in question, improving the perspectives and opportunities starting from best practices, and promoting the development of local skills. In addition, promotion and support from partners and associate partners will allow these experiences to be applied in other similar European and international contexts

The association between pain-induced autonomic reactivity and descending pain control is mediated by the periaqueductal grey.

There is a strict interaction between the autonomic nervous system (ANS) and pain, which might involve descending pain modulatory mechanisms. The periaqueductal grey (PAG) is involved both in descending pain modulation and ANS, but its role in mediating this relationship has not yet been explored. Here, we sought to determine brain regions mediating ANS and descending pain control associations. Thirty participants underwent conditioned pain modulation (CPM) assessments, in which they rated painful pressure stimuli applied to their thumbnail, either alone or with a painful cold contralateral stimulation. Differences in pain ratings between ‘pressure-only’ and ‘pressure + cold’ stimuli provided a measure of descending pain control. In 18 of the 30 participants, structural scans and two functional MRI assessments, one pain-free and one during cold-pain were acquired. Heart rate variability (HRV) was simultaneously recorded. Normalised low-frequency HRV (LF-HRVnu) and the CPM score were negatively correlated; individuals with higher LF-HRVnu during pain reported reductions in pain during CPM. PAG-ventro-medial prefrontal cortex (vmPFC) and PAG-rostral ventromedial medulla (RVM) functional connectivity correlated negatively with the CPM. Importantly, PAG-vmPFC functional connectivity mediated the strength of the LF-HRVnu-CPM association. CPM response magnitude was also negatively correlated with vmPFC GM volume. Our multi-modal approach, using behavioural, physiological and MRI measures, provides important new evidence of interactions between ANS and descending pain mechanisms. ANS dysregulation and dysfunctional descending pain modulation are characteristics of chronic pain. We suggest that further investigation of body-brain interactions in chronic pain patients may catalyse the development of new treatments

Sustained perturbation in functional connectivity induced by cold pain.

BACKGROUND: Functional connectivity (FC) perturbations have been reported in multiple chronic pain phenotypes, but the nature of reported changes varies between cohorts and may relate to the consequences of living with chronic-pain related comorbidities, such as anxiety and depression. Healthy volunteer studies provide opportunities to study the effects of tonic noxious stimulation independently of these sequelae. Connectivity changes in task negative and positive networks, for example, the default mode and salience networks (DMN/SN), respectively, have been described, but how these and other connectivity networks, for example, those governing descending pain control are affected by the presence of tonic, noxious stimulation in healthy, pain-free individuals, remains unknown. METHOD: In 20 healthy volunteers, we assessed FC prior to, during, and following tonic cold painful stimulation in the ventromedial prefrontal cortex (vmPFC), rostral anterior insula (rAI), subgenual anterior cingulate cortex (ACC) and periaqueductal grey (PAG). We also recorded subjectively reported pain using a computerised visual analogue scale. RESULTS: We saw DMN FC changes during painful stimulation and that inter-network connectivity between the rAI with the vmPFC increased during pain, whereas PAG-precuneus FC decreased. Pain-induced FC alterations persisted following noxious stimulation. FC changes related to the magnitude of individuals' subjectively reported pain. CONCLUSIONS: We demonstrate FC changes during and following tonic cold-pain in healthy participants. Similarities between our findings and reports of patients with chronic pain suggest that some FC changes observed in these patients may relate to the presence of an ongoing afferent nociceptive drive. SIGNIFICANCE: How pain-related resting state networks are affected by tonic cold-pain remains unknown. We investigated functional connectivity alterations during and following tonic cold pain in healthy volunteers. Cold pain perturbed the functional connectivity of the ventro-medial prefrontal cortex, anterior insula, and the periacquaductal grey area. These connectivity changes were associated with the magnitude of individuals' reported pain. We suggest that some connectivity changes described in chronic pain patients may be due to an ongoing afferent peripheral drive.This work was funded by a Medical Research Council Experimental Medicine Challenge Grant (MR/N026969/1). MAH, SM, OO and SW are also supported by the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Trust. JOM is supported by a Sir Henry Dale Fellowship jointly funded by the Welcome Trust and the Royal Society (grant number 206675/Z/17/Z) and a Medical Research Council (MRC) Centre grant (MR/N026063/1)

Linking Pain Sensation to the Autonomic Nervous System: The Role of the Anterior Cingulate and Periaqueductal Gray Resting-State Networks.

There are bi-directional interactions between the autonomic nervous system (ANS) and pain. This is likely underpinned by a substantial overlap between brain areas of the central autonomic network and areas involved in pain processing and modulation. To date, however, relatively little is known about the neuronal substrates of the ANS-pain association. Here, we acquired resting state fMRI scans in 21 healthy subjects at rest and during tonic noxious cold stimulation. As indicators of autonomic function, we examined how heart rate variability (HRV) frequency measures were influenced by tonic noxious stimulation and how these variables related to participants' pain perception and to brain functional connectivity in regions known to play a role in both ANS regulation and pain perception, namely the right dorsal anterior cingulate cortex (dACC) and periaqueductal gray (PAG). Our findings support a role of the cardiac ANS in brain connectivity during pain, linking functional connections of the dACC and PAG with measurements of low frequency (LF)-HRV. In particular, we identified a three-way relationship between the ANS, cortical brain networks known to underpin pain processing, and participants' subjectively reported pain experiences. LF-HRV both at rest and during pain correlated with functional connectivity between the seed regions and other cortical areas including the right dorsolateral prefrontal cortex (dlPFC), left anterior insula (AI), and the precuneus. Our findings link cardiovascular autonomic parameters to brain activity changes involved in the elaboration of nociceptive information, thus beginning to elucidate underlying brain mechanisms associated with the reciprocal relationship between autonomic and pain-related systems

A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function.

We report on a homozygous frameshift deletion in DDX59 (c.185del: p.Phe62fs*13) in a family presenting with orofaciodigital syndrome phenotype associated with a broad neurological involvement characterized by microcephaly, intellectual disability, epilepsy, and white matter signal abnormalities associated with cortical and subcortical ischemic events. DDX59 encodes a DEAD-box RNA helicase and its role in brain function and neurological diseases is unclear. We showed a reduction of mutant cDNA and perturbation of SHH signaling from patient-derived cell lines; furthermore, analysis of human brain gene expression provides evidence that DDX59 is enriched in oligodendrocytes and might act within pathways of leukoencephalopathies-associated genes. We also characterized the neuronal phenotype of the Drosophila model using mutant mahe, the homolog of human DDX59, and showed that mahe loss-of-function mutant embryos exhibit impaired development of peripheral and central nervous system. Taken together, our results support a conserved role of this DEAD-box RNA helicase in neurological function