A physical model for state transitions in black hole X-ray binaries

We present an accretion cycle which can explain state transitions and other observed phenomena in black hole X-ray binaries. This model is based on the process of disc tearing, where individual rings of gas break off the disc and precess effectively independently. This occurs when the Lense-Thirring effect is stronger than the local disc viscosity. We discuss implications of this model for quasi-periodic oscillations and the disc-jet-corona coupling. We also speculate on applying this model to active galactic nuclei and other accreting systems.Comment: 6 pages, 3 figures. Accepted to MNRA

Consciousness and Cosmos: Building an Ontological Framework

Contemporary theories of consciousness are based on widely different concepts of its nature, most or all of which probably embody aspects of the truth about it. Starting with a concept of consciousness indicated by the phrase “the feeling of what happens” (the title of a book by Antonio Damásio), we attempt to build a framework capable of supporting and resolving divergent views. We picture consciousness in terms of Reality experiencing itself from the perspective of cognitive agents. Each conscious experience is regarded as composed of momentary feeling events that are combined by recognition and evaluation into extended conscious episodes that bind cognitive contents with a wide range of apparent durations (0.1 secs to 2 or more secs, for us humans, depending on circumstances and context). Three necessary conditions for the existence of consciousness are identified: a) a ground of Reality, envisaged as an universal field of potentiality encompassing all possible manifestations, whether material or 'mental'; b) a transitional zone, leading to; c) a manifest world with its fundamental divisions into material, 'informational' and quale-endowed aspects. We explore ideas about the nature of these necessary conditions, how they may relate to one another and whether our suggestions have empirical implications

Evaluating a new generation of wearable high-density diffuse optical tomography technology via retinotopic mapping of the adult visual cortex

High-density diffuse optical tomography (HD-DOT) has been shown to approach the resolution and localization accuracy of blood oxygen level dependent-functional magnetic resonance imaging in the adult brain by exploiting densely spaced, overlapping samples of the probed tissue volume, but the technique has to date required large and cumbersome optical fiber arrays. : To evaluate a wearable HD-DOT system that provides a comparable sampling density to large, fiber-based HD-DOT systems, but with vastly improved ergonomics. : We investigated the performance of this system by replicating a series of classic visual stimulation paradigms, carried out in one highly sampled participant during 15 sessions to assess imaging performance and repeatability. : Hemodynamic response functions and cortical activation maps replicate the results obtained with larger fiber-based systems. Our results demonstrate focal activations in both oxyhemoglobin and deoxyhemoglobin with a high degree of repeatability observed across all sessions. A comparison with a simulated low-density array explicitly demonstrates the improvements in spatial localization, resolution, repeatability, and image contrast that can be obtained with this high-density technology. : The system offers the possibility for minimally constrained, spatially resolved functional imaging of the human brain in almost any environment and holds particular promise in enabling neuroscience applications outside of the laboratory setting. It also opens up new opportunities to investigate populations unsuited to traditional imaging technologies. [Abstract copyright: © 2021 The Authors.

Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing.

Neurodegenerative disorders of ageing (NDAs) such as Alzheimer disease, Parkinson disease, frontotemporal dementia, Huntington disease and amyotrophic lateral sclerosis represent a major socio-economic challenge in view of their high prevalence yet poor treatment. They are often called 'proteinopathies' owing to the presence of misfolded and aggregated proteins that lose their physiological roles and acquire neurotoxic properties. One reason underlying the accumulation and spread of oligomeric forms of neurotoxic proteins is insufficient clearance by the autophagic-lysosomal network. Several other clearance pathways are also compromised in NDAs: chaperone-mediated autophagy, the ubiquitin-proteasome system, extracellular clearance by proteases and extrusion into the circulation via the blood-brain barrier and glymphatic system. This article focuses on emerging mechanisms for promoting the clearance of neurotoxic proteins, a strategy that may curtail the onset and slow the progression of NDAs

Design and validation of a mechanically flexible and ultra-lightweight high-density diffuse optical tomography system for functional neuroimaging of newborns

Neonates are a highly vulnerable population. The risk of brain injury is greater during the first days and weeks after birth than at any other time of life. Functional neuroimaging that can be performed longitudinally and at the cot-side has the potential to improve our understanding of the evolution of multiple forms of neurological injury over the perinatal period. However, existing technologies make it very difficult to perform repeated and/or long-duration functional neuroimaging experiments at the cot-side. We aimed to create a modular, high-density diffuse optical tomography (HD-DOT) technology specifically for neonatal applications that is ultra-lightweight, low profile and provides high mechanical flexibility. We then sought to validate this technology using an anatomically accurate dynamic phantom. An advanced 10-layer rigid-flexible printed circuit board technology was adopted as the basis for the DOT modules, which allows for a compact module design that also provides the flexibility needed to conform to the curved infant scalp. Two module layouts were implemented: dual-hexagon and triple-hexagon. Using in-built board-to-board connectors, the system can be configured to provide a vast range of possible layouts. Using epoxy resin, thermochromic dyes, and MRI-derived 3D-printed moulds, we constructed an electrically switchable, anatomically accurate dynamic phantom. This phantom was used to quantify the imaging performance of our flexible, modular HD-DOT system. Using one particular module configuration designed to cover the infant sensorimotor system, the device provided 36 source and 48 detector positions, and over 700 viable DOT channels per wavelength, ranging from 10 to over an area of approximately . The total weight of this system is only 70 g. The signal changes from the dynamic phantom, while slow, closely simulated real hemodynamic response functions. Using difference images obtained from the phantom, the measured 3D localization error provided by the system at the depth of the cortex was in the of range 3 to 6 mm, and the lateral image resolution at the depth of the neonatal cortex is estimated to be as good as 10 to 12 mm. The HD-DOT system described is ultra-low weight, low profile, can conform to the infant scalp, and provides excellent imaging performance. It is expected that this device will make functional neuroimaging of the neonatal brain at the cot-side significantly more practical and effective. [Abstract copyright: © 2021 The Authors.

Children’s participation in school grounds developments: creating a place for education that promotes children’s social inclusion

Abstract This paper advances the idea that ‘education for the social inclusion of children’ is similar but different to ‘inclusive education’ as it has come to be understood and used by some authors and UK government documents. ‘Inclusive education’ tends to carry an inward emphasis on the participation of children in the education system (with discussions on school culture, transitions, truancy, exclusion rates, underachievement, and school leaving age). In contrast, education for the promotion of children’s social inclusion requires an outward emphasis on children's participation in 'mainstream' society while they are still children. The latter emphasis is seen to be lacking in educational policy discourse in Scotland though a recent shift in policy towards education for active citizenship is noted. Examples are provided to show how many policy statements enact a limitation on the scope for education to promote children’s social inclusion by emphasising children’s deficits as social actors and focussing on the ‘condition’ of social exclusion. The paper draws on an empirical study of children’s participation in changing school grounds in Scotland. The analysis shows how the enclosure of learning in books, classrooms and normative curricula was challenged. Learning from school grounds developments was constructed relationally and spatially but the scope of what was to be learned was often delineated by adults. The paper closes with a discussion of how education that promotes the social inclusion of children will benefit from seeing both children and adults as current though partial citizens and utilising socio-spatial opportunities for the generation of uncertain curricula through their shared and/or differentiated participation

Electronic clinical decision support tool for assessing stomach symptoms in primary care (ECASS): a feasibility study

Objective: To determine the feasibility of a definitive trial in primary care of electronic clinical decision support (eCDS) for possible oesophago-gastric (O-G) cancer. Design and setting: Feasibility study in 42 general practices in two regions of England, cluster randomised controlled trial design without blinding, nested qualitative and health economic evaluation. Participants: Patients aged 55 years or older, presenting to their general practitioner (GP) with symptoms associated with O-G cancer. 530 patients (mean age 68 years, 58% female) participated. Intervention: Practices randomised 1:1 to usual care (control) or to receive a previously piloted eCDS tool for suspected cancer (intervention), for use at the discretion of the GPs, supported by a theory-based implementation package and ongoing support. We conducted semistructured interviews with GPs in intervention practices. Recruitment lasted 22 months. Outcomes: Patient participation rate, use of eCDS, referrals and route to diagnosis, O-G cancer diagnoses; acceptability to GPs; cost-effectiveness. Participants followed up 6 months after index encounter. Results: From control and intervention practices, we screened 3841 and 1303 patients, respectively; 1189 and 434 were eligible, 392 and 138 consented to participate. Ten patients (1.9%) had O-G cancer. eCDS was used eight times in total by five unique users. GPs experienced interoperability problems between the eCDS tool and their clinical system and also found it did not fit with their workflow. Unexpected restrictions on software installation caused major problems with implementation. Conclusions: The conduct of this study was hampered by technical limitations not evident during an earlier pilot of the eCDS tool, and by regulatory controls on software installation introduced by primary care trusts early in the study. This eCDS tool needed to integrate better with clinical workflow; even then, its use for suspected cancer may be infrequent. Any definitive trial of eCDS for cancer diagnosis should only proceed after addressing these constraints. Trial registration number: ISRCTN125595588

In Vitro and In Vivo Antagonism of a G Protein-Coupled Receptor (S1P3) with a Novel Blocking Monoclonal Antibody

Background: S1P 3 is a lipid-activated G protein-couple receptor (GPCR) that has been implicated in the pathological processes of a number of diseases, including sepsis and cancer. Currently, there are no available high-affinity, subtypeselective drug compounds that can block activation of S1P3. We have developed a monoclonal antibody (7H9) that specifically recognizes S1P3 and acts as a functional antagonist. Methodology/Principal Findings: Specific binding of 7H9 was demonstrated by immunocytochemistry using cells that over-express individual members of the S1P receptor family. We show, in vitro, that 7H9 can inhibit the activation of S1P3mediated cellular processes, including arrestin translocation, receptor internalization, adenylate cyclase inhibiton, and calcium mobilization. We also demonstrate that 7H9 blocks activation of S1P3 in vivo, 1) by preventing lethality due to systemic inflammation, and 2) by altering the progression of breast tumor xenografts. Conclusions/Significance: We have developed the first-reported monoclonal antibody that selectively recognizes a lipidactivated GPCR and blocks functional activity. In addition to serving as a lead drug compound for the treatment of sepsi

A Spatiotemporal Assessment of Extreme Cold in Northwestern North America Following the Unidentified 1809 CE Volcanic Eruption

Two large volcanic eruptions contributed to extreme cold temperatures during the early 1800s, one of the coldest phases of the Little Ice Age. While impacts from the massive 1815 Tambora eruption in Indonesia are relatively well-documented, much less is known regarding an unidentified volcanic event around 1809. Here, we describe the spatial extent, duration, and magnitude of cold conditions following this eruption in northwestern North America using a high-resolution network of tree-ring records that capture past warm-season temperature variability. Extreme and persistent cold temperatures were centered around the Gulf of Alaska, the adjacent Wrangell-St Elias Mountains, and the southern Yukon, while cold anomalies diminished with distance from this core region. This distinct spatial pattern of temperature anomalies suggests that a weak Aleutian Low and conditions similar to a negative phase of the Pacific Decadal Oscillation could have contributed to regional cold extremes after the 1809 eruption

Bacterial Causes of Empyema in Children, Australia, 2007–2009

Most infections were caused by non–7-valent pneumococcal conjugate vaccine serotypes