The Impact of Glucose Variation on Human Astrocytes

Diabetes is a metabolic disorder dysregulating glucose homeostasis. The role of astrocytes in central glucose sensing is poorly understood. But it is recognised they take part in whole-body energy homeostasis, specifically as glucose sensors necessary for the counterregulatory response (CRR) to hypoglycaemia. Iatrogenic hypoglycaemia is the limiting factor to glycaemic control in people with type 1 or type 2 diabetes. Severe hypoglycaemia occurs approximately once per year, whereas, the incidence of minor hypoglycaemia is much greater. Hypoglycaemia impairs awareness of future hypoglycaemia and blunts the CRR, eventually causing hypoglycaemia-associated autonomic failure. The mechanisms of this process are poorly understood. This thesis utilised isolated human astrocytes exposed to acute or recurrent low glucose (RLG) in vitro to mimic glucose variation in diabetes. Cellular responses were characterised of three key astrocyte functions. Firstly, is astrocyte metabolism altered by acute and RLG treatment? Secondly, do isolated human astrocytes become activated by low glucose treatment, and is this affected by RLG? Thirdly, are astrocytic inflammatory pathways altered by acute or RLG? The key findings from this thesis shows for the first time that astrocytic mitochondrial oxidation is increased following RLG, with a concurrent increase in fatty acid dependency but decreased coupling efficiency; glycolytic function is also enhanced. Together, this indicates that astrocytes successfully adapt to low glucose to sustain intracellular nucleotide ratios. Contrary to previous work, these human astrocytes do not respond to low glucose by Ca2+-dependent activation. However, the astrocytes do increase inflammatory cytokine release following acute and RLG. Lastly, for the first time an RNA-sequencing approach has been used to identify low glucose-induced differential gene expression. Together these findings support the argument that astrocytes are sensitive to low glucose and may be important in glucose sensation and the CRR

How do junior medical officers use online information resources? A survey

Background: Online information resources function dually as important learning tools and sources of the latest evidence-based recommendations for junior medical officers (JMOs). However, little is currently known about how JMOs utilise this information when providing care for their patients. This study aimed to examine the usage and experience of online information resources amongst JMOs in South Australia to ascertain (i) the type of resources accessed, (ii) the frequency, (iii) the intended purpose, and (iv) the perceived reliability. Methods: A survey instrument using multiple choices, five-point Likert scales and free-text comments was developed and distributed through SurveyMonkey to South Australian JMOs between 1 May 2014 and 30 June 2014. Results: Of the 142 surveyed, 100 JMOs (70.4 %) used online information resources as their first approach over all other resources available. JMOs overwhelmingly (94.4 %, n = 134) used online information resources at least once per day, with the most frequent purpose for use being information regarding prescription medication (82.4 %, n = 117, reported ‘very frequent’ use). JMOs stated online resources were necessary to perform their work and, of the different types of information accessed, they rated peer-reviewed resources as the most reliable. Conclusions: JMOs strongly rely upon online clinical information in their everyday practice. Importantly, provision of these resources assists JMOs in their education and clinical performance.Heng Teck Chong, Michael James Weightman, Peranada Sirichai and Alison Jone

Alignment of multiple glial cell populations in 3D nanofiber scaffolds: toward the development of multicellular implantable scaffolds for repair of neural injury

Non-neuronal cells of the central nervous system (CNS), termed "neuroglia," play critical roles in neural regeneration; therefore, replacement of glial populations via implantable nanofabricated devices (providing a growth-permissive niche) is a promising strategy to enhance repair. Most constructs developed to date have lacked three-dimensionality, multiple glial populations and control over spatial orientations, limiting their ability to mimic in vivo neurocytoarchitecture. We describe a facile technique to incorporate multiple glial cell populations [astrocytes, oligodendrocyte precursor cells (OPCs) and oligodendrocytes] within a three-dimensional (3D) nanofabricated construct. Highly aligned nanofibers could induce elongation of astrocytes, while OPC survival, elongation and maturation required pre-aligned astrocytes. The potential to scale-up the numbers of constituent nanofiber layers is demonstrated with astrocytes. Such complex implantable constructs with multiple glial sub-populations in defined 3D orientations could represent an effective approach to reconstruct glial circuitry in neural injury sites

Contribution of steps to optical properties of vicinal diamond (100):H surfaces

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The Production of Hospitable Space: Commercial Propositions and Consumer Co-Creation in a Bar Operation

This paper examines the processes through which a commercial bar is transformed into a hospitable space. Drawing on a study of a venue patronized by lesbian, gay, bisexual and transsexual/transgender consumers, it considers how social and commercial forms of hospitality are mobilized. The paper argues that hospitable space has an ideological, normative and situational dimension. More specifically, it suggests the bar’s operation is tied to a set of ideological conceptions, which become the potential basis of association and disassociation among consumers. It examines the forces and processes that shape who participates in the production and consumption of hospitality and how. Finally, it considers the situational, emergent nature of hospitality and the discontinuous production of hospitable space. Rather than focusing exclusively on host-guest or provider-customer relations, which dominates existing work on hospitality, the paper examines how consumers’ perceptions, actions and interactions shape the production of hospitality. By doing so the paper offers an alternative approach to understanding queer spaces, bar operation as well as hospitality

Accounting for Dilution of SARS-CoV-2 in Wastewater Samples Using Physico-Chemical Markers

Most sewer networks collect domestic wastewater and a variable proportion of extraneous water, such as rainwater, through surface runoff and industrial discharges. Accounting for wastewater dilution is essential to properly quantify wastewater particle loads, whether these are molecular fragments of SARS-CoV-2, or other substances of interest such as illicit drugs or microplastics. This paper presents a novel method for obtaining real-time estimates of wastewater dilution and total daily volume through wastewater treatment works, namely when flow data is not available or unreliable. The approach considers the levels of several physico-chemical markers (ammonia, electrical conductivity, and orthophosphate) in the wastewater against their dry-weather levels. Using high-resolution data from the national Wastewater Surveillance Programme of Wales, we illustrate how the method is robust to spikes in markers and can recover peaks in wastewater flow measurements that may have been capped by hydraulic relief valves. We show the method proves effective in normalising SARS-CoV-2 viral loads in wastewater samples and discuss other applications for this method, looking at wastewater surveillance as a vital tool to monitor both human and environmental health

FEL research and development at STFC Daresbury laboratory

In this paper we present an overview of current and proposed FEL developments at STFC Daresbury Laboratory in the UK. We discuss progress on the ALICE IR-FEL since first lasing in October 2010, covering the optimisation of the FEL performance, progress on the demonstration of a single shot cross correlation experiment and the results obtained so far with a Scanning Near-Field Optical Microscopy beamline. We discuss a proposal for a 250 MeV single pass FEL test facility named CLARA to be built at Daresbury and dedicated to research for future light source applications. Finally we present a brief overview of other recent research highlights

Three-Body and One-Body Channels of the Auger Core-Valence-Valence decay: Simplified Approach

We propose a computationally simple model of Auger and APECS line shapes from open-band solids. Part of the intensity comes from the decay of unscreened core-holes and is obtained by the two-body Green's function $G^{(2)}_{\omega}$, as in the case of filled bands. The rest of the intensity arises from screened core-holes and is derived using a variational description of the relaxed ground state; this involves the two-holes-one-electron propagator $G_{\omega}$, which also contains one-hole contributions. For many transition metals, the two-hole Green's function $G^{(2)}_{\omega}$ can be well described by the Ladder Approximation, but the three-body Green's function poses serious further problems. To calculate $G_{\omega}$, treating electrons and holes on equal footing, we propose a practical approach to sum the series to all orders. We achieve that by formally rewriting the problem in terms of a fictitious three-body interaction. Our method grants non-negative densities of states, explains the apparent negative-U behavior of the spectra of early transition metals and interpolates well between weak and strong coupling, as we demonstrate by test model calculations.Comment: AMS-LaTeX file, 23 pages, 8 eps and 3 ps figures embedded in the text with epsfig.sty and float.sty, submitted to Phys. Rev.