Electrochemical characterisation of single crystal boron doped diamond

Interest and employment of boron doped diamond (BDD) as an electrode material has grown rapidly over the last decade, due to its unique advantageous properties over traditional electrode materials. BDD has minimal background currents and can offer an increased potential range allowing for the detection of an increased range of analytes. Furthermore BDD stability in harsh conditions, elevated temperatures and pressures offers a wealth of applications. Polycrystalline BDD (pBDD) is commercially available in large wafers for industrial applications. This material is comparatively easy to grow when compared to single crystal BDD (scBDD) which requires careful homoepitaxial growth. This thesis aims to characterise scBDD grown with differing boron dopant densities, crystal orientation and growth procedures; with a view to determining the most suitable scBDD material for employment in electroanalytical applications. Characterisation is performed using high resolution microscopic and spectroscopic techniques which show sample variations relating to growth parameters. No non-diamond like carbon is detected and boron concentrations are all ~1020 cm-3 or greater. Electrochemical characterisation is performed using the scBDD in disc electrode format, where wide potential windows, minimal background currents and close to reversible behaviour is observed for outer sphere mediators FcTMA+/2+, IrCl6 2-/3- and Ru(NH3)6 3+/2+. Electrode pre-treatments demonstrate the importance of surface termination supporting faster or slower electron transfer kinetics of selected inner sphere mediators. scBDD was functionalised with gold nanoparticles to aid in sample homogeneity determination, highlighted some heterogeneities as a direct result of a failed growth process. This was performed at both macro and micro scales, giving rise to differing nucleation theories. Finally electrochemical imaging using scanning electrochemical microscopy is reported, enabling the determination of FcTMA+/2+ and Ru(NH3)6 3+/2+ kinetic electron transfer rates at well-defined tip-substrate distances

Editorial : The Challenges of Interdisciplinary Publishing

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The effect of fire on ant assemblages does not depend on habitat openness but does select for large, gracile predators

Ecosystems can respond in a variety of ways to the same agent of disturbance. In some contexts, fire causes large and long-lasting changes to ecological communities. In others, fire has a limited or short-lived impact on assemblages of animals and plants. Understanding why this occurs is critical if we are to manage these kinds of disturbances across the globe. A recent synthesis proposed that these seemingly idiosyncratic responses to fire can be understood in the context of habitat openness pre-disturbance. Assemblages in open habitats should respond less to a single fire event that those in closed habitats. We provide a test of this hypothesis by examining the response of ant (Hymenoptera: Formicidae) communities to large-scale fire events in three habitats of different natural canopy openness on the Peloponnese peninsula in Greece. We also test the hypothesis that assemblage responses to fire are trait dependent. Fire simplifies the physical structure of the environment, increases insolation, and limits opportunities for ants to exploit herbivorous feeding strategies. Consequently, we predict that ants will face a strong environmental filter between unburnt and recently burnt plots, which will be reflected in their functional morphology. Our analysis shows that burnt plots have more individual ants, more species and an almost complete compositional change relative to unburnt plots. These changes do not depend on initial canopy openness. Rather, we suggest that openness must be interpreted relative to the study taxon; for ants, openness should be measured closer to the ground level. In our study, ground-level openness does not vary across the plots, which may explain the results. Furthermore, ants in burnt plots are significantly larger, have relatively longer legs, relatively longer mandibles, and more elongate heads. This morphotype fits with our prediction of ants that can move and feed successfully in the burnt micro-landscape. Ultimately, more work is needed to fully explore the relationship between habitat openness and the response to fire. Our results showing a filtered set of ant morphologies in burnt environments suggest that ant traits may offer a further way forward to understand the faunal response to fire and disturbance in general.http://www.esajournals.org/loi/ecspam2022Zoology and Entomolog

Vascular endothelial growth factor-A165b prevents diabetic neuropathic pain and sensory neuronal degeneration

Diabetic peripheral neuropathy affects up to half of diabetic patients. This neuronal damage leads to sensory disturbances, including allodynia and hyperalgesia. Many growth factors have been suggested as useful treatments for prevention of neurodegeneration, including the vascular endothelial growth factor (VEGF) family. VEGF-A is generated as two alternative splice variant families. The most widely studied isoform, VEGF-A165a is both pro-angiogenic and neuroprotective, but pro-nociceptive and increases vascular permeability in animal models. Streptozotocin (STZ)-induced diabetic rats develop both hyperglycaemia and many of the resulting diabetic complications seen in patients, including peripheral neuropathy. In the present study, we show that the anti-angiogenic VEGF-A splice variant, VEGF-A165b, is also a potential therapeutic for diabetic neuropathy. Seven weeks of VEGF-A165b treatment in diabetic rats reversed enhanced pain behaviour in multiple behavioural paradigms and was neuroprotective, reducing hyperglycaemia-induced activated caspase 3 (AC3) levels in sensory neuronal subsets, epidermal sensory nerve fibre loss and aberrant sciatic nerve morphology. Furthermore, VEGF-A165b inhibited a STZ-induced increase in Evans Blue extravasation in dorsal root ganglia (DRG), saphenous nerve and plantar skin of the hind paw. Increased transient receptor potential ankyrin 1 (TRPA1) channel activity is associated with the onset of diabetic neuropathy. VEGF-A165b also prevented hyperglycaemia-enhanced TRPA1 activity in an in vitro sensory neuronal cell line indicating a novel direct neuronal mechanism that could underlie the anti-nociceptive effect observed in vivo. These results demonstrate that in a model of Type I diabetes VEGF-A165b attenuates altered pain behaviour and prevents neuronal stress, possibly through an effect on TRPA1 activity

In vivo molecular dissection of the effects of HIV-1 in active tuberculosis

Author Summary HIV-1 infected people have substantially increased risk of tuberculosis (TB) leading to a large burden of disease worldwide. We aimed to investigate how HIV-1 causes this effect by altering human immune responses. We measured the products of all immune genes at injection sites of sterilized TB under the skin, in order to look for differences between TB patients with and without HIV-1. We found that the predominant effect of early HIV-1 infection was to diminish a component of immune responses that contributes to prevention of harmful inflammation. In more advanced HIV-1, we found almost complete absence of any immune response to TB except for immune activity which is normally part of our defence against viruses, but may also weaken immune protection against TB. In some patients, TB becomes apparent after starting treatment for HIV-1. In these patients we found that most immune responses had recovered to normal levels, but that one type of response sometimes associated with asthma and allergies was exaggerated. Our findings provide new insights into how HIV-1 can affect immune responses and changes to the immune system that are associated with risk of TB, which will inform the development of new strategies to improve protective immunity

Living alone and mental health: parallel analyses in UK longitudinal population surveys and electronic health records prior to and during the COVID-19 pandemic

BACKGROUND: People who live alone experience greater levels of mental illness; however, it is unclear whether the COVID-19 pandemic had a disproportionately negative impact on this demographic. OBJECTIVE: To describe the mental health gap between those who live alone and with others in the UK prior to and during the COVID-19 pandemic. METHODS: Self-reported psychological distress and life satisfaction in 10 prospective longitudinal population surveys (LPSs) assessed in the nearest pre-pandemic sweep and three periods during the pandemic. Recorded diagnosis of common and severe mental illnesses between March 2018 and January 2022 in electronic healthcare records (EHRs) within the OpenSAFELY-TPP. FINDINGS: In 37 544 LPS participants, pooled models showed greater psychological distress (standardised mean difference (SMD): 0.09 (95% CI: 0.04; 0.14); relative risk: 1.25 (95% CI: 1.12; 1.39)) and lower life satisfaction (SMD: −0.22 (95% CI: −0.30; −0.15)) for those living alone pre-pandemic. This gap did not change during the pandemic. In the EHR analysis of c.16 million records, mental health conditions were more common in those who lived alone (eg, depression 26 (95% CI: 18 to 33) and severe mental illness 58 (95% CI: 54 to 62) more cases more per 100 000). For common mental health disorders, the gap in recorded cases in EHRs narrowed during the pandemic. CONCLUSIONS: People living alone have poorer mental health and lower life satisfaction. During the pandemic, this gap in self-reported distress remained; however, there was a narrowing of the gap in service use. CLINICAL IMPLICATIONS: Greater mental health need and potentially greater barriers to mental healthcare access for those who live alone need to be considered in healthcare planning

Tissue Glucocorticoid Metabolism in Adrenal Insufficiency:A Prospective Study of Dual-release Hydrocortisone Therapy

Background: Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy. The use of a once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren®), offers a more physiological cortisol profile and may alter corticosteroid metabolism in vivo.Study Design and Methods: Prospective crossover study assessing the impact of 12 weeks of DR-HC on systemic GC metabolism (urinary steroid metabolome profiling), cortisol activation in the liver (cortisone acetate challenge test), and subcutaneous adipose tissue (microdialysis, biopsy for gene expression analysis) in 51 patients with AI (primary and secondary) in comparison to IR-HC treatment and age- and BMI-matched controls.Results: Patients with AI receiving IR-HC had a higher median 24-hour urinary excretion of cortisol compared with healthy controls (72.1 µg/24 hours [IQR 43.6-124.2] vs 51.9 µg/24 hours [35.5-72.3], P = .02), with lower global activity of 11β-HSD2 and higher 5-alpha reductase activity. Following the switch from IR-HC to DR-HC therapy, there was a significant reduction in urinary cortisol and total GC metabolite excretion, which was most significant in the evening. There was an increase in 11β-HSD2 activity. Hepatic 11β-HSD1 activity was not significantly altered after switching to DR-HC, but there was a significant reduction in the expression and activity of 11β-HSD1 in subcutaneous adipose tissue.Conclusion: Using comprehensive in vivo techniques, we have demonstrated abnormalities in corticosteroid metabolism in patients with primary and secondary AI receiving IR-HC. This dysregulation of pre-receptor glucocorticoid metabolism results in enhanced glucocorticoid activation in adipose tissue, which was ameliorated by treatment with DR-HC