Development of Coherent Raman Scattering Microscopy for Monitoring Drug Delivery

Topical pharmaceuticals are a vitally important part of modern medicine. Currently, characterising the dermatopharmacokinetics of these drugs is very difficult, and not possible in either real-time, or with a high level of accuracy. This thesis applies three coherent Raman scattering microscopy techniques to the challenge of video-rate monitoring of a porcine skin model undergoing penetration by two different, widely used, pharmaceuticals. It was found that the data taken during these time-course experiments could be used in conjunction with a Beer-Lambert expression, and Fick’s second law, to extract valuable permeation data – namely the skin-solute partition coefficient, and diffusion coefficient – of these pharmaceuticals

A fluorescence lifetime-based fibre-optic glucose sensor using glucose/galactose-binding protein

Alternative, non-electrochemistry-based technologies for continuous glucose monitoring are needed for eventual use in diabetes mellitus. As part of a programme investigating fluorescent glucose sensors, we have developed fibre-optic biosensors using glucose/galactose binding protein (GBP) labelled with the environmentally sensitive fluorophore, Badan. GBP-Badan was attached via an oligohistidine-tag to the surface of Ni-nitrilotriacetic acid (NTA)-functionalized agarose or polystyrene beads. Fluorescence lifetime increased in response to glucose, observed by fluorescence lifetime imaging microscopy of the GBP-Badan-beads. Either GBP-Badan agarose or polystyrene beads were loaded into a porous chamber at the end of a multimode optical fibre. Fluorescence lifetime responses were recorded using pulsed laser excitation, high speed photodiode detection and time-correlated single-photon counting. The maximal response was at 100 mM glucose with an apparent K-d of 13 mM (agarose) and 20 mM (polystyrene), and good working-day stability was demonstrated. We conclude that fluorescence lifetime fibre-optic glucose sensors based on GBP-Badan are suitable for development as clinical glucose monitors

Anabranching and maximum flow efficiency in Magela Creek, northern Australia

Anabranching is the prevailing river pattern found along alluvial tracts of the world's largest rivers. Hydraulic geometry and bed material discharge are compared between single channel and anabranching reaches up to 4 times bank-full discharge in Magela Creek, northern Australia. The anabranching channels exhibit greater sediment transporting capacity per unit available stream power, i.e., maximum flow efficiency (MFE). Simple flume experiments corroborate our field results showing the flow efficiency gains associated with anabranching, and highlight the prospect of a dominant anabranch, which is found in many anabranching rivers. These results demonstrate that anabranching can constitute a stable river pattern in dynamic equilibrium under circumstances in which a continuous single channel would be unable to maintain sediment conveyance. We propose the existence of a flow efficiency continuum that embraces dynamic equilibrium and disequilibrium (vertically accreting) anabranching rivers

Mycobacterium avium subspecies paratuberculosis:human exposure through environmental and domestic aerosols

Mycobacterium avium subspecies paratuberculosis (Map) causes Johne’s disease in animals and is significantly associated with Crohn’s disease (CD) in humans. Our previous studies have shown Map to be present in U.K. rivers due to land deposition from chronic livestock infection and runoff driven by rainfall. The epidemiology of CD in Cardiff showed a significant association with the River Taff, in which Map can be detected on a regular basis. We have previously hypothesized that aerosols from the river might influence the epidemiology of CD. In this preliminary study, we detected Map by quantitative PCR in one of five aerosol samples collected above the River Taff. In addition, we examined domestic showers from different regions in the U.K. and detected Map in three out of 30 independent samples. In detecting Map in river aerosols and those from domestic showers, this is the first study to provide evidence that aerosols are an exposure route for Map to humans and may play a role in the epidemiology of CD

Activation of anion redox in P3 structure cobalt-doped sodium manganese oxide via introduction of transition metal vacancies

EJK would like to thank the Alistore ERI for the award of a studentship. This work was supported by the Faraday Institution (grant number FIRG018).Additional capacity delivered by oxygen redox activity may in principle represent a means of enhancing the electrochemical performance of layered sodium transition metal oxides. However, irreversible structural changes occurring during cycling typically cause significant capacity fade with limited reversibility of oxygen redox processes. Here, P3-structure Na0.67Co0.2Mn0.8O2 was synthesised under two different reaction conditions. Both materials exhibit very stable cycling performance in the voltage range 1.8-3.8 V where the redox couples of transition metals entirely dominate the electrochemical reaction. For the compound prepared under more oxidising conditions, anion redox activity is triggered in the wider voltage window 1.8-4.4 V in a reversible manner with exceptionally small voltage hysteresis (20 mV). The presence of vacancies in the transition metal layers is shown to play a critical role not only in generating unpaired O 2p states but also in stabilising the crystal structure in the high voltage region.PostprintPostprintPeer reviewe

In vivo glucose sensing for diabetes management : progress towards non-invasive monitoring

A device for continuous in vivo monitoring of glucose concentration in people with diabetes has been a clinical and research priority for many years but now has an urgency which is probably unquestioned in diabetes care. The purpose of this article is to explain recent advances in technology that are bringing glucose sensors closer to routine use and to highlight some of the remaining problems. Important new technologies include artificial receptors for glucose, tissue fluid sampling techniques, and new approaches to non-invasive sensing, such as fluorescence lifetime measurements

Insulin pump therapy with automated insulin suspension in response to hypoglycemia: reduction in nocturnal hypoglycemia in those at greatest risk.

OBJECTIVE: To evaluate a sensor-augmented insulin pump with a low glucose suspend (LGS) feature that automatically suspends basal insulin delivery for up to 2 h in response to sensor-detected hypoglycemia. RESEARCH DESIGN AND METHODS: The LGS feature of the Paradigm Veo insulin pump (Medtronic, Inc., Northridge, CA) was tested for 3 weeks in 31 adults with type 1 diabetes. RESULTS: There were 166 episodes of LGS: 66% of daytime LGS episodes were terminated within 10 min, and 20 episodes lasted the maximum 2 h. LGS use was associated with reduced nocturnal duration ≤2.2 mmol/L in those in the highest quartile of nocturnal hypoglycemia at baseline (median 46.2 vs. 1.8 min/day, P = 0.02 [LGS-OFF vs. LGS-ON]). Median sensor glucose was 3.9 mmol/L after 2-h LGS and 8.2 mmol/L at 2 h after basal restart. CONCLUSIONS: Use of an insulin pump with LGS was associated with reduced nocturnal hypoglycemia in those at greatest risk and was well accepted by patients

Carbapenemase-producing Enterobacteriaceae in hospital wastewater:a reservoir that may be unrelated to clinical isolates [star]

Summary Background: Carbapenemase-producing Enterobacteriaceae (CPE) are an emerging infection control problem in hospitals worldwide. Identifying carriers can help reduce potential spread and infections. Aim: To assess whether testing hospital wastewater for CPE can supplement patient based screening for infection prevention purposes in a hospital without a recognised endemic CPE problem. Methods: Wastewater collected from hospital pipework on 16 occasions during February-March 2014 was screened for CPE using chromID®CARBA agar and chromID®CPS agar with a 10 μg ertapenem disc and combination disc testing. MICs were determined using British Society for Antimicrobial Chemotherapy methodology and carbapenemase genes detected by PCR or wholegenome sequencing. Selected isolates were typed by PFGE. Findings: Suspected CPE were recovered from all 16 wastewater samples. Of 17 isolates sent to Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, six (four Citrobacter freundii and two Enterobacter cloacae complex) were New Delhi metallo–beta-lactamase (NDM) producers and the remaining 11 (six Klebsiella oxytoca and five Enterobacter cloacae complex), Guiana-Extended-Spectrum-5 (GES-5) producers, the first to be described in Enterobacteriaceae in the UK. The four NDM-producing C. freundii, two NDM-producing E. cloacae complex and 4/5 GES-5-producing E. cloacae complex were each indistinguishable isolates of the same three strains, whereas the six GES-5-producing K. oxytoca overall shared 79% similarity. Conclusion: CPE are readily isolated from hospital wastewater using simple culture methods. There are either undetected carriers of CPE excreting into the wastewater, or these CPE represent colonisation of the pipework. Surveillance of hospital wastewater for CPE does not appear helpful for infection control purposes