The development and evaluation of antibacterial polymer-phyllosilicate composite systems for the treatment of infected wounds

Clays and clay minerals (phyllosilicates) have been used for millennia to treat a range of human maladies, such as infected wounds and diseases of the skin. The unique chemistry of phyllosilicates allows them to support the wound environment and encourage healing. Their physicochemical properties can also be utilised to develop modified drug-release formulations and also enables their incorporation into polymer matrices for the development of advanced wound care materials. By developing novel antibacterial phyllosilicate-polymer composite materials it should be possible to support wound healing, whilst simultaneously treating infections locally to avoid systemic adverse effects and prevent the development of antimicrobial resistance. In this research project the clay minerals kaolin (KN), refined montmorillonite (rMMT), montmorilonite K10 (MMTK10), Laponite® RD (LRD), and Laponite® XL21 (LXL21) were investigated for their differing structure and physicochemical properties. Their ability to adsorb and desorb the antibacterial agents tetracycline (TC), doxycycline (DC) and ciprofloxacin (CIP) was determined through a series of adsorption kinetics and isotherm studies. LRD and LXL21 were shown to have the highest drug-carrying capacity and were also able to relinquish this drug-load to inhibit the proliferation of key wound pathogens; Staphylococcus epidermidis, Propionibacterium acnes, and Pseudomonas aeruginosa. XRD and FTIR analyses demonstrated that these drug molecules could be adsorbed into the interlayer space and edge groups of the Laponite® particles. LXL21-CIP composites were successfully incorporated into alginate polymer matrices through interaction of the exposed edge-groups on LXL21 and the hydroxyl groups of the alginate to produce novel nanocomposite film and foam materials. Selection of candidate materials was initially undertaken qualitatively with the support of a tissue viability nurse at the Royal Liverpool and Broadgreen University Hospitals NHS Trust. Important properties for wound-dressings such as adsorptive capacity, water vapour transmission rate, and keratinocyte compatibility were measured quantitatively and compared to materials already used for wound care in the UK. Both the film and foam materials were shown to have properties that would be beneficial for wound healing and were also able to release CIP in a controlled manner with notable activity against S. epidermidis, P. acnes, and P. aeruginosa. The nanocomposite film formulation developed in this research project showed promise for future clinical applications and future work should be undertaken to further optimise their manufacture and fully characterise their ability to support the healing of infected wounds. Although the nanocomposite foams require further research, the work presented in this thesis suggests they could also be promising materials for wound care applications

Formulation and antibacterial properties of clay mineral-tetracycline and -doxycycline composites

Clay minerals have been used as adsorbents for decades but research into their use within healthcare as drug-carriers and modified drug release materials is an increasingly common area of interest. In current clinical practice the management of acute bacterial skin and skin-structure infections (ABSSSIs) requires patients to take systemic antibacterial treatment due to a lack of appropriate topical options. In this research tetracycline (TC) and doxycycline (DC) were adsorbed onto a range of clay minerals (kaolinite, montmorillonite, acid-activated montmorillonite, Laponite® RD and Laponite® XL21) to evaluate their potential as materials for the delivery of these antibiotics to infected wounds. A dispersion pH that favoured the zwitterionic form of the antibiotic molecules was shown to favour adsorption onto the clay minerals. FTIR and pXRD showed that positively charged groups on the antibiotic molecules interacted with the negatively charged clay mineral surface, whilst negatively charged groups on the antibiotic molecules could interact with the positively charged edge-sites of the clay minerals. Swelling clays such as the two Laponites® were able to adsorb much more TC and DC due to their structure and chemistry. The clay minerals alone did not have any antibacterial effects against Staphylococcus epidermidis, Cutibacterium acnes, and Pseudomonas aeruginosa. Antibiotic containing composites successfully released TC and DC, exhibiting activity against the three bacterial strains proportional to the antibiotic-loading on the composites. This research demonstrates the ability of these clay minerals to deliver TC and DC against common skin pathogens and their potential for future development towards clinical applications

Transverse magnetic focussing of heavy holes in a (100) GaAs quantum well

We perform magnetic focussing of high mobility holes confined in a shallow GaAs/Al0.33Ga0.67As quantum well grown on a (100) GaAs substrate. We observe ballistic focussing of holes over a path length of up to 4.9µm with a large number of focussing peaks. We show that additional structure on the focussing peaks can be caused by a combination of the finite width of the injector QPC and Shubnikov-de Haas oscillations. These results pave the way to studies of spin-dependent magnetic focussing and spin relaxation lengths in 2D hole systems without complications of crystal anisotropies and anisotropic g-tensors.We thank Scott Liles, Samuel Bladwell, Oleg Sushkov and Ulrich Zülicke for numerous discussions. This project was supported by the Australian Research Council (ARC) DP Scheme and the EPSRC (UK). Devices were fabricated using facilities at the UNSW Node of Australian National Fabrication Facility (ANFF).This is the final version of the article. It first appeared from IOP via http://dx.doi.org/10.1088/0268-1242/30/10/10200

Probing Density Fluctuations using the FIRST Radio Survey

We use results of angular clustering measurements in 3000 sq. deg's of the FIRST radio survey to infer information on spatial clustering. Measurements are compared with CDM-model predictions. Clustering of FIRST sources with optical ID's in the APM catalog are also investigated. Finally, we outline a preliminary search for a weak lensing signal in the survey.Comment: 6 pages latex, 2 figures, to appear in Cosmology with the New Radio Surveys (Kluwer

A qualitative analysis of offenders' modus operandi in sexually exploitative interactions with children online

Transcripts of chat logs of naturally-occurring, sexually exploitative interactions between offenders and victims that took place via Internet communication platforms were analyzed. The aim of the study was to examine the modus operandi of offenders in such interactions, with particular focus on the specific strategies they use to engage victims, including discursive tactics. We also aimed to ascertain offenders’ underlying motivation and function of engagement in online interactions with children. Five cases, comprising 29 transcripts, were analyzed using qualitative thematic analysis with a discursive focus. In addition to this, police reports were reviewed for descriptive and case-specific information. Offenders were men aged between 27 and 52 years (M = 33.6, SD = 5.6), and the number of children they communicated with ranged from one to twelve (M = 4.6, SD = 4.5). Victims were aged between 11 and 15 (M = 13.00, SD = 1.2), and were both female and male. Three offenders committed online sexual offenses, and two offenders committed contact sexual offenses in addition to online sexual offenses. The analysis of transcripts revealed that interactions between offenders and victims were of a highly sexual nature, and that offenders employed a range of manipulative strategies to engage victims and achieve their compliance. It appeared that offenders engaged in such interactions for the purpose of sexual arousal and gratification, as well as fantasy fulfillment

Hybrid architecture for shallow accumulation mode AlGaAs/GaAs heterostructures with epitaxial gates

Accumulation mode devices with epitaxially grown gates have excellent electrical stability due to the absence of dopant impurities and surface states. We overcome typical fabrication issues associated with epitaxially gated structures (e.g., gate leakage and high contact resistance) by using separate gates to control the electron densities in the Ohmic and Hall bar regions. This hybrid gate architecture opens up a way to make ultrastable nanoscale devices where the separation between the surface gates and the 2D electron gas is small. In this work, we demonstrate that the hybrid devices made from the same wafer have reproducible electrical characteristics, with identical mobility and density traces over a large range of 2D densities. In addition, thermal cycling does not influence the measured electrical characteristics. As a demonstration of concept, we have fabricated a hybrid single-electron transistor on a shallow (50 nm) AlGaAs/GaAs heterostructure that shows clear Coulomb blockade oscillations in the low temperature conductance.This project was supported by the Australian Government under the Australia-India Strategic Research Fund and by the Australian Research Council (ARC) DP scheme. A.R.H. acknowledges an ARC Outstanding Researcher Award. Devices were fabricated using the facilities at the NSW Node of the Australian National Fabrication Facility (ANFF). J.R., A.L., and A.D.W. acknowledge support from Mercur Pr-2013-0001, BMBF-Q.com-H 16KIS0109, and DFH/UFA CDFA-05-06.Copyright (2015) American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. The following article appeared in MacLeod SJ, See AM, Hamilton AR, Farrer I, Ritchie DA, Ritzmann J, Ludwig A, Wieck AD, Applied Physics Letters 106, 012105 (2015) and may be found at http://dx.doi.org/10.1063/1.4905210

Interactive effects of inbreeding and endocrine disruption on reproduction in a model laboratory fish

This is the final version of the article. Available from Wiley via the DOI in this record.Inbreeding depression is expected to be more severe in stressful environments. However, the extent to which inbreeding affects the vulnerability of populations to environmental stressors, such as chemical exposure, remains unresolved. Here we report on the combined impacts of inbreeding and exposure to an endocrine disrupting chemical (the fungicide clotrimazole) on zebrafish (Danio rerio). We show that whilst inbreeding can negatively affect reproductive traits, not all traits are affected equally. Inbreeding depression frequently only became apparent when fish were additionally stressed by chemical exposure. Embryo viability was significantly reduced in inbred exposed fish and there was a tendency for inbred males to sire fewer offspring when in direct competition with outbred individuals. Levels of plasma 11-ketotestosterone, a key male sex hormone, showed substantial inbreeding depression that was unaffected by addition of the fungicide. In contrast, there was no effect of inbreeding or clotrimazole exposure on egg production. Overall, our data provide evidence that stress may amplify the effects of inbreeding on key reproductive traits, particularly those associated with male fitness. This may have important implications when considering the consequences of exposure to chemical pollutants on the fitness of wild populations.Thanks to NERC's Post Genomics & Proteomics Programme NE/F0077871/1 and AstraZeneca's Safety, Health and Environment Research Programme for funding this work. We thank Alexander Scott (11-ketotestosterone radioimmunoassay) at the Centre for Environment, Fisheries and Aquaculture Science, Jan Shears and Luanne Wilkes at University of Exeter, Gareth Readman, Vicki Cammack, Kate Hurd and Yohanna Glennon at Brixham Environmental Laboratory for their assistance

The 'At-risk mental state' for psychosis in adolescents : clinical presentation, transition and remission.

Despite increased efforts over the last decade to prospectively identify individuals at ultra-high risk of developing a psychotic illness, limited attention has been specifically directed towards adolescent populations (<18 years). In order to evaluate how those under 18 fulfilling the operationalised criteria for an At-Risk Mental State (ARMS) present and fare over time, we conducted an observational study. Participants (N = 30) generally reported a high degree of functional disability and frequent and distressing perceptual disturbance, mainly in the form of auditory hallucinations. Seventy percent (21/30) were found to fulfil the criteria for a co-morbid ICD-10 listed mental health disorder, with mood (affective; 13/30) disorders being most prevalent. Overall transition rates to psychosis were low at 24 months follow-up (2/28; 7.1 %) whilst many participants demonstrated a significant reduction in psychotic-like symptoms. The generalisation of these findings may be limited due to the small sample size and require replication in a larger sample

Ibuprofen intercalation and release from different layered double hydroxides.

AIM: The chemical composition of layered double hydroxides (LDHs) affects their structure and properties. The method of ibuprofen (IBU) intercalation into LDHs may modify its release, reduce adverse effects and decrease the required dosing frequency. METHODOLOGY: This study investigates the effects of four different LDHs; MgAl-LDH, MgFe-LDH, NiAl-LDH and NiFe-LDH on in vitro release of IBU intercalated by coprecipitation and anionic-exchange. RESULTS: MgAl-LDH was the most crystalline and substitution of either cation decreased LDH order. Fourier-transform infrared spectra and power x-ray diffractograms confirmed the intercalation of IBU within the lamellar structure of MgAl-LDH and MgFe-LDH. Intercalation of IBU by anion-exchange resulted in slower, partial, drug release compared with coprecipitation. CONCLUSION: The chemical composition of LDHs affects their crystallinity, IBU intercalation and subsequent release

Noncollinear paramagnetism of a GaAs two-dimensional hole system.

We have performed transport measurements in tilted magnetic fields in a two-dimensional hole system grown on the surface of a (311)A GaAs crystal. A striking asymmetry of Shubnikov-de Haas oscillations occurs upon reversing the in-plane component of the magnetic field along the low-symmetry [2[over ¯]33] axis. As usual, the magnetoconductance oscillations are symmetric with respect to reversal of the in-plane field component aligned with the high-symmetry [011[over ¯]] axis. Our observations demonstrate that an in-plane magnetic field can generate an out-of-plane component of magnetization in a low-symmetry hole system, creating new possibilities for spin manipulation.This work was supported by the Australian Research Council (ARC) under the DP scheme and by the NSF under Grant No. DMR-1310199. ARH acknowledges an ARC DOR award.This is the accepted manuscript. The final version is available from APS at http://journals.aps.org/prl/abstract/10.1103/PhysRevLett.113.236401