Randomised controlled trial of short bursts of a potent topical corticosteroid versus prolonged use of a mild preparation for children with mild or moderate atopic eczema

Objective To determine whether a three day burst of a potent corticosteroid is more effective than a mild preparation used for seven days in children with mild or moderate atopic eczema. Design Randomised, double blind, parallel group study of 18 weeks' duration. Setting 13 general practices and a teaching hospital in the Nottingham area. Participants 174 children with mild or moderate atopic eczema recruited from general practices and 33 from a hospital outpatient clinic. Interventions 0.1% betamethasone valerate applied for three days followed by the base ointment for four days versus 1% hydrocortisone applied for seven days. Main outcome measures Primary outcomes were total number of scratch­free days and number of relapses. Secondary outcomes were median duration of relapses, number of undisturbed nights, disease severity (six area, six sign atopic dermatitis severity scale), scores on two quality of life measures (children's life quality index and dermatitis family impact questionnaire), and number of patients in whom treatment failed in each arm. Results No differences were found between the two groups. This was consistent for all outcomes. The median number of scratch­free days was 118.0 for the mild group and 117.5 for the potent group (difference 0.5, 95% confidence interval - 2.0 to 4.0, P = 0.53). The median number of relapses for both groups was 1.0. Both groups showed clinically important improvements in disease severity and quality of life compared with baseline. Conclusion A short burst of a potent topical corticosteroid is just as effective as prolonged use of a milder preparation for controlling mild or moderate atopic eczema in children.

Association of the solute carrier family 11 member 1 gene polymorphisms with susceptibility to leprosy in a Brazilian sample

Natural resistance-associated macrophage protein 1/solute carrier family 11 member 1 gene (Nramp1/Slc11a1) is a gene that controls the susceptibility of inbred mice to intracellular pathogens. Polymorphisms in the human Slc11a1/Nramp1 gene have been associated with host susceptibility to leprosy. This study has evaluated nine polymorphisms of the Slc11a1/Nramp1 gene [(GT)n, 274C/T, 469+14G/C, 577-18G/A, 823C/T, 1029 C/T, 1465-85G/A, 1703G/A, and 1729+55del4] in 86 leprosy patients (67 and 19 patients had the multibacillary and the paucibacillary clinical forms of the disease, respectively), and 239 healthy controls matched by age, gender, and ethnicity. The frequency of allele 2 of the (GT)n polymorphism was higher in leprosy patients [p = 0.04, odds ratio (OR) = 1.49], whereas the frequency of allele 3 was higher in the control group (p = 0.03; OR = 0.66). Patients carrying the 274T allele (p = 0.04; OR = 1.49) and TT homozygosis (p = 0.02; OR = 2.46), such as the 469+14C allele (p = 0.03; OR = 1.53) of the 274C/T and 469+14G/C polymorphisms, respectively, were more frequent in the leprosy group. The leprosy and control groups had similar frequency of the 577-18G/A, 823C/T, 1029C/T, 1465-85G/A, 1703G/A, and 1729+55del4 polymorphisms. The 274C/T polymorphism in exon 3 and the 469+14G/C polymorphism in intron 4 were associated with susceptibility to leprosy, while the allele 2 and 3 of the (GT)n polymorphism in the promoter region were associated with susceptibility and protection to leprosy, respectively.

Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides

This is the author’s version of a work that was accepted for publication in Nanoscale.

Pharmacists’ knowledge and perception of topical antibacterial drug dispensing in community pharmacy setting in Kedah, Malaysia

Purpose: To assess Pharmacists’ Perceptions and Experiences of Topical Antibacterial Drug Dispensing in Community Pharmacy Setting in Kedah State, Malaysia in order to minimize drug resistance issues. Methods: A cross-sectional study involving a pre-validated questionnaire was conducted in community pharmacies within Kedah State, Malaysia. Descriptive statistics and Spearman’s correlation coefficient were used for data analysis. The collected were analysed using statistical package for social sciences (SPSS) version 18.0. Results: The result shows that, 53.4 % of CPs in Kedah State perceived that topical antibacterial is not necessary for every topical bacterial infection. Fusidic acid was the most frequently dispensed topical antibacterial drug while superficial wound was reported to be the most frequently encountered topical bacterial infection. CPs (12.60 %) encountered antibacterial resistance cases but none reported them. The drug that had resistance issue was neomycin. Conclusion: CPs in Kedah State, Malaysia generally have the right perceptions on the dispensing of topical antibacterial drugs. However, their knowledge on the rational use of topical antibacterial drugs and vigilance on antibacterial resistance issue need improvement.

Formulation and stability of topical water in oil emulsion containing corn silk extract

Purpose: To formulate the water in oil (W/O) emulsion of corn silk (CS) extract and to evaluate its stability at various storage conditions. Methods: Ethanol CS extract was prepared using maceration (cold) technique. A 4 % CS emulsion was prepared using varying concentrations of liquid paraffin, ABIL EM90 and water. The formulations were kept at 40 oC for 28 days and to screen out the less stable formulations. The remaining formulations were further stressed at 50 oC to choose the most stable formulation. The optimized formulation was evaluated for physical characteristics including phase separation, rheology and mean droplet size. The physical stability of the formulation was evaluated by monitoring these parameters over a period of 12 weeks at 8, 25, 40 and 40 oC, and 75 % RH. Results: The chosen formulation showed good resistance to phase separation on centrifugation under all storage conditions. Rheological behavior followed non-Newtonian pseudoplastic pattern at various storage conditions. Mean droplet size of freshly prepared formulation was 2.98 ± 1.32 µm and did not show significant (p < 0.05) changes at normal storage conditions (8 and 25 oC). Conclusion: The findings indicate that the developed CS extract W/O emulsion is stable and therefore may be suitable for topical use on skin as an antioxidant preparation.

Extracting topical phrases from clinical documents

In clinical documents, medical terms are often expressed in multi-word phrases. Traditional topic modelling approaches relying on the “bag-of-words” assumption are not effective in extracting topic themes from clinical documents. This paper proposes to first extract medical phrases using an off-the-shelf tool for medical concept mention extraction, and then train a topic model which takes a hierarchy of Pitman-Yor processes as prior for modelling the generation of phrases of arbitrary length. Experimental results on patients’ discharge summaries show that the proposed approach outperforms the state-of-the-art topical phrase extraction model on both perplexity and topic coherence measure and finds more interpretable topics.

Membrane associated transporter protein gene (SLC45A2) and the genetic basis of normal human pigmentation variation

This work is concerned with the genetic basis of normal human pigmentation variation. Specifically, the role of polymorphisms within the solute carrier family 45 member 2 (SLC45A2 or membrane associated transporter protein; MATP) gene were investigated with respect to variation in hair, skin and eye colour ― both between and within populations. SLC45A2 is an important regulator of melanin production and mutations in the gene underly the most recently identified form of oculocutaneous albinism. There is evidence to suggest that non-synonymous polymorphisms in SLC45A2 are associated with normal pigmentation variation between populations. Therefore, the underlying hypothesis of this thesis is that polymorphisms in SLC45A2 will alter the function or regulation of the protein, thereby altering the important role it plays in melanogenesis and providing a mechanism for normal pigmentation variation. In order to investigate the role that SLC45A2 polymorphisms play in human pigmentation variation, a DNA database was established which collected pigmentation phenotypic information and blood samples of more than 700 individuals. This database was used as the foundation for two association studies outlined in this thesis, the first of which involved genotyping two previously-described non-synonymous polymorphisms, p.Glu272Lys and p.Phe374Leu, in four different population groups. For both polymorphisms, allele frequencies were significantly different between population groups and the 272Lys and 374Leu alleles were strongly associated with black hair, brown eyes and olive skin colour in Caucasians. This was the first report to show that SLC45A2 polymorphisms were associated with normal human intra-population pigmentation variation. The second association study involved genotyping several SLC45A2 promoter polymorphisms to determine if they also played a role in pigmentation variation. Firstly, the transcription start site (TSS), and hence putative proximal promoter region, was identified using 5' RNA ligase mediated rapid amplification of cDNA ends (RLM-RACE). Two alternate TSSs were identified and the putative promoter region was screened for novel polymorphisms using denaturing high performance liquid chromatography (dHPLC). A novel duplication (c.–1176_–1174dupAAT) was identified along with other previously described single nucleotide polymorphisms (c.–1721C>G and c.–1169G>A). Strong linkage disequilibrium ensured that all three polymorphisms were associated with skin colour such that the –1721G, +dup and –1169A alleles were associated with olive skin in Caucasians. No linkage disequilibrium was observed between the promoter and coding region polymorphisms, suggesting independent effects. The association analyses were complemented with functional data, showing that the –1721G, +dup and –1169A alleles significantly decreased SLC45A2 transcriptional activity. Based on in silico bioinformatic analysis that showed these alleles remove a microphthalmia-associated transcription factor (MITF) binding site, and that MITF is a known regulator of SLC45A2 (Baxter and Pavan, 2002; Du and Fisher, 2002), it was postulated that SLC45A2 promoter polymorphisms could contribute to the regulation of pigmentation by altering MITF binding affinity. Further characterisation of the SLC45A2 promoter was carried out using luciferase reporter assays to determine the transcriptional activity of different regions of the promoter. Five constructs were designed of increasing length and their promoter activity evaluated. Constitutive promoter activity was observed within the first ~200 bp and promoter activity increased as the construct size increased. The functional impact of the –1721G, +dup and –1169A alleles, which removed a MITF consensus binding site, were assessed using electrophoretic mobility shift assays (EMSA) and expression analysis of genotyped melanoblast and melanocyte cell lines. EMSA results confirmed that the promoter polymorphisms affected DNA-protein binding. Interestingly, however, the protein/s involved were not MITF, or at least MITF was not the protein directly binding to the DNA. In an effort to more thoroughly characterise the functional consequences of SLC45A2 promoter polymorphisms, the mRNA expression levels of SLC45A2 and MITF were determined in melanocyte/melanoblast cell lines. Based on SLC45A2’s role in processing and trafficking TYRP1 from the trans-Golgi network to stage 2 melanosmes, the mRNA expression of TYRP1 was also investigated. Expression results suggested a coordinated expression of pigmentation genes. This thesis has substantially contributed to the field of pigmentation by showing that SLC45A2 polymorphisms not only show allele frequency differences between population groups, but also contribute to normal pigmentation variation within a Caucasian population. In addition, promoter polymorphisms have been shown to have functional consequences for SLC45A2 transcription and the expression of other pigmentation genes. Combined, the data presented in this work supports the notion that SLC45A2 is an important contributor to normal pigmentation variation and should be the target of further research to elucidate its role in determining pigmentation phenotypes. Understanding SLC45A2’s function may lead to the development of therapeutic interventions for oculocutaneous albinism and other disorders of pigmentation. It may also help in our understanding of skin cancer susceptibility and evolutionary adaptation to different UV environments, and contribute to the forensic application of pigmentation phenotype prediction.

Chasing reporters : Infotainment, intertextuality and media satire

The Chaser’s War on Everything is a night time entertainment program which screened on Australia’s public broadcaster, the ABC in 2006 and 2007. This enormously successful comedy show managed to generate a lot of controversy in its short lifespan (see, for example, Dennehy, 2007; Dubecki, 2007; McLean, 2007; Wright, 2007), but also drew much praise for its satirising of, and commentary on, topical issues. Through interviews with the program’s producers, qualitative audience research and textual analysis, this paper will focus on this show’s media satire, and the segment ‘What Have We Learned From Current Affairs This Week?’ in particular. Viewed as a form of ‘Critical Intertextuality’ (Gray, 2006), this segment (which offered a humorous critique of the ways in which news and current affairs are presented elsewhere on television) may equip citizens with a better understanding of the new genre’s production methods, thus producing a higher level of public media literacy. This paper argues that through its media satire, The Chaser acts not as a traditional news program would in informing the public with new information, but as a text which can inform and shape our understanding of news that already exists within the public sphere. Humorous analyses and critiques of the media (like those analysed in this paper), are in fact very important forms of infotainment, because they can provide “other, ‘improper,’ and yet more media literate and savvy interpretations” (Gray, 2006, p. 4) of the news.

Biomechanical aspects of bone microstructure in vertebrates : potential approach to paleontological investigations

The biomechanical or biophysical principles can be applied to study biological structures in their modern or fossil form. Bone is an important tissue in paleontological studies as it is a commonly preserved element in most fossil vertebrates, and can often allow its microstructures such as lacuna and canaliculi to be studied in detail. In this context, the principles of Fluid Mechanics and Scaling Laws have been previously applied to enhance the understanding of bone microarchitecture and their implications for the evolution of hydraulic structures to transport fluid. It has been shown that the microstructure of bone has evolved to maintain efficient transport between the nutrient supply and cells, the living components of the tissue. Application of the principle of minimal expenditure of energy to this analysis shows that the path distance comprising five or six lamellar regions represents an effective limit for fluid and solute transport between the nutrient supply and cells; beyond this threshold, hydraulic resistance in the network increases and additional energy expenditure is necessary for further transportation. This suggests an optimization of the size of bone’s building blocks (such as osteon or trabecular thickness) to meet the metabolic demand concomitant to minimal expenditure of energy. This biomechanical aspect of bone microstructure is corroborated from the ratio of osteon to Haversian canal diameters and scaling constants of several mammals considered in this study. This aspect of vertebrate bone microstructure and physiology may provide a basis of understanding of the form and function relationship in both extinct and extant taxa.

Survey research

This book aims to provide an overview of approaches to assist researchers and practitioners to explore ways of undertaking research in the information literacy field. The first chapter provides an introductory overview of research by Dr Kirsty Williamson (author of Research Methods for Students, Academics and Professionals: Information Management and Systems) and this sets the scene for the rest of the chapters where each author explores the key aspects of a specific method and explains how it may be applied in practice. The methods covered include those representing qualitative, quantitative and mixed methods. Both a chapter on the topical evidence-based practice approach, and another critiquing it, are also included. The final chapter points the way towards potential new directions for the burgeoning field

Challenging cohesion

Cohesion as a term connotes attraction, unity, and commonness amongst discrete entities. Considering cohesion as a concept is timely with the recent rise of network culture, which comes with both subtle and radical changes in how people connect with, position themselves in relation to, and understand other constituents of society (cf. Varnelis; Castells; Jenkins et al.). Such dis- and inter-connections signify an imminent and immanent epistemological challenge we must confront: how can we understand inherently multi-faceted subjects, components of which are in constant transformation? For researchers, disciplinary complexity is one of the main implications of this situation. While disciplinary integration may be an effective or vital component in pursuit of knowledge (cf. Nicolescu) it may also impart significant conceptual and pragmatic conflicts. What are possible ways to coalesce multiple dimensions of reality that can lead to conceptually cohesive and useful knowledge production? This issue of M/C Journal attempts to answer this question by looking at different perspectives on the notion of cohesion across topical and disciplinary boundaries.

A new future for growth factor complexes as wound therapies?

Background: Topical administration of growth factors (GFs) has displayed some potential in wound healing, but variable efficacy, high doses and costs have hampered their implementation. Moreover, this approach ignores the fact that wound repair is driven by interactions between multiple GFs and extracellular matrix (ECM) proteins. The Problem: Deep dermal partial thickness burn (DDPTB) injuries are the most common burn presentation to pediatric hospitals and also represent the most difficult burn injury to manage clinically. DDPTB often repair with a hypertrophic scar. Wounds that close rapidly exhibit reduced scarring. Thus treatments that shorten the time taken to close DDTPB’s may coincidently reduce scarring. Basic/Clinical Science Advances: We have observed that multi-protein complexes comprised of IGF and IGF-binding proteins bound to the ECM protein vitronectin (VN) significantly enhance cellular functions relevant to wound repair in human skin keratinocytes. These responses require activation of both the IGF-1R and the VN-binding αv integrins. We have recently evaluated the wound healing potential of these GF:VN complexes in a porcine model of DDTPB injury. Clinical Care Relevance: This pilot study demonstrates that GF:VN complexes hold promise as a wound healing therapy. Enhanced healing responses were observed after treatment with nanogram doses of the GF:VN complexes in vitro and in vivo. Critically healing was achieved using substantially less GF than studies in which GFs alone have been used. Conclusion: These data suggest that coupling GFs to ECM proteins, such as VN, may ultimately prove to be an improved technique for the delivery of novel GF-based wound therapies.

The impact of psychosocial factors on adherence to compression therapy to prevent recurrence of venous leg ulcers

Aims To identify self-care activities undertaken and determine relationships between self-efficacy, depression, quality of life, social support and adherence to compression therapy in a sample of patients with chronic venous insufficiency. Background Up to 70% of venous leg ulcers recur after healing. Compression hosiery is a primary strategy to prevent recurrence, however, problems with adherence to this strategy are well documented and an improved understanding of how psychosocial factors influence patients with chronic venous insufficiency will help guide effective preventive strategies. Design Cross-sectional survey and retrospective medical record review. Method All patients previously diagnosed with a venous leg ulcer which healed between 12–36 months prior to the study were invited to participate. Data on health, psychosocial variables and self-care activities were obtained from a self-report survey and data on medical and previous ulcer history were obtained from medical records. Multiple linear regression modelling was used to determine the independent influences of psychosocial factors on adherence to compression therapy. Results In a sample of 122 participants, the most frequently identified self-care activities were application of topical skin treatments, wearing compression hosiery and covering legs to prevent trauma. Compression hosiery was worn for a median of 4 days/week (range 0–7). After adjustment for all variables and potential confounders in a multivariable regression model, wearing compression hosiery was found to be significantly positively associated with participants’ knowledge of the cause of their condition (p=0.002), higher self-efficacy scores (p=0.026) and lower depression scores (p=0.009). Conclusion In this sample, depression, self-efficacy and knowledge were found to be significantly related to adherence to compression therapy. Relevance to clinical practice These findings support the need to screen for and treat depression in this population. In addition, strategies to improve patient knowledge and self-efficacy may positively influence adherence to compression therapy.

Widening the gap between measurement and modelling of secondary organic aerosol properties?

The link between measured sub-saturated hygroscopicity and cloud activation potential of secondary organic aerosol particles produced by the chamber photo-oxidation of α-pinene in the presence or absence of ammonium sulphate seed aerosol was investigated using two models of varying complexity. A simple single hygroscopicity parameter model and a more complex model (incorporating surface effects) were used to assess the detail required to predict the cloud condensation nucleus (CCN) activity from the subsaturated water uptake. Sub-saturated water uptake measured by three hygroscopicity tandem differential mobility analyser (HTDMA) instruments was used to determine the water activity for use in the models. The predicted CCN activity was compared to the measured CCN activation potential using a continuous flow CCN counter. Reconciliation using the more complex model formulation with measured cloud activation could be achieved widely different assumed surface tension behavior of the growing droplet; this was entirely determined by the instrument used as the source of water activity data. This unreliable derivation of the water activity as a function of solute concentration from sub-saturated hygroscopicity data indicates a limitation in the use of such data in predicting cloud condensation nucleus behavior of particles with a significant organic fraction. Similarly, the ability of the simpler single parameter model to predict cloud activation behaviour was dependent on the instrument used to measure sub-saturated hygroscopicity and the relative humidity used to provide the model input. However, agreement was observed for inorganic salt solution particles, which were measured by all instruments in agreement with theory. The difference in HTDMA data from validated and extensively used instruments means that it cannot be stated with certainty the detail required to predict the CCN activity from sub-saturated hygroscopicity. In order to narrow the gap between measurements of hygroscopic growth and CCN activity the processes involved must be understood and the instrumentation extensively quality assured. It is impossible to say from the results presented here due to the differences in HTDMA data whether: i) Surface tension suppression occurs ii) Bulk to surface partitioning is important iii) The water activity coefficient changes significantly as a function of the solute concentration.