Tracking the magmatic evolution of island arc volcanism : insights from a high-precision Pb isotope record of Montserrat, Lesser Antilles

The volcanic succession on Montserrat provides an opportunity to examine the magmatic evolution of island arc volcanism over a ∼2.5 Ma period, extending from the andesites of the Silver Hills center, to the currently active Soufrière Hills volcano (February 2010). Here we present high-precision double-spike Pb isotope data, combined with trace element and Sr-Nd isotope data throughout this period of Montserrat's volcanic evolution. We demonstrate that each volcanic center; South Soufrière Hills, Soufrière Hills, Centre Hills and Silver Hills, can be clearly discriminated using trace element and isotopic parameters. Variations in these parameters suggest there have been systematic and episodic changes in the subduction input. The SSH center, in particular, has a greater slab fluid signature, as indicated by low Ce/Pb, but less sediment addition than the other volcanic centers, which have higher Th/Ce. Pb isotope data from Montserrat fall along two trends, the Silver Hills, Centre Hills and Soufrière Hills lie on a general trend of the Lesser Antilles volcanics, whereas SSH volcanics define a separate trend. The Soufrière Hills and SSH volcanic centers were erupted at approximately the same time, but retain distinctive isotopic signatures, suggesting that the SSH magmas have a different source to the other volcanic centers. We hypothesize that this rapid magmatic source change is controlled by the regional transtensional regime, which allowed the SSH magma to be extracted from a shallower source. The Pb isotopes indicate an interplay between subduction derived components and a MORB-like mantle wedge influenced by a Galapagos plume-like source.

Non-combinatorial library screening reveals subsite cooperativity and identifies new high-efficiency substrates for kallikrein-related peptidase 14

An array of substrates link the tryptic serine protease, kallikrein-related peptidase 14 (KLK14), to physiological functions including desquamation and activation of signaling molecules associated with inflammation and cancer. Recognition of protease cleavage sequences is driven by complementarity between exposed substrate motifs and the physicochemical signature of an enzyme's active site cleft. However, conventional substrate screening methods have generated conflicting subsite profiles for KLK14. This study utilizes a recently developed screening technique, the sparse matrix library, to identify five novel high-efficiency sequences for KLK14. The optimal sequence, YASR, was cleaved with higher efficiency (k(cat)/K(m)=3.81 ± 0.4 × 10(6) M(-1) s(-1)) than favored substrates from positional scanning and phage display by 2- and 10-fold, respectively. Binding site cooperativity was prominent among preferred sequences, which enabled optimal interaction at all subsites as indicated by predictive modeling of KLK14/substrate complexes. These simulations constitute the first molecular dynamics analysis of KLK14 and offer a structural rationale for the divergent subsite preferences evident between KLK14 and closely related KLKs, KLK4 and KLK5. Collectively, these findings highlight the importance of binding site cooperativity in protease substrate recognition, which has implications for discovery of optimal substrates and engineering highly effective protease inhibitors.

Digital Storytelling within a Service-Learning Partnership: Technology as Product and Process for University Students and Culturally and Linguistically Diverse High School Youth

This chapter describes a university/high school partnership focused on digital storytelling. It also explains the multi-stage process used to establish this successful partnership and project. The authors discuss the central role that technology played in developing this university/high school partnership, a collaboration that extended the impact of a digital storytelling project to reach high school students, university students, educators, high school administrators, and the local community. Valuing a reflective process that can lead to the creation of a powerful final product, the authors describe the impact of digital storytelling on multiple stakeholders, including the 13 university students and 33 culturally and linguistically diverse high school youth who participated during the fall of 2009. In addition, the chapter includes reflections from university and high school student participants expressed during focus groups conducted throughout the project. While most participants had a positive experience with the project, complications with the technology component often caused frustrations and additional challenges. Goals for sharing this project are to critically evaluate digital storytelling, describe lessons learned, and recommend good practices for others working within a similar context or with parallel goals.

Reflective practice as a tool for addressing high levels of psychological distress in Australian law schools and the legal profession

This paper discusses: -The need for law schools to use curriculum as a site for positive interventions to support student psychological well-being. -The potential for law school interventions to impact on the psychological well-being of the profession. -Reflective practice as a possible tool for promoting psychological well-being in law school and the profession because it provides a way of coping with ‘indeterminate zones’ of experience.

Assessing the impact of a food supplement on the nutritional status and body composition of HIV-infected Zambian women on ARVs

Background Zambia is a sub-Saharan country with one of the highest prevalence rates of HIV, currently estimated at 14%. Poor nutritional status due to both protein-energy and micronutrient malnutrition has worsened this situation. In an attempt to address this combined problem, the government has instigated a number of strategies, including the provision of antiretroviral (ARV) treatment coupled with the promotion of good nutrition. High-energy protein supplement (HEPS) is particularly promoted; however, the impact of this food supplement on the nutritional status of people living with HIV/AIDS (PLHA) beyond weight gain has not been assessed. Techniques for the assessment of nutritional status utilising objective measures of body composition are not commonly available in Zambia. The aim of this study is therefore to assess the impact of a food supplement on nutritional status using a comprehensive anthropometric protocol including measures of skinfold thickness and circumferences, plus the criterion deuterium dilution technique to assess total body water (TBW) and derive fat-free mass (FFM) and fat mass (FM). Methods/Design This community-based controlled and longitudinal study aims to recruit 200 HIV-infected females commencing ARV treatment at two clinics in Lusaka, Zambia. Data will be collected at four time points: baseline, 4-month, 8-month and 12-month follow-up visits. Outcome measures to be assessed include body height and weight, body mass index (BMI), body composition, CD4, viral load and micronutrient status. Discussion This protocol describes a study that will provide a longitudinal assessment of the impact of a food supplement on the nutritional status of HIV-infected females initiating ARVs using a range of anthropometric and body composition assessment techniques.

A randomised controlled trial to prevent hospital readmissions and loss of functional ability in high risk older adults: a study protocol

Background Older people have higher rates of hospital admission than the general population and higher rates of readmission due to complications and falls. During hospitalisation, older people experience significant functional decline which impairs their future independence and quality of life. Acute hospital services comprise the largest section of health expenditure in Australia and prevention or delay of disease is known to produce more effective use of services. Current models of discharge planning and follow-up care, however, do not address the need to prevent deconditioning or functional decline. This paper describes the protocol of a randomised controlled trial which aims to evaluate innovative transitional care strategies to reduce unplanned readmissions and improve functional status, independence, and psycho-social well-being of community-based older people at risk of readmission. Methods/Design The study is a randomised controlled trial. Within 72 hours of hospital admission, a sample of older adults fitting the inclusion/exclusion criteria (aged 65 years and over, admitted with a medical diagnosis, able to walk independently for 3 meters, and at least one risk factor for readmission) are randomised into one of four groups: 1) the usual care control group, 2) the exercise and in-home/telephone follow-up intervention group, 3) the exercise only intervention group, or 4) the in-home/telephone follow-up only intervention group. The usual care control group receive usual discharge planning provided by the health service. In addition to usual care, the exercise and in-home/telephone follow-up intervention group receive an intervention consisting of a tailored exercise program, in-home visit and 24 week telephone follow-up by a gerontic nurse. The exercise only and in-home/telephone follow-up only intervention groups, in addition to usual care receive only the exercise or gerontic nurse components of the intervention respectively. Data collection is undertaken at baseline within 72 hours of hospital admission, 4 weeks following hospital discharge, 12 weeks following hospital discharge, and 24 weeks following hospital discharge. Outcome assessors are blinded to group allocation. Primary outcomes are emergency hospital readmissions and health service use, functional status, psychosocial well-being and cost effectiveness. Discussion The acute hospital sector comprises the largest component of health care system expenditure in developed countries, and older adults are the most frequent consumers. There are few trials to demonstrate effective models of transitional care to prevent emergency readmissions, loss of functional ability and independence in this population following an acute hospital admission. This study aims to address that gap and provide information for future health service planning which meets client needs and lowers the use of acute care services.

Preliminary validation of a novel high-resolution melt-based typing method based on the multilocus sequence typing scheme of Streptococcus pyogenes

The major limitation of current typing methods for Streptococcus pyogenes, such as emm sequence typing and T typing, is that these are based on regions subject to considerable selective pressure. Multilocus sequence typing (MLST) is a better indicator of the genetic backbone of a strain but is not widely used due to high costs. The objective of this study was to develop a robust and cost-effective alternative to S. pyogenes MLST. A 10-member single nucleotide polymorphism (SNP) set that provides a Simpson’s Index of Diversity (D) of 0.99 with respect to the S. pyogenes MLST database was derived. A typing format involving high-resolution melting (HRM) analysis of small fragments nucleated by each of the resolution-optimized SNPs was developed. The fragments were 59–119 bp in size and, based on differences in G+C content, were predicted to generate three to six resolvable HRM curves. The combination of curves across each of the 10 fragments can be used to generate a melt type (MelT) for each sequence type (ST). The 525 STs currently in the S. pyogenes MLST database are predicted to resolve into 298 distinct MelTs and the method is calculated to provide a D of 0.996 against the MLST database. The MelTs are concordant with the S. pyogenes population structure. To validate the method we examined clinical isolates of S. pyogenes of 70 STs. Curves were generated as predicted by G+C content discriminating the 70 STs into 65 distinct MelTs.

Application of high voltage, high frequency pulsed electromagnetic field on cortical bone tissue

Over the last few decades, electric and electromagnetic fields have achieved important role as stimulator and therapeutic facility in biology and medicine. In particular, low magnitude, low frequency, pulsed electromagnetic field has shown significant positive effect on bone fracture healing and some bone diseases treatment. Nevertheless, to date, little attention has been paid to investigate the possible effect of high frequency, high magnitude pulsed electromagnetic field (pulse power) on functional behaviour and biomechanical properties of bone tissue. Bone is a dynamic, complex organ, which is made of bone materials (consisting of organic components, inorganic mineral and water) known as extracellular matrix, and bone cells (live part). The cells give the bone the capability of self-repairing by adapting itself to its mechanical environment. The specific bone material composite comprising of collagen matrix reinforced with mineral apatite provides the bone with particular biomechanical properties in an anisotropic, inhomogeneous structure. This project hypothesized to investigate the possible effect of pulse power signals on cortical bone characteristics through evaluating the fundamental mechanical properties of bone material. A positive buck-boost converter was applied to generate adjustable high voltage, high frequency pulses up to 500 V and 10 kHz. Bone shows distinctive characteristics in different loading mode. Thus, functional behaviour of bone in response to pulse power excitation were elucidated by using three different conventional mechanical tests applying three-point bending load in elastic region, tensile and compressive loading until failure. Flexural stiffness, tensile and compressive strength, hysteresis and total fracture energy were determined as measure of main bone characteristics. To assess bone structure variation due to pulse power excitation in deeper aspect, a supplementary fractographic study was also conducted using scanning electron micrograph from tensile fracture surfaces. Furthermore, a non-destructive ultrasonic technique was applied for determination and comparison of bone elasticity before and after pulse power stimulation. This method provided the ability to evaluate the stiffness of millimetre-sized bone samples in three orthogonal directions. According to the results of non-destructive bending test, the flexural elasticity of cortical bone samples appeared to remain unchanged due to pulse power excitation. Similar results were observed in the bone stiffness for all three orthogonal directions obtained from ultrasonic technique and in the bone stiffness from the compression test. From tensile tests, no significant changes were found in tensile strength and total strain energy absorption of the bone samples exposed to pulse power compared with those of the control samples. Also, the apparent microstructure of the fracture surfaces of PP-exposed samples (including porosity and microcracks diffusion) showed no significant variation due to pulse power stimulation. Nevertheless, the compressive strength and toughness of millimetre-sized samples appeared to increase when the samples were exposed to 66 hours high power pulsed electromagnetic field through screws with small contact cross-section (increasing the pulsed electric field intensity) compare to the control samples. This can show the different load-bearing characteristics of cortical bone tissue in response to pulse power excitation and effectiveness of this type of stimulation on smaller-sized samples. These overall results may address that although, the pulse power stimulation can influence the arrangement or the quality of the collagen network causing the bone strength and toughness augmentation, it apparently did not affect the mineral phase of the cortical bone material. The results also confirmed that the indirect application of high power pulsed electromagnetic field at 500 V and 10 kHz through capacitive coupling method, was athermal and did not damage the bone tissue construction.

DRD2 C957T and TaqIA genotyping reveals gender effects and unique low-risk and high-risk genotypes in alcohol dependence

AIMS: As recent conflicting reports describe a genetic association between both the C- and the T-alleles of the dopamine D2 receptor (DRD2) C957T polymorphism (rs6277) in alcohol-dependent subjects, our aim was to examine this polymorphism and TaqIA (rs1800497) in Australian alcohol-dependent subjects. METHODS: The C957T polymorphism was genotyped in 228 patients with alcohol dependence (72 females and 156 males) and 228 healthy controls. RESULTS: The C-allele and C/C genotype of C957T was associated with alcohol dependence, whereas the TaqIA polymorphism was not. When analysed separately for C957T, males showed an even stronger association with the C-allele and females showed no association. The C957T and TaqIA haplotyping revealed a strong association with alcohol dependence and a double-genotype analysis (combining C957T and TaqIA genotypes) revealed that the relative risk of different genotypes varied by up to 27-fold with the TT/A1A2 having an 8.5-fold lower risk of alcohol dependence than other genotypes. CONCLUSION: Decreased DRD2 binding associated with the C-allele of the DRD2 C957T polymorphism is likely to be important in the underlying pathophysiology of at least some forms of alcohol dependence, and this effect appears to be limited to males only.

Studies on the surface properties of biodegradable polymer carriers in respiratory delivery of drug from Dry Powder Inhaler formulations

Dry Powder Inhaler (DPI) technology has a significant impact in the treatment of various respiratory disorders. DPI formulations consist of a micronized drug (<5ìm) blended with an inert coarse carrier, for which lactose is widely used to date. DPIs are one of the inhalation devices which are used to target the delivery of drugs to the lungs. Drug delivery via DPI formulations is influenced by the physico-chemical characteristics of lactose particles such as size, shape, surface roughness and adhesional forces. Commercially available DPI formulations, which utilise lactose as the carrier, are not efficient in delivering drug to the lungs. The reasons for this are the surface morphology, adhesional properties and surface roughness of lactose. Despite several attempts to modify lactose, the maximum efficient drug delivery to the lungs remains limited; hence, exploring suitable alternative carriers for DPIs is of paramount importance. Therefore, the objective of the project was to study the performance of spherical polymer microparticles as drug carriers and the factors controlling their performance. This study aimed to use biodegradable polymer microspheres as alternative carriers to lactose in DPIs for achieving efficient drug delivery into the lungs. This project focused on fabricating biodegradable polymer microparticles with reproducible surface morphology and particle shape. The surface characteristics of polymeric carriers and the adhesional forces between the drug and carrier particles were investigated in order to gain a better understanding of their influence on drug dispersion. For this purpose, two biodegradable polymers- polycaprolactone (PCL) and poly (DL-lactide-co-glycolide) (PLGA) were used as the carriers to deliver the anti-asthmatic drug - Salbutamol Sulphate (SS). The first study conducted for this dissertation was the aerosolization of SS from mixtures of SS and PCL or PLGA microparticles. The microparticles were fabricated using an emulsion technique and were characterized by laser diffraction for particle size analysis, Scanning Electron Microscopy (SEM) for surface morphology and X-ray Photoelectron Spectroscopy (XPS) to obtain surface elemental composition. The dispersion of the drug from the DPI formulations was determined by using a Twin Stage Impinger (TSI). The Fine particle Fraction (FPF) of SS from powder mixtures was analyzed by High Performance Liquid Chromatography (HPLC). It was found that the drug did not detach from the surface of PCL microspheres. To overcome this, the microspheres were coated with anti-adherent agents such as magnesium stearate and leucine to improve the dispersion of the drug from the carrier surfaces. It was found that coating the PCL microspheres helped in significantly improving the FPF of SS from the PCL surface. These results were in contrast to the PLGA microspheres which readily allowed detachment of the SS from their surface. However, coating PLGA microspheres with antiadherent agents did not further improve the detachment of the drug from the surface. Thus, the first part of the study demonstrated that the surface-coated PCL microspheres and PLGA microspheres can be potential alternatives to lactose as carriers in DPI formulations; however, there was no significant improvement in the FPF of the drug. The second part of the research studied the influence of the size of the microspheres on the FPF of the drug. For this purpose, four different sizes (25 ìm, 48 ìm, 100 ìm and 150 ìm) of the PCL and PLGA microspheres were fabricated and characterized. The dispersion of the drug from microspheres of different sizes was determined. It was found that as the size of the carrier increased there was a significant increase in the FPF of SS. This study suggested that the size of the carrier plays an important role in the dispersion of the drug from the carrier surface. Subsequent experiments in the third part of the dissertation studied the surface properties of the polymeric carrier. The adhesion forces existing between the drug particle and the polymer surfaces, and the surface roughness of the carriers were quantified using Atomic Force Microscopy (AFM). A direct correlation between adhesion forces and dispersion of the drug from the carrier surface was observed suggesting that adhesion forces play an important role in determining the detachment potential of the drug from the carrier surface. However, no direct relationship between the surface roughness of the PCL or PLGA carrier and the FPF of the drug was observed. In conclusion, the body of work presented in this dissertation demonstrated the potential of coated PCL microspheres and PLGA microspheres to be used in DPI formulations as an alternative carrier to sugar based carriers. The study also emphasized the role of the size of the carrier particles and the forces of interaction prevailing between the drug and the carrier particle surface on the aerosolization performances of the drug.

Serious playground : using Second Life to engage high school students in urban planning

Virtual world platforms such as Second Life have been successfully used in educational contexts to motivate and engage learners. This article reports on an exploratory workshop involving a group of high school students using Second Life for an urban planning project. Young people are traditionally an under-represented demographic when it comes to participating in urban planning and decision making processes. The research team developed activities that combined technology with a constructivist approach to learning. Real world experiences and purposes ensured that the workshop enabled students to see the relevance of their learning. Our design also ensured that play remained an important part of the learning. By conceiving of the workshop as a ‘serious playground’ we investigated the ludic potential of learning in a virtual world.