Bronchiectasis exacerbation study on azithromycin and amoxycillin-clavulanate for respiratory exacerbations in children (BEST-2) : study protocol for a randomized controlled trial

Background Bronchiectasis unrelated to cystic fibrosis (CF) is being increasingly recognized in children and adults globally, both in resource-poor and in affluent countries. However, high-quality evidence to inform management is scarce. Oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations, because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis. Azithromycin has a prolonged half-life, and with its unique anti-bacterial, immunomodulatory, and anti-inflammatory properties, presents an attractive alternative. Our proposed study will test the hypothesis that oral azithromycin is non-inferior (within a 20% margin) to amoxycillin-clavulanate at achieving resolution of non-severe respiratory exacerbations by day 21 of treatment in children with non-CF bronchiectasis. Methods This will be a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group trial involving six Australian and New Zealand centers. In total, 170 eligible children will be stratified by site and bronchiectasis etiology, and randomized (allocation concealed) to receive: 1) azithromycin (5 mg/kg daily) with placebo amoxycillin-clavulanate or 2) amoxycillin-clavulanate (22.5 mg/kg twice daily) with placebo azithromycin for 21 days as treatment for non-severe respiratory exacerbations. Clinical data and a parent-proxy cough-specific quality of life (PC-QOL) score will be obtained at baseline, at the start and resolution of exacerbations, and on day 21. In most children, blood and deep-nasal swabs will also be collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 21. The main secondary outcome is the PC-QOL score. Other outcomes are: time to next exacerbation; requirement for hospitalization; duration of exacerbation, and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood inflammatory markers will be reported where available. Discussion Currently, there are no published randomized controlled trials (RCT) to underpin effective, evidence-based management of acute respiratory exacerbations in children with non-CF bronchiectasis. To help address this information gap, we are conducting two RCTs. The first (bronchiectasis exacerbation study; BEST-1) evaluates the efficacy of azithromycin and amoxycillin-clavulanate compared with placebo, and the second RCT (BEST-2), described here, is designed to determine if azithromycin is non-inferior to amoxycillin-clavulanate in achieving symptom resolution by day 21 of treatment in children with acute respiratory exacerbations. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR) number ACTRN12612000010897. http://www.anzctr.org.au/trial_view.aspx?id=347879

Characteristics of on-road driving performance of persons with central vision loss who use bioptic telescopes

Purpose. To compare the on-road driving performance of visually impaired drivers using bioptic telescopes with age-matched controls. Methods. Participants included 23 persons (mean age = 33 ± 12 years) with visual acuity of 20/63 to 20/200 who were legally licensed to drive through a state bioptic driving program, and 23 visually normal age-matched controls (mean age = 33 ± 12 years). On-road driving was assessed in an instrumented dual-brake vehicle along 14.6 miles of city, suburban, and controlled-access highways. Two backseat evaluators independently rated driving performance using a standardized scoring system. Vehicle control was assessed through vehicle instrumentation and video recordings used to evaluate head movements, lane-keeping, pedestrian detection, and frequency of bioptic telescope use. Results. Ninety-six percent (22/23) of bioptic drivers and 100% (23/23) of controls were rated as safe to drive by the evaluators. There were no group differences for pedestrian detection, or ratings for scanning, speed, gap judgments, braking, indicator use, or obeying signs/signals. Bioptic drivers received worse ratings than controls for lane position and steering steadiness and had lower rates of correct sign and traffic signal recognition. Bioptic drivers made significantly more right head movements, drove more often over the right-hand lane marking, and exhibited more sudden braking than controls. Conclusions. Drivers with central vision loss who are licensed to drive through a bioptic driving program can display proficient on-road driving skills. This raises questions regarding the validity of denying such drivers a license without the opportunity to train with a bioptic telescope and undergo on-road evaluation.

Increase in prevalence of obesity and diabetes and decrease in plasma cholesterol in a central Australian Aboriginal community

Objective: To document change in prevalence of obesity, diabetes and other cardiovascular diease (CVD) risk factors, and trends in dietary macronutrient intake, over an eight-year period in a rural Aboriginal community in central Australia. Design: Sequential cross-sectional community surveys in 1987, 1991 and 1995. Subjects: All adults (15 years and over) in the community were invited to participate. In 1987, 1991 and 1995, 335 (87% of eligible adults), 331 (76%) and 304 (68%), respectively, were surveyed. Main outcome measures: Body mass index and waist : hip ratio; blood glucose level and glucose tolerance; fasting total and high density lipoprotein (HDL) cholesterol and triglyceride levels; and apparent dietary intake (estimated by the store turnover method). Intervention: A community-based nutrition awareness and healthy lifestyle program, 1988-1990. Results: At the eight-year follow-up, the odds ratios (95% CIs) for CVD risk factors relative to baseline were obesity, 1.84 (1.28-2.66); diabetes, 1.83 (1.11-3.03); hypercholesterolaemia, 0.29 (0.20-0.42); and dyslipidaemia (high triglyceride plus low HDL cholesterol level), 4.54 (2.84-7.29). In younger women (15-24 years), there was a trebling in obesity prevalence and a four- to fivefold increase in diabetes prevalence. Store turnover data suggested a relative reduction in the consumption of refined carbohydrates and saturated fats. Conclusion: Interventions targeting nutritional factors alone are unlikely to greatly alter trends towards increasing prevalences of obesity and diabetes. In communities where healthy food choices are limited, the role of regular physical activity in improving metabolic fitness may also need to be emphasised.

Evaluating the impact of high risk foot training on undergraduate podiatry students

Background Diabetes is the leading cause of high risk foot (HRF) complications, admissions and lower limb amputation. Best practice training of podiatrists is known to have a beneficial impact on such outcomes; however, there has been a paucity of studies into undergraduate diabetes podiatry training. The primary aim of this paper was to investigate the changes in final year podiatry students’ confidence, knowledge and clinical practice in the management of HRF complications. Methods This was a prospective longitudinal study of final year podiatry students (n=25) at the Queensland University of Technology. All participants throughout 2011 undertook an intervention of a series of “hands on” HRF workshops, on-campus clinics and external clinical rotations. Outcome measures included customised confidence and knowledge surveys in HRF management across four time points. A timed simulated case scenario was used to evaluate changes in clinical practice at two time points. Friedman and Wilcoxon Signed Rank Tests were used to calculate differences between time points Results Overall improvements between the first and last time points were demonstrated in 20/21 confidence items (p<0.001), 12/27 clinical practice items (p<0.05) and 3/12 knowledge items (p<0.001). Although 8/12 knowledge items recorded high baseline scores of over 80%. Conclusions Overall, it appears student confidence and clinical practice improved with the introduction of designated HRF activities, whilst knowledge remained high. This suggests “hands on” practice and not didactic lectures improve students’ clinical confidence and practice. Results from the 2012 student cohort will also be presented at this conference.

Trace-element modeling of the magmatic evolution of rare-earth-rich carbonatite from the Miaoya deposit, Central China

Carbonatites are known to contain the highest concentrations of rare-earth elements (REE) among all igneous rocks. The REE distribution of carbonatites is commonly believed to be controlled by that of the rock forming Ca minerals (i.e., calcite, dolomite, and ankerite) and apatite because of their high modal content and tolerance for the substitution of Ca by light REE (LREE). Contrary to this conjecture, calcite from the Miaoya carbonatite (China), analyzed in situ by laser-ablation inductively-coupled-plasma mass-spectrometry, is characterized by low REE contents (100–260 ppm) and relatively !at chondrite-normalized REE distribution patterns [average (La/Yb)CN=1.6]. The carbonatite contains abundant REE-rich minerals, including monazite and !uorapatite, both precipitated earlier than the REE-poor calcite, and REE-fluorocarbonates that postdated the calcite. Hydrothermal REE-bearing !uorite and barite veins are not observed at Miaoya. The textural and analytical evidence indicates that the initially high concentrations of REE and P in the carbonatitic magma facilitated early precipitation of REE-rich phosphates. Subsequent crystallization of REE-poor calcite led to enrichment of the residual liquid in REE, particularly LREE. This implies that REE are generally incompatible with respect to calcite and the calcite/melt partition coefficients for heavy REE (HREE) are significantly greater than those for LREE. Precipitation of REE-fluorocarbonates late in the evolutionary history resulted in depletion of the residual liquid in LREE, as manifested by the development of HREE-enriched late-stage calcite [(La/Yb)CN=0.7] in syenites associated with the carbonatite. The observed variations of REE distribution between calcite and whole rocks are interpreted to arise from multistage fractional crystallization (phosphates!calcite!REE-!uorocarbonates) from an initially REE-rich carbonatitic liquid.

Exploring postnatal depression in Thua Thien Hue Province, Central Vietnam

Introduction Postnatal depression (PND) is an important public health issue due to its impact on maternal wellbeing, infant development, and family cohesion. The estimated prevalence of PND during the first 12 months post-partum ranges between10-20% worldwide. Whilst PND used to be considered a syndrome only occurring in western countries, there is now evidence that it occurs throughout the world, and often at higher rates in low and middleincome countries. To date, there has been little research into PND in South East Asia and only two community-based surveys in Vietnam, one in Ho Chi Minh City in 1999 and one in Hanoi and Ha Nam in 2009. This study will investigate health worker attitudes about risk and protective factors for PND among women in Thua Thien Hue province in central Vietnam. Methodology In 2009, 23 health professionals participated in qualitative exploratory research of postnatal depression in Hue. This included two focus groups with 12 health professionals who completed a concept mapping process, and in-depth interviews with another 11 health professionals. Results Many factors relating to postnatal depression were identified including socio-economic status, son preference, mother’s health, infant health, social support from family and the community, and health promoting behaviours. In-depth interviews highlighted community knowledge and attitudes surrounding PND such as traditional confinement practices and fear of experiencing stigma. Conclusion The findings of this research will be used to plan a substantial community-based quantitative survey in order to establish prevalence of PND and surrounding social determinants in central Vietnam.

Is recovery driven by central or peripheral factors? A role for the brain in recovery following intermittent-sprint exercise

Prolonged intermittent-sprint exercise (i.e., team sports) induce disturbances in skeletal muscle structure and function that are associated with reduced contractile function, a cascade of inflammatory responses, perceptual soreness, and a delayed return to optimal physical performance. In this context, recovery from exercise-induced fatigue is traditionally treated from a peripheral viewpoint, with the regeneration of muscle physiology and other peripheral factors the target of recovery strategies. The direction of this research narrative on post-exercise recovery differs to the increasing emphasis on the complex interaction between both central and peripheral factors regulating exercise intensity during exercise performance. Given the role of the central nervous system (CNS) in motor-unit recruitment during exercise, it too may have an integral role in post-exercise recovery. Indeed, this hypothesis is indirectly supported by an apparent disconnect in time-course changes in physiological and biochemical markers resultant from exercise and the ensuing recovery of exercise performance. Equally, improvements in perceptual recovery, even withstanding the physiological state of recovery, may interact with both feed-forward/feed-back mechanisms to influence subsequent efforts. Considering the research interest afforded to recovery methodologies designed to hasten the return of homeostasis within the muscle, the limited focus on contributors to post-exercise recovery from CNS origins is somewhat surprising. Based on this context, the current review aims to outline the potential contributions of the brain to performance recovery after strenuous exercise.

Factors associated with the isolation of Nontuberculous mycobacteria (NTM) from a large municipal water system in Brisbane, Australia

Background Nontuberculous mycobacteria (NTM) are normal inhabitants of a variety of environmental reservoirs including natural and municipal water. The aim of this study was to document the variety of species of NTM in potable water in Brisbane, QLD, with a specific interest in the main pathogens responsible for disease in this region and to explore factors associated with the isolation of NTM. One-litre water samples were collected from 189 routine collection sites in summer and 195 sites in winter. Samples were split, with half decontaminated with CPC 0.005%, then concentrated by filtration and cultured on 7H11 plates in MGIT tubes (winter only). Results Mycobacteria were grown from 40.21% sites in Summer (76/189) and 82.05% sites in winter (160/195). The winter samples yielded the greatest number and variety of mycobacteria as there was a high degree of subculture overgrowth and contamination in summer. Of those samples that did yield mycobacteria in summer, the variety of species differed from those isolated in winter. The inclusion of liquid media increased the yield for some species of NTM. Species that have been documented to cause disease in humans residing in Brisbane that were also found in water include M. gordonae, M. kansasii, M. abscessus, M. chelonae, M. fortuitum complex, M. intracellulare, M. avium complex, M. flavescens, M. interjectum, M. lentiflavum, M. mucogenicum, M. simiae, M. szulgai, M. terrae. M. kansasii was frequently isolated, but M. avium and M. intracellulare (the main pathogens responsible for disease is QLD) were isolated infrequently. Distance of sampling site from treatment plant in summer was associated with isolation of NTM. Pathogenic NTM (defined as those known to cause disease in QLD) were more likely to be identified from sites with narrower diameter pipes, predominantly distribution sample points, and from sites with asbestos cement or modified PVC pipes. Conclusions NTM responsible for human disease can be found in large urban water distribution systems in Australia. Based on our findings, additional point chlorination, maintenance of more constant pressure gradients in the system, and the utilisation of particular pipe materials should be considered.

Repeatability of confocal microscopy measurements on the central and peripheral cornea

Purpose To assess confocal microscopy repeatability (ConfoScan3, Nidek, Italy) when assessing the morphology of the limbus, midperipheral and central cornea. Method The central, mid-peripheral and limbal cornea (temporal and nasal) of the right eye of 8 subjects were examined with a ConfoScan3 in two different visits, at least six months apart. Bland-Altman repeatability was measured for 29 parameters: basal cell density and size, anterior and posterior keratocyte densities (AKD/PKD), endothelial cell density, polymegethism, pleomorphism, mean area and sides of endothelial cells - in the five different corneal areas examined. Results As a percentage of the mean absolute values, repeatability of 0–10% was classified as “excellent”, between 10–30% as “acceptable” and over 30% as “poor”. Repeatability was excellent for 14% of parameters and acceptable for 52% of parameters. The number of endothelial cell sides in the central cornea demonstrated the best repeatability (2.0%) whilst mid-temporal PKD showed the poorest repeatability (53.7%). Conclusions Confocal microscopy is at least an adequately repeatablemethodof evaluating the various corneal layers at different locations. Our dataset supports the ongoing use of the technique in research and clinical practice.

Integrating 40Ar-39Ar, 87Rb-87Sr and 147Sm-143Nd geochronology of authigenic illite to evaluate tectonic reactivation in an intraplate setting, central Australia

The Warburton-Cooper basins, central Australia, include a multitude of reactivated fracture-fault networks related to a complex, and poorly understood, tectonic evolution. We investigated authigenic illites from a granitic intrusion and sedimentary rocks associated with prominent structural features (Gidgealpa-Merrimelia-Innamincka Ridge and the Nappamerri Trough). These were analysed by 40Ar-39Ar, 87Rb-87Sr and 147Sm-143Nd geochronology to explore the thermal and tectonic histories of central Australian basins. The combined age data provide evidence for three major periods of fault reactivation throughout the Phanerozoic. While Carboniferous (323.3 ± 9.4 Ma) and Late Triassic ages (201.7 ± 9.3 Ma) derive from basin-wide hydrothermal circulation, Cretaceous ages (~128 to ~86 Ma) reflect episodic fluid flow events restricted to the synclinal Nappamerri Trough. Such events result from regional extensional tectonism derived from the transferral of far-field stresses to mechanically and thermally weakened regions of the Australian continent. Specifically, Cretaceous ages reflect continent-wide transmission of tensional stress from a > 2500 km long rifting event on the Eastern (and southern) Australian margin associated with break-up of Gondwana and opening of the Tasman Sea. By integrating 40Ar-39Ar, 87Rb-87Sr and 147Sm-143Nd dating, this study highlights the use of authigenic illite in temporally constraining the tectonic evolution of intracontinental basins that would otherwise remain unknown. Furthermore, combining Sr- and Ar-isotopic systems enables more accurate dating of authigenesis whilst significantly reducing geochemical pitfalls commonly associated with these radioisotopic dating methods.

Mifepristone in the central nucleus of the amygdala reduces yohimbine stress-induced reinstatement of ethanol-seeking

Chronic ethanol exposure leads to dysregulation of the hypothalamic-pituitary-adrenal axis, leading to changes in glucocorticoid release and function that have been proposed to maintain pathological alcohol consumption and increase vulnerability to relapse during abstinence. The objective of this study was to determine whether mifepristone, a glucocorticoid receptor antagonist, plays a role in ethanol self-administration and reinstatement. Male, Long-Evans rats were trained to self-administer either ethanol or sucrose in daily 30 min operant self-administration sessions using a fixed ratio 3 schedule of reinforcement. Following establishment of stable baseline responding, we examined the effects of mifepristone on maintained responding and yohimbine-induced increases in responding for ethanol and sucrose. Lever responding was extinguished in separate groups of rats and animals were tested for yohimbine-induced reinstatement and corticosterone release. We also investigated the effects of local mifepristone infusions into the central amygdala (CeA) on yohimbine-induced reinstatement of ethanol- and sucrose-seeking. In addition, we infused mifepristone into the basolateral amygdala (BLA) in ethanol-seeking animals as an anatomical control. We show that both systemic and intra-CeA (but not BLA) mifepristone administration suppressed yohimbine-induced reinstatement of ethanol-seeking, while only systemic injections attenuated sucrose-seeking. In contrast, baseline consumption, yohimbine-induced increases in responding, and circulating CORT levels were unaffected. The data indicate that the CeA plays an important role in the effects of mifepristone on yohimbine-induced reinstatement of ethanol-seeking. Mifepristone may be a valuable pharmacotherapeutic strategy for preventing relapse to alcohol use disorders and, as it is FDA approved, may be a candidate for clinical trials in the near future.

The 10 Australian ecosystems most vulnerable to tipping points

We identify the 10 major terrestrial and marine ecosystems in Australia most vulnerable to tipping points, in which modest environmental changes can cause disproportionately large changes in ecosystem properties. To accomplish this we independently surveyed the coauthors of this paper to produce a list of candidate ecosystems, and then refined this list during a 2-day workshop. The list includes (1) elevationally restricted mountain ecosystems, (2) tropical savannas, (3) coastal floodplains and wetlands, (4) coral reefs, (5) drier rainforests, (6) wetlands and floodplains in the Murray-Darling Basin, (7) the Mediterranean ecosystems of southwestern Australia, (8) offshore islands, (9) temperate eucalypt forests, and (10) salt marshes and mangroves. Some of these ecosystems are vulnerable to widespread phase-changes that could fundamentally alter ecosystem properties such as habitat structure, species composition, fire regimes, or carbon storage. Others appear susceptible to major changes across only part of their geographic range, whereas yet others are susceptible to a large-scale decline of key biotic components, such as small mammals or stream-dwelling amphibians. For each ecosystem we consider the intrinsic features and external drivers that render it susceptible to tipping points, and identify subtypes of the ecosystem that we deem to be especially vulnerable. © 2011 Elsevier Ltd.

Turning points in narratives of research design : research innovation stimulating unique responses to existing challenges for beginning rural teachers

This paper explores methodological turning points in researching narratives of early career resilience mediated by the complexities of remote teaching. Innovative, flexible and discursive research design facilitated exploration of emerging narratives using digital technologies. Data were regularly interrogated with participant-researchers to reveal the undercurrents of imbued meaning. Dialogue with participant-researchers enhanced interpretations of data plots and text-based explanations of narrative turning points, providing valuable insights throughout analysis. Reflections on the affordances and tensions in this process illustrate the significance of innovation but also the complexities associated with online collaboration. Consequently, empowering the participant-researchers throughout the life of the research was critical in understanding their narratives of teaching.

Structural abstraction of process specifications

Software engineers constantly deal with problems of designing, analyzing, and improving process specifications, e.g., source code, service compositions, or process models. Process specifications are abstractions of behavior observed or intended to be implemented in reality which result from creative engineering practice. Usually, process specifications are formalized as directed graphs in which edges capture temporal relations between decisions, synchronization points, and work activities. Every process specification is a compromise between two points: On the one hand engineers strive to operate with less modeling constructs which conceal irrelevant details, while on the other hand the details are required to achieve the desired level of customization for envisioned process scenarios. In our research, we approach the problem of varying abstraction levels of process specifications. Formally, developed abstraction mechanisms exploit the structure of a process specification and allow the generalization of low-level details into concepts of a higher abstraction level. The reverse procedure can be addressed as process specialization.