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

What is an expert? A systems perspective on expertise

1. Expert knowledge continues to gain recognition as a valuable source of information in a wide range of research applications. Despite recent advances in defining expert knowledge, comparatively little attention has been given to how to view expertise as a system of interacting contributory factors, and thereby, to quantify an individual’s expertise. 2. We present a systems approach to describing expertise that accounts for many contributing factors and their interrelationships, and allows quantification of an individual’s expertise. A Bayesian network (BN) was chosen for this purpose. For the purpose of illustration, we focused on taxonomic expertise. The model structure was developed in consultation with professional taxonomists. The relative importance of the factors within the network were determined by a second set of senior taxonomists. This second set of experts (i.e. supra-experts) also provided validation of the model structure. Model performance was then assessed by applying the model to hypothetical career states in the discipline of taxonomy. Hypothetical career states were used to incorporate the greatest possible differences in career states and provide an opportunity to test the model against known inputs. 3. The resulting BN model consisted of 18 primary nodes feeding through one to three higher-order nodes before converging on the target node (Taxonomic Expert). There was strong consistency among node weights provided by the supra-experts for some nodes, but not others. The higher order nodes, “Quality of work” and “Total productivity”, had the greatest weights. Sensitivity analysis indicated that although some factors had stronger influence in the outer nodes of the network, there was relatively equal influence of the factors leading directly into the target node. Despite differences in the node weights provided by our supra-experts, there was remarkably good agreement among assessments of our hypothetical experts that accurately reflected differences we had built into them. 4. This systems approach provides a novel way of assessing the overall level of expertise of individuals, accounting for multiple contributory factors, and their interactions. Our approach is adaptable to other situations where it is desirable to understand components of expertise.

Publicly verifiable ciphertexts

In many applications, where encrypted traffic flows from an open (public) domain to a protected (private) domain, there exists a gateway that bridges the two domains and faithfully forwards the incoming traffic to the receiver. We observe that indistinguishability against (adaptive) chosen-ciphertext attacks (IND-CCA), which is a mandatory goal in face of active attacks in a public domain, can be essentially relaxed to indistinguishability against chosen-plaintext attacks (IND-CPA) for ciphertexts once they pass the gateway that acts as an IND-CCA/CPA filter by first checking the validity of an incoming IND-CCA ciphertext, then transforming it (if valid) into an IND-CPA ciphertext, and forwarding the latter to the recipient in the private domain. “Non-trivial filtering'' can result in reduced decryption costs on the receivers' side. We identify a class of encryption schemes with publicly verifiable ciphertexts that admit generic constructions of (non-trivial) IND-CCA/CPA filters. These schemes are characterized by existence of public algorithms that can distinguish between valid and invalid ciphertexts. To this end, we formally define (non-trivial) public verifiability of ciphertexts for general encryption schemes, key encapsulation mechanisms, and hybrid encryption schemes, encompassing public-key, identity-based, and tag-based encryption flavours. We further analyze the security impact of public verifiability and discuss generic transformations and concrete constructions that enjoy this property.

What can we learn from the crashes of learner riders?

In some parts of Australia, people wanting to learn to ride a motorcycle are required to complete an off-road training course before they are allowed to practice on the road. In the state of Queensland, they are only required to pass a short multiple-choice road rules knowledge test. This paper describes an analysis of police-reported crashes involving learner riders in Queensland that was undertaken as part of research investigating whether pre-learner training is needed and, if so, the issues that should be addressed in training.. The crashes of learner riders and other riders were compared to identify whether there are particular situations or locations in which learner motorcyclists are over-involved in crashes, which could then be targeted in the pre-learner package. The analyses were undertaken separately for riders aged under 25 (330 crashes) versus those aged 25 and over (237 crashes) to provide some insight into whether age or riding inexperience are the more important factors, and thus to indicate whether there are merits in having different licensing or training approaches for younger and older learner riders. Given that the average age of learner riders was 33 years, under 25 was chosen to provide a sufficiently large sample of younger riders. Learner riders appeared to be involved in more severe crashes and to be more often at fault than fully-licensed riders but this may reflect problems in reporting, rather than real differences. Compared to open licence holders, both younger and older learner riders had relatively more crashes in low speed zones and relatively fewer in high speed zones. Riders aged under 25 had elevated percentages of night-time crashes and fewer single unit (potentially involving rider error only) crashes regardless of the type of licence held. The contributing factors that were more prevalent in crashes of learner riders than holders of open licences were: inexperience (37.2% versus 0.5%), inattention (21.5% versus 15.6%), alcohol or drugs (12.0% versus 5.1%) and drink riding (9.9% versus 3.1%). The pattern of contributing factors was generally similar for younger and older learner riders, although younger learners were (not surprisingly) more likely to have inexperience coded as a contributing factor (49.7% versus 19.8%). Some of the differences in crashes between learner riders and fully-licensed riders appear to reflect relatively more riding in urban areas by learners, rather than increased risks relating to inexperience. The analysis of contributing factors in learner rider crashes suggests that hazard perception and risk management (in terms of speed and alcohol and drugs) should be included in a pre-learner program. Currently, most learner riders in Queensland complete pre-licence training and become licensed within one month of obtaining their learner permit. If the introduction of pre-learner training required that the learner permit was held for a minimum duration, then the immediate effect might be more learners riding (and crashing). Thus, it is important to consider how training and licensing initiatives work together in order to improve the safety of new riders (and how this can be evaluated).

Trialling low-cost level crossing warning devices in Australia

This paper discusses the methodology and design of the Cooperative Research Centre for Rail Innovation’s national low-cost level crossing trial programme currently being conducted in Australia. Three suppliers of innovative low-cost level crossing warning devices were chosen through a tendering and evaluation process. The paper outlines the acceptance criteria that were used to select the suppliers and describes the different types of train detection technologies and innovative cost- reduction solutions that are being tested as part of the trial. The trial is being hosted by three major railways in three different regions in Australia, where systems from the three suppliers have been installed parallel to a baseline conventional track-circuit based level crossing at each site. The paper discusses our experience to date, the trialling process and the challenges that the project has confronted in order to develop a nationally consistent trialling programme.

Plaintext awareness in identity-based key encapsulation

The notion of plaintext awareness ( PA ) has many applications in public key cryptography: it offers unique, stand-alone security guarantees for public key encryption schemes, has been used as a sufficient condition for proving indistinguishability against adaptive chosen-ciphertext attacks ( IND-CCA ), and can be used to construct privacy-preserving protocols such as deniable authentication. Unlike many other security notions, plaintext awareness is very fragile when it comes to differences between the random oracle and standard models; for example, many implications involving PA in the random oracle model are not valid in the standard model and vice versa. Similarly, strategies for proving PA of schemes in one model cannot be adapted to the other model. Existing research addresses PA in detail only in the public key setting. This paper gives the first formal exploration of plaintext awareness in the identity-based setting and, as initial work, proceeds in the random oracle model. The focus is laid mainly on identity-based key encapsulation mechanisms (IB-KEMs), for which the paper presents the first definitions of plaintext awareness, highlights the role of PA in proof strategies of IND-CCA security, and explores relationships between PA and other security properties. On the practical side, our work offers the first, highly efficient, general approach for building IB-KEMs that are simultaneously plaintext-aware and IND-CCA -secure. Our construction is inspired by the Fujisaki-Okamoto (FO) transform, but demands weaker and more natural properties of its building blocks. This result comes from a new look at the notion of γ -uniformity that was inherent in the original FO transform. We show that for IB-KEMs (and PK-KEMs), this assumption can be replaced with a weaker computational notion, which is in fact implied by one-wayness. Finally, we give the first concrete IB-KEM scheme that is PA and IND-CCA -secure by applying our construction to a popular IB-KEM and optimizing it for better performance.

Time course-dependent changes in the transcriptome of human skeletal muscle during recovery from endurance exercise: From inflammation to adaptive remodeling

Re-programming of gene expression is fundamental for skeletal muscle adaptations in response to endurance exercise. This study investigated the time-course dependent changes in the muscular transcriptome following an endurance exercise trial consisting of 1 h of intense cycling immediately followed by 1 h of intense running. Skeletal muscle samples were taken at baseline, 3 h, 48 h, and 96 h post-exercise from eight healthy, endurance-trained, male individuals. RNA was extracted from muscle. Differential gene expression was evaluated using Illumina microarrays and validated with qPCR. Gene set enrichment analysis identified enriched molecular signatures chosen from the Molecular Signatures Database. Three h post-exercise, 102 gene sets were up-regulated [family wise error rate (FWER), P < 0.05]; including groups of genes related with leukocyte migration, immune and chaperone activation, and cyclic AMP responsive element binding protein (CREB) 1-signaling. Forty-eight h post-exercise, among 19 enriched gene sets (FWER, P < 0.05), two gene sets related to actin cytoskeleton remodeling were up-regulated. Ninety-six h post-exercise, 83 gene sets were enriched (FWER, P < 0.05), 80 of which were up-regulated; including gene groups related to chemokine signaling, cell stress management, and extracellular matrix remodeling. These data provide comprehensive insights into the molecular pathways involved in acute stress, recovery, and adaptive muscular responses to endurance exercise. The novel 96 h post-exercise transcriptome indicates substantial transcriptional activity, potentially associated with the prolonged presence of leukocytes in the muscles. This suggests that muscular recovery, from a transcriptional perspective, is incomplete 96 h after endurance exercise involving muscle damage.

A grand challenge : reflecting on university science curriculum design, collaborative partnerships and integration of information literacy skills

In 2012, Queensland University of Technology (QUT) committed to the massive project of revitalizing its Bachelor of Science (ST01) degree. Like most universities in Australia, QUT has begun work to align all courses by 2015 to the requirements of the updated Australian Qualifications Framework (AQF) which is regulated by the Tertiary Education Quality and Standards Agency (TEQSA). From the very start of the redesigned degree program, students approach scientific study with an exciting mix of theory and highly topical real world examples through their chosen “grand challenge.” These challenges, Fukushima and nuclear energy for example, are the lenses used to explore science and lead to 21st century learning outcomes for students. For the teaching and learning support staff, our grand challenge is to expose all science students to multidisciplinary content with a strong emphasis on embedding information literacies into the curriculum. With ST01, QUT is taking the initiative to rethink not only content but how units are delivered and even how we work together between the faculty, the library and learning and teaching support. This was the desired outcome but as we move from design to implementation, has this goal been achieved? A main component of the new degree is to ensure scaffolding of information literacy skills throughout the entirety of the three year course. However, with the strong focus on problem-based learning and group work skills, many issues arise both for students and lecturers. A move away from a traditional lecture style is necessary but impacts on academics’ workload and comfort levels. Therefore, academics in collaboration with librarians and other learning support staff must draw on each others’ expertise to work together to ensure pedagogy, assessments and targeted classroom activities are mapped within and between units. This partnership can counteract the tendency of isolated, unsupported academics to concentrate on day-to-day teaching at the expense of consistency between units and big picture objectives. Support staff may have a more holistic view of a course or degree than coordinators of individual units, making communication and truly collaborative planning even more critical. As well, due to staffing time pressures, design and delivery of new curriculum is generally done quickly with no option for the designers to stop and reflect on the experience and outcomes. It is vital we take this unique opportunity to closely examine what QUT has and hasn’t achieved to be able to recommend a better way forward. This presentation will discuss these important issues and stumbling blocks, to provide a set of best practice guidelines for QUT and other institutions. The aim is to help improve collaboration within the university, as well as to maximize students’ ability to put information literacy skills into action. As our students embark on their own grand challenges, we must challenge ourselves to honestly assess our own work.

Always “tasty”, regardless: Art, chocolate and Indigenous Australians

This paper examines race and colour through the metaphor of chocolate. The authors use the metaphor of chocolate to question why some Aboriginal people are chosen ahead of others, with the choosing done by non-Indigenous people, perhaps on the basis of who is most likely to be “soft-centred”, agreeable, and pliable. The authors discuss the development of the Hot Chocolate art exhibition in Adelaide in 2012, with a particular focus on the works of Pamela CroftWarcon. The exhibition combined chocolate (the food), lyrics from Hot Chocolate (the band), and chocolate (the metaphor for skin colour) to encourage visitors to question their assumptions about representations of Aboriginal people in Australia.

Found in translation : debating the abstract elements of cultures through actor training styles

While the synthesis of acting methodologies in intercultural acting has been discussed at length, little discussion has focussed on the potential of diverse actor training styles to affect performance making and audience reception. This article explores a project where the abstract elements of the British and American cultures were translated in rehearsal and in production through the purposeful juxtaposition of two differing actor training styles: the British ‘traditional’ approach and the American Method. William Nicholson’s Shadowlands was produced by Crossbow Productions at the Brisbane Powerhouse in 2010. Nicholson’s play contains a discourse on the cultural cringe of British – American relations. As a research project, the production aimed to extend and augment audience experience of the socio-cultural tensions inherent in the play by juxtaposing two seemingly culturally inscribed approaches to acting. Actors were chosen who had been trained under a traditional conservatoire approach and the American Method. A brief overview of these acting approaches is followed by a discussion centred on the project. This article analyses how from the casting room to the rehearsal room to the mise en scene and into the audience discussions, cultural issues were articulated, translated and debated through the language of acting.

Assessing land-use and transport integration via a spatial composite indexing model

Achieving sustainable urban development is identified as one ultimate goal of many contemporary planning endeavours and has become central to formulation of urban planning policies. Within this concept, land-use and transport integration is highlighted as one of the most important and attainable policy objectives. In many cities, integration is embraced as an integral part of local development plans, and a number of key integration principles are identified. However, the lack of available evaluation methods to measure extent of urban sustainability levels prevents successful implementation of these principles. This paper introduces a new indicator-based spatial composite indexing model developed to measure sustainability performance of urban settings by taking into account land-use and transport integration principles. Model indicators are chosen via a thorough selection process in line with key principles of land-use and transport integration. These indicators are grouped into categories and themes according to their topical relevance. These indicators are then aggregated to form a spatial composite index to portray an overview of the sustainability performance of the pilot study area used for model demonstration. The study results revealed that the model is a practical instrument for evaluating success of local integration policies and visualizing sustainability performance of built environments and useful in both identifying problematic areas as well as formulating policy interventions.

Should Cyberbullying Be Criminalized?

Society’s attitudes towards all forms of bullying have changed in the last thirty years from considering it to be a normal part of childhood, a rite of passage and character building to regarding bullying as a behaviour to be prevented and condemned (Rigby, 2008; Žižek, 2008). This has been brought about by the research into the consequences of bullying during this time, revealing bullying to be detrimental not only to students who have been victimized but also to students who perpetrate the bullying and the bystanders who witness such behaviour. These consequences include increased levels of depression, anxiety and psychosomatic symptoms (Fekkes, Pijpers, Frediks, Vogels, & Verloove-Vanhorrick, 2006; Kim, Leventhal, Koh, Hubbard, & Boyce, 2006; Reijntjs, Kamphuis, Prinzie, & Telch, 2010) for those students who have been victimized. Different detrimental associations have been found for girls and boys who had been bullied in one longitudinal study (Carbone-Lopez, Esbensen, & Bick 2010); girls who had been indirectly bullied increased their drug use whereas boys did not, and while victimized girls showed lower self-esteem, this did not occur for boys.

Fine tuning of elasticity via crosslinking collagen-based materials to mediate mechanotransduction and stability using corona treatment

The common goal of tissue engineering is to develop substitutes that can closely mimic the structure of extracellular matrix (ECM). However, similarly important is the intensive material properties which have often been overlooked, in particular, for soft tissues that are not to bear load assumingly. The mechanostructural properties determine not only the structural stability of biomaterials but also their physiological functionality by directing cellular activity and regulating cell fate decision. The aim here is to emphasize that cells could sense intensive material properties like elasticity and reside, proliferate, migrate and differentiate accordinglyno matter if the construct is from a natural source like cartilage, skin etc. or of synthetic one. Meanwhile, the very objective of this work is to provide a tunable scheme for manipulating the elasticity of collagen-based constructs to be used to demonstrate how to engineer cell behavior and regulate mechanotransduction. Articular cartilage was chosen as it represents one of the most complex hierarchical arrangements of collagen meshwork in both connective tissues and ECM-like biomaterials. Corona discharge treatment was used to produce constructs with varying density of crosslinked collagen and stiffness accordingly. The results demonstrated that elastic modulus increased up to 33% for samples treated up to one minute as crosslink density was found to increase with exposure time. According to the thermal analysis, longer exposure to corona increased crosslink density as the denaturation enthalpy increased. However the spectroscopy results suggested that despite the stabilization of the collagen structure the integrity of the triple helical structure remained intact. The in vitro superficial culture of heterologous chondrocytes also determined that the corona treatment can modulate migration with increased focal adhesion of cells due to enhanced stiffness, without cytotoxicity effects, and providing the basis for reinforcing three-dimensional collagen-based biomaterials in order to direct cell function and mediate mechanotransduction.

Sterilizing tissue-materials using pulsed power plasma

This paper investigates the potential of pulsed power to sterilize hard and soft tissues and its impact on their physico-mechanical properties. It hypothesizes that pulsed plasma can sterilize both vascular and avascular tissues and the transitive layers in between without deleterious effects on their functional characteristics. Cartilage/bone laminate was chosen as a model to demonstrate the concept, treated at low temperature, at atmospheric pressure, in short durations and in buffered environment using a purposed-built pulsed power unit. Input voltage and time of exposure were assigned as controlling parameters in a full factorial design of experiment to determine physical and mechanical alteration pre- and post-treatment. The results demonstrated that, discharges of 11 kV sterilized samples in 45 s, reducing intrinsic elastic modules from 1.4 ± 0.9 to 0.9 ± 0.6 MPa. There was a decrease of 14.1 % in stiffness and 27.8 % in elastic-strain energy for the top quartile. Mechanical impairment was directly proportional to input voltage (P value < 0.05). Bacterial inactivation was proportional to treatment time for input voltages above 32 V (P < 0.001; R Sq = 0.98). Thermal analysis revealed that helix-coil transition decelerated with exposure time and collagen fibrils were destabilized as denaturation enthalpy reduced by 200 μV. We concluded by presenting a safe operating threshold for pulsed power plasma as a feasible protocol for effective sterilization of connective tissues with varying level of loss in mechanical robustness which we argue to be acceptable in certain medical and tissue engineering application.

Adapting Lyubashevsky's signature schemes to the ring signature setting

Basing signature schemes on strong lattice problems has been a long standing open issue. Today, two families of lattice-based signature schemes are known: the ones based on the hash-and-sign construction of Gentry et al.; and Lyubashevsky’s schemes, which are based on the Fiat-Shamir framework. In this paper we show for the first time how to adapt the schemes of Lyubashevsky to the ring signature setting. In particular we transform the scheme of ASIACRYPT 2009 into a ring signature scheme that provides strong properties of security under the random oracle model. Anonymity is ensured in the sense that signatures of different users are within negligible statistical distance even under full key exposure. In fact, the scheme satisfies a notion which is stronger than the classical full key exposure setting as even if the keypair of the signing user is adversarially chosen, the statistical distance between signatures of different users remains negligible. Considering unforgeability, the best lattice-based ring signature schemes provide either unforgeability against arbitrary chosen subring attacks or insider corruption in log-sized rings. In this paper we present two variants of our scheme. In the basic one, unforgeability is ensured in those two settings. Increasing signature and key sizes by a factor k (typically 80 − 100), we provide a variant in which unforgeability is ensured against insider corruption attacks for arbitrary rings. The technique used is pretty general and can be adapted to other existing schemes.