Long-term azithromycin for Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention Study) : a multicentre, double-blind, randomised controlled trial

Background Indigenous children in high-income countries have a heavy burden of bronchiectasis unrelated to cystic fibrosis. We aimed to establish whether long-term azithromycin reduced pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. Methods Between Nov 12, 2008, and Dec 23, 2010, we enrolled Indigenous Australian, Maori, and Pacific Island children aged 1—8 years with either bronchiectasis or chronic suppurative lung disease into a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial. Eligible children had had at least one pulmonary exacerbation in the previous 12 months. Children were randomised (1:1 ratio, by computer-generated sequence with permuted block design, stratified by study site and exacerbation frequency [1—2 vs ≥3 episodes in the preceding 12 months]) to receive either azithromycin (30 mg/kg) or placebo once a week for up to 24 months. Allocation concealment was achieved by double-sealed, opaque envelopes; participants, caregivers, and study personnel were masked to assignment until after data analysis. The primary outcome was exacerbation (respiratory episodes treated with antibiotics) rate. Analysis of the primary endpoint was by intention to treat. At enrolment and at their final clinic visits, children had deep nasal swabs collected, which we analysed for antibiotic-resistant bacteria. This study is registered with the Australian New Zealand Clinical Trials Registry; ACTRN12610000383066. Findings 45 children were assigned to azithromycin and 44 to placebo. The study was stopped early for feasibility reasons on Dec 31, 2011, thus children received the intervention for 12—24 months. The mean treatment duration was 20·7 months (SD 5·7), with a total of 902 child-months in the azithromycin group and 875 child-months in the placebo group. Compared with the placebo group, children receiving azithromycin had significantly lower exacerbation rates (incidence rate ratio 0·50; 95% CI 0·35—0·71; p<0·0001). However, children in the azithromycin group developed significantly higher carriage of azithromycin-resistant bacteria (19 of 41, 46%) than those receiving placebo (four of 37, 11%; p=0·002). The most common adverse events were non-pulmonary infections (71 of 112 events in the azithromycin group vs 132 of 209 events in the placebo group) and bronchiectasis-related events (episodes or investigations; 22 of 112 events in the azithromycin group vs 48 of 209 events in the placebo group); however, study drugs were well tolerated with no serious adverse events being attributed to the intervention. Interpretation Once-weekly azithromycin for up to 24 months decreased pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. However, this strategy was also accompanied by increased carriage of azithromycin-resistant bacteria, the clinical consequences of which are uncertain, and will need careful monitoring and further study.

What knowledge do ICU nurses have with regard to the effects of noise exposure in the Intensive Care Unit?

This small-scale study was undertaken to assess what knowledge nursing staff from a General Intensive Care Unit held with regard to noise exposure. To assess knowledge a self-administered multiple-choice questionnaire was used. Rigorous peer-review insured content validity. This study produced poor results in terms of the knowledge nurses held with regard to noise related issues in particular the psychophysiological effects and current legislation concerning its safe exposure. Non-parametric testing, using Kruskal–Wallis found no significant difference between nursing grades, however, descriptive analysis demonstrated that the staff nurse grade (D and E) performed better overall. Whilst the results of this study may seem self-evident in some respects, it is the problems of exposure to excessive noise levels for both patients and hospital personnel, which are clearly not understood. The effects noise exposure has on individuals for example decreased wound healing; sleep deprivation and cardiovascular stimulation must be of concern especially in terms of patient care but more so for nursing staff especially the effects noise levels can have on cognitive task performance.

Cryptanalysis of LASH

We show that the LASH-x hash function is vulnerable to attacks that trade time for memory, including collision attacks as fast as 2(4x/11) and preimage attacks as fast as 2(4x/7). Moreover, we briefly mention heuristic lattice based collision attacks that use small memory but require very long messages that are expected to find collisions much faster than 2 x/2. All of these attacks exploit the designers’ choice of an all zero IV. We then consider whether LASH can be patched simply by changing the IV. In this case, we show that LASH is vulnerable to a 2(7x/8) preimage attack. We also show that LASH is trivially not a PRF when any subset of input bytes is used as a secret key. None of our attacks depend upon the particular contents of the LASH matrix – we only assume that the distribution of elements is more or less uniform.

A vibrational spectroscopic study of the silicate mineral inesite Ca2(Mn,Fe)₇Si10O28(OH)⋅5H2O

We have studied the hydrated hydroxyl silicate mineral inesite of formula Ca2(Mn,Fe)7Si10O28(OH)⋅5H2O using a combination of scanning electron microscopy with EDX and Raman and infrared spectroscopy. SEM analysis shows the mineral to be a pure monomineral with no impurities. Semiquantitative analysis shows a homogeneous phase, composed by Ca, Mn2+, Si and P, with minor amounts of Mg and Fe. Raman spectrum shows well resolved component bands at 997, 1031, 1051, and 1067 cm-1 attributed to a range of SiO symmetric stretching vibrations of [Si10O28] units. Infrared bands found at 896, 928, 959 and 985 cm-1 are attributed to the OSiO antisymmetric stretching vibrations. An intense broad band at 653 cm-1 with shoulder bands at 608, 631 and 684 cm-1 are associated with the bending modes of the OSiO units of the 6- and 8-membered rings of the [Si10O28] units. The sharp band at 3642 cm-1 with shoulder bands at 3612 and 3662 cm-1 are assigned to the OH stretching vibrations of the hydroxyl units. The broad Raman band at 3420 cm-1 with shoulder bands at 3362 and 3496 cm-1 are assigned to the water stretching vibrations. The application of vibrational spectroscopy has enabled an assessment of the molecular structure of inesite to be undertaken.

Safety climate and injury occurrence of repair, maintenance, minor alteration and addition works : a comparison of workers, supervisors and managers

Purpose The repair, maintenance, minor alteration and addition (RMAA) sector has been expanding in many developed cities. Safety problems of the RMAA sector have attracted the attention of many governments. This study has the objectives of comparing the level of safety climate of workers, supervisors and managers in the RMAA sector; and explaining/ predicting the impact of safety climate on injury occurrence of workers, supervisors and managers. Design/methodology/approach A questionnaire survey was administered to RMAA contracting companies in Hong Kong. Findings When comparing the safety climate perception of workers, supervisors and managers in the RMAA sector, the supervisors group had the lowest mean safety climate score. Results showed that a positive workforce safety attitude and acceptance of safety rules and regulations reduced the workers’ likelihood of having injuries. A reasonable production schedule led to a lower probability of supervisors being injured. Management commitment and effective safety management reduced the probability of managers being injured. Originality/value This study revealed variations of safety climate at the different levels in the organizational hierarchy and their varying influence on safety performance of the RMAA sector. Safety of RMAA works could be improved by promulgating specific safety measures at the different hierarchy levels.

Reducing complexity of large EPCs

Business processes are an important instrument for understanding and improving how companies provide goods and services to customers. Therefore, many companies have documented their business processes well, often in the Event-driven Process Chains (EPC). Unfortunately, in many cases the resulting EPCs are rather complex, so that the overall process logic is hidden in low level process details. This paper proposes abstraction mechanisms for process models that aim to reduce their complexity, while keeping the overall process structure. We assume that functions are marked with efforts and splits are marked with probabilities. This information is used to separate important process parts from less important ones. Real world process models are used to validate the approach.

Health governance : law, regulation and policy

This special issue of Public Health is devoted to health governance, examining the role of law, regulation and policy in safeguarding the public's health. Each of us has devoted a career to thinking carefully about the role of law as a tool to prevent injury and disease and to promote the population's health and wellbeing. 1, 2, 3 and 4 In this Guest Editorial we first explain what we mean by the term ‘governance’, as well as the role of law in a well-regulated society. Next, we explore the increasingly important, and challenging, concept of what we call national and global federalism—the inter-relationships among the various levels of governance (local, national, supranational and transnational) and among various actors in national and global health. Third, we explain the origins of this journal symposium, which arises from three conferences on the topic in Hong Kong and Sydney. Finally, we offer a brief introduction to the articles that follow.

Promoting physical activity to older adults : a preliminary evaluation of three general practice-based strategies

The aim of this study was to explore the feasibility of an exercise scientist (ES) working in general practice to promote physical activity (PA) to 55 to 70 year old adults. Participants were randomised into one of three groups: either brief verbal and written advice from a general practitioner (GP) (G1, N=9); or individualised counselling and follow-up telephone calls from an ES, either with (G3, N=8) or without a pedometer (G2, N=11). PA levels were assessed at week 1, after the 12-wk intervention and again at 24 weeks. After the 12-wk intervention, the average increase in PA was 116 (SD=237) min/wk; N=28, p < 0.001. Although there were no statistically significant between-group differences, the average increases in PA among G2 and G3 participants were 195 (SD=207) and 138 (SD=315) min/wk respectively, compared with no change (0.36, SD=157) in G1. After 24 weeks, average PA levels remained 56 (SD=129) min/wk higher than in week 1. The small numbers of participants in this feasibility study limit the power to detect significant differences between groups, but it would appear that individualised counselling and follow-up contact from an ES, with or without a pedometer, can result in substantial changes in PA levels. A larger study is now planned to confirm these findings.

Crushed tablets : does the administration of food vehicles and thickened fluids to aid medication swallowing alter drug release?

Purpose. To evaluate the influence of co-administered vehicles on in vitro dissolution in simulated gastric fluid of crushed immediate release tablets as an indicator for potential drug bioavailability compromise. Methods. Release and dissolution of crushed amlodipine, atenolol, carbamazepine and warfarin tablets were tested with six foods and drinks that are frequently used in the clinical setting as mixers for crushed medications (water, orange juice, honey, yoghurt, strawberry jam and water thickened with Easythick powder) in comparison to whole tablets. Five commercial thickening agents (Easythick Advanced, Janbak F, Karicare, Nutilis, Viscaid) at three thickness levels were tested for their effect on the dissolution of crushed atenolol tablets. Results. Atenolol dissolution was unaffected by mixing crushed tablets with thin fluids or food mixers in comparison to whole tablets or crushed tablets in water, but amlodipine was delayed by mixing with jam. Mixing crushed warfarin and carbamazepine tablets with honey, jam or yoghurt caused them to resemble the slow dissolution of whole tablets rather than the faster dissolution of crushed tablets in water or orange juice. Crushing and mixing any of the four medications with thickened water caused a significant delay in dissolution. When tested with atenolol, all types of thickening agents at the greatest thickness significantly restricted dissolution, and products that are primarily based on xanthan gum also delayed dissolution at the intermediate thickness level. Conclusions. Dissolution testing, while simplistic, is a widely used and accepted method for comparing drug release from different formulations as an indicator for in vivo bioavailability. Thickened fluids have the potential to retard drug dissolution when used at the thickest levels. These findings highlight potential clinical implications of the addition of these agents to medications for the purpose of dose delivery and indicate that further investigation of thickened fluids and their potential to influence therapeutic outcomes is warranted.

A Bayesian hurdle model for analysis of an insect resistance monitoring database

Motivated by the analysis of the Australian Grain Insect Resistance Database (AGIRD), we develop a Bayesian hurdle modelling approach to assess trends in strong resistance of stored grain insects to phosphine over time. The binary response variable from AGIRD indicating presence or absence of strong resistance is characterized by a majority of absence observations and the hurdle model is a two step approach that is useful when analyzing such a binary response dataset. The proposed hurdle model utilizes Bayesian classification trees to firstly identify covariates and covariate levels pertaining to possible presence or absence of strong resistance. Secondly, generalized additive models (GAMs) with spike and slab priors for variable selection are fitted to the subset of the dataset identified from the Bayesian classification tree indicating possibility of presence of strong resistance. From the GAM we assess trends, biosecurity issues and site specific variables influencing the presence of strong resistance using a variable selection approach. The proposed Bayesian hurdle model is compared to its frequentist counterpart, and also to a naive Bayesian approach which fits a GAM to the entire dataset. The Bayesian hurdle model has the benefit of providing a set of good trees for use in the first step and appears to provide enough flexibility to represent the influence of variables on strong resistance compared to the frequentist model, but also captures the subtle changes in the trend that are missed by the frequentist and naive Bayesian models.

Securing multicast groups in ad hoc networks

We propose a reliable and ubiquitous group key distribution scheme that is suitable for ad hoc networks. The scheme has self-initialisation and self-securing features. The former feature allows a cooperation of an arbitrary number of nodes to initialise the system, and it also allows node admission to be performed in a decentralised fashion. The latter feature allows a group member to determine the group key remotely while maintaining the system security. We also consider a decentralised solution of establishing secure point-to-point communication. The solution allows a new node to establish a secure channel with every existing node if it has pre-existing secure channels with a threshold number of the existing nodes.

Educating for the creative economy in emerging countries

In 1972, the United Nations (UN) Conference on the Human Environment expressed a growing realization that economic and social progress needed to be balanced with a concern for the environment and the stewardship of natural resources. The hard-to-grasp concept of "sustainable development" was first defined as "development that meets the needs of the present without compromising the ability of future generations to meet their needs" (World Commission on Environment and Development [WESDJ, 1987, p. 43). This definition contains two concepts: first, "human needs," with priority given to the world's poor, and, second, the environment's limits for meeting the state of technological and social organization (WESD, 1987, p. 43). At the 2002 World Summit on Sustainable Development (UN, 2002a), the focus on environmental protection broadened to encompass social justice and the fight against poverty as key principles of development that is sustainable. Three interdependent and mutually reinforcing "pillars" were recognized: economic development, social development, and environmental protection. These pillars must be established at local, national, and global levels. The complexity and interrelationship of critical issues such as poverty, wasteful consumption, urban decay, population growth, gender inequality, health, conflict, and the violation of human rights are addressed in all three pillars (Pigozzi, 2003, p. 3). Following the concept of sustainable development, we argue that the challenge for developing countries in contemporary society is to meet the very real need for economic development and opportunities for income generation, while avoiding the unintended and unwanted consequences of economic development and globalization. These consequences include social exclusion, loss of cultural heritage, and environmental and ecological problems.

Human CD141(+) (BDCA-3)(+) dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens

The characterization of human dendritic cell (DC) subsets is essential for the design of new vaccines. We report the first detailed functional analysis of the human CD141(+) DC subset. CD141(+) DCs are found in human lymph nodes, bone marrow, tonsil, and blood, and the latter proved to be the best source of highly purified cells for functional analysis. They are characterized by high expression of toll-like receptor 3, production of IL-12p70 and IFN-beta, and superior capacity to induce T helper 1 cell responses, when compared with the more commonly studied CD1c(+) DC subset. Polyinosine-polycytidylic acid (poly I:C)-activated CD141(+) DCs have a superior capacity to cross-present soluble protein antigen (Ag) to CD8(+) cytotoxic T lymphocytes than poly I:C-activated CD1c(+) DCs. Importantly, CD141(+) DCs, but not CD1c(+) DCs, were endowed with the capacity to cross-present viral Ag after their uptake of necrotic virus-infected cells. These findings establish the CD141(+) DC subset as an important functionally distinct human DC subtype with characteristics similar to those of the mouse CD8 alpha(+) DC subset. The data demonstrate a role for CD141(+) DCs in the induction of cytotoxic T lymphocyte responses and suggest that they may be the most relevant targets for vaccination against cancers, viruses, and other pathogens.

Malaria rapid diagnostic test performance : results of WHO product testing of malaria RDTs : round 5 (2013)

WHO estimates that half the world’s population is at risk of malaria. In 2012, there were an estimated 207 million cases (with an uncertainty range of 135 million to 287 million) and an estimated 627 000 deaths (with an uncertainty range of 473 000 to 789 000). Approximately 90% of all malaria deaths occur in sub-Saharan Africa, and 77% occur in children under 5 years. Malaria remains endemic in 104 countries, and, while parasite-based diagnosis is increasing, most suspected cases of malaria are still not properly confirmed, resulting in over-use of antimalarial drugs and poor disease monitoring (1)...

Experimental studies on web crippling behaviour of hollow flange channel beams under two flange load cases

This paper presents the details of an experimental study of a cold-formed steel hollow flange channel beam known as LiteSteel beam (LSB) subject to web crippling under End Two Flange (ETF) and Interior Two Flange (ITF) load cases. The LSB sections with two rectangular hollow flanges are made using a simultaneous cold-forming and electric resistance welding process. Due to the geometry of the LSB, and its unique residual stress characteristics and initial geometric imperfections, much of the existing research for common cold-formed steel sections is not directly applicable to LSB. Experimental and numerical studies have been carried out to evaluate the behaviour and design of LSBs subject to pure bending, predominant shear and combined actions. To date, however, no investigation has been conducted on the web crippling behaviour and strength of LSB sections. Hence an experimental study was conducted to investigate the web crippling behaviour and capacities of LSBs. Twenty-eight web crippling tests were conducted under ETF and ITF load cases, and the ultimate web crippling capacities were compared with the predictions from the design equations in AS/NZS 4600 and AISI S100. This comparison showed that AS/NZS 4600 and AISI S100 web crippling design equations are unconservative for LSB sections under ETF and ITF load cases. Hence new equations were proposed to determine the web crippling capacities of LSBs based on experimental results. Suitable design rules were also developed under the direct strength method (DSM) format.