Benefits and challenges of antivirulence antimicrobials at the dawn of the post-antibiotic era

In April 2014, the World Health Organization announced the beginning of a post-antibiotic era and declared antimicrobial resistance (AMR) a public health priority demanding global action. If no action is taken, by 2050 AMR will kill more people each year than cancer, with 10 million estimated annual deaths at a cost of $100 trillion to the global economy. New therapies to tackle multidrug resistant bacterial pathogens are urgently needed. Unlike traditional antibiotics, antivirulence drugs inhibit bacterial virulence instead of growth promising to offer a new class of superior therapeutics that will be ‘evolution-proof’ and ‘tailored-spectrum’. This mini-review discusses the latest emerging evidence on the promised benefits of antivirulence drugs over conventional antibiotics, also highlighting the challenges in evaluating these properties for each of the diverse virulence targets that are currently under investigation. The author argues that overcoming such challenges early in the development process constitutes an important step towards successfully progressing each of the expanding number of antivirulence strategies into next-generation therapies for common human and animal infections that are becoming increasingly refractory to all available antibiotics.

Reconstituting identity and history in post-war Mostar, Bosnia-Herzegovina

This paper by Carl Grodach demonstrates the careful unravelling of complexity, diversity, contestation and contradictions involved in the reconstruction of symbolic urban spaces after violent conflict, and the allied processes of cultural reinterpretation, political reconfiguration and material revaluation which accompany it. The paper analyses the reconstruction and redevelopment of the 16th-century historic centre of Mostar, Bosnia-Herzegovina, following the Bosnian Wars of 1992–1995. Reconstruction efforts centre around Stari Most, the 16th-century Ottoman bridge destroyed by Bosnian Croat military in 1993. In Mostar, both international and local organizations are in the process of reinterpreting Bosnia’s legacy of Ottoman city spaces. This research and analysis illuminates how such spaces can be central to contemporary projects to redefine group identities and conceptions of place. It provides insight into the ways various groups are attempting to reshape outside perceptions of the city—and Bosnia’s ethnic conflict—to articulate a new definition of local identity and ethnic relations and to remake a stable tourist economy through Mostar’s urban spaces.

Cluster randomised-control trial for an Australian child protection education program: Study protocol for the Learn to be safe with Emmy and friends™

Background Child maltreatment has severe short-and long-term consequences for children’s health, development, and wellbeing. Despite the provision of child protection education programs in many countries, few have been rigorously evaluated to determine their effectiveness. We describe the design of a multi-site gold standard evaluation of an Australian school-based child protection education program. The intervention has been developed by a not-for-profit agency and comprises 5 1-h sessions delivered to first grade students (aged 5–6 years) in their regular classrooms. It incorporates common attributes of effective programs identified in the literature, and aligns with the Australian education curriculum. Methods/Design A three-site cluster randomised controlled trial (RCT) of Learn to be safe with Emmy and friends™ will be conducted with children in approximately 72 first grade classrooms in 24 Queensland primary (elementary) schools from three state regions, over a period of 2 years. Entire schools will be randomised, using a computer generated list of random numbers, to intervention and wait-list control conditions, to prevent contamination effects across students and classes. Data will be collected at baseline (pre-assessment), immediately after the intervention (post-assessment), and at 6-, 12-, and 18-months (follow-up assessments). Outcome assessors will be blinded to group membership. Primary outcomes assessed are children’s knowledge of program concepts; intentions to use program knowledge, skills, and help-seeking strategies; actual use of program material in a simulated situation; and anxiety arising from program participation. Secondary outcomes include a parent discussion monitor, parent observations of their children’s use of program materials, satisfaction with the program, and parental stress. A process evaluation will be conducted concurrently to assess program performance. Discussion This RCT addresses shortcomings in previous studies and methodologically extends research in this area by randomising at school-level to prevent cross-learning between conditions; providing longer-term outcome assessment than any previous study; examining the degree to which parents/guardians discuss intervention content with children at home; assessing potential moderating/mediating effects of family and child demographic variables; testing an in-vivo measure to assess children’s ability to discriminate safe/unsafe situations and disclose to trusted adults; and testing enhancements to existing measures to establish greater internal consistency.

Prolactin suppresses release of luteinising hormone during lactation in the monkey

STUDIES with rats have shown that during lactation there is an inhibition of luteinising hormone (LH)-dependent physiological events, such as implantation1, and a return to oestrus cyclicity2. This inhibition has been shown to occur only during the intense suckling phase and it has been correlated with the high levels of prolactin present in the circulation at this time. Although exogenous prolactin could substitute for the effects of intense suckling, it could do so only under the permissive influence of minimal suckling stimulus. We have shown that there is, in these conditions, a lowering of LH levels, and that this is due to interference by prolactin with the pituitary responsiveness to LH-releasing hormone (LHRH) (K. Muralidhar, R. M. and N. R. M., unpublished). Using the lactating monkey, we have now demonstrated a similar inhibitory effect of prolactin on pituitary responsiveness to LHRH, suggesting a mechanism by which amenorrhoeic conditions are maintained during lactation.

Pre- and post-copulatory sexual selection in the least killifish, Heterandria formosa

It has been only recently realized that sexual selection does not end at copulation but that post-copulatory processes are often important in determining the fitness of individuals. In this thesis, I experimentally studied both pre- and post-copulatory sexual selection in the least killifish, Heterandria formosa. I found that this species suffers from severe inbreeding depression in male reproductive behaviour, offspring viability and offspring maturation times. Neither sex showed pre-copulatory inbreeding avoidance but when females mated with their brothers, less sperm were retrieved from their reproductive system compared to the situation when females mated with unrelated males. Whether the difference in sperm numbers is due to female or male effect could not be resolved. Based on theory, females should be more eager to avoid inbreeding than males in this species, because females invest more in their offspring than males do. Inbreeding seems to be an important part of this species biology and the severe inbreeding depression has most likely selected for the evolution of the post-copulatory inbreeding avoidance mechanism that I found. In addition, I studied the effects of polyandry on female reproductive success. When females mated with more than one male, they were more likely to get pregnant. However, I also found a cost of polyandry. The offspring of females mated to four males took longer to reach sexual maturity compared to the offspring of monandrous females. This cost may be explained by parent-offspring conflict over maternal resource allocation. In another experiment, in which within-brood relatedness was manipulated, offspring sizes decreased over time when within-brood relatedness was low. This result is partly in accordance with the kinship theory of genomic imprinting. When relatedness decreases, offspring are expected to be less co-operative and demand fewer resources from their mother, which leads to impaired development. In the last chapter of my thesis, I show that H. formosa males do not prefer large females as in other Poeciliidae species. I suggest that males view smaller females as more profitable mates because those are more likely virgin. In conclusion, I found both pre- and post-copulatory sexual selection to be important factors in determining reproductive success in H. formosa.

Occupational release of engineered nanoparticles: A review

Characterising the release of different types of Engineered Nanoparticles (ENPs) from various processes is of critical importance for the assessment of human exposure, as well as understanding the possible health effects of these particles. Therefore, the main aim of this chapter is to present a comprehensive review of studies which report on the release of airborne ENPs in different nanotechnology workplaces. The chapter will cover topics of relevance to the occupational characterisation of ENP emissions, ranging from the identification of different particle release sources and scenarios, to measurement methods and working towards a more uniform approach to characterisation. Furthermore, a brief review of ENP exposure control strategies, together with the application of mathematical modelling as an effective tool for the characterisation of emissions at nanotechnology workplaces is included.

Expecting too much? Can Indigenous sport programs in Australia deliver development and social outcomes?

Sport holds a special place in the national psyche of many nations with claims for sport being far reaching. More recently sport has been identified as a development and an educational tool in the areas of health and behaviour modification. Against the backdrop of the Close the Gap blueprint for Indigenous Australians and within the context of competing claims for sport, this paper discusses whether sport can genuinely contribute to community development in Indigenous Australian communities. Drawing on cases from sports-based programmes that spanned a 5-year research programme and informed by a theoretical framework inspired by Sen’s notion of ‘Development as Freedom’, this paper makes the case that sport can be a robust developmental tool capable of delivering social outcomes to marginalized communities.

The impact of Indigenous Community sports programs: The case of surfing

The objective of this research project was to consider the social impact of sport and physical activity on the lives of Indigenous Australians and their communities. There has been strong research interest in the links between sport and recreation programs and various health and social outcomes and a well-established body of literature exists on the use of sport to address social issues in mainstream society (A Thomson, Darcy and Pearce 2010). The consensus is that physical activity is an important contributor to health for all people (Nelson, Abbott and Macdonald 2010). While there is strong research interest, what remains unclear is the value and impact of sport and physical activity on Indigenous communities (Cairnduff 2001). Nelson (2009) drawing on the work of Jonas and Langton (1994) indicates that an ‘Aboriginal person is a descendant of an Indigenous inhabitant of Australia, identifi es as an Aboriginal, and is recognised as Aboriginal by members of the community in which he or she lives’ (p. 97). Even this defi nition has the potential to be politically charged. At a general level, the collective terms ‘Indigenous’ (capitalised) and ‘Aboriginal and Torres Strait Islander’ people (title capitalised) appear to be broadly acceptable terms. Indigenous groups cannot be considered to be homogenous as there is much diversity between and within groups (Nelson et al. 2010; Parker et al. 2006). It is therefore important this report is not viewed as taking an essentialist view of who Indigenous people are and how they develop. Rather, this paper attempts to describe and discuss the experiences of some individuals and their communities in site-specifi c surfi ng programs.

Encapsulation and release of rifampicin using poly(vinyl pyrrolidone)-poly (methacrylic acid) polyelectrolyte capsules

Poly(vinyl pyrrolidone) and poly(methacrylic acid) multilayer capsules based on hydrogen bonding have been prepared by the layer-by-layer approach and used to encapsulate and release rifampicin, an antituberculosis drug. Removal of silica core using a buffer of ammonium fluoride and hydrofluoric acid at about pH 3 was found to produce better capsules than hydrofluoric acid alone. An eight-layered capsule had a wall thickness of 20 rim. Maximum encapsulation was found to be about 86 mu g at 40 degrees C with 1 +/- 0.2 x 10(6) capsules. Release studies showed a burst kind of release and maximum release was obtained above pH 7 where the capsules disintegrate rapidly thereby releasing the drug in a short period. Interactions studies with Mycobacterium smegmatis showed that the capsules were cytocompatible and the released drug functioned with the same efficacy as the free drug.

Influence of surface chemistry of mesoporous alumina with wide pore distribution on controlled drug release

The crucial role of the drug carrier surface chemical moeities on the uptake and in vitro release of drug is discussed here in a systematic manner. Mesoporous alumina with a wide pore size distribution (2-7 nm) functionalized with various hydrophilic and hydrophobic surface chemical groups was employed as the carrier for delivery of the model drug ibuprofen. Surface functionalization with hydrophobic groups resulted in low degree of drug loading (approximately 20%) and fast rate of release (85% over a period of 5 h) whereas hydrophilic groups resulted in a significantly higher drug payloads (21%-45%) and slower rate of release (12%-40% over a period of 5 h). Depending on the chemical moiety, the diffusion controlled (proportional to time(-0.5)) drug release was additionally observed to be dependent on the mode of arrangement of the functional groups on the alumina surface as well as on the pore characteristics of the matrix. For all mesoporous alumina systems the drug dosages were far lower than the maximum recommended therapeutic dosages (MRTD) for oral delivery. We envisage that the present study would aid in the design of delivery systems capable of sustained release of multiple drugs.

Cu2+-induced room temperature hydrogen release from ammonia borane

Mechanical stirring of ammonia borane with CuCl2 in the solid state resulted in the release of hydrogen at room temperature through the intermediacy of [NH4](+)[BCl4](-).

Post-millennial Australian dramaturgies: Changes in Australian dramaturgy and performance since the 2000s

This chapter examines the burgeoning field of dramaturgy in Australian performance and suggests that the growth of the both the profession and the practices of dramaturgy were a result of structural changes arising from the policies of the Howard Government, globalism and economic rationalism, as well as the demographic pressures of generational reform.

Post-liquefaction undrained monotonic behaviour of sands: experiments and DEM simulations

This paper presents the results of a series of servo-controlled cyclic triaxial tests and numerical simulations using the three- dimensional discrete element method (DEM) on post-liquefaction undrained monotonic strength of granular materials. In a first test series,undrained monotonic tests were carried out after dissipating the excess pore water pressure developed during liquefaction. The influence of different parameters such as amplitude of axial strain,relative density and confining pressure prior to liquefaction on the post-liquefaction undrained response have been investigated.The results obtained highlight an insignificant influence of amplitude of axial strain, confining pressure and a significant influence of relative density on the post-liquefaction undrained monotonic stress-strain response.In the second series, undrained monotonic tests were carried out on similar triaxial samples without dissipating the excess pore water pressure developed during liquefaction. The results highlight that the amplitude of axial strain prior to liquefaction has a significant influence on the post-liquefaction undrained monotonic response.In addition,DEM simulations have been carried out on an assembly of spheres to simulate post-liquefaction behaviour.The simulations were very similar to the experiments with an objective to understand the behaviour of monotonic strength of liquefied samples from the grain scale. The numerical simulations using DEM have captured qualitatively all the features of the post-liquefaction undrained monotonic response in a manner similar to that of the experiments.In addition,a detailed study on the evolution of micromechanical parameters such as the average coordination number and induced anisotropic coefficients has been reported during the post-liquefaction undrained monotonic loading.