Large-scale screening of a targeted Enterococcus faecalis mutant library identifies envelope fitness factors

Spread of antibiotic resistance among bacteria responsible for nosocomial and community-acquired infections urges for novel therapeutic or prophylactic targets and for innovative pathogen-specific antibacterial compounds. Major challenges are posed by opportunistic pathogens belonging to the low GC% gram-positive bacteria. Among those, Enterococcus faecalis is a leading cause of hospital-acquired infections associated with life-threatening issues and increased hospital costs. To better understand the molecular properties of enterococci that may be required for virulence, and that may explain the emergence of these bacteria in nosocomial infections, we performed the first large-scale functional analysis of E. faecalis V583, the first vancomycin-resistant isolate from a human bloodstream infection. E. faecalis V583 is within the high-risk clonal complex 2 group, which comprises mostly isolates derived from hospital infections worldwide. We conducted broad-range screenings of candidate genes likely involved in host adaptation (e.g., colonization and/or virulence). For this purpose, a library was constructed of targeted insertion mutations in 177 genes encoding putative surface or stress-response factors. Individual mutants were subsequently tested for their i) resistance to oxidative stress, ii) antibiotic resistance, iii) resistance to opsonophagocytosis, iv) adherence to the human colon carcinoma Caco-2 epithelial cells and v) virulence in a surrogate insect model. Our results identified a number of factors that are involved in the interaction between enterococci and their host environments. Their predicted functions highlight the importance of cell envelope glycopolymers in E. faecalis host adaptation. This study provides a valuable genetic database for understanding the steps leading E. faecalis to opportunistic virulence.

Early Literacy in Library Storytimes: A Study of Measures of Effectiveness

Across the nation, librarians work with caregivers and children to encourage engagement in their early literacy programs. However, these early literacy programs that libraries provide have been left mostly undocumented by research, especially through quantitative methods. Valuable Initiatives in Early Learning that Work Successfully (VIEWS2) was designed to test new ways to measure the effectiveness of these early literacy programs for young children (birth to kindergarten), leveraging a mixed methods, quasi-experimental design. Using two innovative tools, researchers collected data at 120 public library storytimes in the first year of research, observing approximately 1,440 children ranging from birth to 60 months of age. Analysis of year-one data showed a correlation between the early literacy content of the storytime program and children’s outcomes in terms of early literacy behaviors. These findings demonstrate that young children who attend public library storytimes are responding to the early literacy content in the storytime programs.

A cluster-randomised intervention trial against Schistosoma japonicum in the Peoples' Republic of China: bovine and human transmission

Background Zoonotic schistosomiasis japonica is a major public health problem in China. Bovines, particularly water buffaloes, are thought to play a major role in the transmission of schistosomiasis to humans in China. Preliminary results (1998–2003) of a praziquantel (PZQ)-based pilot intervention study we undertook provided proof of principle that water buffaloes are major reservoir hosts for S. japonicum in the Poyang Lake region, Jiangxi Province. Methods and Findings Here we present the results of a cluster-randomised intervention trial (2004–2007) undertaken in Hunan and Jiangxi Provinces, with increased power and more general applicability to the lake and marshlands regions of southern China. The trial involved four matched pairs of villages with one village within each pair randomly selected as a control (human PZQ treatment only), leaving the other as the intervention (human and bovine PZQ treatment). A sentinel cohort of people to be monitored for new infections for the duration of the study was selected from each village. Results showed that combined human and bovine chemotherapy with PZQ had a greater effect on human incidence than human PZQ treatment alone. Conclusions The results from this study, supported by previous experimental evidence, confirms that bovines are the major reservoir host of human schistosomiasis in the lake and marshland regions of southern China, and reinforce the rationale for the development and deployment of a transmission blocking anti-S. japonicum vaccine targeting bovines.

Advanced paternal age is associated with impaired neurocognitive outcomes during infancy and childhood

Background Advanced paternal age (APA) is associated with an increased risk of neurodevelopmental disorders such as autism and schizophrenia, as well as with dyslexia and reduced intelligence. The aim of this study was to examine the relationship between paternal age and performance on neurocognitive measures during infancy and childhood. Methods and Findings A sample of singleton children (n = 33,437) was drawn from the US Collaborative Perinatal Project. The outcome measures were assessed at 8 mo, 4 y, and 7 y (Bayley scales, Stanford Binet Intelligence Scale, Graham-Ernhart Block Sort Test, Wechsler Intelligence Scale for Children, Wide Range Achievement Test). The main analyses examined the relationship between neurocognitive measures and paternal or maternal age when adjusted for potential confounding factors. Advanced paternal age showed significant associations with poorer scores on all of the neurocognitive measures apart from the Bayley Motor score. The findings were broadly consistent in direction and effect size at all three ages. In contrast, advanced maternal age was generally associated with better scores on these same measures. Conclusions The offspring of older fathers show subtle impairments on tests of neurocognitive ability during infancy and childhood. In light of secular trends related to delayed fatherhood, the clinical implications and the mechanisms underlying these findings warrant closer scrutiny.

Cost-effectiveness of an intervention to reduce emergency re-admissions to hospital among older patients

Background. The objective is to estimate the cost-effectiveness of an intervention that reduces hospital readmission among older people at high risk. A cost-effectiveness model to estimate the costs and health benefits of the intervention was implemented. Methodology/Principal Findings. The model used data from a randomised controlled trial conducted in an Australian tertiary metropolitan hospital. Participants were acute medical admissions aged >65 years with at least one risk factor for readmission: multiple comorbidities, impaired functionality, aged >75 years, 30 recent multiple admissions, poor social support, history of depression. The intervention was a comprehensive nursing and physiotherapy assessment and an individually tailored program of exercise strategies and nurse home visits with telephone follow-up; commencing in hospital and continuing following discharge for 24 weeks. The change to cost outcomes, including the costs of implementing the intervention and all subsequent use of health care services, and, the change to health benefits, represented by quality adjusted life years, were estimated for the intervention as compared to existing practice. The mean change to total costs and quality 38 adjusted life years for an average individual over 24 weeks participating in the intervention were: cost savings of $333 (95% Bayesian credible interval $-1,932:1,282) and 0.118 extra quality adjusted life years (95% Bayesian credible interval 0.1:0.136). The mean net41 monetary-benefit per individual for the intervention group compared to the usual care condition was $7,907 (95% Bayesian credible interval $5,959:$9,995) for the 24 week period. Conclusions/Significance. The estimation model that describes this intervention predicts cost savings and improved health outcomes. A decision to remain with existing practices causes unnecessary costs and reduced health. Decision makers should consider adopting this 46 program for elderly hospitalised patients.

Cost-effectiveness of a telephone-delivered intervention for physical activity and diet

Background: Given escalating rates of chronic disease, broad-reach and cost-effective interventions to increase physical activity and improve dietary intake are needed. The cost-effectiveness of a Telephone Counselling intervention to improve physical activity and diet, targeting adults with established chronic diseases in a low socio-economic area of a major Australian city was examined. Methodology/Principal Findings: A cost-effectiveness modelling study using data collected between February 2005 and November 2007 from a cluster-randomised trial that compared Telephone Counselling with a “Usual Care” (brief intervention) alternative. Economic outcomes were assessed using a state-transition Markov model, which predicted the progress of participants through five health states relating to physical activity and dietary improvement, for ten years after recruitment. The costs and health benefits of Telephone Counselling, Usual Care and an existing practice (Real Control) group were compared. Telephone Counselling compared to Usual Care was not cost-effective ($78,489 per quality adjusted life year gained). However, the Usual Care group did not represent existing practice and is not a useful comparator for decision making. Comparing Telephone Counselling outcomes to existing practice (Real Control), the intervention was found to be cost-effective ($29,375 per quality adjusted life year gained). Usual Care (brief intervention) compared to existing practice (Real Control) was also cost-effective ($12,153 per quality adjusted life year gained). Conclusions/Significance: This modelling study shows that a decision to adopt a Telephone Counselling program over existing practice (Real Control) is likely to be cost-effective. Choosing the ‘Usual Care’ brief intervention over existing practice (Real Control) shows a lower cost per quality adjusted life year, but the lack of supporting evidence for efficacy or sustainability is an important consideration for decision makers. The economics of behavioural approaches to improving health must be made explicit if decision makers are to be convinced that allocating resources toward such programs is worthwhile.

Assessment of heat-related health impacts in Brisbane, Australia : comparison of different heatwave definitions

Background: There is no global definition of a heatwave because local acclimatisation and adaptation influence the impact of extreme heat. Even at a local level there can be multiple heatwave definitions, based on varying temperature levels or time periods. We investigated the relationship between heatwaves and health outcomes using ten different heatwave definitions in Brisbane, Australia. ---------- Methodology/Principal Findings: We used daily data on climate, air pollution, and emergency hospital admissions in Brisbane between January 1996 and December 2005; and mortality between January 1996 and November 2004. Case-crossover analyses were used to assess the relationship between each of the ten heatwave definitions and health outcomes. During heatwaves there was a statistically significant increase in emergency hospital admissions for all ten definitions, with odds ratios ranging from 1.03 to 1.18. A statistically significant increase in the odds ratios of mortality was also found for eight definitions. The size of the heat-related impact varied between definitions.---------- Conclusions/Significance Even a small change in the heatwave definition had an appreciable effect on the estimated health impact. It is important to identify an appropriate definition of heatwave locally and to understand its health effects in order to develop appropriate public health intervention strategies to prevent and mitigate the impact of heatwaves.

Cost-effectiveness of a central venous catheter care bundle

Background: A bundled approach to central venous catheter care is currently being promoted as an effective way of preventing catheter-related bloodstream infection (CR-BSI). Consumables used in the bundled approach are relatively inexpensive which may lead to the conclusion that the bundle is cost-effective. However, this fails to consider the nontrivial costs of the monitoring and education activities required to implement the bundle, or that alternative strategies are available to prevent CR-BSI. We evaluated the cost-effectiveness of a bundle to prevent CR-BSI in Australian intensive care patients. ---------- Methods and Findings: A Markov decision model was used to evaluate the cost-effectiveness of the bundle relative to remaining with current practice (a non-bundled approach to catheter care and uncoated catheters), or use of antimicrobial catheters. We assumed the bundle reduced relative risk of CR-BSI to 0.34. Given uncertainty about the cost of the bundle, threshold analyses were used to determine the maximum cost at which the bundle remained cost-effective relative to the other approaches to infection control. Sensitivity analyses explored how this threshold alters under different assumptions about the economic value placed on bed-days and health benefits gained by preventing infection. If clinicians are prepared to use antimicrobial catheters, the bundle is cost-effective if national 18-month implementation costs are below $1.1 million. If antimicrobial catheters are not an option the bundle must cost less than $4.3 million. If decision makers are only interested in obtaining cash-savings for the unit, and place no economic value on either the bed-days or the health benefits gained through preventing infection, these cost thresholds are reduced by two-thirds.---------- Conclusions: A catheter care bundle has the potential to be cost-effective in the Australian intensive care setting. Rather than anticipating cash-savings from this intervention, decision makers must be prepared to invest resources in infection control to see efficiency improvements.

Support for gold open access publishing strategies at QUT

INTRODUCTION: Since the introduction of its QUT ePrints institutional repository of published research outputs, together with the world’s first mandate for author contributions to an institutional repository, Queensland University of Technology (QUT) has been a leader in support of green road open access. With QUT ePrints providing our mechanism for supporting the green road to open access, QUT has since then also continued to expand its secondary open access strategy supporting gold road open access, which is also designed to assist QUT researchers to maximise the accessibility and so impact of their research. ---------- METHODS: QUT Library has adopted the position of selectively supporting true gold road open access publishing by using the Library Resource Allocation budget to pay the author publication fees for QUT authors wishing to publish in the open access journals of a range of publishers including BioMed Central, Public Library of Science and Hindawi. QUT Library has been careful to support only true open access publishers and not those open access publishers with hybrid models which “double dip” by charging authors publication fees and libraries subscription fees for the same journal content. QUT Library has maintained a watch on the growing number of open access journals available from gold road open access publishers and their increased rate of success as measured by publication impact. ---------- RESULTS: This paper reports on the successes and challenges of QUT’s efforts to support true gold road open access publishers and promote these publishing strategy options to researchers at QUT. The number and spread of QUT papers submitted and published in the journals of each publisher is provided. Citation counts for papers and authors are also presented and analysed, with the intention of identifying the benefits to accessibility and research impact for early career and established researchers.---------- CONCLUSIONS: QUT Library is eager to continue and further develop support for this publishing strategy, and makes a number of recommendations to other research institutions, on how they can best achieve success with this strategy.

Solving navigational uncertainty using grid cells on robots

To successfully navigate their habitats, many mammals use a combination of two mechanisms, path integration and calibration using landmarks, which together enable them to estimate their location and orientation, or pose. In large natural environments, both these mechanisms are characterized by uncertainty: the path integration process is subject to the accumulation of error, while landmark calibration is limited by perceptual ambiguity. It remains unclear how animals form coherent spatial representations in the presence of such uncertainty. Navigation research using robots has determined that uncertainty can be effectively addressed by maintaining multiple probabilistic estimates of a robot's pose. Here we show how conjunctive grid cells in dorsocaudal medial entorhinal cortex (dMEC) may maintain multiple estimates of pose using a brain-based robot navigation system known as RatSLAM. Based both on rodent spatially-responsive cells and functional engineering principles, the cells at the core of the RatSLAM computational model have similar characteristics to rodent grid cells, which we demonstrate by replicating the seminal Moser experiments. We apply the RatSLAM model to a new experimental paradigm designed to examine the responses of a robot or animal in the presence of perceptual ambiguity. Our computational approach enables us to observe short-term population coding of multiple location hypotheses, a phenomenon which would not be easily observable in rodent recordings. We present behavioral and neural evidence demonstrating that the conjunctive grid cells maintain and propagate multiple estimates of pose, enabling the correct pose estimate to be resolved over time even without uniquely identifying cues. While recent research has focused on the grid-like firing characteristics, accuracy and representational capacity of grid cells, our results identify a possible critical and unique role for conjunctive grid cells in filtering sensory uncertainty. We anticipate our study to be a starting point for animal experiments that test navigation in perceptually ambiguous environments.

Upskilling in scholarly communication practices

As the research landscape continues to change with new technologies, advances in data management and new means, expectations and polices surrounding scholarly communication, the role of the Library and Librarian in supporting research is shifting. At the Queensland University of Technology (QUT), the Library has made a positive impact on the scholarly communication practices of QUT researchers in the last decade in several ways: � 1. A university-wide deposit mandate on self-archiving was introduced in 2003. It states that QUT authors must place the author’s accepted manuscript version of refereed research articles and conference papers in the digital repository QUT ePrints. 2. Liaison Librarians remind their researchers to self-deposit their accepted manuscript versions of peer-reviewed research outputs into QUT ePrints, and provide training and support when needed. 3. The Library pays author publication fees for true gold road open access publishers including: BioMed Central, Public Library of Science, Hindawi Press. Liaison Librarians actively assist researchers in the gold road publishing process.� Liaison Librarians play a key role in educating their researchers on university policy and the latest advances in scholarly communication. However, their knowledge and skills related to scholarly communication practices have largely been learnt on the job or self-taught. This poster presents the results of a survey where QUT Liaison Librarians rated their skills in various practices related to eResearch, including scholarly communication.

Chlamydia pneumoniae is genetically diverse in animals and appears to have crossed the host barrier to humans on (at least) two occasions

Chlamydia pneumoniae is a common human and animal pathogen associated with a wide range of diseases. Since the first isolation of C. pneumoniae TWAR in 1965, all human isolates have been essentially clonal, providing little evolutionary insight. To address this gap, we investigated the genetic diversity of 30 isolates from diverse geographical locations, from both human and animal origin (amphibian, reptilian, equine and marsupial). Based on the level of variation that we observed at 23 discreet gene loci, it was clearly evident that the animal isolates were more diverse than the isolates of human origin. Furthermore, we show that C. pneumoniae isolates could be grouped into five major genotypes, A-E, with A, B, D and E genotypes linked by geographical location, whereas genotype C was found across multiple continents. Our evidence strongly supports two separate animal-to-human cross species transfer events in the evolutionary history of this pathogen. The C. pneumoniae human genotype identified in the USA, Canada, Taiwan, Iran, Japan, Korea and Australia (non- Indigenous) most likely originated from a single amphibian or reptilian lineage, which appears to have been previously geographically widespread. We identified a separate human lineage present in two Australian Indigenous isolates (independent geographical locations). This lineage is distinct and is present in Australian amphibians as well as a range of Australian marsupials.

The circadian response of intrinsically photosensitive retinal ganglion cells

Intrinsically photosensitive retinal ganglion cells (ipRGC) signal environmental light level to the central circadian clock and contribute to the pupil light reflex. It is unknown if ipRGC activity is subject to extrinsic (central) or intrinsic (retinal) network-mediated circadian modulation during light entrainment and phase shifting. Eleven younger persons (18–30 years) with no ophthalmological, medical or sleep disorders participated. The activity of the inner (ipRGC) and outer retina (cone photoreceptors) was assessed hourly using the pupil light reflex during a 24 h period of constant environmental illumination (10 lux). Exogenous circadian cues of activity, sleep, posture, caffeine, ambient temperature, caloric intake and ambient illumination were controlled. Dim-light melatonin onset (DLMO) was determined from salivary melatonin assay at hourly intervals, and participant melatonin onset values were set to 14 h to adjust clock time to circadian time. Here we demonstrate in humans that the ipRGC controlled post-illumination pupil response has a circadian rhythm independent of external light cues. This circadian variation precedes melatonin onset and the minimum ipRGC driven pupil response occurs post melatonin onset. Outer retinal photoreceptor contributions to the inner retinal ipRGC driven post-illumination pupil response also show circadian variation whereas direct outer retinal cone inputs to the pupil light reflex do not, indicating that intrinsically photosensitive (melanopsin) retinal ganglion cells mediate this circadian variation.

Prioritizing land and sea conservation investments to protect coral reefs

Background: Coral reefs have exceptional biodiversity, support the livelihoods of millions of people, and are threatened by multiple human activities on land (e.g. farming) and in the sea (e.g. overfishing). Most conservation efforts occur at local scales and, when effective, can increase the resilience of coral reefs to global threats such as climate change (e.g. warming water and ocean acidification). Limited resources for conservation require that we efficiently prioritize where and how to best sustain coral reef ecosystems.----- ----- Methodology/Principal Findings: Here we develop the first prioritization approach that can guide regional-scale conservation investments in land-and sea-based conservation actions that cost-effectively mitigate threats to coral reefs, and apply it to the Coral Triangle, an area of significant global attention and funding. Using information on threats to marine ecosystems, effectiveness of management actions at abating threats, and the management and opportunity costs of actions, we calculate the rate of return on investment in two conservation actions in sixteen ecoregions. We discover that marine conservation almost always trumps terrestrial conservation within any ecoregion, but terrestrial conservation in one ecoregion can be a better investment than marine conservation in another. We show how these results could be used to allocate a limited budget for conservation and compare them to priorities based on individual criteria.----- ----- Conclusions/Significance: Previous prioritization approaches do not consider both land and sea-based threats or the socioeconomic costs of conserving coral reefs. A simple and transparent approach like ours is essential to support effective coral reef conservation decisions in a large and diverse region like the Coral Triangle, but can be applied at any scale and to other marine ecosystems.

The waddlia genome: A window into chlamydial biology

Growing evidence suggests that a novel member of the Chlamydiales order, Waddlia chondrophila, is a potential agent of miscarriage in humans and abortion in ruminants. Due to the lack of genetic tools to manipulate chlamydia, genomic analysis is proving to be the most incisive tool in stimulating investigations into the biology of these obligate intracellular bacteria. 454/Roche and Solexa/Illumina technologies were thus used to sequence and assemble de novo the full genome of the first representative of the Waddliaceae family, W. chondrophila. The bacteria possesses a 2′116′312bp chromosome and a 15′593 bp low-copy number plasmid that might integrate into the bacterial chromosome. The Waddlia genome displays numerous repeated sequences indicating different genome dynamics from classical chlamydia which almost completely lack repetitive elements. Moreover, W. chondrophila exhibits many virulence factors also present in classical chlamydia, including a functional type III secretion system, but also a large complement of specific factors for resistance to host or environmental stresses. Large families of outer membrane proteins were identified indicating that these highly immunogenic proteins are not Chlamydiaceae specific and might have been present in their last common ancestor. Enhanced metabolic capability for the synthesis of nucleotides, amino acids, lipids and other co-factors suggests that the common ancestor of the modern Chlamydiales may have been less dependent on their eukaryotic host. The fine-detailed analysis of biosynthetic pathways brings us closer to possibly developing a synthetic medium to grow W. chondrophila, a critical step in the development of genetic tools. As a whole, the availability of the W. chondrophila genome opens new possibilities in Chlamydiales research, providing new insights into the evolution of members of the order Chlamydiales and the biology of the Waddliaceae.