Nasopharyngeal carriage and macrolide resistance in Indigenous children with bronchiectasis randomized to long-term azithromycin or placebo.

Although long-term azithromycin decreases exacerbation frequency in bronchiectasis, increased macrolide resistance is concerning. We investigated macrolide resistance determinants in a secondary analysis of a multicenter randomized controlled trial. Indigenous Australian children living in remote regions and urban New Zealand Māori and Pacific Islander children with bronchiectasis were randomized to weekly azithromycin (30 mg/kg) or placebo for up to 24 months and followed post-intervention for up to 12 months.

The microbiome of otitis media with effusion in Indigenous Australian children.

Introduction: Indigenous Australian children have a high prevalence of otitis media with effusion (OME) and associated conductive hearing loss. Only three microbiological studies of middle ear fluid (MEF) from Indigenous Australian children with OME have been reported. All of these were reliant on culture or species-specific PCR assays.

An analysis of the attrition of drug candidates from four major pharmaceutical companies.

The pharmaceutical industry remains under huge pressure to address the high attrition rates in drug development. Attempts to reduce the number of efficacy- and safety-related failures by analysing possible links to the physicochemical properties of small-molecule drug candidates have been inconclusive because of the limited size of data sets from individual companies. Here, we describe the compilation and analysis of combined data on the attrition of drug candidates from AstraZeneca, Eli Lilly and Company, GlaxoSmithKline and Pfizer.

Real-time resolution of point mutations that cause phenovariance in mice.

With the wide availability of massively parallel sequencing technologies, genetic mapping has become the rate limiting step in mammalian forward genetics. Here we introduce a method for real-time identification of N-ethyl-N-nitrosourea-induced mutations that cause phenotypes in mice. All mutations are identified by whole exome G1 progenitor sequencing and their zygosity is established in G2/G3 mice before phenotypic assessment.

A mechanistic proposal for the protodeboronation of neat boronic acids: boronic acid mediated reaction in the solid state.

A combined experimental and computational study suggests that a reduction in the entropy of activation in the solid state can lead to the protodeboronation of boronic acids.

Pneumococcal conjugate vaccines PREVenar13 and SynflorIX in sequence or alone in high-risk Indigenous infants (PREV-IX_COMBO): protocol of a randomised controlled trial.

Introduction: Otitis media (OM) starts within weeks of birth in almost all Indigenous infants living in remote areas of the Northern Territory (NT). OM and associated hearing loss persist from infancy throughout childhood and often into adulthood. Educational and social opportunities are greatly compromised.

Measuring the impact of a burns school reintegration programme on the time taken to return to school: A multi-disciplinary team intervention for children returning to school after a significant burn injury.

Introduction: Returning to school can be a major step for burn-injured children, their family, and staff and pupils at the receiving school. Previous literature has recognised the difficulties children may face after a significant injury and factors that may influence a successful reintegration.

Aim: A regional paediatric burns service recognised that some patients were experiencing difficulties in returning to school.

Circumventing seizure activity in a series of G protein coupled receptor 119 (GPR119) agonists.

Agonism of GPR119 is viewed as a potential therapeutic approach for the treatment of type II diabetes and other elements of metabolic syndrome. During progression of a previously disclosed candidate 1 through mice toxicity studies, we observed tonic-clonic convulsions in several mice at high doses. An in vitro hippocampal brain slice assay was used to assess the seizure liability of subsequent compounds, leading to the identification of an aryl sulfone as a replacement for the 3-cyano pyridyl group.

Otitis media in children vaccinated during consecutive 7-valent or 10-valent pneumococcal conjugate vaccination schedules.

Background: In 2001 when 7-valent pneumococcal conjugate vaccine (PCV7) was introduced, almost all (90%) young Australian Indigenous children living in remote communities had some form of otitis media (OM), including 24% with tympanic membrane perforation (TMP). In late 2009, the Northern Territory childhood vaccination schedule replaced PCV7 with 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10).

Methods: We conducted regular surveillance of all forms of OM in children in remote Indigenous communities between September 2008 and December 2012.

Immunogenicity and safety of the candidate RTS,S/AS01 vaccine in young Nigerian children: a randomized, double-blind, lot-to-lot consistency trial.

Background: For regulatory approval, consistency in manufacturing of vaccine lots is expected to be demonstrated in confirmatory immunogenicity studies using two-sided equivalence trials. This randomized, double-blind study (NCT01323972) assessed consistency of three RTS,S/AS01 malaria vaccine batches formulated from commercial-scale purified antigen bulk lots in terms of anti-CS-responses induced.

Methods: Healthy children aged 5-17 months were randomized (1:1:1:1) to receive RTS,S/AS01 at 0-1-2 months from one of three commercial-scale purified antigen bulk lots (1600 litres-fermentation scale; commercial-scale lots), or a comparator vaccine batch made from pilot-scale purified antigen bulk lot (20 litres-fermentation scale; pilot-scale lot).

Strontium vanadium oxide-hydrides: "square-planar" two-electron phases.

A series of strontium vanadium oxide-hydride phases prepared by utilizing a low-temperature synthesis strategy in which oxide ions in Sr(n+1)V(n)O(3n+1) (n=∞, 1, 2) phases are topochemically replaced by hydride ions to form SrVO2H, Sr2VO3H, and Sr3V2O5H2, respectively. These new phases contain sheets or chains of apex-linked V(3+)O4 squares stacked with SrH layers/chains, such that the n=∞ member, SrVO2H, can be considered to be analogous to "infinite-layer" phases, such as Sr(1-x)Ca(x)CuO2 (the parent phase of the high-T(c) cuprate superconductors), but with a d(2) electron count. All three oxide-hydride phases exhibit strong antiferromagnetic coupling, with SrVO2H exhibiting an antiferromagnetic ordering temperature, T(N)>300 K.

Improving the availability of clinical history accompanying radiographic examinations in a large pediatric radiology department.

Objective: The purpose of this quality improvement initiative was to improve the consistency with which radiologists are provided a complete clinical history when interpreting radiography examinations performed in the outpatient and emergency department settings.

Materials And Methods: The clinical history was considered complete if it contained three elements: nature of the symptoms, description of injury, or cause for clinical concern; duration of symptoms or time of injury; and focal site of pain or abnormality, if applicable. This was reduced to three elements: "what-when-where.

Can mobile phone multimedia messages and text messages improve clinic attendance for Aboriginal children with chronic otitis media? A randomised controlled trial.

Aim: Does phone multimedia messages (MMS) to families of Indigenous children with tympanic membrane perforation (TMP): (i) increase clinic attendance; (ii) improve ear health; and (iii) provide a culturally appropriate method of health promotion?

Methods: Fifty-three Australian Aboriginal children with a TMP living in remote community households with a mobile phone were randomised into intervention (n = 30) and control (n = 23) groups. MMS health messages in local languages were sent to the intervention group over 6 weeks.

Primary Outcome: there was no significant difference in clinic attendance, with 1.

Personal nitrogen footprint tool for the United Kingdom.

The global nitrogen (N) cycle has been transformed by human use of reactive N as a consequence of increased demand for food and energy. Given the considerable impact of humans on the N cycle, it is essential that we raise awareness amongst the public and policy makers as this is the first step in providing individuals and governments the opportunity to reduce their impact on the N cycle and reduce the environmental and health consequences of N pollution. Here we describe an N footprint tool for the UK developed as part of the N-PRINT program.

Diversity of nontypeable Haemophilus influenzae strains colonizing Australian Aboriginal and non-Aboriginal children.

Nontypeable Haemophilus influenzae (NTHI) strains are responsible for respiratory-related infections which cause a significant burden of disease in Australian children. We previously identified a disparity in NTHI culture-defined carriage rates between Aboriginal and non-Aboriginal children (42% versus 11%). The aim of this study was to use molecular techniques to accurately determine the true NTHI carriage rates (excluding other culture-identical Haemophilus spp.

Quality Improvement and Confirmation Projects: Facilitating Rapid, Measurable Performance Improvement.

As radiology departments continue to increase in size and complexity, the process of improving and maintaining excellent performance is becoming increasingly challenging. In response, a systematic process for efficiently implementing and sustaining measurable improvement in our radiology department has been developed, which targets focused aspects of individual performance that contribute to overall departmental quality. Projects designed to achieve such improvements have been called quality improvement and confirmation (QuIC) projects.

Comparison of anti-pneumococcal antibodies in cord blood from Australian indigenous and Gambian neonates and the implications for otitis media.

Background: Australian indigenous infants experience the highest incidence of chronic suppurative and acute otitis media in the world with many babies developing disease in the early postnatal period. Streptococcus pneumoniae is the major cause of otitis media in this population. Infants are protected against bacterial disease in the first months of life by passive transfer of maternal antibody across the placenta during the late stages of gestation.

Predicting the activity and toxicity of new psychoactive substances: a pharmaceutical industry perspective.

Predicting the effect that new compounds might have when administered to human beings is a common desire shared by researchers in the pharmaceutical industry and those interested in psychoactive compounds (illicit or otherwise). The experience of the pharmaceutical industry is that making such predictions at a usefully accurate level is not only difficult but that even when billions of dollars are spent to ensure that only compounds likely to have a desired effect without unacceptable side-effects are dosed to humans in clinical trials, they fail in more than 90% of cases. A range of experimental and computational techniques is used and they are placed in their context in this paper.

High nasopharyngeal carriage of non-vaccine serotypes in Western Australian aboriginal people following 10 years of pneumococcal conjugate vaccination.

Background: Invasive pneumococcal disease (IPD) continues to occur at high rates among Australian Aboriginal people. The seven-valent pneumococcal conjugate vaccine (7vPCV) was given in a 2-4-6-month schedule from 2001, with a 23-valent pneumococcal polysaccharide vaccine (23vPPV) booster at 18 months, and replaced with 13vPCV in July 2011. Since carriage surveillance can supplement IPD surveillance, we have monitored pneumococcal carriage in western Australia (WA) since 2008 to assess the impact of the 10-year 7vPCV program.

Psychopathy and deception detection.

Researchers have found that most people have difficulty detecting deception; however, certain individuals are able to consistently detect deception above the level of chance. This study examined whether psychopathic traits are related to deception detection. Undergraduate participants (n = 117) indicated whether individuals in video clips were lying or telling the truth and completed a measure of psychopathy.

Standard method for detecting upper respiratory carriage of Streptococcus pneumoniae: updated recommendations from the World Health Organization Pneumococcal Carriage Working Group.

In 2003 the World Health Organization (WHO) convened a working group and published a set of standard methods for studies measuring nasopharyngeal carriage of Streptococcus pneumoniae (the pneumococcus). The working group recently reconvened under the auspices of the WHO and updated the consensus standard methods. These methods describe the collection, transport and storage of nasopharyngeal samples, as well as provide recommendations for the identification and serotyping of pneumococci using culture and non-culture based approaches.

Absence of an important vaccine and diagnostic target in carriage- and disease-related nontypeable Haemophilus influenzae.

Nontypeable Haemophilus influenzae (NTHi)-associated disease is a major health problem globally. Whole-genome sequence analysis identified the absence of hpd genes encoding Haemophilus protein D in 3 of 16 phylogenetically distinct NTHi isolates. This novel finding is of potential clinical significance, as protein D and hpd represent important NTHi vaccine antigen and diagnostic targets, respectively.

Surveillance of pneumococcal serotype 1 carriage during an outbreak of serotype 1 invasive pneumococcal disease in central Australia 2010-2012.

Background: An outbreak of serotype 1 invasive pneumococcal disease (IPD) occurred in Central Australia from October 2010 to the latter part of 2012. Surveillance of serotype 1 carriage was conducted to determine epidemiological features of asymptomatic carriage that could potentially be driving the outbreak.

Methods: 130 patients and accompanying persons presenting at Alice Springs Hospital Emergency Department consented to nasopharyngeal swab (NPS) collection.

Dominance of Haemophilus influenzae in ear discharge from Indigenous Australian children with acute otitis media with tympanic membrane perforation.

Background: Indigenous Australian children living in remote communities experience high rates of acute otitis media with tympanic membrane perforation (AOMwiP). Otitis media in this population is associated with dense nasopharyngeal colonization of three primary otopathogens; Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. Little is known about the relative abundance of these pathogens during infection.