Research news in brief

Sax Institute’s Research Action Awards applications

Applications close shortly for the Sax Institute’s 2018 Research Action Awards. The Awards honour individuals whose work has made a significant impact on health policy, programs or service delivery. Up to three awards will be granted, and each winner will receive a certificate and prize of $5000 at a ceremony in Sydney attended by NSW Health Secretary Elizabeth Koff and National Health and Medical Research Council Chief Executive Officer Professor Anne Kelso, AO. The closing date for applications is 5 pm on Monday, 10 September 2018. Applications are open to early career researchers who work for one of the Sax Institute’s Ordinary Member organisations, and who have up to 15 years’ post-doctoral or equivalent experience. Applications must describe research that has had an impact on health policy, programs or service delivery, and must demonstrate evidence of the impact. Applications will be reviewed by an independent assessment committee comprised of international and national experts in public health or health services research, policy and knowledge exchange. Professor Nicholas Mays, Professor of Health Policy at the London School of Hygiene and Tropical Medicine and Director of the Policy Innovation Research Unit, will chair the assessment committee. Award winners will be announced at the ceremony on 28 November 2018. Details and application forms can be found here.

Lung damage in ventilated pre-term infants may differ with gestational age

Assisted ventilation is crucial to support very pre-term babies, but the treatment often leads to chronic lung disease. While the survival of pre-term babies has increased over the past 30 years, rates of chronic lung disease have remained static. Researchers from the Murdoch Children’s Research Institute have found that the type of injury caused by ventilation depends on the gestational age of the lungs. The findings, published in Scientific Reports, suggest that individualised respiratory support could reduce risks to infants. In the animal study, researchers mapped protein changes in blood plasma following ventilation of lambs born at term, pre-term (less than 32 weeks) and very pre-term (less than 26 weeks). By examining blood samples taken within the first 60 minutes of life, the researchers found significant changes in coagulant and complement protein expression in the pre-term models. The researchers said that the changes indicated potential for worsening lung injury and inhibiting the effectiveness of treatments options such as surfactant administration. In the study’s next phase, researchers will examine the changes in the lungs of pre-term human infants.

Natural killers may help keep tuberculosis in check

Higher levels of natural killer cells are associated with tuberculosis (TB) latency, according to research from the University of Queensland and Stanford University School of Medicine, published in Nature. The findings raise the question as to whether natural killer cells might play an active role in controlling TB infections. The majority of TB infections are latent — manifesting, without outward symptoms, in a contained state. It is estimated that a quarter of the world’s population has latent TB, although fewer than 10% of latent TB cases end up progressing to an active state. The immune factors that influence a given individual’s infection outcome, however, are poorly understood. To investigate the immune state that leads to latency and how that changes if the disease progresses, the researchers conducted studies of various human cohorts combining mass cytometry analysis with an examination of gene expression datasets to identify differences in immune cell populations between uninfected subjects and those with latent or active TB. They found that latent manifestations of TB were associated with higher numbers of natural killer cells — white blood cells that can kill certain pathogens — with enhanced antitoxin responses in comparison with uninfected individuals. In subjects with an active infection, levels of natural killer cells were diminished, but returned to baseline levels when the infection was cured. However, the findings cannot prove a causal relationship between natural killer cells and TB latency. Additionally, the authors demonstrated that measurements of natural killer cell levels can be used to determine the activity level and burden of TB infection in a patient’s lungs — a finding that could help to assess disease progression and optimise treatments.

How the human immune system protects against Ebola

Two types of human antibodies that target different parts of the Ebola virus synergise their antiviral effects by inhibiting different steps of infection, according to a US study published in PLoS Pathogens. The unprecedented Ebola virus epidemic in West Africa from 2013 to 2016 resulted in more than 11 000 human fatalities, demonstrating the urgent need for treatments against this virus and related highly pathogenic filoviruses. Despite intense international collaborative efforts, there is still no licensed therapeutic available against filovirus disease. Although the human immune system can produce strong antibody responses against filoviruses, the effects on multiple steps of filovirus infection have not been clear. To address this gap in knowledge, the researchers evaluated the mechanisms underlying the antiviral effects of a diverse panel of monoclonal antibodies obtained from several survivors of natural Ebola virus infections. Monoclonal antibodies that targeted either the glycan cap or stem region of the viral glycoprotein interfered with and targeted different steps of filovirus infection. For example, glycan cap-specific antibodies inhibited viral attachment to the cell surface, cell-to-cell transmission and virion budding. By contrast, stem-specific antibodies triggered the activation of natural killer cells and the destruction of infected cells by monocytes and neutrophils. Taken together, the findings suggest that different types of antibodies exert cooperative effects by blocking distinct steps of filovirus infection. According to the authors, antibody cocktails that combine complementary antiviral effects should be tested in future studies.

What’s new online and open access at the MJA

27 August Research: Predictors of inpatient rehabilitation after total knee replacement: an analysis of private hospital claims data
Schilling et al; doi: 10.5694/mja17.01231
Substantial variation in inpatient rehabilitation rates is unexplained by patient factors, suggesting some low value care … OPEN ACCESS permanently

27 August Podcast with Dr Chris Schilling, health economist and associate director of KPMG Australia … OPEN ACCESS permanently

27 August Medical history: Vale “New Medical School” (the Blackburn Building), University of Sydney
Storey; doi: 10.5694/mja18.00038
More than a building: a change in direction of medical education

27 August Study protocol: Cancer Molecular Screening and Therapeutics (MoST): a framework for multiple, parallel signal-seeking studies of targeted therapies for rare and neglected cancers
Thavaneswaran et al; doi: 10.5694/mja18.00227
MoST is an innovative approach for translating molecular opportunities into clinical care … OPEN ACCESS permanently

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