An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression.

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map.

Targeting ATR as Cancer Therapy: A new era for synthetic lethality and synergistic combinations?

The DNA damage response (DDR) machinery is responsible for detecting DNA damage, pausing the cell cycle and initiating DNA repair. Ataxia telangiectasia and Rad3-related (ATR) protein is a key kinase at the heart of the DDR, responsible for sensing replication stress (RS) and signalling it to S and G2/M checkpoints to facilitate repair. In cancer, loss of G1 checkpoint control and activation of oncogenes that drive replication, result in cancer cells more likely to enter S phase with increased RS.

Permanent pacing post-Fontan is not associated with reduced long-term survival.

Background: The Fontan procedure is the final stage of surgical palliation for a single-ventricle circulation. Significant complications are common including rhythm disturbance necessitating implantation of a permanent pacemaker. This has been widely considered a negative prognostic indicator.

Clinical nurse specialist prescribing in a cancer centre supportive and palliative care team.

Objective: To provide insight into the prescribing practices of three independent nurse prescribers (INPs)/clinical nurse specialists (CNSs) working in a supportive and palliative care team (SPCT) in a district general hospital and a specialist tertiary cancer centre in the UK.

Methods: A prospective review of all consultations and the prescribing activity arising from the consultations (and reasons for non-prescribing following a consultation) of 3 INPs/CNSs between 1 August 2018 and 31 October 2018.

Results: Four hundred ninety-three consultations were undertaken on 186 individual patients.

Rural clinical school students do come back: But it may take time.

Background And Objectives: Rural clinical schools (RCSs) help address Australia’s rural workforce shortfall, but they require an investment by rural clinicians and communities. Our objective was to determine the location of RCS graduates as one measure of the effectiveness of RCSs.

Method: This cross-sectional study obtained work location data for Australian National University Medical School (ANUMS) graduates and analysed both RCS and non-RCS data.

Evolution through cold and deep waters: the molecular phylogeny of the Lithodidae (Crustacea: Decapoda).

The objectives of this work are to use gene sequence data to assess the hypothesis that the Lithodinae arose from ancestors with uncalcified abdomens in shallow waters of the North-East Pacific, investigate the monophyly and interrelationships of genera within the Lithodinae and to estimate the scale and minimum number of biogeographic transitions from the shallow environment to the deep sea and vice versa. To do this, phylogenetic analysis from three mitochondrial and three nuclear markers was conducted using minimum evolution, maximum likelihood and Bayesian methods. The Lithodinae as defined to include North Pacific genus Cryptolithodes may be paraphyletic, with the Hapalogastrinae and Cryptolithodes as sister taxa.

Phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) follicular signalling is conserved in the mare ovary.

The mare ovary is unique in its anatomical structure; however, the signalling pathways responsible for physiological processes, such as follicular activation, remain uncharacterised. This provided us with the impetus to explore whether signalling molecules from important folliculogenesis pathways, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and Janus kinase/signal transducer and activator of transcription (JAK/STAT), are conserved in the mare ovary. Messenger RNA expression of six genes important in follicle development was measured using quantitative polymerase chain reaction and protein localisation of key pathway members (PI3K, AKT1, phosphatase and tensin homologue (PTEN), JAK1, STAT3 and suppressor of cytokine signalling 4 (SOCS4)) was compared in tissue from fetal and adult mare ovaries.

Can research that is not intended or unlikely to be published be considered ethical?

Background: For research to be ethically acceptable, the potential benefits must justify any risks involved for participants. Dissemination of research findings through publication is one way of creating benefit, but not all researchers intend to publish their research. Other factors, such as lack of size or representativeness, generalisability or innovativeness, or negative findings mean the research is unlikely to be published in a peer-reviewed medical journal.

Adjusting cryodiluent composition for improved post-thaw quality of rabbit spermatozoa.

Improved fertility following artificial insemination with frozen-thawed spermatozoa would offer rabbit producers faster genetic improvement. Previous work investigating cryoprotectants for rabbit spermatozoa have reported inconsistent results. Semen was collected from three rabbit bucks by artificial vagina and frozen using a standard procedure with varied cryodiluent components.

Electrophilic aldehyde products of lipid peroxidation selectively adduct to heat shock protein 90 and arylsulfatase A in stallion spermatozoa.

Oxidative stress is a major determinant of mammalian sperm function stimulating lipid peroxidation cascades that culminate in the generation of potentially cytotoxic aldehydes. The aim of this study was to assess the impact of such aldehydes on the functionality of stallion spermatozoa. The impact of exposure to exogenous acrolein (ACR) and 4-hydroxynonenal (4HNE) was manifested in a highly significant dose- and time-dependent increase in mitochondrial reactive oxygen species (ROS), total cellular ROS, a decrease in sperm motility, and a time-dependent increase in lipid peroxidation.

Non-surgical sterilisation methods may offer a sustainable solution to feral horse (Equus caballus) overpopulation.

Feral horses are a significant pest species in many parts of the world, contributing to land erosion, weed dispersal and the loss of native flora and fauna. There is an urgent need to modify feral horse management strategies to achieve public acceptance and long-term population control. One way to achieve this is by using non-surgical methods of sterilisation, which are suitable in the context of this mobile and long-lived species.

Aldehyde Dehydrogenase Plays a Pivotal Role in the Maintenance of Stallion Sperm Motility.

Although stallion spermatozoa produce significant quantities of reactive oxygen species, a lag between 4-hydroxynonenal (4HNE) adduction and the loss of motility in stallion spermatozoa suggests the presence of a robust aldehyde detoxification mechanism. Because there is a paucity of studies characterizing the role of aldehyde dehydrogenase (ALDH) in sperm functionality, the aim of this study was to ascertain the relationship between 4HNE production and motility and ALDH expression by stallion spermatozoa. PCR analysis revealed the presence of the ALDH1A3, ALDH1B1, and ALDH2 isoforms in these cells.

The effect of temperature on the evolution of per offspring investment in a globally distributed family of marine invertebrates (Crustacea: Decapoda: Lithodidae).

Within the marine environment, per offspring investment (POI) is associated with modes in larval development; an increase in POI has often been described with a decrease in temperature, as evidenced along latitudinal clines. However, the environmental drivers of POI remain largely hypothetical and have not yet been tested within an evolutionary context. Here, we test the hypothesis that developmental temperature is linked to POI within a globally distributed and diverse family of benthic crustaceans, the Lithodidae, also known as stone or king crab.

Building social capital with interprofessional student teams in rural settings: A service-learning model.

Objective: To describe outcomes of a model of service learning in interprofessional learning (IPL) aimed at developing a sustainable model of training that also contributed to service strengthening.

Design: A total of 57 semi-structured interviews with key informants and document review exploring the impacts of interprofessional student teams engaged in locally relevant IPL activities.

Setting: Six rural towns in South East New South Wales.

Using qualitative mixed methods to study small health care organizations while maximising trustworthiness and authenticity.

Background: The primary health care sector delivers the majority of health care in western countries through small, community-based organizations. However, research into these healthcare organizations is limited by the time constraints and pressure facing them, and the concern by staff that research is peripheral to their work. We developed Q-RARA-Qualitative Rapid Appraisal, Rigorous Analysis-to study small, primary health care organizations in a way that is efficient, acceptable to participants and methodologically rigorous.

The computerized medical record as a tool for clinical governance in Australian primary care.

Background: Computerized medical records (CMR) are used in most Australian general practices. Although CMRs have the capacity to amalgamate and provide data to the clinician about their standard of care, there is little research on the way in which they may be used to support clinical governance: the process of ensuring quality and accountability that incorporates the obligation that patients are treated according to best evidence.

Objective: The objective of this study was to explore the capability, capacity, and acceptability of CMRs to support clinical governance.

Mortality and quality of life in the five years after severe sepsis.

Introduction: Severe sepsis is associated with high levels of morbidity and mortality, placing a high burden on healthcare resources. We aimed to study outcomes in the five years after severe sepsis.

Methods: This was a cohort study using data from a prospective audit in 26 adult ICUs in Scotland.

A spatial analysis of the expanding roles of nurses in general practice.

Background: Changes to the workforce and organisation of general practice are occurring rapidly in response to the Australian health care reform agenda, and the changing nature of the medical profession. In particular, the last five years has seen the rapid introduction and expansion of a nursing workforce in Australian general practices. This potentially creates pressures on current infrastructure in general practice.

Nurses and the wise organisation: techne and phronesis in Australian general practice.

This paper draws on classical theories of wisdom to explore the organisational impact of nurses on Australian general practice. Between 2004 and 2008, numbers of general practice nurses doubled, the most rapid influx of nurses into any Australian workplace over the decade. Using data from the Australian General Practice Nurses Study, we argue that nurses had a positive impact because they introduced techne at the organisational level and amplified phronesis in clinical activities.