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This paper reports on research exploring the academic workload and performance practices of Australian universities. This research has identified a suite of activities associated with teaching, research and service, each with an associated time value (allocation). This led to the development of the academic workload estimation tool (AWET). In 2020, to validate the findings, we contacted academics willing to participate further and conducted interviews. We used the AWET to estimate workload for each individual for the previous year and compared it to the workload allocated according to their institutional workload model. Discrepancies were then discussed to ascertain to what extent the AWET was able to capture their work. In general, the participants thought the AWET provided a more realistic estimate of their actual work and highlighted how much is underestimated or unaccounted for by the workload models used within their institutions. It also showed how academic performance policies, focussed primarily on research output, disadvantaged many individuals because they ignored or minimised many scholarly, teaching and service-related tasks inherent in the academic role. Overall, the findings showed the AWET was a useful tool to discuss academic work and assisted them to better capture the complexity and extent of what they did. We offer the AWET as a validated approach for academics to estimate their workload in a holistic and transparent manner. We suggest its implementation institution-wide, along with an aligned performance policy, will facilitate negotiation of reasonable performance expectations. This will rebuild trust in the processes and improve a university's effectiveness. [ABSTRACT FROM AUTHOR]

Peri-hilar cholangiocarcinoma (pCCA) is chemorefractory and limited genomic analyses have been undertaken in Western idiopathic disease. We undertook comprehensive genomic analyses of a U.K. idiopathic pCCA cohort to characterize its mutational profile and identify new targets. Whole exome and targeted DNA sequencing was performed on forty-two resected pCCA tumors and normal bile ducts, with Gene Set Enrichment Analysis (GSEA) using one-tailed testing to generate false discovery rates (FDR). 60% of patients harbored one cancer-associated mutation, with two mutations in 20%. High frequency somatic mutations in genes not typically associated with cholangiocarcinoma included mTOR, ABL1 and NOTCH1. We identified non-synonymous mutation (p.Glu38del) in MAP3K9 in ten tumors, associated with increased peri-vascular invasion (Fisher's exact, p < 0.018). Mutation-enriched pathways were primarily immunological, including innate Dectin-2 (FDR 0.001) and adaptive T-cell receptor pathways including PD-1 (FDR 0.007), CD4 phosphorylation (FDR 0.009) and ZAP70 translocation (FDR 0.009), with overlapping HLA genes. We observed cancer-associated mutations in over half of our patients. Many of these mutations are not typically associated with cholangiocarcinoma yet may increase eligibility for contemporary targeted trials. We also identified a targetable MAP3K9 mutation, in addition to oncogenic and immunological pathways hitherto not described in any cholangiocarcinoma subtype. [ABSTRACT FROM AUTHOR]

Internationally, much has changed in the governance of universities since the adoption of corporate management approaches. A strong focus on efficiency, productivity and accountability arising from these approaches has been well documented in the literature. Reductions in government funding have caused universities to become more competitive and entrepreneurial. However, little is known about the impacts of these changes on the working lives of individual academics. This paper is part of an ongoing study exploring the lived experiences of 2526 Australian academics who responded to a national questionnaire. This paper builds on earlier work by holistically drawing together the earlier findings which separately analysed the teaching, research and administration/service aspects of their work. In examining the effectiveness of universities through the ability of their academics to undertake their roles, we found the voices of academics that need to be heard in the development and implementation of key policies, such as academic workload and performance, to preserve the essentially self-managed nature of their work. By combining the learning from the project through the literature review, the statistical analysis and themes from the open-ended questions, we developed a set of principles to underpin these policies in universities. These principles can guide universities to shift towards a more collaborative working relationship with academics, based on trust, and actively encourage them to play be more active in institutional decision-making, especially in relation to policies that directly affect their work. These results have implications for improving the productivity of academics and the institutions in which they work. [ABSTRACT FROM AUTHOR]

In recent electoral contests, political observers and media outlets increasingly report on the level of "authenticity" of political candidates. However, even though this term has become commonplace in political commentary, it has received little attention in empirical electoral research. In this study, we identify the characteristics that we argue make a politician "authentic". After theoretically discussing the different dimensions of this trait, we propose a survey battery aimed at measuring perceptions of the authenticity of political candidates. Testing our measure using data sets from different countries, we show that the answers to our items load on one latent concept that we call "authenticity". Furthermore, perceptions of candidate authenticity correlate strongly with evaluations of political parties and leaders, and with vote intention, while they are empirically distinguishable from other traits. We conclude that candidate authenticity is an important trait that should be taken into account by future research. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) is highly polymorphic and encodes 13 proteins which are critical to the production of ATP via oxidative phosphorylation. As mtDNA is maternally inherited and undergoes negligible recombination, acquired mutations have subdivided the human population into several discrete haplogroups. Mitochondrial haplogroup has been found to significantly alter mitochondrial function and impact susceptibility to adverse drug reactions. Despite these findings, there are currently limited models to assess the effect of mtDNA variation upon susceptibility to adverse drug reactions. Platelets offer a potential personalised model of this variation, as their anucleate nature offers a source of mtDNA without interference from the nuclear genome. This study, therefore, aimed to determine the effect of mtDNA variation upon mitochondrial function and drug-induced mitochondrial dysfunction in a platelet model. The mtDNA haplogroup of 383 healthy volunteers was determined using next-generation mtDNA sequencing (Illumina MiSeq). Subsequently, 30 of these volunteers from mitochondrial haplogroups H, J, T and U were recalled to donate fresh, whole blood from which platelets were isolated. Platelet mitochondrial function was tested at basal state and upon treatment with compounds associated with both mitochondrial dysfunction and adverse drug reactions, flutamide, 2-hydroxyflutamide and tolcapone (10–250 μM) using extracellular flux analysis. This study has demonstrated that freshly-isolated platelets are a practical, primary cell model, which is amenable to the study of drug-induced mitochondrial dysfunction. Specifically, platelets from donors of haplogroup J have been found to have increased susceptibility to the inhibition of complex I-driven respiration by 2-hydroxyflutamide. At a time when individual susceptibility to adverse drug reactions is not fully understood, this study provides evidence that inter-individual variation in mitochondrial genotype could be a factor in determining sensitivity to mitochondrial toxicants associated with costly adverse drug reactions. [ABSTRACT FROM AUTHOR]

Alterations in the human microbiome have been observed in a variety of conditions such as asthma, gingivitis, dermatitis and cancer, and much remains to be learned about the links between the microbiome and human health. The fusion of artificial intelligence with rich microbiome datasets can offer an improved understanding of the microbiome's role in human health. To gain actionable insights it is essential to consider both the predictive power and the transparency of the models by providing explanations for the predictions. We combine the collection of leg skin microbiome samples from two healthy cohorts of women with the application of an explainable artificial intelligence (EAI) approach that provides accurate predictions of phenotypes with explanations. The explanations are expressed in terms of variations in the relative abundance of key microbes that drive the predictions. We predict skin hydration, subject's age, pre/post-menopausal status and smoking status from the leg skin microbiome. The changes in microbial composition linked to skin hydration can accelerate the development of personalized treatments for healthy skin, while those associated with age may offer insights into the skin aging process. The leg microbiome signatures associated with smoking and menopausal status are consistent with previous findings from oral/respiratory tract microbiomes and vaginal/gut microbiomes respectively. This suggests that easily accessible microbiome samples could be used to investigate health-related phenotypes, offering potential for non-invasive diagnosis and condition monitoring. Our EAI approach sets the stage for new work focused on understanding the complex relationships between microbial communities and phenotypes. Our approach can be applied to predict any condition from microbiome samples and has the potential to accelerate the development of microbiome-based personalized therapeutics and non-invasive diagnostics. [ABSTRACT FROM AUTHOR]

Neo-liberal reforms in higher education have resulted in corporate managerial practices in universities and a drive for efficiency and productivity in teaching and research. As a result, there has been an intensification of academic work, increased stress for academics and an emphasis on accountability and performativity in universities. The paper proposes that while managerialism in modern universities is now the norm, corporate approaches have disempowered academics in their institutions and reduced productivity because they ignore the nature of academic work. Using Foucault's conception of power relations in institutions, policies that directly affect academic work such as workload allocation and performance management are identified as key ways in which power is exercised in universities. The paper reports on a case study in one university which explored the relationship between the academic workload allocation and performance management policies and concludes that a more balanced power relationship is needed in which academics can have more influence over these key processes which control their work so they preserve the self-managed aspects of academic work and the intrinsic motivations driving their careers. [ABSTRACT FROM AUTHOR]

Neoliberal reforms in higher education have resulted in corporate managerial practices in universities and a drive for efficiency and productivity in teaching and research. As a result, there has been an intensification of academic work, increased stress for academics and an emphasis on accountability and performativity in universities. This paper critically examines these developments in institutions and draws on evidence from universities across the sector and a detailed case study in one university to identify the impacts of these changes on academic work. Given its ubiquity and the link of academic productivity to institutional experience, the paper argues that assumptions underpinning academic performance management need to be rethought to recognise the fundamentally intrinsic motivational nature of academic work. The paper explores the effects of performance management on individual academics as a case study in one institution and proposes a re-design of academic performance management to improve productivity based on the evidence. [ABSTRACT FROM AUTHOR]

The Australian Clinical Dosimetry Service (ACDS) has demonstrated the capacity to perform a basic dosimetry audit on all radiotherapy clinics across Australia. During the ACDS's three and a half year trial the majority of the audits were performed using optically stimulated luminescence dosimeters (OSLD) mailed to facilities for exposure to a reference dose, and then returned to the ACDS for analysis. This technical note investigates the stability of the readout process under the large workload of the national dosimetry audit. The OSLD readout uncertainty contributes to the uncertainty of several terms of the dose calculation equation and is a major source of uncertainty in the audit. The standard deviation of four OSLD readouts was initially established at 0.6 %. Measurements over 13 audit batches-each batch containing 200−400 OSLDs-showed variability (0.5−0.9 %) in the readout standard deviation. These shifts have not yet necessitated a change to the audit scoring levels. However, a standard deviation in OSLD readouts greater than 0.9 % will change the audit scoring levels. We identified mechanical wear on the OSLD readout adapter as a cause of variability in readout uncertainty, however, we cannot rule out other causes. Additionally we observed large fluctuations in the distribution of element correction factors (ECF) for OSLD batches. We conclude that the variability in the width of the ECF distribution from one batch to another is not caused by variability in readout uncertainty, but rather by variations in the OSLD stock. [ABSTRACT FROM AUTHOR]

Basic evaluation research of interim programs conducted to date has employed three of four conceptual models. In the present article, the authors (1) identify these four conceptual models, (2) briefly outline significant studies that have been conducted using three of them, and (3) explore the possible advantages of one model which has not been used or reported in the literature of higher education. It is hoped that some insight into the possible ways to evaluate interim programs was provided, that further thought about objective evaluation programs was initiated, and that creative ventures into areas not yet researched were stimulated. [ABSTRACT FROM AUTHOR]

The endocardium is the endothelial component of the vertebrate heart and plays a key role in heart development. Where, when, and how the endocardium segregates during embryogenesis have remained largely unknown, however. We now show that Nkx2-5+ cardiac progenitor cells (CPCs) that express the Sry-type HMG box gene Sox17 from embryonic day (E) 7.5 to E8.5 specifically differentiate into the endocardium in mouse embryos. Although Sox17 is not essential or sufficient for endocardium fate, it can bias the fate of CPCs toward the endocardium. On the other hand, Sox17 expression in the endocardium is required for heart development. Deletion of Sox17 specifically in the mesoderm markedly impaired endocardium development with regard to cell proliferation and behavior. The proliferation of cardiomyocytes, ventricular trabeculation, and myocardium thickening were also impaired in a non-cell-autonomous manner in the Sox17 mutant, likely as a consequence of down-regulation of NOTCH signaling. An unknown signal, regulated by Sox17 and required for nurturing of the myocardium, is responsible for the reduction in NOTCH-related genes in the mutant embryos. Our results thus provide insight into differentiation of the endocardium and its role in heart development. [ABSTRACT FROM AUTHOR]

Microbial ecology studies are often performed through extraction of metagenomic DNA followed by amplification and sequencing of a marker. It is known that each step may bias the results. These biases have been explored for the study of bacterial communities, but rarely for fungi. Our aim was therefore to evaluate methods for the study of the gut mycobiome. We first evaluated DNA extraction methods in fungal cultures relevant to the gut. Afterwards, to assess how these methods would behave with an actual sample, stool from a donor was spiked with cells from the same cultures. We found that different extraction kits favour some species and bias against others. In terms of amplicon sequencing, we evaluated five primer sets, two for ITS2 and one for ITS1, 18S and 28S rRNA. Results showed that 18S rRNA outperformed the other markers: it was able to amplify all the species in the mock community and to discriminate among them. ITS primers showed both amplification and sequencing biases, the latter related to the variable length of the product. We identified several biases in the characterisation of the gut mycobiome and showed how crucial it is to be aware of these before drawing conclusions from the results of these studies. [ABSTRACT FROM AUTHOR]

Soil biota accounts for ~25% of global biodiversity and is vital to nutrient cycling and primary production. There is growing momentum to study total belowground biodiversity across large ecological scales to understand how habitat and soil properties shape belowground communities. Microbial and animal components of belowground communities follow divergent responses to soil properties and land use intensification; however, it is unclear whether this extends across heterogeneous ecosystems. Here, a national-scale metabarcoding analysis of 436 locations across 7 different temperate ecosystems shows that belowground animal and microbial (bacteria, archaea, fungi, and protists) richness follow divergent trends, whereas β-diversity does not. Animal richness is governed by intensive land use and unaffected by soil properties, while microbial richness was driven by environmental properties across land uses. Our findings demonstrate that established divergent patterns of belowground microbial and animal diversity are consistent across heterogeneous land uses and are detectable using a standardised metabarcoding approach. It is unclear whether microbes and animals residing in soils follow similar distribution patterns. Here, the authors report richness and diversity of soil microbes and invertebrates across soil, vegetation, and land use gradients in Wales, showing that land use affects animals while soil traits affect microbes. [ABSTRACT FROM AUTHOR]

The Ebola virus (EBOV) variant Makona (which emerged in 2013) was the causative agent of the largest outbreak of Ebola Virus Disease recorded. Differences in virus-host interactions between viral variants have potential consequences for transmission, disease severity and mortality. A detailed profile of the cellular changes induced by the Makona variant compared with other Ebola virus variants was lacking. In this study, A549 cells, a human cell line with a robust innate response, were infected with the Makona variant or with the Ecran variant originating from the 1976 outbreak in Central Africa. The abundance of viral and cellular mRNA transcripts was profiled using RNASeq and differential gene expression analysis performed. Differences in effects of each virus on the expression of interferon-stimulated genes were also investigated in A549 NPro cells where the type 1 interferon response had been attenuated. Cellular transcriptomic changes were compared with those induced by human respiratory syncytial virus (HRSV), a virus with a similar genome organisation and replication strategy to EBOV. Pathway and gene ontology analysis revealed differential expression of functionally important genes; including genes involved in the inflammatory response, cell proliferation, leukocyte extravasation and cholesterol biosynthesis. Whilst there was overlap with HRSV, there was unique commonality to the EBOV variants. [ABSTRACT FROM AUTHOR]