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Children and Safety in Australian Policy: Implications for Organisations and Practitioners
No full textChild safety is now a national policy priority in Australia. Extensive inquiries and reviews have escalated legislative and policy responses focused on developing, maintaining and monitoring ‘child safe’ organisations. The recommendations of the Royal Commission into Institutional Responses to Child Sexual Abuse point to the importance of cultural conditions within organisations in supporting child safety and the need for responsive change in some organisations. Drawing on a recent policy analysis, undertaken as part of a larger Australian Research Council Discovery Project, this article examines how children and safety are constructed, within and across relevant state and federal government policies in Australia, and the implications of this. Distinctions are drawn between conceptualisations of children within the broader education policy context and two specific policy contexts in which children are considered particularly vulnerable to abuse – out-of-home care and disability. The findings indicate that policy discourses of ‘child safe’ potentially foster different emphases and approaches in organisations. These have implications for the way children are positioned in relation to their safety, how their rights are recognised and implemented, and what is required to foster cultural conditions within organisations to best support children’s safety and wellbeing
Searching for the author: a performative reading of legal subjection in David Foster Wallace’s The Pale King
Get PDFThis article argues that law is a central character and subject in David Foster Wallace’s unfinished, metafictional novel, The Pale King. As a subject of the novel, the so-called author disclaims this legal character, while also subjecting himself to it, which provides this text with its extra-textual and metafictional aspects. These aspects raise unanswerable questions, like ‘who is the author?’ and ‘is it finished?’ In showing that the ‘Pale King’ is the legal character, this article contends that The Pale King is a meditation on legal subjection that also, importantly and didactically, demands that readers performativity engage in processes of legal subjection
A case study to assess energy availability status amongst professional male rugby league players and identify potential predictors of Low Energy Availability (LEA)
No full textPurpose: It has been identified that elite male athletes are at risk of failing to meet their high energy demands. This issue can cause a bodily state of Low Energy Availability (LEA); the aetiology of harmful syndromes known as Relative Energy Deficiency in Sport (RED-S) and the Female Athlete Triad (Triad). This state can have a wide range of effects on health. Assessing the energy availability (EA) status of rugby league (RL) players has not previously been undertaken. However, it could be an important measure for nutritionists working with this cohort; identifying actual EA status will provide a gage on how at risk these athletes are for LEA. Furthermore, investigating potential influential factors of LEA amongst this population may provide information for future prevention programs. Therefore, the aim of this study is to assess the energy availability of a cohort of elite male rugby league players. Methods: Diet and training records were taken over a 3-day period, at two time points during the preseason. Additionally, blood and saliva samples were taken for the measurement of three different LEA biomarkers (testosterone, blood glucose, and triiodothyronine). Alongside these measurements, an Eating Disorder Inventory-3 questionnaire was distributed amongst the players to obtain body perception ideals. Results: Carbohydrate intake and overall EA status was low and below recommendations. Protein intake was adequate, and fat intake is likely to be overconsumed. LEA biomarkers were within normal physiological range; however, blood glucose and triiodothyronine significantly declined from the first preseason time point (January) to the second (February). Results from the EDI-3 scale indicate that RL players may be at higher risk of body dissatisfaction than is currently known. Lastly, international had no effect on dietary intake or overall EA status amongst these participants. Conclusion: RL players may be consuming less than adequate carbohydrate and overall energy. Additionally, this sporting group may be at higher risk of body dissatisfaction than is perceived
The Content of Mental Health Advance Preference Statements (MAPs): a qualitative assessment of completed advance directives in the Southern District Health Board
No full textBackground
Mental health advance directives support service users' autonomy and provide a voice in their care choices when they may not have capacity to give informed consent. New Zealand's Southern District Health Board has recently introduced advanced directives in mental health services.
Method
Completed advance directives (n = 53) and additional demographic data were accessed from clinical records.
Analysis
Each advance directive was read and analysed by three members of the research team. The advance directive instrument has eight possible fields which could be completed, covering such topics as who should be contacted in a crisis; people service users do, or do not, want involved in their treatment; what service users would, or would not like to have happen should they become unwell; management of personal affairs; other specific preferences; and provision of further relevant information. The number of preferences stated in each field was also calculated.
Results
The advance directives provided expressions of preferences which were personally meaningful for service users and provided practical guidance for clinicians. Service users expressed mainly positive preferences, though some expressed negative treatment preferences, and many service users expressed preferences relating to personal affairs. Friends, family members and clinicians were nominated as preferred contacts in a crisis.
Conclusions
Service users will engage with advance directives if supported to do so. This study's results should help promote the wider availability of advance directives in New Zealand and the current reform of our mental health legislation
Perinatal and Maternal Mortality Review Committee: Third Report to the Minister of Health: July 2008 to June 2009
No full textThe purpose of this report is to provide an accurate estimate of the absolute numbers of perinatal and maternal deaths in New Zealand, to describe the risk factors for perinatal deaths and to attempt to identify where the attention of maternity and neonatal services might best be focused in order to prevent perinatal and maternal deaths
An investigation into the use of pollen from South Mavora Lake for paleoclimate reconstruction
No full textThe proxies embedded within both lake and peat bog sediments provide information on both vegetation and by inference climate changes. When developing paleoclimate records based on pollen, peat bogs are favoured due to passive modes of accumulation and simple proxy source models. However, slow accumulation rates result in low resolutions and poor recording of decadal to centennial scale environmental changes. Lacustrine systems offer higher resolution records, robust chronologies, and multiple supporting proxies. However, modes of accumulation are complex, and the role fluvial processes and lacustrine dynamics play in shaping paleoclimate records are currently poorly understood thus, lacustrine records are currently underutilised in pollen based paleoclimate research. Pollen taphonomy can indicate sediment sources and pre/post depositional processes. Therefore, not only can pollen be used to investigate climate, the role of catchment processes in shaping the final record can be determined. Parallel pollen-based paleoclimate reconstructions have been developed from an adjacent lake/peat bog complex at South Mavora. With the peat bog record acting as a control, pollen taphonomy has been used to investigate inputs into the lacustrine environment and a conceptual pollen input model for South Mavora lake has been constructed. Remobilised terrestrially stored pollen is the dominant pollen source in South Mavora Lake. However, given the similarities seen between the two Mavora records and that the trends seen in these records are seen at other sites, it can be concluded it is a suitable site for pollen reconstruction. Furthermore it can be concluded that lacustrine systems are suitable sources of pollen based paleoclimate information where the influence of catchment and lacustrine processes are carefully considere
Nutritional Immunity: Butyrate and Colon Carcinogenesis
Get PDFEarly-onset of colorectal cancer (EOCRC) is increasing amongst younger populations. A
main contributing factor is modern-day diets. Clinical studies indicate that high fibre nutrition
regimens may be protective against the EOCRC. An abundant metabolite of fibre is butyrate,
which has been observed to mitigate the loss of intestinal mucus and E-cadherin in human
colorectal adenocarcinoma cell lines. E-cadherin facilitates intercellular signalling, which is
essential for the suppression of tumorigenesis and metastasis progression. Bacteroides
fragilis toxin (BFT) is a metalloprotease virulence factor of enterotoxigenic B. fragilis
(ETBF) that induces the cleavage and degradation of E-cadherin. ETBF is commonly found
colonised in the intestinal mucus of patients who were susceptible to developing colorectal
neoplasia and pre-cancerous lesions. Associations between butyrate’s potential level of
protection against BFT is yet to be explored in current literature. Thus, in this study, ETBF
was used as a bacterial model to test the hypothesis that butyrate acts to upregulate E-cadherin
and/or mucus production, which protects against B. fragilis-mediated cellular
responses in colonic adenocarcinoma cells.
The cellular effects of butyrate are conventionally investigated in the undifferentiated HT29
cell line. However, the mucus secreting HT29-MTX cells are postulated to be more
physiologically representative of the colonic epithelia. Both HT29 and HT29-MTX cell lines
were used to model BFT-mediated loss of E-cadherin. These cells were treated with 5 mM of
butyrate and/or B. fragilis for 24-hours. Trypan blue exclusion was applied to quantify cell
proliferation and viability. RT-qPCR was utilized to quantify CDH1 and MUC2 gene
expression, which encodes for E-cadherin and mucin 2 (intestinal mucus) respectively.
Alcian blue staining was implemented to assess acidic mucin expression. Immunofluorescent
microscopy was used to evaluate E-cadherin and mucin 2 protein levels.
Findings of this study indicated 2-8 mM of butyrate had no significant effect on B. fragilis growth or viability. In uninfected HT29 cells, butyrate increased CDH1 (3.30-fold, P<0.05) and plasma membrane-associated E-cadherin expression. This effect was not concentration dependent. Butyrate (5 mM) also increased CDH1 (1.99-fold, P<0.01) and E-cadherin protein levels in ETBF-infected HT29 cells. Similarly, butyrate increased CDH1 expression in uninfected (7.32-fold, P<0.01) and infected (6.11-fold, P<0.05) HT29-MTX cells. Butyrate also upregulated acidic mucin expression in mucin granulae and reduced MUC2 expression. Further investigation is needed to determine the effect of butyrate on E-cadherin and mucin 2 protein expression in HT29-MTX cells. This study provides insight into further investigation of butyrate as a potential chemo-preventative therapy against BFT-mediated colorectal carcinogenesis
Evaluation of VEGF-A165 Glycoforms as Novel Therapeutic Agents for Angiogenic Therapy
No full textVascular endothelial growth factor-A165 (VEGF-A165) is the key mediator of angiogenesis which has been explored as a therapeutic agent to control angiogenesis and revascularisation of ischaemic tissues. Unfortunately, the use of VEGF-A165 has produced poor outcomes in clinical trials, despite showing promising results in vitro and in vivo. We hypothesise that these failures occurred due to therapies using VEGF-A165 lacking appropriate glycosylation. The aim of this project was to test the angiogenic capacity of differentially glycosylated isoforms (glycoforms) of VEGF-A165.
Chemically-synthesised (unglycosylated), Escherichia coli-produced (unglycosylated) and human embryonic kidney (HEK)293 cell-produced (glycosylated) forms of recombinant human VEGF-A165 were evaluated in in vitro angiogenic assays. A Ba/F3 bioassay was employed to quantify cell proliferation upon VEGF receptor (VEGFR)-2 binding. A Matrigel® assay was utilised to assess endothelial cell tube formation upon stimulation from VEGF-A165 glycoforms. An endothelial cell barrier assay was used to measure vascular permeability. A hydrogel release assay was used to measure bioactivity of each VEGF-A165 following incorporation and release from a light-mediated PVA-tyramine gelatine hydrogel. Three replicates were conducted for each assay except for hydrogel release.
VEGFR-2 receptor binding of the VEGF-A165 glycoforms induced similar upregulation of cell proliferation, increasing cell number with the Emax ranging from 2.37 to 3.54-fold compared to control. All VEGF-A165 glycoforms induced a change in endothelial tube formation but not in a dose-response fashion. All VEGF-A165 glycoforms at 25 ng/mL induced a 2.79 to 3.24-fold increase in vascular permeability compared to assay control on the endothelial cell monolayer. Bioactivity was retained for VEGF-A165 glycoforms upon incorporation and release from the hydrogel.
These findings show that the chemically-synthesised VEGF-A165 is biologically active and suggests that VEGF-A165 glycosylation may impact its angiogenic capacity but has resulted in slightly different outcomes compared to the other glycoforms, needing further studies to determine changes in other characteristics such as pharmacokinetics. These may have utility for the treatment of vascular diseases such as diabetic ulcers, ischaemia, and osteonecrosis of the femoral head
Investigating Genomic Imprinting in the Brushtail Possum
Get PDFWhile almost all mammalian genes express their maternally and paternally inherited copies equally, a small subset of genes (~100 in humans) are subject to parent-specific expression. This peculiar form of gene expression, known as genomic imprinting, is controlled by an epigenetic mechanism involving differential DNA methylation and histone modification that is dependent on the sex of the parent from which it is inherited. These genes play their biggest role in development where a parent-offspring conflict arises over parental investment to a growing fetus. Here, paternally expressed genes act to maximise embryonic and fetal growth, even if this restricts maternal reproductive fitness and offspring sired by other fathers. In contrast, maternally expressed genes act to limit fetal growth and share maternal resources equally, irrespective of who the father is.
In marsupials, an ancient mammalian lineage known for their unique and precocious development, genomic imprinting has been observed, yet on a far smaller scale than their eutherian mammal cousins. It has been hypothesised that this difference is due to the short-lived and less invasive marsupial placenta, meaning there is less opportunity for paternally-derived genes to influence maternal resources for the fetus. Previous investigations into genomic imprinting in marsupials have focused on the Australian tammar wallaby and the South American gray short-tailed opossum; however, New Zealand’s large and hybridised population of common brushtail possums, whose genome has recently been sequenced, provides a great opportunity to study the expression of single nucleotide polymorphisms (SNPs) within these imprinted genes in marsupials.
A search for SNPs within known mammalian imprinted genes was conducted in the brushtail possum, as well as a genome-wide search for mono-allelically expressed SNPs within candidate marsupial-specific imprinted genes. DNA amplicons were created to genotype these SNPs in multiple individuals and by creating and using pre-existing RNA sequencing datasets, the expressed allele of these SNPs was assessed to determine monoallelic expression in heterozygous individuals.
For two known mammalian imprinted genes, IGF2R and H19, monoallelic expression was discovered in the brushtail possum; however, the absence of any pairs of homozygous mothers and heterozygous pouch young meant that parent-specific imprinting of these genes could not be confirmed. Preliminary results showed that IGF2, another known imprinted gene, was expressed monoallelically in pouch young but biallelically in possum 'back-rider' juveniles and adults. Efforts to find novel, marsupial-specific imprinted genes initially looked promising, but were later found to be pseudogenes showing false monoallelic expression. Future directions should aim to confirm the monoallelic expression of IGF2R and H19 as genomic imprinting by examining more mother-offspring pairs as well as confirming the switch from monoallelic to biallelic expression of IGF2 as the possum leaves its pouch
Investigation of a Wnt/Cohesin cause for Acute Myeloid Leukaemia (AML)
Get PDFCohesin is a multiprotein complex essential for cell division and three-dimensional genome organisation. Mutations in genes encoding the cohesin-subunits, particularly STAG2, are found in ~13% of acute myeloid leukaemia (AML) cases. This frequency is as high as ~50% in the Down's syndrome-associated AML subtype (DS-AML). AML is an aggressive form of cancer of the bone marrow, with an overall survival rate of less than 30%, with especially poor outcomes for older patients. Previous research has shown that cohesin mutations dysregulate expression of the leukaemia-associated gene RUNX1. In AML, cohesin mutations co-occur with the RUNX1:RUNX1T1 translocation: t(8;21) and with other alterations to
the RUNX1 gene. Wnt signalling also enhances the spatial proximity between RUNX1 and RUNX1T1.
A recent drug screen showed that cohesin-mutant cells were synthetic lethal with Wnt agonism (Chin et al., 2020). The increased sensitivity to Wnt was likely due to enhanced β- catenin stabilisation. Wnt-responsive genes were more sensitized in DS-AML CMK cells engineered to contain a patient-specific mutation in cohesin subunit STAG2. This suggests that that cohesin mutations could progress oncogenesis by enhancing Wnt signalling, but the precise mechanism of this is not known. We hypothesise that Wnt signalling and cohesin mutations cooperate to dysregulate Wnt target genes, and possibly increase the frequency of the AML translocation: t(8;21).
In this project, we aimed to determine whether cohesin mutations alter β-catenin accumulation and/or histone modifications at gene regulatory sites in DS-AML cells. These experiments used isogenic DS-AML CMK cells that are unmodified, or that contain a CRISPR-generated null mutation in the gene encoding the cohesin subunit STAG2. First, we wanted to confirm that CMK cells had stabilised β-catenin in response to Wnt agonism.
Immunofluorescence and cell fractionation followed by immunoblotting showed that the Wnt-agonist CHIR99021 enhances β-catenin nuclear accumulation in STAG2 mutant cells. Experiments in a second STAG2-edited cell line, MCF10A, confirmed that β-catenin accumulation is conserved in STAG2 mutants.
We then used the chromatin immunoprecipitation method CUT&RUN to assess the global binding profile of β-catenin in the parental and STAG2 mutant CMK cells stimulated with CHIR99021. CUT&RUN with antibodies detecting the histone modifications H3K27ac and H3K4me3 was performed to assess whether the chromatin landscape is altered
in STAG2 mutants at key regulatory sites for RUNX1/RUNX1T1 or other Wnt targets. We found increased active histone marks; H3K4me3 and H3K27ac at the P2 promoter
of RUNX1 and increased H3K27ac at regulatory elements of RUNX1 in STAG2 mutant cells upon CHIR99021 treatment. In STAG2 mutants, β-catenin binding to TCF-7 sites was enhanced in the inflammatory-response related IL-10 gene which enhances B cell survival, proliferation, and antibody production, and the KLHL12 gene, an E3 ubiquitin ligase complex that acts as a negative regulator of the Wnt signalling pathway.
We’ve therefore found that STAG2 mutation in addition to Wnt agonism leads to activation of enhancers and increased expression of RUNX1 and RUNX1T1 and an alteration of the chromatin landscape at each of these genes.
These findings are important, as treatments for AML have not altered significantly in more than 30 years and new therapies are urgently needed. Understanding how cohesin mutations co-operate with the Wnt pathway can lead to the development of new AML-therapeutics by contributing new information on the aetiology of AML and identifying new targetable pathways