The Roman mould of the Australian Catholic Church, 1846-1878

An historical analysis of the Roman Catholic Church in the Australian colonies between 1846-1878 presents a number of questions as to origins, composition and attitudes that as yet remain unanswered. This present work has avoided the general themes and tries to explore one limited problem - what was there in the Church of that period that can now be seen as distinctive and primary? If some headway can be made in answering that question it is possible that other aspects of the Church may thereby be illumined. The Church between those years was already sufficiently well established to have taken on the characteristics that marked the course of her future. Given the origins of the majority of her members it is natural that the most notable quality that has caught the attention of historians has been her Irish heritage and its consequences. But from the vantage point of a century and more, it is now possible to ask what distinctive features remain today as a result of that heritage. And if the answer is that little remains, except lightly worn customs such as an occasional procession on 17 March and an Irish page in the Melbourne Advocate, it is possible that some other attribute of the Church of the past was of even greater significance than the Irish background

Multispectral lensless digital holographic microscope: imaging MCF-7 and MDA-MB-231 cancer cell cultures

Digital holography is the process where an object’s phase and amplitude information is retrieved from intensity images obtained using a digital camera (e.g. CCD or CMOS sensor). In-line digital holographic techniques offer full use of the recording device’s sampling bandwidth, unlike off-axis holography where object information is not modulated onto carrier fringes. Reconstructed images are obscured by the linear superposition of the unwanted, out of focus, twin images. In addition to this, speckle noise degrades overall quality of the reconstructed images. The speckle effect is a phenomenon of laser sources used in digital holographic systems. Minimizing the effects due to speckle noise, removal of the twin image and using the full sampling bandwidth of the capture device aids overall reconstructed image quality. Such improvements applied to digital holography can benefit applications such as holographic microscopy where the reconstructed images are obscured with twin image information. Overcoming such problems allows greater flexibility in current image processing techniques, which can be applied to segmenting biological cells (e.g. MCF-7 and MDA-MB- 231) to determine their overall cell density and viability. This could potentially be used to distinguish between apoptotic and necrotic cells in large scale mammalian cell processes, currently the system of choice, within the biopharmaceutical industry

Common dysregulation network in the human prefrontal cortex underlies two neurodegenerative diseases.

Using expression profiles from postmortem prefrontal cortex samples of 624 dementia patients and non-demented controls, we investigated global disruptions in the co-regulation of genes in two neurodegenerative diseases, late-onset Alzheimer's disease (AD) and Huntington's disease (HD). We identified networks of differentially co-expressed (DC) gene pairs that either gained or lost correlation in disease cases relative to the control group, with the former dominant for both AD and HD and both patterns replicating in independent human cohorts of AD and aging. When aligning networks of DC patterns and physical interactions, we identified a 242-gene subnetwork enriched for independent AD/HD signatures. This subnetwork revealed a surprising dichotomy of gained/lost correlations among two inter-connected processes, chromatin organization and neural differentiation, and included DNA methyltransferases, DNMT1 and DNMT3A, of which we predicted the former but not latter as a key regulator. To validate the inter-connection of these two processes and our key regulator prediction, we generated two brain-specific knockout (KO) mice and show that Dnmt1 KO signature significantly overlaps with the subnetwork (P = 3.1 × 10(-12)), while Dnmt3a KO signature does not (P = 0.017)

Evaluating the effectiveness of clinical decision support systems: the case of multimorbidity care

General Practitioners (GPs) and healthcare systems, worldwide, are overwhelmed by the growing number of patients with multimorbidity, particularly in light of the additional complexity and costs involved in treating these patients. While it has been proven that clinical decision support systems (CDSS) play a key role in supporting healthcare decisions, there is little research into their role in the case of multimorbidity. This study examines practice systems currently used in Ireland and evaluates their effectiveness in such circumstances. The findings uncover a number of deficiencies, including: (1) the lack of provision of integrated medical guidelines for multiple chronic diseases within the CDSS, (2) the inability to centralise the patient rather than the disease, (3) the difficulty in seamlessly integrating CDSS into the patient consultation, and (4) the lack of adequate training of GPs on how best to use CDSS in multimorbidity decision making. The study underlines the need for further research into CDSS and multimorbidity, and highlights some of the key issues that must be addressed in order to improve how CDSS support the care of multimorbid patients

Computerized decision support systems for multimorbidity care - an urgent call for research and development

Healthcare organisations and General Practitioners (GPs) in particular, are overwhelmed by the growing number of patients with multiple chronic diseases (i.e. multimorbid) and the additional complexity involved in their associated treatments. There is evidence to suggest that Computerized Decision Support Systems (CDSS) offer many potential benefits to support multimorbidity care, but this remains under investigated. For example CDSS have been shown to improve the quality/safety of medication prescribing; to increase clinician adherence to guideline/protocol based care; as well as to enhance communication and decision making among providers and patients. This chapter draws on extant literature to discuss these and other potential benefits of CDSS for enhancing multiborbidity care and calls for further research and development in this area. The chapter also identifies the required features of such software systems and underlines a number of key challenges that must be overcome for the successful deployment of CDSS in this context

Silent Harm. A training manual for service providers and interpreters who work with deaf, refugee, and migrant women and girls who have experienced gender-based violence

Introduction: The handbook presented here is one of the results of the Justisigns2 project, which was developed to address an important interpreter-mediated communications gap, namely: the need to share information about how to communicate effectively, via interpretation, with deaf and migrant women, refugees or asylum-seekers, victims/survivors of gender-based violence (DSGBV) who use languages other than the official languages of their host states. This gave rise to an analysis of need on the part of service providers and the creation of resources to support service providers working with victims/survivors across a range of sectors (e.g.police-court, social-health and NGO settings) and the interpreters who mediate the communicative exchanges with these victims/survivors. The Justisigns2 project was funded by the Erasmus+program (ref. 2019-1-IE01-KA202-051558) and was carried out by the following project partners: Interesource Group (Ireland), European Union of the Deaf, Trinity College Dublin, Dublin Rape Crisis Centre, An Garda Síochána,Heriot-Watt University and the Universidade de Vigo, with support from a number of organisations and individuals (associate partners). This handbook builds on the results of a survey that was conducted in 2021 (Napier et al. 2022) that invited engagement from interpreters and a broad range of service providers working with deaf or migrant DSGBV victims. This yielded extensive and varied data on the needs of such groups in the three countries surveyed (Ireland, Spain and the United Kingdom). For the purposes of this publication, the focus is on violence against women and girls. It is important to acknowledge that DSGBV is violence directed against a person because of that person’s gender or violence that affects persons of a particular gender disproportionately. Given that sociolinguistic contexts and legislative frameworks vary in the different project partner countries, a general definition of DSGBV is first provided and then the differences that exist in the 3 countries surveyed (Ireland, UK and Spain) are discussed. For example, the term gender-based violence is not widely used in the UK where the term Violence against Women and Girls (VAWG) is in use. As a result, the term Domestic, Sexual and Gender-based violence (DSGBV) is used here

Liver and Adipose Expression Associated SNPs Are Enriched for Association to Type 2 Diabetes

Genome-wide association studies (GWAS) have demonstrated the ability to identify the strongest causal common variants in complex human diseases. However, to date, the massive data generated from GWAS have not been maximally explored to identify true associations that fail to meet the stringent level of association required to achieve genome-wide significance. Genetics of gene expression (GGE) studies have shown promise towards identifying DNA variations associated with disease and providing a path to functionally characterize findings from GWAS. Here, we present the first empiric study to systematically characterize the set of single nucleotide polymorphisms associated with expression (eSNPs) in liver, subcutaneous fat, and omental fat tissues, demonstrating these eSNPs are significantly more enriched for SNPs that associate with type 2 diabetes (T2D) in three large-scale GWAS than a matched set of randomly selected SNPs. This enrichment for T2D association increases as we restrict to eSNPs that correspond to genes comprising gene networks constructed from adipose gene expression data isolated from a mouse population segregating a T2D phenotype. Finally, by restricting to eSNPs corresponding to genes comprising an adipose subnetwork strongly predicted as causal for T2D, we dramatically increased the enrichment for SNPs associated with T2D and were able to identify a functionally related set of diabetes susceptibility genes. We identified and validated malic enzyme 1 (Me1) as a key regulator of this T2D subnetwork in mouse and provided support for the association of this gene to T2D in humans. This integration of eSNPs and networks provides a novel approach to identify disease susceptibility networks rather than the single SNPs or genes traditionally identified through GWAS, thereby extracting additional value from the wealth of data currently being generated by GWAS

Clinicopathologic and gene expression parameters predict liver cancer prognosis

<p>Abstract</p> <p>Background</p> <p>The prognosis of hepatocellular carcinoma (HCC) varies following surgical resection and the large variation remains largely unexplained. Studies have revealed the ability of clinicopathologic parameters and gene expression to predict HCC prognosis. However, there has been little systematic effort to compare the performance of these two types of predictors or combine them in a comprehensive model.</p> <p>Methods</p> <p>Tumor and adjacent non-tumor liver tissues were collected from 272 ethnic Chinese HCC patients who received curative surgery. We combined clinicopathologic parameters and gene expression data (from both tissue types) in predicting HCC prognosis. Cross-validation and independent studies were employed to assess prediction.</p> <p>Results</p> <p>HCC prognosis was significantly associated with six clinicopathologic parameters, which can partition the patients into good- and poor-prognosis groups. Within each group, gene expression data further divide patients into distinct prognostic subgroups. Our predictive genes significantly overlap with previously published gene sets predictive of prognosis. Moreover, the predictive genes were enriched for genes that underwent normal-to-tumor gene network transformation. Previously documented liver eSNPs underlying the HCC predictive gene signatures were enriched for SNPs that associated with HCC prognosis, providing support that these genes are involved in key processes of tumorigenesis.</p> <p>Conclusion</p> <p>When applied individually, clinicopathologic parameters and gene expression offered similar predictive power for HCC prognosis. In contrast, a combination of the two types of data dramatically improved the power to predict HCC prognosis. Our results also provided a framework for understanding the impact of gene expression on the processes of tumorigenesis and clinical outcome.</p

Predictive Genes in Adjacent Normal Tissue Are Preferentially Altered by sCNV during Tumorigenesis in Liver Cancer and May Rate Limiting

Background: In hepatocellular carcinoma (HCC) genes predictive of survival have been found in both adjacent normal (AN) and tumor (TU) tissues. The relationships between these two sets of predictive genes and the general process of tumorigenesis and disease progression remains unclear. Methodology/Principal Findings: Here we have investigated HCC tumorigenesis by comparing gene expression, DNA copy number variation and survival using ~250 AN and TU samples representing, respectively, the pre-cancer state, and the result of tumorigenesis. Genes that participate in tumorigenesis were defined using a gene-gene correlation meta-analysis procedure that compared AN versus TU tissues. Genes predictive of survival in AN (AN-survival genes) were found to be enriched in the differential gene-gene correlation gene set indicating that they directly participate in the process of tumorigenesis. Additionally the AN-survival genes were mostly not predictive after tumorigenesis in TU tissue and this transition was associated with and could largely be explained by the effect of somatic DNA copy number variation (sCNV) in cis and in trans. The data was consistent with the variance of AN-survival genes being rate-limiting steps in tumorigenesis and this was confirmed using a treatment that promotes HCC tumorigenesis that selectively altered AN-survival genes and genes differentially correlated between AN and TU. Conclusions/Significance: This suggests that the process of tumor evolution involves rate-limiting steps related to the background from which the tumor evolved where these were frequently predictive of clinical outcome. Additionally treatments that alter the likelihood of tumorigenesis occurring may act by altering AN-survival genes, suggesting that the process can be manipulated. Further sCNV explains a substantial fraction of tumor specific expression and may therefore be a causal driver of tumor evolution in HCC and perhaps many solid tumor types. © 2011 Lamb et al.published_or_final_versio