Australia's veterinarians and The Frawley review of 2002

This thesis examines the impact of a Commonwealth Government inquiry, the “Review of Rural Veterinary Services” on Australia’s veterinarians and the services they provide. Chaired by Peter Frawley, the inquiry became known as the Frawley Review and examined rural veterinary services, animal quarantine and veterinary education in Australia and made recommendations concerning all three. When Australia began as a penal colony of Great Britain in the 18th century, there was little need for veterinarians. This changed during the latter half of the 19th century with an increase in livestock and diseases. Australia’s first veterinary school was the Melbourne Veterinary College, a private facility, established in 1888. This school was subsequently incorporated into the University of Melbourne in 1909. A further three veterinary schools were established in the 20th century; however today, there are seven veterinary schools in the country and with a population of approximately 24 million, Australia now has more veterinary schools per capita than any comparable Western Nation. Since colonisation, Australia imported livestock from countries where major diseases occurred. However, it was not until the late 19th century that quarantine was considered necessary. With Federation, Australia’s Quarantine Act (1908) was promulgated and it wasn’t until 2016 that this Act was replaced with the Biosecurity Act (2015). Fortunately, when incursions of exotic diseases of livestock have occurred in Australia, they have failed to gain a foothold or were eliminated. During 2015 and 2016, the author conducted an on-line survey of registered veterinarians in Australia and face-to-face interviews of quarantine personnel and academics at all veterinary schools. In the first study, five hundred and fifty-five survey responses were received; the mean age of respondents was 45 and 64% were female. Eighty-seven percent were employed in practice, with the majority in urban, small animal practice, whilst the balance worked in various institutions. Less than 10% performed work on-farm. Fifty-eight percent worked full-time and 22% had taken significant time-out from veterinary service during their career. Forty one percent of respondents were dissatisfied with the income they received and nearly 20% were dissatisfied with their status as a veterinarian. More than half the respondents stated that they had been injured or acquired an illness whilst conducting their veterinary occupation. Respondents concluded that, although the Frawley Review had made valid observations, it had failed to beneficially influence veterinary services in this country. The second study was designed to secure data from veterinarians regarding the review’s impact on animal quarantine. Interviews were conducted with eight leaders of animal quarantine in Australia. Interviewees agreed that livestock quarantine was necessary and required the participation of veterinarians for its success. All expressed misgivings regarding the current status of animal disease quarantine, especially surveillance and monitoring. The participants concluded that although quarantine was essential, our ability to conduct it effectively was questionable and Frawley had done little to ameliorate the situation. The third study was designed to obtain data on the current status of Australia’s veterinary education by conducting interviews with Deans and Heads of Australia’s seven veterinary schools with 17 participating in the research. Interview questions included assessment of the Frawley Review, the purpose and funding of veterinary education, different curricula, student selection, different degrees and the oversupply of veterinary graduates. The consensus was that Frawley failed, not only to halt further schools being established in Australia, but also with its other recommendations relevant to veterinary education. It is concluded that, although veterinarians have functioned in Australia for over 100 years with the nascent profession beginning with great hope, a sense of purpose and confidence in its future, today, there is confusion as to its future role in society and the current models of delivering veterinary services, animal quarantine and veterinary education require modification

A Saliency-based Clustering Framework for Identifying Aberrant Predictions

In machine learning, classification tasks serve as the cornerstone of a wide range of real-world applications. Reliable, trustworthy classification is particularly intricate in biomedical settings, where the ground truth is often inherently uncertain and relies on high degrees of human expertise for labeling. Traditional metrics such as precision and recall, while valuable, are insufficient for capturing the nuances of these ambiguous scenarios. Here we introduce the concept of aberrant predictions, emphasizing that the nature of classification errors is as critical as their frequency. We propose a novel, efficient training methodology aimed at both reducing the misclassification rate and discerning aberrant predictions. Our framework demonstrates a substantial improvement in model performance, achieving a 20\% increase in precision. We apply this methodology to the less-explored domain of veterinary radiology, where the stakes are high but have not been as extensively studied compared to human medicine. By focusing on the identification and mitigation of aberrant predictions, we enhance the utility and trustworthiness of machine learning classifiers in high-stakes, real-world scenarios, including new applications in the veterinary world

Hands-On Network Machine Learning

This thesis is a general overview of spectral methods on networks, and how you can use tools from a network’s eigenspace to understand and explain the network more deeply. Networks are some of the most fundamental building blocks of the universe. Atoms and molecules are connected to each other with chemical bonds. Neurons connect to each other through synapses, and the different parts of the brain connect to each other through groups of neurons interacting with each other. At a larger level, we are interconnected with other humans through social networks, and our economy is a global, interconnected trade network. The Earth’s food chain is an ecological network, and larger still, every object with mass in the universe is connected to every other object through a gravitational network. This thesis covers the fundamentals of spectral methods with respect to network data science, focusing on developing intuition on networks as statistical objects, while paired with relevant Python code. While you can read this thesis without picking up your laptop, I highly recommend you experiment with the code examples available online as Jupyter notebooks at https://loftusa.github.io/thesi

Special Issues in Bioethics and the Law

Genetics and Insurance Discrimination lecture given by Alexander Morgan Capron, Henry W. Bruce University Professor of Law and Medicine, Co-Director of the Pacific Center for Health Policy and Ethics at University of Southern California. The Repression of Memory Controversy lecture given by Elizabeth Loftus, Professor of Psychology and Adjunct Professor Law at the University of Washington, Seattle. Healthcare Reform: Threats to the Patient/Physician Relationship lecture given by David Orentlicher, Director of the Division of Medical Ethics at the American Medical Association. Healthcare and Medical Progress: Can We Afford It? lecture given by Daniel Callahan, Co-Founder and President of the Hastings Center, Briarcliff Manor New York

OSTEOBLAST-DERIVED EXTRACELLULAR VESICLES AND BONE

Extracellular vesicles (EVs) are newly appreciated regulators of tissue homeostasis and a means of intercellular communication. Reports investigated the role of EVs and their cargoes in cellular regulation and have tried to fine-tune their biotechnological use, but to date very little is known on their function in bone biology. To investigate the relevance of EV-mediated communication between bone cells, we isolated EVs from primary mouse osteoblasts and assessed membrane integrity, size and structure by transmission electron microscopy and fluorescence-activated cell sorting. EVs actively shuttled loaded fluorochromes to osteoblasts, monocytes and endothelial cells. Moreover, osteoblast EVs contained mRNAs shared with donor cells. Osteoblasts are known to regulate osteoclastogenesis, osteoclast survival and function by the pro-osteoclastic cytokine, Rankl. Osteoblast EVs were enriched in Rankl, which increased after PTH treatment. These EVs were biologically active, supporting osteoclast survival. EVs isolated from rankl-/- osteoblasts lost this pro-osteoclastic function, indicating its Rankl-dependence. They integrated ex-vivo into murine calvariae, and EV-shuttled fluorochromes were quickly uptaken by the bone upon in vivo EV systemic administration. Rankl-/- mice lack the osteoclast lineage and are negative for its specific marker TRAcP. Treatment of rankl-/- mice with wildtype osteoblast EVs induced the appearance of TRAcP-positive cells in an EV density-dependent manner. Finally, osteoblast EVs internalized and shuttled anti-osteoclast drugs (zoledronate and dasatinib), inhibiting osteoclast activity in vitro and in vivo. We conclude that osteoblast EVs are involved in intercellular communication between bone cells, contribute to the Rankl pro-osteoclastic effect and shuttle anti-osteoclast drugs, representing a potential means of targeted therapeutic delivery. This article is protected by copyright. All rights reserve

The autophagy protein Ambra1 regulates gene expression by supporting novel transcriptional complexes

Ambra1 is considered an autophagy and trafficking protein with roles in neurogenesis and cancer cell invasion. Here, we report that Ambra1 also localizes to the nucleus of cancer cells, where it has a novel nuclear scaffolding function that controls gene expression. Using biochemical fractionation and proteomics, we found that Ambra1 binds to multiple classes of proteins in the nucleus, including nuclear pore proteins, adaptor proteins such as FAK and Akap8, chromatin-modifying proteins, and transcriptional regulators like Brg1 and Atf2. We identified biologically important genes, such as Angpt1, Tgfb2, Tgfb3, Itga8, and Itgb7, whose transcription is regulated by Ambra1-scaffolded complexes, likely by altering histone modifications and Atf2 activity. Therefore, in addition to its recognized roles in autophagy and trafficking, Ambra1 scaffolds protein complexes at chromatin, regulating transcriptional signaling in the nucleus. This novel function for Ambra1, and the specific genes impacted, may help to explain the wider role of Ambra1 in cancer cell biology

Bariatric surgery tourism in the COVID-19 era

Background: Since the start of the Covid-19 pandemic primary and secondary health care services in Northern Ireland have observed an increase in the number of patients who have had bariatric surgery outside of the UK. This study sought to estimate the frequency of bariatric surgery tourism and to audit indications, blood monitoring and medical complications.Methods: All primary care centres within the Western Health Social Care Trust (WHSCT) were invited to document the number of patients undergoing bariatric surgery between January 1, 2017 and December 31, 2022. For one primary care centre, patients who underwent bariatric surgery were assessed against the National Institute of Health and Clinical Excellence (NICE) guideline indications for bariatric surgery. In addition, the blood monitoring of these patients was audited against the British Obesity and Metabolic Surgery Society (BOMSS) guidelines for up to two years following surgery. Medical contacts for surgical complications of bariatric surgery were recorded.Results: Thirty-five of 47 (74.5%) GP surgeries replied to the survey, representing 239,961 patients among 325,126 registrations (73.8%). In the six year study period 463 patients had reported having bariatric surgery to their GP. Women were more likely to have had bariatric surgery than men (85.1% versus 14.9%). There was a marked increase in the number of patients undergoing bariatric surgery with each year of the study (p&lt;0.0001 chi square for trend). Twenty-one of 47 patients (44.7%) evaluated in one primary care centre fulfilled NICE criteria for bariatric surgery. The level of three-month monitoring ranged from 23% (for vitamin D) to 89% (electrolytes), but decreased at two years to 9% (vitamin D) and 64% (electrolytes and liver function tests). Surgical complication prevalence from wound infections was 19% (9 of 44). Antidepressant medications were prescribed for 23 of 47 patients (48.9%).Conclusions: The WHSCT has experienced a growing population of patients availing of bariatric surgery outside of the National Health Service. In view of this and the projected increase in obesity prevalence, a specialist obesity management service is urgently required in Northern Ireland.</p

Characterization of the equine skeletal muscle transcriptome identifies novel functional responses to exercise training

<p>Abstract</p> <p>Background</p> <p>Digital gene expression profiling was used to characterize the assembly of genes expressed in equine skeletal muscle and to identify the subset of genes that were differentially expressed following a ten-month period of exercise training. The study cohort comprised seven Thoroughbred racehorses from a single training yard. Skeletal muscle biopsies were collected at rest from the <it>gluteus medius </it>at two time points: T₁- untrained, (9 ± 0.5 months old) and T₂- trained (20 ± 0.7 months old).</p> <p>Results</p> <p>The most abundant mRNA transcripts in the muscle transcriptome were those involved in muscle contraction, aerobic respiration and mitochondrial function. A previously unreported over-representation of genes related to RNA processing, the stress response and proteolysis was observed. Following training 92 tags were differentially expressed of which 74 were annotated. Sixteen genes showed increased expression, including the mitochondrial genes <it>ACADVL</it>, <it>MRPS21 </it>and <it>SLC25A29 </it>encoded by the nuclear genome. Among the 58 genes with decreased expression, <it>MSTN</it>, a negative regulator of muscle growth, had the greatest decrease.</p> <p>Functional analysis of all expressed genes using FatiScan revealed an asymmetric distribution of 482 Gene Ontology (GO) groups and 18 KEGG pathways. Functional groups displaying highly significant (<it>P </it>< 0.0001) increased expression included mitochondrion, oxidative phosphorylation and fatty acid metabolism while functional groups with decreased expression were mainly associated with structural genes and included the sarcoplasm, laminin complex and cytoskeleton.</p> <p>Conclusion</p> <p>Exercise training in Thoroughbred racehorses results in coordinate changes in the gene expression of functional groups of genes related to metabolism, oxidative phosphorylation and muscle structure.</p