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ItemNo Preview AvailableIntroduction(Melbourne University Publishing, 2024)
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ItemThe Effect of Fabry Disease Therapy on Bone Mineral Density(MDPI, 2024-05)Fabry disease (FD) is an X-linked lysosomal storage disorder, characterised by the cellular accumulation of globotriaosylceramide due to impaired alpha-galactosidase A enzyme activity. FD may manifest with multisystem pathology, including reduced bone mineral density (BMD). Registry data suggest that the introduction of Fabry-specific therapies (enzyme replacement therapy or chaperone therapy) has led to significant improvements in overall patient outcomes; however, there are limited data on the impact on bone density. The aim of this study was to describe the effect of Fabry-specific therapies on longitudinal changes in bone mineral density (BMD) in FD. We performed a retrospective observational study analysing bone densitometry (DXA) in patients with genetically confirmed FD. Patients were grouped based on the use of Fabry-specific therapies. The between-group longitudinal change in BMD Z-score was analysed using linear mixed effects models. A total of 88 FD patients were analysed (50 untreated; 38 treated). The mean age at first DXA was 38.5 years in the untreated group (84% female) and 43.7 years in the treated group (34% female). There was no significant longitudinal between-group difference in the BMD Z-score at the lumbar spine. However, the Z-score per year at the total hip (β = -0.105, p < 0.001) and femoral neck (β = -0.081, p = 0.001) was significantly lower over time in the treated than the untreated group. This may reflect those receiving therapy having a more severe underlying disease. Nevertheless, this suggests that Fabry-specific therapies do not reverse all disease mechanisms and that the additional management of BMD may be required in this patient population.
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ItemCritical review of single-cell mechanotyping approaches for biomedical applications(ROYAL SOC CHEMISTRY, 2024-05-28)Accurate mechanical measurements of cells has the potential to improve diagnostics, therapeutics and advance understanding of disease mechanisms, where high-resolution mechanical information can be measured by deforming individual cells. Here we evaluate recently developed techniques for measuring cell-scale stiffness properties; while many such techniques have been developed, much of the work examining single-cell stiffness is impacted by difficulties in standardization and comparability, giving rise to large variations in reported mechanical moduli. We highlight the role of underlying mechanical theories driving this variability, and note opportunities to develop novel mechanotyping devices and theoretical models that facilitate convenient and accurate mechanical characterisation. Moreover, many high-throughput approaches are confounded by factors including cell size, surface friction, natural population heterogeneity and convolution of elastic and viscous contributions to cell deformability. We nevertheless identify key approaches based on deformability cytometry as a promising direction for further development, where both high-throughput and accurate single-cell resolutions can be realized.
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ItemMass calibration of DES Year-3 clusters via SPT-3G CMB cluster lensing(IOP Publishing, 2024)We measure the stacked lensing signal in the direction of galaxy clusters in the Dark Energy Survey Year 3 (DES Y3) redMaPPer sample, using cosmic microwave background (CMB) temperature data from SPT-3G, the third-generation CMB camera on the South Pole Telescope (SPT). Here, we estimate the lensing signal using temperature maps constructed from the initial 2 years of data fromtheSPT-3G‘Main’survey, covering1500deg2 oftheSouthernsky. Wethenusethislensing signal as a proxy for the meancluster massoftheDESsample. ThethermalSunyaev–Zel’dovich(tSZ) signal, whichcancontaminatethelensingsignalifnotaddressed, isisolatedandremovedfromthedata before obtaining the mass measurement. In this work, we employ three versions of the redMaPPer catalogue: a Flux-Limited sample containing 8865 clusters, a Volume-Limited sample with 5391 clusters, and a Volume&Redshift-Limited sample with 4450 clusters. For the three samples, we detect the CMB lensing signal at a significance of 12.4𝜎, 10.5𝜎 and 10.2𝜎 and find the mean cluster masses to be 𝑀200m = 1.66±0.13 [stat.]±0.03 [sys.], 1.97 ± 0.18 [stat.]±0.05 [sys.], and 2.11 ± 0.20 [stat.]±0.05 [sys.]×1014 M⊙, respectively. This is a factor of ∼ 2 improvement relative to the precision of measurements with previous generations of SPT surveys and the most constraining cluster mass measurements using CMB cluster lensing to date. Overall, we find no significant tensions between our results and masses given by redMaPPer mass–richness scaling relations of previous works, which were calibrated using CMB cluster lensing, optical weak lensing, and velocity dispersion measurements from various combinations of DES, SDSS and Planck data. We then divide our sample into 3 redshift and 3 richness bins, finding no significant discrepancies with optical weak-lensing calibrated masses in these bins. We forecast a 5.7% constraint on the mean cluster mass of the DES Y3 sample with the complete SPT-3G surveys when using both temperature and polarization data and including an additional ∼ 1400 deg2 of observations from the ‘Extended’ SPT-3G survey.
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ItemNo Preview AvailableLove Letters: The Romance of Grace Warne & Vernon Hogg 1933-35(Working Papers, 2024)These letters are a glimpse into another time and place. Passion burned brightly through the hot summer nights and cold winters of Melbourne in 1933-5. Grace Warne and Wilfred John Vernon (Vern) Hogg were head over heels in love. When Vern was posted as a Principal of a small school four hundred and twenty kilometres away in the small town of Walwa on the Murray River, it seemed the end of the earth. Letters became the life force that connected them both. Waited on eagerly every week, if no letter turned up in the post then the disappointment was palpable. The urgency of being together was heartfelt. Love was blind to whatever was happening in the world. At this tumultuous time there is little in these letters of politics, of the Depression and of the tumultuous events in Europe though Grace and Vern were to become passionate environmentalists and stalwarts of the anti-war movement in the 1960s and 1970s. The only thing that mattered at this time in their lives was love. The letters were kept faithfully in a “Remember” box. Grace died nine months before Vern, and the letters were by his bedside. They were together for over fifty years. To have known love like this is a great blessing. The letters are a reminder of something beyond words and even life itself. Non Omnis Moriar (Not all of me will die) was the monogram on some of Vern’s letters to Grace and it has proved to be true in so many ways. Should these private letters be made public? There are many notes from Grace and Vern and their daughter Barbara that are very instructive, as if they knew that at some point something might happen, though the letters may have been their last consideratno. Vernon notes the shyness of Grace in one letter and both did not like the limelight. No doubt to have these letters published while they were both alive may have been too much. But the joy of these letters and the unique way they convey simple values from another time is something that Grace and Vern would have approved of. It is in keeping with the way they lived. I can imagine Grace’s cheeky smile at the thought of current generations putting aside their phones and dating apps to read her beautifully written letters. She was a feminist and an environmentalist and a supporter of Aboriginal rights and yet she was also an adoring partner. Love was everything that made all things right. Each letter glows with devotion, adoration and simplicity. Love was for life. The modern world was held at bay by dreams of a simple life and pleasures: being together, a house and a family in a cocoon of love. It was not a mirage. Grace and Vernon lived, worked together and were inseparable all their lives. They were seminal and inspirational for four generations of their family and beyond. Outwardly they appeared conventional, but they were always something special, unique, wonderful and modern about them. Heterosexuality and the nuclear family with all its traps sure, but wrapped up by the power of an abiding love. Vernon was ten years older than Grace. He probably first met her with her sisters at the Matrons Ball, Mansfield on Sept 15, 1925. Vernon’s program, (see opposite) faithfully kept in the box with the love letters, shows his dance partners penciled in. He danced with four of the six Warne sisters, “Grace” is written next to the third dance, the Fox Trot. She would have only been ten years old. In one of her photo albums Grace suggests that she met Vern while a nurse. Perhaps Vern made the connection to the Mansfield Dance after their 1930s romance. In the summer of 1933 Grace was a Nurse at Madeleine Private Hospital, Parkville. Nursing was never something Grace enjoyed. More than anything else she wanted to be with Vern. Vern was a young teacher at the mercy of the Victorian Department of Education being posted from country school to country school, enduring white-ant infested residences, he was intent on securing a good house that he and Grace could live in and be together. The beauty of these letters comes from their under-stated sensuality and longing at at a time when seeing a show on Friday night, tennis (Saturday) and cricket (Sunday) were all the entertainment on offer and probably all that most could want. ‘Going to the city’ was something Grace and Vernon loved to do all their lives. In their latter years it was something of a rite, Vernon would walk up the laneways from Flinders St Station for chocolates and freshly baked cookies from the basement at Myers, stop in at Fletcher Jones perhaps and Grace would go wider afield up the tram lines to North Carlton and Brunswick doing a prowl of op. shops for her son, daughters, grandson and their friends, always coming up with amazing bargains and sought after fashion items never out of date. Friday night movies in country theatres were mandatory and often Vernon would take his daughter Barbara who had a life long love of cinema and the moving image. Grace’s letters are wonderful, partly because of their rhythm. In 1933/34 Grace would write weekly and then post the letter the next day. Her closest post office was the Carlton North Post Office at 546 Rathdowne St and she almost always (except when letters were entrusted to her brothers!) made the mail the day after her night-time writing. Vern’s letters are more enigmatic but equally passionate. The great love that is expressed in these letters was a primary reason why the generations that followed Grace and Vernon had successful, happy, adventurous and joyful lives. Those of us who are are alive and breathing in Australia in 2024 are invariably spoilt. We have so many things, privileges and capacities. Grace and Vernon lived simply, loved devotedly and unilaterally and they carried successive generations forward. These letters are a glimpse into anothe time and place. A great love was flourishing that would bind us in our families and in our world. We owe so much to the angels of the past. This volume is an attempt to say thank you and to acknowledge the miracle that was Barbara Botsman. Love is the foundation of all that is good. Non Omnis Moriar
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ItemNo Preview AvailableFrom collection to engagement: Indigenous language research at the University of Melbourne(Melbourne University Press, 2024)
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ItemNo Preview AvailableEmbryology of the fat-tailed dunnart (Sminthopsis crassicaudata): A marsupial model for comparative mammalian developmental and evolutionary biology(WILEY, 2024-05-09)BACKGROUND: Marsupials are a diverse and unique group of mammals, but remain underutilized in developmental biology studies, hindering our understanding of mammalian diversity. This study focuses on establishing the fat-tailed dunnart (Sminthopsis crassicaudata) as an emerging laboratory model, providing reproductive monitoring methods and a detailed atlas of its embryonic development. RESULTS: We monitored the reproductive cycles of female dunnarts and established methods to confirm pregnancy and generate timed embryos. With this, we characterized dunnart embryo development from cleavage to birth, and provided detailed descriptions of its organogenesis and heterochronic growth patterns. Drawing stage-matched comparisons with other species, we highlight the dunnarts accelerated craniofacial and limb development, characteristic of marsupials. CONCLUSIONS: The fat-tailed dunnart is an exceptional marsupial model for developmental studies, where our detailed practices for reproductive monitoring and embryo collection enhance its accessibility in other laboratories. The accelerated developmental patterns observed in the Dunnart provide a valuable system for investigating molecular mechanisms underlying heterochrony. This study not only contributes to our understanding of marsupial development but also equips the scientific community with new resources for addressing biodiversity challenges and developing effective conservation strategies in marsupials.
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ItemA Delphi study to obtain consensus on medical emergency team (MET) stand-down decision making.(Wiley, 2023-11)AIM: A medical emergency team (MET) stand-down decision is the decision to end a MET response and hand responsibility for the patient back to ward staff for ongoing management. Little research has explored this decision. This study aimed to obtain expert consensus on the essential elements required to make optimal MET call stand-down decisions and the communication required before MET departure. DESIGN: A Delphi design was utilised. METHODS: An expert panel of 10 members were recruited based on their expert knowledge and recent clinical MET responder experience in acute hospital settings. Participants were emailed a consent form and an electronic interactive PDF for each survey. Two rounds were conducted with no attrition between rounds. The CREDES guidance on conducting and reporting Delphi studies was used to report this study. RESULTS: Consensus by an expert panel of 10 MET responders generated essential elements of MET stand-down decisions. Essential elements comprised of two steps: (1) the stand-down decision that was influenced by both the patient situation and the ward/organisational context; and (2) the communication required before actioning stand-down. Communication after the decision required both verbal discussions and written documentation to hand over patient responsibility. Specific patient information, a management plan and an escalation plan were considered essential. CONCLUSION: The Delphi surveys reached consensus on the actions and communication required to stand down a MET call. Passing responsibility back to ward staff after a MET call requires both patient and ward safety assessments, and a clearly articulated patient plan for ward staff. Observation of MET call stand-down decision-making is required to validate the essential elements. IMPLICATION FOR THE PROFESSION AND PATIENT/OR PATIENT CARE: In specifying the essential elements, this study offers clinical and MET staff a process to support the handing over of clinical responsibility from the MET to the ward staff, and clarification of management plans in order to reduce repeat MET calls and improve patient outcomes. IMPACT: Minimal research has been focussed on the decision to hand responsibility back to ward staff so the MET may leave the ward with safety plan in place. This study provided expert consensus to optimise MET stand-down decision-making and the ultimate decision to end a MET call. Communication of agreed patient treatment and escalation plans is recommended before leaving the ward. This study can be used as a checklist for MET responder staff making these decisions and ward staff responsible for post-MET call care. The aim being to reduce the likelihood of potentially preventable repeat deterioration in the MET patient population. REPORTING METHOD: The CREDES guidance on conducting and reporting Delphi studies. PATIENT OR PUBLIC CONTRIBUTION: None.