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Identification of disordered platelet function is important to guide peri-operative bleeding management as well as long term treatment and prognostic strategies in individuals with platelet bleeding disorders. Light transmission aggregometry (LTA), the current gold standard diagnostic test of platelet function is a time consuming technique almost exclusively performed in specialised laboratories and almost universally unavailable in regional centres in Australia, where there is an unmet need for access to specialised platelet function diagnostic services. 96-well plate-based aggregometry (Optimul, UK), has been utilised in research laboratories as a novel platform to investigate platelet function. We evaluated the Optimul assay at two centres in Australia, one regional and one tertiary metropolitan, to assess its feasibility as a screening test applicable to remote regional centres. Concentration-response curves were established from 45 healthy volunteers at the participating regional hospital and from 31 healthy volunteers at the tertiary institution. Optimul successfully detected anti-platelet effects in individuals taking aspirin (n=4), NSAID (n=2), clopidogrel (n=2) and dual therapy with aspirin and clopidogrel (n=1). When tested in parallel to LTA in individuals referred for the evaluation of abnormal bleeding symptoms there was overall a very good level of agreement between Optimul and LTA [Cohen's kappa (k

Somatic malignant transformation of germ cell tumours is a well-described but poorly understood phenomenon. It is characterized by differentiation of pluripotent teratoma cells into somatic tumour cells. Following malignant transformation, the most common histologies are sarcomas and primitive neuroectodermal tumours; however, other subtypes have been recognized including melanoma, leukaemia, and renal cell carcinoma. We report a case of a 38-year-old male who had recently completed treatment for a mediastinal germ cell tumour with teratomatous components. He presented several months after completion of chemotherapy with metastatic lesions in his spine and liver accompanied with severe pancytopenia. He was subsequently diagnosed with acute megakaryoblastic leukaemia (AMKL), and a biopsy of a liver lesion was consistent with metastatic melanoma. This case illustrates the simultaneous development of 2 rare malignant entities: mediastinal germ cell tumour-associated AMKL and somatic malignant transformation to melanoma. It also highlights the importance of close surveillance to detect these metastatic sequelae and the emerging role of tumour sequencing to establish targetable pathways.

Seasonal flu and pandemics, which account for millions of infections and hundreds of thousands of deaths, require rapid and reliable detection mechanisms for preventive and therapeutic measures. Current methods of viral detection have limitations in speed, accuracy, accessibility, and usability. This project presents a novel, widely applicable viral diagnosis that uses a modified version of the traditional rolling circle amplification (RCA) to be sensitive, specific, direct, colorimetric, and operable at room temperature. We are specifically aiming to detect SARS-CoV-2, Influenza A (H1N1pdm09), and Influenza B (Victoria Lineage). Results using synthetic viral DNA sequences show that the diagnostic test could take as fast as 30 minutes and detect up to picomolar concentrations of DNA strands. The next step for this project is to test the assay with synthetic viral RNA to verify the results. We envision that the implementation of this type of diagnostic test could allow faster responses to outbreaks of related viruses and quicker societal recovery.

Depleted uranium (DU) is a dense heavy metal used primarily in military applications. Although the health effects of occupational uranium exposure are well known, limited data exist regarding the long-term health effects of internalized DU in humans. We established an in vitro cellular model to study DU exposure. Microdosimetric assessment, determined using a Monte Carlo computer simulation based on measured intracellular and extracellular uranium levels, showed that few (0.0014%) cell nuclei were hit by alpha particles. We report the ability of DU-uranyl chloride to transform immortalized human osteoblastic cells (HOS) to the tumorigenic phenotype. DU-uranyl chloride-transformants are characterized by anchorage-independent growth, tumor formation in nude mice, expression of high levels of the k-ras oncogene, reduced production of the Rb tumor-suppressor protein, and elevated levels of sister chromatid exchanges per cell. DU-uranyl chloride treatment resulted in a 9.6 (+/- 2.8)-fold increase in transformation frequency compared to untreated cells. In comparison, nickel sulfate resulted in a 7.1 (+/- 2.1)-fold increase in transformation frequency. This is the first report showing that a DU compound caused human cell transformation to the neoplastic phenotype. Although additional studies are needed to determine if protracted DU exposure produces tumors in vivo, the implication from these in vitro results is that the risk of cancer induction from internalized DU exposure may be comparable to other biologically reactive and carcinogenic heavy-metal compounds (e.g., nickel). Images Figure 1 Figure 2 Figure 3