Key lessons from the COVID-19 public health response in Australia

Australia avoided the worst effects of the COVID-19 pandemic, but still experienced many negative impacts. Reflecting on lessons from Australia's public health response, an Australian expert panel composed of relevant discipline experts identified the following key lessons: 1) movement restrictions were effective, but their implementation requires careful consideration of adverse impacts, 2) disease modelling was valuable, but its limitations should be acknowledged, 3) the absence of timely national data requires re-assessment of national surveillance structures, 4) the utility of advanced pathogen genomics and novel vaccine technology was clearly demonstrated, 5) decision-making that is evidence informed and consultative is essential to maintain trust, 6) major system weaknesses in the residential aged-care sector require fixing, 7) adequate infection prevention and control frameworks are critically important, 8) the interests and needs of young people should not be compromised, 9) epidemics should be recognised as a ‘standing threat’, 10) regional and global solidarity is important. It should be acknowledged that we were unable to capture all relevant nuances and context specific differences. However, the intent of this review of Australia's public health response is to critically reflect on key lessons learnt and to encourage constructive national discussion in countries across the Western Pacific Region

A radium assay technique using hydrous titanium oxide adsorbent for the Sudbury Neutrino Observatory

As photodisintegration of deuterons mimics the disintegration of deuterons by neutrinos, the accurate measurement of the radioactivity from thorium and uranium decay chains in the heavy water in the Sudbury Neutrino Observatory (SNO) is essential for the determination of the total solar neutrino flux. A radium assay technique of the required sensitivity is described that uses hydrous titanium oxide adsorbent on a filtration membrane together with a beta-alpha delayed coincidence counting system. For a 200 tonne assay the detection limit for 232Th is a concentration of 3 x 10^(-16) g Th/g water and for 238U of 3 x 10^(-16) g U/g water. Results of assays of both the heavy and light water carried out during the first two years of data collection of SNO are presented.Comment: 12 pages, 4 figure

Meta-analysis of data from animal studies:A practical guide

AbstractMeta-analyses of data from human studies are invaluable resources in the life sciences and the methods to conduct these are well documented. Similarly there are a number of benefits in conducting meta-analyses on data from animal studies; they can be used to inform clinical trial design, or to try and explain discrepancies between preclinical and clinical trial results. However there are inherit differences between animal and human studies and so applying the same techniques for the meta-analysis of preclinical data is not straightforward. For example preclinical studies are frequently small and there is often substantial heterogeneity between studies. This may have an impact on both the method of calculating an effect size and the method of pooling data. Here we describe a practical guide for the meta-analysis of data from animal studies including methods used to explore sources of heterogeneity

Determinants of mortality in non-neutropenic ICU patients with candidaemia

Introduction: Candidaemia in critically-ill intensive care unit (ICU) patients is associated with high crude mortality. Determinants of mortality – particularly those amenable to potential modification – are incompletely defined. Methods: A nationwide prospective clinical and microbiological cohort study of all episodes of ICU-acquired candidaemia occurring in non-neutropenic adults was undertaken in Australian ICUs between 2001 and 2004. Multivariate Cox regression analyses were performed to determine independently significant variables associated with mortality. Results: 183 episodes of ICU-acquired candidaemia occurred in 183 patients during the study period. Of the 179 with microbiological data, Candida albicans accounted for 111 (62%) episodes and Candida glabrata, 32 (18%). Outcome data were available for 173: crude hospital mortality at 30 days was 56%. Host factors (older age, ICU admission diagnosis, mechanical ventilation and ICU admission diagnosis) and failure to receive systemic antifungal therapy were significantly associated with mortality on multivariate analysis. Among the subset who received initial fluconazole therapy (n = 93), the crude mortality was 52%. Host factors (increasing age and haemodialysis receipt), but not organism- (Candida species, fluconazole MIC), pharmacokinetic- (fluconazole dose, time to initiation), or pharmacodynamic-related parameters (fluconazole dose:MIC ratio) were associated with mortality. Process of care measures advocated in recent guidelines were implemented inconsistently: follow-up blood cultures were obtained in 68% of patients, central venous catheters removed within five days in 80% and ophthalmological examination performed in 36%. Conclusions: Crude mortality remains high in Australian ICU patients with candidaemia and is overwhelmingly related to host factors but not treatment variables (the time to initiation of antifungals or fluconazole pharmacokinetic and pharmacodynamic factors). The role and timing of early antifungal intervention in critically-ill ICU patients requires further investigation.Deborah J.E. Marriott, E. Geoffrey Playford, Sharon Chen, Monica Slavin, Quoc Nguyen, David Ellis and Tania C. Sorrell for the Australian Candidaemia Stud

Measurement and Computation of Energy Separation in the Vortical Wake Flow of a Turbine Nozzle Cascade

This paper describes the observation, measurement, and computation of vortex shedding behind a cascade of turbine nozzle guide vanes that have a blunt trailing edge. At subsonic discharge speeds, periodic wake vortex shedding was observed at all times at a shedding frequency in the range 7–11 kHz. At high subsonic speeds the wake was susceptible to strong energy redistribution. The effect was greatest around an exit Mach number of 0.95 and results are presented for that condition. An unusually cold flow on the wake centerline and hot spots at the edges of the wake were measured. These were found to be a manifestation of Eckert–Weise effect energy separation in the shed vortex street. Experimental identification of these phenomena was achieved using a new stagnation temperature probe of bandwidth approaching 100 kHz. Using phase-averaging techniques, it was possible to plot contours of time-resolved entropy increase at the downstream traverse plane. Computational work has been undertaken that gives qualitative confirmation of the experimental results and provides a more detailed explanation of the fine scale structure of the vortex wake. The topology of the wake vortical structures behind blunt trailing-edged turbine blades is becoming clearer. These measurements are the first instantaneous observations of the energy separation process occurring in turbine blade wake flows. This was also the first demonstration of the use of the probe in the frequency, Mach number, and temperature ranges typical of operation behind the rotors of high-performance turbomachines such as transonic fans

Altitude scaling of ice crystal accretion

This paper describes experiments performed in an altitude chamber at the National Research Council of Canada (NRC) as the first step towards developing altitude scaling laws and procedures that will possibly allow aero-engines to be certified for operation in ice crystal clouds at high altitude by testing in sea level facilities. The principal objective was to test the hypothesis that accretion within a compressor due to ice crystal ingestion occurs when the local ratio of freestream liquid water content (LWC) to total water content (TWC) lies within a critical range at an accretion-susceptible location. If this hypothesis is correct, the local LWC/TWC ratio is the key parameter that must be matched in tests at low and high pressures to match accretions. Experiments were conducted in a small wind tunnel with an axisymmetric test article, consisting of a hemispherical nose attached to a conical afterbody, at a fixed TWC over a range of LWC/TWC ratios at (absolute) pressures of 34.5 kPa and 69 kPa to test the hypothesis. The LWC/TWC ratio was varied by changing the wet bulb temperature. Accretion steady-state volumes and growth rates measured at the two pressures were compared at conditions which were analytically predicted to produce matched LWC/TWC ratios. Good agreement was achieved in all cases. Accretion growth was greatest for LWC/TWC ratios in the range 10-25%. Additional tests demonstrated that wet bulb temperature, which was identified as an important variable in earlier studies, had little influence on accretion growth beyond its effect on LWC/TWC (i.e. ice particle melting). Tests were also conducted to determine whether accretion growth scales linearly with TWC at constant LWC/TWC. Those tests confirmed that not only does the accretion growth rate in the early growth phase scale in direct proportion to TWC, but so does the final size of the accretion. A simple semi-empirical model for predicting this behavior is described. While most of the tests were conducted with an ice particle median volumetric diameter of 45\u3bc, some of the scaling tests were repeated with larger particles, which produced smaller accretions. \ua9 2013 by Her Majesty the Queen in Right of Canada. Published by the American Institute of Aeronautics and Astronautics.Peer reviewed: YesNRC publication: Ye

Cyclic ADP-ribose increases Ca2+ removal in smooth muscle

Ca2+ release via ryanodine receptors (RyRs) is vital in cell signalling and regulates diverse activities such as gene expression and excitation-contraction coupling. Cyclic ADP ribose (cADPR), a proposed modulator of RyR activity, releases Ca2+ from the intracellular store in sea urchin eggs but its mechanism of action in other cell types is controversial. In this study, caged cADPR was used to examine the effect of cADPR on Ca2+ signalling in single voltage-clamped smooth muscle cells that have RyR but lack FKBP12.6, a proposed target for cADPR. Although cADPR released Ca2+ in sea urchin eggs (a positive control), it failed to alter global or subsarcolemma [Ca2+]c, to cause Ca2+-induced Ca2+ release or to enhance caffeine responses in colonic myocytes. By contrast, caffeine (an accepted modulator of RyR) was effective in these respects. The lack of cADPR activity on Ca2+ release was unaffected by the introduction of recombinant FKBP12.6 into the myocytes. Indeed in western blots, using brain membrane preparations as a source of FKBP12.6, cADPR did not bind to FKBPs, although FK506 was effective. However, cADPR increased and its antagonist 8-bromo-cADPR slowed the rate of Ca2+ removal from the cytoplasm. The evidence indicates that cADPR modulates [Ca2+]c but not via RyR; the mechanism may involve the sarcolemma Ca2+ pump

In smooth muscle, FK506-binding protein modulates IP3 receptor-evoked Ca2+ release by mTOR and calcineurin

Ca2+ release from the sarcoplasmic reticulum (SR) by the IP3 receptors (IP3Rs) crucially regulates diverse cell signalling processes from reproduction to apoptosis. Release from the IP3R may be modulated by endogenous proteins associated with the receptor, such as the 12 kDa FK506-binding protein (FKBP12), either directly or indirectly by inhibition of the phosphatase calcineurin. Here, we report that, in addition to calcineurin, FKPBs modulate release through the mammalian target of rapamycin (mTOR), a kinase that potentiates Ca2+ release from the IP3R in smooth muscle. The presence of FKBP12 was confirmed in colonic myocytes and co-immunoprecipitated with the IP3R. In aortic smooth muscle, however, although present, FKBP12 did not co-immunoprecipitate with IP3R. In voltage-clamped single colonic myocytes rapamycin, which together with FKBP12 inhibits mTOR (but not calcineurin), decreased the rise in cytosolic Ca2+ concentration ([Ca2+]c) evoked by IP3R activation (by photolysis of caged IP3), without decreasing the SR luminal Ca2+ concentration ([Ca2+]l) as did the mTOR inhibitors RAD001 and LY294002. However, FK506, which with FKBP12 inhibits calcineurin (but not mTOR), potentiated the IP3-evoked [Ca2+]c increase. This potentiation was due to the inhibition of calcineurin; it was mimicked by the phosphatase inhibitors cypermethrin and okadaic acid. The latter two inhibitors also prevented the FK506-evoked increase as did a calcineurin inhibitory peptide (CiP). In aortic smooth muscle, where FKBP12 was not associated with IP3R, the IP3-mediated Ca2+ release was unaffected by FK506 or rapamycin. Together, these results suggest that FKBP12 has little direct effect on IP3-mediated Ca2+ release, even though it is associated with IP3R in colonic myocytes. However, FKBP12 might indirectly modulate Ca2+ release through two effector proteins: (1) mTOR, which potentiates and (2) calcineurin, which inhibits Ca2+ release from IP3R in smooth muscle