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    Efficacy of Probiotics Compared With Pharmacological Treatments for Maintenance Therapy for Functional Constipation in Children: A Systematic Review and Network Meta-analysis

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    ContextThere has been an increase in randomized controlled trials (RCTs) comparing probiotics with various maintenance therapies, such as polyethylene glycol, lactulose, and mineral oil, to treat functional constipation in children.ObjectiveThe aim was to compare probiotics with all other oral maintenance therapies for functional constipation in children and rank all treatments in terms of effectiveness in a network meta-analysis.MethodsRCTs were identified through systematically searching the MEDLINE, Scopus, EMBASE, and Cochrane Library databases, trial registries, and forward and backward citation searching. Within-study risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and confidence in the estimates was assessed using the CINeMA (Confidence in Network Meta-Analysis) framework. Random-effects network meta-analyses were conducted.ResultsData were pooled from 41 and 29 RCTs for network meta-analysis of defecation frequency and treatment success, respectively. Probiotics did not significantly increase the number of bowel movements per week when compared with any conventional treatment or placebo. A combination of mineral oil and probiotics was the most effective treatment for increasing defecation frequency (mean difference: 3.13; 95% confidence interval [CI]: 0.64, 5.63). The most effective treatments for increasing the risk of treatment success as compared with placebo were mineral oil (relative risk [RR]: 2.41; 95% CI: 1.53, 3.81) and a combined treatment of polyethylene glycol and lactulose (RR: 2.45; 95% CI: 1.21, 4.97). Confidence in the estimates ranged from very low to moderate.ConclusionCurrently, there is no evidence to suggest that probiotics should be used as a standalone treatment for functional constipation in children. More high-quality studies are needed to evaluate different strains of probiotics and their potential benefit as an additional treatment component to conventional treatments. Mineral oil and polyethylene glycol were the most effective treatments to increase defecation frequency and treatment success rates and should remain the first line of treatment for children with functional constipation.Systematic review registrationPROSPERO registration no.CRD42022360977 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=360977).</p

    Empirical essays on the effects of macroeconomic shocks in emerging market economies

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    This thesis consists of three self-contained empirical research papers on the effects of macroeconomic shocks. The focus of the first paper is on the monetary policy transmission in Sri Lanka, a country whose monetary policy underwent transformation during and following a three-decade-long ethnic conflict. Consequently, the first paper empirically explores the effects of monetary policy shocks on the Sri Lankan economy. It places particular emphasis on the strength of the credit and exchange rate channels, employing a Vector Autoregression (VAR) model spanning the years 2003 to 2019. The empirical findings can be summarized as follows: (i) Monetary policy shocks exert a substantial and persistent impact on key macroeconomic variables, although several puzzling results emerge; (ii) The influence of monetary policy shocks is pronounced and more persistent in the post-conflict period compared to the conflict period; (iii) In the post-conflict period, a tight monetary policy effectively curbs inflation; and (iv) The interest rate and exchange rate channels play a dominant role, while the credit channel exhibits a delayed response in the post-conflict era. The second paper explores the international effects of China’s economic and trade policy uncertainty shocks. Uncertainty originating from large economies has been shown to spillover to the rest of the world. However, there is a lack of understanding of the cross-border effects of China’s policy uncertainty shocks. Using panel VAR models, this paper investigates the contagion effects of China’s economic and trade policy uncertainty shocks on macroeconomic and financial variables in 26 advanced and emerging market economies. The empirical results indicate that China’s policy uncertainty shocks lead to a decline in output, exports, imports, net exports, stock prices, and the value of the domestic currency in both advanced and emerging economies. Notably, both economic and trade policy uncertainty shocks have similar adverse effects. Importantly, China’s uncertainty significantly contracts the trade flow in both advanced and emerging economies. The adverse spillover effects on emerging economies are more prominent and persistent than those on advanced economies. Moreover, the effects are more severe across the countries in the Belt and Road initiative and commodity-exporting economies. This heterogeneity in responses can be attributed to countries’ trade link with China and their degree of dependence on commodity export. The third paper examines the impact of technology shocks originating from the US on 11 emerging market economies from 1996 to 2018. Using a structural VAR and proxy-instrumental variable, this study shows that the US technology shocks generate cross-border effects and business cycle co-movements across emerging market economies. These shocks have positive spillover effects on key macroeconomic variables, such as real gross domestic product, investment, consumption, net exports and net FDI. Moreover, due to the technology shocks, there is a persistent exchange rate depreciation and strong stock market performance in emerging economies. Interestingly, the non-investment-specific technology shocks generate a more substantial cross-border impact than the investment-specific technology shocks. The panel local projection model and country-specific VAR model also yield similar results.</p

    Design, Synthesis, and Evaluation of Cephamycin-based Anti-Sporulation Agents targeting Clostridioides difficile

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    Clostridioides difficile is fast becoming a worldwide healthcare concern due to high associated morbidity and mortality rates of hospital associated infections. Current front-line antibiotics used against C. difficile such as vancomycin and fidaxomicin have shown high rates of recovery, however no current antibiotic treatment is able to eliminate the spores of C. difficile which are commonly associated with relapse and recurrence of C. difficile infection (CDI). Previous work from our group has shown that cephamycin-type antibiotics, especially cefotetan, can directly bind to the active site of CdSpoVD — an essential protein for the production of spore cortex — and inhibit the sporulation activity of C. difficile. Thus, a collaborative project was established between UOW and Monash University, with the aim of designing novel cephamycin-type molecules that specifically target the sporulation process of C. difficile using cefotetan as the lead compound. Furthermore, the identification of the sporulation target CdSpoVD, and construction of CdSpoVD homology and AlphaFold (AF) models, enabled further development of structure-based drug design in aid of molecular docking studies. Two synthetic pathways have been established for this project to functionalise the C-7 and the C-3 positions of a cephamycin-type compound, including a feasible method to install a methoxy group on the C-7 position of the molecule. The binding site of CdSpoVD was predicted by blind docking of the lead compound cefotetan with the homology model of CdSpoVD, which identified S311 as the catalytic serine residue. Five AF models of CdSpoVD were prepared by Prof. Haibo Yu, and the accuracies of these models were confirmed by the X-ray crystal structure of CdSpoVD when it was later reported. Methods for both non-covalent and covalent docking were developed and used for virtual screening of the cephamycin derivatives prior to their syntheses. The docking outcomes of synthesised compounds were also used in combination with their biological results to develop structure-activity relationship (SAR) data.</p

    A Single-Cell Interrogation System from Scratch: Microfluidics and Deep Learning

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    Live-cell imaging using fluorescence microscopy enables researchers to study cellular processes in unprecedented detail. These techniques are becoming increasingly popular among microbiologists. The emergence of microfluidics and deep learning has significantly increased the amount of quantitative data that can be extracted from such experiments. However, these techniques require highly specialized expertise and equipment, making them inaccessible to many biologists. Here we present a guide for microbiologists, with a basic understanding of microfluidics, to construct a custom-made live-cell interrogation system that is capable of recording and analyzing thousands of bacterial cell-cycles per experiment. The requirements for different microbiological applications are varied, and experiments often demand a high level of versatility and custom-designed capabilities. This work is intended as a guide for the design and engineering of microfluidic master molds and how to build polydimethylsiloxane chips. Furthermore, we show how state-of-the-art deep-learning techniques can be used to design image processing algorithms that allow for the rapid extraction of highly quantitative information from large populations of individual bacterial cells.</p

    OCTOPUS Database v.2.3: The CRN Denudation Global collection [2024]

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    Database of published cosmogenic Be-10 and Al-26 concentrations from modern river sediment and basin-averaged denudation rates inferred from these data. Ancillary spatial data includes: sample site location (point), basin outline (polygon), digital elevation model (raster), D8 flow direction and flow accumulation grids (raster), topographic gradient (raster), atmospheric pressure (raster), and cosmogenic nuclide production scaling factor and topographic shielding grids (raster). The vector spatial data uses the WGS84/Pseudo-Mercator (EPSG: 3857) projected coordinate reference system. The raster data uses the WGS86/UTM projected coordinate reference system, UTM zones depending on the extent and location of each data package. Sample metadata is comprehensive and includes all necessary information and input files for the recalculation of denudation rates using the CAIRN model (https://github.com/LSDtopotools/LSDTopoTools_CRNBasinwide). All denudation rates were recalculated and harmonised using CAIRN. The extent of the data is global, excluding Australia.</p

    Shellharbour’s food environment

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    Mapping the food environment helps us understand if everyone can easily get healthy food. The healthiness of Shellharbour food environment matters because it directly impacts the dietary choices of local residents and, consequently, their overall health and well-being

    Dr. Faustus and free will: an alternative interpretation of Marlowe’s play

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    Marlowe’s play Dr. Faustus has been the subject of widely differing interpretations, most of them focused on the justice or otherwise of God. Is it a conventional morality play in which, having turned his back on God and salvation, Faustus is rightly condemned to hell? Or is Faustus a tragic hero, unfairly condemned simply for pursuing the Renaissance dream of reaching for heaven through knowledge and learning? This thesis suggests that, in contrast to these two main streams of interpretation which both see the play as essentially theological in nature, Dr. Faustus is primarily a psychological study of a man trying to obtain certainty and meaning in his life but failing dramatically on both counts, and the consequences of that failure in the form of his growing mental anguish. At the centre of his angst is the issue of free will: do we have any control over our own salvation? And if not then how should we live our life so as to give it meaning? Faustus’ unsuccessful attempts to answer these questions are closely examined using some philosophical concepts and theories relating to free will. This close analysis of the text suggests that the dismal failure of Faustus’ attempt to resolve all theological uncertainties concerning free will and salvation by denying the existence of both is the major cause of his psychological breakdown. This failure, along with Faustus’ failure to obtain agency and control in his life through the unconstrained pursuit of his passions following his pact with the devil, point to the main focus of the play: the portrayal of a man at war with himself, torn apart by metaphysical uncertainties and the inherent limitations of what it means to be “but Faustus, and a man.

    Threshold Ring Signature Scheme from Cryptographic Group Actions

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    A t-out-of-N threshold ring signature, which is extended from ring signature scheme, allow t users jointly sign a message on the behalf of a ring of N users, selected in an arbitrary way, while keeping their identities anonymous. This thesis presents a threshold ring signature construction using cryptographic group action, based on the OR proof of group action and the idea of creating a threshold ring signature scheme from a ring signature scheme. We also instantiate the proposed protocol in both isogeny and lattice settings, using the GAIP and MLWE problems, respectively. Our isogeny-based construction provides a smaller signature size than the existing threshold ring signature scheme (e.g. 65 KB signatures compared to 187 KB for the same ring size)

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