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    Effect of storage conditions on the characteristics of cryogenic hydrogen jet dispersion
    Saini, D ; Talei, M ; Yang, Y ; Sandberg, RD ; Berry, JD (Elsevier BV, 2024-05-20)
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    Spatio-temporal spread of artemisinin resistance in Southeast Asia
    Flegg, JA ; Kandanaarachchi, S ; Guerin, PJ ; Dondorp, AM ; Nosten, FH ; Otienoburu, SD ; Golding, N ; Kouyos, RD (PUBLIC LIBRARY SCIENCE, 2024-04)
    Current malaria elimination targets must withstand a colossal challenge-resistance to the current gold standard antimalarial drug, namely artemisinin derivatives. If artemisinin resistance significantly expands to Africa or India, cases and malaria-related deaths are set to increase substantially. Spatial information on the changing levels of artemisinin resistance in Southeast Asia is therefore critical for health organisations to prioritise malaria control measures, but available data on artemisinin resistance are sparse. We use a comprehensive database from the WorldWide Antimalarial Resistance Network on the prevalence of non-synonymous mutations in the Kelch 13 (K13) gene, which are known to be associated with artemisinin resistance, and a Bayesian geostatistical model to produce spatio-temporal predictions of artemisinin resistance. Our maps of estimated prevalence show an expansion of the K13 mutation across the Greater Mekong Subregion from 2000 to 2022. Moreover, the period between 2010 and 2015 demonstrated the most spatial change across the region. Our model and maps provide important insights into the spatial and temporal trends of artemisinin resistance in a way that is not possible using data alone, thereby enabling improved spatial decision support systems on an unprecedented fine-scale spatial resolution. By predicting for the first time spatio-temporal patterns and extents of artemisinin resistance at the subcontinent level, this study provides critical information for supporting malaria elimination goals in Southeast Asia.
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    Three-phase voltage sensitivity estimation and its application to topology identification in low-voltage distribution networks
    Fang, L ; Pengwah, AB ; Andrew, LLH ; Razzaghi, R ; Muñoz, MA (Elsevier BV, 2024-07-01)
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    Prognostic and functional importance of both overt and subclinical left ventricular systolic dysfunction in systemic sclerosis.
    Fairley, JL ; Hansen, D ; Proudman, S ; Sahhar, J ; Ngian, G-S ; Walker, J ; Host, LV ; La Gerche, A ; Prior, D ; Burns, A ; Morrisroe, K ; Stevens, W ; Nikpour, M ; Ross, L (Elsevier BV, 2024-06)
    OBJECTIVES: To quantify the frequency and clinical implications of systemic sclerosis (SSc)-associated left ventricular function (LV) impairment. METHODS: Australian Scleroderma Cohort Study participants meeting ACR/EULAR criteria for SSc with ≥1 echocardiographic LVEF measurement were included. Overt LV dysfunction was indicated by reduced LV ejection fraction (LVEF) and subclinical LV dysfunction was measured using impaired LV global longitudinal strain (LV-GLS>-16 %). Those with secondary causes of LV dysfunction (myocardial ischaemia, valvulopathy and pulmonary arterial hypertension) were excluded. Chi-squared tests, two-sample t-tests or Wilcoxon rank-sum tests were used for between-group comparison as appropriate. Generalised estimating equations(GEE) were used to model longitudinal data. Kaplan-Meier and Cox proportional hazard models were used for survival analyses. RESULTS: Of 1141 participants with no co-morbid cardiac disease, 2.4 % ever recorded a LVEF<50 %, while only 0.6 % ever recorded a LVEF≤40 %. LV-GLS data were available for 90 % of participants at one centre (n = 218). Impaired LV-GLS was detected in 21 % despite LVEF≥50 %. Those with a LVEF<50 % were more frequently male (p = 0.01) with dcSSc (p < 0.01), higher inflammatory markers (p < 0.02) and skeletal muscle disease (p < 0.05). In multivariable analyses, recording a LVEF<50 % was associated with increased mortality (HR2.3, 95 %CI1.0-4.8, p = 0.04). Impaired LV-GLS was also associated with poorer survival in univariable analyses (HR3.4, 95 %CI1.0-11.8, p = 0.05). Those with a LVEF<50 % more frequently recorded WHO Class III/IV dyspnoea (OR3.5, 95 %CI1.6-7.7, p < 0.01), with shorter six-minute walk distance (p = 0.01), higher Health Assessment Questionnaire-Disability Index scores (p < 0.01) and lower Short Form-36 Physical Component Summary scores (p = 0.02). Increased dyspnoea (WHO Class III/IV dyspnoea; OR3.6, 95 %CI1.4-9.2, p < 0.01) was also seen in those with impaired LV-GLS. CONCLUSIONS: Both overt and subclinical SSc-associated LV dysfunction are associated with worse survival and impaired physical function. The frequency of abnormal LV-GLS in those with consistently normal LVEF suggests an under-appreciated burden of subtle LV systolic dysfunction in SSc that has a significant impact on patient symptomatology.
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    Trajectories of job insecurity and the probability of poorer mental health among prime working-age Australian women and men.
    Ervin, J ; LaMontagne, AD ; Taouk, Y ; King, T (Elsevier BV, 2024-05)
    Precarious and insecure employment arrangements are important social determinants of health. Prior evidence has consistently found perceived job insecurity to be associated with poorer mental health. Nonetheless, several key under-researched areas remain in the existing evidence base. This study addresses some of these gaps by examining trajectories of job (in)security and assessing the effect of various persistent job security trajectories on subsequent mental health of both men and women. Utilising 15 waves of data from the Household, Income and Labour Dynamics in Australia (HILDA) Survey, we employed group-based trajectory modelling (GBTM) to identify trajectories of job (in)security through men and women's prime working years (from baseline age of 28-38yrs to 41-51yrs) across 14 years (waves 5-18), before subsequently examining the associations between these estimated trajectories and mental health at wave 19 (aged 42-52yrs). We identified four distinct trajectories of job (in)security for both men and women: persistently secure, becoming more secure, becoming less secure, and persistently insecure. Examining the association between these trajectories and mental health, we found that chronic exposure to any amount of persistent job insecurity (improving, worsening or persistently insecure) is detrimental to the mental health of both men and women. Furthermore, a somewhat incremental or dose dependant effect was found, with persistent job insecurity associated with the largest declines in mental health scores. Given mental health disorders are a substantial cause of disability globally, our study provides evidence that developing policy and practice interventions to reduce job insecurity (as an increasingly recognised and highly modifiable social determinant of mental health) has considerable potential to enact positive population health improvements.
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    Interplay of intracellular and trans-cellular DNA methylation in natural archaeal consortia
    Reva, ON ; La Cono, V ; Crisafi, F ; Smedile, F ; Mudaliyar, M ; Ghosal, D ; Giuliano, L ; Krupovic, M ; Yakimov, MM (WILEY, 2024-04)
    DNA methylation serves a variety of functions across all life domains. In this study, we investigated archaeal methylomics within a tripartite xylanolytic halophilic consortium. This consortium includes Haloferax lucertense SVX82, Halorhabdus sp. SVX81, and an ectosymbiotic Candidatus Nanohalococcus occultus SVXNc, a nano-sized archaeon from the DPANN superphylum. We utilized PacBio SMRT and Illumina cDNA sequencing to analyse samples from consortia of different compositions for methylomics and transcriptomics. Endogenous cTAG methylation, typical of Haloferax, was accompanied in this strain by methylation at four other motifs, including GDGcHC methylation, which is specific to the ectosymbiont. Our analysis of the distribution of methylated and unmethylated motifs suggests that autochthonous cTAG methylation may influence gene regulation. The frequency of GRAGAaG methylation increased in highly expressed genes, while CcTTG and GTCGaGG methylation could be linked to restriction-modification (RM) activity. Generally, the RM activity might have been reduced during the evolution of this archaeon to balance the protection of cells from intruders, the reduction of DNA damage due to self-restriction in stressful environments, and the benefits of DNA exchange under extreme conditions. Our methylomics, transcriptomics and complementary electron cryotomography (cryo-ET) data suggest that the nanohaloarchaeon exports its methyltransferase to methylate the Haloferax genome, unveiling a new aspect of the interaction between the symbiont and its host.
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    Optimised start-up strategy for bioelectrochemical systems operating on hydrolysed human urine.
    Koskue, V ; Freguia, S (Elsevier BV, 2024-04-06)
    Key nutrients, such as nitrogen measured as total ammonium nitrogen (TAN), could be recycled from hydrolysed human urine back to fertiliser use. Bioelectrochemical systems (BESs) are an interesting, low-energy option for realising this. However, the high TAN concentration (> 5 g L-1) and pH (> 9) of hydrolysed urine can inhibit microbial growth and hinder the enrichment of an electroactive biofilm at the anode. This study investigated a new strategy for bioanode inoculation by mixing real hydrolysed urine with thickened waste activated sludge (TWAS) from a municipal wastewater treatment plant at different volumetric ratios. The addition of TWAS diluted the high TAN concentration of hydrolysed urine (5.2 ± 0.3 g L-1) to 2.6-5.1 g L-1, while the pH of the inoculation mixtures remained > 9 and soluble chemical oxygen demand (sCOD) at 5.6-6.7 g L-1. Despite the high pH, current generation started within 24 h for all reactors, and robust bioanodes tolerant of continuous feeding with undiluted hydrolysed urine were enriched within 11 days of start-up. Current output and Coulombic efficiency decreased with increasing initial hydrolysed urine fraction. The anodes inoculated with the highest sCOD-to-TAN ratio (2.1) performed the best, which suggests that high organics levels can protect microbes from inhibition even at elevated TAN concentrations.
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    Drug efflux and lipid A modification by 4-L-aminoarabinose are key mechanisms of polymyxin B resistance in the sepsis pathogen Enterobacter bugandensis.
    García-Romero, I ; Srivastava, M ; Monjarás-Feria, J ; Korankye, SO ; MacDonald, L ; Scott, NE ; Valvano, MA (Elsevier BV, 2024-03-27)
    OBJECTIVES: A concern with the ESKAPE pathogen, Enterobacter bugandensis, and other species of the Enterobacter cloacae complex, is the frequent appearance of multidrug resistance against last-resort antibiotics, such as polymyxins. METHODS: Here, we investigated the responses to polymyxin B (PMB) in two PMB-resistant E. bugandensis clinical isolates by global transcriptomics and deletion mutagenesis. RESULTS: In both isolates, the genes of the CrrAB-regulated operon, including crrC and kexD, displayed the highest levels of upregulation in response to PMB. ∆crrC and ∆kexD mutants became highly susceptible to PMB and lost the heteroresistant phenotype. Conversely, heterologous expression of CrrC and KexD proteins increased PMB resistance in a sensitive Enterobacter ludwigii clinical isolate and in the Escherichia coli K12 strain, W3110. The efflux pump, AcrABTolC, and the two component regulators, PhoPQ and CrrAB, also contributed to PMB resistance and heteroresistance. Additionally, the lipid A modification with 4-L-aminoarabinose (L-Ara4N), mediated by the arnBCADTEF operon, was critical to determine PMB resistance. Biochemical experiments, supported by mass spectrometry and structural modelling, indicated that CrrC is an inner membrane protein that interacts with the membrane domain of the KexD pump. Similar interactions were modeled for AcrB and AcrD efflux pumps. CONCLUSION: Our results support a model where drug efflux potentiated by CrrC interaction with membrane domains of major efflux pumps combined with resistance to PMB entry by the L-Ara4N lipid A modification, under the control of PhoPQ and CrrAB, confers the bacterium high-level resistance and heteroresistance to PMB.