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Non-typhoidal Salmonella (NTS) is a major cause of bacterial enterocolitis globally but also causes invasive bloodstream infections. Antimicrobial resistance (AMR) hampers the treatment of these infections and understanding how AMR spreads between NTS may help in developing effective strategies. We investigated NTS isolates associated with invasive disease, diarrhoeal disease and asymptomatic carriage in animals and humans from Vietnam. Isolates included multiple serovars and both common and rare phenotypic AMR profiles; long- and short-read sequencing was used to investigate the genetic mechanisms and genomic backgrounds associated with phenotypic AMR profiles. We demonstrate concordance between most AMR genotypes and phenotypes but identified large genotypic diversity in clinically relevant phenotypes and the high mobility potential of AMR genes (ARGs) in this setting. We found that 84 % of ARGs identified were located on plasmids, most commonly those containing IncHI1A_1 and IncHI1B(R27)_1_R27 replicons (33%), and those containing IncHI2_1 and IncHI2A_1 replicons (31%). The vast majority (95%) of ARGS were found within 10 kbp of IS6/IS26 elements, which provide plasmids with a mechanism to exchange ARGs between plasmids and other parts of the genome. Whole genome sequencing with targeted long-read sequencing applied in a One Health context identified a comparatively limited number of insertion sequences and plasmid replicons associated with AMR. Therefore, in the context of NTS from Vietnam and likely for other settings as well, the mechanisms by which ARGs move contribute to a more successful AMR profile than the specific ARGs, facilitating the adaptation of bacteria to different environments or selection pressures.

© 2012 IEEE. We consider device-to-device (D2D) wireless information and power transfer systems using an unmanned aerial vehicle (UAV) as a relay-assisted node. As the energy capacity and flight time of UAVs is limited, a significant issue in deploying UAV is to manage energy consumption in real-time application, which is proportional to the UAV transmit power. To tackle this important issue, we develop a real-time resource allocation algorithm for maximizing the energy efficiency by jointly optimizing the energy-harvesting time and power control for the considered (D2D) communication embedded with UAV. We demonstrate the effectiveness of the proposed algorithms as running time for solving them can be conducted in milliseconds.

© 1997-2012 IEEE. This letter applies Han-Kobayashi (H-K) superposition signaling to a network of a multi-antenna transmitter serving two multi-antenna users. By making the rate of the common message for both users contribute to user individual rate, it shows that H-K superposition signaling clearly outperforms both state-of-the-art orthogonal multiaccess and nonorthogonal multiaccess schemes (NOMA) in terms of the worst user rate. More importantly, unlike NOMA, H-K superposition signaling does not require the user channels to be differentiated for efficient implementation.

Much waste arises from operating rooms (ORs). We estimated the practical and financial feasibility of an OR recycling program, weighing all waste from 6 ORs in Melbourne, Australia. Over 1 week, 237 operations produced 1265 kg in total: general waste 570 kg (45%), infectious waste 410 kg (32%), and recyclables 285 kg (23%). The achieved recycling had no infectious contamination. The achieved recycling/potential recycling rate was 285 kg/517 kg (55%). The average waste disposal costs were similar for general waste and recycling. OR recycling rates of 20%-25% total waste were achievable without compromising infection control or financial constraints.

OBJECTIVES: Previous studies indicate a high burden of diarrhoeal disease in Vietnamese children, however longitudinal community-based data on burden and aetiology are limited. The findings from a large, prospective cohort study of diarrhoeal disease in infants in southern Vietnam are presented herein. METHODS: Infants were enrolled at birth in urban Ho Chi Minh City and a semi-rural district in southern Vietnam, and followed for 12 months (n=6706). Diarrhoeal illness episodes were identified through clinic-based passive surveillance, hospital admissions, and self-reports. RESULTS: The minimum incidence of diarrhoeal illness in the first year of life was 271/1000 infant-years of observation for the whole cohort. Rotavirus was the most commonly detected pathogen (50% of positive samples), followed by norovirus (24%), Campylobacter (20%), Salmonella (18%), and Shigella (16%). Repeat infections were identified in 9% of infants infected with rotavirus, norovirus, Shigella, or Campylobacter, and 13% of those with Salmonella infections. CONCLUSIONS: The minimum incidence of diarrhoeal disease in infants in both urban and semi-rural settings in southern Vietnam was quantified prospectively. A large proportion of laboratory-diagnosed disease was caused by rotavirus and norovirus. These data highlight the unmet need for a rotavirus vaccine in Vietnam and provide evidence of the previously unrecognized burden of norovirus in infants.

Much waste arises from operating rooms (ORs). We estimated the practical and financial feasibility of an OR recycling program, weighing all waste from 6 ORs in Melbourne, Australia. Over 1 week, 237 operations produced 1265 kg in total: general waste 570 kg (45%), infectious waste 410 kg (32%), and recyclables 285 kg (23%). The achieved recycling had no infectious contamination. The achieved recycling/potential recycling rate was 285 kg/517 kg (55%). The average waste disposal costs were similar for general waste and recycling. OR recycling rates of 20%-25% total waste were achievable without compromising infection control or financial constraints.

BACKGROUND: A recent genome-wide association study (GWAS) identified susceptibility loci for dengue shock syndrome (DSS) at MICB rs3132468 and PLCE1 rs3740360. The aim of this study was to define the extent to which MICB (rs3132468) and PLCE1 (rs3740360) were associated with less severe clinical phenotypes of pediatric and adult dengue. METHODS: 3961 laboratory-confirmed dengue cases and 5968 controls were genotyped at MICB rs3132468 and PLCE1 rs3740360. Per-allele odds ratios (OR) with 95% confidence intervals (CI) were calculated for each patient cohort. Pooled analyses were performed for adults and paediatrics respectively using a fixed effects model. RESULTS: Pooled analysis of the paediatric and adult cohorts indicated a significant association between MICB rs3132468 and dengue cases without shock (OR = 1.15; 95%CI: 1.07 - 1.24; P = 0.0012). Similarly, pooled analysis of pediatric and adult cohorts indicated a significant association between dengue cases without shock and PLCE1 rs3740360 (OR = 0.92; 95%CI: 0.85 - 0.99; P = 0.018). We also note significant association between both SNPs (OR = 1.48; P = 0.0075 for MICB rs3132468 and OR = 0.75, P = 0.041 for PLCE1 rs3740360) and dengue in infants. DISCUSSION: This study confirms that the MICB rs3132468 and PLCE1 rs3740360 risk genotypes are not only associated with DSS, but are also associated with less severe clinical phenotypes of dengue, as well as with dengue in infants. These findings have implications for our understanding of dengue pathogenesis.

Non-invasive specimens for dengue diagnosis may be preferable where venous blood is difficult to collect and/or process, such as community-based or remote settings or when sampling from young children. We evaluated the performance of oral swabs and dried blood spots (DBS), compared with plasma, in diagnosing acute dengue and screening for past dengue virus (DENV) exposure. DENV-specific immunoglobulin (Ig) M, IgG, and NS1 antigen were detected both in oral swabs and DBS from acute patients. Oral swabs were less sensitive (IgM: 68.7%, IgG: 91.9%, NS1: 64.7%), but retained good specificity (100%, 92.3%, 95.8%, respectively) compared with plasma. DBS displayed high sensitivity (IgM: 100%, IgG: 96%, NS1: 100%) and specificity (IgM: 75%, IgG: 93%). DENV RNA was amplified from DBS (sensitivity 95.6%) but not from oral swabs. DENV-IgG (indicative of past flavivirus exposure) were detected with moderate sensitivity (61.1%) but poor specificity (50%) in oral swabs from healthy volunteers. Dried blood spots allow sensitive and specific diagnosis of acute dengue by serological, molecular, and antigen detection methods. Oral swabs may be an adequate alternative where blood cannot be collected.

Little is known about the rate at which genetic variation is generated within intrahost populations of dengue virus (DENV) and what implications this diversity has for dengue pathogenesis, disease severity, and host immunity. Previous studies of intrahost DENV variation have used a low frequency of sampling and/or experimental methods that do not fully account for errors generated through amplification and sequencing of viral RNAs. We investigated the extent and pattern of genetic diversity in sequence data in domain III (DIII) of the envelope (E) gene in serial plasma samples (n = 49) taken from 17 patients infected with DENV type 1 (DENV-1), totaling some 8,458 clones. Statistically rigorous approaches were employed to account for artifactual variants resulting from amplification and sequencing, which we suggest have played a major role in previous studies of intrahost genetic variation. Accordingly, nucleotide sequence diversities of viral populations were very low, with conservative estimates of the average levels of genetic diversity ranging from 0 to 0.0013. Despite such sequence conservation, we observed clear evidence for mixed infection, with the presence of multiple phylogenetically distinct lineages present within the same host, while the presence of stop codon mutations in some samples suggests the action of complementation. In contrast to some previous studies we observed no relationship between the extent and pattern of DENV-1 genetic diversity and disease severity, immune status, or level of viremia.

Understanding trends in dengue disease burden and risk factors for severe disease can inform health service allocation, clinical management, and planning for vaccines and therapeutics. Dengue admissions at three tertiary hospitals in Ho Chi Minh City, Vietnam, increased between 1996 and 2009, peaking at 22,860 in 2008. Children aged 6-10 years had highest risk of dengue shock syndrome (DSS); however, mortality was highest in younger children and decreased with increasing age (odds ratio [OR] = 0.52, 95% confidence interval [CI] = 0.36-0.75 in 6- to 10- year-old children and OR = 0.27, 95% CI = 0.16-0.44 in 11- to 15-year-old children compared with 1- to 5-year-old children). Males were overrepresented among dengue cases; however, girls had higher risk of DSS (OR = 1.19, 95% CI = 1.14-1.24) and death (OR = 1.57, 95% CI = 1.14-2.17). Young children with dengue had greatest risk of death and should be targeted in dengue vaccine and drug trials. The increased risk of severe outcomes in girls warrants further attention in studies of pathogenesis, health-seeking behavior, and clinical care.

Hypovolemic shock (dengue shock syndrome (DSS)) is the most common life-threatening complication of dengue. We conducted a genome-wide association study of 2,008 pediatric cases treated for DSS and 2,018 controls from Vietnam. Replication of the most significantly associated markers was carried out in an independent Vietnamese sample of 1,737 cases and 2,934 controls. SNPs at two loci showed genome-wide significant association with DSS. We identified a susceptibility locus at MICB (major histocompatibility complex (MHC) class I polypeptide-related sequence B), which was within the broad MHC region on chromosome 6 but outside the class I and class II HLA loci (rs3132468, P(meta) = 4.41 × 10(-11), per-allele odds ratio (OR) = 1.34 (95% confidence interval: 1.23-1.46)). We identified associated variants within PLCE1 (phospholipase C, epsilon 1) on chromosome 10 (rs3765524, P(meta) = 3.08 × 10(-10), per-allele OR = 0.80 (95% confidence interval: 0.75-0.86)). We identify two loci associated with susceptibility to DSS in people with dengue, suggesting possible mechanisms for this severe complication of dengue.

Midazolam is one of many bitter drugs where provision of a suitable oral paediatric formulation, particularly in the pre-anaesthetic setting, remains a challenge. To overcome this problem, a novel chocolate-based tablet formulation has been developed with positive pre-clinical results. To further investigate the potential of this formulation, 150 children aged 3-16 years who were prescribed midazolam as a premedication were randomly assigned to receive 0.5 mg.kg-1 either as the novel formulation or an intravenous solution given orally, which is the current standard at our institution. Tolerability was assessed by each child, parent and nurse using a 5-point facial hedonic scale and efficacy was determined as the time to onset of sedation. Blood samples for midazolam and 1-hydroxymidazolam levels were analysed using high-performance liquid chromatography. Population pharmacokinetics were evaluated using non-linear mixed effects modelling. The novel formulation had significantly improved tolerability scores from children, parents and nurses (all p < 0.001). Time to effect was not different between the groups (p = 0.140). The pharmacokinetics of midazolam and 1-hydroxymidazolam were able to be modelled simultaneously. The novel formulation was subject to a higher estimated first-pass metabolism compared with the intravenous solution (8.6% vs. 5.0%) and a significantly lower relative bioavailability of 82.1% (p = 0.013), with no other significant differences. Exposure relative to dose was in the range previously reported for midazolam syrup. We conclude that the novel chocolate-based formulation of midazolam provides improved tolerability while remaining efficacious with suitable pharmacokinetics when used as a premedicant for children.

Midazolam is one of many bitter drugs where provision of a suitable oral paediatric formulation, particularly in the pre-anaesthetic setting, remains a challenge. To overcome this problem, a novel chocolate-based tablet formulation has been developed with positive pre-clinical results. To further investigate the potential of this formulation, 150 children aged 3-16 years who were prescribed midazolam as a premedication were randomly assigned to receive 0.5 mg.kg-1 either as the novel formulation or an intravenous solution given orally, which is the current standard at our institution. Tolerability was assessed by each child, parent and nurse using a 5-point facial hedonic scale and efficacy was determined as the time to onset of sedation. Blood samples for midazolam and 1-hydroxymidazolam levels were analysed using high-performance liquid chromatography. Population pharmacokinetics were evaluated using non-linear mixed effects modelling. The novel formulation had significantly improved tolerability scores from children, parents and nurses (all p < 0.001). Time to effect was not different between the groups (p = 0.140). The pharmacokinetics of midazolam and 1-hydroxymidazolam were able to be modelled simultaneously. The novel formulation was subject to a higher estimated first-pass metabolism compared with the intravenous solution (8.6% vs. 5.0%) and a significantly lower relative bioavailability of 82.1% (p = 0.013), with no other significant differences. Exposure relative to dose was in the range previously reported for midazolam syrup. We conclude that the novel chocolate-based formulation of midazolam provides improved tolerability while remaining efficacious with suitable pharmacokinetics when used as a premedicant for children.

Silicon (Si) has been recently reconsidered as a beneficial element due to its direct roles in stimulating the growth of many plant species and alleviating metal toxicity. This study aimed at validating the potential of an aquatic macrophyte Eleocharis acicularis for simultaneous removal of heavy metals from aqueous solutions under different dissolved Si. The laboratory experiments designed for determining the removal efficiencies of heavy metals were conducted in the absence or presence of Si on a time scale up to 21 days. Eleocharis acicularis was transplanted into the solutions containing 0.5 mg L−1 of indium (In), gallium (Ga), silver (Ag), thallium (Tl), copper (Cu), zinc (Zn), cadmium (Cd), and lead (Pb) with various Si concentrations from 0 to 4.0 mg L−1. The results revealed that the increase of dissolved Si concentrations enhanced removal efficiencies of E. acicularis for Ga, Cu, Zn, Cd, and Pb, while this increase did not show a clear effect for In, Tl, and Ag. Our study presented a notable example of combining E. acicularis with dissolved Si for more efficient removals of Cu, Zn, Cd, Pb, and Ga from aqueous solutions. The findings are applicable to develop phytoremediation or phytomining strategy for contaminated environment.

Silicon (Si) has been recently reconsidered as a beneficial element due to its direct roles in stimulating the growth of many plant species and alleviating metal toxicity. This study aimed at validating the potential of an aquatic macrophyte Eleocharis acicularis for simultaneous removal of heavy metals from aqueous solutions under different dissolved Si. The laboratory experiments designed for determining the removal efficiencies of heavy metals were conducted in the absence or presence of Si on a time scale up to 21 days. Eleocharis acicularis was transplanted into the solutions containing 0.5 mg L−1 of indium (In), gallium (Ga), silver (Ag), thallium (Tl), copper (Cu), zinc (Zn), cadmium (Cd), and lead (Pb) with various Si concentrations from 0 to 4.0 mg L−1. The results revealed that the increase of dissolved Si concentrations enhanced removal efficiencies of E. acicularis for Ga, Cu, Zn, Cd, and Pb, while this increase did not show a clear effect for In, Tl, and Ag. Our study presented a notable example of combining E. acicularis with dissolved Si for more efficient removals of Cu, Zn, Cd, Pb, and Ga from aqueous solutions. The findings are applicable to develop phytoremediation or phytomining strategy for contaminated environment.