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Femtosecond laser inscribed fiber Bragg gratings in pure-silica suspended-core optical fibers have previously been demonstrated as a promising platform for high temperature sensing. However, the density of gratings that could be written on a single fiber was limited by undesired reflections associated with higher order modes in these high numerical aperture fibers. This resulted in a complex, broadband reflection spectrum with limited multiplexing capability. In this work we utilize modifications to the fine structure of the suspended core optical fibers to fine tune the relative confinement loss of the optical fiber modes, thus reducing the contribution from such higher order modes. The effects of these changes on mode propagation are modeled, giving a range of fibers with different confinement loss properties which can be tailored to the specific length scale of a desired application. We achieve single-peak reflections from individual fiber Bragg gratings, significantly improving performance for multipoint sensing and demonstrate this technique by writing 20 gratings onto a single fiber.

Exposure to phthalates is pervasive and is of concern due to associations with adverse health effects. Exposures and exposure pathways of six phthalates were investigated for 51 women aged 18-44 years in Ontario, Canada, based on measured phthalate concentrations in hand wipes and indoor media in their residences. All six phthalates had detection frequencies of 100% in air (∑ 6 670 ng m -3 geomean) and floor dust (∑ 6 630 μg g -1 ), nearly 100% detection frequencies for hand palms and backs that were significantly correlated and concentrations were repeatable over a 3 week interval. Phthalates on hands were significantly correlated with levels in air and dust, as expected according to partitioning theory. Total exposure was estimated as 4860 ng kg bw -1 day -1 (5th and 95th percentiles 1980-16 950 ng kg bw -1 day -1 ), with dust ingestion, followed by hand-to-mouth transfer, as the dominant pathways. With the exception of diethyl phthalate (DEP), phthalates had over 50% detection frequencies in surface wipes of most electronic devices sampled, including devices in which the use of phthalates was not expected. Phthalate concentrations on surfaces of hand-held devices were ∼10 times higher than on non-hand-held devices and were correlated with levels on hands. The data are consistent with phthalate emissions from sources such as laminate flooring and personal care products (e.g., scented candles), followed by partitioning among air, dust, and surface films that accumulate on electronic devices and skin, including hands. We hypothesize that hands transfer phthalates from emission sources and dust to hand-held electronic devices, which accumulate phthalates due to infrequent washing and which act as a sink and then a secondary source of exposure. The findings support those of others that exposure can be mitigated by increasing ventilation, damp cloth cleaning, and minimizing the use of phthalate-containing products and materials.

Background: HIV is characterized by high levels of genetic variability, including increased numbers of heterogeneous sequences of the envelope region. Therefore, studying genetic variability of HIV in relation to viral replication might facilitate prognosis of disease progression., Methods: The study was designed as cross-sectional; data and samples of participants collected and analyzed env genes were obtained from 23 children enrolled by Vietnam National Children's Hospital., Results: Substantial mutations in the C2 region were found in patients with high levels of viral replication while changes in the C3 region were mostly found in patients with low viral load. In the V1 region, we found profound amino acid modifications in patients with low HIV viral loads in contrast to the V2 sequence, where we identified single point mutations in patients with increased HIV viral load. The V3 region was relatively homogeneous, while profound deletions in the V4 region were detected in patients with increased viral replication., Conclusion: Our results suggest that genetic variations in different regions of the HIV envelope sequence, including both conserved C2 and C3 and variable V1/V2 and V4 regions, might be involved in increased viral infectivity and replication capacity. Such knowledge might help improve prediction of HIV progress and treatment in patients., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Hummingbirds are essential pollinators in many ecosystems, making their conservation critical. As is the case with many species, hummingbirds are now facing a variety of challenges resulting from anthropogenic changes. As populations shift and species interactions change, disease is likely to pose a significant threat. There is a basic understanding of which pathogens currently affect a variety of hummingbird species, however there is a paucity of information about their immune systems capacity to kill pathogens and what specific factors may affect immunity. The objective of this study was to gain a basic understanding of the effect of age, sex, and molt on the constitutive innate immunity of hummingbirds. An in vitro assay was used to assess the microbiocidal capacity of the whole blood of Anna's Hummingbirds (Calypte anna) against three different microbes: Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Candida albicans (C. albicans). The effect of age, sex and molt on anti-microbial capacity varied based on the microbe type. After-hatch-year birds tended to have better anti-microbial capacity compared to hatch-year birds. Male birds had higher anti-microbial activity than female birds, although this was not observed against C. albicans. Molting birds had a weaker antimicrobial activity against E. coli and S. aureus than birds that were not molting. These results represent an important first step towards defining the parameters of constitutive innate immunity of Anna's Hummingbirds as well as providing important knowledge about factors that should be considered when evaluating the health of wild populations., Competing Interests: The authors have declared that no competing interests exist.

Silicone (polydimethylsiloxane or PDMS) wristbands and cotton T-shirts were used to assess the exposure of e-waste recyclers in Dhaka, Bangladesh to polybrominated diphenyl ethers (PBDEs), novel brominated flame retardants (NBFRs), dechlorane plus (DPs), and organophosphate esters (OPEs). The median surface-normalized uptake rates of PBDEs, NBFRs, DPs, and OPEs were 170, 8.5, 4.8, and 270 ng/dm 2 /h for wristbands and 5.4, 2.0, 0.94, and 23 ng/dm 2 /h for T-shirts, respectively. Concentrations of Tris(2-chloroethyl) phosphate (TCEP), Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), Tri-m-cresyl phosphate (TmCP), Bis(2-ethlyhexyl) tetrabromophthalate (BEH-TEBP), and Dechlorane plus (DPs) in wristbands were significantly correlated with those in T-shirts. Wristbands accumulated ~7 times more mass than T-shirts, especially of compounds expected to be mainly in the gas phase. We introduce the silicone "sandwich" method to approximate the easily releasable fraction (ERF) from T-shirts, hypothesized to be related to dermal exposure. ERFs varied from 6 to 75% of total chemical accumulated by T-shirts and were significantly negatively correlated with compounds' octanol-air partition coefficient (log K oa ). The median daily exposure doses via dermal transfer from the front of the T-shirt to the front body trunk were 0.32, 0.13, 0.11, and 9.1 ng/kg-BW/day for PBDEs, NBFRs, DPs, and OPEs, respectively. The evidence of e-waste recycler exposure to flame retardants in this low income country, lacking protective personal equipment, calls for measures to minimize their exposure and for chemical management regulations to consider exposures to chemicals in waste products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

The aim of this study was to describe the spatiotemporal distribution of H5 HPAI outbreak reports for the period 2014-2017 and to identify factors associated with H5 HPAI outbreak reports. Throughout the study period, a total of 139 outbreaks of H5 HPAI in poultry were reported, due to either H5N1 (96 outbreaks) or H5N6 (43 outbreaks) subtype viruses. H5N1 HPAI outbreaks occurred in all areas of Vietnam while H5N6 HPAI outbreaks were only reported in the northern and central provinces. We counted the number of H5N1 and H5N6 outbreak report-positive districts per province over the four-year study period and calculated the provincial-level standardized morbidity ratio for H5N1 and H5N6 outbreak reports as the observed number of positive districts divided by the expected number. A mixed-effects, zero-inflated Poisson regression model was developed to identify risk factors for outbreak reports of each H5N1 and H5N6 subtype virus. Spatially correlated and uncorrelated random effects terms were included in this model to identify areas of the country where outbreak reports occurred after known risk factors had been accounted-for. The presence of an outbreak report in a province in the previous 6-12 months increased the provincial level H5N1 outbreak report risk by a factor of 2.42 (95% Bayesian credible interval [CrI] 1.27-4.60) while 1000 bird increases in the density of chickens decreased provincial level H5N6 outbreak report risk by a factor of 0.65 (95% CrI 0.38 to 0.97). We document distinctly different patterns in the spatial and temporal distribution of H5N1 and H5N6 outbreak reports. Most of the variation in H5N1 report risk was accounted-for by the fixed effects included in the zero-inflated Poisson model. In contrast, the amount of unaccounted-for risk in the H5N6 model was substantially greater than the H5N1 model. For H5N6 we recommend that targeted investigations should be carried out in provinces with relatively large spatially correlated random effect terms to identify likely determinants of disease. Similarly, investigations should be carried out in provinces with relatively low spatially correlated random effect terms to identify protective factors for disease and/or reasons for failure to report., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Previously, we reported that overexpression of AtRH17 , an Arabidopsis DEAD-box RNA helicase gene, confers salt stress-tolerance via a pathway other than the well-known salt stress-responsive pathways. To decipher the salt stress-responsive pathway in AtRH17 -overexpressing transgenic plants (OXs), we performed RNA-Sequencing and identified 397 differentially expressed genes between wild type (WT) and AtRH17 OXs. Among them, 286 genes were upregulated and 111 genes were downregulated in AtRH17 OXs relative to WT. Gene ontology annotation enrichment and KEGG pathway analysis showed that the 397 upregulated and downregulated genes are involved in various biological functions including secretion, signaling, detoxification, metabolic pathways, catabolic pathways, and biosynthesis of secondary metabolites as well as in stress responses. Genevestigator analysis of the upregulated genes showed that nine genes, namely, LEA4-5 , GSTF6 , DIN2 / BGLU30 , TSPO , GSTF7 , LEA18 , HAI1 , ABR , and LTI30 , were upregulated in Arabidopsis under salt, osmotic, and drought stress conditions. In particular, the expression levels of LEA4-5 , TSPO , and ABR were higher in AtRH17 OXs than in WT under salt stress condition. Taken together, our results suggest that a high AtRH17 expression confers salt stress-tolerance through a novel salt stress-responsive pathway involving nine genes, other than the well-known ABA-dependent and ABA-independent pathways.

Enterovirus-A71 (EV-A71) is a common cause of hand-foot-and-mouth disease (HFMD) and, rarely, causes severe neurological disease. This study aimed to elucidate the epidemiological and genetic characteristics and virulence of EV-A71 strains isolated from children diagnosed with HFMD. Rectal and throat swabs were collected from 488 children with HFMD in Hanoi, Vietnam, in 2015-2016. From 391 EV-positive patients, 15 EVs, including coxsackievirus A6 (CV-A6; 47.1%) and EV-A71 (32.5%, n = 127), were identified. Of the 127 EV-A71 strains, 117 (92.1%) were the B5 subgenotype and 10 (7.9%) were the C4 subgenotype. A whole-genome analysis of EV-A71 strains showed that seven of the eight C4a strains isolated in 2016 formed a new lineage, including two possible recombinants between EV-A71 C4 and CV-A8. The proportion of inpatients among C4-infected children was higher than among B5-infected children (80.0% vs. 27.4%; P = 0.002). The virulence of EV-A71 strains was examined in human scavenger receptor class B2 (hSCARB2)-transgenic mice, and EV-A71 C4 strains exhibited higher mortality than B5 strains (80.0% vs. 30.0%, P = 0.0001). Thus, a new EV-A71 C4a-lineage, including two possible recombinants between EV-A71 C4 and CV-A8, appeared in 2016 in Vietnam. The EV-A71 C4 subgenotype may be more virulent than the B5 subgenotype.

Full-duplex (FD) communication and spatial modulation (SM) are two promising techniques to achieve high spectral efficiency. Recent works in the literature have investigated the possibility of combining the FD mode with SM in the relay system to benefit their advantages. In this paper, we analyze the performance of the FD-SM decode-and-forward (DF) relay system and derive the closed-form expression for the symbol error probability (SEP). To tackle the residual self-interference (RSI) due to the FD mode at the relay, we propose a simple yet effective power allocation algorithm to compensate for the RSI impact and improve the system SEP performance. Both numerical and simulation results confirm the accuracy of the derived SEP expression and the efficacy of the proposed optimal power allocation.

Catecholamine excess reflecting an adrenergic overdrive of the sympathetic nervous system (SNS) has been proposed to link to hyperleptinemia in obesity and may contribute to the development of metabolic disorders. However, relationship between the catecholamine level and plasma leptin in obesity has not yet been investigated. Moreover, whether pharmacological blockade of the adrenergic overdrive in obesity by the third-generation beta-blocker agents such as carvedilol could help to prevent metabolic disorders is controversial and remains to be determined. Using the high fat diet (HFD)-induced obese mouse model, we found that basal plasma norepinephrine, the principal catecholamine as an index of SNS activity, was persistently elevated and highly correlated with plasma leptin concentration during obesity development. Targeting the adrenergic overdrive from this chronic norepinephrine excess in HFD-induced obesity with carvedilol, a third-generation beta-blocker with vasodilating action, blunted the HFD-induced hepatic glucose over-production by suppressing the induction of gluconeogenic enzymes, and enhanced the muscular insulin signaling pathway. Furthermore, carvedilol treatment in HFD-induced obese mice decreased the enlargement of white adipose tissue and improved the glucose tolerance and insulin sensitivity without affecting body weight and blood glucose levels. Our results suggested that catecholamine excess in obesity might directly link to the hyperleptinemic condition and the therapeutic targeting of chronic adrenergic overdrive in obesity with carvedilol might be helpful to attenuate obesity-related metabolic disorders., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Antiretroviral monotherapy and treatment interruption are potential strategies for perinatally HIV-infected adolescents (PHIVA) who face challenges maintaining effective combination antiretroviral therapy (ART). We assessed the use and outcomes for adolescents receiving monotherapy or undergoing treatment interruption in a regional Asian cohort., Methods: Regional Asian data (2001-2016) were analyzed to describe PHIVA who experienced ≥2 weeks of lamivudine or emtricitabine monotherapy or treatment interruption and trends in CD4 count and HIV viral load during and after episodes. Survival analyses were used for World Health Organization (WHO) stage III/IV clinical and immunologic event-free survival during monotherapy or treatment interruption, and a Poisson regression to determine factors associated with monotherapy or treatment interruption., Results: Of 3,448 PHIVA, 84 (2.4%) experienced 94 monotherapy episodes, and 147 (4.3%) experienced 174 treatment interruptions. Monotherapy was associated with older age, HIV RNA >400 copies/mL, younger age at ART initiation, and exposure to ≥2 combination ART regimens. Treatment interruption was associated with CD4 count <350 cells/μL, HIV RNA ≥1,000 copies/mL, ART adverse event, and commencing ART age ≥10 years compared with age <3 years. WHO clinical stage III/IV 1-year event-free survival was 96% and 85% for monotherapy and treatment interruption cohorts, respectively. WHO immunologic stage III/IV 1-year event-free survival was 52% for both cohorts. Those who experienced monotherapy or treatment interruption for more than 6 months had worse immunologic and virologic outcomes., Conclusions: Until challenges of treatment adherence, engagement in care, and combination ART durability/tolerability are met, monotherapy and treatment interruption will lead to poor long-term outcomes., (Copyright © 2019 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Importance: Metastatic breast cancer with central nervous system (CNS) metastases carries a poor prognosis. Recently, CDK4/6 inhibitors have demonstrated a progression free survival (PFS) and overall survival benefit when combined with standard endocrine therapy in advanced hormone receptor (HR)+/HER2- breast cancer. Pre-clinical data suggests possible activity of CDK4/6 inhibitors in the brain, but their CNS-specific benefit has not been explored in clinical practice. Methods: We reviewed clinical trials investigating the efficacy of CDK4/6 inhibitors for advanced or metastatic HR+/HER2- breast cancer. We also reviewed pre-clinical studies that demonstrated the ability of CDK4/6 inhibitors to cross the blood-brain barrier (BBB) and halt the growth of brain metastases in animal models. Findings: An ongoing phase II trial (NCT02308020) was designed to investigate the safety and tolerability of abemaciclib for treatment of patients with CNS metastases, with preliminary data showing partial response in some patients. Review of key randomized phase III trials revealed a scarcity of data pertaining to the development of new CNS metastases. Pre-clinical models demonstrate that CDK4/6 inhibitors are able to cross the BBB and can delay the growth of brain metastases. Conclusions: Despite encouraging pre-clinical evidence, there is a lack of clinical data to inform CNS-specific response rates to CDK4/6 inhibitors among patients with metastatic breast cancer. Given that the treatment of patients with breast cancer brain metastases represents an area of unmet medical need, enrollment of patients with CNS metastases in ongoing clinical trials should be encouraged; innovative trials that examine response of CNS metastases to CDK4/6 inhibitors are also of interest., Competing Interests: CONFLICTS OF INTEREST Dr. K. Jerzak served as a consultant for Esai, Genomic Health Inc., Novartis, Purdue Pharma, Pfizer and Roche. She received research support from Astra Zeneca and was a speaker for Apobiologix, Novartis and Purdue Pharma. The other authors declare that there is no conflict of interest., (Copyright: © 2019 Nguyen et al.)

The purpose of this research is to investigate the effect of different oxidation degrees and volume ratios of components on the physical properties and biocompatibility of an in situ cross-linking chitosan-hyaluronic acid-based hydrogel for skin wound healing applications. Carboxymethyl groups (-CH 2 COOH) were introduced to the polymer chain of chitosan, producing N,O - Carboxymethyl Chitosan (NOCC). Hyaluronic acid was oxidized to obtain aldehyde hyaluronic acid (AHA) with three oxidation degrees (AHA40, AHA50 and AHA60). The gelation was induced by forming Schiff base linkage between aldehyde groups of AHA and amino groups of NOCC. Then, the polysaccharide derivatives were combined at three NOCC:AHA volume ratios (3:7, 5:5 and 7:3) to form composite hydrogels without using any additional cross-linker. FT-IR analysis, surface morphology observation and wettability test, in vitro degradation test and rheological analysis were carried out to characterize the hydrogels. Additionally, in vitro cytotoxicity and in vivo wound healing evaluations were also conducted to study the biocompatibility of the composite. Our findings showed that when increasing the volume of NOCC, the homogeneity and hydrophobicity of the resulting hydrogels were also improved and their pore walls became thicker, leading to slower degradation rate. On the other hand, when raising the oxidation degree of AHA, the hydrophilicity of the gels decreased and less time was required to form the gel matrix. Besides, the obtained in vitro and in vivo results indicated that lower oxidation degree of AHA supports cell proliferation, cell attachment and wound healing process better. It is also concluded that NOCC-AHA40 5:5 hydrogel is most suitable for skin wound healing applications since it possesses superior morphology with high uniformity, favorable pore size and suitable density along with appropriate wettability. The NOCC-AHA gel matrix is expected to be used as a delivery system for other factors and employed as an effective bio-glue in further tissue engineering applications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: To evaluate the angiographic and intravascular ultrasound (IVUS) characteristics of coronary mismatch lesions., Background: Better understanding about the characteristics of mismatch lesions may help to achieve more accurate lesion assessment and, thereby, to improve the outcomes of percutaneous coronary intervention (PCI)., Methods: Angiographic and IVUS data from 1369 lesions were analyzed. Mismatch lesion was defined as the difference between proximal and distal reference lumen diameters of ≥1.0 mm or ≥30% of the distal reference lumen diameter., Results: The incidence of mismatch lesions was 20.1% (275/1369). Compared to nonmismatch group, mismatch group had longer lesions (21.3 [6.4] mm vs 18.4 [6.4] mm, P < .001) with smaller minimum lumen diameter (0.87 [0.29] mm vs 1.10 [0.31] mm, P < .001) and more severe diameter stenosis (78.8% [9.2%] vs 66.3% [10.3%], P < .001). On IVUS, mismatch group had larger lumen area (18.7 [5.0] vs 15.8 [5.1] mm 2 , P < .001) but lower plaque burden at the proximal reference segment (41.0% [9.2%] vs 45.7% [9.9%], P < .001) and smaller lumen area (4.83 [1.89] vs 7.36 [2.89] mm, P < .001) but higher plaque burden at the distal reference segment (42.9% [10.4%] vs 41.4% [10.1%], P = .023). Multivariable logistic regression analysis showed that mismatch lesions were frequently accompanied by diffuse lesions (odds ratio [OR] = 2.50; 95% confidence interval [CI]: 1.83-3.40; P < .001), bifurcation lesions (OR = 5.83; 95% CI: 4.40-7.74; P < .001), and lesions with a low TIMI flow grade (OR = 1.70; 95% CI: 1.08-2.67; P = .022) or severe diameter stenosis (OR = 3.05; 95% CI: 2.10-4.43; P < .001)., Conclusions: Mismatch lesions are quite common and characterized by greater lesion complexity compared with nonmismatch lesions. Further studies may be necessary to address the impact of this lesion type on the outcome of PCI.

Exposure of e-waste workers to eight halogenated and five organophosphate ester flame retardant chemicals (FRs) was studied at a Canadian e-waste dismantling facility. FR concentrations were measured in air and dust samples collected at a central location and at four work benches over five-24 hour periods spanning two weeks. The highest concentrations in air from workbenches were of BDE-209 (median 156 ng m -3 ), followed by Tris(2-chloroethyl) phosphate (TCEP, median 59 ng m -3 ). Dust concentrations at the workbenches were higher than those measured at the central location, consistent with the release of contaminated dust during dismantling. Dust concentrations from the workbenches were also dominated by BDE-209 (median 96,300 ng g -1 ), followed by Triphenyl phosphate (TPhP, median 47,000 ng g -1 ). Most FRs were in coarse particles 5.6-18 μm diameter and ~30% were in respirable particles (<~3 μm). Exposure estimates indicated that dust ingestion accounted for 63% of total FR exposure; inhalation and dermal absorption contributed 35 and 2%, respectively. Some air and dust concentrations as well as some estimated exposures in this formal facility in a high-income country exceeded those from informal e-waste facilities located in low and middle income countries. Although there is demonstrated toxicity of some FRs, FR exposure in the e-waste industry has received minimal attention and occupational limits do not exist for most FRs., (Copyright © 2019. Published by Elsevier Ltd.)

Here we report on the concentrations of 79 flame retardants (FRs) and plasticizers, including 34 polybrominated diphenyl ethers or PBDE congeners, 17 "novel" brominated FRs (NBFRs), 15 dechloranes, and 13 organophosphate esters (OPEs) in air (n = 9) and dust (n = 24) samples from an active waste electrical and electronic equipment (WEEE) dismantling facility in Ontario, Canada, collected in February-March 2017. This is the first study of its kind in North America. The facility processes a range of WEEE including monitors, computers, printers, phones, and toys. Of the 79 target compounds, at least 60 were detected at a frequency of at least 50% in both air and dust. Dust and air concentrations were dominated by three compounds: BDE-209 (median 110,000 ng/g and 100 ng/m 3 , respectively), DBDPE (median 41,000 ng/g and 41 ng/m 3 ), and TPhP (median 42,000 ng/g and 27 ng/m 3 ). Levels of PBDEs, NBFRs, and dechloranes were close to two orders-of-magnitude higher in dust from the dismantling facility than in residential homes, while OPEs were one order-of-magnitude higher. Congener profiles of PBDEs indicated debromination of BDE-209. We calculated that a total mass of 44 ± 1 mg day -1 of 79 target analytes were released to air from WEEE processed in the dismantling hall and a further 270 ± 91 mg day -1 were released to dust. It is clear that WEEE dismantling facilities are a serious concern as a source of emissions for a wide range of FRs at relatively high concentrations to both workers and the immediate environment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Recommendations on the optimal frequency of plasma viral load (pVL) monitoring in children living with HIV (CLWH) who are stable on combination antiretroviral therapy (cART) are inconsistent. This study aimed to determine the impact of annual versus semi-annual pVL monitoring on treatment outcomes in Asian CLWH., Methods: Data on children with perinatally acquired HIV aged <18 years on first-line, non-nucleoside reverse transcriptase inhibitor-based cART with viral suppression (two consecutive pVL <400 copies/mL over a six-month period) were included from a regional cohort study; those exposed to prior mono- or dual antiretroviral treatment were excluded. Frequency of pVL monitoring was determined at the site-level based on the median rate of pVL measurement: annual 0.75 to 1.5, and semi-annual >1.5 tests/patient/year. Treatment failure was defined as virologic failure (two consecutive pVL >1000 copies/mL), change of antiretroviral drug class, or death. Baseline was the date of the second consecutive pVL <400 copies/mL. Competing risk regression models were used to identify predictors of treatment failure., Results: During January 2008 to March 2015, there were 1220 eligible children from 10 sites that performed at least annual pVL monitoring, 1042 (85%) and 178 (15%) were from sites performing annual (n = 6) and semi-annual pVL monitoring (n = 4) respectively. Pre-cART, 675 children (55%) had World Health Organization clinical stage 3 or 4, the median nadir CD4 percentage was 9%, and the median pVL was 5.2 log 10 copies/mL. At baseline, the median age was 9.2 years, 64% were on nevirapine-based regimens, the median cART duration was 1.6 years, and the median CD4 percentage was 26%. Over the follow-up period, 258 (25%) CLWH with annual and 40 (23%) with semi-annual pVL monitoring developed treatment failure, corresponding to incidence rates of 5.4 (95% CI: 4.8 to 6.1) and 4.3 (95% CI: 3.1 to 5.8) per 100 patient-years of follow-up respectively (p = 0.27). In multivariable analyses, the frequency of pVL monitoring was not associated with treatment failure (adjusted hazard ratio: 1.12; 95% CI: 0.80 to 1.59)., Conclusions: Annual compared to semi-annual pVL monitoring was not associated with an increased risk of treatment failure in our cohort of virally suppressed children with perinatally acquired HIV on first-line NNRTI-based cART., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

In 2000, the first biphasic modified-release (MR) formulation of methylphenidate (MPH) was approved for the treatment of attention-deficit/hyperactivity disorder (ADHD). An immediate-release (IR) MPH pulse (22% of the dose) facilitates rapid onset of stimulant action, while the remaining MR portion of the dose provides for day-long duration of efficacy. A wide array of oral MR-MPH products has subsequently been approved that also allows for once-daily dosing, though each product is characterized by distinctive exposure time courses. This review compares each member of the current MPH armamentarium to assist in the rational selection of a specific MPH regimen for the individualized treatment of patients with ADHD. The IR portion of biphasic MPH formulations now ranges from 15%, 20%, 22%, 25%, 30%, and 37% IR-MPH, as well as a 50% IR-MPH product whose distinctly pulsatile time course closely resembles that of the pre-century "gold standard" twice-daily IR-MPH regimen. Further, transdermal, suspension, and orally disintegrating tablet products are now available to overcome any solid dosage form swallowing difficulties. Most of these formulations are racemic, though in 2001, a chiral switch drug IR-dexmethylphenidate (dexMPH) was approved, followed by biphasic MR-dexMPH (50% IR) in 2005. New U.S. Food and Drug Administration (FDA) partial area under the curve (pAUC) bioavailability metrics have improved discrimination between specific generic MR-MPH products. This has resulted in two Orange Book MR-MPH products being recoded from "AB" (i.e., meets necessary bioequivalence requirements) to "BX" (i.e., insufficient data to confirm bioequivalence). The metabolic drug interaction between MPH and alcohol, which increases MPH bioavailability, potentiates euphoric effects, and heightens abuse liability, is discussed. This review concludes with brief considerations of pharmacogenomic predictors of ADHD first-line drug selection, carboxylesterase allelic variants influencing interindividual MPH metabolism, and novel MPH formulations in the regulatory pipeline., (© 2018 Pharmacotherapy Publications, Inc.)

Purpose: Management of postoperative pain is a significant challenge following the Nuss procedure. Epidurals, PCAs, and newer analgesia modalities have been used elsewhere without demonstrating consistent improvement in the reported length of hospital stays (LOS). We reviewed a large single surgeon experience identifying three different methods of analgesia used over time to highlight marked improvement in patient LOS., Methods: IRB approval was obtained and patient clinical information was retrospectively reviewed from 2001 to 2017. The primary outcome variable was length of hospital stay. An expanded preoperative consultation reviews the issue of pain, the negative impact of anxiety on recovery, and our current success of shortened hospital stays with our patients., Results: One hundred and seventy-three patients representing three different analgesia approaches had a LOS of 4.4 days (epidural); 2.2 days (PCA/intercostal nerve block); and 1.6 days (scheduled oral pain meds/intercostal nerve blocks). The current LOS for patients is 1.0 day. Patients successfully stop using narcotics by the end of the first week postoperatively., Conclusions: Intraoperative intercostal nerve blocks, scheduled postoperative pain medications, and enhanced preoperative consultation aimed to educate patients about anxiety and reframe patient pain expectations have collectively decreased LOS, and reduced postoperative narcotic usage., Type of Study: Clinical research LEVEL OF EVIDENCE: Level III., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Virologic failure is a major threat to maintaining effective combination antiretroviral therapy, especially for children in need of lifelong treatment. With efforts to expand access to HIV viral load testing, our understanding of pediatric virologic failure is evolving., Setting: An Asian cohort in 16 pediatric HIV services across 6 countries., Methods: From 2005 to 2014, patients younger than 20 years who achieved virologic suppression and had subsequent viral load testing were included. Early virologic failure was defined as a HIV RNA ≥1000 copies per milliliter within 12 months of virologic suppression, and late virologic as a HIV RNA ≥1000 copies per milliliter after 12 months following virologic suppression. Characteristics at combination antiretroviral therapy initiation and virologic suppression were described, and a competing risk time-to-event analysis was used to determine cumulative incidence of virologic failure and factors at virologic suppression associated with early and late virologic failure., Results: Of 1105 included in the analysis, 182 (17.9%) experienced virologic failure. The median age at virologic suppression was 6.9 years, and the median time to virologic failure was 24.6 months after virologic suppression. The incidence rate for a first virologic failure event was 3.3 per 100 person-years. Factors at virologic suppression associated with late virologic failure included older age, mostly rural clinic setting, tuberculosis, protease inhibitor-based regimens, and early virologic failure. No risk factors were identified for early virologic failure., Conclusions: Around 1 in 5 experienced virologic failure in our cohort after achieving virologic suppression. Targeted interventions to manage complex treatment scenarios, including adolescents, tuberculosis coinfection, and those with poor virologic control are required.

Background: Perinatally HIV-infected adolescents (PHIVA) are exposed to a chronic systemic infection and long-term antiretroviral therapy (ART), leaving them susceptible to morbidities associated with inflammation, immunodeficiency and drug toxicity., Methods: Data collected 2001 to 2016 from PHIVA 10-19 years of age within a regional Asian cohort were analyzed using competing risk time-to-event and Poisson regression analyses to describe the nature and incidence of morbidity events and hospitalizations and identify factors associated with disease-related, treatment-related and overall morbidity. Morbidity was defined according to World Health Organization clinical staging criteria and U.S. National Institutes of Health Division of AIDS criteria., Results: A total 3,448 PHIVA contributed 17,778 person-years. Median age at HIV diagnosis was 5.5 years, and ART initiation was 6.9 years. There were 2,562 morbidity events and 307 hospitalizations. Cumulative incidence for any morbidity was 51.7%, and hospitalization was 10.0%. Early adolescence was dominated by disease-related infectious morbidity, with a trend toward noninfectious and treatment-related morbidity in later adolescence. Higher overall morbidity rates were associated with a CD4 count <350 cells/µL, HIV viral load ≥10,000 copies/mL and experiencing prior morbidity at age <10 years. Lower overall morbidity rates were found for those 15-19 years of age compared with 10-14 years and those who initiated ART at age 5-9 years compared with <5 or ≥10 years., Conclusions: Half of our PHIVA cohort experienced a morbidity event, with a trend from disease-related infectious events to treatment-related and noninfectious events as PHIVA age. ART initiation to prevent immune system damage, optimize virologic control and minimize childhood morbidity are key to limiting adolescent morbidity.

Background: Intraventricular haemorrhage (IVH) patients with acute obstructive hydrocephalus (AOH) who require external ventricular drainage (EVD) are at high risk for poor outcomes. Intraventricular fibrinolysis (IVF) with low-dose recombinant tissue plasminogen activator (rtPA) can be used to improve patient outcomes. Here, we evaluated the impact of IVF on the risk of death and the functional outcomes in IVH patients with AOH., Methods: This prospective cohort study included IVH patients with hypertensive intracranial haemorrhage complicated by AOH who required EVD. We evaluated the risk of death and the functional outcomes at 1 and 3 months, with a specific focus on the impact of combined EVD with IVF by low-dose rtPA., Results: Between November 30, 2011 and December 30, 2014, 80 patients were included. Forty-five patients were treated with EVD alone (EVD group) and 35 received IVF (EVD+IVF group). The 30- and 90-day mortality rates were lower in the EVD+IVF group than in the EVD group (42.2 vs. 11.4%, p = 0.003, and 62.2 vs. 20%, p < 0.001, respectively). The Graeb scores were significantly lower in the EVD+IVF group than in the EVD group (p ≤ 0.001) during the first 3 days and on day 7 after assignment. The 30-day good functional outcome (modified Rankin Scale [mRS] score 0-3) was also higher in the EVD+IVF group than in the EVD group (6.7 vs. 28.6%, p = 0.008). However, the 90-day good functional outcome (mRS score 0-3) did not significantly increase in the EVD+IVF group (30.8% in the EVD group vs. 51.6% in the EVD+IVF group, p = 0.112)., Conclusions: In our prospective observational study, EVD+IVF was associated with a lower risk of death in IVH patients. EVD+IVF improved the chance of having a good functional outcome at 1 month; however, this result was no longer observed at 3 months., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Plants adapt to abiotic stresses by complex mechanisms involving various stress-responsive genes. Here, we identified a DEAD-box RNA helicase (RH) gene, AtRH17 , in Arabidopsis , involved in salt-stress responses using activation tagging, a useful technique for isolating novel stress-responsive genes. AT895, an activation tagging line, was more tolerant than wild type (WT) under NaCl treatment during germination and seedling development, and AtRH17 was activated in AT895. AtRH17 possesses nine well-conserved motifs of DEAD-box RHs, consisting of motifs Q, I, Ia, Ib, and II-VI. Although at least 12 orthologs of AtRH17 have been found in various plant species, no paralog occurs in Arabidopsis . AtRH17 protein is subcellularily localized in the nucleus. AtRH17 -overexpressing transgenic plants (OXs) were more tolerant to high concentrations of NaCl and LiCl compared with WT, but no differences from WT were detected among seedlings exposed to mannitol and freezing treatments. Moreover, in the mature plant stage, AtRH17 OXs were also more tolerant to NaCl than WT, but not to drought, suggesting that AtRH17 is involved specifically in the salt-stress response. Notably, transcriptions of well-known abscisic acid (ABA)-dependent and ABA-independent stress-response genes were similar or lower in AtRH17 OXs than WT under salt-stress treatments. Taken together, our findings suggest that AtRH17, a nuclear DEAD-box RH protein, is involved in salt-stress tolerance, and that its overexpression confers salt-stress tolerance via a pathway other than the well-known ABA-dependent and ABA-independent pathways.

Using high-resolution mass spectrometry, we identified tri(2,4-di- t-butylphenyl) phosphate (TDTBPP) in e-waste dust. This is a previously unsuspected pollutant that had not been reported before in the environment. To assess its abundance in the environment, we measured its concentration in e-waste dust, house dust, sediment from the Chicago Ship and Sanitary Canal, Indiana Harbor water filters, and filters from high-volume air samplers deployed in Chicago, IL. To provide a context for interpreting these quantitative results, we also measured the concentrations of triphenyl phosphate (TPhP), a structurally similar compound, in these samples. Median concentrations of TDTBPP and TPhP were 14 400 and 41 500 ng/g, respectively, in e-waste dust and 4900 and 2100 ng/g, respectively, in house dust. TDTBPP was detected in sediment, water, and air with median concentrations of 527 ng/g, 3700 pg/L, and 149 pg/m 3 , respectively. TDTBPP concentrations were generally higher or comparable to those of TPhP in all media analyzed, except for the e-waste dust. Exposure from dust ingestion and dermal absorption in the e-waste recycling facility and in homes was calculated. TDTBPP exposure was 571 ng/kg bw/day in the e-waste recycling facility (pro-rated for an 8-h shift), and 536 ng/kg bw and 7550 ng/kg bw/day for adults and toddlers, respectively, in residential environments.

Biological control, a globally-important ecosystem service, can provide long-term and broad-scale suppression of invasive pests, weeds and pathogens in natural, urban and agricultural environments. Following (few) historic cases that led to sizeable environmental up-sets, the discipline of arthropod biological control has-over the past decades-evolved and matured. Now, by deliberately taking into account the ecological risks associated with the planned introduction of insect natural enemies, immense environmental and societal benefits can be gained. In this study, we document and analyze a successful case of biological control against the cassava mealybug, Phenacoccus manihoti (Hemiptera: Pseudococcidae) which invaded Southeast Asia in 2008, where it caused substantial crop losses and triggered two- to three-fold surges in agricultural commodity prices. In 2009, the host-specific parasitoid Anagyrus lopezi (Hymenoptera: Encyrtidae) was released in Thailand and subsequently introduced into neighboring Asian countries. Drawing upon continental-scale insect surveys, multi-year population studies and (field-level) experimental assays, we show how A. lopezi attained intermediate to high parasitism rates across diverse agro-ecological contexts. Driving mealybug populations below non-damaging levels over a broad geographical area, A. lopezi allowed yield recoveries up to 10.0 t/ha and provided biological control services worth several hundred dollars per ha (at local farm-gate prices) in Asia's four-million ha cassava crop. Our work provides lessons to invasion science and crop protection worldwide. Furthermore, it accentuates the importance of scientifically-guided biological control for insect pest management, and highlights its potentially large socio-economic benefits to agricultural sustainability in the face of a debilitating invasive pest. In times of unrelenting insect invasions, surging pesticide use and accelerating biodiversity loss across the globe, this study demonstrates how biological control-as a pure public good endeavor-constitutes a powerful, cost-effective and environmentally-responsible solution for invasive species mitigation., Competing Interests: Steve Wratten is an Academic Editor for PeerJ, and Jonathan Lundgren is an employee of the Ecdysis Foundation.

Exposure assessments conducted using a personal sampler include the contribution of human activities to exposure that is neglected when using a stationary air sampler. This study evaluated the uptake characteristics and application of the polydimethylsiloxane (PDMS or silicone rubber) brooch as a personal passive air sampler (PPAS) for measuring concentrations of two groups of semi-volatile organic compounds (SVOCs), namely phthalates and organophosphate esters (OPEs), indoors in proximity to the breathing zone. Uptake rates of the PDMS brooch were calibrated against a personal low volume active air sampler (PLV-AAS) co-deployed on each of five study participants working in offices for 8 hs daily for four days. Sampling rates measured here ranged from 0.41 ± 0.33 to 1.33 ± 0.34 m 3 day -1  dm -2 with an average value of 0.86 ± 0.29 m 3 day -1  dm -2 . Personal air concentrations of 1211 to 2640 ng m -3 for ∑ 5 phthalates and 254 to 663 ng m -3 for ∑ 5 OPEs were measured for three study participants who used the PDMS brooches continuously for seven days. These concentrations resulted in estimated inhalation exposures of 19,400 to 42,400 ng day -1 for ∑ 5 phthalates and 4,070 to 10,600 ng day -1 for ∑ 5 OPEs. This study demonstrated that the PDMS brooch can be used to assess inhalation exposure when worn for at least 24 h indoors, for compounds present in >4 ng m -3 in air such as individual phthalates and OPEs tested here., (Copyright © 2018. Published by Elsevier Ltd.)

Tricyclic cores of the daphnane diterpene orthoesters (DDOs) are synthesized in 10 steps from readily available materials. Key to their assembly is the development of a stereocontrolled p-quinol functionalization sequence which enables rapid access to DDO C-ring stereopolyads from simple precursors. Problems encountered in stereo- and regioselectivity are highlighted and solved by exact changes in choreography, although it is shown that the undesired stereochemical outcomes also proceed with high selectivity.

Objectives: The aim of this study was to describe characteristics of perinatally HIV-infected adolescents (PHIVAs), factors associated with mortality, and outcomes at transition., Design: Ongoing observational database collating clinical data on HIV-infected children and adolescents in Asia., Methods: Data from 2001 to 2016 relating to adolescents (10-19 years) with perinatal HIV infection were analysed to describe characteristics at adolescent entry and transition and combination antiretroviral therapy (cART) regimens across adolescence. A competing risk regression analysis was used to determine characteristics at adolescent entry associated with mortality. Outcomes at transition were compared on the basis of age at cART initiation., Results: Of 3448 PHIVA, 644 had reached transition. Median age at HIV diagnosis was 5.5 years, cART initiation 7.2 years and transition 17.9 years. At adolescent entry, 35.0% had CD4+ cell count less than 500 cells/μl and 51.1% had experienced a WHO stage III/IV clinical event. At transition, 38.9% had CD4+ cell count less than 500 copies/ml, and 53.4% had experienced a WHO stage III/IV clinical event. Mortality rate was 0.71 per 100 person-years, with HIV RNA ≥1000 copies/ml, CD4+ cell count less than 500 cells/μl, height-for-age or weight-for-age z-score less than -2, history of a WHO stage III/IV clinical event or hospitalization and at least second cART associated with mortality. For transitioning PHIVA, those who commenced cART age less than 5 years had better virologic and immunologic outcomes, though were more likely to be on at least second cART., Conclusion: Delayed HIV diagnosis and cART initiation resulted in considerable morbidity and poor immune status by adolescent entry. Durable first-line cART regimens to optimize disease control are key to minimizing mortality. Early cART initiation provides the best virologic and immunologic outcomes at transition.

We studied behavioral risks among HIV-infected and uninfected adolescents using an audio computer-assisted self-interview. A prospective cohort study was initiated between 2013 and 2014 in Malaysia, Thailand, and Vietnam. HIV-infected adolescents were matched to uninfected adolescents (4:1) by sex and age group (12-14 and 15-18 years). We enrolled 250 HIV-infected (48% male; median age 14.5 years; 93% perinatally infected) and 59 uninfected (51% male; median age 14.1 years) adolescents. At enrollment, HIV-infected adolescents were on antiretroviral therapy (ART) for a median (IQR) of 7.5 (4.7-10.2) years, and 14% had HIV-RNA >1000 copies/mL; 19% reported adherence <80%. Eighty-four (34%) HIV-infected and 26 (44%) uninfected adolescents reported having ever smoked cigarettes or drunk alcohol (p = 0.13); 10% of HIV-infected and 17% of uninfected adolescents reported having initiated sexual activity; 6 of the HIV-infected adolescents had HIV-RNA >1000 copies/mL. Risk behaviors were common among adolescents, with few differences between those with and without HIV.

Highly pathogenic avian influenza (HPAI) A(H5N1) viruses pose a significant economic burden to the poultry industry worldwide and have pandemic potential. Poultry vaccination against HPAI A(H5N1) viruses has been an important component of HPAI control measures and has been performed in Vietnam since 2005. To systematically assess antigenic matching of current vaccines to circulating field variants, we produced a panel of chicken and ferret antisera raised against historical and contemporary Vietnamese reference viruses representing clade variants that were detected between 2001 and 2014. The antisera were used for hemagglutination inhibition (HI) assays to generate data sets for analysis by antigenic cartography, allowing for a direct comparison of results from chicken or ferret antisera. HI antigenic maps, developed with antisera from both hosts, revealed varying patterns of antigenic relationships and clustering of viruses that were dependent on the clade of viruses analyzed. Antigenic relationships between existing poultry vaccines and circulating field viruses were also aligned with in vivo protection profiles determined by previously reported vaccine challenge studies. Our results establish the feasibility and utility of HPAI A(H5N1) antigenic characterization using chicken antisera and support further experimental and modeling studies to investigate quantitative relationships between genetic variation, antigenic drift and correlates of poultry vaccine protection in vivo.

Functional studies of CCCH-type zinc finger proteins in abiotic stress responses have largely focused on tandem CCCH-type zinc finger (TZF) genes, whereas the study of functional roles of non-TZF genes in abiotic stress responses has largely been neglected. Here, we investigated the functional roles of AtC3H17, a non-TZF gene of Arabidopsis, in salt stress responses. AtC3H17 expression significantly increased under NaCl, mannitol, and ABA treatments. AtC3H17-overexpressing transgenic plants (OXs) were more tolerant under NaCl and MV treatment conditions than the wild type (WT). atc3h17 mutants were more sensitive under NaCl and MV treatment conditions compared with the WT. The transcription of the salt stress-responsive genes in ABA-dependent pathway, such as RAB18, COR15A, and RD22, was significantly higher in AtC3H17 OXs than in WT both under NaCl-free condition and after NaCl treatment. Our results demonstrate that AtC3H17 functions as a positive regulator in salt stress response, via the up-regulation of ABA-dependent salt stress-response pathway., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A high molecular weight compound, 2,4,6-tris(2,4,6-tribromophenoxy)-1,3,5-triazine (TTBP-TAZ), was detected during the analysis of brominated flame retardants in dust samples collected from an electrical and electronic waste (e-waste) recycling facility in Ontario, Canada. Gas chromatography coupled with both high-resolution and low-resolution mass spectrometry (MS) was used to determine TTBP-TAZ's chemical structure and concentrations. To date, TTBP-TAZ has only been detected in plastic casings of electrical and electronic equipment and house dust from The Netherlands. Here we report on the concentrations of TTBP-TAZ in selected samples from North America: e-waste dust ( n = 7) and air ( n = 4), residential dust ( n = 30), and selected outdoor air ( n = 146), precipitation ( n = 19), sediment ( n = 11) and water ( n = 2) samples from the Great Lakes environment. TTBP-TAZ was detected in all the e-waste dust and air samples, and in 70% of residential dust samples. The median concentrations of TTBP-TAZ in these three types of samples were 5540 ng/g, 5.75 ng/m 3 and 6.76 ng/g, respectively. The flame retardants 2,4,6-tribromophenol, tris(2,3-dibromopropyl) isocyanurate, and 3,3',5,5'-tetrabromobisphenol A bis(2,3-dibromopropyl) ether, BDE-47 and BDE-209 were also measured for comparison. None of these other flame retardants concentrations was significantly correlated with those of TTBP-TAZ in any of the sample types suggesting different sources. TTBP-TAZ was not detected in any of the outdoor environmental samples, which may relate to its application history and physicochemical properties. This is the first report of TTBP-TAZ in North America.

Simultaneous integration of photon emission and biocompatibility into nanoparticles is an interesting strategy to develop applications of advanced optical materials. In this work, we present the synthesis of biocompatible optical nanocomposites from the combination of near-infrared luminescent lanthanide nanoparticles and water-soluble chitosan. NaYF 4 :Yb,Er upconverting nanocrystal guests and water-soluble chitosan hosts are prepared and integrated together into biofunctional optical composites. The control of aqueous dissolution, gelation, assembly, and drying of NaYF 4 :Yb,Er nanocolloids and chitosan liquids allowed us to design novel optical structures of spongelike aerogels and beadlike microspheres. Well-defined shape and near-infrared response lead upconverting nanocrystals to serve as photon converters to couple with plasmonic gold (Au) nanoparticles. Biocompatible chitosan-stabilized Au/NaYF 4 :Yb,Er nanocomposites are prepared to show their potential use in biomedicine as we find them exhibiting a half-maximal effective concentration (EC 50 ) of 0.58 mg mL -1 for chitosan-stabilized Au/NaYF 4 :Yb,Er nanorods versus 0.24 mg mL -1 for chitosan-stabilized NaYF 4 :Yb,Er after 24 h. As a result of their low cytotoxicity and upconverting response, these novel materials hold promise to be interesting for biomedicine, analytical sensing, and other applications., Competing Interests: The authors declare no competing financial interest.

In Vietnam, live bird markets are found in most populated centres, providing the means by which fresh poultry can be purchased by consumers for immediate consumption. Live bird markets are aggregation points for large numbers of poultry, and therefore, it is common for a range of avian influenza viruses to be mixed within live bird markets as a result of different poultry types and species being brought together from different geographical locations. We conducted a cross-sectional study in seven live bird markets in four districts of Thua Thien Hue Province in August and December, 2014. The aims of this study were to (i) document the prevalence of avian influenza in live bird markets (as measured by virus isolation); and (ii) quantify individual bird-, seller- and market-level characteristics that rendered poultry more likely to be positive for avian influenza virus at the time of sale. A questionnaire soliciting details of knowledge, attitude and avian influenza practices was administered to poultry sellers in study markets. At the same time, swabs and faecal samples were collected from individual poultry and submitted for isolation of avian influenza virus. The final data set comprised samples from 1,629 birds from 83 sellers in the seven live bird markets. A total of 113 birds were positive for virus isolation; a prevalence of 6.9 (95% CI 5.8-8.3) avian influenza virus-positive birds per 100 birds submitted for sale. After adjusting for clustering at the market and individual seller levels, none of the explanatory variables solicited in the questionnaire were significantly associated with avian influenza virus isolation positivity. The proportions of variance at the individual market, seller and individual bird levels were 6%, 48% and 46%, respectively. We conclude that the emphasis of avian influenza control efforts in Vietnam should be at the individual seller level as opposed to the market level., (© 2017 Blackwell Verlag GmbH.)

Here, we investigated the effects of the probiotic strain Lactobacillus casei Shirota (LcS) on immune profiles and intestinal microbial translocation among children infected with human immunodeficiency virus (HIV). This prospective study included 60 HIV-infected children-including 31 without antiretroviral therapy (ART) (HIV(+)) and 29 who received ART for a median of 3.5 years (ART(+)) and 20 children without HIV infection (HIV(-)). Participants were recruited in Vietnam. All children were given fermented milk containing LcS (6.5 × 10⁸ cfu) daily for 8 weeks. Before and after LcS ingestion, blood samples were collected for virological, immunological, and bacteriological analyses. After LcS ingestion, peripheral CD4⁺ T-cell and Th2 (CXCR3 - CCR6 - CD4⁺) counts significantly increased in both HIV-infected groups; Th17 (CXCR3 - CCR6⁺CD4⁺) counts increased in all three groups; regulatory T-cell (CD25 high CD4⁺) counts decreased in the ART(+) and HIV(-) groups; activated CD8⁺ cells (CD38⁺HLA-DR⁺CD8⁺) decreased from 27.5% to 13.2% ( p < 0.001) in HIV(+) children; and plasma HIV load decreased slightly but significantly among HIV(+) children. No group showed a significantly altered frequency of bacterial 16S/23S rRNA gene detection in the plasma. No serious adverse events occurred. These findings suggest that short-term LcS ingestion is a safe supportive approach with immunological and virological benefits in HIV-infected children., Competing Interests: The authors declare no conflict of interest.

Bioinspired materials have aroused great interest as their inherent biocompatible and structural characteristics have given rise to sustainable applications. In this work, we have reported the phase and morphology transformation of chitosan from crystalline nanofibrils into amorphous sheets for fabricating sustainable materials. Acetylation-induced aqueous dissolution of native chitosan nanofibrils affords water-soluble chitosan as a biopolymeric liquid. Water-soluble chitosan macromolecules self-aggregate into amorphous sheets on solidification, presenting an interesting way to inspire new structures of chitosan assemblies. Through control over gelation, lyophilization, and self-assembled confinement of water-soluble chitosan, we have fabricated novel chitosan materials including filaments, aerogels, microspheres, and plastics that are promising for sustainable use.

Human glioblastomas harbour a subpopulation of glioblastoma stem cells that drive tumorigenesis. However, the origin of intratumoural functional heterogeneity between glioblastoma cells remains poorly understood. Here we study the clonal evolution of barcoded glioblastoma cells in an unbiased way following serial xenotransplantation to define their individual fate behaviours. Independent of an evolving mutational signature, we show that the growth of glioblastoma clones in vivo is consistent with a remarkably neutral process involving a conserved proliferative hierarchy rooted in glioblastoma stem cells. In this model, slow-cycling stem-like cells give rise to a more rapidly cycling progenitor population with extensive self-maintenance capacity, which in turn generates non-proliferative cells. We also identify rare 'outlier' clones that deviate from these dynamics, and further show that chemotherapy facilitates the expansion of pre-existing drug-resistant glioblastoma stem cells. Finally, we show that functionally distinct glioblastoma stem cells can be separately targeted using epigenetic compounds, suggesting new avenues for glioblastoma-targeted therapy.

Chitin nanocrystals have been used as a liquid crystalline template to fabricate layered oxide semiconductor aerogels. Anisotropic chitin liquid crystals are transformed to sponge-like aerogels by hydrothermally cross-linked gelation and lyophilization-induced solidification. The hydrothermal gelation of chitin aqueous suspensions then proceeds with peroxotitanate to form hydrogel composites that recover to form aerogels after freeze-drying. The homogeneous peroxotitanate/chitin composites are calcined to generate freestanding titania aerogels that exhibit the nanostructural integrity of layered chitin template. Our extended investigations show that coassembling chitin nanocrystals with other metal-based precursors also yielded semiconductor aerogels of perovskite BaTiO 3 and CuO x nanocrystals. The potential of these materials is great to investigate these chitin sponges for biomedicine and these semiconductor aerogels for photocatalysis, gas sensing, and other applications. Our results present a new aerogel templating method of highly porous, ultralight materials with chitin liquid crystals.

Purpose: To assess the incidence and predictors of postsuppression virologic rebound (VR) among adolescents on stable combination antiretroviral therapy in Asia., Methods: Perinatally HIV-infected Asian adolescents (10-19 years) with documented virologic suppression (two consecutive viral loads [VLs] <400 copies/mL ≥6 months apart) were included. Baseline was the date of the first VL <400 copies/mL at age ≥10 years or the 10th birthday for those with prior suppression. Cox proportional hazards models were used to identify predictors of postsuppression VR (VL >1,000 copies/mL)., Results: Of 1,379 eligible adolescents, 47% were males. At baseline, 22% were receiving protease inhibitor-containing regimens; median CD4 cell count (interquartile range [IQR]) was 685 (448-937) cells/mm 3 ; 2% had preadolescent virologic failure (VF) before subsequent suppression. During adolescence, 180 individuals (13%) experienced postsuppression VR at a rate of 3.4 (95% confidence interval: 2.9-3.9) per 100 person-years, which was consistent over time. Median time to VR during adolescence (IQR) was 3.3 (2.1-4.8) years. Wasting (weight-for-age z-score <-2.5), being raised by grandparents, receiving second-line protease inhibitor-based regimens, starting combination antiretroviral therapy after 2005, and having preadolescent VF were independent predictors of adolescent VR. At VR, median age, CD4 cell count, and VL (IQR) were 14.8 (13.2-16.4) years, 507 (325-723) cells/mm 3 , and 4.1 (3.5-4.7) log 10 copies/mL, respectively., Conclusions: A modest and consistent incidence of postsuppression VR was documented during adolescence in our cohort. Having poor weight, receiving second-line regimens, and prior VF were associated with an increased VR rate. Adolescents at higher risk of VR may benefit from more intensive VL monitoring to enhance adherence management., (Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background.: Regular CD4 count testing is often used to monitor antiretroviral therapy efficacy. However, this practice may be redundant in children with a suppressed human immunodeficiency virus (HIV) viral load., Methods: Study end points were as follows: (1) a CD4 count <200 cells/mm3 followed by a CD4 count ≥200 cells/mm3 (transient CD4 <200); (2) CD4 count <200 cells/mm3 confirmed within 6 months (confirmed CD4 <200); and (3) a new or recurrent World Health Organization (WHO) stage 3 or 4 illness (clinical failure). Kaplan-Meier curves and Cox regression were used to evaluate rates and predictors of transient CD4 <200, confirmed CD4 <200, and clinical failure among virally suppressed children aged 5-15 years who were enrolled in the TREAT Asia Pediatric HIV Observational Database., Results: Data from 967 children were included in the analysis. At the time of confirmed viral suppression, median age was 10.2 years, 50.4% of children were female, and 95.4% were perinatally infected with HIV. Median CD4 cell count was 837 cells/mm3, and 54.8% of children were classified as having WHO stage 3 or 4 disease. In total, 18 transient CD4 <200 events, 2 confirmed CD4 <200 events, and10 clinical failures occurred at rates of 0.73 (95% confidence interval [95% CI], 0.46-1.16), 0.08 (95% CI, 0.02-0.32), and 0.40 (95% CI, 0.22-0.75) events per 100 patient-years, respectively. CD4 <500 cells/mm3 at the time of viral suppression confirmation was associated with higher rates of both CD4 outcomes., Conclusions: Regular CD4 testing may be unnecessary for virally suppressed children aged 5-15 years with CD4 ≥500 cells/mm3., (© The Author 2016. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We sought to assess the impact of routine HIV viral load (VL) monitoring on the incidence of switching from a first- to a second-line antiretroviral therapy (ART) regimen, and to describe factors associated with switch. Data from a regional cohort of 16 clinical programs in six Asian countries were analyzed. Second-line switch was defined as a change from a non-nucleoside reverse transcriptase inhibitor (NNRTI) to a protease inhibitor (PI) or vice versa, and ≥1 of the following: (1) reported treatment failure by local criteria, (2) switch of ≥1 additional drug, or (3) a preceding HIV VL ≥1,000 copies/ml. Routine VL was having ≥1 test after ≥24 weeks of ART and ≥1 time/year thereafter. Factors associated with time to switch were evaluated with death and loss to follow-up as competing risks. A total of 2,398 children were included in this analysis. At ART initiation, the median (interquartile range) age was 6.0 (3.3-8.9) years, more than half had WHO stage 3 or 4, the median CD4 was 189 (47-456) cells/mm 3 , 93% were on NNRTI-based first-line ART, and 34% had routine VL monitoring. Treatment switch occurred in 17.6% of patients, at a median of 35 (22-49) months. After adjusting for country, sex, first ART regimen, and CD4% at ART initiation, children with routine VL monitoring were 1.46 (95% confidence interval 1.11-1.93) times more likely to be switched (p = .007). Scale-up of VL testing will lead to earlier identification of treatment failure, and it can help guide earlier switches to prevent resistance.

Whole-genome sequences of representative highly pathogenic avian influenza A(H5) viruses from Vietnam were generated, comprising samples from poultry outbreaks and active market surveillance collected from January 2012 to August 2015. Six hemagglutinin gene clades were characterized. Clade 1.1.2 was predominant in southern Mekong provinces throughout 2012 and 2013 but gradually disappeared and was not detected after April 2014. Clade 2.3.2.1c viruses spread rapidly during 2012 and were detected in the south and center of the country. A number of clade 1.1.2 and 2.3.2.1c interclade reassortant viruses were detected with different combinations of internal genes derived from 2.3.2.1a and 2.3.2.1b viruses, indicating extensive cocirculation. Although reassortment generated genetic diversity at the genotype level, there was relatively little genetic drift within the individual gene segments, suggesting genetic stasis over recent years. Antigenically, clade 1.1.2, 2.3.2.1a, 2.3.2.1b, and 2.3.2.1c viruses remained related to earlier viruses and WHO-recommended prepandemic vaccine strains representing these clades. Clade 7.2 viruses, although detected in only low numbers, were the exception, as indicated by introduction of a genetically and antigenically diverse strain in 2013. Clade 2.3.4.4 viruses (H5N1 and H5N6) were likely introduced in April 2014 and appeared to gain dominance across northern and central regions. Antigenic analyses of clade 2.3.4.4 viruses compared to existing clade 2.3.4 candidate vaccine viruses (CVV) indicated the need for an updated vaccine virus. A/Sichuan/26221/2014 (H5N6) virus was developed, and ferret antisera generated against this virus were demonstrated to inhibit some but not all clade 2.3.4.4 viruses, suggesting consideration of alternative clade 2.3.4.4 CVVs. IMPORTANCE Highly pathogenic avian influenza (HPAI) A(H5) viruses have circulated continuously in Vietnam since 2003, resulting in hundreds of poultry outbreaks and sporadic human infections. Despite a significant reduction in the number of human infections in recent years, poultry outbreaks continue to occur and the virus continues to diversify. Vaccination of poultry has been used as a means to control the spread and impact of the virus, but due to the diversity and changing distribution of antigenically distinct viruses, the utility of vaccines in the face of mismatched circulating strains remains questionable. This study assessed the putative amino acid changes in viruses leading to antigenic variability, underscoring the complexity of vaccine selection for both veterinary and public health purposes. Given the overlapping geographic distributions of multiple, antigenically distinct clades of HPAI A(H5) viruses in Vietnam, the vaccine efficacy of bivalent poultry vaccine formulations should be tested in the future., (Copyright © 2017 American Society for Microbiology.)

Main Conclusion: AtNAP , an Arabidopsis NAC transcription factor family gene, functions as a negative regulator via transcriptional repression of AREB1 in salt stress response. AtNAP is an NAC family transcription factor in Arabidopsis and is known to be a positive regulator of senescence. However, its exact function and underlying molecular mechanism in stress responses are not well known. Here, we investigated functional roles of AtNAP in salt stress response. AtNAP expression significantly increased at the seedling stage, with higher expression in both shoots and roots under NaCl, mannitol, and ABA treatments. T-DNA insertional loss-of-function mutants of AtNAP were more tolerant to salt stress than wild type (WT), whereas AtNAP-overexpressing transgenic plants (OXs) were more sensitive to salt stress than WT during germination, seedling development, and mature plant stage. Transcript levels of stress-responsive genes in the ABA-dependent pathway, such as AREB1, RD20, and RD29B, were significantly higher and lower in atnap mutants and AtNAP OXs, respectively, than in WT under salt stress conditions, suggesting that AtNAP might negatively regulate the expression of those genes under salt stress conditions. Indeed, AtNAP repressed the promoter activity of AREB1 under normal and salt stress conditions. These results indicate that AtNAP functions as a negative regulator in the salt stress response. Our results, together with previous studies, suggest that AtNAP functions as a negative regulator in osmotic stress responses, whereas it functions as a positive regulator in senescence.

The damage of buildings and manmade structures, where most of human activities occur, is the major cause of casualties of from earthquakes. In this paper, an improved technique, Earthquake Damage Visualization (EDV) is presented for the rapid detection of earthquake damage using the Synthetic Aperture Radar (SAR) data. The EDV is based on the pre-seismic and co-seismic coherence change method. The normalized difference between the pre-seismic and co-seismic coherences, and vice versa, are used to calculate the forward (from pre-seismic to co-seismic) and backward (from co-seismic to pre-seismic) change parameters, respectively. The backward change parameter is added to visualize the retrospective changes caused by factors other than the earthquake. The third change-free parameter uses the average values of the pre-seismic and co-seismic coherence maps. These three change parameters were ultimately merged into the EDV as an RGB (Red, Green, and Blue) composite imagery. The EDV could visualize the earthquake damage efficiently using Horizontal transmit and Horizontal receive (HH), and Horizontal transmit and Vertical receive (HV) polarizations data from the Advanced Land Observing Satellite-2 (ALOS-2). Its performance was evaluated in the Kathmandu Valley, which was hit severely by the 2015 Nepal Earthquake. The cross-validation results showed that the EDV is more sensitive to the damaged buildings than the existing method. The EDV could be used for building damage detection in other earthquakes as well.

Next generation sequencing technologies have provided numerous opportunities for application in the study of whole plant genomes. In this study, we present the sequencing and bioinformatic analyses of five typical rice landraces including three indica and two japonica with potential blast resistance. A total of 688.4 million 100 bp paired-end reads have yielded approximately 30-fold coverage to compare with the Nipponbare reference genome. Among them, a small number of reads were mapped to both chromosomes and organellar genomes. Over two million and eight hundred thousand single nucleotide polymorphisms (SNPs) and insertions and deletions (InDels) in indica and japonica lines have been determined, which potentially have significant impacts on multiple transcripts of genes. SNP deserts, contiguous SNP-low regions, were found on chromosomes 1, 4, and 5 of all genomes of rice examined. Based on the distribution of SNPs per 100 kilobase pairs, the phylogenetic relationships among the landraces have been constructed. This is the first step towards revealing several salient features of rice genomes in Vietnam and providing significant information resources to further marker-assisted selection (MAS) in rice breeding programs., Competing Interests: The authors declare that they have no competing interests.