Dendritic Surfactants Show Evidence for Frustrated Intercalation: A New Organoclay Morphology

Mixing a smectite clay with some dendritic surfactants shows that despite the large size of some of these molecules, a property that frustrates complete intercalation into the gallery of the clay, organoclay materials are obtained. X-ray powder diffraction (XPD) reveals no significant increases in lattice spacing as these surfactants are added. Infrared (IR) spectroscopy and thermal gravimetric analysis (TGA) show that interlayer water is preserved. Consistent with an undisturbed interlayer, the amount of organic material in organoclays derived from frustrated surfactants does not exceed 15% of the cationic exchange capacity (CEC) of the composite. Smaller dendritic surfactants do not display frustrated intercalation and instead readily enter into the gallery of the smectic clay yielding traditional organoclay materials. A range of organic compositions (5-50% w/w) that exceed the CEC of the materials are observed. The organic content is corroborated by UV spectroscopy and TGA. XPD reveals increasing lattice spacings with increasing organic content. IR spectroscopy and TGA support an increasingly hydrophobic interlayer. A linear isomer of a frustrated surfactant can intercalate into the gallery (5-33% w/w) yielding morphologies that depend on the amount of surfactant added. These results support the hypothesis that shape, and not only size, is important for producing frustrated intercalation

Dielectric Properties of Materials Showing Constant-Phase-Element (CPE) Impedance Response

Constant-Phase Elements (CPE) are often used to fit impedance data arising from a broad range of experimental systems. Four approaches were used to interpret CPE parameters associated with the impedance response of human skin and two metal oxides in terms of characteristic frequencies and film thickness. The values obtained with each approach were compared against independent measurements. The power-law model developed recently by Hirschorn et al.1,2 provided the most reliable interpretation for systems with a normal distribution of properties. Readers are cautioned that the CPE parameter Q does not provide an accurate value for capacitance, even when the CPE exponent α is greater than 0.9

Progressive star formation in the young galactic super star cluster NGC 3603

Early release science observations of the cluster NGC3603 with the WFC3 on the refurbished HST allow us to study its recent star formation history. Our analysis focuses on stars with Halpha excess emission, a robust indicator of their pre-main sequence (PMS) accreting status. The comparison with theoretical PMS isochrones shows that 2/3 of the objects with Halpha excess emission have ages from 1 to 10 Myr, with a median value of 3 Myr, while a surprising 1/3 of them are older than 10 Myr. The study of the spatial distribution of these PMS stars allows us to confirm their cluster membership and to statistically separate them from field stars. This result establishes unambiguously for the first time that star formation in and around the cluster has been ongoing for at least 10-20 Myr, at an apparently increasing rate.Comment: 10 pages, 8 figures, accepted for publication in The Astrophysical Journa

Zika virus pathogenesis in rhesus macaques is unaffected by pre-existing immunity to dengue virus

Zika virus (ZIKV) is a re-emerging virus that has recently spread into dengue virus (DENV) endemic regions and cross-reactive antibodies (Abs) could potentially affect ZIKV pathogenesis. Using DENV-immune serum, it has been shown in vitro that antibody-dependent enhancement (ADE) of ZIKV infection can occur. Here we study the effects of pre-existing DENV immunity on ZIKV infection in vivo. We infect two cohorts of rhesus macaques with ZIKV; one cohort has been exposed to DENV 2.8 years earlier and a second control cohort is naïve to flaviviral infection. Our results, while confirming ADE in vitro, suggest that pre-existing DENV immunity does not result in more severe ZIKV disease. Rather our results show a reduction in the number of days of ZIKV viremia compared to naïve macaques and that the previous exposure to DENV may result in modulation of the immune response without resulting in enhancement of ZIKV pathogenesis

Detection of brown dwarf-like objects in the core of NGC3603

We use near-infrared data obtained with the Wide Field Camera 3 (WFC3) on the Hubble Space Telescope to identify objects having the colors of brown dwarfs (BDs) in the field of the massive galactic cluster NGC 3603. These are identified through use of a combination of narrow and medium band filters spanning the J and H bands, and which are particularly sensitive to the presence of the 1.3-1.5{\mu}m H2O molecular band - unique to BDs. We provide a calibration of the relationship between effective temperature and color for both field stars and for BDs. This photometric method provides effective temperatures for BDs to an accuracy of {\pm}350K relative to spectroscopic techniques. This accuracy is shown to be not significantly affected by either stellar surface gravity or uncertainties in the interstellar extinction. We identify nine objects having effective temperature between 1700 and 2200 K, typical of BDs, observed J-band magnitudes in the range 19.5-21.5, and that are strongly clustered towards the luminous core of NGC 3603. However, if these are located at the distance of the cluster, they are far too luminous to be normal BDs. We argue that it is unlikely that these objects are either artifacts of our dataset, normal field BDs/M-type giants or extra-galactic contaminants and, therefore, might represent a new class of stars having the effective temperatures of BDs but with luminosities of more massive stars. We explore the interesting scenario in which these objects would be normal stars that have recently tidally ingested a Hot Jupiter, the remnants of which are providing a short-lived extended photosphere to the central star. In this case, we would expect them to show the signature of fast rotation.Comment: 26 Pages, 8 Figures, Accepted for publication on Ap

Bridging the gap: evaluating high TB burden country data needs to support the potential introduction of TB vaccines for adolescents and adults: a workshop report

High tuberculosis (TB) burden countries (HBCs) need to prepare for TB vaccine implementation alongside licensure, to ensure rapid rollout. WHO policy/implementation frameworks have been created to support this effort. Using WHO frameworks, we convened a workshop to ask HBC experts about what epidemiological, impact, feasibility and acceptability data they anticipated they would need to guide TB vaccine introduction. For required data, we asked HBC and global experts which data were already available, data collection planned, or gaps. HBC experts expressed high demand for epidemiological, impact, feasibility and acceptability data, reported variable availability of existing epidemiological data, and low availability for impact, feasibility, and acceptability data. Global experts reported additional knowledge of existing data on impact, upcoming collection of infection prevalence, acceptability and feasibility data, and potential epidemiological data collection on adolescents, adults, people living with HIV, and underweight individuals. HBC and global experts made key recommendations for: a coordinated data collation, collection, analysis and sharing system; updating existing HBC health and economic impact estimates and extending impact analyses to other HBCs; demand/market forecasting; resource gap mapping; aligning delivery strategies; addressing manufacturing, procurement, delivery, and regulatory barriers; sharing potential vaccine licensure timing; incorporating TB vaccine introduction strategies into NSPs, immunization programs, and health services; collecting vaccine hesitancy, mistrust, and misinformation data; collecting adolescent/adult vaccine demand generation data, and identifying funding. Experts recommended expanding this analysis to other areas of the WHO frameworks, including more HBC stakeholders, and repeating this analysis after country and community advocacy and socialization around different vaccine candidates

Functional Identification of Api5 as a Suppressor of E2F-Dependent Apoptosis In Vivo

Retinoblastoma protein and E2-promoter binding factor (E2F) family members are important regulators of G1-S phase progression. Deregulated E2F also sensitizes cells to apoptosis, but this aspect of E2F function is poorly understood. Studies of E2F-induced apoptosis have mostly been carried out in tissue culture cells, and the analysis of the factors that are important for this process has been restricted to the testing of a few candidate genes. Using Drosophila as a model system, we have generated tools that allow genetic modifiers of E2F-dependent apoptosis to be identified in vivo and developed assays that allow effects on E2F-induced apoptosis to be studied in cultured cells. Genetic interactions show that dE2F1-dependent apoptosis in vivo involves dArk/Apaf1 apoptosome-dependent activation of both initiator and effector caspases and is sensitive to levels of Drosophila inhibitor of apoptosis-1 (dIAP1). Using these approaches, we report the surprising finding that apoptosis inhibitor-5/antiapoptosis clone-11 (Api5/Aac11) is a critical determinant of dE2F1-induced apoptosis in vivo and in vitro. This functional interaction occurs in multiple tissues, is specific to E2F-induced apoptosis, and is conserved from flies to humans. Interestingly, Api5/Aac11 acts downstream of E2F and suppresses E2F-dependent apoptosis without generally blocking E2F-dependent transcription. Api5/Aac11 expression is often upregulated in tumor cells, particularly in metastatic cells. We find that depletion of Api5 is tumor cell lethal. The strong genetic interaction between E2F and Api5/Aac11 suggests that elevated levels of Api5 may be selected during tumorigenesis to allow cells with deregulated E2F activity to survive under suboptimal conditions. Therefore, inhibition of Api5 function might offer a possible mechanism for antitumor exploitation

Whole-Genome Sequencing of Pharmacogenetic Drug Response in Racially Diverse Children with Asthma

RATIONALE: Albuterol, a bronchodilator medication, is the first-line therapy for asthma worldwide. There are significant racial/ethnic differences in albuterol drug response. OBJECTIVES: To identify genetic variants important for bronchodilator drug response (BDR) in racially diverse children. METHODS: We performed the first whole-genome sequencing pharmacogenetics study from 1,441 children with asthma from the tails of the BDR distribution to identify genetic association with BDR. MEASUREMENTS AND MAIN RESULTS: We identified population-specific and shared genetic variants associated with BDR, including genome-wide significant (P \u3c 3.53 × 10 CONCLUSIONS: The lack of minority data, despite a collaboration of eight universities and 13 individual laboratories, highlights the urgent need for a dedicated national effort to prioritize diversity in research. Our study expands the understanding of pharmacogenetic analyses in racially/ethnically diverse populations and advances the foundation for precision medicine in at-risk and understudied minority populations

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Whole-genome sequencing of pharmacogenetic drug response in racially diverse children with asthma

RATIONALE: Albuterol, a bronchodilator medication, is the first-line therapy for asthma worldwide. There are significant racial/ethnic differences in albuterol drug response. OBJECTIVES: To identify genetic variants important for bronchodilator drug response (BDR) in racially diverse children. METHODS: We performed the first whole-genome sequencing pharmacogenetics study from 1,441 children with asthma from the tails of the BDR distribution to identify genetic association with BDR. MEASUREMENTS AND MAIN RESULTS: We identified population-specific and shared genetic variants associated with BDR, including genome-wide significant (P \u3c 3.53 × 10-7) and suggestive (P \u3c 7.06 × 10-6) loci near genes previously associated with lung capacity (DNAH5), immunity (NFKB1 and PLCB1), and β-adrenergic signaling (ADAMTS3 and COX18). Functional analyses of the BDR-associated SNP in NFKB1 revealed potential regulatory function in bronchial smooth muscle cells. The SNP is also an expression quantitative trait locus for a neighboring gene, SLC39A8. The lack of other asthma study populations with BDR and whole-genome sequencing data on minority children makes it impossible to perform replication of our rare variant associations. Minority underrepresentation also poses significant challenges to identify age-matched and population-matched cohorts of sufficient sample size for replication of our common variant findings. CONCLUSIONS: The lack of minority data, despite a collaboration of eight universities and 13 individual laboratories, highlights the urgent need for a dedicated national effort to prioritize diversity in research. Our study expands the understanding of pharmacogenetic analyses in racially/ethnically diverse populations and advances the foundation for precision medicine in at-risk and understudied minority populations