Exceptional points of any order in a single, lossy waveguide beam splitter by photon-number-resolved detection

Exceptional points (EPs) are degeneracies of non-Hermitian operators where, in addition to the eigenvalues, the corresponding eigenmodes become degenerate. Classical and quantum photonic systems with EPs have attracted tremendous attention due to their unusual properties, topological features, and an enhanced sensitivity that depends on the order of the EP, i.e., the number of degenerate eigenmodes. Yet, experimentally engineering higher-order EPs in classical or quantum domains remain an open challenge due to the stringent symmetry constraints that are required for the coalescence of multiple eigenmodes. Here, we analytically show that the number-resolved dynamics of a single, lossy waveguide beam splitter, excited by indistinguishable photons and post-selected to the -photon subspace, will exhibit an EP of order +1. By using the well-established mapping between a beam splitter Hamiltonian and the perfect state transfer model in the photon-number space, we analytically obtain the time evolution of a general -photon state and numerically simulate the system’s evolution in the post-selected manifold. Our results pave the way toward realizing robust, arbitrary-order EPs on demand in a single device

Oligonucleotide Based Magnetic Bead Capture of Onchocerca volvulus DNA for PCR Pool Screening of Vector Black Flies

The absence of infective larvae of Onchocerca volvulus in the black fly vector of this parasite is a major criterion used to certify that transmission has been eliminated in a focus. This process requires screening large numbers of flies. Currently, this is accomplished by screening pools of flies using a PCR-based assay. The number of flies that may be included in each pool is currently limited by the DNA purification process to 50 flies for Latin American vectors and 100 flies for African vectors. Here, we describe a new method for DNA purification that relies upon a specific oligonucleotide to capture and immobilize the parasite DNA on a magnetic bead. This method permits the reliable detection of a single infective larva of O. volvulus in pools containing up to 200 individual flies. The method described here will dramatically improve the efficiency of pool screening of vector black flies, making the process of elimination certification easier and less expensive to implement

Aedes albopictus in northeast Mexico: An update on adult distribution and first report of parasitism by Ascogregarina taiwanensis

ABSTRACT Background & objectives: Aedes albopictus has been known as efficient vector of dengue in Asian countries and its wide displacement of Ae. aegypti has been documented in many parts of the world. The present survey was carried out to update the distribution of Ae. albopictus in northeast Mexico and to report the first record of parasitism of mosquitoes by Ascogregarina taiwanensis in Mexico

The surface-associated exopolysaccharide of Bifidobacterium longum 35624 plays an essential role in dampening host proinflammatory responses and repressing local TH17 responses

The immune-modulating properties of certain bifidobacterial strains, such as Bifidobacterium longum subsp. longum 35624 (B. longum 35624), have been well described, although the strain-specific molecular characteristics associated with such immune-regulatory activity are not well defined. It has previously been demonstrated that B. longum 35624 produces a cell surface exopolysaccharide (sEPS), and in this study, we investigated the role played by this exopolysaccharide in influencing the host immune response. B. longum 35624 induced relatively low levels of cytokine secretion from human dendritic cells, whereas an isogenic exopolysaccharide-negative mutant derivative (termed sEPSneg) induced vastly more cytokines, including interleukin-17 (IL-17), and this response was reversed when exopolysaccharide production was restored in sEPSneg by genetic complementation. Administration of B. longum 35624 to mice of the T cell transfer colitis model prevented disease symptoms, whereas sEPSneg did not protect against the development of colitis, with associated enhanced recruitment of IL-17+ lymphocytes to the gut. Moreover, intranasal administration of sEPSneg also resulted in enhanced recruitment of IL-17+ lymphocytes to the murine lung. These data demonstrate that the particular exopolysaccharide produced by B. longum 35624 plays an essential role in dampening proinflammatory host responses to the strain and that loss of exopolysaccharide production results in the induction of local TH17 responses. IMPORTANCE: Particular gut commensals, such as B. longum 35624, are known to contribute positively to the development of mucosal immune cells, resulting in protection from inflammatory diseases. However, the molecular basis and mechanisms for these commensal-host interactions are poorly described. In this report, an exopolysaccharide was shown to be decisive in influencing the immune response to the bacterium. We generated an isogenic mutant unable to produce exopolysaccharide and observed that this mutation caused a dramatic change in the response of human immune cells in vitro. In addition, the use of mouse models confirmed that lack of exopolysaccharide production induces inflammatory responses to the bacterium. These results implicate the surface-associated exopolysaccharide of the B. longum 35624 cell envelope in the prevention of aberrant inflammatory responses

Dissemination of Metarhizium anisopliae of low and high virulence by mating behavior in Aedes aegypti

<p>Abstract</p> <p>Background</p> <p>Dengue is a viral disease transmitted by <it>Aedes </it>mosquitoes. It is a threat for public health worldwide and its primary vector <it>Aedes aegypti </it>is becoming resistant to chemical insecticides. These factors have encouraged studies to evaluate entomopathogenic fungi against the vector. Here we evaluated mortality, infection, insemination and fecundity rates in <it>A. aegypti </it>females after infection by autodissemination with two Mexican strains of <it>Metarhizium anisopliae</it>.</p> <p>Methods</p> <p>Two <it>M. anisopliae </it>strains were tested: The Ma-CBG-1 least virulent (lv), and the Ma-CBG-2 highly virulent (hv) strain. The lv was tested as non mosquito-passed (NMP), and mosquito-passed (MP), while the hv was examined only as MP version, therefore including the control four treatments were used. In the first bioassay virulence of fungal strains towards female mosquitoes was determined by indirect exposure for 48 hours to conidia-impregnated paper. In the second bioassay autodissemination of fungal conidia from fungus-contaminated males to females was evaluated. Daily mortality allowed computation of survival curves and calculation of the LT₅₀by the Kaplan-Meier model. All combinations of fungal sporulation and mating insemination across the four treatments were analyzed by χ². The mean fecundity was analyzed by ANOVA and means contrasted with the Ryan test.</p> <p>Results</p> <p>Indirect exposure to conidia allowed a faster rate of mortality, but exposure to a fungal-contaminated male was also an effective method of infecting female mosquitoes. All females confined with the hv strain-contaminated male died in fifteen days with a LT₅₀of 7.57 (± 0.45) where the control was 24.82 (± 0.92). For the lv strain, it was possible to increase fungal virulence by passing the strain through mosquitoes. 85% of females exposed to hv-contaminated males became infected and of them just 10% were inseminated; control insemination was 46%. The hv strain reduced fecundity by up to 99%, and the lv strain caused a 40% reduction in fecundity.</p> <p>Conclusions</p> <p>The hv isolate infringed a high mortality, allowed a low rate of insemination, and reduced fecundity to nearly zero in females confined with a fungus-contaminated male. This pathogenic impact exerted through sexual transmission makes the hv strain of <it>M. anisopliae </it>worthy of further research.</p

Elimination of onchocerciasis in Ecuador: findings of post-treatment surveillance.

BACKGROUND: The Esmeraldas focus of onchocerciasis in Ecuador expanded geographically during the 1980s and was associated with severe ocular and skin disease. Mass drug administration (MDA) with ivermectin started in 1991, initially once but later twice a year, in the principle endemic focus followed by all satellite foci. Treatment was stopped in 2009 when entomological assessments determined that transmission of Onchocerca volvulus had been interrupted. METHODS: Three years after the cessation of ivermectin treatment in 2012, as defined by the WHO guidelines for onchocerciasis elimination, blackfly collections were done in four sentinel sites in former hyperendemic areas. The presence of infective larvae in local vectors, Simulium exiguum and Simulum quadrivittatum, was assessed by detection of O. volvulus DNA by PCR. Additional flies captured in four extra-sentinel sites located in former hyper- and mesoendemic dispersed isolated areas were also assessed. RESULTS: The results from 68,310 captured blackflies, 40,114 from four sentinel villages in the previously hyperendemic areas (Corriente Grande, El Tigre, San Miguel on Río Cayapas and Naranjal on Río Canandé) and 28,197 from extra-sentinel locations, were all negative for the presence of O. volvulus. These extra-sentinel sites (Hualpí on Río Hoja Blanca, Capulí on Río Onzole, La Ceiba on Río Tululví and Medianía on Río Verde) were included to provide additional evidence of the impact of MDA on the transmission of O. volvulus in isolated endemic areas. CONCLUSIONS: Our data indicate that transmission of O. volvulus has been stopped in all endemic areas in Ecuador, including all satellite foci outside the main focus. These findings indicate that a strategy of ivermectin distribution twice a year to over 85% of the treatment-eligible population was effective in eliminating the infection from Ecuador in a focus with a highly competent primary vector, S. exiguum, and where the infection rates were equal to or greater than observed in many onchocerciasis foci in Africa

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

Multi-ancestry genome-wide association study of asthma exacerbations

Altres ajuts: European Regional Development Fund "ERDF A way of making Europe"; Allergopharma-EAACI award 2021; SysPharmPedia grant from the ERACoSysMed 1st Joint Transnational Call from the European Union under the Horizon 2020; Sandler Family Foundation; American Asthma Foundation; RWJF Amos Medical Faculty Development Program; National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HL117004, R01HL128439, R01HL135156, X01HL134589, R01HL141992, R01HL141845); National Institute of Health and Environmental Health Sciences (R01ES015794, R21ES24844); National Institute on Minority Health and Health Disparities (NIMHD) (P60MD006902, R01MD010443, R56MD013312); National Institute of General Medical Sciences (NIGMS) (RL5GM118984); Tobacco-Related Disease Research Program (24RT-0025, 27IR-0030); National Human Genome Research Institute (NHGRI) (U01HG009080); GlaxoSmithKline and Utrecht Institute for Pharmaceutical Sciences; Slovenian Research Agency (P3-0067); SysPharmPediA grant, co-financed by the Ministry of Education, Science and Sport Slovenia (MIZS) (C3330-16-500106); NHS Research Scotland; Wellcome Trust Biomedical Resource (099177/Z/12/Z); Genotyping National Centre (CeGEN) CeGen-PRB3-ISCIII (AC15/00015); UK Medical Research Council and Wellcome (102215/2/13/2); University of Bristol; Swedish Heart-Lung Foundation, Swedish Research Council; Region Stockholm (ALF project and database maintenance); NHS Chair of Pharmacogenetics via the UK Department of Health; Innovative Medicines Initiative (IMI) (115010); European Federation of Pharmaceutical Industries and Associations (EFPIA); Spanish National Cancer Research Centre; Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC19/17); Erasmus Medical Center; Erasmus University Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF); U.S. National Institutes of Health (HL07966); European Social Fund "ESF Investing in your future"; Ministerio de Ciencia, Innovación y Universidades; Universidad de La Laguna (ULL); European Academy of Allergy and Clinical Immunology (EAACI); European Respiratory Society (ERS) (LTRF202101-00861); Ministry of Education, Science and Sport of the Republic of Slovenia (C3330-19-252012); Singapore Ministry of Education Academic Research Fund; Singapore Immunology Network (SIgN); National Medical Research Council (NMRC Singapore); Biomedical Research Council (BMRC Singapore); Agency for Science Technology and Research (A*STAR Singapore, N-154-000-038-001, R-154-000-191-112, R-154-000-404-112, R-154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154-000-A27-597, R-154-000-A91-592, R-154-000-A95-592, R-154-000-B99-114, BMRC/01/1/21/18/077, BMRC/04/1/21/19/315, SIgN-06-006, SIgN-08-020, NMRC/1150/2008, H17/01/a0/008); Sime Darby Technology Centre; First Resources Ltd; Genting Plantation; Olam International; U.S. National Institutes of Health (HL138098).Background: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of genome-wide association studies (meta-GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression. Methods: A meta-GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10) were assessed for replication in 36,477 European and 1078 non-European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico. Results: One hundred and twenty-six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 (VCAM1/EXTL2) (discovery: odds ratio (OR) = 0.82, p = 9.05 × 10 and replication: OR = 0.89, p = 5.35 × 10) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: OR = 0.85, p = 3.10 × 10 and replication: OR = 0.89, p = 1.30 × 10). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood. Conclusions: This multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense

The LOFT mission concept: a status update

The Large Observatory For x-ray Timing (LOFT) is a mission concept which was proposed to ESA as M3 and M4 candidate in the framework of the Cosmic Vision 2015-2025 program. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument and the uniquely large field of view of its wide field monitor, LOFT will be able to study the behaviour of matter in extreme conditions such as the strong gravitational field in the innermost regions close to black holes and neutron stars and the supra-nuclear densities in the interiors of neutron stars. The science payload is based on a Large Area Detector (LAD, >8m2 effective area, 2-30 keV, 240 eV spectral resolution, 1 degree collimated field of view) and a Wide Field Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e.g., GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the current technical and programmatic status of the mission