SeqSero, launched in 2015, is a software tool for
serotype determination from whole-genome sequencing (WGS) data. Despite its routine use in public health and food safety laboratories in the United ...States and other countries, the original SeqSero pipeline is relatively slow (minutes per genome using sequencing reads), is not optimized for draft genome assemblies, and may assign multiple serotypes for a strain. Here, we present SeqSero2 (github.com/denglab/SeqSero2; denglab.info/SeqSero2), an algorithmic transformation and functional update of the original SeqSero. Major improvements include (i) additional sequence markers for identification of
species and subspecies and certain serotypes, (ii) a k-mer based algorithm for rapid serotype prediction from raw reads (seconds per genome) and improved serotype prediction from assemblies, and (iii) a targeted assembly approach for specific retrieval of serotype determinants from WGS for serotype prediction, new allele discovery, and prediction troubleshooting. Evaluated using 5,794 genomes representing 364 common U.S. serotypes, including 2,280 human isolates of 117 serotypes from the National Antimicrobial Resistance Monitoring System, SeqSero2 is up to 50 times faster than the original SeqSero while maintaining equivalent accuracy for raw reads and substantially improving accuracy for assemblies. SeqSero2 further suggested that 3% of the tested genomes contained reads from multiple serotypes, indicating a use for contamination detection. In addition to short reads, SeqSero2 demonstrated potential for accurate and rapid serotype prediction directly from long nanopore reads despite base call errors. Testing of 40 nanopore-sequenced genomes of 17 serotypes yielded a single H antigen misidentification.
Serotyping is the basis of public health surveillance of
It remains a first-line subtyping method even as surveillance continues to be transformed by whole-genome sequencing. SeqSero allows the integration of
serotyping into a whole-genome-sequencing-based laboratory workflow while maintaining continuity with the classic serotyping scheme. SeqSero2, informed by extensive testing and application of SeqSero in the United States and other countries, incorporates important improvements and updates that further strengthen its application in routine and large-scale surveillance of
by whole-genome sequencing.
Species and subspecies within the Salmonella genus have been defined for public health purposes by biochemical properties; however, reference laboratories have increasingly adopted sequence-based, ...and especially whole genome sequence (WGS), methods for surveillance and routine identification. This leads to potential disparities in subspecies definitions, routine typing, and the ability to detect novel subspecies. A large-scale analysis of WGS data from the routine sequencing of clinical isolates was employed to define and characterise Salmonella subspecies population structure, demonstrating that the Salmonella species and subspecies were genetically distinct, including those previously identified through phylogenetic approaches, namely: S. enterica subspecies londinensis (VII), subspecies brasiliensis (VIII), subspecies hibernicus (IX) and subspecies essexiensis (X). The analysis also identified an additional novel subspecies, reptilium (XI). Further, these analyses indicated that S. enterica subspecies arizonae (IIIa) isolates were divergent from the other S. enterica subspecies, which clustered together and, on the basis of ANI analysis, subspecies IIIa was sufficiently distinct to be classified as a separate species, S. arizonae. Multiple phylogenetic and statistical approaches generated congruent results, suggesting that the proposed species and subspecies structure was sufficiently biologically robust for routine application. Biochemical analyses demonstrated that not all subspecies were distinguishable by these means and that biochemical approaches did not capture the genomic diversity of the genus. We recommend the adoption of standardised genomic definitions of species and subspecies and a genome sequence-based approach to routine typing for the identification and definition of novel subspecies.
•A large-scale analysis of genomic data demonstrate Salmonella species and subspecies are genetically distinct.•Biochemical analysis does not capture the genomic diversity of the Salmonella genus but routine species and subspecies identification can be achieved with rMLST•Average Nucleotide Identify (ANI) with a 95% criteria was suitable to distinguish species and 98% to distinguish subspecies.•Five novel S. enteric subspecies (VII-XI) type strains are defined.•Reclassification of S. arizonae as a separate species is recommended.
This multiagency report developed by the Interagency Collaboration for Genomics for Food and Feed Safety provides an overview of the use of and transition to whole genome sequencing (WGS) technology ...for detection and characterization of pathogens transmitted commonly by food and for identification of their sources. We describe foodborne pathogen analysis, investigation, and harmonization efforts among the following federal agencies: National Institutes of Health; Department of Health and Human Services, Centers for Disease Control and Prevention (CDC) and U.S. Food and Drug Administration (FDA); and the U.S. Department of Agriculture, Food Safety and Inspection Service, Agricultural Research Service, and Animal and Plant Health Inspection Service. We describe single nucleotide polymorphism, core-genome, and whole genome multilocus sequence typing data analysis methods as used in the PulseNet (CDC) and GenomeTrakr (FDA) networks, underscoring the complementary nature of the results for linking genetically related foodborne pathogens during outbreak investigations while allowing flexibility to meet the specific needs of Interagency Collaboration partners. We highlight how we apply WGS to pathogen characterization (virulence and antimicrobial resistance profiles) and source attribution efforts and increase transparency by making the sequences and other data publicly available through the National Center for Biotechnology Information. We also highlight the impact of current trends in the use of culture-independent diagnostic tests for human diagnostic testing on analytical approaches related to food safety and what is next for the use of WGS in the area of food safety.
We present Hubble Space Telescope (HST) spectroscopy of the nucleus of M31 obtained with the Space Telescope Imaging Spectrograph (STIS). Spectra that include the Ca II infrared triplet (l 8500 Ae) ...see only the red giant stars in the double brightness peaks P1 and P2. In contrast, spectra taken at l 3600-5100 Ae are sensitive to the tiny blue nucleus embedded in P2, the lower surface brightness nucleus of the galaxy. P2 has a K-type spectrum, but we find that the blue nucleus has an A-type spectrum: it shows strong Balmer absorption lines. Hence, the blue nucleus is blue not because of AGN light but rather because it is dominated by hot stars. We show that the spectrum is well described by A0 giant stars, A0 dwarf stars, or a 200 Myr old, single-burst stellar population. White dwarfs, in contrast, cannot fit the blue nucleus spectrum. Given the small likelihood for stellar collisions, recent star formation appears to be the most plausible origin of the blue nucleus. In stellar population, size, and velocity dispersion, the blue nucleus is so different from P1 and P2 that we call it P3 and refer to the nucleus of M31 as triple. Because P2 and P3 have very different spectra, we can make a clean decomposition of the red and blue stars and hence measure the light distribution and kinematics of each uncontaminated by the other. The line-of-sight velocity distributions of the red stars near P2 strengthen the support for Tremaine's eccentric disk model. Their wings indicate the presence of stars with velocities of up to 1000 km s super(-1) on the anti-P1 side of P2. The kinematics of P3 are consistent with a circular stellar disk in Keplerian rotation around a supermassive black hole. If the P3 disk is perfectly thin, then the inclination angle i 55 is identical within the errors to the inclination of the eccentric disk models for P1+P2 by Peiris & Tremaine and by Salow & Statler. Both disks rotate in the same sense and are almost coplanar. The observed velocity dispersion of P3 is largely caused by blurred rotation and has a maximum value of s = 1183 c 201 km s super(-1). This is much larger than the dispersion s 250 km s super(-1) of the red stars along the same line of sight and is the largest integrated velocity dispersion observed in any galaxy. The rotation curve of P3 is symmetric around its center. It reaches an observed velocity of V = 618 c 81 km s super(-1) at radius 0.05 = 0.19 pc, where the observed velocity dispersion is s = 674 c 95 km s super(-1). The corresponding circular rotation velocity at this radius is 61700 km s super(-1). We therefore confirm earlier suggestions that the central dark object interpreted as a supermassive black hole is located in P3. Thin-disk and Schwarzschild models with intrinsic axial ratios b/a < 0.26 corresponding to inclinations between 55 and 58 match the P3 observations very well. Among these models, the best fit and the lowest black hole mass are obtained for a thin-disk model with sub(; ) = 1.4 x 10 super(8) M sub(z). Allowing P3 to have some intrinsic thickness and considering possible systematic errors, the 1 s confidence range becomes (1.1-2.3) x 10 super(8) M sub(z). The black hole mass determined from P3 is independent of but consistent with Peiris & Tremaine's mass estimate based on the eccentric disk model for P1+P2. It is 62 times larger than the prediction by the correlation between M sub(; ) and bulge velocity dispersion s sub(bulge). Taken together with other reliable black hole mass determinations in nearby galaxies, notably the Milky Way and M32, this strengthens the evidence that the M sub(; )-s sub(bulge) relation has significant intrinsic scatter, at least at low black hole masses. We show that any dark star cluster alternative to a black hole must have a half-mass radius <0.03 = 0.11 pc in order to match the observations. Based on this, M31 becomes the third galaxy (after NGC 4258 and our Galaxy) in which clusters of brown dwarf stars or dead stars can be excluded on astrophysical grounds.
Objective Breast cancer control in Ghana is characterised by low awareness, late‐stage treatment and poor survival. In settings with severely constrained health resources, there is a need to spend ...money wisely. To achieve this and to guide policy makers in their selection of interventions, this study systematically compares costs and effects of breast cancer control interventions in Ghana.
Methods We used a mathematical model to estimate costs and health effects of breast cancer interventions in Ghana from the healthcare perspective. Analyses were based on the WHO‐CHOICE method, with health effects expressed in disability‐adjusted life years (DALYs), costs in 2009 US dollars (US$) and cost‐effectiveness ratios (CERs) in US$ per DALY averted. Analyses were based on local demographic, epidemiological and economic data, to the extent these data were available.
Results Biennial screening by clinical breast examination (CBE) of women aged 40–69 years, in combination with treatment of all stages, seems the most cost‐effective intervention (costing $1299 per DALY averted). The intervention is also economically attractive according to international standards on cost‐effectiveness. Mass media awareness raising (MAR) is the second best option (costing $1364 per DALY averted). Mammography screening of women of aged 40–69 years (costing $12 908 per DALY averted) cannot be considered cost‐effective.
Conclusions Both CBE screening and MAR seem economically attractive interventions. Given the uncertainty about the effectiveness of these interventions, only their phased introduction, carefully monitored and evaluated, is warranted. Moreover, their implementation is only meaningful if the capacity of basic cancer diagnostic, referral and treatment and possibly palliative services is simultaneously improved.
Objectif: La lutte contre le cancer du sein au Ghana se caractérise par une faible sensibilisation, un traitement tardif et une faible survie. Dans les contextes où les ressources en santé sont extrêmement limitées, il est nécessaire de dépenser l’argent à bon escient. Pour atteindre cet objectif et pour guider les décideurs dans leur choix des interventions, cette étude compare systématiquement les coûts et les effets des interventions pour la lutte contre le cancer du sein au Ghana.
Méthodes: Nous avons utilisé un modèle mathématique pour estimer les coûts et les effets sur la santé des interventions pour le cancer du sein au Ghana selon les perspectives des soins de santé. Les analyses ont été basées sur la méthode OMS‐CHOICE, avec les effets de santé exprimés en années de vie ajustées pour l’incapacité (DALY), les coûts en valeur du dollar américains (US$) de 2009 et le rapport coût‐efficacité (RCE) en US$ par DALY évitée. Les analyses ont été basées sur des données locales démographiques, épidémiologiques et économiques, dans la mesure où ces données étaient disponibles.
Résultats: Le dépistage biennal par un examen clinique des seins (ECS) des femmes âgées de 40 à 69 ans, en combinaison avec le traitement de tous les stades, semble l’intervention la plus rentable (coûtant 1299 US$ par DALY évitée). L’intervention est aussi économiquement attractive selon les normes internationales de rentabilité. La sensibilisation de masse par les médias (MAR) est la deuxième meilleure option (coûtant 1364 US$ par DALY évitée). Le dépistage par mammographie des femmes de 40 à 69 ans (coûtant 12.908 US$ par DALY évitée) ne peut pas être considéré comme rentable.
Conclusions: Le dépistage ECS et la MAR semblent tous deux des interventions économiquement attrayantes. Compte tenu de l’incertitude quant à l’efficacité de ces interventions, seule leur implémentation progressive, soigneusement surveillée et évaluée, est justifiée. De plus, leur implémentation n’a de sens que si les capacités de diagnostic de base du cancer, d’aiguillage et de traitement et, éventuellement, des services de soins palliatifs sont simultanément améliorés.
Objetivo: El control del cáncer de mama en Ghana está caracterizado por una baja concienciación, el tratamiento en estados tardíos y una baja supervivencia. En emplazamientos con una gran escasez de recursos es necesario realizar los gastos de manera sensata. Para alcanzar este objetivo y guiar a los políticos en la selección de intervenciones, este estudio compara de forma sistemática los costes y efectos de las intervenciones de control del cáncer de mama en Ghana.
Métodos: Hemos utilizado un modelo matemático para estimar los costes y efectos sobre la salud de las intervenciones para el control del cáncer de mama en Ghana desde una perspectiva de salud pública. Los análisis estaban basados en el método OMS‐CHOICE, con los efectos sobre la salud expresados como años de vida ajustados por discapacidad (AVADs), costes en el 2009 en dólares americanos (US$), y ratios de coste‐efectividad (CERs) en US$ por AVAD evitado. Los análisis estaban basados en datos demográficos, epidemiológicos y económicos, en la medida en que estos datos estaban disponibles.
Resultados: El cribado cada dos años mediante un examen clínico de los senos (ECS) de las mujeres con edades comprendidas entre los 40‐69 años, en combinación con tratamiento en todas las etapas, parece ser la intervención más coste‐efectiva (coste $1,299 por AVAD evitado). La intervención también es económicamente atractiva según los estándares internacionales en coste‐efectividad. El concienciar a la población mediante el uso de medios masivos de comunicación (CMMC) es la segunda mejor opción (coste $1,364 por AVAD evitado). El cribado por mamografía en mujeres con edades entre 40‐69 años (coste $12,908 por AVAD evitado)no puede considerarse coste‐efectivo.
Conclusiones: Tanto el ECS como la CMMC parecen ser intervenciones económicamente atractivas. Dada la incertidumbre sobre la efectividad de estas intervenciones, solo se garantiza una introducción en fases, cuidadosamente monitorizada y evaluada. Más aún, su implementación solo tendrá sentido si simultáneamente se aumenta la capacidad del diagnóstico básico del cáncer, la derivación y el tratamiento y los posibles cuidados paliativos.
To report on the safety of the first 5 cohorts of a gene therapy trial using recombinant equine infectious anemia virus expressing ABCA4 (EIAV-ABCA4) in adults with Stargardt dystrophy due to ...mutations in ABCA4.
Nonrandomized multicenter phase I/IIa clinical trial.
Patients received a subretinal injection of EIAVABCA4 in the worse-seeing eye at 3 dose levels and were followed for 3 years after treatment.
The primary end point was ocular and systemic adverse events. The secondary end points were best-corrected visual acuity, static perimetry, kinetic perimetry, total field hill of vision, full field electroretinogram, multifocal ERG, color fundus photography, short-wavelength fundus autofluorescence, and spectral domain optical coherence tomography.
The subretinal injections were well tolerated by all 22 patients across 3 dose levels. There was 1 case of a treatment-related ophthalmic serious adverse event in the form of chronic ocular hypertension. The most common adverse events were associated with the surgical procedure. In 1 patient treated with the highest dose, there was a significant decline in the number of macular flecks as compared with the untreated eye. However, in 6 patients, hypoautofluorescent changes were worse in the treated eye than in the untreated eye. Of these, 1 patient had retinal pigment epithelium atrophy that was characteristic of tissue damage likely associated with bleb induction. No patients had any clinically significant changes in best-corrected visual acuity, static perimetry, kinetic perimetry, total field hill of vision, full field electroretinogram, or multifocal ERG attributable to the treatment.
Subretinal treatment with EIAV-ABCA4 was well tolerated with only 1 case of ocular hypertension. No clinically significant changes in visual function tests were found to be attributable to the treatment. However, 27% of treated eyes showed exacerbation of retinal pigment epithelium atrophy on fundus autofluorescence. There was a significant reduction in macular flecks in 1 treated eye from the highest dose cohort. Additional follow-up and continued investigation in more patients will be required to fully characterize the safety and efficacy of EIAV-ABCA4.
Vegetable tannins are complex polyphenols, which occur widely in nature. Traditionally, natural tannins have been used for tanning leather. In Brazil, the main tannin-based products are obtained from
...Acacia mearnsii,
which is a leguminous tree native to Southeastern of Australia, and the first seeds were brought to Brazil in 1928. The main cultivation of acacia was established in Rio Grande do Sul state due to the possibility of raw material for charcoal, adhesives to fuel and for tanning leather. The leather tanning processes based on plant tannins are thought to be less harmful than chromium-based tanning, and it has been used as a sustainable alternative. However, there is scarce information about the environmental impact of the leather tanning processes, with most studies reporting inhibitory effects against microorganisms at high doses and stimulatory and positive health effects at low concentrations. The aim of this study was to evaluate the toxicity of tannin preparations extracted from
A. mearnsii
in
Saccharomyces cerevisiae
. Vegetable tannin toxicity in yeast was tested using two tannin treatments in different concentrations. In general, the results showed toxicity of vegetable in yeast, BY4741 and
gsh1Δ
strains.
Objectives. This study was designed to estimate the prevalence of coronary artery calcification in young adult men and women and to examine the association between the presence of coronary artery ...calcification and coronary risk factors measured in childhood and young adult life.
Background. Electron beam computed tomography is a sensitive, noninvasive method for detecting coronary artery calcification, a marker of the atherosclerotic process. Coronary artery calcification is associated with coronary risk factors in older adults.
Methods. Subjects (197 men, 187 women) had coronary risk factors measured in childhood (mean age 15 years) and twice during young adult life (mean ages 27 and 33 years). Each underwent an electron beam computed tomographic study at their second young adult examination.
Results. The prevalence of coronary artery calcification was 31% in men and 10% in women. Increased body size, increased blood pressure and decreased high density lipoprotein (HDL) cholesterol levels were the coronary risk factors that showed the strongest association with coronary artery calcification. Significant odds ratios for coronary artery calcification, using standardized risk factor measurements at a mean age of 33 years in men and women, respectively, were 6.4 and 13.6 for the highest decile of body mass index, 6.4 and 6.4 for the highest decile of systolic blood pressure and 4.3 and 4.7 for the lowest decile of HDL cholesterol.
Conclusions. Coronary artery calcification is more prevalent in men in this young adult population. Coronary risk factors measured in children and young adults are associated with the early development of coronary artery calcification. Increased body mass index measured during childhood and young adult life and increased blood pressure and decreased HDL cholesterol levels measured during young adult life are associated with the presence of coronary artery calcification in young adults.
The New Horizons spacecraft extended the range in solar phase angle coverage for Pluto's moon Charon from 1 8-the maximum observable from Earth-to 170°. This extraordinary expansion in range has ...enabled photometric modeling and a robust determination of Charon's phase integral and Bond albedo at visible wavelengths. Photometric modeling shows that Charon is similar in its photometric properties to other icy moons, except that its single particle phase function is more isotropic, suggesting the Kuiper Belt may represent a new regime for surface alteration processes. Charon's phase integral is 0.70 0.04 and its Bond albedo is 0.29 0.05.
A clock comparison experiment, analyzing the ratio of spin precession frequencies of stored ultracold neutrons and 199Hg atoms, is reported. No daily variation of this ratio could be found, from ...which is set an upper limit on the Lorentz invariance violating cosmic anisotropy field b perpendicular < 2 x 10(-20) eV (95% C.L.). This is the first limit for the free neutron. This result is also interpreted as a direct limit on the gravitational dipole moment of the neutron |gn| < 0.3 eV/c2 m from a spin-dependent interaction with the Sun. Analyzing the gravitational interaction with the Earth, based on previous data, yields a more stringent limit |gn| < 3 x 10(-4) eV/c2 m.
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