Evolution of virulence in a novel family of transmissible mega-plasmids

Some Serratia entomophila isolates have been successfully exploited in biopesticides due to their ability to cause amber disease in larvae of the Aotearoa (New Zealand) endemic pasture pest, Costelytra giveni. Anti-feeding prophage and ABC toxin complex virulence determinants are encoded by a 153-kb single-copy conjugative plasmid (pADAP; amber disease-associated plasmid). Despite growing understanding of the S. entomophila pADAP model plasmid, little is known about the wider plasmid family. Here, we sequence and analyse mega-plasmids from 50 Serratia isolates that induce variable disease phenotypes in the C. giveni insect host. Mega-plasmids are highly conserved within S. entomophila, but show considerable divergence in Serratia proteamaculans with other variants in S. liquefaciens and S. marcescens, likely reflecting niche adaption. In this study to reconstruct ancestral relationships for a complex mega-plasmid system, strong co-evolution between Serratia species and their plasmids were found. We identify 12 distinct mega-plasmid genotypes, all sharing a conserved gene backbone, but encoding highly variable accessory regions including virulence factors, secondary metabolite biosynthesis, Nitrogen fixation genes and toxin-antitoxin systems. We show that the variable pathogenicity of Serratia isolates is largely caused by presence/absence of virulence clusters on the mega-plasmids, but notably, is augmented by external chromosomally encoded factors

Pneumococcal carriage in sub-Saharan Africa--a systematic review.

BACKGROUND: Pneumococcal epidemiology varies geographically and few data are available from the African continent. We assess pneumococcal carriage from studies conducted in sub-Saharan Africa (sSA) before and after the pneumococcal conjugate vaccine (PCV) era. METHODS: A search for pneumococcal carriage studies published before 2012 was conducted to describe carriage in sSA. The review also describes pneumococcal serotypes and assesses the impact of vaccination on carriage in this region. RESULTS: Fifty-seven studies were included in this review with the majority (40.3%) from South Africa. There was considerable variability in the prevalence of carriage between studies (I-squared statistic = 99%). Carriage was higher in children and decreased with increasing age, 63.2% (95% CI: 55.6-70.8) in children less than 5 years, 42.6% (95% CI: 29.9-55.4) in children 5-15 years and 28.0% (95% CI: 19.0-37.0) in adults older than 15 years. There was no difference in the prevalence of carriage between males and females in 9/11 studies. Serotypes 19F, 6B, 6A, 14 and 23F were the five most common isolates. A meta-analysis of four randomized trials of PCV vaccination in children aged 9-24 months showed that carriage of vaccine type (VT) serotypes decreased with PCV vaccination; however, overall carriage remained the same because of a concomitant increase in non-vaccine type (NVT) serotypes. CONCLUSION: Pneumococcal carriage is generally high in the African continent, particularly in young children. The five most common serotypes in sSA are among the top seven serotypes that cause invasive pneumococcal disease in children globally. These serotypes are covered by the two PCVs recommended for routine childhood immunization by the WHO. The distribution of serotypes found in the nasopharynx is altered by PCV vaccination

Mycobacterium tuberculosis osteomyelitis in a patient with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): a case report

The incidence of tuberculosis is increasing in the United States. Extra-pulmonary involvement is more common in patients with HIV/AIDS. The diagnosis of Tuberculosis osteomyelitis requires a high degree of suspicion for accurate and timely diagnosis

Do contaminants originating from state-of-the-art treated wastewater impact the ecological quality of surface waters?

Since the 1980s, advances in wastewater treatment technology have led to considerably improved surface water quality in the urban areas of many high income countries. However, trace concentrations of organic wastewater-associated contaminants may still pose a key environmental hazard impairing the ecological quality of surface waters. To identify key impact factors, we analyzed the effects of a wide range of anthropogenic and environmental variables on the aquatic macroinvertebrate community. We assessed ecological water quality at 26 sampling sites in four urban German lowland river systems with a 0–100% load of state-of-the-art biological activated sludge treated wastewater. The chemical analysis suite comprised 12 organic contaminants (five phosphor organic flame retardants, two musk fragrances, bisphenol A, nonylphenol, octylphenol, diethyltoluamide, terbutryn), 16 polycyclic aromatic hydrocarbons, and 12 heavy metals. Non-metric multidimensional scaling identified organic contaminants that are mainly wastewater-associated (i.e., phosphor organic flame retardants, musk fragrances, and diethyltoluamide) as a major impact variable on macroinvertebrate species composition. The structural degradation of streams was also identified as a significant factor. Multiple linear regression models revealed a significant impact of organic contaminants on invertebrate populations, in particular on Ephemeroptera, Plecoptera, and Trichoptera species. Spearman rank correlation analyses confirmed wastewater-associated organic contaminants as the most significant variable negatively impacting the biodiversity of sensitive macroinvertebrate species. In addition to increased aquatic pollution with organic contaminants, a greater wastewater fraction was accompanied by a slight decrease in oxygen concentration and an increase in salinity. This study highlights the importance of reducing the wastewater-associated impact on surface waters. For aquatic ecosystems in urban areas this would lead to: (i) improvement of the ecological integrity, (ii) reduction of biodiversity loss, and (iii) faster achievement of objectives of legislative requirements, e.g., the European Water Framework Directive

What drives the 'August effect'?: an observational study of the effect of junior doctor changeover on out of hours work

Objective: To investigate whether measurements of junior doctor on-call workload and performance can clarify the mechanisms underlying the increase in morbidity and mortality seen after junior doctor changeover: the ‘August effect’. Design: Quantitative retrospective observational study of routinely collected data on junior doctor workload. Setting: Two large teaching hospitals in England. Participants: Task level data from a wireless out of hours system (n = 29,885 requests) used by medical staff, nurses, and allied health professionals. Main outcome measures: Number and type of tasks requested by nurses, time to completion of tasks by junior doctors. Results: There was no overall change in the number of tasks requested by nurses out of hours around the August changeover (median requests per hour 15 before and 14 after, p = 0.46). However, the number of tasks classified as urgent was greater (p = 0.016) equating to five more urgent tasks per day. After changeover, doctors took less time to complete tasks overall due to a reduction in time taken for routine tasks (median 74 vs. 66 min; p = 3.9 × 10−9). Conclusion: This study suggests that the ‘August effect’ is not due to new junior doctors completing tasks more slowly or having a greater workload. Further studies are required to investigate the causes of the increased number of urgent tasks seen, but likely factors are errors, omissions, and poor prioritization. Thus, improved training and quality control has the potential to address this increased duration of unresolved patient risk. The study also highlights the potential of newer technologies to facilitate quantitative study of clinical activity

ResearchGate versus Google Scholar: Which finds more early citations?

ResearchGate has launched its own citation index by extracting citations from documents uploaded to the site and reporting citation counts on article profile pages. Since authors may upload preprints to ResearchGate, it may use these to provide early impact evidence for new papers. This article assesses the whether the number of citations found for recent articles is comparable to other citation indexes using 2675 recently-published library and information science articles. The results show that in March 2017, ResearchGate found less citations than did Google Scholar but more than both Web of Science and Scopus. This held true for the dataset overall and for the six largest journals in it. ResearchGate correlated most strongly with Google Scholar citations, suggesting that ResearchGate is not predominantly tapping a fundamentally different source of data than Google Scholar. Nevertheless, preprint sharing in ResearchGate is substantial enough for authors to take seriously

Application of Biomarkers in Cancer Risk Management: Evaluation from Stochastic Clonal Evolutionary and Dynamic System Optimization Points of View

Aside from primary prevention, early detection remains the most effective way to decrease mortality associated with the majority of solid cancers. Previous cancer screening models are largely based on classification of at-risk populations into three conceptually defined groups (normal, cancer without symptoms, and cancer with symptoms). Unfortunately, this approach has achieved limited successes in reducing cancer mortality. With advances in molecular biology and genomic technologies, many candidate somatic genetic and epigenetic “biomarkers” have been identified as potential predictors of cancer risk. However, none have yet been validated as robust predictors of progression to cancer or shown to reduce cancer mortality. In this Perspective, we first define the necessary and sufficient conditions for precise prediction of future cancer development and early cancer detection within a simple physical model framework. We then evaluate cancer risk prediction and early detection from a dynamic clonal evolution point of view, examining the implications of dynamic clonal evolution of biomarkers and the application of clonal evolution for cancer risk management in clinical practice. Finally, we propose a framework to guide future collaborative research between mathematical modelers and biomarker researchers to design studies to investigate and model dynamic clonal evolution. This approach will allow optimization of available resources for cancer control and intervention timing based on molecular biomarkers in predicting cancer among various risk subsets that dynamically evolve over time

Conservative treatment of a comminuted cervical fracture in a racehorse

The 'classical' or 'Hangman' neck fracture involves the odontoid peg (process) of the second cervical vertebra (C2), and is described as an axial, dens or odontoid peg fracture in both the veterinary and human literature. Possible surgical treatment in both foals and adult horses requires a technique that allows decompression, anatomical alignment and stabilisation of the odontoid fracture. A limited number of surgical cases in foals have been reported in literature, but never in an adult horse. A mature Irish Thoroughbred racehorse was diagnosed with a type 2a odontoid peg fracture. Clinical signs included reluctance to move the head and neck, a left hind limb lameness and a neurological status of grade 2. The horse was treated conservatively and raced successfully five months after the diagnosed injury

Identifying Experimental Tool Use Through Confocal Microscopy

Characterizing use-wear traces quantitatively is a valid way to improve the capacity of use-wear analysis. This aim has been on specialists’ agenda since the beginning of the discipline. Micropolish quantification is especially important, as this type of trace allows the identification of worked materials. During the last decade, confocal microscopy has been used as a promising approach to address this question. Following previous efforts in plant microwear characterization (Ibáñez et al. Journal of Archaeological Science, 48, 96–103, 2014; Journal of Archaeological Science, 73, 62–81, 2016), here we test the capacity of the method for correctly grouping experimental tools used for working eight types of materials: bone, antler, wood, fresh hide, dry hide, wild cereals, domestic cereals, and reeds. We demonstrate, for the first time, that quantitative texture analysis of use-wear micropolish based on confocal microscopy can consistently identify tools used for working different contact materials. In this way, we are able to move toward using texture analysis as part of the standard functional analysis of prehistoric instruments.This study is part of the projects HAR2016-74999-P, HAR2015-68566-P, and HAR2016-81971-REDT funded by the Spanish Ministerio de Ciencia, Innovación y Universidades.Peer reviewe