A multi-center blinded study on the efficiency of phenotypic screening methods to detect glycopeptide intermediately susceptible Staphylococcus aureus (GISA) and heterogeneous GISA (h-GISA)

Contains fulltext : 52338.pdf (publisher's version ) (Open Access)BACKGROUNDS: To determine the true incidence of hGISA/GISA and its consequent clinical impact, methods must be defined that will reliably and reproducibly discriminate these resistant phenotypes from vancomycin susceptible S. aureus (VSSA). METHODS: This study assessed and compared the ability of eight Dutch laboratories under blinded conditions to discriminate VSSA from hGISA/GISA phenotypes and the intra- and inter-laboratory reproducibility of agar screening plates and the Etest method. A total of 25 blinded and unique strains (10 VSSA, 9 hGISA and 6 GISA) were categorized by the PAP-AUC method and PFGE typed to eliminate clonal duplication. All strains were deliberately added in quadruplets to evaluate intra-laboratory variability and reproducibility of the methods. Strains were tested using three agar screening methods, Brain Heart Infusion agar (BHI) + 6 microg/ml vancomycin, Mueller Hinton agar (MH) + 5 microg/ml vancomycin and MH + 5 microg/ml teicoplanin) and the Etest macromethod using a 2 McFarland inoculum. RESULTS AND DISCUSSION: The ability to detect the hGISA/GISA phenotypes varied significantly between methods and phenotypes. BHI vancomycin and MH vancomycin agar screens lacked the ability to detect hGISA. The MH teicoplanin agar screen was more sensitive but still inferior to Etest that had a sensitivity of 98.5% and 99.5%, for hGISA and GISA, respectively. Intra- and inter-laboratory reproducibility varied between methods with poorest performance seen with BHI vancomycin. CONCLUSION: This is the first multi-center blinded study to be undertaken evaluating various methods to detect GISA and hGISA. These data showed that the ability of clinical laboratories to detect GISA and hGISA varied considerably, and that screening plates with vancomycin have a poor performance in detecting hGISA

The genome and developmental transcriptome of the strongylid nematode Haemonchus contortus

Background: The barber's pole worm, Haemonchus contortus, is one of the most economically important parasites of small ruminants worldwide. Although this parasite can be controlled using anthelmintic drugs, resistance against most drugs in common use has become a widespread problem. We provide a draft of the genome and the transcriptomes of all key developmental stages of H. contortus to support biological and biotechnological research areas of this and related parasites. Results: The draft genome of H. contortus is 320 Mb in size and encodes 23,610 protein-coding genes. On a fundamental level, we elucidate transcriptional alterations taking place throughout the life cycle, characterize the parasite's gene silencing machinery, and explore molecules involved in development, reproduction, host-parasite interactions, immunity, and disease. The secretome of H. contortus is particularly rich in peptidases linked to blood-feeding activity and interactions with host tissues, and a diverse array of molecules is involved in complex immune responses. On an applied level, we predict drug targets and identify vaccine molecules. Conclusions: The draft genome and developmental transcriptome of H. contortus provide a major resource to the scientific community for a wide range of genomic, genetic, proteomic, metabolomic, evolutionary, biological, ecological, and epidemiological investigations, and a solid foundation for biotechnological outcomes, including new anthelmintics, vaccines and diagnostic tests. This first draft genome of any strongylid nematode paves the way for a rapid acceleration in our understanding of a wide range of socioeconomically important parasites of one of the largest nematode orders

Revolution postponed? Tracing the development and limitations of open content filmmaking

Networked information technologies have brought about extensive changes in the production and distribution of creative cultural work. Inspired by the widespread success of Free-Libre/Open Source Software (FLOSS), many proponents of open access advocate reconceptualisation of existing legal protection frameworks in creative works. This paper traces the attempted appropriation of Creative Commons (CC) licences by filmmakers and the consequent formation of an Open Content Filmmaking (OCF) movement. OCF proponents articulated notions of technology-enabled transformation in content creation and distribution, similar to those that inspire the visions of FLOSS and CC advocates. It examines how these creators attempted to address the relevance of openness to their own activities and develop practical open models for filmmaking. Difficulties experienced in establishing viable livelihoods with OCF (as FLOSS developers had done), created tensions between those with a pragmatic or more ideological orientation. The initial vision of a consistent OCF movement, enabled by CC, thus became fragmented. In contrast to FLOSS, where many actors were able to find ways to develop sustainable careers within the industry while contributing to Open Source Software, such generic strategies have not readily emerged for OCF. Drawing insights from Sørensen’s (1996) Social Learning framework (Learning technology, constructing culture. Sociotechnical change as social learning: University of Trondheim, STS working paper 18/96) in this paper we untangle the elaborate but often messy strategies deployed by Open Content Filmmakers (OCFs) and trace the multiple and often partial ways they have worked out to utilise CC elements and tools in producing, monetising and distributing their films

Psychosocial Treatment of Children in Foster Care: A Review

A substantial number of children in foster care exhibit psychiatric difficulties. Recent epidemiologi-cal and historical trends in foster care, clinical findings about the adjustment of children in foster care, and adult outcomes are reviewed, followed by a description of current approaches to treatment and extant empirical support. Available interventions for these children can be categorized as either symptom-focused or systemic, with empirical support for specific methods ranging from scant to substantial. Even with treatment, behavioral and emotional problems often persist into adulthood, resulting in poor functional outcomes. We suggest that self-regulation may be an important mediat-ing factor in the appearance of emotional and behavioral disturbance in these children

Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects

Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects

Breast cancer epithelial-to-mesenchymal transition: examining the functional consequences of plasticity

The epithelial-to-mesenchymal transition (EMT) is a critical developmental process that has recently come to the forefront of cancer biology. In breast carcinomas, acquisition of a mesenchymal-like phenotype that is reminiscent of an EMT, termed oncogenic EMT, is associated with pro-metastatic properties, including increased motility, invasion, anoikis resistance, immunosuppression and cancer stem cell characteristics. This oncogenic EMT is a consequence of cellular plasticity, which allows for interconversion between epithelial and mesenchymal-like states, and is thought to enable tumor cells not only to escape from the primary tumor, but also to colonize a secondary site. Indeed, the plasticity of cancer cells may explain the range of pro-metastatic traits conferred by oncogenic EMT, such as the recently described link between EMT and cancer stem cells and/or therapeutic resistance. Continued research into this relationship will be critical in developing drugs that block mechanisms of breast cancer progression, ultimately improving patient outcomes

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16–20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement