Pipeline for Large-Scale Microdroplet Bisulfite PCR-Based Sequencing Allows the Tracking of Hepitype Evolution in Tumors

Cytosine methylation provides an epigenetic level of cellular plasticity that is important for development, differentiation and cancerogenesis. We adopted microdroplet PCR to bisulfite treated target DNA in combination with second generation sequencing to simultaneously assess DNA sequence and methylation. We show measurement of methylation status in a wide range of target sequences (total 34 kb) with an average coverage of 95% (median 100%) and good correlation to the opposite strand (rho = 0.96) and to pyrosequencing (rho = 0.87). Data from lymphoma and colorectal cancer samples for SNRPN (imprinted gene), FGF6 (demethylated in the cancer samples) and HS3ST2 (methylated in the cancer samples) serve as a proof of principle showing the integration of SNP data and phased DNA-methylation information into “hepitypes” and thus the analysis of DNA methylation phylogeny in the somatic evolution of cancer

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Interdependence

How should we respond to the increasingly dense bundle of economic, cultural and ecological interconnections that span the globe and stretch into the future? What kinds of ethical and public engagements are demanded of researchers who work on global environmental, economic and social issues? The term interdependence may provide a powerful framework for advancing thinking and debate both within academia and among wider publics in relation to these questions. Members of the Open University's Geography Department have been working with partners to build the Interdependence Day project. The project combines research, cultural work, communications and public participation in an attempt to make sense of our responsibilities to people distant in space and time, and to the nonhuman natural world. This article reviews nearly a century of deployments of the term interdependence in political and academic writing, introduces the distinctive work that might be done with the term in the critical social sciences, and outlines the Interdependence Day project

Before Disaster Strikes: A Pilot Intervention to Improve Pediatric Trainees\u27 Knowledge of Disaster Medicine

OBJECTIVE: Because training in pediatric disaster medicine (PDM) is neither required nor standardized for pediatric residents, we designed and integrated a PDM course into the curriculum of a pediatric residency program and assessed if participation increased participants\u27 knowledge of managing disaster victims. METHODS: We adapted and incorporated a previously studied PDM course into a small-sized pediatric residency program. The curriculum consisted of didactic lectures and experiential learning via simulation with structured debriefing. With IRB approval, the authors conducted a longitudinal series of pretests and posttests to assess knowledge and perceptions. RESULTS: Sixteen eligible residents completed the intervention. Before the course, none of the residents reported experience treating disaster victims. Pairwise comparison of scores revealed a 35% improvement in scores immediately after completing the course (95% confidence interval, 22.73%-47.26%; P \u3c 0.001) and a 23.73% improvement 2 months later (95% confidence interval, 7.12%-40.34%; P \u3c 0.01). CONCLUSIONS: Residents who completed this course increased their knowledge of PDM with moderate retention of knowledge gained. There was a significant increase in perceived ability to manage patients in a disaster situation after this educational intervention and the residents\u27 confidence was preserved 2 months later. This PDM course may be used in future formulation of a standardized curriculum

Investigating the Gap Between Research and Practice in Additive Manufacturing

Additive manufacturing (AM) provides opportunities to design objects differently than traditional manufacturing methods allow, but only if designers understand the possibilities AM presents. In this study, we examined whether an AM workshop combined with an idea generation session could inspire engineering professionals to use AM solutions to solve current technical problems they face. All subjects were employees at an organization that will be referred to as Company X, a multinational commercial organization based in North America. During the study, we collected ideas for 24 projects generated before and after a training workshop focused on design for AM. In the workshop, we provided three hours of instruction about design for two metal-based AM processes. The participants’ ideas were assessed using four specific metrics: (1) cost, (2) time, (3) completeness of solution, and (4) quality, which was a function of feasibility, usefulness, and novelty. Using these data, we explored whether the workshop was effective in inspiring the participants to use AM methods and techniques from AM research in their concept generation and whether participants’ AM solutions showed improvement in cost, implementation time, and quality over non-AM designs generated before the workshop.Mechanical Engineerin

Surf and turf vision: Patterns and predictors of visual acuity in compound eye evolution

Eyes have the flexibility to evolve to meet the ecological demands of their users. Relative to camera-type eyes, the fundamental limits of optical diffraction in arthropod compound eyes restrict the ability to resolve fine detail (visual acuity) to much lower degrees. We tested the capacity of several ecological factors to predict arthropod visual acuity, while simultaneously controlling for shared phylogenetic history. In this study, we have generated the most comprehensive review of compound eye visual acuity measurements to date, containing 385 species that span six of the major arthropod classes. An arthropod phylogeny, made custom to this database, was used to develop a phylogenetically-corrected generalized least squares (PGLS) linear model to evaluate four ecological factors predicted to underlie compound eye visual acuity: environmental light intensity, foraging strategy (predator vs. non-predator), horizontal structure of the visual scene, and environmental medium (air vs. water). To account for optical constraints on acuity related to animal size, body length was also included, but this did not show a significant effect in any of our models. Rather, the PGLS analysis revealed that the strongest predictors of compound eye acuity are described by a combination of environmental medium, foraging strategy, and environmental light intensity

Role of the AcrAB-TolC efflux pump in determining susceptibility of Haemophilus influenzae to the novel peptide deformylase inhibitor LBM415.

Haemophilus influenzae isolates vary widely in their susceptibilities to the peptide deformylase inhibitor LBM415 (MIC range, 0.06 to 32 microg/ml); however, on average, they are less susceptible than gram-positive organisms, such as Staphylococcus aureus and Streptococcus pneumoniae. Insertional inactivation of the H. influenzae acrB or tolC gene in strain NB65044 (Rd strain KW20) increased susceptibility to LBM415, confirming a role for the AcrAB-TolC pump in determining resistance. Consistent with this, sequencing of a PCR fragment generated with primers flanking the acrRA region from an LBM415-hypersusceptible H. influenzae clinical isolate revealed a genetic deletion of acrA. Inactivation of acrB or tolC in several clinical isolates with atypically reduced susceptibility to LBM415 (MIC of 16 microg/ml or greater) significantly increased susceptibility, confirming that the pump is also a determinant of decreased susceptibility in these clinical isolates. Examination of acrR, encoding the putative repressor of pump gene expression, from several of these strains revealed mutations introducing frameshifts, stop codons, and amino acid changes relative to the published sequence, suggesting that loss of pump repression leads to decreased susceptibility. Supporting this, NB65044 acrR mutants selected by exposure to LBM415 at 8 microg/ml had susceptibilities to LBM415 and other pump substrates comparable to the least sensitive clinical isolates and showed increased expression of pump genes