Barriers to supportive care during the Ebola virus disease outbreak in West Africa: Results of a qualitative study

© 2018 Loignon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background During the 2013–2016 West Africa Ebola outbreak, supportive care was the only non-experimental treatment option for patients with Ebola virus disease (EVD). However, providing care that would otherwise be routine for most clinical settings in the context of a highly contagious and lethal pathogen is much more challenging. The objective of this study was to document and deepen understanding of barriers to provision of supportive care in Ebola treatment units (ETUs) as perceived by those involved in care delivery during the outbreak. Methods This qualitative study consisted of 29 in-depth semi-structured interviews with stakeholders (decision-makers, physicians, nurses) involved in patient care delivery during the outbreak. Analysis consisted of interview debriefing and team-based transcript coding in NVivo10 software using thematic analysis. Findings Participants emphasized three interconnected barriers to providing high-quality supportive care during the outbreak: 1) lack of material and human resources in ETUs; 2) ETU organizational structure limiting the provision of supportive clinical care; and 3) delayed and poorly coordinated policies limiting the effectiveness of global and national responses. Participants also noted the ethical complexities of defining and enacting best clinical practices in low-income countries. They noted tension between, on one hand, scaling up minimal care and investing in clinical care preparedness to a level sustainable in West Africa and, on the other, providing a higher level of supportive care, which in low-resource health systems would require important investments. Conclusion Our findings identified potentially modifiable barriers to the delivery of supportive care to patients with EVD in West Africa. Addressing these in the inter-outbreak period will be useful to improve patient care and outcomes during inevitable future outbreaks. Promoting community trust and engagement through long-term capacity building of the healthcare workforce and infrastructure would increase both health system resilience and ability to handle other outbreaks of emerging diseases

The expression of genes involved in excitatory and inhibitory neurotransmission in turtle (Trachemys scripta) brain during anoxic submergence at 21°C and 5°C reveals the importance of cold as a preparatory cue for anoxia survival

We investigated if transcriptional responses are consistent with the arrest of synaptic activity in the anoxic turtle (Trachemys scripta) brain. Thirty-nine genes of key receptors, transporters, enzymes and regulatory proteins of inhibitory and excitatory neurotransmission were partially cloned and their expression in telencephalon of 21 °Cand 5 °C-acclimated normoxic, anoxic (24 h at 21 °C; 1 and 14 days at 5 °C) and reoxygenated (24 h at 21 °C; 13 days at 5 °C) turtles quantified by real-time RT-PCR. Gene expression was largely sustained with anoxia at 21 °C and 5 °C. However, the changes in gene expression that did occur were congruous with the decline in glutamatergic activity and the increase in GABAergic activity observed at cellular and whole organism levels. Moreover, at 21 °C, the alterations in gene expression with anoxia induced a distinct gene expression pattern compared to normoxia and reoxygenation. Strikingly, acclimation from 21 °C to 5 °C in normoxia effectuated substantial transcriptional responses. Most prominently, 56% of the excitatory neurotransmission genes were down-regulated, including most of the ones encoding the subunits composing excitatory N-methyl-D-aspartate (NMDA) and 3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) glutamate receptors. By contrast, only 26% of the inhibitory neurotransmission genes were down-regulated. Consequently, the gene expression pattern of 5 °C normoxic turtles was statistically distinct compared to that of 21 °C normoxic turtles. Overall, this study highlights that key transcriptional responses are consonant with the synaptic arrest that occurs in the anoxic turtle brain. In addition, the findings reveal that transcriptional remodelling induced by decreased temperature may serve to precondition the turtle brain for winter anoxia.publishedVersio

Maintaining Life-saving Testing for Patients With Infectious Diseases: Infectious Diseases Society of America, American Society for Microbiology, and Pan American Society for Clinical Virology Recommendations on the Regulation of Laboratory-developed Tests

In 2014, the US Food and Drug Administration (FDA) proposed to regulate laboratory-developed tests (LDTs)-diagnostics designed, manufactured, and used within a single laboratory. The Infectious Diseases Society of America, the American Society for Microbiology, and the Pan American Society for Clinical Virology recognize that the FDA is committed to protecting patients. However, our societies are concerned that the proposed regulations will limit access to testing and negatively impact infectious diseases (ID) LDTs. In this joint commentary, our societies discuss why LDTs are critical for ID patient care, hospital infection control, and public health responses. We also highlight how the FDA's proposed regulation of LDTs could impair patient access to life-saving tests and stifle innovation in ID diagnostics. Finally, our societies make specific recommendations for the FDA's consideration to reduce the burden of the proposed new rules on clinical laboratories and protect patients' access to state-of-the art, quality LDTs

The mutational landscape of melanoma brain metastases presenting as the first visceral site of recurrence.

Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440Brain metastases are a major cause of melanoma-related mortality and morbidity. We undertook whole-exome sequencing of 50 tumours from patients undergoing surgical resection of brain metastases presenting as the first site of visceral disease spread and validated our findings in an independent dataset of 18 patients. Brain metastases had a similar driver mutational landscape to cutaneous melanomas in TCGA. However, KRAS was the most significantly enriched driver gene, with 4/50 (8%) of brain metastases harbouring non-synonymous mutations. Hotspot KRAS mutations were mutually exclusive from BRAFV600, NRAS and HRAS mutations and were associated with a reduced overall survival from the resection of brain metastases (HR 10.01, p = 0.001). Mutations in KRAS were clonal and concordant with extracranial disease, suggesting that these mutations are likely present within the primary. Our analyses suggest that KRAS mutations could help identify patients with primary melanoma at higher risk of brain metastases who may benefit from more intensive, protracted surveillance

A citizen science approach: A detailed ecological assessment of subtropical reefs at point lookout, Australia

Subtropical reefs provide an important habitat for flora and fauna, and proper monitoring is required for conservation. Monitoring these exposed and submerged reefs is challenging and available resources are limited. Citizen science is increasing in momentum, as an applied research tool and in the variety of monitoring approaches adopted. This paper aims to demonstrate an ecological assessment and mapping approach that incorporates both top-down (volunteer marine scientists) and bottom-up (divers/community) engagement aspects of citizen science, applied at a subtropical reef at Point Lookout, Southeast Queensland, Australia. Marine scientists trained fifty citizen scientists in survey techniques that included mapping of habitat features, recording of substrate, fish and invertebrate composition, and quantifying impacts (e.g., occurrence of substrate damage, presence of litter). In 2014 these volunteers conducted four seasonal surveys along semi-permanent transects, at five sites, across three reefs. The project presented is a model on how citizen science can be conducted in a marine environment through collaboration of volunteer researchers, non-researchers and local marine authorities. Significant differences in coral and algal cover were observed among the three sites, while fluctuations in algal cover were also observed seasonally. Differences in fish assemblages were apparent among sites and seasons, with subtropical fish groups observed more commonly in colder seasons. The least physical damage occurred in the most exposed sites (Flat Rock) within the highly protected marine park zones. The broad range of data collected through this top-down/bottomup approach to citizen science exemplifies the projects' value and application for identifying ecosystem trends or patterns. The results of the project support natural resource and marine park management, providing a valuable contribution to existing scientific knowledge and the conservation of local reefs

Systematic meta-analyses, field synopsis and global assessment of the evidence of genetic association studies in colorectal cancer

Objective: To provide an understanding of the role of common genetic variations in colorectal cancer (CRC) risk, we report an updated field synopsis and comprehensive assessment of evidence to catalogue all genetic markers for CRC (CRCgene2). Design: We included 869 publications after parallel literature review and extracted data for 1063 polymorphisms in 303 different genes. Meta-Analyses were performed for 308 single nucleotide polymorphisms (SNPs) in 158 different genes with at least three independent studies available for analysis. Scottish, Canadian and Spanish data from genome-wide association studies (GWASs) were incorporated for the meta-Analyses of 132 SNPs. To assess and classify the credibility of the associations, we applied the Venice criteria and Bayesian False-Discovery Probability (BFDP). Genetic associations classified as â € positive' and â € less-credible positive' were further validated in three large GWAS consortia conducted in populations of European origin. Results: We initially identified 18 independent variants at 16 loci that were classified as â € positive' polymorphisms for their highly credible associations with CRC risk and 59 variants at 49 loci that were classified as â € less-credible positive' SNPs; 72.2% of the â € positive' SNPs were successfully replicated in three large GWASs and the ones that were not replicated were downgraded to â € less-credible' positive (reducing the â € positive' variants to 14 at 11 loci). For the remaining 231 variants, which were previously reported, our meta-Analyses found no evidence to support their associations with CRC risk. Conclusion: The CRCgene2 database provides an updated list of genetic variants related to CRC risk by using harmonised methods to assess their credibility.</p

A Global Overview of the Genetic and Functional Diversity in the Helicobacter pylori cag Pathogenicity Island

The Helicobacter pylori cag pathogenicity island (cagPAI) encodes a type IV secretion system. Humans infected with cagPAI–carrying H. pylori are at increased risk for sequelae such as gastric cancer. Housekeeping genes in H. pylori show considerable genetic diversity; but the diversity of virulence factors such as the cagPAI, which transports the bacterial oncogene CagA into host cells, has not been systematically investigated. Here we compared the complete cagPAI sequences for 38 representative isolates from all known H. pylori biogeographic populations. Their gene content and gene order were highly conserved. The phylogeny of most cagPAI genes was similar to that of housekeeping genes, indicating that the cagPAI was probably acquired only once by H. pylori, and its genetic diversity reflects the isolation by distance that has shaped this bacterial species since modern humans migrated out of Africa. Most isolates induced IL-8 release in gastric epithelial cells, indicating that the function of the Cag secretion system has been conserved despite some genetic rearrangements. More than one third of cagPAI genes, in particular those encoding cell-surface exposed proteins, showed signatures of diversifying (Darwinian) selection at more than 5% of codons. Several unknown gene products predicted to be under Darwinian selection are also likely to be secreted proteins (e.g. HP0522, HP0535). One of these, HP0535, is predicted to code for either a new secreted candidate effector protein or a protein which interacts with CagA because it contains two genetic lineages, similar to cagA. Our study provides a resource that can guide future research on the biological roles and host interactions of cagPAI proteins, including several whose function is still unknown

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements