Genome editing in context

Genome editing has created a new continuum between what might occur in nature and what can only occur in the laboratory. Remarkable though it is that we have developed the capacity to predictably and finely alter genetic codes it is perhaps as remarkable that a new technology enabling this has appeared, spread widely and become easily affordable and accessible within such a short timescale. The speed at which the CRISPR/Cas9 technology use has grown almost defies comparison. A factor contributing to this, and also to the complexity of the surrounding debates, is the sheer breadth of possible applications of the technology, in terms of target organisms and genetic constructs, and in terms of the processes it could be used to influence. These combined characteristics, while opening a world of possibilities for science and society, also present a pressing and complex set of questions about governance and regulation; it is difficult to have appropriately informed discussion let alone for regulation to keep pace.

Clinical stakeholders' opinions on the use of selective decontamination of the digestive tract in critically ill patients in intensive care units : an international Delphi study

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Accessibility, sustainability, excellence: How to expand access to research publications. Executive summary

This article is a summary, by the authors, of a 140-page report prepared in 2012 by the UK Working Group on Expanding Access to Published Research Findings, chaired by British sociologist and academic administrator Janet Finch, DBE. The Working Group was charged with recommending how to develop a model that would be effective and sustainable over time, for expanding access to the published fi ndings of research. The whole report, which can be accessed at http://www.researchinfonet.org/wp-content/uploads/2012/06/Finch-Group-report-FINAL-VERSION.pdf [http://tinyurl.com/d2lxqks], has been published under a Creative Commons License Attribution 3.0 Unported. This is the fi rst of a series of Perspectives articles devoted to the Open Access Initiative that will be published in INTERNATIONAL MICROBIOLOGY. Our journal already published an Editorial on the topic in 2004 (Guerrero R & Piqueras M, Int Microbiol 7:157-161), and strongly supports open access. [Int Microbiol 2013; 16(2):125-132

Accessibility, sustainability, excellence: how to expand access to research publications. Executive summary

This article is a summary, by the authors, of a 140-page report prepared in 2012 by the UK Working Group on Expanding Access to Published Research Findings, chaired by British sociologist and academic administrator Janet Finch, DBE. The Working Group was charged with recommending how to develop a model that would be effective and sustainable over time, for expanding access to the published fi ndings of research. The whole report, which can be accessed at http://www.researchinfonet.org/wp-content/uploads/2012/06/Finch-Group-report-FINAL-VERSION.pdf [http://tinyurl.com/d2lxqks], has been published under a Creative Commons License Attribution 3.0 Unported. This is the fi rst of a series of Perspectives articles devoted to the Open Access Initiative that will be published in INTERNATIONAL MICROBIOLOGY. Our journal already published an Editorial on the topic in 2004 (Guerrero R & Piqueras M, Int Microbiol 7:157-161), and strongly supports open access. [Int Microbiol 2013; 16(2):125-132

The views of health care professionals about selective decontamination of the digestive tract: An international, theoretically informed interview study

Purpose: Selective Decontamination of the Digestive tract (SDD) as a prophylactic intervention improves hospital-acquired infection and survival rates. Uptake of SDD is low and remains controversial. This study applied the Theoretical Domains Framework (TDF) to assess ICU clinicians’ views about SDD in regions with limited or no adoption of SDD. Materials and Methods: Participants were health professionals with ‘decisional authority’ for the adoption of SDD. Semistructured interviews were conducted as the first round of a Delphi study. Views about SDDadoption, delivery and further SDD research were explored. Directed content analysis of interview data identified sub-themes which informed item development for subsequent Delphi rounds. Linguistic features of interview data were also explored. Results: 141 participants provided interview data. Fifty-six sub-themes were identified; 46 were common across regions. Beliefs about consequences was the most widely elaborated theme. Linguistic features of how participants discussed SDD included caution expressed when discussing the risks and benefits and words such as worry, anxiety and fear when discussing potential antibiotic resistance associated with SDD. Conclusions: We identified salient beliefs, barriers and facilitators to SDD adoption and delivery. What participants said about SDD and the way in which they said it demonstrated the degree of clinical caution, uncertainty and concern that SDD evokes

Developing a collaborative agenda for humanities and social scientific research on laboratory animal science and welfare.

Improving laboratory animal science and welfare requires both new scientific research and insights from enquiry in the humanities and social sciences. Whilst scientific research provides evidence to replace, reduce and refine procedures involving laboratory animals (the ‘3Rs’), work in the humanities and social sciences can help understand the social, economic and cultural processes that enhance or impede humane ways of knowing and working with laboratory animals. However, communication across these disciplinary perspectives is currently limited, and they frame questions, generate results, engage users, and seek to influence policy in different ways. To facilitate dialogue and future research at this interface, we convened an interdisciplinary group of 45 life scientists, social scientists, humanities scholars, non-governmental organisations and policy-makers to generate a collaborative research agenda. This drew on other agenda-setting exercises in science policy, using a collaborative and deliberative approach for the identification of research priorities. Participants were recruited from across the community, invited to submit research questions and vote on their priorities. They then met at an interactive workshop in the UK, discussed all 136 questions submitted, and collectively defined the 30 most important issues for the group. The output is a collaborative future agenda for research in the humanities and social sciences on laboratory animal science and welfare. The questions indicate a demand for new research in the humanities and social sciences to inform emerging discussions and priorities on the governance and practice of laboratory animal research, including around: international harmonisation, openness and public engagement, ‘cultures of care’, harm-benefit analysis and the future of the 3Rs. The process underlines the value of interdisciplinary exchange for improving mutual understanding of different research cultures and identifies ways of enhancing the effectiveness of future research at the interface between the humanities, social sciences, science and science policy

Effect of a Perioperative, Cardiac Output-Guided Hemodynamic Therapy Algorithm on Outcomes Following Major Gastrointestinal Surgery A Randomized Clinical Trial and Systematic Review

Importance: small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm.Objective: to evaluate the clinical effectiveness of a perioperative, cardiac output–guided hemodynamic therapy algorithm.Design, setting, and participants: OPTIMISE was a pragmatic, multicenter, randomized, observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom. An updated systematic review and meta-analysis were also conducted including randomized trials published from 1966 to February 2014.Interventions: patients were randomly assigned to a cardiac output–guided hemodynamic therapy algorithm for intravenous fluid and inotrope (dopexamine) infusion during and 6 hours following surgery (n=368) or to usual care (n=366).Main outcomes and measures: the primary outcome was a composite of predefined 30-day moderate or major complications and mortality. Secondary outcomes were morbidity on day 7; infection, critical care–free days, and all-cause mortality at 30 days; all-cause mortality at 180 days; and length of hospital stay.Results: baseline patient characteristics, clinical care, and volumes of intravenous fluid were similar between groups. Care was nonadherent to the allocated treatment for less than 10% of patients in each group. The primary outcome occurred in 36.6% of intervention and 43.4% of usual care participants (relative risk [RR], 0.84 [95% CI, 0.71-1.01]; absolute risk reduction, 6.8% [95% CI, ?0.3% to 13.9%]; P?=?.07). There was no significant difference between groups for any secondary outcomes. Five intervention patients (1.4%) experienced cardiovascular serious adverse events within 24 hours compared with none in the usual care group. Findings of the meta-analysis of 38 trials, including data from this study, suggest that the intervention is associated with fewer complications (intervention, 488/1548 [31.5%] vs control, 614/1476 [41.6%]; RR, 0.77 [95% CI, 0.71-0.83]) and a nonsignificant reduction in hospital, 28-day, or 30-day mortality (intervention, 159/3215 deaths [4.9%] vs control, 206/3160 deaths [6.5%]; RR, 0.82 [95% CI, 0.67-1.01]) and mortality at longest follow-up (intervention, 267/3215 deaths [8.3%] vs control, 327/3160 deaths [10.3%]; RR, 0.86 [95% CI, 0.74-1.00]).Conclusions and relevance: in a randomized trial of high-risk patients undergoing major gastrointestinal surgery, use of a cardiac output–guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and 30-day mortality. However, inclusion of these data in an updated meta-analysis indicates that the intervention was associated with a reduction in complication rate

An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection.peer-reviewe