Faecal microbiota transplant to ERadicate gastrointestinal carriage of Antibiotic Resistant Organisms (FERARO): a prospective, randomised placebo-controlled feasibility trial.

INTRODUCTION: Antimicrobial resistance is rising, largely due to the indiscriminate use of antimicrobials. The human gut is the largest reservoir of antibiotic resistant bacteria (ARB). Individuals colonised with ARB have the potential to spread these organisms both in the community and hospital settings. Infections with ARB such as extended spectrum beta-lactamase producing enterobacteriales (ESBL-E) and carbapenemase producing enterobacteriales (CPE) are more difficult to treat and are associated with an increased morbidity and mortality. Presently, there is no effective decolonisation strategy for these ARB. Faecal microbiota transplant (FMT) has emerged as a potential strategy for decolonisation of ARB from the human gut, however there is significant uncertainty about the feasibility, effectiveness and safety of using this approach. METHODS AND ANALYSIS: Prospective, randomised, patient-blinded, placebo-controlled feasibility trial of FMT to eradicate gastrointestinal carriage of ARB. Eighty patients with a recent history of invasive infection secondary to ESBL-E or CPE and persistent gastrointestinal carriage will be randomised 1:1 to receive encapsulated FMT or placebo. The primary outcome measure is consent rate (as a proportion of patients who fulfil inclusion/exclusion criteria); this will be used to determine if a substantive trial is feasible. Participants will be followed up at 1 week, 1 month, 3 months and 6 months and monitored for adverse events as well as gastrointestinal carriage rates of ARB after intervention. ETHICS AND DISSEMINATION: Research ethics approval was obtained by London-City and East Research Ethics Committee (ref 20/LO/0117). Trial results will be published in a peer-reviewed journal and presented at international conferences. TRIAL REGISTRATION NUMBER: ISRCTN registration number 34 467 677 and EudraCT number 2019-001618-41.

Regulation, risk and safety of Faecal Microbiota Transplant.

From its origins as a left-field, experimental, and even "maverick" intervention, faecal microbiota transplantation (FMT) is now a well-recognised, accepted, and potentially life-saving therapeutic strategy, for the management of recurrent Clostridiodes difficile infection (rCDI). It is being investigated as a treatment for a growing number of diseases including hepatic encephalopathy and eradication of antimicrobial resistant organisms, and the list of indications will likely expand in the future. There is no universally accepted definition of what FMT is, and its mechanism of action remains incompletely understood; this has likely contributed to the breadth of approaches to regulation depending on interpretation. In the UK FMT is considered a medicinal product, in North America, a biological product, whereas in parts of Europe, it is considered a human cell/tissue product. Regulation seeks to improve quality and safety, however, lack of standardisation creates confusion, and overly restrictive regulation may hamper widespread access and discourage research using FMT. FMT is generally considered safe, especially if rigorous donor screening and testing is conducted. Most short-term risks are associated with the delivery method (e.g. colonoscopy). Longer term risks are less well described but longitudinal follow-up of treated cohorts is in place to assess for this, and no signal towards harm has been found to date. Rarely it has been associated with adverse outcomes including the transmission of antibiotic resistant bacteria, and even death. It is vital patients undergoing FMT are well informed to the currently appreciated risks and benefits before proceeding.

An open toolkit for tracking open science partnership implementation and impact.

Serious concerns about the way research is organized collectively are increasingly being raised. They include the escalating costs of research and lower research productivity, low public trust in researchers to report the truth, lack of diversity, poor community engagement, ethical concerns over research practices, and irreproducibility. Open science (OS) collaborations comprise of a set of practices including open access publication, open data sharing and the absence of restrictive intellectual property rights with which institutions, firms, governments and communities are experimenting in order to overcome these concerns. We gathered two groups of international representatives from a large variety of stakeholders to construct a toolkit to guide and facilitate data collection about OS and non-OS collaborations. Ultimately, the toolkit will be used to assess and study the impact of OS collaborations on research and innovation. The toolkit contains the following four elements: 1) an annual report form of quantitative data to be completed by OS partnership administrators; 2) a series of semi-structured interview guides of stakeholders; 3) a survey form of participants in OS collaborations; and 4) a set of other quantitative measures best collected by other organizations, such as research foundations and governmental or intergovernmental agencies. We opened our toolkit to community comment and input. We present the resulting toolkit for use by government and philanthropic grantors, institutions, researchers and community organizations with the aim of measuring the implementation and impact of OS partnership across these organizations. We invite these and other stakeholders to not only measure, but to share the resulting data so that social scientists and policy makers can analyse the data across projects.

Building the infrastructure to make science metrics more scientific.

Research leaders, policy makers and science strategists need evidence to support decision-making around research funding investment, policy and strategy.  In recent years there has been a rapid expansion in the data sources available that shed light onto aspects of research quality, excellence, use, re-use and attention, and engagement. This is at a time when the modes and routes to share and communicate research findings and data are also changing.  In this opinion piece, we outline a series of considerations and interventions that are needed to ensure that research metric development is accompanied by appropriate scrutiny and governance, to properly support the needs of research assessors and decision-makers, while securing the confidence of the research community. Key among these are: agreed 'gold standards' around datasets and methodologies; full transparency around the calculation and derivation of research-related indicators; and a strategy and roadmap to take the discipline of scientific indicators and research assessment to a more robust and sustainable place.

Alternative perspectives on impact: the potential of ALMs and altmetrics to inform funders about research impact.

More evidence of the meaning and validity of ALMs and altmetrics, coupled with greater consistency and transparency in their presentation, would enable research funders to explore their potential value and identify appropriate use cases.

Mapping global health research investments, time for new thinking--a Babel Fish for research data.

Today we have an incomplete picture of how much the world is spending on health and disease-related research and development (R&D). As such it is difficult to align, or even begin to coordinate, health R&D investments with international public health priorities. Current efforts to track and map global health research investments are complex, resource-intensive, and caveat-laden. An ideal situation would be for all research funding to be classified using a set of common standards and definitions. However, the adoption of such a standard by everyone is not a realistic, pragmatic or even necessary goal. It is time for new thinking informed by the innovations in automated online translation - e.g. Yahoo's Babel Fish. We propose a feasibility study to develop a system that can translate and map the diverse research classification systems into a common standard, allowing the targeting of scarce research investments to where they are needed most.

Tracking the impact of research on policy and practice: investigating the feasibility of using citations in clinical guidelines for research evaluation.

OBJECTIVES: To investigate the feasibility of using research papers cited in clinical guidelines as a way to track the impact of particular funding streams or sources. SETTING: In recent years, medical research funders have made efforts to enhance the understanding of the impact of their funded research and to provide evidence of the 'value' of investments in particular areas of research. One of the most challenging areas of research evaluation is around impact on policy and practice. In the UK, the National Institute of Health and Clinical Excellence (NICE) provide clinical guidelines, which bring together current high-quality evidence on the diagnosis and treatment of clinical problems. Research referenced in these guidelines is an indication of its potential to have real impact on health policy and practice. DESIGN: This study is based on analysis of the authorship and funding attribution of research cited in two NICE clinical guidelines: dementia and chronic obstructive pulmonary disease. RESULTS: Analysis identified that around a third of papers cited in the two NICE guidelines had at least one author based in the UK. In both cases, about half of these UK attributed papers contained acknowledgements which allowed the source of funding for the research to be identified. The research cited in these guidelines was found to have been supported by a diverse set of funders from different sectors. The study also investigated the contribution of research groups based in universities, industry and the public sector. CONCLUSIONS: The study found that there is great potential for guidelines to be used as sources of information on the quality of the research used in their development and that it is possible to track the source of the funding of the research. The challenge is in harnessing the relevant information to track this in an efficient way.

Looking for landmarks: the role of expert review and bibliometric analysis in evaluating scientific publication outputs.

OBJECTIVE: To compare expert assessment with bibliometric indicators as tools to assess the quality and importance of scientific research papers. METHODS AND MATERIALS: Shortly after their publication in 2005, the quality and importance of a cohort of nearly 700 Wellcome Trust (WT) associated research papers were assessed by expert reviewers; each paper was reviewed by two WT expert reviewers. After 3 years, we compared this initial assessment with other measures of paper impact. RESULTS: Shortly after publication, 62 (9%) of the 687 research papers were determined to describe at least a 'major addition to knowledge' -6 were thought to be 'landmark' papers. At an aggregate level, after 3 years, there was a strong positive association between expert assessment and impact as measured by number of citations and F1000 rating. However, there were some important exceptions indicating that bibliometric measures may not be sufficient in isolation as measures of research quality and importance, and especially not for assessing single papers or small groups of research publications. CONCLUSION: When attempting to assess the quality and importance of research papers, we found that sole reliance on bibliometric indicators would have led us to miss papers containing important results as judged by expert review. In particular, some papers that were highly rated by experts were not highly cited during the first three years after publication. Tools that link expert peer reviews of research paper quality and importance to more quantitative indicators, such as citation analysis would be valuable additions to the field of research assessment and evaluation.

Identification of human and mouse CatSper3 and CatSper4 genes: characterisation of a common interaction domain and evidence for expression in testis.

BACKGROUND: CatSper1 and CatSper2 are two recently identified channel-like proteins, which show sperm specific expression patterns. Through targeted mutagenesis in the mouse, CatSper1 has been shown to be required for fertility, sperm motility and for cAMP induced Ca2+ current in sperm. Both channels resemble a single pore forming repeat from a four repeat voltage dependent Ca2+ /Na+ channel. However, neither CatSper1 or CatSper2 have been shown to function as cation channels when transfected into cells, singly or in conjunction. As the pore forming units of voltage gated cation channels form a tetramer it has been suggested that the known CatSper proteins require additional subunits and/or interaction partners to function. RESULTS: Using in silico gene identification and prediction techniques, we have identified two further members of the CatSper family, CatSper3 and Catsper4. Each carries a single channel-forming domain with the predicted pore-loop containing the consensus sequence TxDxW. Each of the new CatSper genes has evidence for expression in the testis. Furthermore we identified coiled-coil protein-protein interaction domains in the C-terminal tails of each of the CatSper channels, implying that CatSper channels 1,2,3 and 4 may interact directly or indirectly to form a functional tetramer. CONCLUSIONS: The topological and sequence relationship of CatSper1 and CatSper2 to the four repeat Ca2+ /Na+ channels suggested other members of this family may exist. We have identified a further two novel CatSper genes, conserved in both the human and mouse genomes. Furthermore, all four of the CatSper proteins are predicted to contain a common coiled-coil protein-protein interaction domain in their C-terminal tail. Coupled with expression data this leads to the hypothesis that the CatSper proteins form a functional hetero-tetrameric channel in sperm.