Improving planning, design, reporting and scientific quality of animal experiments by using the Gold Standard Publication Checklist, in addition to the ARRIVE guidelines

Several studies have demonstrated serious omissions in the way research that use animals is reported. In order to improve the quality of reporting of animal experiments, the Animals in research: reporting in vivo experiments (ARRIVE) Guidelines were published in the British Journal of Pharmacology in August 2010

The Gold Standard Publication Checklist (GSPC) for improved design, reporting and scientific quality of animal studies GSPC versus ARRIVE guidelines

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Enhancing search efficiency by means of a search filter for finding all studies on animal experimentation in PubMed

Collecting and analysing all available literature before starting an animal experiment is important and it is indispensable when writing a systematic review (SR) of animal research. Writing such review prevents unnecessary duplication of animal studies and thus unnecessary animal use (Reduction). One of the factors currently impeding the production of ‘high-quality’ SRs in laboratory animal science is the fact that searching for all available literature concerning animal experimentation is rather difficult. In order to diminish these difficulties, we developed a search filter for PubMed to detect all publications concerning animal studies. This filter was compared with the method most frequently used, the PubMed Limit: Animals, and validated further by performing two PubMed topic searches. Our filter performs much better than the PubMed limit: it retrieves, on average, 7% more records. Other important advantages of our filter are that it also finds the most recent records and that it is easy to use. All in all, by using our search filter in PubMed, all available literature concerning animal studies on a specific topic can easily be found and assessed, which will help in increasing the scientific quality and thereby the ethical validity of animal experiments

Quantitative MR in dystrophic muscle : It's more than fat

The overall aim of this thesis was to combine various quantitative MR measurements and compare these combined measurements between Duchenne Muscular Dystrophy (DMD) patients and healthy age-matched controls both on a cross-sectional and longitudinal level, in order to generate a better understanding of the underlying pathophysiology of the disease and ideally to determine the potential of these MRI outcome parameters for monitoring muscle tissue changes in a clinical setting. In order to achieve this aim, we assessed the effect of spatial localization, data quality and confounding effects on the quantification process for various MR outcome parameters. We found that, sufficient SNR is a prerequisite for reliable MR measurements. In addition, we found that út and water T2 changes need to be monitored in DTI in skeletal muscle. Second, we used a combination of quantitative MRI and spatially resolved 31P MRS to contribute to the understanding of the pathophysiology in DMD. We found that PDE-levels and water T2 changes occurred prior to the replacement of muscle tissue by fat. Subsequently, we found that PDE-levels had the potential to function as a marker to monitor muscle tissue changes in DMDPhilips Medical HealthcareLUMC / Geneeskunde Repositoriu

Are Electronic Editions Inherently Obsolete?

This paper looks at some of the theoretical background behind technologies being developed at the Australian Scholarly Editions Centre for a new form of resource for the study of historical works of literature. Some of the unique features of these technologies are that they support conflicting points of view (including conflicting structural markup) and also allow simultaneous, parallel development by multiple researchers on the same parts of the work. Archivists talk about maintaining digital assets through use rather than preservation so that demand for the asset will ensure its propagation long-term. To achieve this end a digital asset must be as versatile as possible so as to meet all requirements for those who might want to use it. If it does not do this it will be superseded by something that does meet those needs creating new witness states in the record and confusion for future literary researchers. The word "edition" is a term from the print paradigm and implies a fixed publication with features proscribed by the medium. Technical and feature obsolescence will eventually cause these "electronic editions" to be either superseded or lost from the human record. A better type of resource is one that can be continually developed by its multiple users, while maintaining its textual authenticity, thereby ensuring its continued maintenance long after its original creator is gone. This paper looks at the reasoning behind the need for a new paradigm for creating and maintaining text-based digital assets and provides examples of a work in progress that solves some of the inherent limitations of the print-based "edition" paradigm.Hosted by the Scholarly Text and Imaging Service (SETIS), the University of Sydney Library, and the Research Institute for Humanities and Social Sciences (RIHSS), the University of Sydney

A search filter for increasing the retrieval of animal studies in Embase

Collecting and analysing all available literature before starting a new animal experiment is important and it is indispensable when writing systematic reviews of animal research. In practice, finding all animal studies relevant to a specific research question turns out to be anything but simple. In order to facilitate this search process, we previously developed a search filter for retrieving animal studies in the most often used biomedical database, PubMed. It is a general requirement for systematic reviews, however, that at least two databases are searched. In this report, we therefore present a similar search filter for a second important database, namely Embase. We show that our filter retrieves more animal studies than (a combination of) the options currently available in Embase. Our search filters for PubMed and Embase therefore represent valuable tools for improving the quality of (systematic) reviews and thereby of new animal experiments

Retrospective harm benefit analysis of pre-clinical animal research for six treatment interventions

The harm benefit analysis (HBA) is the cornerstone of animal research regulation and is considered to be a key ethical safeguard for animals. The HBA involves weighing the anticipated benefits of animal research against its predicted harms to animals but there are doubts about how objective and accountable this process is.i. To explore the harms to animals involved in pre-clinical animal studies and to assess these against the benefits for humans accruing from these studies; ii. To test the feasibility of conducting this type of retrospective HBA.Data on harms were systematically extracted from a sample of pre-clinical animal studies whose clinical relevance had already been investigated by comparing systematic reviews of the animal studies with systematic reviews of human studies for the same interventions (antifibrinolytics for haemorrhage, bisphosphonates for osteoporosis, corticosteroids for brain injury, Tirilazad for stroke, antenatal corticosteroids for neonatal respiratory distress and thrombolytics for stroke). Clinical relevance was also explored in terms of current clinical practice. Harms were categorised for severity using an expert panel. The quality of the research and its impact were considered. Bateson's Cube was used to conduct the HBA.The most common assessment of animal harms by the expert panel was 'severe'. Reported use of analgesia was rare and some animals (including most neonates) endured significant procedures with no, or only light, anaesthesia reported. Some animals suffered iatrogenic harms. Many were kept alive for long periods post-experimentally but only 1% of studies reported post-operative care. A third of studies reported that some animals died prior to endpoints. All the studies were of poor quality. Having weighed the actual harms to animals against the actual clinical benefits accruing from these studies, and taking into account the quality of the research and its impact, less than 7% of the studies were permissible according to Bateson's Cube: only the moderate bisphosphonate studies appeared to minimise harms to animals whilst being associated with benefit for humans.This is the first time the accountability of the HBA has been systematically explored across a range of pre-clinical animal studies. The regulatory systems in place when these studies were conducted failed to safeguard animals from severe suffering or to ensure that only beneficial, scientifically rigorous research was conducted. Our findings indicate a pressing need to: i. review regulations, particularly those that permit animals to suffer severe harms; ii. reform the processes of prospectively assessing pre-clinical animal studies to make them fit for purpose; and iii. systematically evaluate the benefits of pre-clinical animal research to permit a more realistic assessment of its likely future benefits

S-adenosylmethionine and S-adenosylhomocysteine levels in the aging brain of APP/PS1 Alzheimer mice

Hyperhomocysteinemia and factors of homocysteine metabolism, S-adenosylhomocysteine (AdoHcy) and S-adenosylmethionine (AdoMet), may play a role in Alzheimer’s disease (AD). With liquid-chromatography-tandem-mass-spectrometry AdoMet and AdoHcy were determined in brains of 8- and 15-month-old APP/PS1 Alzheimer mice, and their possible roles in AD brains investigated. The finding that AdoMet levels do not differ between the genotypes in (young) 8-month-old mice, but are different in (older) 15-month-old APP/PS1 mice compared to their wild-type littermates, suggests that alterations in AdoMet are a consequence of AD pathology rather than a cause. During aging, AdoMet levels decreased in the brains of wild-type mice, whereas AdoHcy levels diminished in both wild type and APP/PS1 mice. The finding that AdoMet levels in APP/PS1 mice are not decreased during aging (in contrast to wild-type mice), is probably related to less demand due to neurodegeneration. No effect of the omega-3 fatty acid docosahexaenoic acid (DHA) or cholesterol-enriched diets on AdoMet or AdoHcy levels were found