Recognizing and assessing pain,suffering and distress in laboratory animals: a survey of current practice in the UK with recommendations

A survey was undertaken to evaluate how animal pain, suffering and distress are recognized and assessed in UK scientific procedure establishments designated under the Animals (Scientific Procedures) Act 1986. A total of 28 institutions were visited between June 1999 and April 2001, within which 137 people were interviewed including scientists, veterinarians and animal technicians. All 28 establishments use clinical observation sheets to assist the recognition of adverse effects, nine use score sheets and seven use computerized data management systems. Clinical signs used as indicators of potential pain, suffering or distress are largely subjective. The survey also addressed protocols and methods for avoiding and alleviating adverse effects, record keeping, review of policies and protocols and issues relating to team work and training. Respondents use a range of techniques for reducing suffering including analgesia, humane endpoints, ensuring competence and refining husbandry. All establishments review projects regularly but few have the time or resources formally to review adverse effects noted in practice and to compare observations with predictions made in licence applications. Training is very consistent between different establishments and most aim to achieve a 'team approach' for monitoring and assessing animals. Results are summarized in the present, abridged paper and set out in full in a report that can be downloaded at http://www.lal.org.uk/pain/(Hawkins 2002). The present paper and the full report, including its recommendations, are intended to provide a source of information, discussion topics and ideas for all establishments that need to monitor animal well-being.     

Recommendations for improving the home office project licence abstracts

The Freedom of Information Act 2000 prompted the Government to evaluate how public understanding about the use of animals in scientific research can be improved and how animal experimentation is regulated within the UK. This resulted in the publication of anonymous project licence abstracts. Here, the abstracts published between December 2004 and October 2005 have been evaluated, by using a scoring system which takes into account their content and format, in order to assess whether they provide information that will facilitate the increased implementation of reduction, refinement and replacement strategies. The potential impact of freely-available Home Office project licence abstracts on public attitudes to animal testing and on the quality of animal-based research, is also discussed. Although some abstracts scored well, in general, the abstracts were found to be severely lacking in detail about the welfare of experimental animals. Thus, the abstracts tend to present a distorted picture of animal-based research. Many abstracts lack the details which would reveal how the licensing criteria had been met. It is concluded that, in their current form, the project abstracts are not sufficiently informative. A number of recommendations are made, which address this problem.     

The effectiveness of US mitigation and monitoring practices for the threatened Valley elderberry longhorn beetle

Habitat mitigation frequently leads to planting of new habitat, assuming that it can replace lost natural habitat. Yet this practice has rarely been examined in detail. In the USA habitat mitigation is frequently allowed under the US Endangered Species Act, providing monitoring reports which represent a potentially valuable data source for imperiled species. We used publicly available reports for the US threatened Valley elderberry longhorn beetle (Desmocerus californicus dimorphus) to assess record keeping practices used by US Fish and Wildlife Service (FWS), and the utility of such analyses for improving conservation. A large portion of mitigation reports known to exist were missing from FWS files, indicating problems with data management, and a loss of important information. Transplanted brought mature beetle host plants and beetles to sites, promoting beetle colonization. Conversely, few sites with seedlings were colonized. Results indicate a need for improved data management by FWS and longer term monitoring.     

Dr. Steinhart replies

Despite recommendations supporting annual influenza vaccination for people aged 65 years or older, vaccination rates remain low. Several studies have evaluated the effect of sending mailed reminders, but few have compared alternative ways of reminding patients to receive the vaccine. In a randomized trial of 939 patients aged 65 years or older in four family practices carried out between Oct. 23 and Dec. 31, 1984, we compared three ways of reminding elderly patients to receive the vaccine: personal reminder by the physician, telephone reminder by the nurse and reminder by letter. The vaccination rates for the three groups were 22.9%, 37% and 35.1% respectively. No reminder was issued to a control group, and the rate was 9.8%. Some patients could not be reached by telephone, and some did not see the physician during the specified time. Among the patients whom the nurse actually contacted, the vaccination rate was 43.5%; the rate for patients whom the doctor actually saw was 45.1%. Overall, a telephone reminder by the nurse was the most effective method, and at an hourly salary of $16 or less this method would also be the most cost-effective. The reminders used in this study were automatically generated from a computerized medical record system. The study shows how a computerized system can be used to identify patients for whom preventive procedures are due.     

The Computerized Laboratory Notebook concept for genetic toxicology experimentation and testing

We describe a microcomputer system utilizing the Computerized Laboratory Notebook (CLN) concept developed in our laboratory for the purpose of automating the Battery of Leukocyte Tests (BLT). The BLT was designed to evaluate blood specimens for toxic, immunotoxic, and genotoxic effects after in vivo exposure to putative mutagens. A system was developed with the advantages of low cost, limited spatial requirements, ease of use for personnel inexperienced with computers, and applicability to specific testing yet flexibility for experimentation. This system eliminates cumbersome record keeping and repetitive analysis inherent in genetic toxicology bioassays. Statistical analysis of the vast quantity of data produced by the BLT would not be feasible without a central database. Our central database is maintained by an integrated package which we have adapted to develop the CLN. The clonal assay of lymphocyte mutagenesis (CALM) section of the CLN is demonstrated. PC-Slaves expand the microcomputer to multiple workstations so that our computerized notebook can be used next to a hood while other work is done in an office and instrument room simultaneously. Communication with peripheral instruments is an indispensable part of many laboratory operations, and we present a representative program, written to acquire and analyze CALM data, for communicating with both a liquid scintillation counter and an ELISA plate reader. In conclusion we discuss how our computer system could easily be adapted to the needs of other laboratories.     

An efficient medical database system implementation with its tool and data structure consideration

The development of a new system for medical database application running on minicomputer under MUMPS system is described. Two kinds of data representation in global structure are briefly reviewed. The use of a subject oriented multi-dimensional data structure greatly simplifies database design and facilitates data manipulation, organization, selective retrieval and software development. It is concluded that the program generator approach can provide the flexibility necessary for various applications and future growth of computerized medical record system. The final system has been proven effective in practical operation. The future extension concerns the introduction of multi-microprocessor structure and logic representation is presented.     

Clinical Decision Support: Effectiveness in Improving Quality Processes and Clinical Outcomes and Factors That May Influence Success

The use of electronic health records has skyrocketed following the 2009 HITECH Act, which provides financial incentives to health care providers for the “meaningful use” of electronic medical record systems. An important component of the “Meaningful Use” legislation is the integration of Clinical Decision Support Systems (CDSS) into the computerized record, providing up-to-date medical knowledge and evidence-based guidance to the physician at the point of care. As reimbursement is increasingly tied to process and clinical outcomes, CDSS will be integral to future medical practice. Studies of CDSS indicate improvement in preventive services, appropriate care, and clinical and cost outcomes with strong evidence for CDSS effectiveness in process measures. Increasing provider adherence to CDSS recommendations is essential in improving CDSS effectiveness, and factors that influence adherence are currently under study.     

Tough tobacco-control legislation begins to have an impact in Ontario.

In 1994 the Ontario government passed one of the world''s toughest packages of antitobacco legislation. The Tobacco Control Act places restrictions on who can sell tobacco products, provides for severe penalties for retailers who sell to minors, bans smoking in many public places and severely restricts the use of designated smoking areas in others. The province has had antismoking legislation before, but enforcement was lax; this time enforcement of the law, particularly as it concerns retailers who sell to minors, has been given priority Brenda Gibson asks if these tough new measures are working.     

Study of United Kingdom product licence applications containing new active substances, 1987-9.

OBJECTIVES--To investigate the fate of product licence applications containing new active substances in relation to their degree of innovation and therapeutic category. To assess the numbers of volunteers and patients exposed to a new active substance when marketing autorisation is first sought. DESIGN AND SETTING--Observational study of records for each licence application submitted to the United Kingdom licensing authority for marketing authorisation from 1987 to 1989. SUBJECTS--118 product licence applications containing one or more new active substances. MAIN OUTCOME MEASURES--Success of application for product licence as assessed by the decision of the Committee on Safety of Medicines to advise the granting of a licence (with or without conditions) or provisionally advise its refusal on the grounds of quality, safety, or efficacy. Assessment of numbers of volunteers and patients exposed to each substance during premarketing studies and clinical trials, and the numbers of treated patients available for an assessment of safety. RESULTS--118 relevant product licence applications were submitted during the review. Although 60% (52/86) of semi-innovative products fell into one of three therapeutic categories (cardiovascular, central nervous system, or anti-infective agents), only 41% (13/32) of fully innovative products fell into these categories. 47 applications were granted (conditionally or unconditionally) but the success rate for fully innovative products (56%, 18/32) was greater than that for semi-innovative products (34%, 29/86). The number of volunteers and patients exposed to a new product at submission varied widely and tended to be greater for successful applications. CONCLUSION--The results suggest a broadening of the pharmaceutical industry''s research and development programmes and that a more liberal licensing policy exists for fully innovative products than for semi-innovative products. The relatively limited exposure of patients to new active substances at licensing underlines the importance of rigorous postmarketing surveillance.     

Self-harm in laboratory-housed primates: where is the evidence that the Animal Welfare Act amendment has worked?

The 1985 amendment to the United States Animal Welfare Act (AWA) to promote psychological well being of primates in the laboratory represents an acknowledgment of an important welfare problem concerning nonhuman animals. How effective has this amendment been? Perhaps the best-known contributor to psychological distress in primates in the laboratory is nonsocial housing; yet, available analyses suggest that little progress has been made in avoiding single-caging of these animals. Another way to assess psychological well being is to examine rates of self-abusive behavior in laboratory primates. If the AWA has been effective, then post-AWA self-harm rates might be lower than pre-AWA rates. However, when we attempted to determine those rates from published studies, data were too sparse to allow a rigorous statistical analysis; of 139 studies reporting primate self-harming behavior, only 9 contained data allowing estimation of self-harming behavior rates. We conclude that the current system of laboratory animal care and record keeping is inadequate to properly assess AWA impacts on primate psychological well being and that more is required to ensure the psychological well being of primates.     

Bio-stretch, a computerized cell strain apparatus for three-dimensional organotypic cultures

Summary In the present study, a unique mechanical strain apparatus for three-dimensional organotypic cultures was developed into a computerized system. It consists of a personal computer running Windows-based software, the Bio-Stretch Manager, a Bio-Stretch Controller, and three sets of magnet boards. Cells are cultured on a Gelfoam? sponge that is placed in a 35-mm petri dish with one end glued to the dish, and the other end attached to a coated steel bar. The petri dish is placed in front of a magnet, and the movement of the steel bar is controlled by dynamically changing the magnetic field. Up to five stretch patterns of variable frequency, duty cycle, and magnitude can be designed for each stretch regimen. Three different stretch regimens can be tested simultaneously. The operational characteristics of sponges were examined. Attachment of cells to the sponges was observed on several cell types. These features provide wide options for using this system to study the effects of mechanical stretch on cells.     

Research with animals: requirement, responsibility, welfare

Recognition of unacceptable cruelty to animals in pasttimes such as bull-baiting, dates in Britain from the early 19th century. The Society for the Prevention of Cruelty to Animals was founded in 1824. Several bills to curb cruelty were discussed in Parliament, and the Cruel and Improper Treatment of Cattle Act was passed in 1822. Other Acts have followed over the years. Cruelty in the form of painful scientific experiments, including dissection of living, conscious animals, vivisection, was proscribed by the Cruelty to Animals Act 1876. That Act required anyone wishing to experiment with animals to obtain a licence from the Secretary of State. Conditions for issue of licences were strict and remain so to this day. The Act is still valid, and is enforced by the Home Office, with its medical and veterinary Inspectors. The Cruelty to Animals Act 1876 allows experiments on animals under strictly controlled conditions. Experiments must have the clear objective of improving the welfare of man and/or animals. Benefits from experiments carried out under the Act have been enormous, covering every aspect of diagnosis, treatment, and prophylaxis in human and veterinary medicine. Coincidentally, the welfare of laboratory animals has also been greatly improved. There has always been some opposition to the use of animals in biomedical research. The subject is emotive but, by and large, discussion has been rational and within the law. In recent years, however, the morality of using experimental animals has been examined more closely. The possibility of replacing them by alternative methods has been investigated. Where these alternatives are applicable, they are used and further research on them continues. The questioning of animal experiments has emphasized the need to look constantly at animal welfare to ensure humane treatment of all animals, especially those restricted in a laboratory or on a farm. Attention has been drawn in this work to our existing laws protecting animals, but new legislation is being demanded, not only by some lay welfare groups but also by scientists. Hence, it has become very important to discuss various ways of ensuring animal welfare, including by legislation, especially with those knowledgeable in laboratory animal science and animal experiments.(ABSTRACT TRUNCATED AT 400 WORDS)     

Computerized Determination of Adipocyte Size

Objective: Fat cell size is a fundamental parameter in the study of adipose tissue metabolism, because it markedly influences the cellular rates of metabolism. Previous techniques for the sizing of adipocytes are often complicated or time‐consuming. The aim of this study was to develop a new, computerized method for rapid and accurate determination of adipocyte size in a cell suspension obtained by incubating human or rat adipose tissue biopsies with collagenase. Research Methods and Procedures: The cell suspension was placed between a siliconized glass slide and a cover slip. Using the reference method [designated as (R)], the cell diameters were determined manually using a microscope with a calibrated ocular. The new method presented here [designated as (C)] was based on computerized image analysis. Results: After two well‐defined corrective adjustments, measurements with (R) and (C) agreed very well. The small remaining differences seemed, in fact, to depend on inconsistencies in (R). Discussion: We propose that (C) constitutes a valuable tool to study fat cell size, because this method is fast and allows the assessment of a sufficient number of cells to get reliable data on size distribution. Furthermore, images of cell preparations may be stored for future reference.     

Word-processor macro for restriction endonuclease analysis

This paper describes a Microsoft Word 97 macro designed for restriction endonuclease analysis. Selected DNA fragments in the active Word document can be analyzed through a dynamic dialog box that formats the enzyme restriction lists for further analysis. The results can be obtained in a new Word document with the name of the enzymes, number of cuts and positions. This macro has several advantages: the results can be printed in a format suitable for record keeping, no additional programs are required and it is simple to use.     

Regulatory affairs and biotechnology in Europe

The high cost and risks associated with the research and development of new drugs demand an alert as well as realistic legislative policy at both national and international levels. Registration of a new drug required before a marketing licence is granted, is important for all branches of the pharmaceutical industry but is crucial for success in the innovative biotechnological sector.Innovation as such is no guarantee to be profitable. Increasing government demands have introduced uncertainty on whether new products will secure registration and have led to a disproportionate increase in the economical risks for innovative industry. Preparation and submission of an application for registration should be undertaken seriously and professionally since it has significantly more consequences than simply obtaining a marketing licence. It will influence marketing strategies and results. It is proposed — since dealing with regulatory affairs can be considered as an essential specialism — to apply a Quality Assurance approach. Activities in this context should comply with the same performance standards as developed for GMP, GLP and GCP leading to Good Regulatory Practice (GRP).By acknowledging regulatory affairs as a quality assurance means one can define a set of standard procedures within an organization to ensure that decisions are made on current and future regulations. In such a setup regulatory affairs becomes a marketing tool.This paper illustrates the complex problems found in registration activities. It underlines the necessity of introducing a GRP-approach of performance resulting in substantive evidence of regulatory efficacy.     

Actinomyces fulvoviolaceus ver. achromogenes var. nov., a producer of the new heptaene complex, fulvomycin]

An actinomycetous culture designated as LIA-0721 was isolated from a soil sample. It was close to Act. fulvoviolaceus by its morphologo-cultural features and differed from it in production of melanoid pigments and the spectrum of carbohydrate assimilation. This justified its classification as Act. fulvoviolaceus var. achromogenes var. nov. The culture produced new aromatic heptaens, i. e. fulvomycins A, B and C. Their physico- chemical and biological characteristics are presented.     

The Data Governance Act and the EU's move towards facilitating data sharing

The implementation of the EU General Data Protection Regulation (GDPR) has had significant impacts on biomedical research, often complicating data sharing among researchers. The recently announced proposal for a new EU Data Governance Act is a promising step towards facilitating data sharing, if it can interplay well with the GDPR.Subject Categories: S&S: Ethics

The EU General Data Protection Regulation (GDPR) has affected biomedical research, often complicating data sharing. The recently announced proposal for a new EU Data Governance Act, is a promising step towards facilitating data sharing.

In an attempt to improve and increase data sharing in the EU and to optimize the re‐use of personal and non‐personal data, the European Commission has recently announced the proposal for a new EU Data Governance Act (https://ec.europa.eu/digital‐single‐market/en/news/proposal‐regulation‐european‐data‐governance‐data‐governance‐act). If approved, it will enable the creation and regulation of “secure spaces” where various types of data, including health data, can be shared and re‐used for both commercial and altruistic purposes, including scientific research. The Data Governance Act, within the framework of a European Strategy for Data, (https://ec.europa.eu/info/sites/info/files/communication‐european‐strategy‐dat‐19feb2020_en.pdf), would address some of the shortcomings and drawbacks of the current regulatory framework which holds back sharing and re‐using data for biomedical research purposes.While the proposed Act would apply to all types of personal and non‐personal data, the increasing demand for sharing health data has most likely been a major rationale for this new legislation of data governance. Notably, sharing health and genetic data for scientific research entails an extra layer of complexity, owing to concerns over data protection and privacy when sharing sensitive personal data. Vice versa, there are also concerns in the scientific community over the negative impact of regulatory restrictions on sharing health data in data‐driven biomedical research. The pressing question here is how far the EU’s proposed legislative and policy framework can offset either concerns?     

Computerized recording and reporting system for cytology and colposcopy

The computerized system for recording and reporting cytologic and colposcopic data at the Madrid Provincial Hospital is discussed. Cytodiagnostic codes based on standard international nomenclature, and yet open to constant updating, were created for the anatomic sites from which samples are currently examined (vagina and cervix, endometrium, vulva and breast), with areas allocated for expansion to other sites. A similar novel code was devised for colposcopic data. Specific forms were developed for each anatomic site; the cervicovaginal and endometrial forms are used for both cytology and colposcopy. The system has provided the laboratory with automation of its managerial, clerical and administrative tasks, including (1) record keeping, (2) reporting, (3) statistics, (4) correlation of clinical, cytologic, colposcopic and histopathologic data, (5) patient follow-up, (6) technical support in research programs and (7) quality control. Use of the system led to an improvement in the efficiency of the laboratory and resulted in reports of better quality. The program has been of help in our research and has not increased the total cost of cytologic studies.     

Computerized ordering of experimental animals and test authorization

The authorization procedure required by law in Switzerland and the internal set-up at Roche for acquiring experimental animals has made a computerized system for monitoring authorizations and animal deliveries essential. The INQUIRE software program, which can be run on the central computer, was used to set-up databases with information on all personnel who place orders and perform experiments (PERI), authorization matters (BEWI), orders (ORDR), deliveries (SPED), animal species (SPEC), animal strains (STRE), populations (POPU) and the management of various data (BARA). The authorizations database (BEWI) permits sequential searches on specific questions. The animals ordered in the ORDR database are constantly updated in BEWI, thus ensuring that the authorized animal quotas are not exceeded. Expiry of an authorization or an unregistered experimenter will come to light in the course of the plausibility study. Through ORDR the experimenter has a good overview of the animals that he has ordered or have been ordered for him, and he can select the most appropriate strain or population for his studies in STRE or POPU, which contain data on the genetic and physiological characteristics as well as the breeding and keeping of all sublines and stocks. Realization of the IFIS project has made it a simple matter to keep a check on the legal requirements pertaining to animal experimentation and to update the information and evaluate the entire stock of data at any time.