Typology of conflict of commitment (COC) in the era of inappropriate foreign influence in research.

Conflicts, in the form of conflicts of interest and conflicts of commitment, have become increasingly prominent discussion points for US federal funding agencies and academic research institutions in the era of inappropriate foreign influence in research. Conflict of interest, specifically financial conflict of interest, is precisely defined within U.S. federal regulation precipitating the subsequent establishment of institutional processes for conflict of interest evaluation. Conflicts of commitment, however, have been increasingly referenced but less frequently codified. The variety of scenarios to which conflict of commitment may be applied is also vast, with no typology being presented heretofore. Therefore, a review of the typology of conflict of commitment, particularly as it is used to address research security concerns stemming from inappropriate foreign influence in research, is timely and relevant. This manuscript will review the history of conflicts of commitment in the scientific literature, correlate the focus on inappropriate foreign influence with conflict of commitment, and suggest a contemporary typology for conflict of commitment for practical and regulatory use based on significant references to COI in the literature and federal government documents.

Evaluating IACUCs: Previous Research and Future Directions.

IACUCs serve a critical role in animal care and use programs, ensuring that institutions which use animals in research and teaching do so responsibly and humanely. This role is defined in part by federal regulations, policies, and guidelines that prescribe the establishment and function of these committees. Often, IACUC administrators are expected to evaluate IACUC performance to ensure that committees execute these functions effectively, and in a manner that is suitable to the institution. However, methods for IACUC performance evaluation have not been well described in the peer-reviewed literature. To address this deficit, we conducted a systematic review using MEDLINE to identify methods that have been used to assess IACUCs. The scope of this review was intentionally broad to capture evaluation methods used by other institutional committees with similar responsibilities in overseeing research conduct, including animal ethics committees (AECs), institutional biosafety committees (IBCs), and institutional review boards (IRBs). Over 100 publications that included empirical evaluation methods were identified, although only 17 evaluated IACUCs in the United States. A substantial number of the studies used qualitative methods, such as surveys or questionnaires, interviews, and observations. The IACUC functions and characteristics most often assessed in the 17 publications included components of the protocol review processes and committee membership. We compiled this information to offer IACUC administrators a source of methodologies that can be incorporated into quality improvement and IACUC performance evaluation efforts. We also suggest ways in which organizations may evaluate IACUCs using methods described in the literature for other types of committees.

Institutional Animal Care and Use Committee Postapproval Monitoring Programs: A Proposed Comprehensive Classification Scheme.

Introduced over 20 y ago, IACUCs undertaking postapproval monitoring (PAM) of animal research procedures as a means to ensure researcher compliance is now widely used as an oversight tool in laboratory animal research. Through a literature review evaluating the history of PAM in the United States, discussions of controversy surrounding PAM activities, and reflections on how PAM activities are described within the IACUC community, we present an up-to-date and comprehensive classification system for PAM program methodologies that could serve to standardize how such activities are characterized in IACUC policies, communicated to research staff, used in training programs, implemented for the desired impact by individuals involved in animal research oversight, and referenced by regulatory agencies.

Ensuring due process in the IACUC and animal welfare setting: considerations in developing noncompliance policies and procedures for institutional animal care and use committees and institutional officials.

Every institution that is involved in research with animals is expected to have in place policies and procedures for the management of allegations of noncompliance with the Animal Welfare Act and the U.S. Public Health Service Policy on the Humane Care and Use of Laboratory Animals. We present here a model set of recommendations for institutional animal care and use committees and institutional officials to ensure appropriate consideration of allegations of noncompliance with federal Animal Welfare Act regulations that carry a significant risk or specific threat to animal welfare. This guidance has 3 overarching aims: 1) protecting the welfare of research animals; 2) according fair treatment and due process to an individual accused of noncompliance; and 3) ensuring compliance with federal regulations. Through this guidance, the present work seeks to advance the cause of scientific integrity, animal welfare, and the public trust while recognizing and supporting the critical importance of animal research for the betterment of the health of both humans and animals.-Hansen, B. C., Gografe, S., Pritt, S., Jen, K.-L. C., McWhirter, C. A., Barman, S. M., Comuzzie, A., Greene, M., McNulty, J. A., Michele, D. E., Moaddab, N., Nelson, R. J., Norris, K., Uray, K. D., Banks, R., Westlund, K. N., Yates, B. J., Silverman, J., Hansen, K. D., Redman, B. Ensuring due process in the IACUC and animal welfare setting: considerations in developing noncompliance policies and procedures for institutional animal care and use committees and institutional officials.

The Interplay of Ethics, Animal Welfare, and IACUC Oversight on the Reproducibility of Animal Studies.

Reproducibility in animal studies has been defined as the ability of a result to be replicated through independent experiments within the same or among different laboratories. Over the past few years, much has been written and said about the lack of reproducibility of animal studies. Reasons that are commonly cited for this lack of reproducibility include inappropriate study design, errors in conducting the research, and potential fraud. In the quest to understand the basis for this lack of reproducibility, scientists have not fully considered the potential ramifications on ethical constructs for animal research, animal welfare considerations in animal research programs, the regulatory environment, and oversight by IACUCs. Here, we review how ethical theories behind animal research, policies, and practices meant to enhance animal welfare and the IACUC oversight process influence the reproducibility of animal studies, a previously undiscussed topic in the peer-reviewed literature.

Decreasing institutionally imposed regulatory burden for animal research.

With the ever-increasing call to reduce self-imposed regulatory and administrative burden in the animal research oversight process, knowledge of the regulations and a desire to streamline policies and procedures are needed to affect a change in culture. In this opinion piece, we provide details on why institutionally imposed regulatory burden can arise.

Effect of sedation with xylazine and ketamine on intraocular pressure in New Zealand white rabbits.

To determine the effects of intravenous and intramuscular xylazine-ketamine on intraocular pressure (IOP) in laboratory rabbits, 10 New Zealand white rabbits received xylazine (0.46 mg/kg) and ketamine (1.5 mg/kg) intravenously whereas another 10 rabbits received intramuscular xylazine (10 mg/kg) and ketamine (50 mg/kg). IOP was measured at baseline and 5, 10, 20, and 25 min after administration in rabbits that were injected intravenously and at baseline and 10, 20, 30, and 45 min in rabbits injected intramuscularly. Baseline IOP (mean ± 1 SD; intravenous group, 20.15 ± 2.24 mm Hg; intramuscular group, 19.03 ± 1.77 mm Hg) did not differ between groups. Compared with baseline values, IOP decreased significantly after intravenous administration at 10, 20, and 25 min (decreases of 2.73, 4.10, and 4.55 mm Hg, respectively) but not at 5 min (decrease of 1.40 mm Hg). IOP in intramuscularly dosed rabbits showed significant differences from baseline at 10, 20, 30, and 45 min (decreases of 2.88, 3.30, 3.95, and 4.60 mm Hg, respectively). In the intravenous group, IOP differed at 10 min compared with 25 min (1.83 mm Hg, P = 0.0143) but not at 20 min compared with 25 min (0.450 mm Hg). In the intramuscular group, differences in IOP at 10 min compared with 20 min, 20 min compared with 30 min, and 30 min compared with 45 min were nonsignificant. Intravenous and intramuscular xylazine-ketamine decreased IOP in laboratory rabbits and may be used safely during ocular procedures for which increased IOP is a concern.

The effect of a wound care solution containing polyhexanide and betaine on bacterial counts: results of an in vitro study .

Polyhexanide and betaine topical solution is used in the management of infected wounds as a cleaning agent. An in vitro study was conducted to examine the antimicrobial effects of a solution containing 0.1% of the antimicrobial agent polyhexanide and 0.1% of the surfactant betaine. Three batches of each product were tested, and culture results of 13 microorganisms were evaluated after 7, 14, and 28 days using USP <51> methodology. Growth reduction was identical at each day following exposure to the solution in all micro-organisms except Aspergillus brasiliensis. A range of 5.3-log to 5.8-log reduction was seen for the following micro-organisms: Staphylococcus epidermidis, Pseudomonas aeruginosa, Serratia marcescens, Candida albicans, S. aureus, vancomycin-resistant Enterococcus faecalis, Proteus mirabilis, Escherichia coli, methicillin-resistant S. aureus, Acinetobacter baumannii, Enterobacter cloacae, and E. faecalis. For A. brasiliensis, reductions were 2.1-log, 2.3-log and 2.8-log at 7, 14, and 28 days, respectively. The results of this study indicate a 4+ log inhibition of activity in 12 of 13 micro-organisms exposed to the solution. Research to elucidate the potential clinical effects of these observations is needed.

Sinus of Valsalva aneurysm in a Göttingen minipig.

A 26.6-kg, intact, 9-mo-old female Göttingen minipig was presented for a coronary stent study. Angiography revealed a sinus of Valsalva aneurysm (SVA) in the aortic root that involved both the left and noncoronary sinuses of the heart. Gross histologic examination of the heart revealed 2 regions of aneurysmal formation: one at the ostium to the left main coronary artery, with aortic sinus involvement, and the other at the dorsal aspect of the aortic root involving the noncoronary aortic sinus. With no history of any infectious diseases, and the microscopic findings showing no evidence of necrosis, degeneration, or infection, confirmed that the aneurysmal-like dilation of the sinuses was most likely a congenital anomaly. This case illustrates the diagnosis and comparative findings of a rare cardiac anomaly found in only a few species to date. To our knowledge, antemortem diagnosis of unruptured SVA involving both the left and noncoronary aortic sinuses of the minipig heart has not been reported previously.

Incidence of spontaneous ocular lesions in laboratory rabbits.

Laboratory rabbits are commonly used for ocular drug and device studies. The purpose of this study was to determine the incidence of spontaneous ocular lesions in laboratory rabbits with respect to sex, breed, and supplier. We retrospectively evaluated ophthalmic examination records of rabbits screened between April 2008 and April 2010. These 1840 records represented 572 black Dutch belted (DB), 1022 New Zealand white (NZW), and 246 NZW × New Zealand red F(1) crosses (WRF1). Rabbits were between 6 and 16 wk of age and had been received from 5 suppliers. Ocular structures evaluated were the cornea, lens, iris and vitreous with respect to sex, breed and supplier. A total of 177 rabbits (9.6%) and 233 eyes (6.3%) were effected. Of total rabbits, 15.3% males and 7.3% females were affected. The most common structure affected was the cornea in 5.7% of rabbits, (DB 11.7%, NZW 3.0%, and NZR 3.3%). The lens at 3.6% was second most common (DB 2.1%, NZW 4.6%, and NZR 3.3%). Both iris (0.2%) and vitreous (0.3%) were not significantly affected. Significant sex-breeder-supplier combinations were: cornea DB supplier D, supplier D females, supplier D males, DB males and NZR females; and lens: NZW females; and at least one affected ocular structure: NZW supplier D, supplier D females, DB males, NZW females, and NZR females. Breed, sex, and supplier were significant variables of ocular lesions in laboratory rabbits. Investigators should consider each of these variables when choosing rabbits for ocular studies.

Identifying the age cohort responsible for transmission in a natural outbreak of Bordetella bronchiseptica.

Identifying the major routes of disease transmission and reservoirs of infection are needed to increase our understanding of disease dynamics and improve disease control. Despite this, transmission events are rarely observed directly. Here we had the unique opportunity to study natural transmission of Bordetella bronchiseptica--a directly transmitted respiratory pathogen with a wide mammalian host range, including sporadic infection of humans--within a commercial rabbitry to evaluate the relative effects of sex and age on the transmission dynamics therein. We did this by developing an a priori set of hypotheses outlining how natural B. bronchiseptica infections may be transmitted between rabbits. We discriminated between these hypotheses by using force-of-infection estimates coupled with random effects binomial regression analysis of B. bronchiseptica age-prevalence data from within our rabbit population. Force-of-infection analysis allowed us to quantify the apparent prevalence of B. bronchiseptica while correcting for age structure. To determine whether transmission is largely within social groups (in this case litter), or from an external group, we used random-effect binomial regression to evaluate the importance of social mixing in disease spread. Between these two approaches our results support young weanlings--as opposed to, for example, breeder or maternal cohorts--as the age cohort primarily responsible for B. bronchiseptica transmission. Thus age-prevalence data, which is relatively easy to gather in clinical or agricultural settings, can be used to evaluate contact patterns and infer the likely age-cohort responsible for transmission of directly transmitted infections. These insights shed light on the dynamics of disease spread and allow an assessment to be made of the best methods for effective long-term disease control.

Transnational organizational considerations for sociocultural differences in ethics and virtual team functioning in laboratory animal science.

Business models for transnational organizations include linking different geographies through common codes of conduct, policies, and virtual teams. Global companies with laboratory animal science activities (whether outsourced or performed inhouse) often see the need for these business activities in relation to animal-based research and benefit from them. Global biomedical research organizations can learn how to better foster worldwide cooperation and teamwork by understanding and working with sociocultural differences in ethics and by knowing how to facilitate appropriate virtual team actions. Associated practices include implementing codes and policies transcend cultural, ethnic, or other boundaries and equipping virtual teams with the needed technology, support, and rewards to ensure timely and productive work that ultimately promotes good science and patient safety in drug development.

The basics of animal biosafety and biocontainment training.

The threat of biocontamination in an animal facility is best subdued by training. 'Training' is an ambiguous designation that may not be adequately appreciated in all animal facilities. The authors set down concrete training topics and provide practical advice on incorporating the basic principles of facility biosafety training--as well as the precautions and procedures that employees must know in case of accident or emergency--into various training models. They also discuss the current biosafety publications and guidelines and their relationship to biosafety training.

Training strategies for animal care technicians and veterinary technical staff.

An institutional training program for animal care and veterinary technicians should be planned and implemented to provide these individuals with knowledge and skills for performing their duties within a laboratory animal care and use program. The complexity in the regulatory and scientific features of the animal research environment necessitates a strong training program on diverse topics according to staff duties. Orientation training should include ethics and compliance with relevant laws, policies, and guidelines. Depending on specific staff responsibilities, training may be general or in depth on topics of species-specific biology and behavior, animal facility equipment and operations, animal health procedures, animal research policies, occupational health and safety equipment and practices, computer usage, training, and management. Staff training should be an ongoing mission for incorporating new equipment, practices, and procedures in the laboratory animal program; for providing periodic refresher training to maintain a high level of staff qualifications; and for retraining when skills or knowledge are found deficient. Large institutions often have a dedicated training staff to implement the institutional training program.

Management of unanticipated outcomes in transgenic mouse facilities.

Experimental manipulations of rodents may result in unexpected adverse phenotypes that present problems from both regulatory and animal care-veterinary perspectives. The authors discuss the implications of unanticipated outcomes and describe a cage card-based tracking system used at the Harvard Medical School for the early detection and handling of unanticipated phenotypes in genetically altered rodents.

Creating a comprehensive training documentation program.

The regulations mandate that individuals involved in research animal care and use receive adequate training, but they fail to address the documentation of the training. The authors provide guidelines for training documentation and, as an example, describe the program in place at the University of Pennsylvania.