Guidance for management of free-roaming community cats: a bioeconomic analysis.

OBJECTIVES: This study used computer simulation modeling to estimate and compare costs of different free-roaming cat (FRC) management options (lethal and non-lethal removal, trap-neuter-return, combinations of these options and no action) and their ability to reduce FRC population abundance in open demographic settings. The findings provide a resource for selecting management approaches that are well matched for specific communities, goals and timelines, and they represent use of best available science to address FRC issues. METHODS: Multiple FRC management approaches were simulated at varying intensities using a stochastic individual-based model in the software package Vortex. Itemized costs were obtained from published literature and expert feedback. Metrics generated to evaluate and compare management scenarios included final population size, total cost and a cost efficiency index, which was the ratio between total cost and population size reduction. RESULTS: Simulations suggested that cost-effective reduction of FRC numbers required sufficient management intensity, regardless of management approach, and greatly improved when cat abandonment was minimized. Removal yielded the fastest initial reduction in cat abundance, but trap-neuter-return was a viable and potentially more cost-effective approach if performed at higher intensities over a sufficient duration. Of five management scenarios that reduced the final population size by approximately 45%, the three scenarios that relied exclusively on removal were considerably more expensive than the two scenarios that relied exclusively or primarily on sterilization. CONCLUSIONS AND RELEVANCE: FRCs present a challenge in many municipalities, and stakeholders representing different perspectives may promote varying and sometimes incompatible population management policies and strategies. Although scientific research is often used to identify FRC impacts, its use to identify viable, cost-effective management solutions has been inadequate. The data provided by simulating different interventions, combined with community-specific goals, priorities and ethics, provide a framework for better-informed FRC policy and management outcomes.

A Long-Term Lens: Cumulative Impacts of Free-Roaming Cat Management Strategy and Intensity on Preventable Cat Mortalities.

This study used a previously developed stochastic simulation model (1) to estimate the impact of different management actions on free-roaming kitten and cat mortality over a 10-year period. These longer-term cumulative impacts have not been systematically examined to date. We examined seven management scenarios, including: (1) taking no action, (2) low-intensity removal, (3) high-intensity removal, (4) low-intensity episodic culling, (5) high-intensity episodic culling, (6) low-intensity trap-neuter-return (TNR), and (7) high-intensity TNR. For each scenario we tracked within the model the number of kittens born, the number of kittens surviving to adulthood, and the number of adults removed using lethal control over the entire 10-year simulation. We further defined all kitten deaths and lethal removal of adults as "preventable" deaths because they could potentially be reduced by certain management actions. Our simulation results suggested that the cumulative number of preventable deaths over 10 years for an initial population of 50 cats is highest for a "no-action" scenario, estimated at 1,000 deaths. It is lowest for a high-intensity TNR scenario, estimated at 32 deaths, a 31-fold difference. For all management scenarios tested, including removal and culling, the model predicted fewer preventable deaths than for a no-action scenario. For all management scenarios, the model predicted that the higher-intensity option (defined in terms of the proportion of animals sterilized or removed within a given time period) would result in fewer preventable deaths over time than the lower-intensity option. Based on these findings, we conclude that management intensity is important not only to reduce populations more quickly, but also to minimize the number of preventable deaths that occur over time. Accordingly, the lessons for the animal welfare community are both encouraging and cautionary. With sufficient intensity, management by TNR offers significant advantages in terms of combined lifesaving and population size reduction. At lower intensity levels, these advantages are greatly reduced or eliminated. We recommend that those who seek to minimize suffering and maximize lifesaving for free-roaming cats attempt to balance prospective goals (i.e., saving lives tomorrow) with proximate goals (i.e., saving lives today), and recognize that thoughtful choice of management strategies can ensure that both of these complementary goals are achieved.

Simulating free-roaming cat population management options in open demographic environments.

Large populations of free-roaming cats (FRCs) generate ongoing concerns for welfare of both individual animals and populations, for human public health, for viability of native wildlife populations, and for local ecological damage. Managing FRC populations is a complex task, without universal agreement on best practices. Previous analyses that use simulation modeling tools to evaluate alternative management methods have focused on relative efficacy of removal (or trap-return, TR), typically involving euthanasia, and sterilization (or trap-neuter-return, TNR) in demographically isolated populations. We used a stochastic demographic simulation approach to evaluate removal, permanent sterilization, and two postulated methods of temporary contraception for FRC population management. Our models include demographic connectivity to neighboring untreated cat populations through natural dispersal in a metapopulation context across urban and rural landscapes, and also feature abandonment of owned animals. Within population type, a given implementation rate of the TR strategy results in the most rapid rate of population decline and (when populations are isolated) the highest probability of population elimination, followed in order of decreasing efficacy by equivalent rates of implementation of TNR and temporary contraception. Even low levels of demographic connectivity significantly reduce the effectiveness of any management intervention, and continued abandonment is similarly problematic. This is the first demographic simulation analysis to consider the use of temporary contraception and account for the realities of FRC dispersal and owned cat abandonment.

Metamodels for transdisciplinary analysis of wildlife population dynamics.

Wildlife population models have been criticized for their narrow disciplinary perspective when analyzing complexity in coupled biological - physical - human systems. We describe a "metamodel" approach to species risk assessment when diverse threats act at different spatiotemporal scales, interact in non-linear ways, and are addressed by distinct disciplines. A metamodel links discrete, individual models that depict components of a complex system, governing the flow of information among models and the sequence of simulated events. Each model simulates processes specific to its disciplinary realm while being informed of changes in other metamodel components by accessing common descriptors of the system, populations, and individuals. Interactions among models are revealed as emergent properties of the system. We introduce a new metamodel platform, both to further explain key elements of the metamodel approach and as an example that we hope will facilitate the development of other platforms for implementing metamodels in population biology, species risk assessments, and conservation planning. We present two examples - one exploring the interactions of dispersal in metapopulations and the spread of infectious disease, the other examining predator-prey dynamics - to illustrate how metamodels can reveal complex processes and unexpected patterns when population dynamics are linked to additional extrinsic factors. Metamodels provide a flexible, extensible method for expanding population viability analyses beyond models of isolated population demographics into more complete representations of the external and intrinsic threats that must be understood and managed for species conservation.

Inbreeding avoidance influences the viability of reintroduced populations of African wild dogs (Lycaon pictus).

The conservation of many fragmented and small populations of endangered African wild dogs (Lycaon pictus) relies on understanding the natural processes affecting genetic diversity, demographics, and future viability. We used extensive behavioural, life-history, and genetic data from reintroduced African wild dogs in South Africa to (1) test for inbreeding avoidance via mate selection and (2) model the potential consequences of avoidance on population persistence. Results suggested that wild dogs avoided mating with kin. Inbreeding was rare in natal packs, after reproductive vacancies, and between sibling cohorts (observed on 0.8%, 12.5%, and 3.8% of occasions, respectively). Only one of the six (16.7%) breeding pairs confirmed as third-order (or closer) kin consisted of animals that were familiar with each other, while no other paired individuals had any prior association. Computer-simulated populations allowed to experience inbreeding had only a 1.6% probability of extinction within 100 years, whereas all populations avoiding incestuous matings became extinct due to the absence of unrelated mates. Populations that avoided mating with first-order relatives became extinct after 63 years compared with persistence of 37 and 19 years for those also prevented from second-order and third-order matings, respectively. Although stronger inbreeding avoidance maintains significantly more genetic variation, our results demonstrate the potentially severe demographic impacts of reduced numbers of suitable mates on the future viability of small, isolated wild dog populations. The rapid rate of population decline suggests that extinction may occur before inbreeding depression is observed.

Non-peptidic antagonists of the CGRP receptor, BIBN4096BS and MK-0974, interact with the calcitonin receptor-like receptor via methionine-42 and RAMP1 via tryptophan-74.

The receptor for calcitonin gene-related peptide (CGRP) has been the target for the development of novel small molecule antagonists for the treatment of migraine. Two such antagonists, BIBN4096BS and MK-0974, have shown great promise in clinical trials and hence a deeper understanding of the mechanism of their interaction with the receptor is now required. The structure of the CGRP receptor is unusual since it is comprised of a hetero-oligomeric complex between the calcitonin receptor-like receptor (CRL) and an accessory protein (RAMP1). Both the CLR and RAMP1 components have extracellular domains which interact with each other and together form part of the peptide-binding site. It seems likely that the antagonist binding site will also be located on the extracellular domains and indeed Trp-74 of RAMP1 has been shown to form part of the binding site for BIBN4096BS. However, despite a chimeric study demonstrating the role of the N-terminal domain of CLR in antagonist binding, no specific residues have been identified. Here we carry out a mutagenic screen of the extreme N-terminal domain of CLR (residues 23-63) and identify a mutant, Met-42-Ala, which displays 48-fold lower affinity for BIBN4096BS and almost 900-fold lower affinity for MK-0974. In addition, we confirm that the Trp-74-Lys mutation at human RAMP1 reduces BIBN4096BS affinity by over 300-fold and show for the first time a similar effect for MK-0974 affinity. The data suggest that the non-peptide antagonists occupy a binding site close to the interface of the N-terminal domains of CLR and RAMP1.

Mapping interaction sites within the N-terminus of the calcitonin gene-related peptide receptor; the role of residues 23-60 of the calcitonin receptor-like receptor.

The calcitonin receptor-like receptor (CLR) acts as a receptor for the calcitonin gene-related peptide (CGRP) but in order to recognize CGRP, it must form a complex with an accessory protein, receptor activity modifying protein 1 (RAMP1). Identifying the protein/protein and protein/ligand interfaces in this unusual complex would aid drug design. The role of the extreme N-terminus of CLR (Glu23-Ala60) was examined by an alanine scan and the results were interpreted with the help of a molecular model. The potency of CGRP at stimulating cAMP production was reduced at Leu41Ala, Gln45Ala, Cys48Ala and Tyr49Ala; furthermore, CGRP-induced receptor internalization at all of these receptors was also impaired. Ile32Ala, Gly35Ala and Thr37Ala all increased CGRP potency. CGRP specific binding was abolished at Leu41Ala, Ala44Leu, Cys48Ala and Tyr49Ala. There was significant impairment of cell surface expression of Gln45Ala, Cys48Ala and Tyr49Ala. Cys48 takes part in a highly conserved disulfide bond and is probably needed for correct folding of CLR. The model suggests that Gln45 and Tyr49 mediate their effects by interacting with RAMP1 whereas Leu41 and Ala44 are likely to be involved in binding CGRP. Ile32, Gly35 and Thr37 form a separate cluster of residues which modulate CGRP binding. The results from this study may be applicable to other family B GPCRs which can associate with RAMPs.

Selective Breeding Programs for Rare Alleles: Examples from the Przewalski's Horse and California Condor Pedigrees.

As extinction due to loss of habitat grows more imminent for a wide variety of species, population management has been recognized as an important means toward species survival and recovery in the wild. Genetic management practices generally seek to preserve population variation at the level of the genome. It has been proposed, however, that such efforts should instead be directed to specific loci barboring alleles with particular selective benefits. This strategy may in fact result in greater loss of variation in the rest of the genome, potentially threatening population viability. Pedigrees of Przewalski's horse (Equus prezewalskii) and the California Condor (Gymnogyps californianus) were used to evaluate a "rare kinship" management strategy in which a single individual known to carry a unique allele is repeatedly bred to mates chosen by mean kinship in order to increase the frequency of the rare allele. This strategy led to increased population mean kinship and reduced gene diversity and founder genome equivalents relative to a no-management control pedigree and performed considerably worse than a pedigree managed for mean kinship. Reduced success in the breeding program can be directly attributed to significant deviations of founders' representations from their respective target values. As a result, a strategy for increasing the frequency of rare alleles cannot be generally recommended for management of captive populations. Under strict conditions; however, limited use of this strategy may be applicable only if used for a short time under careful monitoring by pedigree analysis. Even if these conditions are met, managing by a more conventional method such as mean kinship is preferable. These results illustrate the utility of thoughtful analysis of pedigree information to successful population management. Programas de cría selectivos para alelos raros: Ejemplos de los pedigrés de los caballos de Przewalski y de los condores de California.

Resumen: La extinción debido a la pérdida de hábitat crece más inminentemente para una amplia variedad de especies, el manejo de las poblaciones ha sido reconocido como un componente importante de la supervivencia y recuperación de especies en estado salvaje. Las prácticas de manejo genético buscan en general preservar la variabilidad poblacional al nivel del genoma. Sin embargo, se ha propuesto que tales esfuerzos se dirijan en cambio a locus especificos que albergarían alelos con beneficios selectivos particulares. Esta estrategia podria resultar en una mayor pérdida de variabilidad en el resto del genoma, amenazando potencialmente la viabilidad poblacional. Se usaron los pedigres del caballo de Przewalski (Equus prezewalskii) y de los condores de California (Gymnogyps californianus), para evaluar la técnica de manejo de "parentesco raro" en la cual un sólo individuo que posee un alelo único, es apareado repetidamente con un compañero/a elegido por medio de la técnica de parentesco promedio a efecto de incrementar la frecuencia del alelo raro. Esta estrategia llevó a un mayor parentesco promedio de la población y a una diversidad genética y equivalentes de genomas fundadores menores en elación con un pedigree control no manejado y se desempeñó considerablemente peor que un pedigre manejado en función del parentesco promedio. El reducido éxito del programa de cría peude ser directamente atribuído a desviaciones significativas de la representación de los fundadores de sus repectivos valores propuestos como objectivos. Como resultado, la estrategia para incrementar la frecuencia de alelos raros no puede ser recomendada en forma general para el manejo de poblaciones cautivas. Sin embargo, bajo ciertas condiciones estrictas, el uso limitado de esta estrategia sería apropiado pero sólo si fuese usada por un corto periodo de tiempo y bajo un monitoreo cuidadoso utilizando análisis de pedigre Aún si estas condiciones son alcanzadas, es preferible el manejo por medio de métodos más convencionales tales como el de parentesco promedio. Estos resultados ilustran la utilidad del análisis cuidadoso de la información de pedigre para el manejo exitoso de las poblaciones.

Conservation Genetics: Techniques and Fundamentals.

Conservation genetics utilizes the tools and concepts of genetics and applies them to problems in conservation biology. For example, molecular genetic techniques, such as protein electrophoresis, and analysis of mitochondrial DNA and highly variable nuclear genes (including DNA fingerprinting), have been important in documenting the extent and pattern of genetic variation in endangered species. We review these techniques and their advantages and disadvantages, and give examples of their application to endangered species. For captive animal populations, pedigree analysis has become the basic approach to evaluate breeding priority of particular individuals. Several pedigree analysis techniques are commonly used, but peeling and gene dropping give the most information. We compared these techniques and illustrate their value with applications to the Guam Rail, Przewalski's horse, and other endangered captive animals. The rationale for much conservation genetic interpretation is base in evolutionary genetics. We discuss the avoidance of inbreeding depression and the maintenance of genetic variation-both primary conservation genetic goals-from this perspective. In addition, we suggest aspects of these factors that deserve greater attention in their overall application to conservation planning. Finally, we briefly mention three evolutionary topics-the relationship of heterozygosity and fitness, population bottlenecks, and outbreeding depression-that have implications for conservation genetics. Although simple interpretation in these areas is appealing, we feel that because they are only generally understood and often quite controversial, their application to endangered-species management should be carefully evaluated and monitored.