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In recent years, there has been considerable interest in investigating how animal social structure is affected by the loss of individuals. This is often achieved using simulations that generate predictions regarding how the removal of ‘key’ individuals from a group affects network structure. However, little is known about the effects of such removals in wild and free-ranging populations, particularly the extent to which naturally occurring mortality events and the loss of a large proportion of individuals from a social group affects the overall structure of a social network. Here, we used data from a population of wild Barbary macaques (Macaca sylvanus) that was exposed to an exceptionally harsh winter, culminating in the death of 64% of the adults from two groups. We analysed how social interaction patterns among surviving individuals were affected by the natural loss of group members using social networks based on affiliative (i.e., grooming) and aggressive social interactions. We show that only the structure of the pre-decline grooming networks was conserved in the post-decline networks, suggesting that grooming, but not aggression networks are resilient against the loss of group members. Surviving group members were not significantly different from the non-survivors in terms of their affiliative and agonistic relationships, and did not form assorted communities in the pre-decline networks. Overall, our results suggest that in primates, patterns of affiliative interactions are more resilient to changes in group composition than aggressive interaction patterns, which tend to be used more flexibly in new conditions.

The Standards Coordinating Body for Gene, Cell, and Regenerative Medicines and Cell-Based Drug Discovery (SCB) supports the development and commercialization of regenerative medicine products by identifying and addressing industry-wide challenges through standards. Through extensive stakeholder engagement, the implementation of rapid microbial testing methods (RMTMs) was identified as a high-priority need that must be addressed to facilitate more timely release of products. Since 2017, SCB has coordinated efforts to develop standards for this area through surveys, weekly meetings, workshops, leadership in working groups and participation in standards development organizations. This article describes the results of these efforts and discusses the current landscape of RMTMs for regenerative medicine products. Based on discussions with stakeholders across the field, an overview of traditional culture-based methods and limitations, alternative microbial testing technologies and current challenges, fit-for-purpose rapid microbial testing and case studies, risk-based strategies for selection of novel rapid microbial test methods and ongoing standards efforts for rapid microbial testing are captured here. To this end, SCB is facilitating several initiatives to address challenges associated with rapid microbial testing for regenerative medicine products. Two documentary standards are under development: an International Organization for Standardization standard to provide the framework for a risk-based approach to selecting fit-for-purpose assays primarily intended for cell and gene therapy products and an ASTM standard guide focused on sampling methods for microbial testing methods in tissue-engineered medical products. Working with the National Institute of Standards and Technology, SCB expects to facilitate the process of developing publicly available microbial materials for inter-laboratory testing. These studies will help collect the data necessary to facilitate validation of novel rapid methods. Finally, SCB has been working to increase awareness of, dialog about and participation in efforts to develop standards in the regenerative medicine field.

Most primates, including humans, give birth during the inactive phase of the daily cycle. Practical constraints therefore limit our knowledge of the precise timing of nocturnal birth in wild diurnal primates and so limit our understanding of selective pressures and consequences. We measured maternal core body temperature ( T b ) across 24 births in a population of wild vervet monkeys using biologgers. We identified distinct perturbations in T b during the birth period, including declining T b during labour and the rapid recovery of T b post-parturition. Vervet monkeys typically gave birth during their inactive phase in synchrony with the nadir of the maternal nychthemeral T b rhythm but also showed remarkable inter-individual variability in their absolute T b during birth. Our findings support the view that selection may have favoured a nocturnal timing of primate birth to coincide with lower night-time T b and environmental temperatures, which improve thermal efficiency during birth.

Fevers are considered an adaptive response by the host to infection. For gregarious animals, however, fever and the associated sickness behaviors may signal a temporary loss of capacity, offering other group members competitive opportunities. We implanted wild vervet monkeys (Chlorocebus pygerythrus) with miniature data loggers to obtain continuous measurements of core body temperature. We detected 128 fevers in 43 monkeys, totaling 776 fever-days over a 6-year period. Fevers were characterized by a persistent elevation in mean and minimum 24-h body temperature of at least 0.5 °C. Corresponding behavioral data indicated that febrile monkeys spent more time resting and less time feeding, consistent with the known sickness behaviors of lethargy and anorexia, respectively. We found no evidence that fevers influenced the time individuals spent socializing with conspecifics, suggesting social transmission of infection within a group is likely. Notably, febrile monkeys were targeted with twice as much aggression from their conspecifics and were six times more likely to become injured compared to afebrile monkeys. Our results suggest that sickness behavior, together with its agonistic consequences, can carry meaningful costs for highly gregarious mammals. The degree to which social factors modulate the welfare of infected animals is an important aspect to consider when attempting to understand the ecological implications of disease.

Males in female-philopatric social groupings leave their natal groups to pursue successive reproductive opportunities in one or more other groups. In vervet monkeys, Chlorocebus pygerythrus , adult males coexist and physical eviction is not a driver of male movement. Migratory decisions are expected to turn on an evaluation of future reproductive opportunity, as indexed principally by local operational sex ratio and relative competitive ability. Although vervet males' reproductive success is correlated with dominance, they are distinctive in that the attainment of rank is contingent on integration into female sociospatial networks and we expect decisions about continued residency to reflect this. We used 8 years' data from three groups to confirm that male dispersal between groups is seasonal in our population, with a peak that is coterminous with androgen levels and precedes peak mating and conception by 4 weeks. The average length of completed residency was 459 days, with an increase in the logged rate of departure after 1428 days, which is 150 days longer than the estimated modal age at first conception by putative daughters. There were positive correlations between a male's initial and highest rank, and between his highest rank and the length of time to reach it. We found that a male's residency was positively and independently associated with his highest achieved rank and both his grooming centrality and proximity degree. Additionally, increasing rank and proximity degree also had positive effects on residency length subsequent to the attainment of his highest rank. The probability of emigration was associated negatively with both female number and grooming centrality scores. We conclude that emigration from a group is linked to male rank attainment and mediated by a male's integration into female sociospatial networks. We found no evidence that emigration preceded the sexual maturity of putative daughters.

International audience; The Signature Series Symposium "Cellular Therapies for Orthopaedics and Musculoskeletal Disease Proven and Unproven Therapies-Promise, Facts and Fantasy" was held as a pre-meeting of the 26th International Society for Cellular Therapy (ISCT) annual congress in Montreal, Canada, May 2, 2018. This was the first ISCT program that was entirely dedicated to the advancement of cell-based therapies for musculoskeletal diseases. Cellular therapies in musculoskeletal medicine are a source of great promise and opportunity. They are also the source of public controversy, confusion and misinformation. Patients, clinicians, scientists, industry and government share a commitment to clear communication and responsible development of the field. Therefore, this symposium convened thought leaders from around the world in a forum designed to catalyze communication and collaboration to bring the greatest possible innovation and value to patients with musculoskeletal conditions.

In the face of climate change there is an urgent need to understand how animal performance is affected by environmental conditions. Biophysical models that use principles of heat and mass transfer can be used to explore how an animal's morphology, physiology, and behavior interact with its environment in terms of energy, mass and water balances to affect fitness and performance. We used Niche Mapper™ (NM) to build a vervet monkey (Chlorocebus pygerythrus) biophysical model and tested the model's ability to predict core body temperature (Tb) variation and thermal stress against Tb and behavioral data collected from wild vervets in South Africa. The mean observed Tb in both males and females was within 0.5 °C of NM's predicted Tbs for 91% of hours over the five-year study period. This is the first time that NM's Tb predictions have been validated against field data from a wild endotherm. Overall, these results provide confidence that NM can accurately predict thermal stress and can be used to provide insight into the thermoregulatory consequences of morphological (e.g., body size, shape, fur depth), physiological (e.g. Tb plasticity) and behavioral (e.g., huddling, resting, shade seeking) adaptations. Such an approach allows users to test hypotheses about how animals adapt to thermoregulatory challenges and make informed predictions about potential responses to environmental change such as climate change or habitat conversion. Importantly, NM's animal submodel is a general model that can be adapted to other species, requiring only basic information on an animal's morphology, physiology and behavior.

Understanding the physiological processes that underpin primate performance is key if we are to assess how a primate might respond when navigating new and changing environments. Given the connection between an animal’s ability to thermoregulate and the changing demands of its thermal environment, increasing attention is being devoted to the study of thermoregulatory processes as a means to assess primate performance. Infrared thermography can be used to record the body surface temperatures of free-ranging animals. However, some uncertainty remains as to how these measurements can be used to approximate core body temperature. Here, we use data collected from wild vervet monkeys (Chlorocebus pygerythrus) to examine the relationship between infrared body surface, core body, and local climate, to determine to what extent surface temperatures reflect core body temperature. While we report a positive association between surface and core body temperature – a finding that has previously been used to justify the use of surface temperature measurements as a proxy for core temperature regulation – when we controlled for the effect of the local climate in our analyses, this relationship was no longer observed. That is, body surface temperatures were solely predicted by local climate, and not core body temperatures, suggesting that surface temperatures tell us more about the environment a primate is in, and less about the thermal status of its body core in that environment. Despite the advantages of a non-invasive means to detect and record animal temperatures, infrared thermography alone cannot be used to approximate core body temperature in wild primates.

Objectives: Climate change is having a significant impact on biodiversity and increasing attention is therefore being devoted to identifying the behavioral strategies that a species uses to cope with climatic stress. We explore how wild vervet monkeys (Chlorocebus pygerythrus) respond to heat stress, and how behavioral adaptations are used to regulate body temperature.\ud \ud Materials and methods: We implanted wild vervet monkeys with temperature-sensitive data loggers and related the body temperature rhythms of these animals to their use of thermoregulatory behaviors.\ud \ud Results: Environmental temperature had a positive effect on the mean, minima and maxima of daily body temperatures. Environmental temperature had a positive effect on the amount of time that vervet monkeys spent in the shade, and animals that spent more time in the shade had lower body temperature maxima. Drinking water did not have a proximate effect on body temperature, most likely a consequence of their regular access to drinking water. Body temperatures were observed to decrease after swimming events, but tended to return to pre-swim temperatures within 1 hr, suggesting a limited thermal benefit of this behavior.\ud \ud Conclusions: Our data support the view that vervet monkeys cope well in the heat, and use behavior as a means to aid thermoregulation. The ability of primates to be flexible in their use of thermoregulatory behaviors can contribute positively to their capacity to cope with environmental variability. However, given its broad effect on plant productivity and habitat loss, climate change is a major threat to species' biogeographical distribution and survival.

Sexual conflict theory expects females to avoid nonoptimal mating attempts by males. Although female vervet monkeys, Chlorocebus pygerythrus, can resist direct mating attempts, higher-ranking males still have more mating opportunities than lower-ranking ones. We presume that rank-related access reflects maleemale competition that may conflict with female reproductive objectives. We extend an earlier report of codominance in this species to show that powerful females can undermine the restrictions imposed through maleemale competition by improving the dominance rank of preferred male associates. We found that the dominance hierarchies of the sexes were comprehensively interdigitated and that males who had more female spatial associates, and who groomed with well-connected females, were more likely improve their Elo-ratings, which we use as an index of male power. The effects of partner number and integration, which predicted the probability of the initiation of aggression by lower-ranking males, suggest that association with females offered the prospect of protected threat if this likelihood increased. Although female rank and aggression were not directly consequential for males, we argue that female power and influence are intertwined and that both stem from the strength of female reproductive control.

While most primates are tropical animals, a number of species experience markedly cold winters. In a high latitude arid environment, wild female vervet monkeys (Chlorocebus pygerythrus) that are socially integrated experience reduced cold stress. Here, we ask whether sociability is similarly salient for male vervet monkeys, who reside in non-natal groups as adults and who must, therefore, develop social relationships on arrival. We use body temperature and social data from 15 free-ranging male vervet monkeys to determine whether the number of grooming partners is as important for males during winter and whether the length of residency is positively associated with body temperature. We also assess whether larger body size and higher dominance rank mitigate the need for social partnerships. Like females, male vervets respond to lower 24 h ambient temperatures and winter's progression by decreasing minimum and mean 24 h body temperatures and by regulating their temperatures less precisely. Male rank had no effect, while larger body size was associated primarily with reduced temperature fluctuations. Males with more social partners sustained higher minimum and mean body temperatures but, unexpectedly, regulated their temperatures less tightly. Further analysis revealed that higher minimum and mean temperatures were best accounted for by the number of female partners, while increased temperature fluctuation was driven by the number of male partners. As winter and the mating season overlap, we interpret this as indicating that a need to sustain male associations incurs physiological stress that is reflected as a thermoregulatory cost. Lastly, we show that longer residency is associated with higher minimum body temperatures and lower temperature fluctuations independently of social affiliation.

This chapter provides a brief historical review of the US Food and Drug Administration (FDA) and its organizational structure and discusses the regulation of regenerative medicine products, possible regulatory pathways for combination products, and relevant jurisdictional issues. Sources of information concerning FDA regulatory policies important to regenerative medicine product developers are also discussed. Suggestions are provided regarding how to engage the FDA effectively during the development of a novel regenerative medicine product.

A strong case has been made that the primary function of grooming is hygienic. Nevertheless, its persistence in the absence of hygienic demand, and its obvious tactical importance to members of primate groups, underpins the view that grooming has become uncoupled from its utilitarian objectives and is now principally of social benefit. We identify improved thermoregulatory function as a previously unexplored benefit of grooming and so broaden our understanding of the utilitarian function of this behavior. Deriving the maximum thermal benefits from the pelt requires that it be kept clean and that the loft of the pelt is maintained (i.e., greater pelt depth), both of which can be achieved by grooming. In a series of wind-tunnel experiments, we measured the heat transfer characteristics of vervet monkey (Chlorocebus pygerythrus) pelts in the presence and absence of backcombing, which we used as a proxy for grooming. Our data indicate that backcombed pelts have improved thermal performance, offering significantly better insulation than flattened pelts and, hence, better protection from the cold. Backcombed pelts also had significantly lower radiant heat loads compared to flattened pelts, providing improved protection from radiant heat. Such thermal benefits, therefore, furnish grooming with an additional practical value to which its social use is anchored. Given the link between thermoregulatory ability and energy expenditure, our findings suggest that grooming for thermal benefits may be an important explanatory variable in the relationship between levels of sociability and individual fitness. Am. J. Primatol. 78:456-461, 2016. © 2015 Wiley Periodicals, Inc.

Male reproductive strategies have been well studied in primate species where the ability of males to monopolize reproductive access is high. Less is known about species where males cannot monopolize mating access. Vervet monkeys (Chlorocebus pygerythrus) are interesting in this regard as female codominance reduces the potential for male monopolization. Under this condition, we assessed whether male dominance rank still influences male mating and reproductive success, by assigning paternities to infants in a population of wild vervets in the Eastern Cape, South Africa. To determine paternity, we established microsatellite markers from noninvasive fecal samples via cross-species amplification. In addition, we evaluated male mating and reproductive success for 3 groups over 4 mating seasons. We identified 21 highly polymorphic microsatellites (number of alleles = 7.5 ± 3.1 [mean ± SD], observed heterozygosity = 0.691 ± 0.138 [mean ± SD]) and assigned paternity to 94 of 97 sampled infants (96.9%) with high confidence. Matings pooled over 4 seasons were significantly skewed across 3 groups, although skew indices were low (B index = 0.023-0.030) and mating success did not correlate with male dominance. Paternities pooled over 4 seasons were not consistently significantly skewed (B index = 0.005-0.062), with high-ranking males siring more offspring than subordinates only in some seasons. We detected 6 cases of extra-group paternity (6.4%) and 4 cases of natal breeding (4.3%). Our results suggest that alternative reproductive strategies besides priority of access for dominant males are likely to affect paternity success, warranting further investigation into the determinants of paternity among species with limited male monopolization potential.

International audience; Among nonhuman primates, the evolutionary underpinnings of variation in social structure remain debated, with both ancestral relationships and adaptation to current conditions hypothesized to play determining roles. Here we assess whether interspecific variation in higher‐order aspects of female macaque (genus: Macaca ) dominance and grooming social structure show phylogenetic signals, that is, greater similarity among more closely‐related species. We use a social network approach to describe higher‐order characteristics of social structure, based on both direct interactions and secondary pathways that connect group members. We also ask whether network traits covary with each other, with species‐typical social style grades, and/or with sociodemographic characteristics, specifically group size, sex‐ratio, and current living condition (captive vs. free‐living). We assembled 34–38 datasets of female‐female dyadic aggression and allogrooming among captive and free‐living macaques representing 10 species. We calculated dominance (transitivity, certainty), and grooming (centrality coefficient, Newman's modularity, clustering coefficient) network traits as aspects of social structure. Computations of K statistics and randomization tests on multiple phylogenies revealed moderate‐strong phylogenetic signals in dominance traits, but moderate‐weak signals in grooming traits. GLMMs showed that grooming traits did not covary with dominance traits and/or social style grade. Rather, modularity and clustering coefficient, but not centrality coefficient, were strongly predicted by group size and current living condition. Specifically, larger groups showed more modular networks with sparsely‐connected clusters than smaller groups. Further, this effect was independent of variation in living condition, and/or sampling effort. In summary, our results reveal that female dominance networks were more phylogenetically conserved across macaque species than grooming networks, which were more labile to sociodemographic factors. Such findings narrow down the processes that influence interspecific variation in two core aspects of macaque social structure. Future directions should include using phylogeographic approaches, and addressing challenges in examining the effects of socioecological factors on primate social structure.

Zika virus (ZIKV) infection of pregnant women can cause fetal microcephaly and other neurologic defects. We describe the development of a non-human primate model to better understand fetal pathogenesis. To reliably induce fetal infection at defined times, four pregnant rhesus macaques are inoculated intravenously and intraamniotically with ZIKV at gestational day (GD) 41, 50, 64, or 90, corresponding to first and second trimester of gestation. The GD41-inoculated animal, experiencing fetal death 7 days later, has high virus levels in fetal and placental tissues, implicating ZIKV as cause of death. The other three fetuses are carried to near term and euthanized; while none display gross microcephaly, all show ZIKV RNA in many tissues, especially in the brain, which exhibits calcifications and reduced neural precursor cells. Given that this model consistently recapitulates neurologic defects of human congenital Zika syndrome, it is highly relevant to unravel determinants of fetal neuropathogenesis and to explore interventions., Zika virus infection of pregnant women can cause congenital brain defects. Here, Coffey et al. establish a pregnant rhesus macaque model, using intravenous and intraamniotic route of infection, that reliably reproduces fetal neurologic defects of congenital Zika syndrome in humans.

Regenerative medicine (RM) is a popular term for a field of scientific and medical research. There is not one universally accepted definition of RM, but it is generally taken to mean the translation of multidisciplinary biology and engineering science into therapeutic approaches to regenerate, replace, or repair tissues and organs. RM products have the potential to provide treatments for a number of unmet needs but have substantial scientific and regulatory challenges that need to be addressed for this potential to be fully realized. FDA has established formal regulatory definitions for biologics, medical devices, and combination products, as well as human cells and tissues. Regenerative medicine products regulated by FDA are classified on the basis of these definitions, and the classification forms the basis for determining the regulatory requirements to each specific product. FDA regulations are generally written to allow the agency flexibility to accommodate new scientific questions raised by novel and evolving technologies. FDA efforts to facilitate product development in this novel and promising area include working with individual sponsors, interacting with the scientific and industry communities, participating in standards development, and developing policy and guidance. Significance Regenerative medicine is generally taken to mean the translation of multidisciplinary biology and engineering science into therapeutic approaches to regenerate, replace, or repair tissues and organs. This article provides an overview of the efforts of the U.S. Food and Drug Administration (FDA) to facilitate product development in the field commonly known was regenerative medicine. It provides an introduction to the processes by which FDA works with individual sponsors, interacts with the scientific and industry communities, participates in standards development, and develops formal FDA policy and guidance.

Responses to environmental variability sheds light on how individuals are able to survive in a particular habitat and provides an indication of the scope and limits of its niche. To understand whether climate has a direct impact on activity, and determine whether vervet monkeys have the behavioral flexibility to respond to environmental change, we examined whether the amount of time spent resting and feeding in the nonmating and mating seasons were predicted by the thermal and energetic constraints of ambient temperature. Our results show that high temperatures during the nonmating season were associated with an increase in time spent resting, at the expense of feeding. Cold temperatures during the nonmating season were associated with an increase in time spent feeding, at the expense of resting. In contrast, both feeding and resting time during the mating season were independent of temperature, suggesting that animals were not adjusting their activity in relation to temperature during this period. Our data indicate that climate has a direct effect on animal activity, and that animals may be thermally and energetically compromised in the mating season. Our study animals appear to have the behavioral flexibility to tolerate current environmental variability. However, future climate change scenarios predict that the time an animal has available for behaviors critical for survival will be constrained by temperature. Further investigations, aimed at determining the degree of behavioral and physiological flexibility displayed by primates, are needed if we are to fully understand the consequences of environmental change on their distribution and survival.

Regulatory authorities require safety and potency testing prior to the release of each production lot of acellular pertussis (aP)-containing vaccines. Currently, the murine histamine sensitization test (HIST) is used to evaluate the presence of residual pertussis toxin in aP containing vaccines. However, the testing requires the use of a significant number of mice and results in unrelieved pain and distress. NICEATM, ICCVAM, their partners in the International Cooperation on Alternative Test Methods, and the International Working Group for Alternatives to HIST organized a workshop to discuss recent developments in alternative assays to the HIST, review data from an international collaborative study on non-animal alternative tests that might replace the HIST, and address the path toward global acceptance of this type of method. Currently, there are three potential alternative methods to HIST. Participants agreed that no single in vitro method was sufficiently developed for harmonized validation studies at this time. It is unlikely that any single in vitro method would be applicable to all aP vaccines without modification, due to differences between vaccines. Workshop participants recommended further optimization of cell-based assays under development. Participants agreed that the next international collaborative studies should commence in 2013 based on discussions during this workshop.

Climatic conditions can significantly affect the behavior of animals and constrain their activity or geographic distribution. Barbary macaques (Macaca sylvanus) are one of the few primates that live outside the tropics. Here we analyze if and how the activity budgets of Barbary macaques are affected by climatic variables, i.e., air temperature, relative humidity, rainfall, and snow coverage. We collected scan sampling data on the activity budgets of four groups of macaques living in the Middle Atlas Mountains of Morocco from June 2008 to January 2011. This habitat is characterized by extreme seasonal changes, from cold and snowy winters to hot and dry summers. The activity budgets of the macaques differed across months but not across the time of day (with the exception of time spent feeding). The monkeys spent significantly more time feeding or foraging when there was no snow than when snow coverage was moderate or major. Daily rainfall was positively related to resting time and negatively to time spent moving or in social behavior. Air temperature was negatively related to time spent feeding or foraging. Finally, time spent on social behavior was significantly lower when relative humidity was high. These data indicate that environmental factors significantly affect the time budgets of endangered Barbary macaques, a species that has been little studied in the wild. Our findings support previous studies on temperate primates in showing that snow coverage can have negative consequences on the feeding ecology and survival of these species.

Assessmentof animal activity patterns can shed lighton a rangeof behavioural and ecological processes. The timing of activity canhelp improve understanding of a species’ spatial ecology, chrono-biology, energetic demands, reproductive strategy and nutritionalrequirements (Halle & Stenseth 2000; Erkert 2003). Activity dataare also useful for the assessment of animal welfare and conser-vation planning (Kitchen & Martin 1996; Broom & Fraser 2007;Cooke 2008); Activity patterns allow us to measure the impact ofhuman disturbance on habitat viability and behaviour (Williamset al. 2006; Yang et al. 2007), and to predict the influence of localor global climate change on the survival and distribution of a spe-cies or population (Walther et al. 2002; Hetem et al. 2012). Reliablemeasures of activity are thus fundamental to furthering our un-derstanding of animal behaviour and ecology.Two main methodological approaches have been used to recordthe activity patterns of free-ranging animals: behavioural obser-vation and biologging (reviewed in Cooke et al. 2004; Nathan et al.2012; Ropert-Coudert et al. 2012). Instantaneous scan sampling(Altmann 1974) is the most commonly used method to record ac-tivity and behaviour data in traditional studies of animal behav-ioural ecology. Scan sampling involves human observers recordingthe activity state (i.e. resting, foraging, travelling or social) of studyanimals at predetermined time intervals, to provide a descriptivemeasure of an individual’s or group’s activity. Scan sampling allowsarangeofbehaviouralinformation(e.g.diet, posture andproximityto conspecifics), in addition to states of activity, to be recordedsimultaneously. However, scan sampling often requires studysubjects to be individually identifiable and habituated to thepresence of human observers, and data can, by definition, only becollected during those periods when human observers are present.These prerequisites for successful scan sampling mayconstrain thecollectionofactivitydata.Insomespeciesorpopulationsitmaynotbe feasible to follow animals regularly, for example, if they arenocturnal or live in an inaccessible habitat, or if the researcher’spresence disrupts normal activity patterns.Biologgers,eitherattachedexternallyorimplantedintheanimal’sbody, have become increasingly popular for recording activityremotely(Cookeetal.2004;Ropert-Coudertetal.2012).Thesedevices

In order to understand the factors that cause and mediate stress in social animals, many studies have examined differences in male physiological stress levels between mating and non-mating seasons, and related these differences to levels of male-male competition. Very few have explicitly tested whether variation in stress levels is related to mating behaviour itself. We provide preliminary evidence of a negative relationship between faecal levels of glucocorticoid metabolites and mounting frequency in free-ranging male rhesus macaques (Macaca mulatta). This finding may help explain the previous observation that male rhesus macaques show no difference in their levels of faecal glucocortocoids between the breeding and non-breeding season, despite the former being associated with elevated levels of aggression. Our study highlights the importance of directly quantifying mating behaviour when investigating the potential impact of reproductive competition and seasonality on stress physiology.

Reconciliation is the most extensively studied conflict resolution mechanism in animal societies. However, despite the extensive literature on this topic, behaviors considered to represent postconflict affiliation have not been consistent across studies of reconciliation. Critically, reconciliation is usually defined as postconflict contact affiliation, e.g., grooming, and the importance of including interopponent distance regulation is often neglected. Moreover, to date, no study has simultaneously investigated different behavioral forms of reconciliation. We tested in two groups of wild Barbary macaques (Macaca sylvanus) the relative importance of postconflict close proximity and grooming in the mediation of two important costs of aggression: damage to the opponent’s social relationship and elevated postconflict anxiety. We provide evidence that close-proximity approaches function to resolve conflicts: Close-proximity approaches reduced the victim’s postconflict anxiety and were predicted by the quality of the social relationship with the opponent. Moreover, postconflict grooming alone, although predicted by the quality of the opponent’s social relationship, did not influence the victim’s elevated postconflict anxiety. Our results suggest that interopponent distance regulation plays an important role in reconciling the costs of aggression in Barbary macaques. We advocate that further efforts should be made to test which behaviors play a role in conflict resolution in different species. This is important because even closely related species may differ in the function of behaviors that superficially appear to be rather similar. Moreover, the choice of behaviors used to study conflict resolution determines the frequency with which reconciliation is observed and can thus bias comparisons across species.

The first guidance on Good Cell Culture Practice (GCCP) dates back to 2005. This document expands this to include aspects of quality assurance for in vitro cell culture focusing on the increasingly diverse cell types and culture formats used in research, product development, testing and manufacture of biotechnology products and cell-based medicines. It provides a set of basic principles of best practice that can be used in training new personnel, reviewing and improving local procedures, and helping to assure standard practices and conditions for the comparison of data between laboratories and experimentation performed at different times. This includes recommendations for the documentation and reporting of culture conditions. It is intended as guidance to facilitate the generation of reliable data from cell culture systems, and is not intended to conflict with local or higher level legislation or regulatory requirements. It may not be possible to meet all recommendations in this guidance for practical, legal or other reasons. However, when it is necessary to divert from the principles of GCCP, the risk of decreasing the quality of work and the safety of laboratory staff should be addressed and any conclusions or alternative approaches justified. This workshop report is considered a first step toward a revised GCCP 2.0.

It has long been shown that the social environment of individuals can have strong effects on health, well-being, and longevity in a wide range of species. Several recent studies found that an individual’s number of affiliative partners positively relates to its probability of survival. Here, we build on these previous results to test how both affiliation and aggression networks predict Barbary macaque (Macaca sylvanus) survival in a “natural experiment.” Thirty out of 47 wild Barbary macaques, living in 2 groups, died during an exceptionally cold winter in the Middle Atlas Mountains, Morocco. We analyzed the affiliation and aggression networks of both groups in the 6 months before the occurrences of these deaths, to assess which aspects of their social relationships enhanced individual survivorship. Using only the affiliation network, we found that network clustering was highly predictive of individual survival probability. Using only the aggression network, we found that individual survival probability increased with a higher number of aggression partners and lower clustering coefficient. Interestingly, when both affiliation and aggression networks were considered together, only parameters from the aggression network were included into the best model predicting individual survival. Aggressive relationships might serve to stabilize affiliative social relationships, thereby positively impacting on individual survival during times of extreme weather conditions. Overall, our findings support the view that aggressive social interactions are extremely important for individual well-being and fitness.

The majority of studies investigating conflict management in animal societies have focused on the role of reconciliation in mediating the costs of aggression. The function of bystander affiliation (i.e. the selective attraction between an opponent and a bystander in the minutes immediately following aggression) is less well understood. We examined, in wild Barbary macaques, four potential functions of bystander affiliation with the victim of aggression: (1) bystander-initiated affiliation to reduce the victim's postconflict (PC) anxiety (i.e. ‘consolation’), (2) victim-initiated affiliation (i.e. ‘solicited consolation’), (3) victim- and bystander-initiated affiliation to avert redirected aggression (i.e. self-protection), and (4) bystander-initiated affiliation to exploit grooming from the victim. We found partial support for the consolation function as bystander-initiated affiliation occurred more frequently between high-quality social partners but had no effect on the victim's PC anxiety. In support of the solicited-consolation function, victim-initiated affiliation occurred more frequently between high-quality social partners and also caused a reduction in the victim's PC anxiety. These findings suggest that solicited consolation may substitute for the stress alleviation role of reconciliation. We found no support for a self-protective function as neither the bystander's nor the victim's risk of receiving PC aggression was reduced following bystander affiliation with the victim. Finally, bystanders received significantly more PC grooming than victims, suggesting that grooming exploitation of the victim may drive the bystander's PC behaviour. Our results indicate that bystander affiliation has different functions and benefits for the victim of aggression and the bystander, and highlights the importance of considering which individual initiates this behaviour.

Potency testing of most human and veterinary rabies vaccines requires vaccination of mice followed by a challenge test using an intracerebral injection of live rabies virus. NICEATM, ICCVAM, and their international partners organized a workshop to review the availability and validation status of alternative methods that might reduce, refine, or replace the use of animals for rabies vaccine potency testing, and to identify research and development efforts to further advance alternative methods. Workshop participants agreed that general anesthesia should be used for intracerebral virus injections and that humane endpoints should be used routinely as the basis for euthanizing animals when conducting the mouse rabies challenge test. Workshop participants recommended as a near-term priority replacement of the mouse challenge with a test validated to ensure potency, such as the mouse antibody serum neutralization test for adjuvanted veterinary rabies vaccines for which an international collaborative study was recently completed. The workshop recommended that an in vitro antigen quantification test should be a high priority for product-specific validation of human and non-adjuvanted veterinary rabies vaccines. Finally, workshop participants recommended greater international cooperation to expedite development, validation, regulatory acceptance, and implementation of alternative test methods for rabies vaccine potency testing.

The ‘integrated hypothesis’ predicts that reconciliation (the post-conflict friendly interaction between former opponents observed in various group-living species) functions to reduce anxiety and the risk of aggression from the former opponent or a bystander in the aftermath of a conflict. It also predicts that relationship quality between opponents affects the occurrence of reconciliation and modulates the anxious response of the opponents after a conflict. Because of the asymmetric nature of aggressive interactions, the cost of aggression is likely to differ between the victim and the aggressor. The aim of this study was to test the predictions of the ‘integrated hypothesis’ independently for the victim and the aggressor of a conflict. We collected data on two wild groups of Barbary macaques. This study represents, to our knowledge, the first systematic test of the integrated hypothesis on wild, non-provisioned animals. Victims of aggression were at a greater risk of receiving aggression from the former opponent or a bystander after a conflict and showed elevated anxiety. We found no such costs for the aggressor. Reconciliation reduced anxiety in the victim but did not reduce their risk of receiving aggression. Finally, relationship quality affected the occurrence of reconciliation but did not modulate post-conflict anxiety. The results of our study show that the costs of aggression are asymmetrically distributed between the victim and the aggressor. Such differences are likely to lead to different social tactics used by the victim and the aggressor in the aftermath of a conflict.

Vaccines contribute to improved animal and human health and welfare by preventing diseases and deaths from infectious diseases. However, testing necessary to ensure vaccine effectiveness and safety can involve large numbers of animals and significant pain and distress. NICEATM and ICCVAM recently convened an international workshop to review the state of the science of available alternative methods and approaches that can further reduce, refine, and replace the use of animals for human and veterinary vaccine potency and safety testing, and to identify research, development, and validation efforts necessary to further advance new and improved alternative methods. Workshop participants identified human and veterinary vaccines that should have the highest priority for future efforts. Prioritization criteria included testing that involves significant pain and distress, large numbers of animals, and pathogens that are dangerous to people and animals. Participants noted that in vitro antigen quantification assays have replaced animals for potency testing for some killed vaccines, and recommended that this approach be expanded to other vaccines. Recommendations to support more humane animal use included development and use of humane endpoints for all challenge tests, development of serologic assays to replace challenge tests, and development of in vitro toxin neutralization tests (TNT) to replace in vivo TNTs. Workshop participants recommended several approaches that might further reduce the number of animals required for specific potency tests. Participants also recommended priority vaccines for which alternative safety testing methods should be pursed and that would have the greatest impact on avoiding pain and distress and reducing animal numbers. Finally, workshop participants recommended enhanced international harmonization and cooperation efforts and closer collaborations between human and veterinary researchers to expedite progress. Implementation of the workshop recommendations is expected to advance new methods for vaccine testing that will reduce animal use, benefit animal welfare, and ensure continued and improved protection of human and animal health.

NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods, and to identify opportunities to advance new and improved methods that can further reduce, refine, and replace animal use. This report addresses methods and strategies identified by workshop participants for replacement of animals used for potency testing of human vaccines. Vaccines considered to have the highest priority for future efforts were (1) vaccines for which antigen quantification methods are already developed but not validated, (2) vaccines/components that require the largest number of animals, (3) vaccines that require an in vivo challenge test, and (4) vaccines with in vivo tests that are highly variable and cause a significant number of invalid tests. Vaccine potency tests identified as the highest priorities for replacement were those for diphtheria and tetanus, pertussis (whole cell and acellular), rabies, anthrax, polio vaccine (inactivated) and complex combination vaccines based on DT or DTwP/aP. Research into understanding the precise mechanism of protection afforded by vaccines and the identification of clinically relevant immunological markers are needed to facilitate the successful implementation of in vitro testing alternatives. This report also identifies several priority human vaccines and associated research objectives that are necessary to successfully implement in vitro vaccine potency testing alternatives.

A strong case has been made that the primary function of grooming is hygienic. Nevertheless, its persistence in the absence of hygienic demand, and its obvious tactical importance to members of primate groups, underpins the view that grooming has become uncoupled from its utilitarian objectives and is now principally of social benefit. We identify improved thermoregulatory function as a previously unexplored benefit of grooming and so broaden our understanding of the utilitarian function of this behavior. Deriving the maximum thermal benefits from the pelt requires that it be kept clean and that the loft of the pelt is maintained (i.e., greater pelt depth), both of which can be achieved by grooming. In a series of wind-tunnel experiments, we measured the heat transfer characteristics of vervet monkey (Chlorocebus pygerythrus) pelts in the presence and absence of backcombing, which we used as a proxy for grooming. Our data indicate that backcombed pelts have improved thermal performance, offering significantly better insulation than flattened pelts and, hence, better protection from the cold. Backcombed pelts also had significantly lower radiant heat loads compared to flattened pelts, providing improved protection from radiant heat. Such thermal benefits, therefore, furnish grooming with an additional practical value to which its social use is anchored. Given the link between thermoregulatory ability and energy expenditure, our findings suggest that grooming for thermal benefits may be an important explanatory variable in the relationship between levels of sociability and individual fitness. Am. J. Primatol. 78:456-461, 2016. © 2015 Wiley Periodicals, Inc.

The field of regenerative medicine encompasses a breathtaking array of interdisciplinary scientific approaches with the promise of delivering future therapies to meet current unmet medical needs for patients. Increasingly more of these innovative products are being translated into human clinical trials in the United States, and general familiarity of the FDA is important to efficiently navigate the process. The basics of FDA history, organization, and processes are described herein for those new to clinical translation, with more detailed content added regarding approval pathways, regulations, guidances, and select special topics of relevance to regenerative medicine. In addition to the cumulative experience of previous products, the FDA regulatory approach to medical products evaluation includes an ongoing assessment of how the science of those products informs regulatory policy. FDA engages in ongoing dialogue with the scientific community and product sponsors to continue to develop science-based regulatory review policies that are robust and predictable in order to meet the needs of the challenging array of products that are on the horizon.

1. Sociality has been shown to have adaptive value for gregarious species, with more socially integrated animals within groups experiencing higher reproductive success and longevity. The value of social integration is often suggested to derive from an improved ability to deal with social stress within a group; other potential stressors have received less attention.\ud 2. We investigated the relationship between environmental temperature, an important non-social stressor, and social integration in wild female vervet monkeys (Chlorocebus pygerythrus), using implanted data loggers to obtain direct measures of core body temperature.\ud 3. Heterothermy (as measured by 24-h amplitude of body temperature) increased, and 24-h minima of body temperature decreased, as the 24-h minimum ambient temperature decreased. As winter progressed, monkeys became increasingly heterothermic and displayed lower 24-h minima of body temperature.\ud 4. Monkeys with a greater number of social partners displayed a smaller 24-h amplitude (that is, were more homoeothermic) and higher 24-h minima of body temperature (that is, became less hypothermic), than did animals with fewer social partners.\ud 5. Our findings demonstrate that social integration has a direct influence on thermoregulatory ability: individual animals that form and maintain more social relationships within their group experience improved thermal competence compared to those with fewer social relationships.\ud 6. Given the likely energetic consequences of thermal benefits, our findings offer a viable physiological explanation that can help account for variations in fitness in relation to individual differences in social integration.