Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer.

BACKGROUND: Post-treatment detection of circulating tumour DNA (ctDNA) in early-stage triple-negative breast cancer (TNBC) patients predicts high risk of relapse. c-TRAK TN assessed the utility of prospective ctDNA surveillance in TNBC and the activity of pembrolizumab in patients with ctDNA detected [ctDNA positive (ctDNA+)]. PATIENTS AND METHODS: c-TRAK TN, a multicentre phase II trial, with integrated prospective ctDNA surveillance by digital PCR, enrolled patients with early-stage TNBC and residual disease following neoadjuvant chemotherapy, or stage II/III with adjuvant chemotherapy. ctDNA surveillance comprised three-monthly blood sampling to 12 months (18 months if samples were missed due to coronavirus disease), and ctDNA+ patients were randomised 2 : 1 to intervention : observation. ctDNA results were blinded unless patients were allocated to intervention, when staging scans were done and those free of recurrence were offered pembrolizumab. A protocol amendment (16 September 2020) closed the observation group; all subsequent ctDNA+ patients were allocated to intervention. Co-primary endpoints were (i) ctDNA detection rate and (ii) sustained ctDNA clearance rate on pembrolizumab (NCT03145961). RESULTS: Two hundred and eight patients registered between 30 January 2018 and 06 December 2019, 185 had tumour sequenced, 171 (92.4%) had trackable mutations, and 161 entered ctDNA surveillance. Rate of ctDNA detection by 12 months was 27.3% (44/161, 95% confidence interval 20.6% to 34.9%). Seven patients relapsed without prior ctDNA detection. Forty-five patients entered the therapeutic component (intervention n = 31; observation n = 14; one observation patient was re-allocated to intervention following protocol amendment). Of patients allocated to intervention, 72% (23/32) had metastases on staging at the time of ctDNA+, and 4 patients declined pembrolizumab. Of the five patients who commenced pembrolizumab, none achieved sustained ctDNA clearance. CONCLUSIONS: c-TRAK TN is the first prospective study to assess whether ctDNA assays have clinical utility in guiding therapy in TNBC. Patients had a high rate of metastatic disease on ctDNA detection. Findings have implications for future trial design, emphasising the importance of commencing ctDNA testing early, with more sensitive and/or frequent ctDNA testing regimes.

The impacts of seasonal variation and climate on food utilization in a population of critically endangered cotton-top tamarins (Saguinus oedipus) in Colombia: A 22-year longitudinal study.

To examine how precipitation patterns and climate change impact feeding choices made by a population of critically endangered cotton-top tamarins (Saguinus oedipus), we examined 22 years of feeding data (1999-2020) from 21 groups collected at Parque Natural Regional Bosque Seco El Ceibal Mono Tití in Santa Catalina, Colombia. We describe the diet and examine the role of seasonal rainfall and annual variation in rainfall on diet. Rainfall is highly seasonal (mean annual rainfall 1562 mm [range 940-2680 mm]) with a dry, early rainy, and late rainy season in each year. Over 80 species of plants formed part of the fruit, nectar, and exudate components of the diet. Fruits, although available year-round, were more commonly available and consumed during the late rainy seasons (August-November). Exudates were consumed more frequently in the dry season (December-March) and invertebrate consumption was stable across the year. Nectar feeding from a single species (Combretum fruticosum) peaked in November. Rainfall varied over the years, with 13 years exceeding the 99% confidence intervals for mean rainfall. Ten of these extreme years (both drought and extremely wet) occurred in the last 11 years. Fruit consumption did not vary between extreme and average years, but cotton-top tamarins consumed more invertebrates and exudates in wet years. Presently, cotton-top tamarins appear to be able to cope with these extreme variations in rainfall due to their highly varied diet. However, the forests that these primates depend upon for survival are threatened by human exploitation making it critically important to maintain a generalist feeding strategy for survival as many fruiting trees that compose a large proportion of the diet are removed. As conservation efforts continue, plant species consumed by cotton-top tamarins provide useful data when selecting species for habitat restoration programs.

Written versus verbal consent: a qualitative study of stakeholder views of consent procedures used at the time of recruitment into a peripartum trial conducted in an emergency setting.

BACKGROUND: Obtaining prospective written consent from women to participate in trials when they are experiencing an obstetric emergency is challenging. Alternative consent pathways, such as gaining verbal consent at enrolment followed, later, by obtaining written consent, have been advocated by some clinicians and bioethicists but have received little empirical attention. We explored women's and staff views about the consent procedures used during the internal pilot of a trial (GOT-IT), where the protocol permitted staff to gain verbal consent at recruitment. METHODS: Interviews with staff (n = 27) and participating women (n = 22). Data were analysed thematically and interviews were cross-compared to identify differences and similarities in participants' views about the consent procedures used. RESULTS: Women and some staff highlighted benefits to obtaining verbal consent at trial enrolment, including expediting recruitment and reducing the burden on those left exhausted by their births. However, most staff with direct responsibility for taking consent expressed extreme reluctance to proceed with enrolment until they had obtained written consent, despite being comfortable using verbal procedures in their clinical practice. To account for this resistance, staff drew a strong distinction between research and clinical care and suggested that a higher level of consent was needed when recruiting into trials. In doing so, staff emphasised the need to engage women in reflexive decision-making and highlighted the role that completing the consent form could play in enabling and evidencing this process. While most staff cited their ethical responsibilities to women, they also voiced concerns that the absence of a signed consent form at recruitment could expose them to greater risk of litigation were an individual to experience a complication during the trial. Inexperience of recruiting into peripartum trials and limited availability of staff trained to take consent also reinforced preferences for obtaining written consent at recruitment. CONCLUSIONS: While alternative consent pathways have an important role to play in advancing emergency medicine research, and may be appreciated by potential recruits, they may give rise to unintended ethical and logistical challenges for staff. Staff would benefit from training and support to increase their confidence and willingness to recruit into trials using alternative consent pathways. TRIAL REGISTRATION: This qualitative research was undertaken as part of the GOT-IT Trial (trial registration number: ISCRTN 88609453 ). Date of registration 26/03/2014.

Long-term assessment of quality of life in the Intergroup Exemestane Study: 5 years post-randomisation.

BACKGROUND: The Intergroup Exemestane Study (IES) (ISRCTN11883920) demonstrated improved survival for postmenopausal women with ER-positive/unknown primary breast cancer who switched to exemestane after 2-3 years tamoxifen, compared with those continuing on tamoxifen to complete 5 years therapy. This was achieved without detriment to on-treatment quality-of-life (QoL). We report on- and post-treatment QoL impact in IES. METHODS: A total of 582 patients from 8 countries participated in the QoL substudy. Functional Assessment of Cancer Therapy-Breast (FACT-B) and endocrine symptom subscale (ES) were completed at baseline, 3, 6, 9, 12, 18, 24, 30, 36, 48 and 60 months. The primary endpoint was FACT-B Trial Outcome Index (TOI); secondary endpoints included severity of individual endocrine symptoms. RESULTS: Both the groups showed gradual improvement in overall QoL and lessening of total endocrine symptoms post treatment compared with baseline (P<0.002). There was no evidence of any between-group differences in TOI. Vasomotor complaints remained high on treatment. Vaginal discharge was more frequent (P<0.01) with tamoxifen up to 24 months from baseline. In both the groups, post-treatment libido did not recover to baseline levels. CONCLUSION: Clinical benefits of switching to exemestane are accompanied by good overall QoL. Although some symptoms persist, the majority of endocrine symptoms improve after treatment completion.

Long-term endometrial effects in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES)--a randomised controlled trial of exemestane versus continued tamoxifen after 2-3 years tamoxifen.

BACKGROUND: The antiestrogen tamoxifen may have partial estrogen-like effects on the postmenopausal uterus. Aromatase inhibitors (AIs) are increasingly used after initial tamoxifen in the adjuvant treatment of postmenopausal early breast cancer due to their mechanism of action: a potential benefit being a reduction of uterine abnormalities caused by tamoxifen. PATIENTS AND METHODS: Sonographic uterine effects of the steroidal AI exemestane were studied in 219 women participating in the Intergroup Exemestane Study: a large trial in postmenopausal women with estrogen receptor-positive (or unknown) early breast cancer, disease free after 2-3 years of tamoxifen, randomly assigned to continue tamoxifen or switch to exemestane to complete 5 years adjuvant treatment. The primary end point was the proportion of patients with abnormal (> or =5 mm) endometrial thickness (ET) on transvaginal ultrasound 24 months after randomisation. RESULTS: The analysis included 183 patients. Two years after randomisation, the proportion of patients with abnormal ET was significantly lower in the exemestane compared with tamoxifen arm (36% versus 62%, respectively; P = 0.004). This difference emerged within 6 months of switching treatment (43.5% versus 65.2%, respectively; P = 0.01) and disappeared within 12 months of treatment completion (30.8% versus 34.7%, respectively; P = 0.67). CONCLUSION: Switching from tamoxifen to exemestane significantly reverses endometrial thickening associated with continued tamoxifen.

An investigation of patients' motivations for their participation in genetics-related research.

DESIGN: Qualitative interview study. PARTICIPANTS: Fifty-nine patients with a family history of cancer who attend a regional cancer genetics clinic in the UK were interviewed about their current and previous research experiences. FINDINGS: Interviewees gave a range of explanations for research participation. These were categorised as (a) social--research participation benefits the wider society by progressing science and improving treatment for everyone; (b) familial--research participation may improve healthcare and benefit current or future generations of the participant's family; and (c) personal--research participation provides therapeutic or non-therapeutic benefits for oneself. CONCLUSIONS: We discuss the distinction drawn between motives for research participation focused upon self (personal) and others (familial/social), and observe that personal, social and familial motives can be seen as interdependent. For example, research participation that is undertaken to benefit others, particularly relatives, may also offer a number of personal benefits for self, such as enabling participants to feel that they have discharged their social or familial obligations. We argue for the need to move away from simple, static, individualised notions of research participation to a more complex, dynamic and inherently social account.

Male parenting and response to infant stimuli in the common marmoset (Callithrix jacchus).

Callithrix jacchus infants are raised in complex family environments where most members participate in rearing the young. Many studies examining male parental behavior have focused on the carrying of infants with observations made within the family context. However, interference from family members can make it difficult to assess the father's motivation to care for infants. Our goals were to develop a testing paradigm for determining an individual's response to infant stimuli separate from family influences, compare a male's motivation to respond to an infant stimulus outside the family with his paternal behavior within the family, to compare responses to infant stimuli of parentally experienced versus inexperienced males and finally to develop a reproducible and standardized method of testing male responsiveness to infant stimulus that could serve to evaluate hormonal manipulations. Fifteen experienced common marmoset fathers were evaluated using three different measures of parental behavior: (1) instantaneous scan sampling, (2) continuous focal sampling in the family, and (3) continuous focal sampling of males presented with four infant stimuli: familiar and unfamiliar infants, familiar and unfamiliar infant vocalizations. Six parentally inexperienced males (non-fathers) served as controls. Males that carried the most in the family were typically the same males that responded most to the infant vocalization tests. Experienced fathers did not differ in their latency to enter the stimulus cage for any of the four infant stimuli response tests while inexperienced males took significantly longer to enter the stimulus cage. In addition, fathers expressed a greater frequency of infant-directed behavior than did the inexperienced males during the unfamiliar infant and unfamiliar vocalization tests. These studies show that experienced male marmosets are highly motivated to interact with infant stimuli and that there is interindividual variability in response to infant vocalizations. Testing males outside of the family allows for a clear assessment of male's interest in infant stimuli in both parentally experienced fathers and inexperienced males.

Recruitment to randomised trials: strategies for trial enrollment and participation study. The STEPS study.

OBJECTIVES: To identify factors associated with good and poor recruitment to multicentre trials. DATA SOURCES: Part A: database of trials started in or after 1994 and were due to end before 2003 held by the Medical Research Council and Health Technology Assessment Programmes. Part B: interviews with people playing a wide range of roles within four trials that their funders identified as 'exemplars'. Part C: a large multicentre trial (the CRASH trial) of treatment for head injury. REVIEW METHODS: The study used a number of different perspectives ('multiple lenses'), and three components. Part A: an epidemiological review of a cohort of trials. Part B: case studies of trials that appeared to have particularly interesting lessons for recruitment. Part C: a single, in-depth case study to examine the feasibility of applying a business-orientated analytical framework as a reference model in future trials. RESULTS: In the 114 trials found in Part A, less than one-third recruited their original target within the time originally specified, and around one-third had extensions. Factors observed more often in trials that recruited successfully were: having a dedicated trial manager, being a cancer or drug trial, and having interventions only available inside the trial. The most commonly reported strategies to improve recruitment were newsletters and mailshots, but it was not possible to assess whether they were causally linked to changes in recruitment. The analyses in Part B suggested that successful trials were those addressing clinically important questions at a timely point. The investigators were held in high esteem by the interviewees, and the trials were firmly grounded in existing clinical practices, so that the trial processes were not alien to clinical collaborators, and the results could be easily applicable to future practice. The interviewees considered that the needs of patients were well served by participation in the trials. Clinical collaborators particularly appreciated clear delineation of roles, which released them from much of the workload associated with trial participation. There was a strong feeling from interviewees that they were proud to be part of a successful team. This pride fed into further success. Good groundwork and excellent communications across many levels of complex trial structures were considered to be extremely important, including training components for learning about trial interventions and processes, and team building. All four trials had faced recruitment problems, and extra insights into the working of trials were afforded by strategies invoked to address them. The process of the case study in Part C was able to draw attention to a body of research and practice in a different discipline (academic business studies). It generated a reference model derived from a combination of business theory and work within CRASH. This enabled identification of weaker managerial components within CRASH, and initiatives to strengthen them. Although it is not clear, even within CRASH, whether the initiatives that follow from developing and applying the model will be effective in increasing recruitment or other aspects of the success of the trial, the reference model could provide a template, with potential for those managing other trials to use or adapt it, especially at foundation stages. The model derived from this project could also be used as a diagnostic tool if trials have difficulties and hence as a basis for deciding what type of remedial action to take. It may also be useful for auditing the progress of trials, such as during external review. CONCLUSIONS: While not producing sufficiently definitive results to make strong recommendations, the work here suggests that future trials should consider the different needs at different phases in the life of trials, and place greater emphasis on 'conduct' (the process of actually doing trials). This implies learning lessons from successful trialists and trial managers, with better training for issues relating to trial conduct. The complexity of large trials means that unanticipated difficulties are highly likely at some time in every trial. Part B suggested that successful trials were those flexible and robust enough to adapt to unexpected issues. Arguably, the trialists should also expect agility from funders within a proactive approach to monitoring ongoing trials. Further research into different recruitment patterns (including 'failures') may help to clarify whether the patterns seen in the 'exemplar' trials differ or are similar. The reference model from Part C needs to be further considered in other similar and different trials to assess its robustness. These and other strategies aimed at increasing recruitment and making trials more successful need to be formally evaluated for their effectiveness in a range of trials.

Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial.

BACKGROUND: Early improvements in disease-free survival have been noted when an aromatase inhibitor is given either instead of or sequentially after tamoxifen in postmenopausal women with oestrogen-receptor-positive early breast cancer. However, little information exists on the long-term effects of aromatase inhibitors after treatment, and whether these early improvements lead to real gains in survival. METHODS: 4724 postmenopausal patients with unilateral invasive, oestrogen-receptor-positive or oestrogen-receptor-unknown breast cancer who were disease-free on 2-3 years of tamoxifen, were randomly assigned to switch to exemestane (n=2352) or to continue tamoxifen (n=2372) for the remainder of a 5-year endocrine treatment period. The primary endpoint was disease-free survival; overall survival was a secondary endpoint. Efficacy analyses were intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN11883920. RESULTS: After a median follow-up of 55.7 months (range 0-89.7), 809 events contributing to the analysis of disease-free survival had been reported (354 exemestane, 455 tamoxifen); unadjusted hazard ratio 0.76 (95% CI 0.66-0.88, p=0.0001) in favour of exemestane, absolute benefit 3.3% (95% CI 1.6-4.9) by end of treatment (ie, 2.5 years after randomisation). 222 deaths occurred in the exemestane group compared with 261 deaths in the tamoxifen group; unadjusted hazard ratio 0.85 (95% CI 0.71-1.02, p=0.08), 0.83 (0.69-1.00, p=0.05) when 122 patients with oestrogen-receptor-negative disease were excluded. CONCLUSIONS: Our results suggest that early improvements in disease-free survival noted in patients who switch to exemestane after 2-3 years on tamoxifen persist after treatment, and translate into a modest improvement in overall survival.

Fruit availability, chimpanzee diet, and grouping patterns on Rubondo Island, Tanzania.

We examined seasonal patterns of fruit availability, dietary quality, and group size in the descendants of an introduced chimpanzee population on Rubondo Island, Tanzania. The site has supported a free-ranging population without provisioning for 40 years. Our goals were to determine whether Rubondo chimpanzees experience periods of fruit shortage, and whether they respond to changes in fruit availability similarly to chimpanzees at endemic sites. We indexed the fruit availability of tree and liana species on transects stratified across three chimpanzee ranging areas. We used fecal analyses to evaluate seasonal changes in diet, and used data on party size and nesting group size to examine seasonal patterns of grouping. Tree fruit availability was positively correlated with rainfall, with a period of relative tree fruit scarcity corresponding with the long dry season. Liana fruit availability was not related to rainfall, and lianas exhibited less variable fruiting patterns across seasons. Fruits made up the majority of the chimpanzee diet, with lianas accounting for 35% of dietary fruit species. Fruits of the liana Saba comorensis were available during all months of phenological monitoring, but they were consumed more when tree fruit was scarce, suggesting that Saba comorensis fruits may be a fallback food for Rubondo chimpanzees. There were no increases in consumption of lower-quality plant parts between seasons, and there were no changes in group size between seasons. These results contrast with evidence from several endemic chimpanzee study sites, and indicate that Rubondo chimpanzees may have access to abundant and high-quality foods year round.

Perinatal pathology in the context of a clinical trial: attitudes of bereaved parents.

BACKGROUND: Interviews with neonatologists in a related study had revealed a degree of discomfort with approaching bereaved parents for postmortem examinations (PMs) and a widespread concern that parents should not be further distressed or feel under pressure to consent. OBJECTIVE: To report the attitudes of bereaved parents to trial related perinatal PMs, in the light of declining perinatal PM rates and poor levels of participation in pathology studies. METHODS: A qualitative study was carried out, using semistructured interviews. The study involved 11 interviews with 18 bereaved parents from five UK neonatal units. The parents had consented to the enrolment of their baby in one of two neonatal trials. RESULTS: The data provide support for the careful approach described by neonatologists in a related study, but also suggest that it may be possible to approach more parents without undermining their wellbeing. The interviews show the variety of reactions to PMs that one would expect, from parents who were clear that they did not want a PM to others who felt that they needed the information from the examination. Between these extremes were parents who were initially discomforted by the idea but who then made the decision to go ahead. Parents who elected to have a PM did so for their own needs, or to contribute to a trial, or for both reasons. The fact that the subject was raised was generally not seen as inappropriate, and none stated that they felt that they were actually pressured into making their decision. The data also suggest that for some parents the degree of caution and selectivity exercised by the neonatologists may not be entirely appropriate. In two cases, consent for the PM was driven by a sense of making an altruistic contribution to research, and, in another two, altruism was expressed in the context of their own desire for information from a PM. CONCLUSIONS: It is important to determine whether trial related pathology studies are considered by professionals and lay people to be worth while and feasible. If there is support for such studies, the challenge is to develop the means to approach more parents in the most sensitive way.

Perinatal pathology in the context of a clinical trial: attitudes of neonatologists and pathologists.

OBJECTIVE: To describe the attitudes of neonatologists to trial related perinatal postmortem examinations (PMs), in the light of declining perinatal PM rates and poor levels of participation in pathology studies. METHODS: A qualitative study was carried out, using semistructured interviews. Twenty six neonatologists from five UK neonatal units were interviewed; five UK perinatal pathologists also contributed to the study. The professionals involved were all linked to one or both of two neonatal trials. RESULTS: Pathologists expressed concern over the difficulties experienced in UK perinatal pathology and the impact on research of inadequate levels of samples. The interviews with neonatologists reveal discomfort over approaching bereaved parents for PMs, and a widespread concern that parents should not be further distressed or feel under pressure to consent. Although there was support for neonatal trials, the study highlights a view that PMs may be unnecessary if the cause of death seems apparent or when a baby was born prematurely, and a devaluation of PMs among some younger staff. Poor rates of participation in pathology studies may be accounted for by a notable sense of disconnection between trial interventions and pathology studies. CONCLUSIONS: Neonatologists were concerned to protect vulnerable parents and varied in whether they saw this as compatible with inclusion in trial related pathology studies. Dedicated research is needed to document and gain an understanding of the consent process and should examine the usefulness and impact of consent forms. It should assess whether professionals might benefit from training, to help parents to come to their decisions.

Perinatal pathology in the context of a clinical trial: a review of the literature.

Perinatal postmortem rates are declining world wide. In the United Kingdom, perinatal pathology has recently been seriously undermined by controversy. There are important consequences for perinatal trials that include pathology studies. This review looks at the reasons for the decline in perinatal postmortem examinations and the effects on research.

Are subordinates always stressed? A comparative analysis of rank differences in cortisol levels among primates.

Among primate species there is pronounced variation in the relationship between social status and measures of stress physiology. An informal meta-analysis was designed to investigate the basis of this diversity across different primate societies. Species were included only if a substantial amount of published information was available regarding both social behavior and rank-related differences in stress physiology. Four Old World and three New World species met these criteria, including societies varying from small-group, singular cooperative breeders (common marmoset and cotton top tamarin) to large-troop, multi-male, multi-female polygynous mating systems (rhesus, cynomolgus, talapoin, squirrel monkeys, and olive baboon). A questionnaire was formulated to obtain information necessary to characterize the stress milieu for individuals in particular primate societies. We standardized cortisol values within each species by calculating the ratio of basal cortisol concentrations of subordinates to those of dominants in stable dominance hierarchies and expressing the ratio as a percentage (relative cortisol levels). The meta-analysis identified two variables that significantly predicted relative cortisol levels: subordinates exhibited higher relative cortisol levels when they (1). were subjected to higher rates of stressors, and (2). experienced decreased opportunities for social (including close kin) support. These findings have important implications for understanding the different physiological consequences of dominant and subordinate social status across primate societies and how social rank may differ in its behavioral and physiological manifestations among primate societies.

Functional imaging of brain activity in conscious monkeys responding to sexually arousing cues.

Olfactory cues can elicit intense emotional responses. This study used fMRI in male common marmoset monkeys to identify brain areas associated with sexual arousal in response to odors of ovulating female monkeys. Under light anesthesia, monkeys were secured in a specially designed restrainer and positioned in a 9.4 T magnetic resonance spectrometer. When fully conscious, they were presented with the scents of both ovariectomized and ovulating monkeys. The sexually arousing odors of the ovulating monkeys enhanced signal intensity in the preoptic area and anterior hypothalamus compared to the odors of ovariectomized monkeys. These data corroborate previous findings in monkeys based on invasive electrical lesion and stimulation techniques and demonstrate the feasibility of using non-invasive functional imaging on fully conscious common marmosets to study cue-elicited emotional responses.

Social processes in communication and cognition in callitrichid monkeys: a review.

Studies of vocal development in nonhuman primates have found little evidence for plasticity in vocal production, somewhat more for usage of calls, with the greatest plasticity arising in response to calls of others. Generally, similar results were obtained with callitrichid monkeys, the marmosets and tamarins, but with several interesting exceptions. Infant pygmy marmosets show babbling behavior with improvement in adult call structure related to the amount and diversity of babbling. Adult marmosets alter call structure in response to changes in social partners, and wild marmosets have vocal dialects and modify call structure according to how far they are from other group members, suggesting the potential to modify call structure in different social and environmental contexts, though direct learning of novel vocalizations has not been observed. Infant cotton-top tamarins do not produce adult-like calls in appropriate contexts, at least in the first few months of life, but through food sharing from adults infants learn about appropriate foods and the appropriate contexts for food vocalizations. Tamarins modify call structure and usage with changes in social status. Tamarins, unlike other monkeys tested, can learn to avoid noxious foods through observation of other group members, and can learn about novel food locations. Recent studies provide evidence of contextual imitation in marmosets. The plasticity in vocal communication and evidence of social learning in marmosets and tamarins relative to other monkeys may be related to the cooperative breeding system of marmosets and tamarins. With a high degree of behavioral coordination among group members, there is a priority on monitoring signals and behavior of others and adjusting one's own signals and behavior. This creates the context for vocal plasticity and social learning.

Preparental hormone levels and parenting experience in male cotton-top tamarins, Saguinus oedipus.

Male cotton-top tamarins, Saguinus oedipus, display hormonal changes associated with parenting prior to the birth of their infants. Here we examined the hormonal changes that occurred in experienced and inexperienced fathers during the postconception period, prior to the birth of infants. Noninvasive techniques were used to collect urine from 10 male cotton-top tamarins (5 experienced and 5 inexperienced breeders) three times weekly during the 6-month gestation period. Samples were analyzed for prolactin, testosterone, dihydrotestosterone (DHT), and cortisol, averaged by gestational month. Experienced males showed elevated prolactin during the mate's 3rd gestational month, and the elevation correlated with the number of infants surviving from the previous birth (0, 1, and 2) but not with outcome of the current pregnancy. However, an experienced male with no infants present still showed elevated prolactin and some inexperienced males showed elevated prolactin just before parturition, suggesting noninfant cues are also important. While prolactin levels were influenced by the male's prior infant experience, testosterone levels did not differ between experienced and inexperienced males. Testosterone levels were significantly elevated for all males during the 3rd, 4th and 5th months but had no relationship with number of infants present or with outcome of current pregnancy. DHT decreased during the second half of pregnancy compared with testosterone but this finding was not consistent for every male. No significant changes occurred in cortisol levels. These results suggest that infant-rearing experience affected the hormonal responsitivty of the male to his mate's current pregnancy.

Prolactin levels during the periparturitional period in the biparental cotton-top tamarin (Saguinus oedipus): interactions with gender, androgen levels, and parenting.

Unlike biparental bird and rodent species, mating and parenting occur simultaneously in cotton-top tamarins, Saguinus oedipus, providing a unique model for examining endocrine interactions. This study was designed to determine the relationship of prolactin to testicular androgens during parenting and mating. Specifically we examined (1) the patterns of postpartum prolactin excretion in male and female tamarins with and without infant survival; (2) the relationship between androgen and prolactin levels during the periparturitional period in male tamarins; and (3) male hormonal response to the postpartum mating that occurs simultaneously with paternal care. All females showed an elevation in prolactin during the first week postpartum and when infants died, female prolactin levels decreased significantly. Infant survival during the first 15 days did not influence male levels of prolactin, cortisol, or the testicular androgens testosterone and dihydrotestosterone (DHT). Prolactin did not show an inverse relationship with any of the androgens (testosterone, DHT) studied during the postpartum period. No significant differences in hormones were found between prepartum levels and the first, second, and third 5-day blocks postpartum for all 10 males. Males who had infant-care experience showed an increase in testosterone during the first 5 days postpartum and prolactin levels correlated with the number of previous births a male had experienced. However, the most significant changes in testosterone occurred in males whose mates ovulated during the first 15 days following birth in contrast to males whose mates ovulated later than 15 days. These results indicate that unlike females, male tamarins are not showing hormonal changes in response to infants. Urinary androgens did not show an inverse relationship to prolactin in male tamarins, but were elevated concurrent with the female's fertile period.