A Mixed-method Approach to Develop an Ambulatory Module of the SMA Independence Scale.

BACKGROUND: Limited qualitative data exist on the symptoms and impacts of spinal muscular atrophy (SMA) experienced by ambulant individuals. An ambulant module of the SMA Independence Scale (SMAIS) was developed to quantify the assistance required to perform everyday mobility-related activities. OBJECTIVE: The objective of this study was to develop a patient-centered module that provides key insights into what constitutes independence for ambulant and near-ambulant individuals with SMA. METHODS: A stepwise, mixed-method approach was used. Semi-structured interviews were conducted in three waves with individuals with SMA and caregivers of children with SMA who were ambulant or near-ambulant (can walk ≥5 steps with support). Wave 1 interviews (n = 20) focused on concept elicitation. Wave 2 and 3 interviews (n = 15, both) involved completion and cognitive debriefing of items generated based on Wave 1 interviews. Therapeutic area experts were consulted throughout all key steps of the study. In particular, feedback was provided for item refinement and response option decisions. A macro-level preliminary, exploratory analysis, using Rasch Measurement Theory (RMT), provided insight on measurement properties. RESULTS: Wave 1 resulted in 42 mobility and 11 instrumental activity of daily living (iADL) items. During Wave 2, participants defined independence as completing a task with supportive aids but without help from another person, leading to item refinement and modifications to the response scale. Lack of conceptual relevance and ceiling effects led to the removal of all iADL items after Wave 2, and 41 mobility items were tested in Wave 3. Final exploratory RMT and item refinement to reduce overlap led to a 27-item set related to mobility tasks. CONCLUSIONS: Our study provides preliminary support for using the 27-item SMAIS-Ambulatory Module for ambulant or near-ambulant individuals with SMA. Larger-scale analyses to further assess the psychometric properties of the scale are warranted.

Estimates of life history parameters in a high latitude, arid-country vervet monkey population.

We present data on life history parameters from a long-term study of vervet monkeys in the Eastern Cape, South Africa. Estimates are presented of age at first conception for females and age at natal dispersal for males, along with the probability of survival to adulthood for infants born during the study, female reproductive life-span, reproductive output (including lifetime reproductive success for a subset of females), and inter-birth interval (IBI) duration. We also assess the effect of maternal age and infant survival on length of IBI. We then go on to compare life history parameters for our population with those from two East African populations in Kenya (Amboseli and Laikipia). We find there is broad consensus across the three populations, although mean infant survival was considerably lower for the two East African sites. Such comparisons must be made cautiously, however, as local ecology across the duration of the studies obviously has an impact on the estimates obtained. With this caveat in place, we consider that the concordance between values is sufficient to enable the values reported here to be used in comparative studies of primate life history, although data from habitats with higher rainfall and lower levels of seasonality are needed, and the results presented here should not be seen as canonical.

A Mixed-Methods Study to Better Measure Patient-Reported Pain and Fatigue in Soft Tissue Sarcoma.

INTRODUCTION: Pain and fatigue are commonly reported by patients with soft tissue sarcoma (STS) as distressing symptoms, yet no patient-reported outcome (PRO) measures have been validated or developed specifically for STS. This study aimed to develop novel PRO scales using existing item banks to measure pain and fatigue in STS. METHODS: A three-stage mixed-methods approach was used. Stage 1: a literature review examined the development and validation of the European Organization for Research and Treatment of Cancer (EORTC) library, Patient-Reported Outcomes Measurement Information System (PROMIS) pain/fatigue item banks, Functional Assessment of Cancer Therapy-General, and FACIT-Fatigue. Conceptual models were developed for pain and fatigue. Stage 2: semi-structured interviews were conducted with clinical experts (n = 3) and STS patients (n = 28) to ensure conceptual coverage and cognitively debrief the selected PRO items. Stage 3: exploratory Rasch measurement theory (RMT) analyses were performed to examine the measurement properties of the proposed scales. RESULTS: Stage 1: The conceptual model for fatigue was organized into two overarching domains: fatigability and fatigue, further split into two subdomains: symptoms and impact. The conceptual model for pain had one overarching domain split into two subdomains: descriptors and impact. Pain (n = 56) and fatigue (n = 40) items were selected from the EORTC item library. Stage 2: qualitative findings ensured conceptual coverage, provided insight into the relevance and comprehension of the items, and informed subsequent item reduction. Stage 3: The total item number was reduced to 43 (pain n = 18, fatigue n = 25). Exploratory RMT analyses supported the final scales' psychometric properties. CONCLUSIONS: This mixed-methods research generated important information on the experience of pain and fatigue in specific subtypes of STS. Five novel PRO scales have been developed through careful item selection in consultation with experts and supported by qualitative and quantitative evidence. These scales may be of value to future clinical trials for STS.

Using network synchrony to identify drivers of social dynamics.

Social animals frequently show dynamic social network patterns, the consequences of which are felt at the individual and group level. It is often difficult, however, to identify what drivers are responsible for changes in these networks. We suggest that patterns of network synchronization across multiple social groups can be used to better understand the relative contributions of extrinsic and intrinsic drivers. When groups are socially separated, but share similar physical environments, the extent to which network measures across multiple groups covary (i.e. network synchrony) can provide an estimate of the relative roles of extrinsic and intrinsic drivers. As a case example, we use allogrooming data from three adjacent vervet monkey groups to generate dynamic social networks. We found that network strength was strongly synchronized across the three groups, pointing to shared extrinsic environmental conditions as the driver. We also found low to moderate levels of synchrony in network modularity, suggesting that intrinsic social processes may be more important in driving changes in subgroup formation in this population. We conclude that patterns of network synchronization can help guide future research in identifying the proximate mechanisms behind observed social dynamics in animal groups.

Measuring the Patient Experience in Rare Disorders: Benefit of Pragmatic Mixed-Methods Research in NUT Carcinoma.

INTRODUCTION: Patient-centered outcome measurement (PCOM) is essential to capture the outcomes important to patients. However, it presents unique challenges in rare diseases, particularly those that are "young" (not diagnosed before the twenty-first century), with limited literature, lack of disease-specific patient-reported outcome (PRO) measures, and difficult sampling and data collection. One example of this is NUT (nuclear protein in testis) carcinoma (NUTca), a rare and rapidly progressing cancer, with tumors preliminary in the head, neck, and lungs. The published literature on NUTca is scarce. The limited number of case reports focus primarily on the clinical development and presentation of tumors. Currently, there are no publications describing the patient experience of NUTca and no specific PRO measures to assess the patient experience. We conducted mixed-methods research, including concept elicitation interviews, cognitive debriefing, and quantitative data analyses, to fill this evidence gap and describe challenges and solutions in the context of NUTca. METHODS: As published previously, our conceptualization of NUTca was based on elicitation interviews with 27 participants (n = 10 patients; n = 17 caregivers) using a semi-structured format; this framework formed the basis for a bolt-on strategy to develop a bespoke PRO measure based on the EORTC QLQ-C30, supplemented by targeted items from the EORTC Item Library and new items. In this publication, 20 participants were interviewed (n = 10 patients; n = 10 caregivers) to debrief items. Given the variety of tumor locations and related symptoms, and the small sample of patients providing responses to location-specific symptom items, we used response option endorsement frequencies to illuminate the variability of response for the concepts measured. RESULTS: This study highlights the challenges in implementing patient-centric research to inform and develop PRO measures in rare diseases. CONCLUSIONS: Our mixed-methods research used pragmatic solutions to collect patient experience data and provides an evidence base to inform PCOM in clinical programs in this rapidly progressing rare cancer with high unmet need.

The thermal consequences of primate birth hour and its evolutionary implications.

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 (Tb) across 24 births in a population of wild vervet monkeys using biologgers. We identified distinct perturbations in Tb during the birth period, including declining Tb during labour and the rapid recovery of Tb post-parturition. Vervet monkeys typically gave birth during their inactive phase in synchrony with the nadir of the maternal nychthemeral Tb rhythm but also showed remarkable inter-individual variability in their absolute Tb during birth. Our findings support the view that selection may have favoured a nocturnal timing of primate birth to coincide with lower night-time Tb and environmental temperatures, which improve thermal efficiency during birth.

Development of the SMA independence scale-upper limb module (SMAIS-ULM): A novel scale for individuals with Type 2 and non-ambulant Type 3 SMA.

BACKGROUND: The amount of assistance required to perform daily activities for individuals with Type 2 and non-ambulant Type 3 spinal muscular atrophy (SMA) is often cited as meaningful for quality of life, and important to routinely assess. METHODS: The SMA Independence Scale (SMAIS), a patient-reported outcome measure for individuals with SMA aged ≥12 years, and an observer-reported outcome measure for caregivers of individuals aged ≥2 years, was developed and evaluated in two phases. In Phase 1, 30 draft items were developed following review of the literature. Semi-structured interviews were then conducted with individuals with SMA and caregivers to establish content validity, resulting in a 29-item measure. In Phase 2, classical test theory and Rasch measurement theory methods were used to examine the cross-sectional and longitudinal measurement performance of the SMAIS in two independent datasets. RESULTS: Phase 1 qualitative findings supported the relevance, acceptability, and comprehensibility of 29 items. In Phase 2, psychometric analyses indicated that the five response options were poorly discriminated and were thus collapsed to three options for subsequent analyses. Items showed statistical misfit, implying that the SMAIS was not assessing a single underlying construct. Based on conceptual evaluation of the items, and assessment of item performance, a more targeted 22-item upper limb score was derived. Reliability and validity analyses confirmed acceptable measurement properties of this score. CONCLUSIONS: Qualitative and quantitative analyses support the use of the 22-item SMAIS-Upper Limb Module in individuals with Type 2 and non-ambulant Type 3 SMA, aged ≥2 years.

Experts in action: why we need an embodied social brain hypothesis.

The anthropoid primates are known for their intense sociality and large brain size. The idea that these might be causally related has given rise to a large body of work testing the 'social brain hypothesis'. Here, the emphasis has been placed on the political demands of social life, and the cognitive skills that would enable animals to track the machinations of other minds in metarepresentational ways. It seems to us that this position risks losing touch with the fact that brains primarily evolved to enable the control of action, which in turn leads us to downplay or neglect the importance of the physical body in a material world full of bodies and other objects. As an alternative, we offer a view of primate brain and social evolution that is grounded in the body and action, rather than minds and metarepresentation. This article is part of the theme issue 'Systems neuroscience through the lens of evolutionary theory'.

Fevers and the social costs of acute infection in wild vervet monkeys.

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.

Formidable females redux: male social integration into female networks and the value of dynamic multilayer networks.

The development of multilayer network techniques is a boon for researchers who wish to understand how different interaction layers might influence each other, and how these in turn might influence group dynamics. Here, we investigate how integration between male and female grooming and aggression interaction networks influences male power trajectories in vervet monkeys Chlorocebus pygerythrus. Our previous analyses of this phenomenon used a monolayer approach, and our aim here is to extend these analyses using a dynamic multilayer approach. To do so, we constructed a temporal series of male and female interaction layers. We then used a multivariate multilevel autoregression model to compare cross-lagged associations between a male's centrality in the female grooming layer and changes in male Elo ratings. Our results confirmed our original findings: changes in male centrality within the female grooming network were weakly but positively tied to changes in their Elo ratings. However, the multilayer network approach offered additional insights into this social process, identifying how changes in a male's centrality cascade through the other network layers. This dynamic view indicates that the changes in Elo ratings are likely to be short-lived, but that male centrality within the female network had a much stronger impact throughout the multilayer network as a whole, especially on reducing intermale aggression (i.e., aggression directed by males toward other males). We suggest that multilayer social network approaches can take advantage of increased amounts of social data that are more commonly collected these days, using a variety of methods. Such data are inherently multilevel and multilayered, and thus offer the ability to quantify more precisely the dynamics of animal social behaviors.

Tolerance of muzzle contact underpins the acquisition of foraging information in vervet monkeys (Chlorocebus pygerythrus).

Muzzle contact, where one animal brings its muzzle into close proximity to that of another, has often been hypothesized as a straightforward means of socially mediated food investigation. Using 2,707 observations of muzzle contact occurring across 3 troops of wild vervet monkeys (Chlorocebus pygerythrus), we tested this social learning hypothesis. We first explored the social structuring of muzzle contact by analyzing the characteristics of initiators and receivers. Similar to previous research, juveniles initiated contact at higher rates than adults, particularly toward adult females and animals with lower dominance rankings. The highest number of contacts occurred between kin compared to contacts between nonkin. However, on the whole, contacts occurred at low rates, even among kin dyads. We next determined whether muzzle contact was used as a means to learn socially, specifically by animals seeking foraging information. We found that initiators did not overwhelmingly target foragers, meaning animals do not appear to directly seek information about food during muzzle contact. However, animals that contacted foragers were more likely forage themselves in comparison to those that contacted nonforagers, suggesting that foragers do provide food information. These findings indicate that both kin and low-ranking animals serve as discriminative stimuli for social tolerance and that foraging animals serve as discriminative stimuli for food availability. We conclude that broad social tolerance, rather than the recipient's knowledge, is the most likely antecedent to muzzle contact and that animals engage in this behavior as a low-cost means of maintaining a baseline level of information about their environment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Field data confirm the ability of a biophysical model to predict wild primate body temperature.

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.

Infrared thermography cannot be used to approximate core body temperature in wild primates.

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 a mammal'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 temperature, core body (intra-abdominal) temperature, 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 noninvasive means to detect and record animal temperatures, infrared thermography alone cannot be used to approximate core body temperature in wild primates.

Modeling variation in the growth of wild and captive juvenile vervet monkeys in relation to diet and resource availability.

OBJECTIVES: To compare longitudinal weight gain in captive and wild juvenile vervet monkeys and conduct an empirical assessment of different mechanistic growth models. METHODS: Weights were collected from two groups of captive monkeys and two consecutive cohorts of wild monkeys until the end of the juvenile period (~800 days). The captive groups were each fed different diets, while the wild groups experienced different ecological conditions. Three different growth curve models were compared. RESULTS: By 800 days, the wild juveniles were lighter, with a slower maximum growth rate, and reached asymptote earlier than their captive counterparts. There were overall differences in weight and growth rate across the two wild cohorts. This corresponded to differences in resource availability. There was considerable overlap in growth rate and predicted adult weight of male and females in the first, but not the second, wild cohort. Maternal parity was not influential. While the von Bertalanffy curve provided the best fit to the data sets modeled together, the Logistic curve best described growth in the wild cohorts when considered separately. CONCLUSIONS: The growth curves of the two captive cohorts are likely to lie near the maximum attainable by juvenile vervets. It may be helpful to include deviations from these rates when assessing the performance of wild vervet monkeys. The comparison of wild and captive juveniles confirmed the value of comparing different growth curve models, and an appreciation that the best models may well differ for different populations. Choice of mechanistic growth model can, therefore, be empirically justified, rather than theoretically predetermined.

Keeping cool in the heat: Behavioral thermoregulation and body temperature patterns in wild vervet monkeys.

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. 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. 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. 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.

Climate induced stress and mortality in vervet monkeys.

As the effects of global climate change become more apparent, animal species will become increasingly affected by extreme climate and its effect on the environment. There is a pressing need to understand animal physiological and behavioural responses to climatic stressors. We used the reactive scope model as a framework to investigate the influence of drought conditions on vervet monkey (Chlorocebus pygerythrus) behaviour, physiological stress and survival across 2.5 years in South Africa. Data were collected on climatic, environmental and behavioural variables and physiological stress via faecal glucocorticoid metabolites (fGCMs). There was a meaningful interaction between water availability and resource abundance: when food availability was high but standing water was unavailable, fGCM concentrations were higher compared to when food was abundant and water was available. Vervet monkeys adapted their behaviour during a drought period by spending a greater proportion of time resting at the expense of feeding, moving and social behaviour. As food availability decreased, vervet mortality increased. Peak mortality occurred when food availability was at its lowest and there was no standing water. A survival analysis revealed that higher fGCM concentrations were associated with an increased probability of mortality. Our results suggest that with continued climate change, the increasing prevalence of drought will negatively affect vervet abundance and distribution in our population. Our study contributes to knowledge of the limits and scope of behavioural and physiological plasticity among vervet monkeys in the face of rapid environmental change.

Insights into the evolution of social systems and species from baboon studies.

Baboons, members of the genus Papio, comprise six closely related species distributed throughout sub-Saharan Africa and southwest Arabia. The species exhibit more ecological flexibility and a wider range of social systems than many other primates. This article summarizes our current knowledge of the natural history of baboons and highlights directions for future research. We suggest that baboons can serve as a valuable model for complex evolutionary processes, such as speciation and hybridization. The evolution of baboons has been heavily shaped by climatic changes and population expansion and fragmentation in the African savanna environment, similar to the processes that acted during human evolution. With accumulating long-term data, and new data from previously understudied species, baboons are ideally suited for investigating the links between sociality, health, longevity and reproductive success. To achieve these aims, we propose a closer integration of studies at the proximate level, including functional genomics, with behavioral and ecological studies.

Gastrointestinal Parasites of Vervet Monkeys (Chlorocebus pygerythrus) in a High Latitude, Semi-Arid Region of South Africa.

Given a changing climate and large-scale human migration, understanding infectious diseases in wildlife and the factors that drive the spread of these diseases is becoming increasingly important. Owing to the close phylogenetic relationship between nonhuman primates and humans, primate parasites are of particular interest due to the potential for zoonotic disease transmission and for the study of social transmission within gregarious social groups. There is a wide range of social and environmental factors that influence the prevalence and transmission of pathogens, and identifying these, and their effects, is crucial to understanding the population-level consequences of climate change for animals that live in obligate social groups. Here we investigated gastrointestinal parasite species richness and used fecal egg counts to estimate worm intensities in 3 vervet monkey troops (Chlorocebus pygerythrus) in a high latitude, semi-arid region of South Africa. This region is characterized by unpredictable rainfall and temperature extremes in summer and winter. We identified the gastrointestinal parasites in the population and explored potential demographic predictors, namely sex and troop membership, of parasite species richness and estimated intensity. Additionally, we assessed whether there was short-term intra-individual, inter-sample consistency in egg counts. Six species of gastrointestinal helminths were identified from 3 study troops, with egg counts ranging from 0 eggs/g to 1,100 eggs/g. Neither age nor sex predicted species richness or estimated intensity. This population had the highest prevalence of parasites with an insect vector compared with all other vervet populations studied, and distinctively high prevalences of Trichostrongylus sp. (71%) and Ternidens sp. (27%). Additionally, we found intra-individual egg count consistency in the short term (mean: 32 days).

Functional social structure in baboons: Modeling interactions between social and environmental structure in group-level foraging.

In mobile social groups, cohesion is thought to be driven by patterns of attraction at both the individual and group level. In long-lived species with high group stability and repeated interactions, such as baboons, individual-to-individual attractions have the potential to play a large role in group cohesion and overall movement patterns. In previous work, we found that the patterning of inter-individual attraction gave rise to an emergent group-level structure, whereby a core of more influential, inter-dependent individuals exerted a unidirectional influence on the movements of peripheral animals. Here, we use agent-based modeling of baboon groups to investigate whether this core-periphery structure has any functional consequences for foraging behavior. By varying individual level attractions, we produced baboon groups that contained influence structures that varied from more to less centralized. Our results suggest that varying centrality affects both the ability of the group to detect resource structure in the environment, as well as the ability of the group to exploit these resources. Our models predict that foraging groups with more centralized social structures will show a reduction in detection and an increase in exploitation of resources in their environment, and will produce more extreme foraging outcomes. More generally, our results highlight how a group's internal social structure can result in mobile social animals being able to more (or less) effectively exploit environmental structure, and capitalize on the distribution of resources. In addition, our agent-based model can be used to generate testable predictions that can be tested among the extant baboon allotaxa. This will add value to the existing body of work on responses to local ecology, as well as providing a means to test hypotheses relating to the phylogeography of the baboons and, by analogy, shed light on patterns of hominin evolution in time and space.