Pre-natal exposure to glucocorticoids causes changes in developmental circadian clock gene expression and post-natal behaviour in the Japanese quail.

The embryonic environment is critical in shaping developmental trajectories and consequently post-natal phenotypes. Exposure to elevated stress hormones during this developmental stage is known to alter a variety of post-natal phenotypic traits, and it has been suggested that pre-natal stress can have long term effects on the circadian rhythm of glucocorticoid hormone production. Despite the importance of the circadian system, the potential impact of developmental glucocorticoid exposure on circadian clock genes, has not yet been fully explored. Here, we showed that pre-natal exposure to corticosterone (CORT, a key glucocorticoid) resulted in a significant upregulation of two key hypothalamic circadian clock genes during the embryonic period in the Japanese quail (Coturnix japonica). Altered expression was still present 10 days into post-natal life for both genes, but then disappeared by post-natal day 28. At post-natal day 28, however, diel rhythms of eating and resting were influenced by exposure to pre-natal CORT. Males exposed to pre-natal CORT featured an earlier acrophase, alongside spending a higher proportion of time feeding. Females exposed to pre-natal CORT featured a less pronounced shift in acrophase and spent less time eating. Both males and females exposed to pre-natal CORT spent less time inactive during the day. Pre-natal CORT males appeared to feature a delay in peak activity levels. Our novel data suggest that these circadian clock genes and aspects of diurnal behaviours are highly susceptible to glucocorticoid disruption during embryonic development, and these effects are persistent across developmental stages, at least into early post-natal life.

Maternal developmental history alters transfer of circadian clock genes to offspring in Japanese quail (Coturnix japonica).

Maternal signals shape embryonic development, and in turn post-natal phenotypes. RNA deposition is one such method of maternal signalling and circadian rhythms are one trait thought to be maternally inherited, through this mechanism. These maternal circadian gene transcripts aid development of a functioning circadian system. There is increasing evidence that maternal signals can be modified, depending on prevailing environmental conditions to optimise offspring fitness. However, currently, it is unknown if maternal circadian gene transcripts, and consequently early embryonic gene transcription, are altered by maternal developmental conditions. Here, using avian mothers who experienced either pre-natal corticosterone exposure, and/or post-natal stress as juveniles we were able to determine the effects of the timing of stress on downstream circadian RNA deposition in offspring. We demonstrated that maternal developmental history does indeed affect transfer of offspring circadian genes, but the timing of stress was important. Avian mothers who experienced stress during the first 2 weeks of post-natal life increased maternally deposited transcript levels of two core circadian clock genes, BMAL1 and PER2. These differences in transcript levels were transient and disappeared at the point of embryonic genome transcription. Pre-natal maternal stress alone was found to elicit delayed changes in circadian gene expression. After activation of the embryonic genome, both BMAL1 and PER2 expression were significantly decreased. If both pre-natal and post-natal stress occurred, then initial maternal transcript levels of BMAL1 were significantly increased. Taken together, these results suggest that developmental stress differentially produces persistent transgenerational effects on offspring circadian genes.

Acute social isolation alters neurogenomic state in songbird forebrain.

Prolonged social isolation has negative effects on brain and behavior in humans and other social organisms, but neural mechanisms leading to these effects are not understood. Here we tested the hypothesis that even brief periods of social isolation can alter gene expression and DNA methylation in higher cognitive centers of the brain, focusing on the auditory/associative forebrain of the highly social zebra finch. Using RNA sequencing, we first identified genes that individually increase or decrease expression after isolation and observed general repression of gene sets annotated for neurotrophin pathways and axonal guidance functions. We then pursued 4 genes of large effect size: EGR1 and BDNF (decreased by isolation) and FKBP5 and UTS2B (increased). By in situ hybridization, each gene responded in different cell subsets, arguing against a single cellular mechanism. To test whether effects were specific to the social component of the isolation experience, we compared gene expression in birds isolated either alone or with a single familiar partner. Partner inclusion ameliorated the effect of solo isolation on EGR1 and BDNF, but not on FKBP5 and UTS2B nor on circulating corticosterone. By bisulfite sequencing analysis of auditory forebrain DNA, isolation caused changes in methylation of a subset of differentially expressed genes, including BDNF. Thus, social isolation has rapid consequences on gene activity in a higher integrative center of the brain, triggering epigenetic mechanisms that may influence processing of ongoing experience.

The many faces of medical treatment imperatives: Biopower and the cultural authority of medicine in late-life treatment decisions in the United States.

Despite changes in specific features of the US health-care system and policy environment in the past 50 years, professional dominance of medicine remains consistent. Extant social science research has considered how the cultural authority of medicine manifests and persists, sometimes emphasizing institutional structural influences and other times focusing on how individuals' agentic behaviour shapes their decisions and strategies regarding the consumption of health-care. We build on and extend these literatures using qualitative in-depth interview data to explore a typology of ways palliative care patients and their caregivers experience medical treatment imperatives across a range of social contexts. Rather than viewing or validating these lived experiences through a medical lens, we foreground the accounts of patients and caregivers as they describe their experiences of where, when, and how they perceive pressure to engage in medical treatment in late life. We adopt a Foucauldian lens to examine how this biopower is both an internal and external experience in our modern biomedicalized society. Our work reveals how treatment imperatives are generated within clinical medical encounters, but also coproduced through multiple and overlapping forces that compel individuals to pursue medical solutions to bodily problems.

Sociological contributions to race and health: Diversifying the ontological and methodological agenda.

Sociologists have made fundamental contributions to the study of race and health in the United States. They have disrupted biological assumptions of race, uncovered individual and structural factors that drive racial health disparities and explored the effects of racism on health. In recent years, however, with broader shifts towards big data, the work to understand the dynamics between race and health has been increasingly pursued from a quantitative perspective. Often, such analyses isolate intermediary mechanisms to further explain race as a cause of disease. While important, these approaches potentially limit our investigations of underlying assumptions about race and the complexity of this critical social construct. We argue that the resulting dearth of qualitative research on race and health substantially limits the knowledge being produced. After providing an overview of the overwhelming shift towards quantitative methods in the study of race and health, we present three areas of study that would benefit from greater qualitative inquiry as follows: (1) Healthy Immigrant Effect, (2) Maternal Health and (3) End-of-Life Care. We conclude with a call to the discipline to embrace the critical role of qualitative research in exploring the dynamics of race and health in the United States.

Social experience during adolescence in female rats increases 50 kHz ultrasonic vocalizations in adulthood, without affecting anxiety-like behavior.

Adolescents are highly motivated to engage in social interactions, and researchers have hypothesized that positive social relationships during adolescence can have long term, beneficial effects on stress reactivity and mental well-being. Studies of laboratory rodents provide the opportunity to investigate the relationship between early social experiences and later behavioral and physiological responses to stressors. In this study, female Lister-hooded rats (N = 12 per group) were either (a) provided with short, daily encounters (10 min/day) with a novel partner during mid-adolescence (postnatal day 34-45; "social experience," SE, subjects) or (b) underwent the same protocol with a familiar cagemate during mid-adolescence ("control experience," CE, subjects), or (c) were left undisturbed in the home cage (non-handled "control," C, subjects). When tested in adulthood, the groups did not differ in behavioral responses to novel environments (elevated plus maze, open field, and light-dark box) or in behavioral and physiological (urinary corticosterone) responses to novel social partners. However, SE females emitted significantly more 50 kHz ultrasonic vocalizations than control subjects both before and after social separation from a familiar social partner, which is consistent with previous findings in male rats. Thus, enhanced adolescent social experience appears to have long-term effects on vocal communication and could potentially modulate adult social relationships.

Early-life adversity programs long-term cytokine and microglia expression within the HPA axis in female Japanese quail.

Stress exposure during prenatal and postnatal development can have persistent and often dysfunctional effects on several physiological systems, including immune function, affecting the ability to combat infection. The neuroimmune response is inextricably linked to the action of the hypothalamic-pituitary-adrenal (HPA) axis. Cytokines released from neuroimmune cells, including microglia, activate the HPA axis, while glucocorticoids in turn regulate cytokine release from microglia. Because of the close links between these two physiological systems, coupled with potential for persistent changes to HPA axis activity following developmental stress, components of the neuroimmune system could be targets for developmental programming. However, little is known of any programming effects of developmental stress on neuroimmune function. We investigated whether developmental stress exposure via elevated prenatal corticosterone (CORT) or postnatal unpredictable food availability had long-term effects on pro- (IL-1ß) and anti-inflammatory (IL-10) cytokine and microglia-dependent gene (CSF1R) expression within HPA axis tissues in a precocial bird, the Japanese quail (Coturnix japonica). Following postnatal stress, we observed increased IL-1ß expression in the pituitary gland, reduced IL-10 expression in the amygdala and hypothalamus, and reduced CSF1R expression within the hypothalamus and pituitary gland. Postnatal stress disrupted the ratio of IL-1ß:IL-10 expression within the hippocampus and hypothalamus. Prenatal stress only increased IL-1ß expression in the pituitary gland. We found no evidence for interactive or cumulative effects across life stages on basal cytokine and glia expression in adulthood. We show that postnatal stress may have a larger impact than elevated prenatal CORT on basal immunity in HPA-axis-specific brain regions, with changes in cytokine homeostasis and microglia abundance. These results provide evidence for postnatal programming of a pro-inflammatory neuroimmune phenotype at the expense of reduced microglia, which could have implications for central nervous system health and subsequent neuroimmune responses.

Group housing during adolescence has long-term effects on the adult stress response in female, but not male, zebra finches (Taeniopygia guttata).

Adolescent social interactions can have long-term effects on physiological responses to stressors in later-life. A larger adolescent group size can result in higher stressor-induced secretion of glucocorticoids in adulthood. The effect may be due to a socially-mediated modulation of gonadal hormones, e.g. testosterone. However, group size (number of animals) has been conflated with social density (space per animal). Therefore it is hard to determine the mechanisms through which adolescent group size can affect the stress response. The current study aimed to tease apart the effects of group size and social density during adolescence on the physiological stress response and gonadal hormone levels in adulthood. Adolescent zebra finches were housed in groups varying in size (2 vs. 5 birds per cage) and density (0.03m3 vs. 0.06m3 per bird) during early adolescence (day 40-60). Density was only manipulated in birds raised in groups of five. Glucocorticoid concentration secreted in response to a standard capture and restraint stressor was quantified in adolescence (day 55±1) and adulthood (day 100+). Basal gonadal hormone concentrations (male testosterone, female estradiol) were also quantified in adulthood. Female birds housed in larger groups, independent of social density, secreted a higher glucocorticoid concentration 45min into restraint regardless of age, and had higher peak glucocorticoid concentration in adulthood. Adult gonadal hormone concentrations were not affected by group size or density. Our results suggest that group size, not density, is a social condition that influences the development of the endocrine response to stressors in female zebra finches, and that these effects persist into adulthood. The findings have clear relevance to the social housing conditions necessary for optimal welfare in captive animals, but also elucidate the role of social rearing conditions in the emergence of responses to stressors that may persist across the lifespan and affect fitness of animals in wild populations.

Glucocorticoid programming of neuroimmune function.

Throughout life physiological systems strive to maintain homeostasis and these systems are susceptible to exposure to maternal or environmental perturbations, particularly during embryonic development. In some cases, these perturbations may influence genetic and physiological processes that permanently alter the functioning of these physiological systems; a process known as developmental programming. In recent years, the neuroimmune system has garnered attention for its fundamental interactions with key hormonal systems, such as the hypothalamic pituitary adrenal (HPA) axis. The ultimate product of this axis, the glucocorticoid hormones, play a key role in modulating immune responses within the periphery and the CNS as part of the physiological stress response. It is well-established that elevated glucocorticoids induced by developmental stress exert profound short and long-term physiological effects, yet there is relatively little information of how these effects are manifested within the neuroimmune system. Pre and post-natal periods are prime candidates for manipulation in order to uncover the physiological mechanisms that underlie glucocorticoid programming of neuroimmune responses. Understanding the potential programming role of glucocorticoids may be key in uncovering vulnerable windows of CNS susceptibility to stressful experiences during embryonic development and improve our use of glucocorticoids as therapeutics in the treatment of neurodegenerative diseases.

Correction to: The prognosis in palliative care study II (PiPS2): study protocol for a multi-centre, prospective, observational, cohort study.

After publication, the authors noticed some minor errors in "Nested qualitative sub-study" section, first paragraph of the section, page 7 of the published article.

The Prognosis in Palliative care Study II (PiPS2): study protocol for a multi-centre, prospective, observational, cohort study.

BACKGROUND: More accurate methods of prognostication are likely to lead to improvements in the quality of care of patients approaching the ends of their lives. The Prognosis in Palliative care Scales (PiPS) are prognostic models of survival. The scores are calculated using simple clinical data and observations. There are two separate PiPS models; PiPS-A for patients without blood test results and PiPS-B for patients with blood test results. Both models predict whether a patient is likely to live for "days", "weeks" or "months" and have been shown to perform as well as clinicians' estimates of survival. PiPS-B has also been found to be significantly better than doctors' estimates of survival. We report here a protocol for the validation of PiPS and for the evaluation of the accuracy of other prognostic tools in a new, larger cohort of patients with advanced cancer. METHODS: This is a national, multi-centre, prospective, observational cohort study, aiming to recruit 1778 patients via palliative care services across England and Wales. Eligible patients have advanced, incurable cancer and have recently been referred to palliative care services. Patients with or without capacity are included in the study. The primary outcome is the accuracy of PiPS predictions and the difference in accuracy between these predictions and the clinicians' estimates of survival; with PiPS-B being the main model of interest. The secondary outcomes include the accuracy of predictions by the Palliative Prognostic Index (PPI), Palliative Performance Scale (PPS), Palliative Prognostic score (PaP) and the Feliu Prognostic Nomogram (FPN) compared with actual patient survival and clinicians' estimates of survival. A nested qualitative sub-study using face-to-face interviews with patients, carers and clinicians is also being undertaken to assess the acceptability of the prognostic models and to identify barriers and facilitators to clinical use. DISCUSSION: The study closed to recruitment at the end of April 2018 having exceeded the required sample size of 1778 patients. The qualitative sub-study is nearing completion. This demonstrates the feasibility of recruiting large numbers of participants to a prospective palliative care study. TRIAL REGISTRATION: ISRCTN13688211 (registration date: 28/06/2016).

Long-term effects of adolescent stress on neophobic behaviors in zebra finches are modulated by social context when in adulthood.

Experiencing stress during adolescence can increase neophobic behaviors in adulthood, but most tests have been conducted in the absence of conspecifics. Conspecifics can modulate responses to stressors, for example by acting as 'social buffers' to attenuate the aversive appraisal of stressors. Here, we investigate the long-term effects of adolescent stress on the behavioral responses to novel stimuli (a mild stressor) across social contexts in an affiliative passerine bird, the zebra finch. During early (days 40-60) or late (days 65-85) adolescence the birds (n=66) were dosed with either saline or the hormone corticosterone (CORT). CORT was given in order to mimic a physiological stress response and saline was given as a control. In adulthood, the birds' behavioral responses to a novel environment were recorded in both the presence and absence of conspecifics. An acute CORT response was also quantified in adolescence and adulthood. Our findings show clear evidence of social context mediating any long-term effects of adolescent stress. In the presence of familiar conspecifics no treatment effects were detected. Individually, birds dosed with CORT in early adolescence were slower to enter a novel environment, spent more time perching in the same novel environment, and, if female, engaged in more risk assessment. Birds dosed in late adolescence were unaffected. No treatment effects were detected on CORT, but adolescents had a higher CORT concentration than adults. Our results are the first to suggest that familiar conspecifics in adulthood can buffer the long-term effects of stress that occurred during early adolescence.

Wild jackdaws' reproductive success and their offspring's stress hormones are connected to provisioning rate and brood size, not to parental neophobia.

Many species show individual variation in neophobia and stress hormones, but the causes and consequences of this variation in the wild are unclear. Variation in neophobia levels could affect the number of offspring animals produce, and more subtly influence the rearing environment and offspring development. Nutritional deficits during development can elevate levels of stress hormones that trigger long-term effects on learning, memory, and survival. Therefore measuring offspring stress hormone levels, such as corticosterone (CORT), helps determine if parental neophobia influences the condition and developmental trajectory of young. As a highly neophobic species, jackdaws (Corvus monedula) are excellent for exploring the potential effects of parental neophobia on developing offspring. We investigated if neophobic responses, alongside known drivers of fitness, influence nest success and offspring hormone responses in wild breeding jackdaws. Despite its consistency across the breeding season, and suggestions in the literature that it should have importance for reproductive fitness, parental neophobia did not predict nest success, provisioning rates or offspring hormone levels. Instead, sibling competition and poor parental care contributed to natural variation in stress responses. Parents with lower provisioning rates fledged fewer chicks, chicks from larger broods had elevated baseline CORT levels, and chicks with later hatching dates showed higher stress-induced CORT levels. Since CORT levels may influence the expression of adult neophobia, variation in juvenile stress responses could explain the development and maintenance of neophobic variation within the adult population.

Patient Perspectives on Sharing Anonymized Personal Health Data Using a Digital System for Dynamic Consent and Research Feedback: A Qualitative Study.

BACKGROUND: Electronic health records are widely acknowledged to provide an important opportunity to anonymize patient-level health care data and collate across populations to support research. Nonetheless, in the wake of public and policy concerns about security and inappropriate use of data, conventional approaches toward data governance may no longer be sufficient to respect and protect individual privacy. One proposed solution to improve transparency and public trust is known as Dynamic Consent, which uses information technology to facilitate a more explicit and accessible opportunity to opt out. In this case, patients can tailor preferences about whom they share their data with and can change their preferences reliably at any time. Furthermore, electronic systems provide opportunities for informing patients about data recipients and the results of research to which their data have contributed. OBJECTIVE: To explore patient perspectives on the use of anonymized health care data for research purposes. To evaluate patient perceptions of a Dynamic Consent model and electronic system to enable and implement ongoing communication and collaboration between patients and researchers. METHODS: A total of 26 qualitative interviews and three focus groups were conducted that included a video presentation explaining the reuse of anonymized electronic patient records for research. Slides and tablet devices were used to introduce the Dynamic Consent system for discussion. A total of 35 patients with chronic rheumatic disease with varying levels of illness and social deprivation were recruited from a rheumatology outpatient clinic; 5 participants were recruited from a patient and public involvement health research network. RESULTS: Patients were supportive of sharing their anonymized electronic patient record for research, but noted a lack of transparency and awareness around the use of data, making it difficult to secure public trust. While there were general concerns about detrimental consequences of data falling into the wrong hands, such as insurance companies, 39 out of 40 (98%) participants generally considered that the altruistic benefits of sharing health care data outweighed the risks. Views were mostly positive about the use of an electronic interface to enable greater control over consent choices, although some patients were happy to share their data without further engagement. Participants were particularly enthusiastic about the system as a means of enabling feedback regarding data recipients and associated research results, noting that this would improve trust and public engagement in research. This underlines the importance of patient and public involvement and engagement throughout the research process, including the reuse of anonymized health care data for research. More than half of patients found the touch screen interface easy to use, although a significant minority, especially those with limited access to technology, expressed some trepidation and felt they may need support to use the system. CONCLUSIONS: Patients from a range of socioeconomic backgrounds viewed a digital system for Dynamic Consent positively, in particular, feedback about data recipients and research results. Implementation of a digital Dynamic Consent system would require careful interface design and would need to be located within a robust data infrastructure; it has the potential to improve trust and engagement in electronic medical record research.

Peri-pubertal exposure to testicular hormones organizes response to novel environments and social behaviour in adult male rats.

Previous research has shown that exposure to testicular hormones during the peri-pubertal period of life has long-term, organizational effects on adult sexual behaviour and underlying neural mechanisms in laboratory rodents. However, the organizational effects of peri-pubertal testicular hormones on other aspects of behaviour and brain function are less well understood. Here, we investigated the effects of manipulating peri-pubertal testicular hormone exposure on later behavioural responses to novel environments and on hormone receptors in various brain regions that are involved in response to novelty. Male rodents generally spend less time in the exposed areas of novel environments than females, and this sex difference emerges during the peri-pubertal period. Male Lister-hooded rats (Rattus norvegicus) were castrated either before puberty or after puberty, then tested in three novel environments (elevated plus-maze, light-dark box, open field) and in an object/social novelty task in adulthood. Androgen receptor (AR), oestrogen receptor (ER1) and corticotropin-releasing factor receptor (CRF-R2) mRNA expression were quantified in the hypothalamus, hippocampus and medial amygdala. The results showed that pre-pubertally castrated males spent more time in the exposed areas of the elevated-plus maze and light-dark box than post-pubertally castrated males, and also confirmed that peri-pubertal hormone exposure influences later response to an opposite-sex conspecific. Hormone receptor gene expression levels did not differ between pre-pubertally and post-pubertally castrated males in any of the brain regions examined. This study therefore demonstrates that testicular hormone exposure during the peri-pubertal period masculinizes later response to novel environments, although the neural mechanisms remain to be fully elucidated.

Reduced resistance to oxidative stress during reproduction as a cost of early-life stress.

Stress exposure during early-life development can have long-term consequences for a variety of biological functions including oxidative stress. The link between early-life stress and oxidative balance is beginning to be explored and previous studies have focused on this link in adult non-breeding or immature individuals. However, as oxidative stress is considered as the main physiological mechanism underlying the trade-off between self-maintenance and investment in reproduction, it is necessary to look at the consequences of early-life stress on oxidative status during reproduction. Here, we investigated the effects of exposure to pre- and/or post-natal stress on oxidative balance during reproduction under benign or stressful environmental conditions in an avian model species, the Japanese quail. We determined total antioxidant status (TAS), total oxidant status (TOS) and resistance to a free-radical attack in individual exposed to pre-natal stress, post-natal stress or both and in control individuals exposed to none of the stressors. TAS levels decreased over time in all females that reproduced under stressful conditions. TOS decreased between the beginning and the end of reproductive period in pre-natal control females. In all females, resistance to a free-radical attack decreased over the reproductive event but this decrease was more pronounced in females from a pre-natal stress development. Our results suggest that pre-natal stress may be associated with a higher cost of reproduction in terms of oxidative stress. These results also confirm that early-life stress can be associated with both benefits and costs depending of the life-history stage or environmental context.

Developmental stress predicts social network position.

The quantity and quality of social relationships, as captured by social network analysis, can have major fitness consequences. Various studies have shown that individual differences in social behaviour can be due to variation in exposure to developmental stress. However, whether these developmental differences translate to consistent differences in social network position is not known. We experimentally increased levels of the avian stress hormone corticosterone (CORT) in nestling zebra finches in a fully balanced design. Upon reaching nutritional independence, we released chicks and their families into two free-flying rooms, where we measured daily social networks over five weeks using passive integrated transponder tags. Developmental stress had a significant effect on social behaviour: despite having similar foraging patterns, CORT chicks had weaker associations to their parents than control chicks. Instead, CORT chicks foraged with a greater number of flock mates and were less choosy with whom they foraged, resulting in more central network positions. These findings highlight the importance of taking developmental history into account to understand the drivers of social organization in gregarious species.

Early life stress shapes female reproductive strategy through eggshell pigmentation in Japanese quail.

Physiological constraints on colouration have been widely reported; especially in birds, which trade-off antioxidant responses against colourful costly signals. One female extended phenotypic trait, which might also highlight important physiological trade-offs, is the pigmentation of their eggshells. In ground-nesting species, producing eggs that are visually undetectable by predators is the best camouflage strategy. However, the condition-dependence of eggshell pigmentation, and the pigments role in oxidative stress, may constrain females to trade-off between their antioxidant capacity and maximising the camouflage of their eggs when they deposit eggshell pigments. Developmental stress is one factor that influences female antioxidant capacity, and could lead to variations in eggshell pigmentation that might have crucial consequences on individual fitness if egg crypsis is compromised especially under stressful conditions. We investigated the interaction between developmental and breeding conditions with respect to eggshell pigmentation in Japanese quail. We studied 30 females that bred under both control and stressful conditions, and were exposed to pre- and/or post-natal stress, or neither. Pre- and post-natal stress independently influenced eggshell pigmentation strategies under stressful breeding conditions. Under stressful reproduction, eggshell protoporphyrin concentration and maculation were affected by pre-natal stress, whereas eggshell reflectance and biliverdin concentration were influenced by post-natal stress. These changes may reflect potential adaptive strategies shaped by developmental stress, but additional data on the benefit of egg crypsis in quail, combined with studies on the role of both pigments on chick survival, will help to clarify whether early life stress can enhance fitness through eggshell pigmentation when developmental and reproductive environments match.

Co-occurring Epilepsy and Attention-Deficit/Hyperactivity Disorder in a 6-Year-Old Boy.

CASE: "Andrew" is a 6-year-old, right-handed, cisgender boy who presents for neuropsychological testing to determine whether he meets criteria for attention-deficit/hyperactivity disorder (ADHD). Andrew's parents report that he is easily distracted, has poor concentration, and is unable to sustain attention for discrete periods of time. Andrew is the product of an uncomplicated pregnancy and delivery, and there were no reported concerns in the postnatal period. Andrew met all of his language and motor milestones on time. He was described as having an "easy" temperament in his infancy and toddler years. Difficulties with attention started in preschool in that Andrew was described as frequently "getting lost" in his play or the task he was working on. He was easy to redirect and responded to cues and reminders. Socially, Andrew was described as friendly but not always "picking up on social cues." Andrew's kindergarten teachers first noted that sometimes Andrew would "blank out" and appear to stare off, which was attributed to inattention. His teachers brought their concerns to Andrew's parents, and his parents began to observe Andrew more carefully and noted that these episodes also occurred at home daily. When queried, his parents reported that these episodes would last 4 to 5 seconds and Andrew would not respond to his name being called or to being physically touched. Andrew's medical history, and that of his immediate and extended family, is unremarkable. Routine hearing and vision screenings are also unremarkable. There are no reports of head injuries or concussions. Andrew's gait is stable, and there are no signs of motor weakness. There are no reports of sensory seeking or avoiding behaviors. There are no reports of witnessing or experiencing trauma; motor or vocal tics; or compulsions, ritualized behaviors, or restricted interests.Testing revealed high average verbal comprehension skills, average perceptual and fluid reasoning, and lower end of average working memory and processing speed. During testing, the examiner noted a rapid eye flutter, which Andrew did not see to recognize himself but did ask the examiner to repeat the previous question. Parent and teacher rating scales of emotional and behavioral functioning showed elevations in the areas of inattention and adaptability and 1 scale of executive functioning noted elevations in task monitoring but no other difficulties. Socially, Andrew is well liked by his peers, although he can present as "silly." He has many same-aged friends and enjoys group activities. His parents have been hesitant to get him involved in sports because he has been known to have these staring episodes right after competing in sporting events. He also tends to have them more often during the school week when he has less sleep, which his parents attribute to having a difficult time falling asleep at night. What would you do next?

Developmental programming: cumulative effects of increased pre-hatching corticosterone levels and post-hatching unpredictable food availability on physiology and behaviour in adulthood.

Prolonged exposure to stress during development can have long-term detrimental effects on health and wellbeing. However, the environmental matching hypothesis proposes that developmental stress programs physiology and behaviour in an adaptive way that can enhance fitness if early environments match those experienced later in life. Most research has focused on the harmful effects that stress during a single period in early life may exert in adulthood. In this study, we tested the potential additive and beneficial effects that stress experienced during both pre- and post-hatching development may have on adult physiology and behaviour. Japanese quail experienced different stress-related treatments across two developmental life stages: pre-hatching corticosterone (CORT) injection, post-hatching unpredictable food availability, both pre- and post-hatching treatments, or control. In adulthood, we determined quails' acute stress response, neophobia and novel environment exploration. The pre-hatching CORT treatment resulted in attenuated physiological responses to an acute stressor, increased activity levels and exploration in a novel environment. Post-hatching unpredictable food availability decreased adults' latency to feed. Furthermore, there were cumulative effects of these treatments across the two developmental stages: quail subjected to both pre- and post-hatching treatments were the most explorative and risk-taking of all treatment groups. Such responses to novel environments could enhance survival in unpredictable environments in later life. Our data also suggest that these behavioural responses may have been mediated by long-term physiological programming of the adrenocortical stress response, creating phenotypes that could exhibit fitness-enhancing behaviours in a changing environment.