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?

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.

High-Stakes Treatment Negotiations Gone Awry: The Importance of Interactions for Understanding Treatment Advocacy and Patient Resistance.

Doctors (and sociologists) have a long history of struggling to understand why patients seek medical help yet resist treatment recommendations. Explanations for resistance have pointed to macrostructural changes, such as the rise of the engaged patient or decline of physician authority. Rather than assuming that concepts such as resistance, authority, or engagement are exogenous phenomena transmitted via conversational conduits, we examine how they are dynamically co-constituted interactionally. Using conversation analysis to analyze a videotaped interaction of an oncology patient resisting the treatment recommendation even though she might die without treatment, we show how sustained resistance manifests in and through her doctor's actions. This paradox, in which the doctor can both recommend life-prolonging care and condition resistance to it, has broad relevance beyond cancer treatment; it also can help us to understand other doctor-patient decisional conflicts, for instance, medication nonadherence, delaying emergent care, and vaccine refusal.

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.

Light-induced asymmetries in embryonic retinal gene expression are mediated by the vascular system and extracellular matrix.

Left-right asymmetries in the nervous system (lateralisation) influence a broad range of behaviours, from social responses to navigation and language. The role and pathways of endogenous and environmental mechanisms in the ontogeny of lateralisation remains to be established. The domestic chick is a model of both endogenous and experience-induced lateralisation driven by light exposure. Following the endogenous rightward rotation of the embryo, the asymmetrical position in the egg results in a greater exposure of the right eye to environmental light. To identify the genetic pathways activated by asymmetric light stimulation, and their time course, we exposed embryos to different light regimes: darkness, 6 h of light and 24 h of light. We used RNA-seq to compare gene expression in the right and left retinas and telencephalon. We detected differential gene expression in right vs left retina after 6 h of light exposure. This difference was absent in the darkness condition and had already disappeared by 24 h of light exposure, suggesting that light-induced activation is a self-terminating phenomenon. This transient effect of light exposure was associated with a downregulation of the sensitive-period mediator gene DIO2 (iodothyronine deiodinase 2) in the right retina. No differences between genes expressed in the right vs. left telencephalon were detected. Gene networks associated with lateralisation were connected to vascularisation, cell motility, and the extracellular matrix. Interestingly, we know that the extracellular matrix-including the differentially expressed PDGFRB gene-is involved in morphogenesis, sensitive periods, and in the endogenous chiral mechanism of primary cilia, that drives lateralisation. Our data show a similarity between endogenous and experience-driven lateralisation, identifying functional gene networks that affect lateralisation in a specific time window.

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.

Study recruitment factors in advanced cancer: the Prognosis in Palliative care Study II (PiPS2) - a multicentre, prospective, observational cohort project.

OBJECTIVES: The Prognosis in Palliative care Study II (PiPS2) was a large multicentre observational study validating prognostic tools in patients with advanced cancer. Many palliative care studies fail to reach their recruitment target. To inform future studies, PiPS2 rigorously monitored and identified any potential recruitment barriers. METHODS: Key recruitment stages (ie, whether patients were eligible for the study, approached by the researchers and whether consent was obtained for enrolment) were monitored via comprehensive screening logs at participating sites (inpatient hospices, hospitals and community palliative care teams). The reasons for patients' ineligibility, inaccessibility or decision not to consent were documented. RESULTS: 17 014 patients were screened across 27 participating sites over a 20-month recruitment period. Of those, 4642 (27%) were ineligible for participation in the study primarily due to non-cancer diagnoses. Of 12 372 eligible patients, 9073 (73%) were not approached, the most common reason being a clinical decision not to do so. Other reasons included patients' death or discharge before they were approached by the researchers. Of the 3299 approached patients, 1458 (44%) declined participation mainly because of feeling too unwell, experiencing severe distress or having other competing priorities. 11% (n=1841/17 014) of patients screened were enrolled in the study, representing 15% (n=1841/12 372) of eligible patients. Different recruitment patterns were observed across inpatient hospice, hospital and community palliative care teams. CONCLUSIONS: The main barrier to recruitment was 'accessing' potentially eligible patients. Monitoring key recruitment stages may help to identify barriers and facilitators to enrolment and allow results to be put into better context. TRIAL REGISTRATION NUMBER: ISRCTN13688211.

Prognostic models of survival in patients with advanced incurable cancer: the PiPS2 observational study.

BACKGROUND: The Prognosis in Palliative care Study (PiPS) prognostic survival models predict survival in patients with incurable cancer. PiPS-A (Prognosis in Palliative care Study - All), which involved clinical observations only, and PiPS-B (Prognosis in Palliative care Study - Blood), which additionally required blood test results, consist of 14- and 56-day models that combine to create survival risk categories: 'days', 'weeks' and 'months+'. OBJECTIVES: The primary objectives were to compare PIPS-B risk categories against agreed multiprofessional estimates of survival and to validate PiPS-A and PiPS-B. The secondary objectives were to validate other prognostic models, to assess the acceptability of the models to patients, carers and health-care professionals and to identify barriers to and facilitators of clinical use. DESIGN: This was a national, multicentre, prospective, observational, cohort study with a nested qualitative substudy using interviews with patients, carers and health-care professionals. SETTING: Community, hospital and hospice palliative care services across England and Wales. PARTICIPANTS: For the validation study, the participants were adults with incurable cancer, with or without capacity to consent, who had been recently referred to palliative care services and had sufficient English language. For the qualitative substudy, a subset of participants in the validation study took part, along with informal carers, patients who declined to participate in the main study and health-care professionals. MAIN OUTCOME MEASURES: For the validation study, the primary outcomes were survival, clinical prediction of survival and PiPS-B risk category predictions. The secondary outcomes were predictions of PiPS-A and other prognostic models. For the qualitative substudy, the main outcomes were participants' views about prognostication and the use of prognostic models. RESULTS: For the validation study, 1833 participants were recruited. PiPS-B risk categories were as accurate as agreed multiprofessional estimates of survival (61%; p = 0.851). Discrimination of the PiPS-B 14-day model (c-statistic 0.837, 95% confidence interval 0.810 to 0.863) and the PiPS-B 56-day model (c-statistic 0.810, 95% confidence interval 0.788 to 0.832) was excellent. The PiPS-B 14-day model showed some overfitting (calibration in the large -0.202, 95% confidence interval -0.364 to -0.039; calibration slope 0.840, 95% confidence interval 0.730 to 0.950). The PiPS-B 56-day model was well-calibrated (calibration in the large 0.152, 95% confidence interval 0.030 to 0.273; calibration slope 0.914, 95% confidence interval 0.808 to 1.02). PiPS-A risk categories were less accurate than agreed multiprofessional estimates of survival (p < 0.001). The PiPS-A 14-day model (c-statistic 0.825, 95% confidence interval 0.803 to 0.848; calibration in the large -0.037, 95% confidence interval -0.168 to 0.095; calibration slope 0.981, 95% confidence interval 0.872 to 1.09) and the PiPS-A 56-day model (c-statistic 0.776, 95% confidence interval 0.755 to 0.797; calibration in the large 0.109, 95% confidence interval 0.002 to 0.215; calibration slope 0.946, 95% confidence interval 0.842 to 1.05) had excellent or reasonably good discrimination and calibration. Other prognostic models were also validated. Where comparisons were possible, the other prognostic models performed less well than PiPS-B. For the qualitative substudy, 32 health-care professionals, 29 patients and 20 carers were interviewed. The majority of patients and carers expressed a desire for prognostic information and said that PiPS could be helpful. Health-care professionals said that PiPS was user friendly and may be helpful for decision-making and care-planning. The need for a blood test for PiPS-B was considered a limitation. LIMITATIONS: The results may not be generalisable to other populations. CONCLUSIONS: PiPS-B risk categories are as accurate as agreed multiprofessional estimates of survival. PiPS-A categories are less accurate. Patients, carers and health-care professionals regard PiPS as potentially helpful in clinical practice. FUTURE WORK: A study to evaluate the impact of introducing PiPS into routine clinical practice is needed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13688211. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 28. See the NIHR Journals Library website for further project information.

A prognosis is a prediction about how long someone will live after a diagnosis of illness. The Prognosis in Palliative care Study (PiPS) tools [PiPS-A (Prognosis in Palliative care Study ­ All) and PiPS-B (Prognosis in Palliative care Study ­ Blood), respectively] were designed to predict survival in patients with incurable cancer. Previously, they were found to be as accurate as health-care professionals. The purpose of this study was to find out whether PiPS was more accurate at prognosticating than health-care professionals, to evaluate other prognostic tools and to ask patients, their carers and health-care professionals what they thought about using them. We studied 1833 patients with advanced cancer and calculated their PiPS score and other prognostic scores. We asked health-care professionals to estimate how long the patients would live. We then followed up the patients to find out how long they actually lived and if the predictions made by health-care professionals were as accurate as the predictions made by the prognostic tools. We interviewed patients, their carers and health-care professionals to ask them what they thought about using these prognostic tools. We found that PiPS-B was as accurate as the combined wisdom of a doctor and a nurse at predicting whether patients would live for 'days', 'weeks' or 'months+'. We found that PiPS-A predictions were not as accurate as predictions made by health-care professionals. We found that (where direct comparisons could be made) PiPS-B was better than other prognostic tools. Finally, we found that patients, carers and health-care professionals thought that PiPS tools could be helpful in clinical practice because they would be less subjective than clinicians' intuition. This means that PiPS-B could be considered as a tool to support clinician predictions of survival and may lead to patients and families being able to take more control at the end of their lives. Further research will be required to investigate whether or not this approach actually leads to improvements in care.

Does Palliative Care Utilization Facilitate Conversion to Hospice Care? A Qualitative Study of the "Soft No".

BACKGROUND: Facilitating patient conversion to hospice at end of life is a prominent clinical concern. Enrollment in outpatient palliative care services is often assumed to encourage seamless transition to hospice care, but this has not been demonstrated. Moreover, decisions to convert from palliative care to hospice are generally treated as dichotomous, thus hampering our ability to understand decision processes. OBJECTIVE: To examine medical decision-making among patients who are prospectively evaluating whether to convert from palliative care to hospice. DESIGN: Qualitative case study, using in-depth interviews and constant comparative method. SETTING/PATIENTS: Terminally ill patients currently enrolled in outpatient palliative care services (N = 26) and their caregivers (N = 16), selected purposely for maximum variation in condition and personal background. MEASUREMENTS: Themes identified in qualitative in-depth interviews. RESULTS: Patients rarely refused hospice outright but more often postponed using a "soft no," in which they neither accepted nor overtly refused hospice. Justifications patients and caregivers offered for why hospice was not needed (yet) appeared in these themes: (1) not seeing the value added of hospice, (2) assuming the timing is premature, and (3) relying on extensive health-related support networks that justify or endorse continuation of active care. CONCLUSIONS: Despite assumptions to the contrary, benefits associated with utilization of outpatient palliative care services have the potential to incentivize the delay of hospice in some cases. Clinical interactions with outpatient palliative care patients should consider the influence of these broad social support systems when discussing hospice options.

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.

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.

Blood is thicker than water: Flaws in a National Toxicology Program study.

Municipal fluoridation was a mid-twentieth century innovation based on the medical hypothesis that consuming low doses of fluoride when young provided protection against cavities with only a small risk of mild dental fluorosis, a cosmetic effect. In the 21st century, more than half of American teens are afflicted by dental fluorosis with approximately one in five having moderate to severe dental fluorosis in at least two teeth. Scientific literature since the 1990s has found that even low doses of fluoride adversely affect cognitive-behavioral development and that deficits are correlated with the severity of dental fluorosis in afflicted individuals. Evidence of neurotoxic impact from low dose systemic exposure to fluoride prompted an investigation by a branch of the governmental agency that has promoted fluoridation policy since its 1940's inception. This review identifies ten significant flaws in the design of an animal experiment conducted by the U.S. National Toxicology Program as part of that investigation into the neurotoxic impact of systemic prenatal and postnatal fluoride exposure. The authors hypothesize that organizational bias can and does compromise the integrity of fluoride research.

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.

Chronological age, biological age, and individual variation in the stress response in the European starling: a follow-up study.

The strength of the avian stress response declines with age. A recently published study of European starlings (Sturnus vulgaris) found that a marker of biological age predicted the strength of the stress response even in individuals of the same chronological age. Specifically, birds that had experienced greater developmental telomere attrition (DTA) showed a lower peak corticosterone (CORT) response to an acute stressor, and more rapid recovery of CORT levels towards baseline. Here, we performed a follow-up study using the same capture-handling-restraint stressor in a separate cohort of starlings that had been subjected to a developmental manipulation of food availability and begging effort. We measured the CORT response at two different age points (4 and 18 months). Our data suggest a decline in the strength of the CORT response with chronological age: peak CORT was lower at the second age point, and there was relatively more reduction in CORT between 15 and 30 min. Individual consistency between the two age points was low, but there were modest familial effects on baseline and peak CORT. The manipulation of begging effort affected the stress response (specifically, the reduction in CORT between 15 and 30 min) in an age-dependent manner. However, we did not replicate the associations with DTA observed in the earlier study. We meta-analysed the data from the present and the earlier study combined, and found some support for the conclusions of the earlier paper.

Stress hormones, social associations and song learning in zebra finches.

The use of information provided by others is a common short-cut adopted to inform decision-making. However, instead of indiscriminately copying others, animals are often selective in what, when and whom they copy. How do they decide which 'social learning strategy' to use? Previous research indicates that stress hormone exposure in early life may be important: while juvenile zebra finches copied their parents' behaviour when solving novel foraging tasks, those exposed to elevated levels of corticosterone (CORT) during development copied only unrelated adults. Here, we tested whether this switch in social learning strategy generalizes to vocal learning. In zebra finches, juvenile males often copy their father's song; would CORT-treated juveniles in free-flying aviaries switch to copying songs of other males? We found that CORT-treated juveniles copied their father's song less accurately as compared to control juveniles. We hypothesized that this could be due to having weaker social foraging associations with their fathers, and found that sons that spent less time foraging with their fathers produced less similar songs. Our findings are in line with a novel hypothesis linking early-life stress and social learning: early-life CORT exposure may affect social learning indirectly as a result of the way it shapes social affiliations.This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.

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).

Transforming Patient Compliance Research in an Era of Biomedicalization.

The term patient noncompliance emerged in the 1970s as a tool for analyzing why people do not follow medical directives. Despite its early popularity, the term has languished in sociology while flourishing in biomedical arenas. It seems flaccid in a contemporary healthcare context as it overestimates physician authority and is tone-deaf to biomedicalization. I draw from sociological and anthropological traditions, as well as qualitative interviews with terminally ill patients ( N = 26) and their caregivers ( N = 16), to consider facets of a biomedicalized health experience and implications for an updated vision of compliance. First, pathways to care have proliferated under biomedicalization. With increased pathways comes increased need for understanding how treatment plans are socially constituted and assessed. Finally, increased complexity demands a more diverse vocabulary for understanding health related decisions. This paper is a call to sociologists to take the lead in transforming and updating this consequential concept.