Ecological and social pressures interfere with homeostatic sleep regulation in the wild.

Sleep is fundamental to the health and fitness of all animals. The physiological importance of sleep is underscored by the central role of homeostasis in determining sleep investment - following periods of sleep deprivation, individuals experience longer and more intense sleep bouts. Yet, most sleep research has been conducted in highly controlled settings, removed from evolutionarily relevant contexts that may hinder the maintenance of sleep homeostasis. Using triaxial accelerometry and GPS to track the sleep patterns of a group of wild baboons (Papio anubis), we found that ecological and social pressures indeed interfere with homeostatic sleep regulation. Baboons sacrificed time spent sleeping when in less familiar locations and when sleeping in proximity to more group-mates, regardless of how long they had slept the prior night or how much they had physically exerted themselves the preceding day. Further, they did not appear to compensate for lost sleep via more intense sleep bouts. We found that the collective dynamics characteristic of social animal groups persist into the sleep period, as baboons exhibited synchronized patterns of waking throughout the night, particularly with nearby group-mates. Thus, for animals whose fitness depends critically on avoiding predation and developing social relationships, maintaining sleep homeostasis may be only secondary to remaining vigilant when sleeping in risky habitats and interacting with group-mates during the night. Our results highlight the importance of studying sleep in ecologically relevant contexts, where the adaptive function of sleep patterns directly reflects the complex trade-offs that have guided its evolution.

Corrigendum to: "Task syndromes: linking personality and task allocation in social animal groups" by J. C. Loftus, A. Perez, and A. Sih. 32:1-17.

[This corrects the article DOI: 10.1093/beheco/araa083.].

Locomotor compromises maintain group cohesion in baboon troops on the move.

When members of a group differ in locomotor capacity, coordinating collective movement poses a challenge: some individuals may have to move faster (or slower) than their preferred speed to remain together. Such compromises have energetic repercussions, yet research in collective behaviour has largely neglected locomotor consensus costs. Here, we integrate high-resolution tracking of wild baboon locomotion and movement with simulations to demonstrate that size-based variation in locomotor capacity poses an obstacle to the collective movement. While all baboons modulate their gait and move-pause dynamics during collective movement, the costs of maintaining cohesion are disproportionately borne by smaller group members. Although consensus costs are not distributed equally, all group-mates do make locomotor compromises, suggesting a shared decision-making process drives the pace of collective movement in this highly despotic species. These results highlight the importance of considering how social dynamics and locomotor capacity interact to shape the movement ecology of group-living species.

Task syndromes: linking personality and task allocation in social animal groups.

Studies of eusocial insects have extensively investigated two components of task allocation: how individuals distribute themselves among different tasks in a colony and how the distribution of labor changes to meet fluctuating task demand. While discrete age- and morphologically-based task allocation systems explain much of the social order in these colonies, the basis for task allocation in non-eusocial organisms and within eusocial castes remains unknown. Building from recent advances in the study of among-individual variation in behavior (i.e., animal personalities), we explore a potential mechanism by which individuality in behaviors unrelated to tasks can guide the developmental trajectories that lead to task specialization. We refer to the task-based behavioral syndrome that results from the correlation between the antecedent behavioral tendencies and task participation as a task syndrome. In this review, we present a framework that integrates concepts from a long history of task allocation research in eusocial organisms with recent findings from animal personality research to elucidate how task syndromes and resulting task allocation might manifest in animal groups. By drawing upon an extensive and diverse literature to evaluate the hypothesized framework, this review identifies future areas for study at the intersection of social behavior and animal personality.

Evolution and characteristics of the use of valproate in women of childbearing age with bipolar disorder: Results from the FACE-BD cohort.

BACKGROUND: Valproate is associated with teratogenic and neurodevelopmental effects. Several agencies have restricted the conditions of its prescription in bipolar disorders (BD). We aimed to assess the evolution of valproate prescription and the clinical profile of BD women of childbearing age receiving valproate. METHODS: Based on a large national cohort, we included all BD women 16-50 years old. Sociodemographic, clinical and pharmacological data were recorded. Logistic regression analyses were used to describe variables associated with valproate prescription. RESULTS: Of the 1018 included women 16-50 years old, 26.9% were treated with valproate with a mean daily dosage of 968 mg. The prevalence of BD women using valproate was 32.6% before May 2015 and 17.3% after May 2015 (p<0.001), the date of French regulatory publication of restriction of valproate prescription. The multivariate analysis revealed that the inclusion period after May 2015 (OR=0.54, CI 95% 0.37-0.78, p=0.001), the age lower than 40 years (OR=0.65, CI 95% 0.43-0.98, p=0.040) and the number of lifetime mood episodes (OR=0.98, CI 95% 0.95-0.99, p=0.040) were the variables negatively associated with the use of valproate. LIMITATIONS: Study could be underpowered to determine a clinical profile associated with valproate prescription. CONCLUSIONS: The regulatory change in BD women of childbearing age had a significant impact on valproate prescription, even if the prescription rate remains high. Important efforts are needed to help clinicians and patients to improve quality of care in BD women of childbearing age.

Psychiatric comorbidities in bipolar disorders: An examination of the prevalence and chronology of onset according to sex and bipolar subtype.

OBJECTIVES: Bipolar Disorder (BD) is frequently comorbid with other psychiatric disorders. However, few studies systematically examine which disorders are more likely to occur pre- or post-BD onset. We examine the prevalence and Age At Onset (AAO) of psychiatric conditions in adults with BD. METHODS: A structured clinical interview was used to assess lifetime history and AAO of alcohol and cannabis misuse, suicide attempts, anxiety and eating disorders in a French sample of euthymic patients with BD (n = 739). Regression analyses were used to test for statistically significant associations between rates and AAO of comorbidities in BD groups stratified by sex or subtype. RESULTS: Prevalence of alcohol and cannabis misuse was associated with male sex and BD-I subtype; whilst most anxiety and eating disorders were associated with female sex. The AAO of most comorbid conditions preceded that of BD, except for panic disorder, agoraphobia and alcohol misuse. Few variations were observed in AAO of comorbidities according to groups. LIMITATIONS: All assessments were retrospective, so estimates of prevalence rates and especially exact AAO of some comorbidities are at risk of recall bias. CONCLUSIONS: Sex and BD subtype are associated with different rates of comorbid disorders. However, there were minimal between group differences in median AAO of comorbidities. By describing the chronological sequence of comorbidities in BD we were able to demonstrate that a minority of comorbidities typically occurred post-onset of BD. This is noteworthy as these disorders might be amenable to interventions aimed at early secondary prevention.

Affect lability predicts occurrence of suicidal ideation in bipolar patients: a two-year prospective study.

OBJECTIVE: The aim of our study was to investigate, in bipolar patients, whether affect lability was associated with suicidal ideation incidence during 2-year follow-up, and which subtype of affect lability was associated with suicidal ideation. METHOD: A total of 319 euthymic or mildly depressed bipolar outpatients recruited in the French FondaMental Advanced Centres of Expertise for Bipolar Disorder were divided into two subgroups according to the occurrence of suicidal ideation during a 2-year follow-up. Affect lability was assessed by the French version of the Affect Lability Scale. RESULTS: Bipolar patients with high affect lability were more likely to report suicidal ideation during follow-up, even after adjustment for age, study level, rapid cycling, current depression level, anxiety disorder, and lifetime history SA (OR = 2.47; 95% CI [1.15-5.30], P = 0.01). The risk of suicidal ideation increased with the level of affect lability. More specifically, the propensity to switch from neutral to elation affect, from anxious to depressive affect (or inversely), and from neutral to anger affect predicted suicidal ideation. CONCLUSION: Reducing affective lability could become a new therapeutic target of suicidal prevention in bipolar disorder.

Association between childhood dimensions of attention deficit hyperactivity disorder and adulthood clinical severity of bipolar disorders.

BACKGROUND: Clinical features of attention deficit hyperactivity disorder can be frequently observed in cases with bipolar disorders and associated with greater severity of bipolar disorders. Although designed as a screening tool for attention deficit hyperactivity disorder, the Wender Utah Rating Scale could, given its factorial structure, be useful in investigating the early history of impulsive, inattentive or mood-related symptoms among patients with bipolar disorders. METHODS: We rated the Wender Utah Rating Scale in 276 adult bipolar disorder cases and 228 healthy controls and tested its factorial structure and any associations with bipolar disorder phenomenology. RESULTS: We confirmed a three-factor structure for the Wender Utah Rating Scale (' impulsivity/temper', ' inattentiveness' and ' mood/self-esteem'). Cases and controls differed significantly on Wender Utah Rating Scale total score and sub-scale scores ( p-values < 10-5). About 23% of bipolar disorder cases versus 5% of controls were classified as ' WURS positive' (odds ratio = 5.21 [2.73-9.95]). In bipolar disorders, higher Wender Utah Rating Scale score was associated with earlier age at onset, severity of suicidal behaviors and polysubstance misuse; multivariate analyses, controlling for age and gender, confirmed the associations with age at onset ( p = 0.001) and alcohol and substance misuse ( p = 0.001). CONCLUSION: Adults with bipolar disorders who reported higher levels of childhood symptoms on the Wender Utah Rating Scale presented a more severe expression of bipolar disorders in terms of age at onset and comorbidity. The Wender Utah Rating Scale could be employed to screen for attention deficit hyperactivity disorder but also for ' at-risk behaviors' in adult bipolar disorder cases and possibly for prodromal signs of early onset in high-risk subjects.

Effect of early trauma on the sleep quality of euthymic bipolar patients.

OBJECTIVE: Poor quality of sleep is frequent in euthymic bipolar patients and conveys worse clinical outcomes. We investigated the features of euthymic bipolar patients associated with poor sleep quality, with a focus on the effect of childhood trauma. METHOD: 493 euthymic patients with DSM-IV-defined bipolar disorders were recruited in FondaMental Advanced Centers of Expertize for Bipolar Disorders (FACE-BD) between 2009 and 2014. Clinical variables were recorded. Subjective sleep quality and history of childhood trauma were respectively measured by the Pittsburgh Sleep Quality Index (PSQI) and the Childhood Trauma Questionnaire (CTQ). RESULTS: Poor sleepers were older, less professionally active, had significantly higher anxiety levels, took more anxiolytic drugs and did endorse more suicide attempts and suicidal ideas than good sleepers after adjusting for anxiety levels and age. Emotional abuse was associated with poor sleep quality after adjustment for BMI, age, professional activity, and bipolar disorders (BD) type (OR=1.83; 95% CI [1.30; 3.10]; p=0.02). However, this association was lost after adjustment for anxiety levels, anxiolytic treatment and suicide ideation/attempts. LIMITATIONS: The main limitation was the type of sleep assessment, which only measured the subjective part of sleep complaints. CONCLUSION: A history of emotional abuse might underlie sleep problems in many bipolar patients but anxiety seems to act as a confounding factor in this relationship. New studies are needed to elucidate the role of childhood maltreatment on poor sleep among bipolar patients.

How Honey Bee Colonies Survive in the Wild: Testing the Importance of Small Nests and Frequent Swarming.

The ectoparasitic mite, Varroa destructor, and the viruses that it transmits, kill the colonies of European honey bees (Apis mellifera) kept by beekeepers unless the bees are treated with miticides. Nevertheless, there exist populations of wild colonies of European honey bees that are persisting without being treated with miticides. We hypothesized that the persistence of these wild colonies is due in part to their habits of nesting in small cavities and swarming frequently. We tested this hypothesis by establishing two groups of colonies living either in small hives (42 L) without swarm-control treatments or in large hives (up to 168 L) with swarm-control treatments. We followed the colonies for two years and compared the two groups with respect to swarming frequency, Varroa infesttion rate, disease incidence, and colony survival. Colonies in small hives swarmed more often, had lower Varroa infestation rates, had less disease, and had higher survival compared to colonies in large hives. These results indicate that the smaller nest cavities and more frequent swarming of wild colonies contribute to their persistence without mite treatments.

The 5-lipoxygenase inhibitor tepoxalin induces oxidative damage and altered PTEN status prior to apoptosis in canine osteosarcoma cell lines.

The 5-lipoxygenase (5-LOX) inhibitor tepoxalin has been shown to slow canine osteosarcoma (OSA) tumour xenografts growth, yet the mechanisms are poorly elucidated. Further examination of tepoxalin in canine OSA cell lines shows that tepoxalin treated cells undergo apoptosis through caspase-3 activation and annexin staining. Interestingly, apoptosis is superseded by an increase in reactive oxygen species (ROS), as measured by activation of dihydrorhodamine 123 and mitosox. This increase in ROS appears to be related to the 5-LOX inhibitor regardless of cellular 5-LOX status, and was not observed after treatment with the tepoxalin metabolite RWJ20142. Additionally, 5-LOX inhibition by tepoxalin appears to increase phosphatase and tensin (PTEN) homolog activity by preventing its alkylation or oxidation. PTEN modification or inhibition allows phosphoinositide-3 (PI3) kinase activity thereby heightening activation of protein kinase B (AKT) phosphorylation. Our data suggest that off target oxidation and LOX inhibition play roles in the apoptotic response.

Increased risk of suicide attempt in bipolar patients with severe tobacco dependence.

BACKGROUND: The aim of our study was to investigate, in bipolar patients, the association between tobacco status (use and dependence) and history of suicide attempt, and to assess the possible role of inflammation as a missing link in the association between smoking status and history of suicide attempt. METHODS: A total of 453 adult bipolar out-patients recruited in the French FondaMental Advanced Centres of Expertise for Bipolar Disorder were divided into two subgroups: 274 patients without past history of suicide attempt (non-SA), and 179 patients with a past history of suicide attempt (SA). Tobacco use and dependence, psychiatric and somatic comorbidities, history of childhood abuse, family history of suicide were assessed. Fasting blood tests yielded samples collected for the measurement of high sensitivity (hs-)CRP. RESULTS: The risk of suicide attempt increased with smoking dependence. Notably, bipolar patients with a history of suicide attempt were three times more likely to have severe tobacco dependence, independently of confounding factors. However, we failed to find arguments promoting the hypothesis of inflammatory markers (through hs-CRP measure) in the link between tobacco dependence and suicidal behavior. CONCLUSIONS: We found a significant association between severe tobacco dependence and history of suicide attempt, but not with level of CRP, independently of confusing factors. Longitudinal studies taken into account all these potential confusing factors are needed to confirm our results.

The use of weighted health-related Quality of Life scores in people with diabetic macular oedema at baseline in a randomized clinical trial.

AIMS: To examine the relationship between visual acuity in each eye and Quality of Life (QoL) outcomes in people with diabetic macular oedema. METHODS: Cross sectional retrospective analysis of data collected at baseline in 289 people entered into a randomized clinical trial with diabetic macular oedema which investigated the safety and efficacy of a vascular endothelial growth factor inhibitor, pegaptanib sodium. At the baseline visit, visual acuity was measured through refraction and using retro-illuminated modified Early Treatment Diabetic Retinopathy Study Log MAR charts, and patient health-related QoL was determined using the European Quality of Life EQ-5D-3L and the Visual Functioning Questionnaire-25 (NEI-VFQ25). A regression analysis with QoL score from each vision-related domain as the dependent variable was fitted using linear and quadratic terms of the better and worse eye, age, gender, adjusted for number of concurrent conditions, ethnicity and level of diabetes control. RESULTS: For all vision-related QoL domains from NEI-VFQ25 and EQ-5D-3L except ocular pain, both visual acuity in the better-seeing and the worse-seeing eye gave a significant increase in correlation coefficient over that obtained from clinical and demographic data. The NEI-VFQ25 correlation was most closely associated with a weighted visual acuity measure of 0.75 in the better and 0.25 in the worse eye or 0.60 in the better and 0.40 in the worse eye. CONCLUSIONS: We recommend that a weighted visual acuity measure from both eyes is considered in future diabetic macular oedema trials.

Clinical and neuropsychological characteristics of euthymic bipolar patients having a history of severe suicide attempt.

OBJECTIVE: Identifying bipolar patients at high-suicide risk is a major health issue. To improve their identification, we compared dimensional and neuropsychological profile of bipolar patients with or without history of suicide attempt, taking into account suicidal severity (i.e. admission to intensive ward). METHOD: A total of 343 adult euthymic bipolar out-patients recruited in the French FondaMental Advanced Centres of Expertise for Bipolar Disorder were divided into three subgroups: 214 patients without history of suicide attempt, 88 patients with past history of non-severe suicide attempt and 41 patients with past history of severe suicide attempt. General intellectual functioning, speed of information processing, verbal learning and memory, verbal fluency and executive functioning were assessed. RESULTS: Severe suicide attempters had lower affective intensity and lability than non-severe attempters. Severe suicide attempters outperformed non-severe attempters for verbal learning and non-attempters for Stroop word reading part after adjustment for study centre, age, gender, educational level, antipsychotics use, depression score, anxious and addictive comorbidities. CONCLUSION: Neuropsychological tasks commonly used to assess bipolar patients do not seem accurate to identify suicide attempters in euthymic patients. In the future, decision-making and emotional recognition tasks should be assessed. Moreover, clinical and neuropsychological profiles should be considered together to better define suicidal risk.

A critical number of workers in a honeybee colony triggers investment in reproduction.

Social insect colonies, like individual organisms, must decide as they develop how to allocate optimally their resources among survival, growth, and reproduction. Only when colonies reach a certain state do they switch from investing purely in survival and growth to investing also in reproduction. But how do worker bees within a colony detect that their colony has reached the state where it is adaptive to begin investing in reproduction? Previous work has shown that larger honeybee colonies invest more in reproduction (i.e., the production of drones and queens), however, the term 'larger' encompasses multiple colony parameters including number of adult workers, size of the nest, amount of brood, and size of the honey stores. These colony parameters were independently increased in this study to test which one(s) would increase a colony's investment in reproduction via males. This was assayed by measuring the construction of drone comb, the special type of comb in which drones are reared. Only an increase in the number of workers stimulated construction of drone comb. Colonies with over 4,000 workers began building drone comb, independent of the other colony parameters. These results show that attaining a critical number of workers is the key parameter for honeybee colonies to start to shift resources towards reproduction. These findings are relevant to other social systems in which a group's members must adjust their behavior as a function of the group's size.

The effects of baicalein on canine osteosarcoma cell proliferation and death.

Flavonoids are a group of modified triphenolic compounds from plants with medicinal properties. Baicalein, a specific flavone primarily isolated from plant roots (Scutellaria baicalensis), is commonly used in Eastern medicine for its anti-inflammatory and antineoplastic properties. Previous research shows greater efficacy for baicalein than most flavonoids; however, there has been little work examining their effects on sarcoma cells, let alone canine cells. Three canine osteosarcoma cell lines (HMPOS, D17 and OS 2.4) were treated with baicalein to examine cell viability, cell cycle kinetics, anchorage-independent growth and apoptosis. Results showed that osteosarcoma cells were sensitive to baicalein at concentrations from approximately 1 to 25 µM. Modest cell cycle changes were observed in one cell line. Baicalein was effective in inducing apoptosis and did not prevent doxorubicin cell proliferation inhibition in all the cell lines. The mechanism for induction of apoptosis has not been fully elucidated; however, changes in mitochondrial permeability supersede the apoptotic response.

Effect of intravenous lidocaine administration on laminar inflammation in the black walnut extract model of laminitis.

REASONS FOR PERFORMING STUDY: Laminitis is a serious complication of horses suffering from sepsis/endotoxaemia-related events. Laminitis in horses and organ injury in human sepsis are both reported to involve inflammatory injury to the laminae/organs including early activation of endothelium and leucocytes leading to emigration of neutrophils into the tissue interstitium. In the black walnut extract (BWE) model, systemic inflammatory events coincide with marked increase in laminar mRNA concentrations of inflammatory genes including proinflammatory cytokines (i.e. IL-1beta, IL-6), COX-2, chemokines (i.e. IL-8) and endothelial adhesion molecules (i.e. ICAM-1 and E-selectin). In models of human sepsis, i.v. lidocaine has been reported to decrease leucocyte and endothelial activation, and the expression of proinflammatory cytokines and chemokines. OBJECTIVES: To evaluate the effect of i.v. lidocaine therapy on the inflammatory processes documented to occur in the BWE model of laminitis. METHODS: Twelve horses were administered BWE and treated immediately with either lidocaine (1.3 mg/kg bwt bolus, followed by 0.05 mg/kg bwt/min CRI, n=6) or saline (n=6) for 10 h. At 10 h post BWE administration, laminar samples were obtained under general anaesthesia for assessment of proinflammatory gene expression (using RT-qPCR) and leucocyte emigration (via CD13 immunohistochemistry). At 0, 3 and 10 h post BWE administration, skin samples were obtained for assessment of leucocyte emigration (via calprotectin immunohistochemistry). RESULTS: No significant differences between groups were noted for inflammatory gene mRNA concentrations (IL-1beta, IL-6, IL-8, COX-2) or for number of leucocytes present within the laminar interstitium or skin dermis. Increased (P<0.05) laminar E-selectin mRNA concentrations were present in the LD group (vs. SAL group). CONCLUSIONS: Continuous administration of i.v. lidocaine does not inhibit inflammatory events in either the laminae or skin in the horse administered black walnut extract. POTENTIAL RELEVANCE: This work questions the use of continuous i.v. administration of lidocaine as an effective anti-inflammatory therapy for systemic inflammation.

Mixed treatment comparison and meta-regression of the efficacy and safety of prostaglandin analogues and comparators for primary open-angle glaucoma and ocular hypertension.

OBJECTIVES: Primary open-angle glaucoma (POAG) is a chronic condition characterised by optic neuropathy and vision loss. Elevated intraocular pressure (IOP) can damage the optic nerve and is a risk factor for glaucoma, thus treatment usually comprises topical hypotensives. This analysis aims to address methodological issues associated with the synthesis of glaucoma clinical trial data, given variations in study methodology and IOP measurement. METHODS: Meta-regression was used to estimate how IOP varies over time for patients receiving treatment. Relative treatment effects were assessed using a random-effects mixed treatment comparison (MTC) in order to preserve randomisation and avoid selection bias. To produce clinically meaningful outputs, these analyses were combined to obtain the mean on-treatment IOP and the proportion of patients achieving different IOP targets at different time points. A further MTC estimated the probability of hyperaemia events. RESULTS: The analysis showed that after 3 months' treatment, between 58 and 83% of patients will have a > or =20% reduction in IOP and 70-93% of patients will have an absolute IOP <20 mmHg. Latanoprost and bimatoprost were found to produce significantly lower on-treatment IOP compared with timolol (p < 0.05); the difference between latanoprost and bimatoprost was not significant. Travoprost produced a lower mean IOP compared with timolol (not significant). Latanoprost-timolol was found to produce significantly lower IOP than latanoprost alone or beta-blockers. The probability of hyperaemia-type events varied between treatments from 14.8 to 63.03%. Latanoprost had significantly lower odds of hyperaemia than travoprost, bimatoprost, travoprost-timolol, or bimatoprost-timolol. CONCLUSION: This analysis suggests that latanoprost and bimatoprost produce a statistically significant reduction in IOP compared with timolol, but are associated with a higher risk of hyperaemia. Out of all the prostaglandins, latanoprost may achieve a good balance between tolerability and IOP efficacy. As with all forms of meta-analysis, the results are based on the assumption that the studies and intervention groupings are sufficiently similar to be compared.