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The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5–90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology.

This report examines the relationship between pediatric anxiety disorders and implicit bias evoked by threats. To do so, the report uses two tasks that assess implicit bias to negative-valence faces, the first by eye-gaze and the second by measuring body-movement parameters. The report contrasts task performance in 51 treatment-seeking, medication-free pediatric patients with anxiety disorders and 36 healthy peers. Among these youth, 53 completed an eye-gaze task, 74 completed a body-movement task, and 40 completed both tasks. On the eye-gaze task, patients displayed longer gaze duration on negative relative to non-negative valence faces than healthy peers, F(1, 174) = 8.27, p = .005. In contrast, on the body-movement task, patients displayed a greater tendency to behaviorally avoid negative-valence faces than healthy peers, F(1, 72) = 4.68, p = .033. Finally, implicit bias measures on the two tasks were correlated, r(38) = .31, p = .049. In sum, we found an association between pediatric anxiety disorders and implicit threat bias on two tasks, one measuring eye-gaze and the other measuring whole-body movements. Converging evidence for implicit threat bias encourages future research using multiple tasks in anxiety.

Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA‐Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA‐Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA‐Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders., Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA‐Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA‐Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders.

To arrive at a coherent understanding of the relation between glucocorticoids and the human brain, we systematically reviewed the literature for studies examining the associations between endogenous or exogenous cortisol and human brain function. Higher levels of endogenous cortisol during psychological stress were related to increased activity in the middle temporal gyrus and perigenual anterior cingulate cortex (ACC), decreased activity in the ventromedial prefrontal cortex, and altered function (i.e., mixed findings, increased or decreased) in the amygdala, hippocampus and inferior frontal gyrus. Moreover, endogenous cortisol response to psychological stress was related to increased activity in the inferior temporal gyrus and altered function in the amygdala during emotional tasks that followed psychological stress. Exogenous cortisol administration was related to increased activity in the postcentral gyrus, superior frontal gyrus and ACC, and altered function in the amygdala and hippocampus during conditioning, emotional and reward-processing tasks after cortisol administration. These findings were in line with those from animal studies on amygdala activity during and after stress.

Excessive expression of threat-anticipatory defensive responses is central in anxiety. Animal research indicates that anticipatory responses are dynamically organized by threat imminence and rely on conserved circuitry. Insight from translational work on threat imminence could guide mechanistic research mapping abnormal function in this circuitry to aberrant defensive responses in anxiety. Here, we initiate such research.Fifty pediatric anxiety patients and healthy-comparisons (33 females) completed a threat-anticipation task whereby cues signaled delivery of highly-painful (threat) or non-painful (safety) heat. Temporal changes in skin-conductance indexed defensive responding as function of threat imminence. Resting-state functional connectivity data were used to identify intrinsic-function correlates of anticipatory response within a specific functional network derived from translational research.Results indicate that anxiety was associated with greater increase in anticipatory response as threats became more imminent. Magnitude of increase in threat-anticipatory responses corresponded to intrinsic connectivity within a cortical-subcortical circuit; importantly, more severe anxiety was associated with greater connectivity between ventromedial prefrontal cortex and hippocampus and basolateral amygdala, a circuit implicated in animal models of anxiety. These findings link basic-translational and clinical research, highlighting aberrant intrinsic function in conserved defensive circuitry as potential pathophysiological mechanism in anxiety.

Objectives: To describe the initial care practices for children with Pierre Robin sequence (PRS) and analyze the factors predicting the severity of the obstruction breathing disorders. Design: A retrospective single-center study of 150 children with PRS. Setting: Single tertiary care center, Regional Competence Center for the diagnosis and treatment of PRS. Patients: A total of 150 children with PRS consecutively followed between 1986 and 2017. Group 1 comprises children without specific respiratory management; group 2, children requiring prone positioning to alleviate their respiratory distress symptoms; and group 3, children requiring nasopharyngeal airway tube (NT) or nonconservative surgical treatment. Main outcome measures: Evolution and results of the initial treatment of PRS. Results: Forty-two percent (n = 63) were attributed to group 1, 39% (n = 50) to group 2, and 19% (n = 29) to group 3. Preterm birth, birth weight, or associated congenital malformations were not significantly different between the groups. However, the age of exclusive oral feeding was significantly different: 1 day (quartiles: 0-3) for group 1; 11 days (quartiles: 1-28) for group 2; 39 days (quartiles: 19-111) for group 3 ( P < .0001). Considering the NT, its use relieves the upper airway obstruction, assessed by a respiratory polygraphy, in 14 children. Conclusions: Nasopharyngeal airway tube has become our major first-line treatment, avoiding more complex procedures in most of the cases. The achievement of exclusive oral feeding seems to be a good predictor of the severity of respiratory symptoms in PRS.

Background Aberrations in both neural reward processing and stress reactivity are associated with increased risk for mental illness; yet, how these two factors relate to each other remains unclear. Several studies suggest that stress exposure impacts reward function, thus increasing risk for psychopathology. However, the alternative hypothesis, in which reward dysfunction impacts stress reactivity, has been rarely examined. The current study aimed to test both hypotheses using a longitudinal design. Methods Participants were 38 children (23 girls; 61%) from a prospective cohort study. A standard stress-exposure measure was collected at 7 years of age. Children performed a well-validated imaging reward paradigm at age 10, and a standardized acute psychological stress laboratory protocol was administered both at age 10 and at age 13. Structural equation modeling was used to examine bidirectional associations between stress and neural response to reward anticipation. Results Higher exposure to stressful life events at age 7 predicted lower neural response to reward anticipation in regions of the basal ganglia at age 10, which included ventral caudate, nucleus accumbens, putamen, and globus pallidus. Lower response to reward anticipation in medial prefrontal and anterior cingulate cortex predicted higher stress reactivity at age 13. Conclusions Our findings provide support for bidirectional associations between stress and reward processing, in that stress may impact reward anticipation, but also in that reduced reward anticipation may increase susceptibility to stress.

This study identified a shared pathophysiological mechanism of pediatric anxiety and irritability. Clinically, anxiety and irritability are common, co-occurring problems, both characterized by high-arousal negative affective states. Behaviorally, anxiety and irritability are associated with aberrant threat processing. To build on these findings, we examined eye-tracking measures of attention bias in relation to the unique and shared features of anxiety and irritability in a transdiagnostic sample of youth (n = 97, 58% female, Mage = 13.03, SDage = 2.82). We measured attention bias to negative versus non-negative emotional faces during a passive viewing task. We employed bifactor analysis to parse the unique and shared variance of anxiety and irritability symptoms from self- and parent-report questionnaires. Negative affectivity is the derived latent factor reflecting shared variance of anxiety and irritability. We found that higher negative affectivity was associated with looking longer at negative versus non-negative faces, reflecting a shared mechanism of anxiety and irritability. This finding suggests that modification of elevated attention to negative emotional faces may represent a common potential treatment target of anxiety and irritability.

Background: Threat anticipation engages neural circuitry that has evolved to promote defensive behaviours; perturbations in this circuitry could generate excessive threat-anticipation response, a key characteristic of pathological anxiety. Research into such mechanisms in youth faces ethical and practical limitations. Here, we use thermal stimulation to elicit pain-anticipatory psychophysiological response and map its correlates to brain structure among youth with anxiety and healthy youth. Methods: Youth with anxiety (n = 25) and healthy youth (n = 25) completed an instructed threat-anticipation task in which cues predicted nonpainful or painful thermal stimulation; we indexed psychophysiological response during the anticipation and experience of pain using skin conductance response. High-resolution brain-structure imaging data collected in another visit were available for 41 participants. Analyses tested whether the 2 groups differed in their psychophysiological cue-based pain-anticipatory and pain-experience responses. Analyses then mapped psychophysiological response magnitude to brain structure. Results: Youth with anxiety showed enhanced psychophysiological response specifically during anticipation of painful stimulation (b = 0.52, p = 0.003). Across the sample, the magnitude of psychophysiological anticipatory response correlated negatively with the thickness of the dorsolateral prefrontal cortex (pFWE < 0.05); psychophysiological response to the thermal stimulation correlated positively with the thickness of the posterior insula (pFWE < 0.05). Limitations: Limitations included the modest sample size and the cross-sectional design. Conclusion: These findings show that threat-anticipatory psychophysiological response differentiates youth with anxiety from healthy youth, and they link brain structure to psychophysiological response during pain anticipation and experience. A focus on threat anticipation in research on anxiety could delineate relevant neural circuitry.

Cognitive-behavioral therapy (CBT), a first-line treatment for pediatric anxiety disorders, is based on principles of threat learning and extinction. However, CBT does not work sufficiently for up to 40% of clinically anxious youth. The neural and behavioral correlates of conditioned inhibition might provide promising targets for attempts to improve CBT response. During conditioned inhibition, threat and safety cues appear together, forming a safety compound. Here, we test whether this safety compound elicits a reduced fear response compared to pairing the threat cue with a novel cue (novel compound). The current pilot study compares behavioral, physiological, and neural correlates of conditioned inhibition between children with (n = 17, Mage = 13.09, SDage = 3.05) and without (n = 18, Mage = 14.49, SDage = 2.38) anxiety disorders. Behavioral and physiological measures did not differ between children with and without anxiety disorders during fear acquisition. During testing, children with anxiety disorders showed overall higher skin conductance response and expected to hear the aversive sound following the novel compound more often than children without anxiety disorders. Children with anxiety disorders showed more activity in the right ventromedial prefrontal cortex (vmPFC) to the safety versus novel compound. Children without anxiety disorders showed the opposite pattern – more right vmPFC activity to the novel versus safety compound (F(1,31) = 5.40, p = 0.03). No group differences manifested within the amygdala, dorsal anterior cingulate cortex, or hippocampus. These pilot findings suggest a feasible approach for examining conditioned inhibition in pediatric anxiety disorders. If replicated in larger samples, findings may implicate perturbed conditioned inhibition in pediatric anxiety disorders and provide targets for CBT.

The current study examined neural and behavioral responses to social-evaluative feedback processing in social anxiety. Twenty-two non-socially and 17 socially anxious females (mean age = 19.57 years) participated in a Social Judgment Paradigm in which they received peer acceptance/rejection feedback that was either congruent or incongruent with their prior predictions. Results indicated that socially anxious participants believed they would receive less social acceptance feedback than non-socially anxious participants. EEG results demonstrated that unexpected social rejection feedback elicited a significant increase in theta (4-8 Hz) power relative to other feedback conditions. This theta response was only observed in non-socially anxious individuals. Together, results corroborate cognitive-behavioral studies demonstrating a negative expectancy bias in socially anxiety with respect to social evaluation. Furthermore, the present findings highlight a functional role for theta oscillatory dynamics in processing cues that convey social-evaluative threat, and this social threat-monitoring mechanism seems less sensitive in socially anxious females.

Previous studies have indicated that children who stutter show not only speech-related problems, but also wider difficulties in self-control. In this study we test the novel hypothesis that children who stutter may experience difficulties with inhibitory control over voluntary actions. We used functional MRI to compare brain activity between children who stutter and children who do not stutter in a task that captures key cognitive aspects of voluntary action control. Participants performed a rolling marble task, in which they were instructed to press a key to stop a rolling marble from crashing on some of the trials (instructed action condition). They were also asked to choose voluntarily whether to execute or inhibit this prepotent response in other trials (volition condition). Children who stutter reported less motor and cognitive impulsivity and had shorter stop-signal reaction times when controlled for IQ, consistent with greater inhibition, compared to children who do not stutter. At the neural level, children who stutter showed decreased activation in the rostral cingulate zone during voluntary action selection compared to children who do not stutter. This effect was more pronounced for children who were rated as showing more stuttered syllables in the stutter screening, and was furthermore correlated with stop-signal reaction times and impulsivity ratings. These findings suggest that stuttering in childhood could reflect wider difficulties in self-control, also in the non-verbal domain. Understanding these neural mechanisms could potentially lead to more focused treatments of stuttering.

Neuroimaging studies typically focus on either resting state or task-based fMRI data. Prior research has shown that similarity in functional connectivity between rest and cognitive tasks, interpreted as reconfiguration efficiency, is related to task performance and IQ. Here, we extend this approach from adults to children, and from cognitive tasks to a threat-based attention task. The goal of the current study was to examine whether similarity in functional connectivity during rest and an attention bias task relates to threat bias, IQ, anxiety symptoms, and social reticence. fMRI was measured during resting state and during the dot-probe task in 41 children (M = 13.44, SD = 0.70). Functional connectivity during rest and dot-probe was positively correlated, suggesting that functional hierarchies in the brain are stable. Similarity in functional connectivity between rest and the dot-probe task only related to threat bias (p(uncorr) < .03). This effect did not survive correction for multiple testing. Overall, children who allocate more attention towards threat also may possess greater reconfiguration efficiency in switching from intrinsic to threat-related attention states. Finally, functional connectivity correlated negatively across the two conditions of the dot-probe task. Opposing patterns of modulation of functional connectivity by threat-congruent and threat-incongruent trials may reflect task-specific network changes during two different attentional processes.

Social anxiety disorder is an invalidating psychiatric disorder characterized by extreme fear and avoidance of one or more social situations in which patients might experience scrutiny by others. The goal of this two-generation family study was to delineate behavioral and electrocortical endophenotypes of social anxiety disorder related to social evaluation. Nine families of patients with social anxiety disorder (their spouse and children, and siblings of these patients with spouse and children) performed a social judgment paradigm in which they believed to be evaluated by peers. For each peer, participants indicated their expectation about the evaluative outcome, after which they received social acceptance or rejection feedback. Task behavior, as well as the feedback-related EEG brain potentials (N1, FRN, P3) and theta power were tested as candidate endophenotypes based on two criteria: co-segregation with social anxiety disorder within families and heritability. Results indicated that reaction time for indicating acceptance-expectations might be a candidate behavioral endophenotype of social anxiety disorder, possibly reflecting increased uncertainty or self-focused attention and vigilance during the social judgment paradigm. N1 in response to expected rejection feedback and P3 in response to acceptance feedback might be candidate electrocortical endophenotypes of social anxiety disorder, although the heritability analyses did not remain significant after correcting for multiple tests. Increased N1 possibly reflects hypervigilance to socially threatening stimuli, and increased P3 might reflect that positive feedback is more important for, and/or less expected by, participants with social anxiety disorder. Finally, increased feedback-related negativity and theta power in response to unexpected rejection feedback compared to the other conditions co-segregated with social anxiety disorder, but these EEG measures were not heritable. The candidate endophenotypes might play a new and promising role in future research on genetic mechanisms, early detection and/or prevention of social anxiety disorder., Highlights • This two-generation family study examined candidate endophenotypes of social anxiety. • Reaction time for indicating acceptance-expectations might be an endophenotype. • Increased N1 after expected rejection might be an electrocortical endophenotype. • Increased P3 after acceptance feedback might be an endophenotype of SAD.

BACKGROUND: Clinical researchers face challenges when trying to quantify diverse processes engaged during social interactions. We report results from two studies, each demonstrating the potential utility of tools for examining processes engaged during social interactions. METHOD: In the first study, youth (n = 57) used a smartphone‐based tool to rate mood and responses to social events. A subset (n = 20) completed the second, functional magnetic resonance imaging study. This second study related anxiety to error‐evoked brain responses in two social conditions—while being observed and when alone. We also combined these tools to bridge clinical, social‐contextual, and neural levels of measurement. RESULTS: Results from the first study showed an association between negatively-perceived social experiences and a range of negative emotions. In the second study there was a positive correlation during error monitoring between social‐anxiety severity and context‐specific activation of the pregenual anterior cingulate cortex. Finally, during imaging, the perceived quality of peer interactions as assessed using the smartphone‐based tool, interacted with social context to predict levels of activation in the hippocampus and superior frontal gyrus. CONCLUSIONS: By improving measurement, enhanced tools may provide new means for studying relationships among anxiety, brain function, and social interactions.

International audience; Objective: To study recent epidemiologic trends of sudden unexpected death in infancy (SUDI) in Western Europe. Study design: Annual national statistics of death causes for 14 Western European countries from 2005 to 2015 were analyzed. SUDI cases were defined as infants younger than 1 year with the underlying cause of death classified as “sudden infant death syndrome,” “unknown/unattended/unspecified cause,” or “accidental threats to breathing.” Poisson regression models were used to study temporal trends of SUDI rates and source of variation. Results: From 2005 to 2015, SUDI accounted for 15 617 deaths, for an SUDI rate of 34.9 per 100 000 live births. SUDI was the second most common cause of death after the neonatal period (22.2%) except in Belgium, Finland, France, and the UK, where it ranked first. The overall SUDI rate significantly decreased from 40.2 to 29.9 per 100 000, with a significant rate reduction experienced for 6 countries, no significant evolution for 7 countries, and a significant increase for Denmark. The sudden infant death syndrome/SUDI ratio was 56.7%, with a significant decrease from 64.9% to 49.7% during the study period, and ranged from 6.1% in Portugal to 97.8% in Ireland. We observed between-country variations in SUDI and sudden infant death syndrome sex ratios. Conclusions: In studied countries, SUDI decreased during the study period but remained a major cause of infant deaths, with marked between-country variations in rates, trends, and components. Standardization is needed to allow for comparing data to improve the implementation of risk-reduction strategies.

Cross-frequency coupling (CFC) between frontal delta (1–4 Hz) and beta (14–30 Hz) oscillations has been suggested as a candidate neural correlate of social anxiety disorder, a disorder characterized by fear and avoidance of social and performance situations. Prior studies have used amplitude-amplitude correlation (AAC) as a CFC measure and hypothesized it as a candidate neural mechanism of affective control. However, using this metric has yielded inconsistent results regarding the direction of CFC, and the functional significance of coupling strength is uncertain. To offer a better understanding of CFC in social anxiety, we compared frontal delta-beta AAC with phase-amplitude coupling (PAC) – a mechanism for information transfer through neural circuits. Twenty high socially anxious (HSA) and 32 low socially anxious (LSA) female undergraduates participated in a social performance task (SPT). Delta-beta PAC and AAC were estimated during the resting state, as well as the anticipation and recovery conditions. Results showed significantly more AAC in LSA than HSA participants during early anticipation, as well as significant values during all conditions in LSA participants only. PAC did not distinguish between LSA and HSA participants, and instead was found to correlate with state nervousness during early anticipation, but in LSA participants only. Together, these findings are interpreted to suggest that delta-beta AAC is a plausible neurobiological index of adaptive stress regulation and can distinguish between trait high and low social anxiety during stress, while delta-beta PAC might be sensitive enough to reflect mild state anxiety in LSA participants. Electronic supplementary material The online version of this article (10.3758/s13415-018-0603-7) contains supplementary material, which is available to authorized users.

Behavioral inhibition (BI) is an early temperamental precursor of anxiety disorders, characterized by withdrawal from novel situations. Some but not all young children with BI go on to display anxiety disorders. Neural correlates, such as frontal alpha asymmetry or event-related negativity (ERN), could moderate the relations between early BI and later anxiety. The goal of this longitudinal study was to test frontal alpha asymmetry as a potential moderator of the relation between BI and later anxiety, and of the relation between BI and the social-effect ERN. 100 children were assessed for BI at ages 2 and 3, and we collected EEG during resting state and the social Flanker task at age 12. Frontal alpha asymmetry did not correlate with BI or anxiety, nor did it moderate the relation between early BI and later anxiety. However, frontal alpha asymmetry did moderate the relation between BI and the social-effect ERN. This suggests that, in adolescents who previously manifested BI, a pattern of resting EEG associated with avoidance predicts hypersensitivity to errors in a social context.

Introduction Even after ‘back-to-sleep’ campaigns, sudden unexpected infant death (SUID) continues to be the leading cause of death for infants 1 month to 1 year old in developed countries, with devastating social, psychological and legal implications for families. To sustainably tackle this problem and decrease the number of SUIDs, a French SUID registry was initiated in 2015 to (1) inform prevention with standardised data, (2) understand the mechanisms leading to SUID and the contribution of the already known or newly suggested risk factors and (3) gather a multidisciplinary group of experts to coordinate and develop innovative and urgent research in the SUID area. Methods and analysis This observational multisite prospective observatory includes all cases of sudden unexpected deaths in children younger than 2 years occurring in the French territory covered by the 35 participating French referral centres. From these cases, various data concerning sociodemographic conditions, death scene, personal and family medical history, parental behaviours, sleep environment, clinical examinations, biological and imagery investigations and autopsy are systematically collected. These data will be complemented as of 2018 with a biobank of diverse biological samples (blood, hair, urine, faeces and cerebrospinal fluid), with other administrative health-related data (health claim reimbursements and hospital admissions) and socioenvironmental data. Insights from exploratory descriptive statistics and thematic analysis will be combined for the design of targeted strategies to effectively reduce preventable infant deaths. Ethics and dissemination The French sudden unexpected infant death registry (Observatoire National des Morts Inattendues du Nourrisson registry;OMIN) was approved in 2015 by the French Data Protection Authority in clinical research (Commission Nationale de l’Informatique et des Libertes: number 915273) and by an independent ethics committee (Groupe Nantais d’Ethique dans le Domaine de la Sante: number 2015-01-27). Results will be discussed with associations of families affected by SUID, caregivers, funders of the registry, medical societies and researchers and will be submitted to international peer-reviewed journals and presented at international conferences.

In France, nearly 500 infants still die unexpectedly every year. In 2009, the French Institute for Public Health Surveillance published a survey showing great heterogeneity in the management of sudden unexpected infant death (SUID) cases. The aim of this study was to evaluate the actual diagnostic approach to SUID in the different reference centers in France and to determine the degree to which the 2007 recommendations of the French National Authority for Health (Haute Autorite de sante [HAS]) are applied. We conducted a multicenter cross-sectional epidemiological study by email sent to the 36 SIDS reference centers with questions on examinations usually performed in SIDS cases. We also submitted six SUID test cases for death classification to the different reference physicians. Twenty-nine of 36 centers (80.5%) responded. Among the recommended tests, only blood cultures, analysis of cerebrospinal fluid, and a proposal to autopsy are done in 100% of the centers. Other investigations are not carried out systematically: skeleton radiography (65.5%), cranial CT scan (58%), eye fundus (20.7%), metabolic analysis (65.5%), and blood toxicology (62%). The main reasons for non-completion of these tests were hospital practices, lack of resources, technical difficulties, cost of tests, and difficulty in interpreting results (50% reported not knowing the postmortem biological standards). None of the institutions apply the HAS recommendations entirely. The classification of causes-of-death test cases also varied between the centers, with a maximum of 62% concordance in their responses. In 2013, in France, there is still substantial heterogeneity in the diagnostic set-up of SUIDS, a non-exhaustive implementation of the recommendations of the French National Authority for Health, and an unsatisfactory SUIDS classification tool because of considerable discordance between physicians. These results explain the current difficulties in obtaining reliable epidemiological data, because many teams do not use all the investigations recommended to find the cause of death. Therefore, the establishment of a national registry would provide accurate and up-to-date epidemiological, environmental, medical, and biological data to identify the events causing death and propose appropriate means of prevention.

Social anxiety disorder (SAD) is characterized by information processing biases, however, their underlying neural mechanisms remain poorly understood. The goal of this review was to give a comprehensive overview of the most frequently studied EEG spectral and event-related potential (ERP) measures in social anxiety during rest, anticipation, stimulus processing, and recovery. A Web of Science search yielded 35 studies reporting on electrocortical measures in individuals with social anxiety or related constructs. Social anxiety was related to increased delta-beta cross-frequency correlation during anticipation and recovery, and information processing biases during early processing of faces (P1) and errors (error-related negativity). These electrocortical measures are discussed in relation to the persistent cycle of information processing biases maintaining SAD. Future research should further investigate the mechanisms of this persistent cycle and study the utility of electrocortical measures in early detection, prevention, treatment and endophenotype research.

The goal of the present study was to examine whether frontal alpha asymmetry and delta–beta cross-frequency correlation during resting state, anticipation, and recovery are electroencephalographic (EEG) measures of social anxiety. For the first time, we jointly examined frontal alpha asymmetry and delta–beta correlation during resting state and during a social performance task in high (HSA) versus low (LSA) socially anxious females. Participants performed a social performance task in which they first watched and evaluated a video of a peer, and then prepared their own speech. They believed that their speech would be videotaped and evaluated by a peer. We found that HSA participants showed significant negative delta–beta correlation as compared to LSA participants during both anticipation of and recovery from the stressful social situation. This negative delta–beta correlation might reflect increased activity in subcortical brain regions and decreased activity in cortical brain regions. As we hypothesized, no group differences in delta–beta correlation were found during the resting state. This could indicate that a certain level of stress is needed to find EEG measures of social anxiety. As for frontal alpha asymmetry, we did not find any group differences. The present frontal alpha asymmetry results are discussed in relation to the evident inconsistencies in the frontal alpha asymmetry literature. Together, our results suggest that delta–beta correlation is a putative EEG measure of social anxiety. Electronic supplementary material The online version of this article (doi:10.3758/s13415-016-0455-y) contains supplementary material, which is available to authorized users.

We report on a male newborn with a rarely described congenital limb deficiency syndrome consisting of shortening and anterior bowing of the right lower limb at the distal third of the tibia with associated overlying soft tissue dimpling, oligodactyly of the right foot, and a left-sided oligosyndactyly of the hand. The right hand and left lower limb were clinically normal. Radiographic examination revealed complete absence of the right fibula, absence of the right-sided Vth ray, and anterior bowing and shortening of the right-sided tibia. Femora, humeri, ulnae, and radii were normal. The infant had neither facial dysmorphia nor other associated anomalies. A limb deficiency syndrome comparable to this case has been reported in a female by Hecht and Scott, the only report classified under OMIM 246570 so far. We found two other reports describing three cases comparable to our case and the female reported by Hecht and Scott, and reviewed these cases. The major common findings in all the five cases consist of fibular aplasia, tibial campomelia, and oligosyndactyly. Therefore, we propose to name it fibular aplasia-tibial campomelia-oligosyndactyly (FATCO) syndrome. Additional case reports are needed for further delineation of this rare limb deficiency syndrome.

Within the framework of the broader ethical discussion on end-of-life decision making in neonatology and the need to obtain more quantifiable data, we performed a multicenter study in four Dutch neonatal intensive care units. All infants who died in these units in 1993 were included in the study. Aside from cases in which foregoing treatment was not under discussion, cases in which death appeared inevitable (A cases) and cases in which foregoing treatment because of extremely poor prognosis was the decisive factor (B cases) were distinguished. A total of 181 neonatal deaths occurred. Thirty-five infants died even after full continuation of treatment. In 98 A cases and 48 B cases, which together represented 81% of all deaths, treatment was foregone either because the infants had no chance to survive or because of extremely poor prognoses. In these cases, the medical team ultimately achieved consensus of opinion, although in some instances several sessions were required. In three cases, the parents did not agree with the team advice. In one A case death appeared inevitable. In two B cases, the parents' wish to continue treatment was followed. In a large majority of B cases, the decisions to forego treatment were based on the presence of severe cerebral damage. In A cases there was no real choice because death appeared inevitable. However, in B cases neonatologists were obliged to determine whether continuation of treatment was justifiable or if withdrawal of treatment in view of extremely poor prognoses was preferred.

Pymetrozine inhibits feeding in aphids immediately after application without producing visible neurotoxic effects, as previously reported. In the present work, Locusta migratoria, though not a plant-sucking insect, was found to respond to pymetrozine by displaying unique symptoms, which were lifting and stretching of the hindlegs, in addition to inhibition of feeding. In locust, pymetrozine enhanced spontaneous spike discharge of the metathoracic and suboesophageal ganglia in situ at nanomolar concentrations. Similarly, pymetrozine increased the spontaneous rhythmic contractions of the isolated foregut with maximal effects also in the nanomolar range. The actions of pymetrozine were counteracted by biogenic amine receptor antagonists and mimicked by serotonin, not by dopamine and octopamine. Moreover, pymetrozine and serotonin strongly potentiated the effects of each other. Pymetrozine was inactive at all neurotransmitter receptors present on isolated locust neuronal somata, and at all other examined neuronal sites. In Myzus persicae, electrical penetration graph experiments revealed that serotonin, like pymetrozine, inhibited stylet penetration, and strongly enhanced the action of pymetrozine, comparable to the locust. Amine receptor antagonists were not specifically active in the aphid. We conclude from the present results that pymetrozine acts via a novel mechanism that is linked to the signalling pathway of serotonin.

Background Ibuprofen is used for treatment and prevention of patent ductus arteriosus in low-birthweight infants. Its effects on regional circulations differ from those of indometacin. Because prophylactic indometacin reduces the frequency of severe intraventricular haemorrhage and patent ductus arteriosus, we aimed to study the efficacy of early ibuprofen in reducing these outcomes in a double-blind, multicentre trial. Methods Within 6 h after birth, 415 low-birthweight infants (gestational age

Within organisms, terpenoids are known for their physiological activities on cell level. They can influence cell stage and mitosis, resulting in changes in morphology and differentiation. Terpenoid endproducts and certain precursors of the mevalonate metabolism and other exogenous terpenoids can affect the synthesis of endproducts and intermediates of other branches or interfere with gene expression, or more directly, act as enzyme or key enzyme regulators. The preciseness with which the enzymes of the various steps of the biosynthesis of terpenoid endproducts operate and the effective feedback systems acting on enzymes and key enzymes are the result of a long evolutionary process. Between organisms, functions of specific terpenoids as messengers are likewise the outcome of a long process of selection of adequate production and reception. This chapter covers the basic regulatory processes involved in the biosynthesis of isoprene units in plants, insects and vertebrates. As in many biochemical processes, overproduction of endproducts is in some way prevented. Once produced in an efficient way, the same terpenoid can acquire a number of messenger functions in completely different organisms. Chapter 3 will discuss the development of regulatory mechanisms during evolution, whereas chapter 4 focusses on the relationship between chemical and physical characteristics of terpenoids and their effects on the receptor sites.

Feeding behavior and scar production of male and female F. occidentalis (Pergande) (Thysanoptera: Thripidae) were studied in relation to transmission of tomato spotted wilt tospovirus (TSWV). Electrical penetration graph (EPG) analysis showed that females feed more frequently and intensively than males. The feeding intensity, reflected by silvery scar production and studied by an image analysis system, demonstrated that females induced more numerous scars than males. At the same time, males transmitted TSWV with a higher efficiency than females, indicating that TSWV transmission and scar production are not positively correlated. Furthermore, males produced significantly more local lesions of TSWV than females. These quantitative differences in scar production and transmission of TSWV can be explained by the lower mobility and higher consumption rate of females. The influence of the sex-ratio on crop damage and virus transmission, and thus to the spread of TSWV, is emphasized.