Of Scaredy Cats and Cold Fish: The autonomic nervous system and behaviour in young children

__Abstract__ The autonomic nervous system regulates the body’s internal functions. The goal of this regulation is to maintain bodily homeostasis in a changing external environment. The autonomic nervous system acts largely independent of volition and controls heart rate, respiratory rate, digestion, and perspiration. It is divided into two partially antagonistic systems: the sympathetic nervous system and the parasympathetic or vagal nervous system. In general, the vagal system primarily regulates “rest and digest” functions. In contrast, the sympathetic nervous system can elicit the “fi ght or fl ight” response with increased arousal and energy generation in response to stress or threat. Together with the hypothalamic-pituitary adrenal (HPA) axis, the autonomic nervous system mediates the body’s response to stress. Because of this central role in stress response and the close relation of stress with the onset and recurrence of psychiatric disorders, both systems are potential biomarkers for psychiatric disorders. The current thesis investigates possible determinants of stress regulation, as well as the associations of stress regulation with emotional and behavioural symptoms very young age. The majority of the studies in this thesis were performed within the Generation R study. The Generation R Study is a large population-based prospective cohort study from fetal life onwards. It was designed to identify early environmental as well as genetic causes of abnormal growth, development and health from fetal life onwards. In total, 9,778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. The studies presented here concern children who participated in the Focus Cohort. The Focus Cohort consists of a randomly selected subgroup of Dutch children of Caucasian origin and their parents. Studies conducted in the Focus Cohort were able to utilise more in-depth assessments. The research discussed in chapter 6 was performed within the “Beren van de Weg” study. This is a clinical, outpatient study, conducted by the departments of Child and Adolescent Psychiatry of either the Erasmus Medical Center in Rotterdam and Leiden University Medical Center— Curium. All consecutive referrals with a primary diagnosis of Generalized Anxiety Disorder, Separation Anxiety Disorder, Social Phobia or Specifi c Phobia were eligible for inclusion . In chapter 2 we examined the potential impact of maternal psychopathology on infant heart rate and heart rate variability. We showed that a maternal history of psychopathology before childbirth was associated with increased heart rate and lower vagal modulation in the infant. Similarly, postnatal maternal symptoms, especially anxiety and depression symptoms, were related to increased heart rate in the infant. Both genetic and environmental mechanisms, which are certainly not mutually exclusive, could underlie the association between maternal psychopathology and infant heart rate. In chapter 3 we assessed the putative benefi cial effect of breastfeeding on child autonomic functioning. To address the issue of residual confounding, we compared the effect of breastfeeding with that of a contrasting variable, infant fruitpurée consumption. It is related to similar environmental epiphenomena as breastfeeding. We found that infants, who were exclusively breastfed at two months of age, had lower sympathetic modulation than infants not breastfed. However, our data showed that, similar to breastfeeding, infants who ate more fruitpurée had lower sympathetic modulation as well. Association does not imply causation. In fact, in both instances the causal pathways linking the risk factors to autonomic functioning remain unclear. Moreover, in the case of breast feeding, a limited effect size with a similar order of magnitude as the effect of another, seemingly trivial dietary component, calls into question the clinical relevance of the association, 8 105 even if it contains a causal component. In chapter 4 we addressed the relation between infant autonomic functioning at 14 months and behaviour at age 18 months. We found that the association between autonomic functioning and infant externalising behaviour, was moderated by maternal psychiatric symptoms. We observed that low heart rate was associated with aggressive behaviour, only in a subgroup of children whose mothers had high psychiatric symptoms. This suggests that in the presence of maternal risk factors, low autonomic arousal renders children particularly susceptible to externalising behaviour. This lends support to the fearlessness theory, which posits that low autonomic arousal in children is an indicator of fearlessness. We hypothesize that in the presence of maternal psychopathology, with less adequate parenting and maternal guidance in coping with fearless behaviour, these children actually develop aggressive behaviour. In chapter 5 we examined the association between a child’s heart rate at 14 months and behavior at 3 years. Low heart rate was specifi cally and strongly associated with the odds of the child lying during the gift delay task as well as with low levels of anxiety. We suggest that low anxiety and a tendency to lie are indicative of low levels of emotional reactivity. Low heart rate may thus delineate a small group of children that are composed and calculating, rather than overly emotionally reactive and overtly aggressive. However, we could not demonstrate an association between heart rate and parent rated aggressive behaviour. This could be because the children in our study were considerably younger than those in earlier studies. In young children aggressive behaviour is common, but usually time limited. Proactive, planned aggression, which is commonly accompanied by low levels of emotional reactivity, develops later in life than reactive aggression. Chapter 6 details the course of an anxiety disorder during treatment and the concomitant changes in cortisol levels in a clinical sample of 116 children and adolescents. When we compared cortisol levels at baseline and one-year follow-up, persistence of the anxiety disorder was associated with both increased daytime cortisol production and a trend towards a decreased cortisol morning rise. Persistence of an anxiety disorder may change HPA-axis functioning, underscoring the importance adequate treatment of anxiety disorders. Chapter 7 highlights the main results of the previous chapters and places them in a broader context. The main body of the chapter details the different methodological issues encountered during this research. Clinicial implications and recommendations for future research are discussed as well

Fermionic Quasi-free States and Maps in Information Theory

This paper and the results therein are geared towards building a basic toolbox for calculations in quantum information theory of quasi-free fermionic systems. Various entropy and relative entropy measures are discussed and the calculation of these reduced to evaluating functions on the one-particle component of quasi-free states. The set of quasi-free affine maps on the state space is determined and fully characterized in terms of operations on one-particle subspaces. For a subclass of trace preserving completely positive maps and for their duals, Choi matrices and Jamiolkowski states are discussed.Comment: 19 page

Additivity of the Renyi entropy of order 2 for positive-partial-transpose-inducing channels

We prove that the minimal Renyi entropy of order 2 (RE2) output of a positive-partial-transpose(PPT)-inducing channel joint to an arbitrary other channel is equal to the sum of the minimal RE2 output of the individual channels. PPT-inducing channels are channels with a Choi matrix which is bound entangled or separable. The techniques used can be easily recycled to prove additivity for some non-PPT-inducing channels such as the depolarizing and transpose depolarizing channels, though not all known additive channels. We explicitly make the calculations for generalized Werner-Holevo channels as an example of both the scope and limitations of our techniques.Comment: 4 page

Pétrographie characterization of rocks from the Mirabello bay region, Crete, and its application to Minoan archaeology: the provenance of stone implements from Minoan sites

Οι άνθρωποι της Μινωικής Εποχής, στην Ανατολική Κρήτη, χρησιμοποιούσαν μαγματικά και μεταμορφωμένα πετρώματα για την κατασκευή διαφόρων λίθινων σκευών. Αυτά τα συνέλλεγαν από τις κοίτες των ποταμών και την ακτή στην περιοχή κατά μήκος του κόλπου του Μιραμπέλλο ή από ένα κροκαλοπαγές επίκλυσης, το οποίο κυριαρχεί γεωλογικά στην περιοχή αυτή και περιέχει κροκάλες από μαγματικά, μεταμορφωμένα και ιζηματογενή πετρώματα. Η λεπτομερής πετρογραφική περιγραφή φυσικών δειγμάτων, που συλλέχθηκαν από αυτούς τους σχηματισμούς και η σύγκριση τους με λίθινα σκεύη από ανασκαφές, αφενός καθιστά γνωστούς τους λιθολογικούς τύπους που χρησιμοποιήθηκαν και αφετέρου επιβεβαιώνει την πηγή προέ?χυσής τους. Με τη έρευνα αυτή καθίσταται προφανές ότι οι άνθρωποι της Μινωικής Εποχής μπορούσαν μα εκτιμήσουν τη σκληρότητα των λίθων που συνέλλεγαν, σύμφωνα με την επιθυμητή χρήση, καθώς και την αναμενόμενη κόπωση των υλικών, ανάλογα με τη χρήση για την οποία τα προόριζαν, αποφεύγοντας παράλληλα την ανεπιθύμητα χρονοβόρα κατεργασία τους. Με την επιβεβαίωση της λιθολογίας και της πηγής προέλευσης των λίθινων πρώτων υλών γίνεται επίσης αντιληπτό το γεγονός ότι οι άνθρωποι της Μινωικής Εποχής ήταν γνώστες του φυσικού περιβάλλοντος, στον ευρύτερο χώρο των οικισμών τους. Επίσης, μπορεί να εκτιμηθεί και ο χρόνος τον οποίο διέθεταν προκειμένου να βρουν και να συλλέξουν την πρώτη ύλη αλλά και να αξιολογηθεί ο χρόνος κατεργασίας των υλικών, προκειμένου να διαμορφωθούν σε κατάλληλα σκεύη, ανάλογα με τη σκληρότητα τους.The Minoans of East Crete used a variety of igneous and metamorphic rocks as stone implements. These were probably procured in dry riverbeds and beaches located in a region along the Bay of Mirabello or from an onlap conglomerate, which geologically dominates that region and contains rock types of igneous, metamorphic and sedimentary origin. Several rock samples were collected for pétrographie investigation to examine and confirm the source for the igneous rocks. Detailed pétrographie description of natural samples provides the identification of the rocks employed by Minoans and confirms the source of their origin. Apparently the Minoans were able to evaluate the hardness of the stones procured according to the desirable usage and their expected fatigue, thus avoiding unnecessary timeconsuming treatment. The identification of the variable lithotypes used for these implements and the verification of their source regions reveal the time it took to procure the raw materials as well as the time period during which the rocks were employed

One pot ‘click’ reactions: tandem enantioselective biocatalytic epoxide ring opening and [3+2] azide alkyne cycloaddition

Halohydrin dehalogenase (HheC) can perform enantioselective azidolysis of aromatic epoxides to 1,2-azido alcohols which are subsequently ligated to alkynes producing chiral hydroxy triazoles in a one-pot procedure with excellent enantiomeric excess.

November 12, 1976

The Breeze is the student newspaper of James Madison University in Harrisonburg, Virginia

Validation of the AUDIT and AUDIT-C for hazardous drinking in community-dwelling older adults

Background: One of the best-known tools in screening for hazardous drinking is the Alcohol Use Disorders Identification Test (AUDIT) and its abbreviated form, the AUDIT-C. The aim of the present study is to determine the cut-offs of both instruments in identifying hazardous drinking in older adults. Method: A sample of 1577 older adults completed a questionnaire regarding alcohol behavior. Hazardous drinking was defined as drinking >10 units/week. Receiver operating characteristics (ROC) curves of AUDIT and AUDIT-C were calculated and cut-off scores were derived. Results: Respectively 27.3% and 12.3% of older men and women drank >10 units/week. For the AUDIT the best trade-off between sensitivity and specificity was using a cut-off of ≥5 for men and ≥4 for women, which yielded in men sensitivity and specificity values respectively of 80.7% and 81.3% and in women 100% and 71.7%, respectively. We found the AUDIT-C to perform well with an optimal cut-off of ≥5 for men and ≥4 for women, which generated in men sensitivity and specificity values respectively of 76.5% and 85.3% and in women 100% and 74.1%, respectively. Conclusion: The AUDIT-C is accurate and sufficient in screening for hazardous drinking in community-dwelling older adults if the cut-offs are tailored by gender

Liver fibrosis staging by deep learning:a visual-based explanation of diagnostic decisions of the model

OBJECTIVES: Deep learning has been proven to be able to stage liver fibrosis based on contrast-enhanced CT images. However, until now, the algorithm is used as a black box and lacks transparency. This study aimed to provide a visual-based explanation of the diagnostic decisions made by deep learning. METHODS: The liver fibrosis staging network (LFS network) was developed at contrast-enhanced CT images in the portal venous phase in 252 patients with histologically proven liver fibrosis stage. To give a visual explanation of the diagnostic decisions made by the LFS network, Gradient-weighted Class Activation Mapping (Grad-cam) was used to produce location maps indicating where the LFS network focuses on when predicting liver fibrosis stage. RESULTS: The LFS network had areas under the receiver operating characteristic curve of 0.92, 0.89, and 0.88 for staging significant fibrosis (F2-F4), advanced fibrosis (F3-F4), and cirrhosis (F4), respectively, on the test set. The location maps indicated that the LFS network had more focus on the liver surface in patients without liver fibrosis (F0), while it focused more on the parenchyma of the liver and spleen in case of cirrhosis (F4). CONCLUSIONS: Deep learning methods are able to exploit CT-based information from the liver surface, liver parenchyma, and extrahepatic information to predict liver fibrosis stage. Therefore, we suggest using the entire upper abdomen on CT images when developing deep learning-based liver fibrosis staging algorithms. KEY POINTS: • Deep learning algorithms can stage liver fibrosis using contrast-enhanced CT images, but the algorithm is still used as a black box and lacks transparency. • Location maps produced by Gradient-weighted Class Activation Mapping can indicate the focus of the liver fibrosis staging network. • Deep learning methods use CT-based information from the liver surface, liver parenchyma, and extrahepatic information to predict liver fibrosis stage

Shopping centre siting and modal choice in Belgium: a destination based analysis

Although modal split is only one of the elements considered in decision-making on new shopping malls, it remarkably often arises in arguments of both proponents and opponents. Today, this is also the case in the debate on the planned development of three major shopping malls in Belgium. Inspired by such debates, the present study focuses on the impact of the location of shopping centres on the travel mode choice of the customers. Our hypothesis is that destination-based variables such as embeddedness in the urban fabric, accessibility and mall size influence the travel mode choice of the visitors. Based on modal split data and location characteristics of seventeen existing shopping centres in Belgium, we develop a model for a more sustainable siting policy. The results show a major influence of the location of the shopping centre in relation to the urban form, and of the size of the mall. Shopping centres that are part of a dense urban fabric, measured through population density, are less car dependent. Smaller sites will attract more cyclists and pedestrians. Interestingly, our results deviate significantly from the figures that have been put forward in public debates on the shopping mall issue in Belgium