Optimal control approach to gradient-index design for beam reshaping.

We address the problem of reshaping light in the Schrödinger optics regime from the perspective of the optimal control theory. In technological applications, Schrödinger optics is often used to model a slowly varying amplitude of a para-axially propagating electric field where the square of the waveguide's index of refraction is treated as the potential. The objective of the optimal control problem is to find the controlling potential which, together with the constraining Schrödinger dynamics, optimally reshapes the intensity distribution of Schrödinger eigenfunctions from one end of the waveguide to the other. This work considers reshaping problems found in work by Kunkel and Leger, and addresses computational needs by adopting tools from the quantum control literature. The success of the optimal control approach is demonstrated numerically.

Reduction-based strategy for optimal control of Bose-Einstein condensates.

Applications of Bose-Einstein condensates (BEC) often require that the condensate be prepared in a specific complex state. Optimal control is a reliable framework to prepare such a state while avoiding undesirable excitations, and, when applied to the time-dependent Gross-Pitaevskii equation (GPE) model of BEC in multiple space dimensions, results in a large computational problem. We propose a control method based on first reducing the problem, using a Galerkin expansion, from a partial differential equation to a low-dimensional Hamiltonian ordinary differential equation system. We then apply a two-stage hybrid control strategy. At the first stage, we approximate the control using a second Galerkin-like method known as the chopped random basis to derive a finite-dimensional nonlinear programing problem, which we solve with a differential evolution algorithm. This search method then yields a candidate local minimum which we further refine using a variant of gradient descent. This hybrid strategy allows us to greatly reduce excitations both in the reduced model and the full GPE system.

Importance of neuroanatomical data from domestic animals to the development and testing of the KNDy hypothesis for GnRH pulse generation.

Work during the last decade has led to a novel hypothesis for a question that is half a century old: how is the secretory activity of GnRH neurons synchronized to produce episodic GnRH secretion. This hypothesis posits that a group of neurons in the arcuate nucleus (ARC) that contain kisspeptin, neurokinin B (NKB), and dynorphin (known as KNDy neurons) fire simultaneously to drive each GnRH pulse. Kisspeptin is proposed to be the output signal to GnRH neurons with NKB and dynorphin acting within the KNDy network to initiate and terminate each pulse, respectively. This review will focus on the importance of neuroanatomical studies in general and, more specifically, on the work of Dr Marcel Amstalden during his postdoctoral fellowship with the authors, to the development and testing of this hypothesis. Critical studies in sheep that laid the foundation for much of the KNDy hypothesis included the report that a group of neurons in the ARC contain both NKB and dynorphin and appear to form an interconnected network capable of firing synchronously, and Marcel's observations that the NKB receptor is found in most KNDy neurons, but not in any GnRH neurons. Moreover, reports that almost all dynorphin-NKB neurons and kisspeptin neurons in the ARC contained steroid receptors led directly to their common identification as "KNDy" neurons. Subsequent anatomical work demonstrating that KNDy neurons project to GnRH somas and terminals, and that kisspeptin receptors are found in GnRH, but not KNDy neurons, provided important tests of this hypothesis. Recent work has explored the time course of dynorphin release onto KNDy neurons and has begun to apply new approaches to the issue, such as RNAscope in situ hybridization and the use of whole tissue optical clearing with light-sheet microscopy. Together with other approaches, these anatomical techniques will allow continued exploration of the functions of the KNDy population and the possible role of other ARC neurons in generation of GnRH pulses.

An architectural understanding of natural sway frequencies in trees.

The relationship between form and function in trees is the subject of a longstanding debate in forest ecology and provides the basis for theories concerning forest ecosystem structure and metabolism. Trees interact with the wind in a dynamic manner and exhibit natural sway frequencies and damping processes that are important in understanding wind damage. Tree-wind dynamics are related to tree architecture, but this relationship is not well understood. We present a comprehensive view of natural sway frequencies in trees by compiling a dataset of field measurement spanning conifers and broadleaves, tropical and temperate forests. The field data show that a cantilever beam approximation adequately predicts the fundamental frequency of conifers, but not that of broadleaf trees. We also use structurally detailed tree dynamics simulations to test fundamental assumptions underpinning models of natural frequencies in trees. We model the dynamic properties of greater than 1000 trees using a finite-element approach based on accurate three-dimensional model trees derived from terrestrial laser scanning data. We show that (1) residual variation, the variation not explained by the cantilever beam approximation, in fundamental frequencies of broadleaf trees is driven by their architecture; (2) slender trees behave like a simple pendulum, with a single natural frequency dominating their motion, which makes them vulnerable to wind damage and (3) the presence of leaves decreases both the fundamental frequency and the damping ratio. These findings demonstrate the value of new three-dimensional measurements for understanding wind impacts on trees and suggest new directions for improving our understanding of tree dynamics from conifer plantations to natural forests.

The relationship between exclusion from school and mental health: a secondary analysis of the British Child and Adolescent Mental Health Surveys 2004 and 2007.

BACKGROUND: Children with poor mental health often struggle at school. The relationship between childhood psychiatric disorder and exclusion from school has not been frequently studied, but both are associated with poor adult outcomes. We undertook a secondary analysis of the British Child and Adolescent Mental Health Surveys from 2004 and its follow-up in 2007 to explore the relationship between exclusion from school and psychopathology. We predicted poorer mental health among those excluded. METHOD: Psychopathology was measured using the Strengths and Difficulties Questionnaire, while psychiatric disorder was assessed using the Development and Well-Being Assessment and applying Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM IV) criteria. Exclusion from school and socio-demographic characteristics were reported by parents. Multi-variable regression models were used to examine the impact of individual factors on exclusion from school or psychological distress. RESULTS: Exclusion from school was commoner among boys, secondary school pupils and those living in socio-economically deprived circumstances. Poor general health and learning disability among children and poor parental mental health were also associated with exclusion. There were consistently high levels of psychological distress among those who had experienced exclusion at baseline and follow-up. CONCLUSIONS: We detected a bi-directional association between psychological distress and exclusion. Efforts to identify and support children who struggle with school may therefore prevent both future exclusion and future psychiatric disorder.

Kisspeptin, gonadotrophin-releasing hormone and oestrogen receptor α colocalise with neuronal nitric oxide synthase neurones in prepubertal female sheep.

Puberty is a process that integrates multiple inputs ultimately resulting in an increase in gonadotrophin-releasing hormone (GnRH) secretion. Although kisspeptin neurones play an integral role in GnRH secretion and puberty onset, other systems are also likely important. One potential component is nitric oxide (NO), a gaseous neurotransmitter synthesised by nitric oxide synthase (NOS). The present study aimed to neuroanatomically characterise neuronal NOS (nNOS) in prepubertal female sheep and determine whether oestradiol exerts effects on this system. Luteinising hormone secretion was reduced by oestradiol treatment in prepubertal ovariectomised ewes. Neurones immunoreactive for nNOS were identified in several areas, with the greatest number present in the ventrolateral portion of the ventromedial hypothalamus, followed by the ventromedial hypothalamus, preoptic area (POA) and arcuate nucleus (ARC). Next, we determined whether nNOS neurones contained oestrogen receptor (ER)α and could potentially communicate oestradiol (E2 ) feedback to GnRH neurones. Neuronal NOS neurones contained ERα with the percentage of coexpression (12%-40%) depending upon the area analysed. We next investigated whether a neuroanatomical relationship existed between nNOS and kisspeptin or nNOS and GnRH neurones. A high percentage of kisspeptin neurones in the POA (79%) and ARC (98%) colocalised with nNOS. Kisspeptin close contacts were also associated with nNOS neurones. A greater number of close contacts were observed in the ARC than the POA. A high percentage of POA GnRH neurones (79%) also expressed nNOS, although no GnRH close contacts were observed onto nNOS neurones. Neither the numbers of nNOS neurones in the POA or hypothalamus, nor the percentage of nNOS coexpression with GnRH, kisspeptin or ERα were influenced by oestradiol. These experiments reveal that a neuroanatomical relationship exists between both nNOS and kisspeptin and nNOS and GnRH in prepubertal ewes. Therefore, nNOS may act both directly and indirectly to influence GnRH secretion in prepubertal sheep.

The predictors of persistent DSM-IV disorders in 3-year follow-ups of the British Child and Adolescent Mental Health Surveys 1999 and 2004.

BACKGROUND: The identification of the factors that influence the persistence of psychiatric disorder may assist practitioners to focus on young people who are particularly prone to poor outcomes, but population-based samples of sufficient size are rare. METHOD: This secondary analysis combined data from two large, population-based cross-sectional surveys in Great Britain (1999 and 2004) and their respective follow-ups (2002 and 2007), to study homotypic persistence among the 998 school-age children with psychiatric disorder at baseline. Psychiatric disorder was measured using the Development and Well-Being Assessment applying DSM-IV criteria. Factors relating to the child, family, and the severity and type of psychopathology at baseline were analysed using logistic regression. RESULTS: Approximately 50% of children with at least one psychiatric disorder were assigned the same diagnostic grouping at 3-year follow-up. Persistent attention-deficit/hyperactivity disorder and anxiety were predicted by poor peer relationship scores. Persistent conduct disorder was predicted by intellectual disability, rented housing, large family size, poor family function and by severer baseline psychopathology scores. CONCLUSIONS: Homotypic persistence was predicted by different factors for different groups of psychiatric disorders. Experimental research in clinical samples should explore whether these factors also influence response to interventions.

Disentangling the autism-anxiety overlap: fMRI of reward processing in a community-based longitudinal study.

Up to 40% of youth with autism spectrum disorder (ASD) also suffer from anxiety, and this comorbidity is linked with significant functional impairment. However, the mechanisms of this overlap are poorly understood. We investigated the interplay between ASD traits and anxiety during reward processing, known to be affected in ASD, in a community sample of 1472 adolescents (mean age=14.4 years) who performed a modified monetary incentive delay task as part of the Imagen project. Blood-oxygen-level dependent (BOLD) responses to reward anticipation and feedback were compared using a 2x2 analysis of variance test (ASD traits: low/high; anxiety symptoms: low/high), controlling for plausible covariates. In addition, we used a longitudinal design to assess whether neural responses during reward processing predicted anxiety at 2-year follow-up. High ASD traits were associated with reduced BOLD responses in dorsal prefrontal regions during reward anticipation and negative feedback. Participants with high anxiety symptoms showed increased lateral prefrontal responses during anticipation, but decreased responses following feedback. Interaction effects revealed that youth with combined ASD traits and anxiety, relative to other youth, showed high right insula activation when anticipating reward, and low right-sided caudate, putamen, medial and lateral prefrontal activations during negative feedback (all clusters PFWE<0.05). BOLD activation patterns in the right dorsal cingulate and right medial frontal gyrus predicted new-onset anxiety in participants with high but not low ASD traits. Our results reveal both quantitatively enhanced and qualitatively distinct neural correlates underlying the comorbidity between ASD traits and anxiety. Specific neural responses during reward processing may represent a risk factor for developing anxiety in ASD youth.

Surge-Like Luteinising Hormone Secretion Induced by Retrochiasmatic Area NK3R Activation is Mediated Primarily by Arcuate Kisspeptin Neurones in the Ewe.

The neuropeptides neurokinin B (NKB) and kisspeptin are potent stimulators of gonadotrophin-releasing hormone (GnRH)/luteinsing hormone (LH) secretion and are essential for human fertility. We have recently demonstrated that selective activation of NKB receptors (NK3R) within the retrochiasmatic area (RCh) and the preoptic area (POA) triggers surge-like LH secretion in ovary-intact ewes, whereas blockade of RCh NK3R suppresses oestradiol-induced LH surges in ovariectomised ewes. Although these data suggest that NKB signalling within these regions of the hypothalamus mediates the positive-feedback effects of oestradiol on LH secretion, the pathway through which it stimulates GnRH/LH secretion remains unclear. We proposed that the action of NKB on RCh neurones drives the LH surge by stimulating kisspeptin-induced GnRH secretion. To test this hypothesis, we quantified the activation of the preoptic/hypothalamic populations of kisspeptin neurones in response to POA or RCh administration of senktide by dual-label immunohistochemical detection of kisspeptin and c-Fos (i.e. marker of neuronal activation). We then administered the NK3R agonist, senktide, into the RCh of ewes in the follicular phase of the oestrous cycle and conducted frequent blood sampling during intracerebroventricular infusion of the kisspeptin receptor antagonist Kp-271 or saline. Our results show that the surge-like secretion of LH induced by RCh senktide administration coincided with a dramatic increase in c-Fos expression within arcuate nucleus (ARC) kisspeptin neurones, and was completely blocked by Kp-271 infusion. We substantiate these data with evidence of direct projections of RCh neurones to ARC kisspeptin neurones. Thus, NKB-responsive neurones in the RCh act to stimulate GnRH secretion by inducing kisspeptin release from KNDy neurones.

Impact of psychosocial stress on gonadotrophins and sexual behaviour in females: role for cortisol?

This review focuses on the importance of cortisol in mediating the inhibitory effects of psychosocial stress on reproduction in females. In particular, we have summarized our research in sheep where we have systematically established whether cortisol is both sufficient and necessary to suppress reproductive hormone secretion and inhibit sexual behaviour. Our findings are put into context with previous work and are used to develop important concepts as well as to identify productive further lines of investigation. It is clear that cortisol is necessary to inhibit some, but not all, aspects of reproduction in female sheep. These actions vary with reproductive state, and there are important interactions with gonadal steroids. The impact of cortisol on the tonic secretion of gonadotrophin-releasing hormone and luteinizing hormone has been investigated extensively, but less is known about the surge secretion of these hormones and their effects on sexual behaviour. Furthermore, there are separate effects of cortisol in the brain (hypothalamus) and at the anterior pituitary, illustrating that there are different mechanisms of action. Thus, although cortisol is important in mediating some of the effects of stress on reproduction, we need to look beyond cortisol and investigate some of the other mechanisms and mediators that relay the effects of stress on reproduction. In this regard, we propose that a group of neurons in the hypothalamus that co-synthesize kisspeptin, neurokinin B and dynorphin, termed KNDy cells, play important roles in mediating the effects of cortisol on reproduction. This hypothesis needs to be rigorously tested.

Does Dynorphin Play a Role in the Onset of Puberty in Female Sheep?

Puberty onset involves increased gonadotrophin-release (GnRH) release as a result of decreased sensitivity to oestrogen (E2 )-negative feedback. Because GnRH neurones lack E2 receptor α, this pathway must contain interneurones. One likely candidate is KNDy neurones (kisspeptin, neurokinin B, dynorphin). The overarching hypothesis of the present study was that the prepubertal hiatus in luteinising hormone (LH) release involves reduced kisspeptin and/or heightened dynorphin input. We first tested the specific hypothesis that E2 would reduce kisspeptin-immunopositive cell numbers and increase dynorphin-immunopositive cell numbers. We found that kisspeptin cell numbers were higher in ovariectomised (OVX) lambs than OVX lambs treated with E2 (OVX+ E2 ) or those left ovary-intact. Very few arcuate dynorphin cells were identified in any group. Next, we hypothesised that central blockade of κ-opioid receptor (KOR) would increase LH secretion at a prepubertal (6 months) but not postpubertal (10 months) age. Luteinising hormone pulse frequency and mean LH increased during infusion of a KOR antagonist, norbinaltorphimine, in OVX + E2 lambs at the prepubertal age but not in the same lambs at the postpubertal age. We next hypothesised that E2 would increase KOR expression in GnRH neurones or alter synaptic input to KNDy neurones in prepubertal ewes. Oestrogen treatment decreased the percentage of GnRH neurones coexpressing KOR (approximately 68%) compared to OVX alone (approximately 78%). No significant differences in synaptic contacts per cell between OVX and OVX + E2 groups were observed. Although these initial data are consistent with dynorphin inhibiting pulsatile LH release prepubertally, additional work will be necessary to define the source and mechanisms of this inhibition.

Evidence for Changes in Numbers of Synaptic Inputs onto KNDy and GnRH Neurones during the Preovulatory LH Surge in the Ewe.

Kisspeptin neurones located in the arcuate nucleus (ARC) and preoptic area (POA) are critical mediators of gonadal steroid feedback onto gonadotrophin-releasing hormone (GnRH) neurones. ARC kisspeptin cells that co-localise neurokinin B (NKB) and dynorphin (Dyn), are collectively referred to as KNDy (Kisspeptin/NKB/Dyn) neurones, and have been shown in mice to also co-express the vesicular glutamate transporter, vGlut2, an established glutamatergic marker. The ARC in rodents has long been known as a site of hormone-induced neuroplasticity, and changes in synaptic inputs to ARC neurones in rodents occur over the oestrous cycle. Based on this evidence, the the present study aimed to examine possible changes across the ovine oestrous cycle in synaptic inputs onto kisspeptin cells in the ARC (KNDy) and POA, and inputs onto GnRH neurones. Gonadal-intact breeding season ewes were perfused using 4% paraformaldehyde during either the luteal or follicular phase of the oestrous cycle, with the latter group killed at the time of the luteinising hormone (LH) surge. Hypothalamic sections were processed for triple-label immunodetection of kisspeptin/vGlut2/synaptophysin or kisspeptin/vGlut2/GnRH. The total numbers of synaptophysin- and vGlut2-positive inputs to ARC KNDy neurones were significantly increased at the time of the LH surge compared to the luteal phase; because these did not contain kisspeptin, they do not arise from KNDy neurones. By contrast to the ARC, the total number of synaptophysin-positive inputs onto POA kisspeptin neurones did not differ between luteal phase and surge animals. The total number of kisspeptin and vGlut2 inputs onto GnRH neurones in the mediobasal hypothalamus (MBH) was also increased during the LH surge, and could be attributed to an increase in the number of KNDy (double-labelled kisspeptin + vGlut2) inputs. Taken together, these results provide novel evidence of synaptic plasticity at the level of inputs onto KNDy and GnRH neurones during the ovine oestrous cycle. Such changes may contribute to the generation of the preovulatory GnRH/LH surge.

Ignition's glow: Ultra-fast spread of global cortical activity accompanying local "ignitions" in visual cortex during conscious visual perception.

Despite extensive research, the spatiotemporal span of neuronal activations associated with the emergence of a conscious percept is still debated. The debate can be formulated in the context of local vs. global models, emphasizing local activity in visual cortex vs. a global fronto-parietal "workspace" as the key mechanisms of conscious visual perception. These alternative models lead to differential predictions with regard to the precise magnitude, timing and anatomical spread of neuronal activity during conscious perception. Here we aimed to test a specific aspect of these predictions in which local and global models appear to differ - namely the extent to which fronto-parietal regions modulate their activity during task performance under similar perceptual states. So far the main experimental results relevant to this debate have been obtained from non-invasive methods and led to conflicting interpretations. Here we examined these alternative predictions through large-scale intracranial measurements (Electrocorticogram - ECoG) in 43 patients and 4445 recording sites. Both ERP and broadband high frequency (50-150 Hz - BHF) responses were examined through the entire cortex during a simple 1-back visual recognition memory task. Our results reveal short latency intense visual responses, localized first in early visual cortex followed (at ∼200 ms) by higher order visual areas, but failed to show significant delayed (300 ms) visual activations. By contrast, oddball image repeat events, linked to overt motor responses, were associated with a significant increase in a delayed (300 ms) peak of BHF power in fronto-parietal cortex. Comparing BHF responses with ERP revealed an additional peak in the ERP response - having a similar latency to the well-studied P3 scalp EEG response. Posterior and temporal regions demonstrated robust visual category selectivity. An unexpected observation was that high-order visual cortex responses were essentially concurrent (at ∼200 ms) with an ultra-fast spread of signals of lower magnitude that invaded selected sites throughout fronto-parietal cortical areas. Our results are compatible with local models in demonstrating a clear task-dependence of the 300 ms fronto-parietal activation. However, they also reveal a more global component of low-magnitude and poor content selectivity that rapidly spreads into fronto-parietal sites. The precise functional role of this global "glow" remains to be elucidated.

Resilience and corpus callosum microstructure in adolescence.

BACKGROUND: Resilience is the capacity of individuals to resist mental disorders despite exposure to stress. Little is known about its neural underpinnings. The putative variation of white-matter microstructure with resilience in adolescence, a critical period for brain maturation and onset of high-prevalence mental disorders, has not been assessed by diffusion tensor imaging (DTI). Lower fractional anisotropy (FA) though, has been reported in the corpus callosum (CC), the brain's largest white-matter structure, in psychiatric and stress-related conditions. We hypothesized that higher FA in the CC would characterize stress-resilient adolescents. METHOD: Three groups of adolescents recruited from the community were compared: resilient with low risk of mental disorder despite high exposure to lifetime stress (n = 55), at-risk of mental disorder exposed to the same level of stress (n = 68), and controls (n = 123). Personality was assessed by the NEO-Five Factor Inventory (NEO-FFI). Voxelwise statistics of DTI values in CC were obtained using tract-based spatial statistics. Regional projections were identified by probabilistic tractography. RESULTS: Higher FA values were detected in the anterior CC of resilient compared to both non-resilient and control adolescents. FA values varied according to resilience capacity. Seed regional changes in anterior CC projected onto anterior cingulate and frontal cortex. Neuroticism and three other NEO-FFI factor scores differentiated non-resilient participants from the other two groups. CONCLUSION: High FA was detected in resilient adolescents in an anterior CC region projecting to frontal areas subserving cognitive resources. Psychiatric risk was associated with personality characteristics. Resilience in adolescence may be related to white-matter microstructure.

Neurokinin-3 receptor activation in the retrochiasmatic area is essential for the full pre-ovulatory luteinising hormone surge in ewes.

Neurokinin B (NKB) is essential for human reproduction and has been shown to stimulate luteinising hormone (LH) secretion in several species, including sheep. Ewes express the neurokinin-3 receptor (NK3R) in the retrochiasmatic area (RCh) and there is one report that placement of senktide, an NK3R agonist, therein stimulates LH secretion that resembles an LH surge in ewes. In the present study, we first confirmed that local administration of senktide to the RCh produced a surge-like increase in LH secretion, and then tested the effects of this agonist in two other areas implicated in the control of LH secretion and where NK3R is found in high abundance: the preoptic area (POA) and arcuate nucleus (ARC). Bilateral microimplants containing senktide induced a dramatic surge-like increase in LH when given in the POA similar to that seen with RCh treatment. By contrast, senktide treatment in the ARC resulted in a much smaller but significant increase in LH concentrations suggestive of an effect on tonic secretion. The possible role of POA and RCh NK3R activation in the LH surge was next tested by treating ewes with SB222200, an NK3R antagonist, in each area during an oestradiol-induced LH surge. SB222200 in the RCh, but not in the POA, reduced the LH surge amplitude by approximately 40% compared to controls, indicating that NK3R activation in the former region is essential for full expression of the pre-ovulatory LH surge. Based on these data, we propose that the actions of NKB in the RCh are an important component of the pre-ovulatory LH surge in ewes.

Update of the WHO/IUIS Allergen Nomenclature Database based on analysis of allergen sequences.

The IUIS Allergen Nomenclature Sub-Committee, under the auspices of the World Health Organization and the International Union of Immunological Societies, maintains the systematic nomenclature of allergenic proteins and publishes a database of approved allergen names on its Web site, www.allergen.org. In this paper, we summarize updates of allergen names approved at the meetings of the committee in 2011 through 2013. These changes reflect recent progress in identification, cloning, and sequencing of allergens. The goals of this update were to increase consistency in the classification of allergens, isoallergens, and variants and in the incorporation of the evolutionary classification of proteins into allergen nomenclature, while keeping changes of established names to a minimum in the interest of continuity. Allergens for which names have been updated include respiratory allergens from birch and ragweed pollen, midge larvae, and horse dander; food allergens from peanut, cow's milk, and tomato; and cereal grain allergens. The IUIS Allergen Nomenclature Sub-Committee encourages researchers to use these updated allergen names in future publications.

White-matter microstructure and gray-matter volumes in adolescents with subthreshold bipolar symptoms.

Abnormalities in white-matter (WM) microstructure, as lower fractional anisotropy (FA), have been reported in adolescent-onset bipolar disorder and in youth at familial risk for bipolarity. We sought to determine whether healthy adolescents with subthreshold bipolar symptoms (SBP) would have early WM microstructural alterations and whether those alterations would be associated with differences in gray-matter (GM) volumes. Forty-two adolescents with three core manic symptoms and no psychiatric diagnosis, and 126 adolescents matched by age and sex, with no psychiatric diagnosis or symptoms, were identified after screening the IMAGEN database of 2223 young adolescents recruited from the general population. After image quality control, voxel-wise statistics were performed on the diffusion parameters using tract-based spatial statistics in 25 SBP adolescents and 77 controls, and on GM and WM images using voxel-based morphometry in 30 SBP adolescents and 106 controls. As compared with healthy controls, adolescents with SBP displayed lower FA values in a number of WM tracts, particularly in the corpus callosum, cingulum, bilateral superior and inferior longitudinal fasciculi, uncinate fasciculi and corticospinal tracts. Radial diffusivity was mainly higher in posterior parts of bilateral superior and inferior longitudinal fasciculi, inferior fronto-occipital fasciculi and right cingulum. As compared with controls, SBP adolescents had lower GM volume in the left anterior cingulate region. This is the first study to investigate WM microstructure and GM morphometric variations in adolescents with SBP. The widespread FA alterations in association and projection tracts, associated with GM changes in regions involved in mood disorders, suggest altered structural connectivity in those adolescents.

A new diagnostic approach for Turkish speaking populations DAWBA Turkish Version.

Aims. Turkey has the youngest population in Europe with about 25 million people aged below 19 years and Turkish-speaking people comprise the biggest migrant group in Europe with 2.5 million people dispersed in different countries, but conducting epidemiologic surveys on Turkish people is challenging due to the lack of a suitable diagnostic tool. The Development and Well-Being Assessment (DAWBA) is one of the most widely used diagnostic interviews in child and adolescent psychiatry. In this study, we aimed at translating the DAWBA into Turkish and then examined its validity and reliability. Methods. The validity of the Turkish version was examined in clinical (n = 50) and community (n = 104) samples. The interrater reliability was also evaluated on 20 cases. Results. The translation method used in the study achieved semantic, conceptual, content, technical, item and criterion equivalence between the Turkish and original forms. The validity of the Turkish DAWBA was good or excellent for different diagnostic categories (κ: 0.43-0.84); the interrater reliability was also excellent (κ: 0.85-1). Conclusions. The Turkish DAWBA may be useful for future prevalence studies in Turkey. European clinicians and researchers who work with Turkish-speaking families can use the online Turkish DAWBA to gather structured information from Turkish-speaking informants and review the answers in their own language.

Challenges in testing genetically modified crops for potential increases in endogenous allergen expression for safety.

Premarket, genetically modified (GM) plants are assessed for potential risks of food allergy. The major risk would be transfer of a gene encoding an allergen or protein nearly identical to an allergen into a different food source, which can be assessed by specific serum testing. The potential that a newly expressed protein might become an allergen is evaluated based on resistance to digestion in pepsin and abundance in food fractions. If the modified plant is a common allergenic source (e.g. soybean), regulatory guidelines suggest testing for increases in the expression of endogenous allergens. Some regulators request evaluating endogenous allergens for rarely allergenic plants (e.g. maize and rice). Since allergic individuals must avoid foods containing their allergen (e.g. peanut, soybean, maize, or rice), the relevance of the tests is unclear. Furthermore, no acceptance criteria are established and little is known about the natural variation in allergen concentrations in these crops. Our results demonstrate a 15-fold difference in the major maize allergen, lipid transfer protein between nine varieties, and complex variation in IgE binding to various soybean varieties. We question the value of evaluating endogenous allergens in GM plants unless the intent of the modification was production of a hypoallergenic crop.

Propagation of epileptiform activity on a submillimeter scale.

Microseizures are highly focal low-frequency epileptiform-appearing events recorded from the neocortex of epilepsy patients. Because of their tiny, often submillimeter distribution, they may be regarded as a high-resolution window into the epileptic process, providing an excellent opportunity to study the fine temporal structure of their origin and spread. A 16 mm² 96-microelectrode array with 400-µm interelectrode spacing was implanted in seven patients undergoing invasive EEG monitoring for medically refractory epilepsy. Seven microdischarge populations were tested for a substantial contribution by volume conduction to the observed waveform amplitudes. Single-unit activity was examined for specific evidence of neural activity at multiple sites within the microdischarge fields. We found that microdischarges appear to originate at a highly focal source location, likely within a single cortical macrocolumn, and spread to local and more distant sites via neural propagation.