Factors associated with hospitalization after suicide spectrum behaviors: results from a multicentre study in Spain

Objectives: to identify factors associated with admission after suicide spectrum behaviors. Methods: Patient's characteristics, the nature of their suicidal behavior, admission rates between centres, and factors associated with admission have been examined in suicide spectrum presentations to emergency departments in three Spanish cities. Results: Intent of the suicidal behavior had the greatest impact on hospitalization. Older age, living alone, self-harm method not involving drug overdose, previous history of suicide spectrum behaviors and psychiatric diagnosis of schizophrenia, mood or personality disorder were independently associated with being admitted. There was a three-fold between-centre difference in the rate of hospitalization. Conclusions: widespread differences in the rate of hospitalization were primarily accounted for by characteristics of the individual patients and their suicidal behavior.

The effects of aging on the BTBR mouse model of autism spectrum disorder.

Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder characterized by alterations in social functioning, communicative abilities, and engagement in repetitive or restrictive behaviors. The process of aging in individuals with autism and related neurodevelopmental disorders is not well understood, despite the fact that the number of individuals with ASD aged 65 and older is projected to increase by over half a million individuals in the next 20 years. To elucidate the effects of aging in the context of a modified central nervous system, we investigated the effects of age on the BTBR T + tf/j mouse, a well characterized and widely used mouse model that displays an ASD-like phenotype. We found that a reduction in social behavior persists into old age in male BTBR T + tf/j mice. We employed quantitative proteomics to discover potential alterations in signaling systems that could regulate aging in the BTBR mice. Unbiased proteomic analysis of hippocampal and cortical tissue of BTBR mice compared to age-matched wild-type controls revealed a significant decrease in brain derived neurotrophic factor and significant increases in multiple synaptic markers (spinophilin, Synapsin I, PSD 95, NeuN), as well as distinct changes in functional pathways related to these proteins, including "Neural synaptic plasticity regulation" and "Neurotransmitter secretion regulation." Taken together, these results contribute to our understanding of the effects of aging on an ASD-like mouse model in regards to both behavior and protein alterations, though additional studies are needed to fully understand the complex interplay underlying aging in mouse models displaying an ASD-like phenotype.

Hippocampal Transcriptomic and Proteomic Alterations in the BTBR Mouse Model of Autism Spectrum Disorder.

Autism spectrum disorders (ASD) are complex heterogeneous neurodevelopmental disorders of an unclear etiology, and no cure currently exists. Prior studies have demonstrated that the black and tan, brachyury (BTBR) T+ Itpr3tf/J mouse strain displays a behavioral phenotype with ASD-like features. BTBR T+ Itpr3tf/J mice (referred to simply as BTBR) display deficits in social functioning, lack of communication ability, and engagement in stereotyped behavior. Despite extensive behavioral phenotypic characterization, little is known about the genes and proteins responsible for the presentation of the ASD-like phenotype in the BTBR mouse model. In this study, we employed bioinformatics techniques to gain a wide-scale understanding of the transcriptomic and proteomic changes associated with the ASD-like phenotype in BTBR mice. We found a number of genes and proteins to be significantly altered in BTBR mice compared to C57BL/6J (B6) control mice controls such as BDNF, Shank3, and ERK1, which are highly relevant to prior investigations of ASD. Furthermore, we identified distinct functional pathways altered in BTBR mice compared to B6 controls that have been previously shown to be altered in both mouse models of ASD, some human clinical populations, and have been suggested as a possible etiological mechanism of ASD, including "axon guidance" and "regulation of actin cytoskeleton." In addition, our wide-scale bioinformatics approach also discovered several previously unidentified genes and proteins associated with the ASD phenotype in BTBR mice, such as Caskin1, suggesting that bioinformatics could be an avenue by which novel therapeutic targets for ASD are uncovered. As a result, we believe that informed use of synergistic bioinformatics applications represents an invaluable tool for elucidating the etiology of complex disorders like ASD.

Gaussian Process Kernels for Cross-Spectrum Analysis in Electrophysiological Time Series

Multi-output Gaussian processes provide a convenient framework for multi-task problems. An illustrative and motivating example of a multi-task problem is multi-region electrophysiological time-series data, where experimentalists are interested in both power and phase coherence between channels. Recently, the spectral mixture (SM) kernel was proposed to model the spectral density of a single task in a Gaussian process framework. This work develops a novel covariance kernel for multiple outputs, called the cross-spectral mixture (CSM) kernel. This new, flexible kernel represents both the power and phase relationship between multiple observation channels. The expressive capabilities of the CSM kernel are demonstrated through implementation of 1) a Bayesian hidden Markov model, where the emission distribution is a multi-output Gaussian process with a CSM covariance kernel, and 2) a Gaussian process factor analysis model, where factor scores represent the utilization of cross-spectral neural circuits. Results are presented for measured multi-region electrophysiological data.

Neural mechanisms of negative reinforcement in children and adolescents with autism spectrum disorders.

BACKGROUND: Previous research has found accumulating evidence for atypical reward processing in autism spectrum disorders (ASD), particularly in the context of social rewards. Yet, this line of research has focused largely on positive social reinforcement, while little is known about the processing of negative reinforcement in individuals with ASD. METHODS: The present study examined neural responses to social negative reinforcement (a face displaying negative affect) and non-social negative reinforcement (monetary loss) in children with ASD relative to typically developing children, using functional magnetic resonance imaging (fMRI). RESULTS: We found that children with ASD demonstrated hypoactivation of the right caudate nucleus while anticipating non-social negative reinforcement and hypoactivation of a network of frontostriatal regions (including the nucleus accumbens, caudate nucleus, and putamen) while anticipating social negative reinforcement. In addition, activation of the right caudate nucleus during non-social negative reinforcement was associated with individual differences in social motivation. CONCLUSIONS: These results suggest that atypical responding to negative reinforcement in children with ASD may contribute to social motivational deficits in this population.

Adults with autism spectrum disorders exhibit decreased sensitivity to reward parameters when making effort-based decisions.

BACKGROUND: Efficient effort expenditure to obtain rewards is critical for optimal goal-directed behavior and learning. Clinical observation suggests that individuals with autism spectrum disorders (ASD) may show dysregulated reward-based effort expenditure, but no behavioral study to date has assessed effort-based decision-making in ASD. METHODS: The current study compared a group of adults with ASD to a group of typically developing adults on the Effort Expenditure for Rewards Task (EEfRT), a behavioral measure of effort-based decision-making. In this task, participants were provided with the probability of receiving a monetary reward on a particular trial and asked to choose between either an "easy task" (less motoric effort) for a small, stable reward or a "hard task" (greater motoric effort) for a variable but consistently larger reward. RESULTS: Participants with ASD chose the hard task more frequently than did the control group, yet were less influenced by differences in reward value and probability than the control group. Additionally, effort-based decision-making was related to repetitive behavior symptoms across both groups. CONCLUSIONS: These results suggest that individuals with ASD may be more willing to expend effort to obtain a monetary reward regardless of the reward contingencies. More broadly, results suggest that behavioral choices may be less influenced by information about reward contingencies in individuals with ASD. This atypical pattern of effort-based decision-making may be relevant for understanding the heightened reward motivation for circumscribed interests in ASD.

HELPING YOUTH WITH AUTISM SPECTRUM DISORDER DEVELOP SOCIAL COMPETENCE IN COMMUNITY-BASED SETTINGS

The purpose of the current dissertation is to identify the features of effective interventions by exploring the experiences of youth with ASD who participate in such interventions, through two intervention studies (Studies 1 and 2) and one interview study (Study 3). Studies 1 and 2 were designed to support the development of social competence of youth with ASD through Structured Play with LEGO TM (Study 1, 12 youths with ASD, ages 7–12) and Minecraft TM (Study 2, 4 youths with ASD, ages 11–13). Over the course of the sessions, the play of the youth developed from parallel play (children playing alone, without interacting) to co-operative play (playing together with shared objectives). The results of Study 2 showed that rates of initiations and levels of engagement increased from the first session to the final session. In Study 3, 12 youths with ASD (ages 10–14) and at least one of their parents were interviewed to explore what children and their parents want from programs designed to improve social competence, which activities and practices were perceived to promote social competence by the participants, and which factors affected their decisions regarding these programs. The adolescents and parents looked for programs that supported social development and emotional wellbeing, but did not always have access to the programs they would have preferred, with factors such as cost and location reducing their options. Three overarching themes emerged through analysis of the three studies: (a) interests of the youth; (b) structure, both through interactions and instruction; and (c) naturalistic settings. Adolescents generally engage more willingly in interventions that incorporate their interests, such as play with Minecraft TM in Study 2. Additionally, Structured Play and structured instruction were crucial components of providing safe and supportive contexts for the development of social competence. Finally, skills learned in naturalistic settings tend to be applied more successfully in everyday situations. The themes are analysed through the lens of Vygotsky’s (1978) perspectives on learning, play, and development. Implications of the results for practitioners and researchers are discussed.

SCAPHOID AND LUNATE CARPAL MECHANICS OVER THE SPECTRUM OF HEALTHY FUNCTION

When ligaments within the wrist are damaged, the resulting loss in range of motion and grip strength can lead to reduced earning potential and restricted ability to perform important activities of daily living. Left untreated, ligament injuries ultimately lead to arthritis and chronic pain. Surgical repair can mitigate these issues but current procedures are often non-anatomic and unable to completely restore the wrist’s complex network of ligaments. An inability to quantitatively assess wrist function clinically, both before and after surgery, limits the ability to assess the response to clinical intervention. Previous work has shown that bones within the wrist move in a similar pattern across people, but these patterns remain challenging to predict and model. In an effort to quantify and further develop the understanding of normal carpal mechanics, we performed two studies using 3D in vivo carpal bone motion analysis techniques. For the first study, we measured wrist laxity and performed CT scans of the wrist to evaluate 3D carpal bone positions. We found that through mid-range radial-ulnar deviation range of motion the scaphoid and lunate primarily flexed and extended; however, there was a significant relationship between wrist laxity and row-column behaviour. We also found that there was a significant relationship between scaphoid flexion and active radial deviation range of motion. For the second study, an analysis was performed on a publicly available database. We evaluated scapholunate relative motion over a full range of wrist positions, and found that there was a significant amount of variation in the location and orientation of the rotation axis between the two bones. Together the findings from the two studies illustrate the complexity and subject specificity of normal carpal mechanics, and should provide insights that can guide the development of anatomical wrist ligament repair surgeries that restore normal function.

The differential impact of oxytocin receptor (OXTR) genotypes on the risk of autism spectrum disorder (ASD) and resulting social communication deficits

Background: Autism spectrum disorder (ASD) is multifactorial and is likely the result of complex interactions between multiple environmental and genetic factors. Recently, it has been suggested that each symptom cluster of the disorder, such as poor social communication, may be mediated by different genetic influences. Genes in the oxytocin pathway, which mediates social behaviours in humans, have been studied with single nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR) being implicated in ASD. This thesis examines the presence of different oxytocin receptor genotypes, and their associations with ASD and resulting social communication deficits. Methods: The relationship between four OXTR variants and ASD was evaluated in 607 ASD simplex (SPX) families. Cases were compared to their unaffected siblings using a conditional logistic approach. Odds ratios and associated 95 percent confidence intervals were obtained. A second sample of 235 individuals with a diagnosis of ASD was examined to evaluate whether these four OXTR variants were associated with social communication scores on the Autism Diagnostic Interview – Revised (ADI-R). Parameter estimates and associated 95 percent confidence intervals were generated using a linear regression approach. Multiple testing issues were addressed using false discovery adjustments. Results: The rs53576 AG genotype was significantly associated with a lower risk of ASD (OR = 0.707, 95% CI: 0.512-0.975). A single genotype (AG) provided by the rs2254298 marker was found to be significantly associated with higher social communication scores (Parameter estimate = 1.833, SE = 0.762, p = 0.0171). This association was also seen in a Caucasian only and mothers as the respondent samples. No association was significant following false discovery rate adjustments. Conclusion: The findings from these studies provide limited support for the role of OXTR SNPs in ASD, especially in social communication skills. The clinical significance of these associations remains unknown, however, it is likely that these associations do not play a role in the severity of symptoms associated with ASD. Rather, they may be important in the appearance of social deficits due to the rs2254298 markers association with enlarged amygdalas.

Achievable rates and outage probability of cognitive radio with dynamic frequency hopping under imperfect spectrum sensing

In this study, the authors propose simple methods to evaluate the achievable rates and outage probability of a cognitive radio (CR) link that takes into account the imperfectness of spectrum sensing. In the considered system, the CR transmitter and receiver correlatively sense and dynamically exploit the spectrum pool via dynamic frequency hopping. Under imperfect spectrum sensing, false-alarm and miss-detection occur which cause impulsive interference emerged from collisions due to the simultaneous spectrum access of primary and cognitive users. That makes it very challenging to evaluate the achievable rates. By first examining the static link where the channel is assumed to be constant over time, they show that the achievable rate using a Gaussian input can be calculated accurately through a simple series representation. In the second part of this study, they extend the calculation of the achievable rate to wireless fading environments. To take into account the effect of fading, they introduce a piece-wise linear curve fitting-based method to approximate the instantaneous achievable rate curve as a combination of linear segments. It is then demonstrated that the ergodic achievable rate in fast fading and the outage probability in slow fading can be calculated to achieve any given accuracy level.

Applied behavior analysis: What do teachers of students with autism spectrum disorder know?

With rising numbers of school-aged children with autism educated in mainstream classroomsand applied behavior analysis (ABA) considered the basis of best practice, teachers’ knowledgein this field has become a key concern for inclusion. Self-reported knowledge of ABA of specialneeds teachers (n=165) was measured and compared to their actual knowledge of ABAdemonstrated in accurate responses to a multiple-choice test. Findings reported here show thatteachers’ self-perceived knowledge exceeded actual knowledge and that actual knowledge ofABA was not

Evaluating laser-driven Bremsstrahlung radiation sources for imaging and analysis of nuclear waste packages

A small scale sample nuclear waste package, consisting of a 28 mm diameter uranium penny encased in grout, was imaged by absorption contrast radiography using a single pulse exposure from an X-ray source driven by a high-power laser. The Vulcan laser was used to deliver a focused pulse of photons to a tantalum foil, in order to generate a bright burst of highly penetrating X-rays (with energy >500 keV), with a source size of <0.5 mm. BAS-TR and BAS-SR image plates were used for image capture, alongside a newly developed Thalium doped Caesium Iodide scintillator-based detector coupled to CCD chips. The uranium penny was clearly resolved to sub-mm accuracy over a 30 cm2 scan area from a single shot acquisition. In addition, neutron generation was demonstrated in situ with the X-ray beam, with a single shot, thus demonstrating the potential for multi-modal criticality testing of waste materials. This feasibility study successfully demonstrated non-destructive radiography of encapsulated, high density, nuclear material. With recent developments of high-power laser systems, to 10 Hz operation, a laser-driven multi-modal beamline for waste monitoring applications is envisioned.

Full-Duplex Spectrum Sharing in Cooperative Single Carrier Systems

We propose cyclic prefix single carrier full-duplex transmission in amplify-and-forward cooperative spectrum sharing networks to achieve multipath diversity and full-duplex spectral efficiency. Integrating full-duplex transmission into cooperative spectrum sharing systems results in two intrinsic problems: 1) the residual loop interference occurs between the transmit and the receive antennas at the secondary relays and 2) the primary users simultaneously suffer interference from the secondary source (SS) and the secondary relays (SRs). Thus, examining the effects of residual loop interference under peak interference power constraint at the primary users and maximum transmit power constraints at the SS and the SRs is a particularly challenging problem in frequency selective fading channels. To do so, we derive and quantitatively compare the lower bounds on the outage probability and the corresponding asymptotic outage probability for max–min relay selection, partial relay selection, and maximum interference relay selection policies in frequency selective fading channels. To facilitate comparison, we provide the corresponding analysis for half-duplex. Our results show two complementary regions, named as the signal-to-noise ratio (SNR) dominant region and the residual loop interference dominant region, where the multipath diversity and spatial diversity can be achievable only in the SNR dominant region, however the diversity gain collapses to zero in the residual loop interference dominant region.

Secure Full-Duplex Small-Cell Networks in a Spectrum Sharing Environment

In this paper, we propose three relay selection schemes for full-duplex heterogeneous networks in the presence of multiple cognitive radio eavesdroppers. In this setup, the cognitive small-cell nodes (secondary network) can share the spectrum licensed to the macro-cell system (primary network) on the condition that the quality-of-service of the primary network is always satisfied subjected to its outage probability constraint. The messages are delivered from one small-cell base station to the destination with the help of full-duplex small-cell base stations, which act as relay nodes. Based on the availability of the network’s channel state information at the secondary information source, three different selection criteria for full-duplex relays, namely: 1) partial relay selection; 2) optimal relay selection; and 3) minimal self-interference relay selection, are proposed. We derive the exact closed-form and asymptotic expressions of the secrecy outage probability for the three criteria under the attack of non-colluding/colluding eavesdroppers. We demonstrate that the optimal relay selection scheme outperforms the partial relay selection and minimal self-interference relay selection schemes at the expense of acquiring full channel state information knowledge. In addition, increasing the number of the full-duplex small-cell base stations can improve the security performance. At the illegitimate side, deploying colluding eavesdroppers and increasing the number of eavesdroppers put the confidential information at a greater risk. Besides, the transmit power and the desire outage probability of the primary network have great influences on the secrecy outage probability of the secondary network.