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Investigations of mental illness have been enriched by the advent and maturation of neuroimaging technologies and the rapid pace and increased affordability of molecular sequencing techniques, however, the increased volume, variety and velocity of research data, presents a considerable technical and analytic challenge to curate, federate and interpret. Aggregation of high-dimensional datasets across brain disorders can increase sample sizes and may help identify underlying causes of brain dysfunction, however, additional barriers exist for effective data harmonization and integration for their combined use in research. To help realize the potential of multi-modal data integration for the study of mental illness, the Centre for Addiction and Mental Health (CAMH) constructed a centralized data capture, visualization and analytics environment—the CAMH Neuroinformatics Platform—based on the Ontario Brain Institute (OBI) Brain-CODE architecture, towards the curation of a standardized, consolidated psychiatric hospital-wide research dataset, directly coupled to high performance computing resources.

This paper shows how methods from statistical relational learning can be used to address problems in grammatical inference using model-theoretic representations of strings. These model-theoretic representations are the basis of representing formal languages logically. Conventional representations include a binary relation for order and unary relations describing mutually exclusive properties of each position in the string. This paper presents experiments on the learning of formal languages, and their stochastic counterparts, with unconventional models, which relax the mutual exclusivity condition. Unconventional models are motivated by domain-specific knowledge. Comparison of conventional and unconventional word models shows that in the domains of phonology and robotic planning and control, Markov Logic Networks With unconventional models achieve better performance and less runtime with smaller networks than Markov Logic Networks With conventional models.

Historically, research databases have existed in isolation with no practical avenue for sharing or pooling medical data into high dimensional datasets that can be efficiently compared across databases. To address this challenge, the Ontario Brain Institute’s “Brain-CODE” is a large-scale neuroinformatics platform designed to support the collection, storage, federation, sharing and analysis of different data types across several brain disorders, as a means to understand common underlying causes of brain dysfunction and develop novel approaches to treatment. By providing researchers access to aggregated datasets that they otherwise could not obtain independently, Brain-CODE incentivizes data sharing and collaboration and facilitates analyses both within and across disorders and across a wide array of data types, including clinical, neuroimaging and molecular. The Brain-CODE system architecture provides the technical capabilities to support (1) consolidated data management to securely capture, monitor and curate data, (2) privacy and security best-practices, and (3) interoperable and extensible systems that support harmonization, integration, and query across diverse data modalities and linkages to external data sources. Brain-CODE currently supports collaborative research networks focused on various brain conditions, including neurodevelopmental disorders, cerebral palsy, neurodegenerative diseases, epilepsy and mood disorders. These programs are generating large volumes of data that are integrated within Brain-CODE to support scientific inquiry and analytics across multiple brain disorders and modalities. By providing access to very large datasets on patients with different brain disorders and enabling linkages to provincial, national and international databases, Brain-CODE will help to generate new hypotheses about the biological bases of brain disorders, and ultimately promote new discoveries to improve patient care.

Introduction: The focused assessment with sonography for trauma (FAST) is a commonly used and life-saving tool in the initial assessment of trauma patients. The recommended emergency medicine (EM) curriculum includes ultrasound and studies show the additional utility of ultrasound training for medical students. EM clerkships vary and often do not contain formal ultrasound instruction. Time constraints for facilitating lectures and hands-on learning of ultrasound are challenging. Limitations on didactics call for development and inclusion of novel educational strategies, such as simulation. The objective of this study was to compare the test, survey, and performance of ultrasound between medical students trained on an ultrasound simulator versus those trained via traditional, hands-on patient format. Methods: This was a prospective, blinded, controlled educational study focused on EM clerkship medical students. After all received a standardized lecture with pictorial demonstration of image acquisition, students were randomized into two groups: control group receiving traditional training method via practice on a human model and intervention group training via practice on an ultrasound simulator. Participants were tested and surveyed on indications and interpretation of FAST and training and confidence with image interpretation and acquisition before and after this educational activity. Evaluation of FAST skills was performed on a human model to emulate patient care and practical skills were scored via objective structured clinical examination (OSCE) with critical action checklist. Results: There was no significant difference between control group (N=54) and intervention group (N=39) on pretest scores, prior ultrasound training/education, or ultrasound comfort level in general or on FAST. All students (N=93) showed significant improvement from pre- to post-test scores and significant improvement in comfort level using ultrasound in general and on FAST (p

When ACL2 is used to model the operational semantics of computing machines, machine states are typically represented by terms recording the contents of the state components. When models are realistic and are stepped through thousands of machine cycles, these terms can grow quite large and the cost of simplifying them on each step grows. In this paper we describe an ACL2 book that uses HIDE and metafunctions to facilitate the management of large terms representing such states. Because the metafunctions for each state component updater are solely responsible for creating state expressions (i.e., "writing") and the metafunctions for each state component accessor are solely responsible for extracting values (i.e., "reading") from such state expressions, they can maintain their own normal form, use HIDE to prevent other parts of ACL2 from inspecting them, and use honsing to uniquely represent state expressions. The last feature makes it possible to memoize the metafunctions, which can improve proof performance in some machine models. This paper describes a general-purpose ACL2 book modeling a byte-addressed memory supporting "mixed" reads and writes. By "mixed" we mean that reads need not correspond (in address or number of bytes) with writes. Verified metafunctions simplify such "read-over-write" expressions while hiding the potentially large state expression. A key utility is a function that determines an upper bound on the value of a symbolic arithmetic expression, which plays a role in resolving writes to addresses given by symbolic expressions. We also report on a preliminary experiment with the book, which involves the production of states containing several million function calls.

Background: Mild behavioral impairment (MBI) is a syndrome characterized by later life onset, persistent neuropsychiatric symptoms (NPS) in non‐demented older adults. MBI can co‐occur with Mild Cognitive Impairment (MCI) and has a range of neurodegenerative etiologies including Alzheimer's disease (AD), Cerebrovascular Disease (CVD), and Parkinson's disease (PD). MBI is associated with poorer cognitive and psychosocial function and an increased risk of developing dementia. Thus, we aimed to explore the structural neural correlates of MBI, specifically in the regions known to be associated with cognitive impairment (i.e., corticolimbic and frontal‐executive circuits), across multiple neurodegenerative diagnoses from the Ontario Neurodegenerative Disease Research Initiative (ONDRI). Method: We assessed the association between MBI and brain structural alterations via T1‐weighted imaging in three groups with Montreal Cognitive Assessment scores ³19: individuals with MCI (due to AD; n = 37), CVD (n = 129), and PD (n = 127). NPS scores were derived from the Neuropsychiatric Inventory (NPI‐Q) domains, and categorized as NPS+ (i.e., NPI score>0); and NPS‐ (NPI score = 0). We selected regions of interest from the corticolimbic and frontal‐executive circuits to measure brain structure using cortical thickness and subcortical volume. Partial correlation, corrected for age, sex, and education was used to assess the association between MBI and brain structural alterations. Result: Overall, apathy, depression, and anxiety, which map to the decreased motivation and emotional dysregulation MBI domains, had a high prevalence across all the groups. In the brain‐MBI association analysis, apathy was associated with decreased thickness of the l‐rostral middle frontal, r‐superior temporal, and frontal pole in the PD and CVD (but not MCI) groups. Anxiety was associated with decreased volume of the right hippocampus and amygdala in the MCI group, but not CVD or PD (FDR p< 0.05). No structural correlates were found for depression. Conclusion: Our findings provide evidence of a specific association between apathy and reduced efficiency of the frontal‐executive system in individuals with PD and CVD. In addition, the well‐established AD corticolimbic atrophy patterns (e.g., hippocampus and amygdala) seen in MCI are prominent in the presence of anxiety. Overall, the relatively distinct brain‐MBI associations across neurodegenerative disorders suggest that pathological substrates may alter MBI neural correlates. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine the effects on four-year-olds' knowledge of mathematics by introducing professional development and center-based mathematics activities around four mathematical domains to early educators' teaching in Head Start programs. Because of the need to provide necessary mathematical experiences to young children to improve their early understanding and skills and provide the foundation for future success in mathematics, we provided the treatment group of early educators with professional development and center-based activities to promote four critical areas in mathematics. By randomly selecting Head Start centers to participate as the treatment group or control group, we were able to examine the effects of the professional development and set of activities on preschool children's knowledge over a six-month period. We found children in the treatment group were more fluent and flexible with number concepts, were better at solving contextual problems, and had better measurement and spatial abilities than children in the control group.

The use of calcium silicate–based sealers (CSSs) is increasing in dentistry as a result of their favorable properties. The inadvertent extrusion of these sealers into the mandibular canal (MC) can result in temporary or permanent neurosensory alterations. Three different recovery outcomes of CSS extrusion into the MC after endodontic treatment of mandibular molars confirmed by cone-beam computed tomographic imaging are described. In Case 1, CSS from the mesiolingual canal of tooth #31 was extruded into the MC during obturation. The patient reported paresthesia. The symptoms of paresthesia were completely resolved by 9 months. In Case 2, CSS from the mesial canals of tooth #30 was extruded into the MC during obturation. A "plasmalike spreading pattern" of the extruded sealer was observed on the radiographs. The patient reported paresthesia and dysesthesia. In addition, the patient complained of hyperalgesia with heat and mechanical allodynia. The symptoms continued to persist during follow-up. At 22 months, the patient still reported persistent paresthesia, hyperalgesia, and mechanical allodynia, affecting the ability to eat. In Case 3, CSS from the distal canal of tooth #31 was extruded into the MC during obturation. The patient did not report any paresthesia or dysesthesia. All 3 patients elected a follow-up approach and monitoring rather than surgical intervention. These cases illustrate the need for the development of guidelines for the management of iatrogenic CSS extrusion into the MC because such an occurrence may result in permanent, temporary, or no neurosensory alterations. [ABSTRACT FROM AUTHOR]

Background: Seasonal Affective Disorder (SAD) is a subtype of Major Depressive Disorder characterized by seasonally occurring depression that often presents with atypical vegetative symptoms such as hypersomnia and carbohydrate craving. It has recently been shown that unlike healthy people, patients with SAD fail to globally downregulate their cerebral serotonin transporter (5-HTT) in winter, and that this effect seemed to be particularly pronounced in female S-carriers of the 5-HTTLPR genotype. The purpose of this study was to identify a 5-HTT brain network that accounts for the adaption to the environmental stressor of winter in females with the short 5-HTTLPR genotype, a specific subgroup previously reported to be at increased risk for developing SAD.Methods: Nineteen females, either S' carriers (LG- and S-carriers) without SAD (N = 13, mean age 23.6 ± 3.2 year, range 19–28) or S' carriers with SAD (N = 6, mean age 23.7 ± 2.4, range 21–26) were PET-scanned with [11C]DASB during both summer and winter seasons (asymptomatic and symptomatic phase, 38 scans in total) in randomized order, defined as a 12-week interval centered on summer or winter solstice. We used a multivariate Partial Least Squares (PLS) approach with NPAIRS split-half cross-validation, to identify and map a whole-brain pattern of 5-HTT levels that distinguished the brains of females without SAD from females suffering from SAD.Results: We identified a pattern of 5-HTT levels, distinguishing females with SAD from those without SAD; it included the right superior frontal gyrus, brainstem, globus pallidus (bilaterally) and the left hippocampus. Across seasons, female S' carriers without SAD showed nominally higher 5-HTT levels in these regions compared to female S' carriers with SAD, but the group difference was only significant in the winter. Female S' carriers with SAD, in turn, displayed robustly increased 5-HTT levels in the ventral striatum (bilaterally), right orbitofrontal cortex, middle frontal gyrus (bilaterally), extending to the left supramarginal gyrus, left precentral gyrus and left postcentral gyrus during winter compared to female S' carriers without SAD.Limitations: The study is preliminary and limited by small sample size in the SAD group (N = 6).Conclusions: These findings provide novel exploratory evidence for a wintertime state-dependent difference in 5-HTT levels that may leave SAD females with the short 5-HTTLPR genotype more vulnerable to persistent stressors like winter. The affected brain regions comprise a distributed set of areas responsive to emotion, voluntary, and planned movement, executive function, and memory. The preliminary findings provide additional insight into the neurobiological components through which the anatomical distribution of serotonergic discrepancies between individuals genetically predisposed to SAD, but with different phenotypic presentations during the environmental stressor of winter, may constitute a potential biomarker for resilience against developing SAD.

The rate of progress in human neurosciences is limited by the inability to easily apply a wide range of analysis methods to the plethora of different datasets acquired in labs around the world. In this work, we introduce a framework for creating, testing, versioning and archiving portable applications for analyzing neuroimaging data organized and described in compliance with the Brain Imaging Data Structure (BIDS). The portability of these applications (BIDS Apps) is achieved by using container technologies that encapsulate all binary and other dependencies in one convenient package. BIDS Apps run on all three major operating systems with no need for complex setup and configuration and thanks to the comprehensiveness of the BIDS standard they require little manual user input. Previous containerized data processing solutions were limited to single user environments and not compatible with most multi-tenant High Performance Computing systems. BIDS Apps overcome this limitation by taking advantage of the Singularity container technology. As a proof of concept, this work is accompanied by 22 ready to use BIDS Apps, packaging a diverse set of commonly used neuroimaging algorithms.

We perceive structure through a process of perceptual organization. Here we report a new perceptual organization phenomenon--the facilitation of visual grouping by global curvature. Observers viewed patterns that they perceived as organized into collections of curves. The patterns were perceptually ambiguous such that the perceived orientation of the patterns varied from trial to trial. When patterns were sufficiently dense and proximity was equated for the predominant perceptual alternatives, observers tended to perceive the organization with the greatest curvature. This effect is tantamount to "visual grouping by maximal curvature" and thus demonstrates an unprecedented effect of global structure on perceptual organization. We account for this result with a model that predicts the perceived organization of a pattern as function of its "nonaccidentality", which we define as the probability that it could have occurred by chance. Our findings demonstrate a novel relationship between the geometry of a pattern and the visual salience of global structure. (Contains 1 table and 4 figures.)

We report on improvements to ACL2 made since the 2013 ACL2 Workshop.

During language acquisition, sighted children have immediate and temporally stable access to the ‘gestalt’ of an object, including particular features that suggest its categorization as part of a class of objects. Blind children, however, must effectively and productively constitute the whole object from its constitutive parts in order to categorize them. While prior studies have suggested that varied experience and appropriate sensory access can contribute to this process, little attention has been given to how this is accomplished. The present study aims to address this issue by using conversation analysis to explore embodied understanding and categorization work between a 26-month-old congenitally blind child and her sighted mother as they play with various animal toys. Here we provide an analysis of a segment involving a particular toy (a cow plush), and ask two questions: (1) During play, how does Mother scaffold embodied routines for the identification of criterial information about a category, and (2) How is knowledge of varied exemplars, not directly accessible within the current activity, then made available to the child? Detailed examination of the linguistic and embodied practices employed by this mother–child dyad provides a concrete example of how non-visual modalities help scaffold the learning of categorization techniques, as well as illustrates the import that the examination of naturally occurring social interaction can have for theories of language and embodied cognition.

Frontotemporal lobar degeneration (FTLD) often presents with asymmetric atrophy. We assessed whether premorbid occupations in FTLD patients were associated with these hemispheric asymmetries. In a multi-center chart review of 588 patients, occupation information was related to location of tissue loss or dysfunction. Patients with atrophy lateralized to the right had professions more dependent on verbal abilities than patients with left-lateralized or symmetrical atrophy. In a subgroup of 96 well-characterized patients with quantified neuroimaging data, the lateralization effect was localized to the temporal lobes and included verbal and mathematical ability. Patients whose professions placed high demands on language and mathematics had relatively preserved left temporal relative to right temporal volumes. Thus, occupation selection occurring in early adulthood is related to lateralized brain asymmetry in patients who develop FTLD decades later in the relatively deficient hemisphere. The finding suggests that verbal and mathematical occupations may have been pursued due to developmental right-lateralized functional impairment that precedes the neurodegenerative process. Alternatively, long-term engagement of activities associated with these occupations contributed to left-lateralized reserve, right-lateralized dysfunction, or both. (Contains 3 tables and 2 figures.)

The hereditary ataxias constitute a group of degenerative diseases that progress over years or decades. With principal pathology involving the cerebellum, dysarthria is an early feature of many of the ataxias. Positron emission tomography was used to study regional cerebral blood flow changes during speech production over a 21 month period in a group of seven right-handed subjects with hereditary ataxia (6 females and 1 male, 3 SCA1 and 4 SCA5, aged 38.3+/-18.9years). The decline in blood flow was greatest in cerebellar regions. In contrast, blood flow actually increased during speech production in the classic speech area (Broca's area) but not in its right-hemisphere homologue at the second evaluation. This increase in cortical flow may have been compensatory for cerebellar degeneration as speech intelligibility did not decline significantly during this period. Compensation was not complete, though, as syllable timing shifted in the direction of equal syllable duration, one of the characteristics of ataxic dysarthria. These results are consistent with previous functional imaging studies of ataxia demonstrating a pattern of brain activity that reflects both loss of function and relative compensation when clinical signs and symptoms are still mild. The combination of disease-relevant tasks, behavioral measurement, and functional imaging may provide insight into the early changes associated with neurodegenerative disease. (Contains 3 tables and 4 figures.)

Objectives: To develop and refine a scale of motivational factors related to healthy weight achievement and maintenance and to examine differences by gender and weight status. Methods: A cross-sectional survey of 300 university students aged 18-24 years. Results: Factor analysis yielded 6 factors--Intrinsic (Cronbach's alpha = 0.73): affective motivation, self-efficacy/interest; Extrinsic (Cronbach's alpha = 0.68): social reward, peer pressure, lack of choice, and authority influence. Males and normal-weight students showed higher affective motivation and overall intrinsic motivation compared to females and overweight students, (P less than 0.001). Conclusion: Intrinsic motivational factors and gender differences should be considered in developing obesity prevention interventions in this age-group.

Formal schooling began centuries before scientists would discover how the brains of children actually learn. Not surprisingly, traditional teaching was often boring and brain antagonistic. But great teachers in every era intuitively recognized what has now been validated by neuroscience: powerful learning is an adventure of the mind. Students, strongly connected to esteemed mentors, engage in novel risk-taking experiences while exploring challenging problems. This article highlights ten key principles from brain science for creating a passion for learning, providing examples from the education of Nobel prize-winning physicist, Richard P. Feynman.

A century ago, John Dewey proposed educating children through a curriculum rich in real-life problem-solving experiences. While many traditional schools have been slow to adopt such methods, experiential learning is making a significant impact in alternative education, youth development, and treatment settings. Challenge and adventure activities create powerful learning environments which fully engage youth and foster the development of courage, resilience, and responsibility. (Contains 1 table.)

The authors conducted 3 experiments to explore the roles of curvature, density, and relative proximity in the perceptual organization of ambiguous dot patterns. To this end, they developed a new family of regular dot patterns that tend to be perceptually grouped into parallel contours, dot-sampled structured grids (DSGs). DSGs are similar to the dot lattices used to study grouping by proximity, except that only one of the potential organizations is rectilinear; the others are curvilinear. The authors used the method of M. Kubovy and J. Wagemans (1995) to study grouping by proximity in DSGs. They found that in the competition between the most likely organizations, one rectilinear and the other curvilinear, the latter is more salient. This phenomenon cannot be explained by contemporary accounts of grouping by proximity or contour integration.

Little is known about obesity and insulin resistance in college students. Leptin is a hormone secreted by fat cells and has been shown to strongly correlate with both obesity and insulin resistance in children and adults. We investigated associations of leptin with insulin secretion and action in 119 normal-weight students aged 18-24 years. Leptin was strongly correlated with total fat mass (r = 0.67, p less than 0.001), percentage body fat (r = 0.81, p less than 0.001), and to a lesser degree Body Mass Index, or BMI, (r = 0.23, p less than 0.02). Leptin was associated with fasting insulin (Beta plus or minus SE = 0.30 plus or minus 0.06, p less than 0.001) and insulin resistance (Beta plus or minus SE = 0.41 plus or minus 0.20, p less than 0.001) independent of total fat, gender, and age, suggesting other mechanisms of leptin and insulin regulation besides obesity. Leptin resistance is present even among young and normal-weight college students. Leptin, even more so than BMI, is an important marker of adiposity and hyperinsulinemia in normal-weight college students and may potentially be used to predict type 2 diabetes. (Contains 2 tables and 1 endnote.)

In contrast to the many studies that have examined parenting in low-income families from a deficit perspective, this study examines their strengths by proposing and testing a model of parenting goals derived from social and developmental theories on goal-orientation, motivation, attachment, and child socialization. The model posits two categories of parenting goals, empathy goals, and socialization goals, as described by Dix (1992), and extends previous theories of parenting, e.g., Darling's and Steinberg's (1993), by suggesting that empathy goals operate more distally to academic achievement, through the mediator of socialization goals. The model, tested in a sample of 220 Head Start pre-schoolers of largely African American descent, suggests that establishing an environment of responsiveness to a child's emotional needs is an important precursor to parents' efforts at improving academic performance. Based on the results of these tests, a number of theoretical and practical implications are offered regarding increasing parental involvement in the early education of low-income children. (Contains 1 figure, 5 tables, and 2 footnotes.)

We report on highlights of the ACL2 enhancements introduced in ACL2 releases since the 2011 ACL2 Workshop. Although many enhancements are critical for soundness or robustness, we focus in this paper on those improvements that could benefit users who are aware of them, but that might not be discovered in everyday practice.

It remains unclear to what extent cerebrovascular burden relates to amyloid beta (Aβ) deposition, neurodegeneration, and cognitive dysfunction in mixed disease populations with small vessel disease and Alzheimer's disease (AD) pathology. In 120 subjects, we investigated the association of vascular burden (white matter hyperintensity [WMH] volumes) with cognition. Using mediation analyses, we tested the indirect effects of WMH on cognition via Aβ deposition (18F‐AV45 positron emission tomography [PET]) and neurodegeneration (cortical thickness or 18F fluorodeoxyglucose PET) in AD signature regions. We observed that increased total WMH volume was associated with poorer performance in all tested cognitive domains, with the strongest effects observed for semantic fluency. These relationships were mediated mainly via cortical thinning, particularly of the temporal lobe, and to a lesser extent serially mediated via Aβ and cortical thinning of AD signature regions. WMH volumes differentially impacted cognition depending on lobar location and Aβ status. In summary, our study suggests mainly an amyloid‐independent pathway in which vascular burden affects cognitive function via localized neurodegeneration. Highlights: Alzheimer's disease often co‐exists with vascular pathology.We studied a unique cohort enriched for high white matter hyperintensities (WMH).High WMH related to cognitive impairment of semantic fluency and executive function.This relationship was mediated via temporo‐parietal atrophy rather than metabolism.This relationship was, to lesser extent, serially mediated via amyloid beta and atrophy. [ABSTRACT FROM AUTHOR]

Background: Cancer is becoming a major cause of mortality in low- and middle-income countries. Unlike infectious disease, malignancy and other chronic conditions require significant supportive infrastructure for diagnostics, staging and treatment. In addition to morphologic diagnosis, diagnostic pathways in oncology frequently require immunohistochemistry (IHC) for confirmation. We present the experience of a tertiary-care hospital serving rural western Kenya, which developed and validated an IHC laboratory in support of a growing cancer care service. Objectives, methods and outcomes: Over the past decade, in an academic North-South collaboration, cancer services were developed for the catchment area of Moi Teaching and Referral Hospital in western Kenya. A major hurdle to treatment of cancer in a resource-limited setting has been the lack of adequate diagnostic services. Building upon the foundations of a histology laboratory, strategic investment and training were used to develop IHC services. Key elements of success in this endeavour included: translation of resource-rich practices to are source-limited setting, such as using manual, small-batch IHC instead of disposable- and maintenance-intensive automated machinery, engagement of outside expertise to develop reagent-efficient protocols and supporting all levels of staff to meet the requirements of an external quality assurance programme. Conclusion: Development of low- and middle-income country models of services, such as the IHC laboratory presented in this paper, is critical for the infrastructure in resource-limited settings to address the growing cancer burden. We provide a low-cost model that effectively develops these necessary services in a challenging laboratory environment.

Deficits in the visual processing of faces in autism spectrum disorder (ASD) individuals may be due to atypical brain organization and function. Studies assessing asymmetric brain function in ASD individuals have suggested that facial processing, which is known to be lateralized in neurotypical (NT) individuals, may be less lateralized in ASD. Here we used functional near-infrared spectroscopy (fNIRS) to first test this theory by comparing patterns of lateralized brain activity in homologous temporal-occipital facial processing regions during observation of faces in an ASD group and an NT group. As expected, the ASD participants showed reduced right hemisphere asymmetry for human faces, compared to the NT participants. Based on recent behavioral reports suggesting that robots can facilitate increased verbal interaction over human counterparts in ASD, we also measured responses to faces of robots to determine if these patterns of activation were lateralized in each group. In this exploratory test, both groups showed similar asymmetry patterns for the robot faces. Our findings confirm existing literature suggesting reduced asymmetry for human faces in ASD and provide a preliminary foundation for future testing of how the use of categorically different social stimuli in the clinical setting may be beneficial in this population.

The last several years have seen major enhancements to ACL2 functionality, largely driven by requests from its user community, including utilities now in common use such as 'make-event', 'mbe', and trust tags. In this paper we provide user-level summaries of some ACL2 enhancements introduced after the release of Version 3.5 (in May, 2009, at about the time of the 2009 ACL2 workshop) up through the release of Version 4.3 in July, 2011, roughly a couple of years later. Many of these features are not particularly well known yet, but most ACL2 users could take advantage of at least some of them. Some of the changes could affect existing proof efforts, such as a change that treats pairs of functions such as 'member' and 'member-equal' as the same function.

Robert Strother1,2, Daniela Matei1–51Department of Medicine, 2Indiana University Melvin and Bren Simon Cancer Center, 3Department of Obstetrics and Gynecology, 4Department of Biochemistry and Molecular Biology, 5VA Roudebush Hospital Indiana University School of Medicine, 535 Barnhill Drive, Indianapolis, IN, 46202Abstract: The encapsulation of doxorubicin in a pegylated liposomal matrix led to a reformulated agent with a different toxicity profile and improved clinical utility. Liposomal doxorubicin is devoid of the cardiac toxicity associated with doxorubicin, but is associated with predictable muco-cutaneous toxicity. The liposomal formulation leads to improved delivery to the target tumor tissue, allowing enhanced uptake by cancer cells. These properties translate into clinical utility in recurrent ovarian cancer as demonstrated by phase II and III trials, this proven clinical efficacy leading to FDA approval in second-line therapy for ovarian cancer. New combinations with cytotoxics, in particular with carboplatin, have demonstrated an acceptable toxicity profile and clinical utility in platinum-sensitive ovarian cancer. A favorable toxicity profile renders liposomal doxorubicin an ideal partner for combination regimens with other cytotoxics, and more recently with biological agents. Such combinations are the subject of ongoing clinical trials.Keywords: ovarian cancer, doxorubicin, liposomes, pegylated liposomal doxorubicin

Local government leaders in the U. S. employ a multitude of programs and policies in the name of economic development to increase the number of firms, employment, wages, and, of course, the tax base. The past few decades have seen a surge in local economic development policies, yet research analyzing their effectiveness is sparse. This study analyzes the relationship between local economic development policy and economic growth in a data set of 412 U. S. cities. Results indicate that policy has only has a weak correlation with economic growth, suggesting that growth is determined more by market conditions rather than government intervention. The article concludes with an entrepreneurial policy approach this author believes may yield development results in an era of limited policy effectiveness.

Neuropsychological tests - behavioral tasks that very commonly involve handwriting and drawing - are widely used in the clinic to detect abnormal brain function. Functional magnetic resonance imaging (fMRI) may be useful in increasing the specificity of such tests. However, performing complex pen-and-paper tests during fMRI involves engineering challenges. Previously, we developed an fMRI-compatible, computerized tablet system to address this issue. However, the tablet did not include visual feedback of hand position (VFHP), a human factors component that may be important for fMRI of certain patient populations. A real-time system was thus developed to provide VFHP and integrated with the tablet in an augmented reality display. The effectiveness of the system was initially tested in young healthy adults who performed various handwriting tasks in front of a computer display with and without VFHP. Pilot fMRI of writing tasks were performed by two representative individuals with and without VFHP. Quantitative analysis of the behavioral results indicated improved writing performance with VFHP. The pilot fMRI results suggest that writing with VFHP requires less neural resources compared to the without VFHP condition, to maintain similar behavior. Thus, the tablet system with VFHP is recommended for future fMRI studies involving patients with impaired brain function and where ecologically valid behavior is important.

BOLD fMRI is sensitive to blood-oxygenation changes correlated with brain function; however, it is limited by relatively weak signal and significant noise confounds. Many preprocessing algorithms have been developed to control noise and improve signal detection in fMRI. Although the chosen set of preprocessing and analysis steps (the "pipeline") significantly affects signal detection, pipelines are rarely quantitatively validated in the neuroimaging literature, due to complex preprocessing interactions. This paper outlines and validates an adaptive resampling framework for evaluating and optimizing preprocessing choices by optimizing data-driven metrics of task prediction and spatial reproducibility. Compared to standard "fixed" preprocessing pipelines, this optimization approach significantly improves independent validation measures of within-subject test-retest, and between-subject activation overlap, and behavioural prediction accuracy. We demonstrate that preprocessing choices function as implicit model regularizers, and that improvements due to pipeline optimization generalize across a range of simple to complex experimental tasks and analysis models. Results are shown for brief scanning sessions (

Unlike mixtures consisting solely of non-Gaussian sources, mixtures including two or more Gaussian components cannot be separated using standard independent components analysis methods that are based on higher order statistics and independent observations. The mixed Independent Components Analysis/Principal Components Analysis (mixed ICA/PCA) model described here accommodates one or more Gaussian components in the independent components analysis model and uses principal components analysis to characterize contributions from this inseparable Gaussian subspace. Information theory can then be used to select from among potential model categories with differing numbers of Gaussian components. Based on simulation studies, the assumptions and approximations underlying the Akaike Information Criterion do not hold in this setting, even with a very large number of observations. Cross-validation is a suitable, though computationally intensive alternative for model selection. Application of the algorithm is illustrated using Fisher's iris data set and Howells' craniometric data set. Mixed ICA/PCA is of potential interest in any field of scientific investigation where the authenticity of blindly separated non-Gaussian sources might otherwise be questionable. Failure of the Akaike Information Criterion in model selection also has relevance in traditional independent components analysis where all sources are assumed non-Gaussian.