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Infant-directed singing is a culturally universal musical phenomenon known to promote the bonding of infants and caregivers. Entrainment is a widely observed physical phenomenon by which diverse physical systems adjust rhythmic activity through interaction. Here we show that the simple act of infant-directed singing entrains infant social visual behavior on subsecond timescales, increasing infants’ looking to the eyes of a singing caregiver: as early as 2 months of age, and doubling in strength by 6 months, infants synchronize their eye-looking to the rhythm of infant-directed singing. Rhythmic entrainment also structures caregivers’ own cueing, enhancing their visual display of social-communicative content: caregivers increase wide-eyed positive affect, reduce neutral facial affect, reduce eye motion, and reduce blinking, all in time with the rhythm of their singing and aligned in time with moments when infants increase their eye-looking. In addition, if the rhythm of infant-directed singing is experimentally disrupted—reducing its predictability—then infants’ time-locked eye-looking is also disrupted. These results reveal generic processes of entrainment as a fundamental coupling mechanism by which the rhythm of infant-directed singing attunes infants to precisely timed social-communicative content and supports social learning and development.

To better understand early brain development in health and disorder, it is critical to accurately segment infant brain magnetic resonance (MR) images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF). Deep learning-based methods have achieved state-of-the-art performance; h owever, one of the major limitations is that the learning-based methods may suffer from the multi-site issue, that is, the models trained on a dataset from one site may not be applicable to the datasets acquired from other sites with different imaging protocols/scanners. To promote methodological development in the community, the iSeg-2019 challenge ( http://iseg2019.web.unc.edu ) provides a set of 6-month infant subjects from multiple sites with different protocols/scanners for the participating methods. T raining/validation subjects are from UNC (MAP) and testing subjects are from UNC/UMN (BCP), Stanford University, and Emory University. By the time of writing, there are 30 automatic segmentation methods participated in the iSeg-2019. In this article, 8 top-ranked methods were reviewed by detailing their pipelines/implementations, presenting experimental results, and evaluating performance across different sites in terms of whole brain, regions of interest, and gyral landmark curves. We further pointed out their limitations and possible directions for addressing the multi-site issue. We find that multi-site consistency is still an open issue. We hope that the multi-site dataset in the iSeg-2019 and this review article will attract more researchers to address the challenging and critical multi-site issue in practice.

BackgroundThe 3q29 deletion (3q29Del) is a copy number variant (CNV) with the highest known effect size for psychosis-risk (>40-fold increased risk). Systematic research on this CNV offers promising avenues for identifying mechanisms underlying psychosis and related disorders. Relative to other high-impact CNVs like 22q11.2Del, far less is known about the phenotypic presentation and pathophysiology of 3q29Del. Emerging findings indicate that posterior fossa abnormalities are common among 3q29Del carriers; however, their clinical relevance is unknown.MethodsHere, we report the first in-depth evaluation of psychotic symptoms in study participants with 3q29Del (N=23), using the Structured Interview for Psychosis-Risk Syndromes (SIPS), and compare to SIPS data from 22q11.2Del participants (N=31) and healthy controls (N=279). We also investigate the relationship between psychotic symptoms, cerebellar morphology, and cystic/cyst-like malformations of the posterior fossa in 3q29Del by structural brain imaging.ResultsCumulatively, 48% of the 3q29Del sample exhibited a psychotic disorder (N=4) or attenuated positive symptoms (N=7), with three individuals with attenuated symptoms meeting the frequency and timing criteria for clinical high risk for psychosis. Males with 3q29Del scored higher in negative symptoms than females. 3q29Del participants had more severe ratings than controls on all domains and exhibited less severe negative symptoms than 22q11.2Del participants. An inverse relationship was identified between positive symptom severity and cerebellar cortex volume in 3q29Del, while cystic/cyst-like malformations yielded no clinical link with psychosis.ConclusionsOverall, our findings establish the unique and shared profiles of psychotic symptoms across two CNVs and highlight cerebellar involvement in elevated psychosis-risk in 3q29Del.

BackgroundHigh-impact genetic variants associated with neurodevelopmental disorders provide biologically defined entry points for etiological discovery. The 3q29 deletion (3q29Del) is one such variant that confers a ∼40-fold increased risk for schizophrenia, and a ∼30-fold increased risk for autism. However, the specific neural mechanisms underlying this link remain largely unknown.MethodsHere, we report the first in vivo quantitative neuroimaging study in 3q29Del individuals (N=24) and healthy controls (N=1,608) using structural MRI. Given prior reports of posterior fossa abnormalities in 3q29Del, we focus our investigation on the cerebellum and its primary tissue-types. Additionally, we compare the prevalence of cystic/cyst-like malformations of the posterior fossa between 3q29Del participants and controls, and examine the association between neuroanatomical findings and standardized behavioral measures to probe gene-brain-behavior relationships.Results3q29Del participants had smaller cerebellar cortex volumes than controls, both before and after correction for intracranial volume (ICV). 3q29Del participants also had larger cerebellar white matter volumes than controls following ICV-correction. The 3q29Del group displayed an elevated rate of posterior fossa arachnoid cysts and mega cisterna magna findings independent of cerebellar volume. Sex played a moderating role in a subset of findings. Cerebellar white matter volume was positively associated with visual-motor integration skills and cognitive ability, while cystic/cyst-like malformations yielded no behavioral link.ConclusionsAbnormal development of posterior fossa structures may represent neuroimaging-based biomarkers in 3q29Del. Results reveal cerebellar associations with sensorimotor and cognitive deficits in 3q29Del and present a novel point of genetic convergence with cerebellar pathology reported in idiopathic forms of neurodevelopmental disease.

Purpose To understand the consequences of the 3q29 deletion on medical, neurodevelopmental, psychiatric, brain structural, and neurological sequalae by systematic evaluation of affected individuals. To develop evidence-based recommendations using these data for effective clinical care. Methods Thirty-two individuals with the 3q29 deletion were evaluated using a defined phenotyping protocol and standardized data collection instruments. Results Medical manifestations were varied and reported across nearly every organ system. The most severe manifestations were congenital heart defects (25%) and the most common were gastrointestinal symptoms (81%). Physical examination revealed a high proportion of musculoskeletal findings (81%). Neurodevelopmental phenotypes represent a significant burden and include intellectual disability (34%), autism spectrum disorder (38%), executive function deficits (46%), and graphomotor weakness (78%). Psychiatric illness manifests across the lifespan with psychosis prodrome (15%), psychosis (20%), anxiety disorders (40%), and attention deficit–hyperactivity disorder (ADHD) (63%). Neuroimaging revealed structural anomalies of the posterior fossa, but on neurological exam study subjects displayed only mild or moderate motor vulnerabilities. Conclusion By direct evaluation of 3q29 deletion study subjects, we document common features of the syndrome, including a high burden of neurodevelopmental and neuropsychiatric phenotypes. Evidence-based recommendations for evaluation, referral, and management are provided to help guide clinicians in the care of 3q29 deletion patients.

Eye-blinking has emerged as a promising means of measuring viewer engagement with visual content. This method capitalizes on the fact that although we remain largely unaware of our eye-blinking in everyday situations, eye-blinks are inhibited at precise moments in time so as to minimize the loss of visual information that occurs during a blink. Probabilistically, the more important the visual information is to the viewer, the more likely he or she will be to inhibit blinking. In the present study, viewer engagement was experimentally manipulated in order to: (1) replicate past studies suggesting that a group of viewers will blink less often when watching content that they perceive as more important or relevant; (2) test the reliability of the measure by investigating constraints on the timescale over which blink rate patterns can be used to accurately quantify viewer engagement; and (3) examine whether blink rate patterns can be used to quantify what an individual – as opposed to a group of viewers—perceives as engaging. Results demonstrate that blink rate patterns can be used to measure changes in individual and group engagement that unfold over relatively short (1 second) and long (60 second) timescales. However, for individuals with lower blink rates, blink rate patterns may provide less optimal measures when engagement shifts rapidly (at intervals of 1 second or less). Findings support the use of eye-blink measures in future studies investigating a person’s subjective perception of how engaging a stimulus is.

Although a large body of research has identified discrete neuroanatomical regions involved in social cognition and behavior (the "social brain"), the existing findings are based largely on studies of specific brain structures defined within the context of particular tasks or for specific types of social behavior. The objective of the current work was to view these regions as nodes of a larger collective network and to quantitatively characterize both the topology of that network and the relative criticality of its many nodes. Large-scale data mining was performed to generate seed regions of the social brain. High-quality diffusion MRI data of typical adults were used to map anatomical networks of the social brain. Network topology and nodal centrality were analyzed using graph theory. The structural social brain network demonstrates a high degree of global functional integration with strong local segregation. Bilateral dorsomedial prefrontal cortices and amygdala play the most central roles in the network. Strong probabilistic evidence supports modular divisions of the social brain into subnetworks bearing good resemblance to functionally classified clusters. The present network-driven approach quantifies the structural topology of the social brain as a whole. This work can serve as a critical benchmark against which to compare (1) developmental change in social brain topology over time (from infancy through adolescence and beyond) and (2) atypical network topologies that may be a sign or symptom of disorder (as in conditions such as autism, Williams syndrome, schizophrenia, and others).

Within the context of early infant–caregiver interaction, we review a series of pivotal transitions that occur within the first 6 months of typical infancy, with emphasis on behavior and brain mechanisms involved in preferential orientation towards, and interaction with, other people. Our goal in reviewing these transitions is to better understand how they may lay a necessary and/or sufficient groundwork for subsequent phases of development, and also to understand how the breakdown thereof, when development is atypical and those transitions become derailed, may instead yield disability. We review these developmental processes in light of recent studies documenting disruptions to early-emerging brain and behavior mechanisms in infants later diagnosed with autism spectrum disorder, shedding light on the brain–behavior pathogenesis of autism.

Background Nursing interruptions are a costly and dangerous variable in acute care hospitals. Malfunctioning technology equipment interrupts nursing care and prevents full utilization of computer safety systems to prevent patient care errors. Aims This paper identifies an innovative approach to nursing interruptions related to computer and computer cart malfunctions. The impact on human resources is defined and outcome measures were proposed. A multifaceted proposal, based on a literature review, aimed at reducing nursing interruptions is presented. This proposal is expected to increase patient safety, as well as patient and nurse satisfaction. Setting Acute care hospitals utilizing electronic medical records and bar-coded medication administration technology. Participants Nurses, information technology staff, nursing informatics staff, and all leadership teams affected by technology problems and their proposed solutions. Methods Literature from multiple fields was reviewed to evaluate research related to computer/computer cart failures, and the approaches used to resolve these issues. Results Outcome measured strategic goals related to patient safety, and nurse and patient satisfaction. Specific help desk metrics will demonstrate the effect of interventions. Conclusions This paper addresses a gap in the literature and proposes practical and innovative solutions. A comprehensive computer and computer cart repair program is essential for patient safety, financial stewardship, and utilization of resources.

Preferential attention to biological motion is an early-emerging mechanism of adaptive action that plays a critical role in social development. The present study provides a comprehensive longitudinal mapping of developmental change in preferential attention to biological motion in 116 infants at 7 longitudinal time points. Tested repeatedly from 2 until 24 months of age, results reveal that preferential attention to biological motion changes considerably during the first months of life. Previously reported preferences in both neonates and older infants are absent in the second month but do reemerge by month 3 and become increasingly pronounced during the subsequent two years. These results highlight the second month of life as a potentially critical transition period in social visual engagement.

While decades of research have demonstrated that a region of the right fusiform gyrus (FG) responds selectively to faces, a second line of research suggests that the FG responds to a range of animacy cues, including biological motion and goal-directed actions, even in the absence of faces or other human-like surface features. These findings raise the question of whether the FG is indeed sensitive to faces or to the more abstract category of animate agents. The current study uses fMRI to examine whether the FG responds to all faces in a category-specific way or whether the FG is especially sensitive to the faces of animate agents. Animate agents are defined here as intentional agents with the capacity for rational goal-directed actions. Specifically, we examine how the FG responds to an entity that looks like an animate agent but that lacks the capacity for goal-directed, rational action. Region-of-interest analyses reveal that the FG activates more strongly to the animate compared with the inanimate entity, even though the surface features of both animate and inanimate entities were identical. These results suggest that the FG does not respond to all faces in a category-specific way, and is instead especially sensitive to whether an entity is animate.

Decades of research have demonstrated that a region of the right fusiform gyrus (FG) and right posterior superior temporal sulcus (pSTS) responds preferentially to static faces and biological motion, respectively. Despite this view, both regions activate in response to both stimulus categories and to a range of other stimuli, such as goal-directed actions, suggesting that these regions respond to characteristics of animate agents more generally. Here we propose a neural model for animacy detection composed of processing streams that are initially differentially sensitive to cues signaling animacy, but that ultimately act in concert to support reasoning about animate agents. We use dynamic causal modeling, a measure of effective connectivity, to demonstrate that the directional flow of information between the FG and pSTS is initially dependent on the characteristics of the animate agent presented, a key prediction of our proposed network for animacy detection.

How does the brain’s response to speech change over the first months of life? Although behavioral findings indicate that neonates’ listening biases are sharpened over the first months of life, with a species-specific preference for speech emerging by 3 months, the neural substrates underlying this developmental change are unknown. We examined neural responses to speech compared with biological non-speech sounds in 1- to 4-month-old infants using fMRI. Infants heard speech and biological non-speech sounds, including heterospecific vocalizations and human non-speech. We observed a left-lateralized response in temporal cortex for speech compared to biological non-speech sounds, indicating that this region is highly selective for speech by the first month of life. Specifically, this brain region becomes increasingly selective for speech over the next 3 months as neural substrates become less responsive to non-speech sounds. These results reveal specific changes in neural responses during a developmental period characterized by rapid behavioral changes.

Achieving a mechanistic explanation of brain function requires understanding causal relationships among regions. A relatively new technique to assess effective connectivity in fMRI data is Dynamic Causal Modeling (DCM). As DCM is more frequently used, it becomes increasingly important to further validate the technique and understand its limitations. With DCM, Bayesian Model Selection (BMS) is used to select the most likely causal model. We conducted simulations to test the degree to which BMS is robust to two types of challenges when applied to DCMs, those inherent to data (Category 1) and those inherent to model space (Category 2). Category 1 challenges tested properties of the data (low signal-to-noise, different response magnitudes and shapes across regions) that could either blur the distinction between models or potentially bias model selection. These challenges are impossible or difficult to measure and control in real data, so investigating their effect upon BMS through simulation is critical. Category 2 challenges tested properties of model space that create subsets of confusable models. Our results suggest that given data that conform to the prior assumptions of DCM, BMS is robust to challenges from Category 1. However, in the face of Category 2 challenges (when a more homogenous model space was tested) the false positive rate rose above an acceptable level. We show that such errors are neither trivial nor easily avoided with existing approaches. However, we argue that it is possible to detect Category 2 challenges, and avoid inappropriate interpretations by conducting simulations prior to applying DCM.AcronymsDCMDynamic Causal ModelingBMSBayesian Model SelectionfMRIfunctional magnetic resonance imagingBOLDblood oxygen level dependentFMCFamily Model ComparisonHRFhemodynamic response functionROIregion of interestSNRsignal to noise ratioR1region 1R2region 2U1input 1

Spontaneous eye blinking serves a critical physiological function, but it also interrupts incoming visual information. This tradeoff suggests that the inhibition of eye blinks might constitute an adaptive reaction to minimize the loss of visual information, particularly information that a viewer perceives to be important. To test this hypothesis, we examined whether the timing of blink inhibition, during natural viewing, is modulated between as well as within tasks, and also whether the timing of blink inhibition varies as a function of viewer engagement and stimulus event type. While viewing video scenes, we measured the timing of blinks and blink inhibition, as well as visual scanning, in a group of typical two-year-olds, and in a group of two-year-olds known for attenuated reactivity to affective stimuli: toddlers with Autism Spectrum Disorders (ASD). Although both groups dynamically adjusted the timing of their blink inhibition at levels greater than expected by chance, they inhibited their blinking and shifted visual fixation differentially with respect to salient onscreen events. Moreover, typical toddlers inhibited their blinking earlier than toddlers with ASD, indicating active anticipation of the unfolding of those events. These findings indicate that measures of blink inhibition can serve as temporally precise markers of perceived stimulus salience and are useful quantifiers of atypical processing of social affective signals in toddlers with ASD.

The conditions under which we identify entities as animate agents and the neural mechanisms supporting this ability are central questions in social neuroscience. Prior studies have focused upon 2 perceptual cues for signaling animacy: 1) surface features representing body forms such as faces, torsos, and limbs and 2) motion cues associated with biological forms. Here, we consider a third cue--the goal-directedness of an action. Regions in the social brain network, such as the right posterior superior temporal sulcus (pSTS) and fusiform face area (FFA), are activated by human-like motion and body form perceptual cues signaling animacy. Here, we investigate whether these same brain regions are activated by goal-directed motion even when performed by entities that lack human-like perceptual cues. We observed an interaction effect whereby the presence of either human-like perceptual cues or goal-directed actions was sufficient to activate the right pSTS and FFA. Only stimuli that lacked human-like perceptual cues and goal-directed actions failed to activate the pSTS and FFA at the same level.

The expression of autism spectrum disorder (ASD) is highly heterogeneous, owing to the complex interactions between genes, the brain, and behavior throughout development. Here we present a model of ASD that implicates an early and initial failure to develop the specialized functions of one or more of the set of neuroanatomical structures involved in social information processing (i.e., the 'social brain'). From this early and primary disruption, abnormal brain development is canalized because the individual with an ASD must develop in a highly social world without the specialized neural systems that would ordinarily allow him or her to partake in the fabric of social life, which is woven from the thread of opportunities for social reciprocity and the tools of social engagement. This brain canalization gives rise to other characteristic behavioral deficits in ASD including deficits in communication, restricted interests, and repetitive behaviors. We propose that focused efforts to explore the brain mechanisms underlying the core, pathognomic deficits in the development of mechanisms for social engagement in ASD will greatly elucidate our understanding and treatment of this complex, devastating family of neurodevelopmental disorders. In particular, developmental studies (i.e., longitudinal studies of young children with and without ASD, as well as infants at increased risk for being identified with ASD) of the neural circuitry supporting key aspects of social information processing are likely to provide important insights into the underlying components of the full-syndrome of ASD. These studies could also contribute to the identification of developmental brain endophenotypes to facilitate genetic studies. The potential for this kind of approach is illustrated via examples of functional neuroimaging research from our own laboratory implicating the posterior superior temporal sulcus (STS) as a key player in the set of neural structures giving rise to ASD.

Functional magnetic resonance imaging of brain responses to biological motion in children with autism spectrum disorder (ASD), unaffected siblings (US) of children with ASD, and typically developing (TD) children has revealed three types of neural signatures: ( i ) state activity, related to the state of having ASD that characterizes the nature of disruption in brain circuitry; ( ii ) trait activity, reflecting shared areas of dysfunction in US and children with ASD, thereby providing a promising neuroendophenotype to facilitate efforts to bridge genomic complexity and disorder heterogeneity; and ( iii ) compensatory activity, unique to US, suggesting a neural system–level mechanism by which US might compensate for an increased genetic risk for developing ASD. The distinct brain responses to biological motion exhibited by TD children and US are striking given the identical behavioral profile of these two groups. These findings offer far-reaching implications for our understanding of the neural systems underlying autism.

Human infants show a preference for listening to speech, but little is known about how infants listen to other naturally occurring sounds. Here, we test infants' listening bias for speech against a range of naturally occurring sounds that share properties of speech to varying extents and we aim to better characterize the speech properties that attract infant attention. We compared 3-month-olds' listening patterns for five types of sounds: nonnative speech, rhesus macaque vocalizations, human noncommunicative vocalizations, human communicative nonspeech vocalizations, and environmental sounds. Across three experiments, 3-month-olds preferred speech to the other four types of sounds. The set of acoustic properties we measured—pitch, peak amplitude, nonzero-root mean square amplitude, frequency difference and amplitude variance—did not predict infant looking time. Our results demonstrate that young infants attend selectively to speech over many other naturally occurring stimuli, an important tool for learnin...

From the first moments of life, typically developing infants perceive social stimuli as relatively more salient than other competing stimuli. Through ongoing cycles of seeking and acting upon such stimuli, infants transform their understanding of the social world, leading to increasingly refined social abilities and specialized brain circuitry for social processing. By contrast, diminished interest in a wide variety of adaptive social stimuli is a pervasive, early emerging, and enduring feature of autism spectrum disorder (ASD). Reduced attention to such stimuli exerts a compounding influence on development as a child with ASD fails to accrue an increasingly longer list of social experiences that would otherwise play a foundational role in social development and functional brain specialization. In this chapter, we review the canalizing role of preferential attention to social stimuli on behavior and brain development in typical infancy. We also review what is known about the early development of infants who are later diagnosed with ASD, with a focus on early departures from normative developmental trajectories of social visual engagement. We focus primarily on visual attention to the eyes of others as a paradigmatic example of an early emerging foundational social ability, that, when disrupted, is both a marker of emerging social disability and a compounding influence on subsequent development. Finally, we examine the accumulative consequences of departures from normative developmental trajectories of social visual engagement, as children with ASD develop increasingly greater specialization in things other than the social world.

The levels of social impairment experienced by different individuals with autism spectrum disorder strongly correlate with the degrees of dysfunction within each individual’s superior temporal sulcus (STS), a key region in social perception, in general, and in the perception of biological motion, in specific. From a developmental perspective, while STS responsiveness becomes increasingly selective for human movement in typical children, observers with autism show less selective tuning. Brain imaging research is reviewed that supports an interactive development model of the social brain and social perception.

Processing the vocalizations of conspecifics is critical for adaptive social interaction. A species-specific voice-selective region has been identified in the right STS that responds more strongly to human vocal sounds compared with a variety of nonvocal sounds. However, the STS also activates in response to a wide range of signals used in communication, such as eye gaze, biological motion, and speech. These findings raise the possibility that the voice-selective region of the STS may be especially sensitive to vocal sounds that are communicative, rather than to all human vocal sounds. Using fMRI, we demonstrate that the voice-selective region of the STS responds more strongly to communicative vocal sounds (such as speech and laughter) compared with noncommunicative vocal sounds (such as coughing and sneezing). The implications of these results for understanding the role of the STS in voice processing and in disorders of social communication, such as autism spectrum disorder, are discussed.

The expression of autism spectrum disorder (ASD) is highly heterogeneous, owing to the complex interactions between genes, the brain, and behavior throughout development. Here we present a model of ASD that implicates an early and initial failure to develop the specialized functions of one or more of the set of neuroanatomical structures involved in social information processing (i.e., the 'social brain'). From this early and primary disruption, abnormal brain development is canalized because the individual with an ASD must develop in a highly social world without the specialized neural systems that would ordinarily allow him or her to partake in the fabric of social life, which is woven from the thread of opportunities for social reciprocity and the tools of social engagement. This brain canalization gives rise to other characteristic behavioral deficits in ASD including deficits in communication, restricted interests, and repetitive behaviors. We propose that focused efforts to explore the brain mechanisms underlying the core, pathognomic deficits in the development of mechanisms for social engagement in ASD will greatly elucidate our understanding and treatment of this complex, devastating family of neurodevelopmental disorders. In particular, developmental studies (i.e., longitudinal studies of young children with and without ASD, as well as infants at increased risk for being identified with ASD) of the neural circuitry supporting key aspects of social information processing are likely to provide important insights into the underlying components of the full-syndrome of ASD. These studies could also contribute to the identification of developmental brain endophenotypes to facilitate genetic studies. The potential for this kind of approach is illustrated via examples of functional neuroimaging research from our own laboratory implicating the posterior superior temporal sulcus (STS) as a key player in the set of neural structures giving rise to ASD.

ADME-Tox testing examines the effects of an organism, tissue or cell on a compound, as well as the effects that the compound has on an organism, tissue or cell, and has gained in importance in the overall drug discovery process over the past twenty years. This is due to the rising percentage of drug candidate attrition in the 1990s and early 2000s due to adverse ADME/Tox profiles. The increased importance placed upon ADME/Tox testing has brought about new types of in-vitro assay technologies utilizing microplates to deliver the most pharmacologically relevant data. These tests, however, have typically been performed sequentially, where multiple assays over multiple microplates are used. This typically leads to increased time and cost required to generate the required information, and can sacrifice data quality. Multiplexed assays, however, where more than one piece of data can be attained from a single well or a single microplate, performed using appropriate liquid handling and detection instrumentation, can improve data quality and reduce the time and expense required to attain this information.

Prior studies have demonstrated that the posterior superior temporal sulcus (pSTS) is involved in analyzing the intentions underlying actions and is sensitive to the context within which actions occur. However, it is debated whether the pSTS is actually sensitive to goals underlying actions, or whether previous studies can be interpreted to suggest that the pSTS is instead involved in the allocation of visual attention towards unexpected events. In addition, little is known about whether the pSTS is specialized for reasoning about the actions of social agents or whether the pSTS is sensitive to the actions of both animate and inanimate entities. Here, using functional magnetic resonance imaging, we investigated activation in response to passive viewing of successful and unsuccessful animate and inanimate goal-directed actions. Activation in the right pSTS was stronger in response to failed actions compared to successful actions, suggesting that the pSTS plays a role in encoding the goals underlying actions. Activation in the pSTS did not differentiate between animate and inanimate actions, suggesting that the pSTS is sensitive to the goal-directed actions of both animate and inanimate entities.

The determination of inhibitory effects that lead compounds have on cytochrome P450 (CYP) ezymes is an important part of today's drug discovery process. Assays can be performed early in the discovery process to predict adverse drug—drug interactions caused by CYP inhibition and to minimize the costs associated with terminating candidates in late stage development or worse, removing a drug from the market after launch. For early discovery work, testing substantial numbers of compounds is desirable, thus automated “mix and read” assays are beneficial. Here, we demonstrate the automation of the CYP profiling process using a simple, yet robust robotic platform. Compound titration, as well as transfer of compounds and assay components was performed by the same automated pipetting system. IC50s of small molecule drugs were determined using recombinant CYP enzymes, CYP3A4, −2C9, and −2D6 and luminogenic substrates specific to each. Compounds were profiled against all three enzymes on the same 384-well assay plate.

Hospitals continue to experience high nurse turnover rates. Based on the need to retain skilled nurses, differences in job satisfaction of experienced medical-surgical and critical care nurses were examined.