Resistance and Tolerance Screening of Spring Wheat Cultivars to Cereal Cyst Nematode (Heterodera avenae) in Southeastern Idaho.

Increased populations of Heterodera avenae in southeastern Idaho are associated with increased planting of susceptible cereal cultivars and lack of crop rotation. Identifying high-yield, resistant spring wheat cultivars with tolerance requires testing new genotypes and susceptibility assessments of marketed cultivars. We conducted two experiments to determine whether cultivars with putative resistance could maintain acceptable yield in the presence of H. avenae. We also evaluated the tolerance response in relation to previously tested cultivars. Seven spring wheat cultivars were planted in two irrigated commercial fields that were naturally infested with high populations of H. avenae. Measures of resistance, tolerance, and grain yield were assessed in aldicarb-treated versus nontreated plots. In aldicarb-treated plots in both years, grain yield of the susceptible cultivars Snow Crest, WestBred 936, WB9411, Patwin-515, and WB9668 was significantly increased. The expected yield increase with aldicarb was limited for the moderately susceptible Expresso due to water stress. 'WB-Rockland', carrying the Cre5 resistance gene, maintained its standard yield, while none of the other cultivars in the experiment showed resistance or tolerance. Our results indicated that aldicarb improves wheat grain yield in irrigated crop production systems, and although removed from the market, it is effective and has utility for research. The results also support the hypothesis that high yield susceptible cultivars can mask the effect of H. avenae on grain yield when managed appropriately.

Adaptation and validation of a computerized neurocognitive battery in the Xhosa of South Africa.

OBJECTIVE: Large-scale studies have revolutionized biomedical research, and neurocognitive tests can help elucidate the biological basis of neuropsychiatric diseases. However, studies have predominantly been conducted in Western settings. We describe the development and validation of a computerized battery (PennCNB) with the Xhosa population of South Africa. METHOD: Individuals with schizophrenia (n = 525) and a normative comparison group (n = 744) were balanced on age, sex, education, and region. Participants provided blood samples, were assessed psychiatrically, and were administered a PennCNB translation to isiXhosa, including measures of executive functions, episodic memory, complex cognition, social cognition, and sensorimotor speed. Feasibility was examined with test completion rates and input from administrators, and psychometric structural validity and associations with clinical and demographic characteristics were examined. RESULTS: Tests were well tolerated by participants, as >87% had one (or fewer) test missing. Results suggested a similar factor structure to prior PennCNB studies in Western contexts, and expected age and sex effects were apparent. Furthermore, a similar profile of schizophrenia was observed, with neurocognitive deficits most pronounced for executive functions, especially attention, as well as memory, social cognition, and motor speed relative to complex cognition and sensorimotor speed. CONCLUSIONS: Results support the feasibility of implementing a culturally adapted computerized neurocognitive battery in sub-Saharan African settings and provide evidence supporting the concurrent validity of the translated instrument. Thus, the PennCNB is implementable on a large scale in non-Western contexts, shows expected factor structure, and can detect cognitive deficits associated with neuropsychiatric disorders. Obtaining valid measures of cognition by nonspecialized proctors is especially suitable in resource-limited settings, where traditional testing is prohibitive. Future work should establish normative standards, test-retest reliability, and sensitivity to treatment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Fate and Management of Incompletely Excised Solitary Fibrous Tumor of the Orbit: A Case Series and Literature Review.

PURPOSE: There is an imperfect correlation between the histology and behavior of solitary fibrous tumor (SFT). In addition, recurrence is common, and dedifferentiation may occur over time. Preferred primary treatment is intact excision, but friable pseudocapsules and tenacious attachments can thwart this goal in the crowded, visually sensitive orbit. This study addresses the fate and appropriate management of incompletely excised orbital SFT. METHODS: Among a single surgeon's 7-case experience with orbital SFT, 3 cases involved incomplete primary excision, either before (2 cases) or after (1 case) referral. We reviewed the clinicopathologic data in these 3 cases, with follow-up intervals of 18, 21, and 52 years after initial presentation. We reviewed the English-language literature on SFT, with special attention to evolving nomenclature, orbital involvement, recurrence, malignant transformation, and management options. RESULTS: Benign versus malignant designations of SFT vary with histological and behavioral criteria. Approximately 150 orbital cases have been reported. Published rates of primary malignancy and recurrence across all histologic categories are 6% to 12% and 30% to 37%, respectively. We identified 43 well-documented recurrences (range, 6 months-33 years; median, 3 years) and 10 cases of histological dedifferentiation (range, 14 months-33 years). Because of SFT's rarity and needed follow-up intervals, the value of adjuvant therapy is not yet proven. In follow up of 18, 21, and 52 years after initial presentation, our 3 cases with incomplete excision showed either no recurrence (Case 1) or no morphological dedifferentiation (Cases 2, 3). CONCLUSION: A treatment algorithm is predicated on the completeness of surgical excision and histological features. However, we recommend case-by-case multidisciplinary decisions in a tumor-board setting.

Photoperiodic effects on monoamine signaling and gene expression throughout development in the serotonin and dopamine systems.

Photoperiod or the duration of daylight has been implicated as a risk factor in the development of mood disorders. The dopamine and serotonin systems are impacted by photoperiod and are consistently associated with affective disorders. Hence, we evaluated, at multiple stages of postnatal development, the expression of key dopaminergic (TH) and serotonergic (Tph2, SERT, and Pet-1) genes, and midbrain monoamine content in mice raised under control Equinox (LD 12:12), Short winter-like (LD 8:16), or Long summer-like (LD 16:8) photoperiods. Focusing in early adulthood, we evaluated the midbrain levels of these serotonergic genes, and also assayed these gene levels in the dorsal raphe nucleus (DRN) with RNAScope. Mice that developed under Short photoperiods demonstrated elevated midbrain TH expression levels, specifically during perinatal development compared to mice raised under Long photoperiods, and significantly decreased serotonin and dopamine content throughout the course of development. In adulthood, Long photoperiod mice demonstrated decreased midbrain Tph2 and SERT expression levels and reduced Tph2 levels in the DRN compared Short photoperiod mice. Thus, evaluating gene × environment interactions in the dopaminergic and serotonergic systems during multiple stages of development may lead to novel insights into the underlying mechanisms in the development of affective disorders.

Impact of a Non-small Cell Lung Cancer Educational Program for Interdisciplinary Teams.

BACKGROUND: Successful implementation of non-small cell lung cancer (NSCLC) evidence-based guideline recommendations requires effective educational programs that target all clinicians from interdisciplinary teams. This study describes and evaluates the Engaging an Interdisciplinary Team for NSCLC (GAIN 3.0) experiential learning-based educational curriculum. METHODS: GAIN 3.0 was designed to enhance interdisciplinary collaboration for effective NSCLC diagnosis, assessment, and treatment. The program used a flipped classroom model that included an e-learning component prior to a live 6-hour interactive program. The interactive program included hands-on simulations, small group workshops, gamification, and case discussions. Participants included academic and community members of multidisciplinary lung cancer teams. Assessments included an online baseline survey, a pretest and posttest, a program evaluation, a long-term survey (LTS), and on-site faculty evaluation of participants. RESULTS: Of 416 attendees to 13 live GAIN 3.0 programs (nine in the United States and four in Europe), 304 (73%) completed the pretest and 187 (45%) completed the posttest. Out of a perfect score of 12 points, program participants had a mean test score of 6.3 ± 2.1 on the pretest (52%) and 7.8 ± 2.1 on the posttest (65%) (P = .03). There was an overall knowledge increase of 13% from pretest to posttest. Most LTS respondents (65%) rated the GAIN 3.0 live programs as "high impact." On the LTS, the areas with the greatest gains in participants who had very high confidence were communication across disciplines, use of a team-based approach, and personalized treatment. CONCLUSIONS: GAIN 3.0 was a highly successful interdisciplinary activity that improved participants' knowledge, competence, and likely the clinical care provided to patients with NSCLC.

Is dopamine transporter-mediated dopaminergic signaling in the retina a noninvasive biomarker for attention-deficit/ hyperactivity disorder? A study in a novel dopamine transporter variant Val559 transgenic mouse model.

BACKGROUND: Dopamine (DA) is a critical neuromodulator in the retina. Disruption of retinal DA synthesis and signaling significantly attenuates light-adapted, electroretinogram (ERG) responses, as well as contrast sensitivity and acuity. As these measures can be detected noninvasively, they may provide opportunities to detect disease processes linked to perturbed DA signaling. Recently, we identified a rare, functional DA transporter (DAT, SLC6A3) coding substitution, Ala559Val, in subjects with attention-deficit/hyperactivity disorder (ADHD), demonstrating that DAT Val559 imparts anomalous DA efflux (ADE) with attendant physiological, pharmacological, and behavioral phenotypes. To understand the broader impact of ADE on ADHD, noninvasive measures sensitive to DAT reversal are needed. METHODS: Here, we explored this question through ERG-based analysis of retinal light responses, as well as HPLC measurements of retinal DA in DAT Val559 mice. RESULTS: Male mice homozygous (HOM) for the DAT Val559 variant demonstrated increased, light-adapted ERG b-wave amplitudes compared to wild type (WT) and heterozygous (HET) mice, whereas dark-adapted responses were indistinguishable across genotypes. The elevated amplitude of the photopic light responses in HOM mice could be mimicked in WT mice by applying D1 and D4 DA receptor agonists and suppressed in HOM mice by introducing D4 antagonist, supporting elevated retinal DA signaling arising from ADE. Following the challenge with amphetamine, WT exhibited an increase in light-adapted response amplitudes, while HOM did not. Total retinal DA content was similar across genotypes. Interestingly, female DAT Val559 HOM animals revealed no significant difference in photopic ERG responses when compared with WT and HET littermates. CONCLUSIONS: These data reveal that noninvasive, in vivo evaluation of retinal responses to light can reveal physiological signatures of ADE, suggesting a possible approach to the segregation of neurobehavioral disorders based on the DAT-dependent control of DA signaling.

Validation of the Cognition Test Battery for Spaceflight in a Sample of Highly Educated Adults.

BACKGROUND: Neuropsychological changes that may occur due to the environmental and psychological stressors of prolonged spaceflight motivated the development of the Cognition Test Battery. The battery was designed to assess multiple domains of neurocognitive functions linked to specific brain systems. Tests included in Cognition have been validated, but not in high-performing samples comparable to astronauts, which is an essential step toward ensuring their usefulness in long-duration space missions. METHODS: We administered Cognition (on laptop and iPad) and the WinSCAT, counterbalanced for order and version, in a sample of 96 subjects (50% women; ages 25-56 yr) with at least a Master's degree in science, technology, engineering, or mathematics (STEM). We assessed the associations of age, sex, and administration device with neurocognitive performance, and compared the scores on the Cognition battery with those of WinSCAT. Confirmatory factor analysis compared the structure of the iPad and laptop administration methods using Wald tests. RESULTS: Age was associated with longer response times (mean ß = 0.12) and less accurate (mean ß = -0.12) performance, women had longer response times on psychomotor (ß = 0.62), emotion recognition (ß = 0.30), and visuo-spatial (ß = 0.48) tasks, men outperformed women on matrix reasoning (ß = -0.34), and performance on an iPad was generally faster (mean ß = -0.55). The WinSCAT appeared heavily loaded with tasks requiring executive control, whereas Cognition assessed a larger variety of neurocognitive domains. DISCUSSION: Overall results supported the interpretation of Cognition scores as measuring their intended constructs in high performing astronaut analog samples.Moore TM, Basner M, Nasrini J, Hermosillo E, Kabadi S, Roalf DR, McGuire S, Ecker AJ, Ruparel K, Port AM, Jackson CT, Dinges DF, Gur RC. Validation of the Cognition Test Battery for spaceflight in a sample of highly educated adults. Aerosp Med Hum Perform. 2017; 88(10):937-946.

Effects of military service and deployment on clinical symptomatology: The role of trauma exposure and social support.

The Marine Resiliency Study-II examined changes in symptomatology across a deployment cycle to Afghanistan. U.S. Servicemembers (N = 1041) received clinical testing at two time points either bracketing a deployment (855) or not (186). Factor analyses were used to generate summary and change scores from Time 1 to Time 2. A between-subject design was used to examine changes across the deployment cycle with deployment (low-trauma, high-trauma, and non-deployed) and social support (low vs. high) as the grouping variables. Insomnia increased post-deployment regardless of deployment trauma (std. effect for high-trauma and low-trauma = 0.39 and 0.26, respectively). Only the high-trauma group showed increased PTSD symptoms and non-perspective-taking (std. effect = 0.40 and 0.30, respectively), while low-trauma showed decreased anxiety symptoms after deployment (std. effect = -0.17). These associations also depend on social support, with std. effects ranging from -0.22 to 0.51. When the groups were compared, the high-trauma deployed group showed significantly worse PTSD and non-perspective-taking than all other groups. Similar to studies in other military divisions, increased clinical symptoms were associated with high deployment stress in active duty Servicemembers, and social support shows promise as a moderator of said association.

Cognitive functioning of adolescent and young adult cannabis users in the Philadelphia Neurodevelopmental Cohort.

Cannabis use in youth is rising and has been linked to deficits in cognitive functioning. However, cognitive findings have primarily been based on small samples of users seeking treatment, and few studies have evaluated cognition in occasional cannabis users. Here, we examined 4,568 adolescents and young adults (ages 14-21 years) drawn from the Philadelphia Neurodevelopmental Cohort, a prospective, population-based study. Participants were classified as cannabis Non-Users (n = 3,401), Occasional Users (twice per week or less; n = 940), or Frequent Users (>3 times per week; n = 227). Mixed-model analyses examined main effects of cannabis use and interactions between age and cannabis use on cognitive functioning. There was a significant interaction between cannabis group and age such that adolescent (but not young adult) Frequent Users performed worse than Non-Users on measures of executive control (p = .002). Earlier age of cannabis use was associated with worse performance in executive control in Occasional Users (p = .04). Unexpectedly, Occasional Users exhibited better executive control, memory, and social cognition than Non-Users (ps < .05). Although mild executive control deficits in adolescent frequent users and a relation between early cannabis initiation and cognitive performance are partially consistent with prior research, cognitive deficits were not found in other hypothesized domains in this community-based sample. Moreover, occasional cannabis users displayed equivalent or even slightly better executive control, social-cognitive, and memory abilities compared with nonusers, suggesting complex relationships between cannabis use and cognition in youth. Longitudinal studies with community samples are needed to identify variables affecting risk and resilience to cognitive deficits associated with cannabis. (PsycINFO Database Record

Development of an itemwise efficiency scoring method: Concurrent, convergent, discriminant, and neuroimaging-based predictive validity assessed in a large community sample.

Traditional "paper-and-pencil" testing is imprecise in measuring speed and hence limited in assessing performance efficiency, but computerized testing permits precision in measuring itemwise response time. We present a method of scoring performance efficiency (combining information from accuracy and speed) at the item level. Using a community sample of 9,498 youths age 8-21, we calculated item-level efficiency scores on 4 neurocognitive tests, and compared the concurrent, convergent, discriminant, and predictive validity of these scores with simple averaging of standardized speed and accuracy-summed scores. Concurrent validity was measured by the scores' abilities to distinguish men from women and their correlations with age; convergent and discriminant validity were measured by correlations with other scores inside and outside of their neurocognitive domains; predictive validity was measured by correlations with brain volume in regions associated with the specific neurocognitive abilities. Results provide support for the ability of itemwise efficiency scoring to detect signals as strong as those detected by standard efficiency scoring methods. We find no evidence of superior validity of the itemwise scores over traditional scores, but point out several advantages of the former. The itemwise efficiency scoring method shows promise as an alternative to standard efficiency scoring methods, with overall moderate support from tests of 4 different types of validity. This method allows the use of existing item analysis methods and provides the convenient ability to adjust the overall emphasis of accuracy versus speed in the efficiency score, thus adjusting the scoring to the real-world demands the test is aiming to fulfill. (PsycINFO Database Record

Common and Dissociable Mechanisms of Executive System Dysfunction Across Psychiatric Disorders in Youth.

OBJECTIVE: Disruption of executive function is present in many neuropsychiatric disorders. However, determining the specificity of executive dysfunction across these disorders is challenging given high comorbidity of conditions. Here the authors investigate executive system deficits in association with dimensions of psychiatric symptoms in youth using a working memory paradigm. The authors hypothesize that common and dissociable patterns of dysfunction would be present. METHOD: The authors studied 1,129 youths who completed a fractal n-back task during functional magnetic resonance imaging at 3-T as part of the Philadelphia Neurodevelopmental Cohort. Factor scores of clinical psychopathology were calculated using an item-wise confirmatory bifactor model, describing overall psychopathology as well as four orthogonal dimensions of symptoms: anxious-misery (mood and anxiety), behavioral disturbance (attention deficit hyperactivity disorder and conduct disorder), psychosis-spectrum symptoms, and fear (phobias). The effect of psychopathology dimensions on behavioral performance and executive system recruitment (2-back > 0-back) was examined using both multivariate (matrix regression) and mass-univariate (linear regression) analyses. RESULTS: Overall psychopathology was associated with both abnormal multivariate patterns of activation and a failure to activate executive regions within the cingulo-opercular control network, including the frontal pole, cingulate cortex, and anterior insula. In addition, psychosis-spectrum symptoms were associated with hypoactivation of the left dorsolateral prefrontal cortex, whereas behavioral symptoms were associated with hypoactivation of the frontoparietal cortex and cerebellum. In contrast, anxious-misery symptoms were associated with widespread hyperactivation of the executive network. CONCLUSIONS: These findings provide novel evidence that common and dissociable deficits within the brain's executive system are present in association with dimensions of psychopathology in youth.

The impact of quality assurance assessment on diffusion tensor imaging outcomes in a large-scale population-based cohort.

BACKGROUND: Diffusion tensor imaging (DTI) is applied in investigation of brain biomarkers for neurodevelopmental and neurodegenerative disorders. However, the quality of DTI measurements, like other neuroimaging techniques, is susceptible to several confounding factors (e.g., motion, eddy currents), which have only recently come under scrutiny. These confounds are especially relevant in adolescent samples where data quality may be compromised in ways that confound interpretation of maturation parameters. The current study aims to leverage DTI data from the Philadelphia Neurodevelopmental Cohort (PNC), a sample of 1601 youths with ages of 8-21 who underwent neuroimaging, to: 1) establish quality assurance (QA) metrics for the automatic identification of poor DTI image quality; 2) examine the performance of these QA measures in an external validation sample; 3) document the influence of data quality on developmental patterns of typical DTI metrics. METHODS: All diffusion-weighted images were acquired on the same scanner. Visual QA was performed on all subjects completing DTI; images were manually categorized as Poor, Good, or Excellent. Four image quality metrics were automatically computed and used to predict manual QA status: Mean voxel intensity outlier count (MEANVOX), Maximum voxel intensity outlier count (MAXVOX), mean relative motion (MOTION) and temporal signal-to-noise ratio (TSNR). Classification accuracy for each metric was calculated as the area under the receiver-operating characteristic curve (AUC). A threshold was generated for each measure that best differentiated visual QA status and applied in a validation sample. The effects of data quality on sensitivity to expected age effects in this developmental sample were then investigated using the traditional MRI diffusion metrics: fractional anisotropy (FA) and mean diffusivity (MD). Finally, our method of QA is compared with DTIPrep. RESULTS: TSNR (AUC=0.94) best differentiated Poor data from Good and Excellent data. MAXVOX (AUC=0.88) best differentiated Good from Excellent DTI data. At the optimal threshold, 88% of Poor data and 91% Good/Excellent data were correctly identified. Use of these thresholds on a validation dataset (n=374) indicated high accuracy. In the validation sample 83% of Poor data and 94% of Excellent data was identified using thresholds derived from the training sample. Both FA and MD were affected by the inclusion of poor data in an analysis of an age, sex and race matched comparison sample. In addition, we show that the inclusion of poor data results in significant attenuation of the correlation between diffusion metrics (FA and MD) and age during a critical neurodevelopmental period. We find higher correspondence between our QA method and DTIPrep for Poor data, but we find our method to be more robust for apparently high-quality images. CONCLUSION: Automated QA of DTI can facilitate large-scale, high-throughput quality assurance by reliably identifying both scanner and subject induced imaging artifacts. The results present a practical example of the confounding effects of artifacts on DTI analysis in a large population-based sample, and suggest that estimates of data quality should not only be reported but also accounted for in data analysis, especially in studies of development.

The Philadelphia Neurodevelopmental Cohort: A publicly available resource for the study of normal and abnormal brain development in youth.

The Philadelphia Neurodevelopmental Cohort (PNC) is a large-scale study of child development that combines neuroimaging, diverse clinical and cognitive phenotypes, and genomics. Data from this rich resource is now publicly available through the Database of Genotypes and Phenotypes (dbGaP). Here we focus on the data from the PNC that is available through dbGaP and describe how users can access this data, which is evolving to be a significant resource for the broader neuroscience community for studies of normal and abnormal neurodevelopment.

Photoperiod programs dorsal raphe serotonergic neurons and affective behaviors.

The serotonergic raphe nuclei of the midbrain are principal centers from which serotonin neurons project to innervate cortical and sub-cortical structures. The dorsal raphe nuclei receive light input from the circadian visual system and indirect input from the biological clock nuclei. Dysregulation of serotonin neurotransmission is implicated in neurobehavioral disorders, such as depression and anxiety, and alterations in the serotonergic phenotype of raphe neurons have dramatic effects on affective behaviors in rodents. Here, we demonstrate that day length (photoperiod) during development induces enduring changes in mouse dorsal raphe serotonin neurons­programming their firing rate, responsiveness to noradrenergic stimulation, intrinsic electrical properties, serotonin and norepinephrine content in the midbrain, and depression/anxiety-related behavior in a melatonin receptor 1 (MT1)-dependent manner. Our results establish mechanisms by which seasonal photoperiods may dramatically and persistently alter the function of serotonin neurons.

Development of an abbreviated form of the Penn Line Orientation Test using large samples and computerized adaptive test simulation.

Visuospatial processing is a commonly assessed neurocognitive domain with deficits linked to dysfunction in right posterior regions of the brain. With the growth of large-scale clinical research studies, there is an increased need for efficient and scalable assessments of neurocognition, including visuospatial processing. The purpose of the current study was to use a novel method that combines item response theory (IRT) and computerized adaptive testing (CAT) approaches to create an abbreviated form of the computerized Penn Line Orientation Test (PLOT). The 24-item PLOT was administered to 8,498 youths (aged 8-21 years) as part of the Philadelphia Neurodevelopmental Cohort study and, by Web-based data collection, in an independent sample of 4,593 adults from Great Britain as part of a TV documentary. IRT-based CAT simulations were used to select the best PLOT items for an abbreviated form by performing separate simulations in each group and choosing only items that were selected as useful (i.e., high item discrimination and in the appropriate difficulty range) in at least 1 of the simulations. Fifteen items were chosen for the final, short form of the PLOT, indicating substantial agreement among the models in how they evaluated each item's usefulness. Moreover, this abbreviated version performed comparably to the full version in tests of sensitivity to age and sex effects. This abbreviated version of the PLOT cuts administration time by 50% without detectable loss of information, which points to its feasibility for large-scale clinical and genomic studies.

Functional neuroimaging abnormalities in youth with psychosis spectrum symptoms.

IMPORTANCE: The continuum view of the psychosis spectrum (PS) implies that, in population-based samples, PS symptoms should be associated with neural abnormalities similar to those found in help-seeking clinical risk individuals and in schizophrenia. To our knowledge, functional neuroimaging has not previously been applied in large population-based PS samples and can help us understand the neural architecture of psychosis more broadly and identify brain phenotypes beyond symptoms that are associated with the extended psychosis phenotype. OBJECTIVE: To examine the categorical and dimensional relationships of PS symptoms to prefrontal hypoactivation during working memory and to amygdala hyperactivation during threat emotion processing. DESIGN, SETTING, AND PARTICIPANTS: The Philadelphia Neurodevelopmental Cohort is a genotyped, prospectively accrued, population-based sample of almost 10,000 youths who received a structured psychiatric evaluation and a computerized neurocognitive battery. The study was conducted at an academic and children's hospital health care network, between November 1, 2009 to November 30, 2011. A subsample of 1445 youths underwent neuroimaging, including functional magnetic resonance imaging tasks examined herein. Participants were youth aged 11 to 22 years old identified through structured interview as having PS features (PS group) (n = 260) and typically developing (TD) comparison youth without significant psychopathology (TD group) (n = 220). MAIN OUTCOMES AND MEASURES: Two functional magnetic resonance imaging paradigms were used: a fractal n-back working memory task probing executive system function and an emotion identification task probing amygdala responses to threatening faces. RESULTS: In the n-back task, working memory evoked lower activation in the PS group than the TD group throughout the executive control circuitry, including dorsolateral prefrontal cortex (cluster-corrected P < .05). Within the PS group, dorsolateral prefrontal cortex activation correlated with cognitive deficits (r = .32, P < .001), but no correlation was found with positive symptom severity. During emotion identification, PS demonstrated elevated responses to threatening facial expressions in amygdala, as well as left fusiform cortex and right middle frontal gyrus (cluster-corrected P < .05). The response in the amygdala correlated with positive symptom severity (r = .16, P = .01) but not with cognitive deficits. CONCLUSIONS AND RELEVANCE: The pattern of functional abnormalities observed in the PS group is similar to that previously found in schizophrenia and help-seeking risk samples. Specific circuit dysfunction during cognitive and emotion-processing tasks is present early in the development of psychopathology and herein could not be attributed to chronic illness or medication confounds. Hypoactivation in executive circuitry and limbic hyperactivation to threat could reflect partly independent risk factors for PS symptoms, with the former relating to cognitive deficits that increase the risk for developing psychotic symptoms and the latter contributing directly to positive psychotic symptoms.

A Substantial Fraction of Barley (Hordeum vulgare L.) Low Phytic Acid Mutations Have Little or No Effect on Yield across Diverse Production Environments.

The potential benefits of the low phytic acid (lpa) seed trait for human and animal nutrition, and for phosphorus management in non-ruminant animal production, are well documented. However, in many cases the lpa trait is associated with impaired seed or plant performance, resulting in reduced yield. This has given rise to the perception that the lpa trait is tightly correlated with reduced yield in diverse crop species. Here we report a powerful test of this correlation. We measured grain yield in lines homozygous for each of six barley (Hordeum vulgare L.) lpa mutations that greatly differ in their seed phytic acid levels. Performance comparisons were between sibling wild-type and mutant lines obtained following backcrossing, and across two years in five Idaho (USA) locations that greatly differ in crop yield potential. We found that one lpa mutation (Hvlpa1-1) had no detectable effect on yield and a second (Hvlpa4-1) resulted in yield losses of only 3.5%, across all locations. When comparing yields in three relatively non-stressful production environments, at least three lpa mutations (Hvlpa1-1, Hvlpa3-1, and Hvlpa4-1) typically had yields similar to or within 5% of the wild-type sibling isoline. Therefore in the case of barley, lpa mutations can be readily identified that when simply incorporated into a cultivar result in adequately performing lines, even with no additional breeding for performance within the lpa line. In conclusion, while some barley lpa mutations do impact field performance, a substantial fraction appears to have little or no effect on yield.

Heritability of subcortical and limbic brain volume and shape in multiplex-multigenerational families with schizophrenia.

BACKGROUND: Brain abnormalities of subcortical and limbic nuclei are common in patients with schizophrenia, and variation in these structures is considered a putative endophenotype for the disorder. Multiplex-multigenerational families with schizophrenia provide an opportunity to investigate the impact of shared genetic ancestry, but these families have not been previously examined to study structural brain abnormalities. We estimate the heritability of subcortical and hippocampal brain volumes in multiplex-multigenerational families and the heritability of subregions using advanced shape analysis. METHODS: The study comprised 439 participants from two sites who underwent 3T structural magnetic resonance imaging. The participants included 190 European-Americans from 32 multiplex-multigenerational families with schizophrenia and 249 healthy comparison subjects. Subcortical and hippocampal volume and shape were measured in 14 brain structures. Heritability was estimated for volume and shape. RESULTS: Volume and shape were heritable in families. Estimates of heritability in subcortical and limbic volumes ranged from .45 in the right hippocampus to .84 in the left putamen. The shape of these structures was heritable (range, .40-.49), and specific subregional shape estimates of heritability tended to exceed heritability estimates of volume alone. CONCLUSIONS: These results demonstrate that volume and shape of subcortical and limbic brain structures are potential endophenotypic markers in schizophrenia. The specificity obtained using shape analysis may improve selection of imaging phenotypes that better reflect the underlying neurobiology. Our findings can aid in the identification of specific genetic targets that affect brain structure and function in schizophrenia.

Impact of puberty on the evolution of cerebral perfusion during adolescence.

Puberty is the defining biological process of adolescent development, yet its effects on fundamental properties of brain physiology such as cerebral blood flow (CBF) have never been investigated. Capitalizing on a sample of 922 youths ages 8-22 y imaged using arterial spin labeled MRI as part of the Philadelphia Neurodevelopmental Cohort, we studied normative developmental differences in cerebral perfusion in males and females, as well as specific associations between puberty and CBF. Males and females had conspicuously divergent nonlinear trajectories in CBF evolution with development as modeled by penalized splines. Seventeen brain regions, including hubs of the executive and default mode networks, showed a robust nonlinear age-by-sex interaction that surpassed Bonferroni correction. Notably, within these regions the decline in CBF was similar between males and females in early puberty and only diverged in midpuberty, with CBF actually increasing in females. Taken together, these results delineate sex-specific growth curves for CBF during youth and for the first time to our knowledge link such differential patterns of development to the effects of puberty.

Circadian perinatal photoperiod has enduring effects on retinal dopamine and visual function.

Visual system development depends on neural activity, driven by intrinsic and light-sensitive mechanisms. Here, we examined the effects on retinal function due to exposure to summer- and winter-like circadian light cycles during development and adulthood. Retinal light responses, visual behaviors, dopamine content, retinal morphology, and gene expression were assessed in mice reared in seasonal photoperiods consisting of light/dark cycles of 8:16, 16:8, and 12:12 h, respectively. Mice exposed to short, winter-like, light cycles showed enduring deficits in photopic retinal light responses and visual contrast sensitivity, but only transient changes were observed for scotopic measures. Dopamine levels were significantly lower in short photoperiod mice, and dopaminergic agonist treatment rescued the photopic light response deficits. Tyrosine hydroxylase and Early Growth Response factor-1 mRNA expression were reduced in short photoperiod retinas. Therefore, seasonal light cycles experienced during retinal development and maturation have lasting influence on retinal and visual function, likely through developmental programming of retinal dopamine.