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Objectives/Goals: To support the growing number of clinical research professionals (CRP) working in behavioral and social science contexts, relevant formative assessments of research skills are needed. This study examines the development of an objective formative assessment designed to assess skills relevant to conducting social and behavioral research. Methods/Study Population: A multidisciplinary group at the University of Michigan was convened to develop the assessment. Case studies depicting clinical and translational research conducted in behavioral and social science contexts were used to measure proficiency in seven of the eight ECRPTQ competencies: Scientific Concepts & Research Design, Ethical & Participant Safety Concerns, Clinical Trial Operations (Good Clinical Practice), Study & Site Management, Data Management & Informatics, Leadership & Professionalism, Communication, and Teamwork & Team Science. Three difficulty levels of questions were developed: basic, intermediate, and advanced. To reinforce knowledge and skill development, the assessment was designed to give respondents formative feedback after responding to each question. Results/Anticipated Results: A preliminary “pre-pilot” test was conducted with three postdoctoral scholars to ensure that the assessment items were understandable. The assessment was then pilot tested with a larger group of 40 clinical research professionals (CRP) to test for the clarity and difficulty level of the items. A smaller group of 20 of these CRPs agreed to participate in focus groups to obtain feedback on their user experience. Data regarding years of experience as a CRP, types of studies engaged with, and information regarding professional certification were collected and used in the analyses. Demographic data collected were not connected to user responses. Results of the pilot test and focus groups were used to revise the questions on the final version of the assessment. Discussion/Significance of Impact: To our knowledge, this is the first objective assessment of research skills for CRP working in behavioral and social science contexts. We will discuss how other institutions can use this instrument to evaluate the training needs of their social and behavioral research workforce.
The spatial distribution of in situ sessile organisms, including those from the fossil record, provides information about life histories, such as possible dispersal and/or settlement mechanisms, and how taxa interact with one another and their local environments. At Nilpena Ediacara National Park (NENP), South Australia, the exquisite preservation and excavation of 33 fossiliferous bedding planes from the Ediacara Member of the Rawnsley Quartzite reveals in situ communities of the Ediacara Biota. Here, the spatial distributions of three relatively common taxa, Tribrachidium, Rugoconites, and Obamus, occurring on excavated surfaces were analyzed using spatial point pattern analysis. Tribrachidium have a variable spatial distribution, implying that settlement or post-settlement conditions/preferences had an effect on populations. Rugoconites display aggregation, possibly related to their reproductive methods in combination with settlement location availability at the time of dispersal and/or settlement. Additionally, post-settlement environmental controls could have affected Rugoconites on other surfaces, resulting in lower populations and densities. Both Tribrachidium and Rugoconites also commonly occur as individuals or in low numbers on a number of beds, thus constraining possible reproductive strategies and environmental/substrate preferences. The distribution of Obamus is consistent with selective settlement, aggregating near conspecifics and on substrates of mature microbial mat. This dispersal process is the first example of substrate-selective dispersal among the Ediacara Biota, thus making Obamus similar to numerous modern sessile invertebrates with similar dispersal and settlement strategies.
Intrauterine growth restriction (IUGR) due to uteroplacental insufficiency results in a placenta that is unable to provide adequate nutrients and oxygen to the fetus. These growth-restricted babies have an increased risk of hypertension and chronic kidney disease later in life. In rats, both male and female growth-restricted offspring have nephron deficits but only males develop kidney dysfunction and high blood pressure. In addition, there is transgenerational transmission of nephron deficits and hypertension risk. Therefore, epigenetic mechanisms may explain the sex-specific programming and multigenerational transmission of IUGR-related phenotypes. Expression of DNA methyltransferases (Dnmt1and Dnmt3a) and imprinted genes (Peg3, Snrpn, Kcnq1, and Cdkn1c) were investigated in kidney tissues of sham and IUGR rats in F1 (embryonic day 20 (E20) and postnatal day 1 (PN1)) and F2 (6 and 12 months of age, paternal and maternal lines) generations (n = 6–13/group). In comparison to sham offspring, F1 IUGR rats had a 19% decrease in Dnmt3a expression at E20 (P < 0.05), with decreased Cdkn1c (19%, P < 0.05) and increased Kcnq1 (1.6-fold, P < 0.01) at PN1. There was a sex-specific difference in Cdkn1c and Snrpn expression at E20, with 29% and 34% higher expression in IUGR males compared to females, respectively (P < 0.05). Peg3 sex-specific expression was lost in the F2 IUGR offspring, only in the maternal line. These findings suggest that epigenetic mechanisms may be altered in renal embryonic and/or fetal development in growth-restricted offspring, which could alter kidney function, predisposing these offspring to kidney disease later in life.
Prior research has shown that sipping of alcohol begins to emerge during childhood and is potentially etiologically significant for later substance use problems. Using a large, community sample of 9- and 10-year-olds (N = 11,872; 53% female), we examined individual differences in precocious alcohol use in the form of alcohol sipping. We focused explicitly on features that are robust and well-demonstrated correlates of, and antecedents to, alcohol excess and related problems later in the lifespan, including youth- and parent-reported externalizing traits (i.e., impulsivity, behavioral inhibition and activation) and psychopathology. Seventeen percent of the sample reported sipping alcohol outside of a religiously sanctioned activity by age 9 or 10. Several aspects of psychopathology and personality emerged as small but reliable correlates of sipping. Nonreligious sipping was related to youth-reported impulsigenic traits, aspects of behavioral activation, prodromal psychotic-like symptoms, and mood disorder diagnoses, as well as parent-reported externalizing disorder diagnoses. Religious sipping was unexpectedly associated with certain aspects of impulsivity. Together, our findings point to the potential importance of impulsivity and other transdiagnostic indicators of psychopathology (e.g., emotion dysregulation, novelty seeking) in the earliest forms of drinking behavior.
Firefighting service is known to involve high rates of exposure to potentially traumatic situations, and research on mental health in firefighting populations is of critical importance in understanding the impact of occupational exposure. To date, the literature concerning prevalence of trauma-related mental disorders such as posttraumatic stress disorder (PTSD) has not distinguished between symptomology associated routine duty-related exposure and exposure to large-scale disaster. The present systematic review synthesizes a heterogeneous cross-national literature on large-scale disaster exposure in firefighters and provides support for the hypothesis that the prevalence of PTSD, major depressive disorder, and anxiety disorders are elevated in firefighters compared with rates observed in the general population. In addition, we conducted narrative synthesis concerning several commonly assessed predictive factors for disorder and found that sociodemographic factors appear to bear a weak relationship to mental disorder, while incident-related factors, such as severity and duration of disaster exposure, bear a stronger and more consistent relationship to the development of PTSD and depression in cross-national samples. Future work should expand on these preliminary findings to better understand the impact of disaster exposure in firefighting personnel.
Depressive episodes experienced in unipolar (UD) and bipolar (BD) disorders are characterized by anhedonia and have been associated with abnormalities in reward processes related to reward valuation and error prediction. It remains however unclear whether these deficits are associated with familial vulnerability to mood disorders.
Methods
In a functional magnetic resonance imaging study, we evaluated differences in the expected value (EV) and reward prediction error (RPE) signals in ventral striatum (VS) and prefrontal cortex between three groups of monozygotic twins: affected twins in remission for either UD or BD (n = 53), their high-risk unaffected co-twins (n = 34), and low-risk twins with no family history of mood disorders (n = 25).
Results
Compared to low-risk twins, affected twins showed lower EV signal bilaterally in the frontal poles and lower RPE signal bilaterally in the VS, left frontal pole and superior frontal gyrus. The high-risk group did not show a significant change in the EV or RPE signals in frontostriatal regions, yet both reward signals were consistently lower compared with low-risk twins in all regions where the affected twins showed significant reductions.
Conclusion
Our findings strengthen the notion that reduced valuation of expected rewards and reduced error-dependent reward learning may underpin core symptom of depression such as loss of interest in rewarding activities. The trend reduction in reward-related signals in unaffected co-twins warrants further investigation of this effect in larger samples and prospective follow-up to confirm possible association with increased familial vulnerability to mood disorders.
Lithium (Li) is the gold standard treatment for bipolar disorder (BD). However, its mechanisms of action remain unknown but include neurotrophic effects. We here investigated the influence of Li on cortical and local grey matter (GM) volumes in a large international sample of patients with BD and healthy controls (HC).
Methods
We analyzed high-resolution T1-weighted structural magnetic resonance imaging scans of 271 patients with BD type I (120 undergoing Li) and 316 HC. Cortical and local GM volumes were compared using voxel-wise approaches with voxel-based morphometry and SIENAX using FSL. We used multiple linear regression models to test the influence of Li on cortical and local GM volumes, taking into account potential confounding factors such as a history of alcohol misuse.
Results
Patients taking Li had greater cortical GM volume than patients without. Patients undergoing Li had greater regional GM volumes in the right middle frontal gyrus, the right anterior cingulate gyrus, and the left fusiform gyrus in comparison with patients not taking Li.
Conclusions
Our results in a large multicentric sample support the hypothesis that Li could exert neurotrophic and neuroprotective effects limiting pathological GM atrophy in key brain regions associated with BD.
Individuals with bipolar disorder (BD) show aberrant brain activation patterns during reward and loss anticipation. We examined for the first time longitudinal changes in brain activation during win and loss anticipation to identify trait markers of aberrant anticipatory processing in BD.
Methods
Thirty-four euthymic and depressed individuals with BD-I and 17 healthy controls (HC) were scanned using functional magnetic resonance imaging twice 6 months apart during a reward task.
Results
HC, but not individuals with BD, showed longitudinal reductions in the right lateral occipital cortex (RLOC) activation during processing of cues predicting possible money loss (p-corrected <0.05). This result was not affected by psychotropic medication, mood state or the changes in depression/mania severity between the two scans in BD. Elevated symptoms of subthreshold hypo/mania at baseline predicted more aberrant longitudinal patterns of RLOC activation explaining 12.5% of variance in individuals with BD.
Conclusions
Increased activation in occipital cortex during negative outcome anticipation may be related to elevated negative emotional arousal during anticipatory cue processing. One interpretation is that, unlike HC, individuals with BD were not able to learn at baseline that monetary losses were smaller than monetary gains and were not able to reduce emotional arousal for negative cues 6 months later. Future research in BD should examine how modulating occipital cortical activation affects learning from experience in individuals with BD.
Trauma exposure is associated with development of depression and anxiety; yet, some individuals are resilient to these trauma-associated effects. Differentiating mechanisms underlying development of negative affect and resilience following trauma is critical for developing effective interventions. One pathway through which trauma could exert its effects on negative affect is reward-learning networks. In this study, we examined relationships among lifetime trauma, reward-learning network function, and emotional states in young adults.
Methods
One hundred eleven young adults self-reported trauma and emotional states and underwent functional magnetic resonance imaging during a monetary reward task. Trauma-associated neural activation and functional connectivity were analyzed during reward prediction error (RPE). Relationships between trauma-associated neural functioning and affective and anxiety symptoms were examined.
Results
Number of traumatic events was associated with greater ventral anterior cingulate cortex (vACC) activation, and lower vACC connectivity with the right insula, frontopolar, inferior parietal, and temporoparietal regions, during RPE. Lower trauma-associated vACC connectivity with frontoparietal regions implicated in regulatory and decision-making processes was associated with heightened affective and anxiety symptoms; lower vACC connectivity with insular regions implicated in interoception was associated with lower affective and anxiety symptoms.
Conclusions
In a young adult sample, two pathways linked the impact of trauma on reward-learning networks with higher v. lower negative affective and anxiety symptoms. The disconnection between vACC and regions implicated in decision-making and self-referential processes may reflect aberrant regulatory but appropriate self-focused mechanisms, respectively, conferring risk for v. resilience against negative affective and anxiety symptoms.
Crop yield loss–weed density relationships critically influence calculation of economic thresholds and the resulting management recommendations made by a bioeconomic model. To examine site-to-site and year-to-year variation in winter Triticum aestivum L. (winter wheat)–Aegilops cylindrica Host. (jointed goatgrass) interference relationships, the rectangular hyperbolic yield loss function was fit to data sets from multiyear field experiments conducted at Colorado, Idaho, Kansas, Montana, Nebraska, Utah, Washington, and Wyoming. The model was fit to three measures of A. cylindrica density: fall seedling, spring seedling, and reproductive tiller densities. Two parameters: i, the slope of the yield loss curve as A. cylindrica density approaches zero, and a, the maximum percentage yield loss as A. cylindrica density becomes very large, were estimated for each data set using nonlinear regression. Fit of the model to the data was better using spring seedling densities than fall seedling densities, but it was similar for spring seedling and reproductive tiller densities based on the residual mean square (RMS) values. Yield loss functions were less variable among years within a site than among sites for all measures of weed density. For the one site where year-to-year variation was observed (Archer, WY), parameter a varied significantly among years, but parameter i did not. Yield loss functions differed significantly among sites for 7 of 10 comparisons. Site-to-site statistical differences were generally due to variation in estimates of parameter i. Site-to-site and year-to-year variation in winter T. aestivum–A. cylindrica yield loss parameter estimates indicated that management recommendations made by a bioeconomic model cannot be based on a single yield loss function with the same parameter values for the winter T. aestivum-producing region. The predictive ability of a bioeconomic model is likely to be improved when yield loss functions incorporating time of emergence and crop density are built into the model's structure.
Three models that empirically predict crop yield from crop and weed density were evaluated for their fit to 30 data sets from multistate, multiyear winter wheat–jointed goatgrass interference experiments. The purpose of the evaluation was to identify which model would generally perform best for the prediction of yield (damage function) in a bioeconomic model and which model would best fulfill criteria for hypothesis testing with limited amounts of data. Seven criteria were used to assess the fit of the models to the data. Overall, Model 2 provided the best statistical description of the data. Model 2 regressions were most often statistically significant, as indicated by approximate F tests, explained the largest proportion of total variation about the mean, gave the smallest residual sum of squares, and returned residuals with random distribution more often than Models 1 and 3. Model 2 performed less well based on the remaining criteria. Model 3 outperformed Models 1 and 2 in the number of parameters estimated that were statistically significant. Model 1 outperformed Models 2 and 3 in the proportion of regressions that converged on a solution and more readily exhibited an asymptotic relationship between winter wheat yield and both winter wheat and jointed goatgrass density under the constraint of limited data. In contrast, Model 2 exhibited a relatively linear relationship between yield and crop density and little effect of increasing jointed goatgrass density on yield, thus overpredicting yield at high weed densities when data were scarce. Model 2 had statistical properties that made it superior for hypothesis testing; however, Model 1's properties were determined superior for the damage function in the winter wheat–jointed goatgrass bioeconomic model because it was less likely to cause bias in yield predictions based on data sets of minimum size.
The extent to which observed differences in emotion processing and
regulation neural circuitry in adolescents with a history of suicide attempt
are paralleled by structural differences is unknown. We measured brain
cortical thickness and grey- and white-matter volumes in 100 adolescents: 28
with a history of suicide attempt and major depressive disorder (MDD); 31
with a history of MDD but no suicide attempt; and a healthy control group
(n = 41). The first group compared with controls showed
reduction in grey-matter volume in the right superior temporal gyrus (BA38),
a region important for social emotion processing.
Despite its heterogeneous symptomatology, obsessive-compulsive disorder (OCD) is currently conceptualized as a unitary diagnostic entity. Recent factor-analytic studies have identified several OCD symptom dimensions that are associated with different demographic variables, comorbidity, patterns of genetic transmission, and treatment response. Functional abnormalities in neural systems important for emotion perception, including the orbitofrontal cortex, lateral prefrontal cortex, anterior cingulate gyrus, and limbic regions, have been reported in OCD. In this review, we discuss the extent to which neurobiological markers may distinguish these different symptom dimensions and whether specific symptom dimensions, such as contamination/washing, are associated with abnormalities in emotion and, in particular, disgust, perception in OCD. Also discussed are findings that indicate that anxiety can be induced in healthy volunteers in response to OCD symptom-related material, and that associated increases in activity within neural systems important for emotion perception occur to washing- and hoarding-related material in particular in these subjects. Further examination of neural responses during provocation of different symptom dimensions in OCD patients will help determine the extent to which specific abnormalities in neural systems underlying emotion perception are associated with different symptom dimensions and predict treatment response in OCD.
Edited by
Susanna Pietropaolo, Centre National de la Recherche Scientifique (CNRS), Paris,Frans Sluyter, University of Portsmouth,Wim E. Crusio, Centre National de la Recherche Scientifique (CNRS), Paris
The cerebral mechanisms of traits associated with depersonalization-derealization disorder (DPRD) remain poorly understood.
Method
Happy and sad emotion expressions were presented to DPRD and non-referred control (NC) subjects in an implicit event-related functional magnetic resonance imaging (fMRI) design, and correlated with self report scales reflecting typical co-morbidities of DPRD: depression, dissociation, anxiety, somatization.
Results
Significant differences between the slopes of the two groups were observed for somatization in the right temporal operculum (happy) and ventral striatum, bilaterally (sad). Discriminative regions for symptoms of depression were the right pulvinar (happy) and left amygdala (sad). For dissociation, discriminative regions were the left mesial inferior temporal gyrus (happy) and left supramarginal gyrus (sad). For state anxiety, discriminative regions were the left inferior frontal gyrus (happy) and parahippocampal gyrus (sad). For trait anxiety, discriminative regions were the right caudate head (happy) and left superior temporal gyrus (sad).
Discussion
The ascertained brain regions are in line with previous findings for the respective traits. The findings suggest separate brain systems for each trait.
Conclusion
Our results do not justify any bias for a certain nosological category in DPRD.