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Do students learn better with material that is perceptually hard to process? While evidence is mixed, recent claims suggest that placing materials in Sans Forgetica, a perceptually difficult-to-process typeface, has positive impacts on student learning. Given the weak evidence for other similar perceptual disfluency effects, we examined the mnemonic effects of Sans Forgetica more closely in comparison to other learning strategies across three preregistered experiments. In Experiment 1, participants studied weakly related cue-target pairs with targets presented in either Sans Forgetica or with missing letters (e.g., cue: G_RL, the generation effect). Cued recall performance showed a robust effect of generation, but no Sans Forgetica memory benefit. In Experiment 2, participants read an educational passage about ground water with select sentences presented in either Sans Forgetica typeface, yellow pre-highlighting, or unmodified. Cued recall for select words was better for pre-highlighted information than an unmodified pure reading condition. Critically, presenting sentences in Sans Forgetica did not elevate cued recall compared to an unmodified pure reading condition or a pre-highlighted condition. In Experiment 3, individuals did not have better discriminability for Sans Forgetica relative to a fluent condition in an old-new recognition test. Our findings suggest that Sans Forgetica really is forgettable.

Research suggests testing improves the retention of previously learned information. Here, we examined whether this might be due (in part) to the fact that tests help learners stay on task during the review stages of learning. In two experiments, participants encoded a list of words and later had an opportunity to review the material via a free recall test or re-reading the words. During review, participants provided self-reports as to whether their minds were on or off task. Results from both experiments show testing decreased mind-wandering. Importantly, this reduction in mind-wandering was associated with improved performance on a final memory test. These results suggest the mnemonic benefits associated with testing may stem not only from act of retrieval itself, but also from the fact that taking tests encourages a more efficient and engaged review of the material.

There is an increasing need in eyewitness identification research to identify factors that not only influence identification accuracy but may also impact the confidence–accuracy (CA) relationship. One such variable that has a notable impact on memory for faces is viewing distance, with faces encoded from a shorter distance remembered better than faces encoded at longer differences. In four pre-registered experiments, using both laboratory and online samples, we compared faces viewed at a simulated viewing distance at two different levels (medium and far) to faces that were viewed at a very near-simulated distance. Distance was simulated using a Gaussian blur function with higher levels of blur corresponding to greater simulated distance. We found that both medium and far simulated distances impaired memory performance overall relative to no simulated distance, with increased distance resulting in poorer memory. However, only far simulated distances impaired the CA relationship. In a fourth experiment, we found that a pre-test warning did not ameliorate this impairment of the CA relationship for faces viewed at a far simulated distance. These findings suggest that even high-confidence identifications made for faces viewed from long distances should be disregarded, and that estimator variables that impact memory may degrade the CA relationship when memory is reduced to critical levels.

Presenting information in a perceptually disfluent format sometimes enhances memory. Recent work examining 1 type of perceptual disfluency manipulation, Sans Forgetica typeface, has yielded discrepant findings; some studies find support for the idea that the disfluent typeface improves memory whereas others do not. The current study examined a boundary condition that determines when disfluency is and is not beneficial to learning to explore this discrepancy. Specifically, we investigated whether knowledge about an upcoming test (high test expectancy) versus not (low test expectancy) helps clarify when mnemonic benefits arise for perceptually disfluent stimuli. In Experiment 1 (preregistered, N = 231), we found that Sans Forgetica is a memory-improving desirable difficulty, but only when there was no expectation of a final test. In Experiment 2 (preregistered, N = 232), we conceptually replicated the Sans Forgetica effect using a cued-recall test. In Experiment 3 (preregistered, N = 232), we ruled out a time-on-task explanation while replicating the results of Experiment 2. Though these data provide some evidence of San Forgetica's mnemonic benefits, caution should be taken in interpreting these results. Not only were the effect sizes moderate, but low test expectancy may not be realistically achievable in actual educational contexts. Though more research is warranted, we echo our prior arguments that students wanting to remember more and forget less should stick to other, more empirically supported desirable difficulties. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

When eyewitnesses see a crime, they often do so under physiological stress. Research suggests that stress disrupts memory accuracy, but less is known about whether stress impacts the relationship between confidence and accuracy. Whereas researchers generally agree that pristine encoding and retrieval conditions lead to a strong relationship between the two ( Wixted & Wells, 2017 ), how violations of pristine conditions affect the relationship is unclear. In two experiments, participants encoded faces either under physiological stress (via a cold pressor task) or under control conditions. Participants were later given a recognition memory test for the faces and provided confidence judgments in their old/new decisions. As expected, stress impaired face recognition accuracy. However, we observed similar confidence–accuracy relationships regardless of stress condition. Though participants in the stress condition were less accurate in their identifications overall, they had the metacognitive awareness to scale back their confidence judgments.

Objectives: To evaluate segmented diffusion tensor imaging (DTI) white matter tract fractional anisotropy (FA) and mean diffusivity (MD) values in acute cervical spinal cord injury (CSCI). Methods: 15 patients with acute CSCI and 12 control subjects were prospectively recruited and underwent axial DTI as part of the spine trauma MRI. Datasets were put through a semi-automated probabilistic segmentation algorithm that analyzed white matter, motor and sensory tracts. FA and MD values were calculated for white matter, sensory (spinal lemniscal) and motor tracts (ventral/lateral corticospinal) at the level of clinical injury, levels remote from injury and in normal controls. Results: There were significant differences in FA between the level of injury and controls for total white matter (0.65 ± .09 vs 0.68 ± .07; p = .044), motor tracts (0.64 ± .07 vs 0.7 ± .09; p = .006), and combined motor/sensory tracts (0.63 ± .09 vs 0.69 ± .08; p = .022). In addition, there were significant FA differences between the level of injury and one level caudal to the injury for combined motor tracts (0.64 ± .07 vs 0.69 ± .05; p = .002) and combined motor/sensory tracts (0.63 ± .09 vs 0.7 ± .07; p = .011). There were no significant differences for MD between the level of injury and one level caudal to the injury or normal controls. Conclusion: Abnormalities in DTI metrics of DTI-segmented white matter tracts were detected at the neurological level of injury relative to normal controls and levels remote from the injury site, confirming its value in CSCI assessment. Advances in knowledge: Segmented DTI analysis can help identify microstructural spinal cord abnormalities in the setting of traumatic cervical spinal cord injury.

Although tests typically improve long-term retention, recent research suggests that certain types of tests may disrupt memory, referred to as the negative testing effect. According to one explanatory framework, this detrimental effect on memory results from tests disrupting organizational processing, which hinders the ability to make associations between items. From an educational perspective, these outcomes are concerning because they suggest contexts in which taking a test may impair subsequent retention. However, no research has explored whether the negative testing effect extends to more educational designs and materials. The goal of the current research was twofold: investigate the replicability of the negative testing effect by examining the original demonstration with a novel participant population and explore whether such organizational disruptions generalize to more ecologically valid materials. Outcomes establish the replicability of the negative testing effect and provide evidence that the detrimental effects of testing may not extend to educational material.

Researchers generally agree that retrieval practice of previously learned material facilitates subsequent recall of same material, a phenomenon known as the testing effect. There is debate, however, about when such benefits transfer to related (though not identical) material. The current study examines the phenomenon of transfer in the domain of analogical problem-solving. In Experiments 1 and 2, learners were presented a source text describing a problem and solution to read which was subsequently either restudied or recalled. Following a short (Experiment 1) or long (Experiment 2) delay, learners were given a new target text and asked to solve a problem. The two texts shared a common structure such that the provided solution for the source text could be applied to solve the problem in the target text. In a combined analysis of both experiments, learners in the retrieval practice condition were more successful at solving the problem than those in the restudy condition. Experiment 3 explored the degree to which retrieval practice promotes cued versus spontaneous transfer by manipulating whether participants were provided with an explicit hint that the source and target texts were related. Results revealed no effect of retrieval practice.

BACKGROUND AND PURPOSE: DTI is a tool for microstructural spinal cord injury evaluation. This study evaluated the reproducibility of a semiautomated segmentation algorithm of spinal cord DTI. MATERIALS AND METHODS: Forty-two consecutive patients undergoing acute trauma cervical spine MR imaging underwent 2 axial DTI scans in addition to their clinical scan. The datasets were put through a semiautomated probabilistic segmentation algorithm that selected white matter, gray matter, and 24 individual white matter tracts. Regional and white matter tract volume, fractional anisotropy, and mean diffusivity values were calculated. Two readers performed the nonautomated steps to evaluate interreader reproducibility. The coefficient of variation and intraclass correlation coefficient were used to assess test-retest and interreader reproducibility. RESULTS: Of 42 patients, 30 had useable data. Test-retest reproducibility of fractional anisotropy was high for white matter as a whole (coefficient of variation, 3.8%; intraclass correlation coefficient, 0.93). Test-retest coefficient-of-variation ranged from 8.0%–18.2% and intraclass correlation coefficients from 0.47–0.80 across individual white matter tracts. Mean diffusivity metrics also had high test-retest reproducibility (white matter: coefficient-of-variation, 5.6%; intraclass correlation coefficient, 0.86) with coefficients of variation from 11.6%–18.3% and intraclass correlation coefficients from 0.57–0.74 across individual tracts, with better agreement for larger tracts. The coefficients of variation of fractional anisotropy and mean diffusivity both had significant negative relationships with white matter volume (26%–27% decrease for each doubling of white matter volume, P < .01). CONCLUSIONS: DTI spinal cord segmentation is reproducible in the setting of acute spine trauma, specifically for larger white matter tracts and total white or gray matter.

Neonatal quinpirole (NQ) treatment to rats increases dopamine D2 receptor sensitivity persistent throughout the animal's lifetime. In Experiment 1, we analyzed the role of α7 and α4β2 nicotinic receptors (nAChRs) in nicotine behavioral sensitization and on the brain-derived neurotrophic factor (BDNF) response to nicotine in NQ- and neonatally saline (NS)-treated rats. In Experiment 2, we analyzed changes in α7 and α4β2 nAChR density in the nucleus accumbens (NAcc) and dorsal striatum in NQ and NS animals sensitized to nicotine. Male and female Sprague-Dawley rats were neonatally treated with quinpirole (1mg/kg) or saline from postnatal days (P)1-21. Animals were given ip injections of either saline or nicotine (0.5mg/kg free base) every second day from P33 to P49 and tested on behavioral sensitization. Before each injection, animals were ip administered the α7 nAChR antagonist methyllycaconitine (MLA; 2 or 4mg/kg) or the α4β2 nAChR antagonist dihydro beta erythroidine (DhβE; 1 or 3mg/kg). Results revealed NQ enhanced nicotine sensitization that was blocked by DhβE. MLA blocked the enhanced nicotine sensitization in NQ animals, but did not block nicotine sensitization. NQ enhanced the NAcc BDNF response to nicotine which was blocked by both antagonists. In Experiment 2, NQ enhanced nicotine sensitization and enhanced α4β2, but not α7, nAChR upregulation in the NAcc. These results suggest a relationship between accumbal BDNF and α4β2 nAChRs and their role in the behavioral response to nicotine in the NQ model which has relevance to schizophrenia, a behavioral disorder with high rates of tobacco smoking.

Background Indirect immunofluorescence (IIF) is the most prevalent screening antinuclear antibody test for systemic autoimmune rheumatic disease (SARD). Certain IIF patterns have known antibody and disease associations, but the dense fine speckled (ANA-DFS) pattern has no confirmed clinical associations. Our objective was to determine the prevalence of SARD among a group of ANA-DFS positive individuals and to identify final diagnoses among non-SARD individuals in order to determine possible clinical associations with the ANA-DFS pattern. Methods A retrospective study of 425 patients from a university health care system with a positive ANA-DFS pattern consecutively between August 2017 and September 2018. Sera samples underwent ANA testing by IIF on HEp-2 cell substrates (Euroimmun, Germany). Clinical information was retrieved from electronic health records and stored in a de-identified database. Results The prevalence of SARD was 24%. Undetermined diagnosis (17%), skin disorders (12.1%), and fibromyalgia/chronic pain syndrome/chronic fatigue syndrome (11.8%) were the most common non-SARD diagnoses. Taking into account past medical history, the most common non-SARD were atopic disorders (21.2%), fibromyalgia/chronic pain syndrome/chronic fatigue syndrome (17.6%), and skin disorders (16.7%). Conclusions The ANA-DFS pattern may be indicative of an underlying antigen-antibody interaction that plays a role in either the initiation or propagation of immunologic reactions. DFS70/LEDGF is a transcription factor involved in cell survival and stress protection, and autoantibodies may inhibit its function. It is likely that there are other antibodies producing the ANA-DFS pattern besides anti-DFS70/LEDGF, and more research is necessary to identify additional antibody specificities. The ANA-DFS pattern may be an indicator of a proinflammatory microenvironment given the high frequency of symptomatic patients and disease processes with an immunologic basis (including SARD).

Currently, the process of obtaining a 3D model from a structural MRI requires specialized knowlege and skills. This is not due to the fundamental difficulty and complexity of the process, but is a result of the fact that the neccessary tools were developed for and by neuroimaging researchers. This project describes a publically available utility implemented as a Docker image that takes a structural MRI as input, and gives files for 3D printing as output, along with a rendered image of the surface.

In students in grades 4 to 9 (22 males, 20 females), two reading disability groups—dyslexia (n = 20) or oral and written language learning disability (OWL LD) (n = 6)—were compared to each other and two kinds of control groups—typical readers (n = 6) or dysgraphia (n = 10) on word reading/spelling skills and fMRI imaging before and after completing 18 computerized reading lessons. Mixed ANOVAs showed significant time effects on repeated measures within participants and between groups effects on three behavioral markers of reading disabilities—word reading/spelling: All groups improved on the three behavioral measures, but those without disabilities remained higher than those with reading disabilities. On fMRI reading tasks, analyzed for graph theory derived clustering coefficients within a neural network involved in cognitive control functions, on a word level task the time × group interaction was significant in right medial cingulate; on a syntax level task the time × group interaction was significant in left superior frontal and left inferior frontal gyri; and on a multi-sentence text level task the time × group interaction was significant in right middle frontal gyrus. Three white matter-gray matter correlations became significant only after reading instruction: axial diffusivity in left superior frontal region with right inferior frontal gyrus during word reading judgments; mean diffusivity in left superior corona radiata with left middle frontal gyrus during sentence reading judgments; and mean diffusivity in left anterior corona radiata with right middle frontal gyrus during multi-sentence reading judgments. Significance of results for behavioral and brain response to reading instruction (RTI) is discussed., Graphical abstract

To understand mental self-government of the developing reading and writing brain, correlations of clustering coefficients on fMRI reading or writing tasks with BASC 2 Adaptivity ratings (time 1 only) or working memory components (time 1 before and time 2 after instruction previously shown to improve achievement and change magnitude of fMRI connectivity) were investigated in 39 students in grades 4 to 9 who varied along a continuum of reading and writing skills. A Philips 3T scanner measured connectivity during six leveled fMRI reading tasks (subword-letters and sounds, word-word-specific spellings or affixed words, syntax comprehension-with and without homonym foils or with and without affix foils, and text comprehension) and three fMRI writing tasks-writing next letter in alphabet, adding missing letter in word spelling, and planning for composing. The Brain Connectivity Toolbox generated clustering coefficients based on the cingulo-opercular (CO) network; after controlling for multiple comparisons and movement, significant fMRI connectivity clustering coefficients for CO were identified in 8 brain regions bilaterally (cingulate gyrus, superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus, superior temporal gyrus, insula, cingulum-cingulate gyrus, and cingulum-hippocampus). BASC2 Parent Ratings for Adaptivity were correlated with CO clustering coefficients on three reading tasks (letter-sound, word affix judgments and sentence comprehension) and one writing task (writing next letter in alphabet). Before instruction, each behavioral working memory measure (phonology, orthography, morphology, and syntax coding, phonological and orthographic loops for integrating internal language and output codes, and supervisory focused and switching attention) correlated significantly with at least one CO clustering coefficient. After instruction, the patterning of correlations changed with new correlations emerging. Results show that the reading and writing brain's mental government, supported by both CO Adaptive Control and multiple working memory components, had changed in response to instruction during middle childhood/early adolescence.

There are but a handful of experimental or quasi-experimental studies comparing student outcomes from flipped or inverted classrooms to more traditional lecture formats. In the current study, I present cumulative exam performance and student evaluation data from two sections of a statistics course I recently taught: one a traditional lecture ( N = 19) and the other a flipped class ( N = 24). Independent samples t-tests revealed students in the flipped classroom outperformed their lecture peers by more than a letter grade on the final exam. Further, these students were more satisfied with the course overall, a novel finding in this burgeoning area of research. This latter point, I argue, is likely due to the strong cohesion between the in-class and out-of-class content.

Objective Sexual dimorphism is evident in attention-deficit/hyperactivity disorder (ADHD), including subtype prevalence, adverse outcomes, and neural phenotype. Neurobiological studies of ADHD suggest that boys show more abnormalities in motor and premotor structure and function, whereas girls differ from typically developing (TD) peers in prefrontal circuitry. We applied diffusion tensor imaging (DTI) to identify ADHD-related sex-specific differences in motor/premotor and prefrontal white matter (WM) microstructure in children. Method DTI estimated differences in WM microstructure among 120 children 8 to 12 years of age, 60 with ADHD (30 boys and 30 girls) and 60 controls (30 boys and 30 girls), matched on age, IQ, and handedness. Effects of diagnosis and sex on fractional anisotropy (FA) were assessed in motor/premotor and prefrontal regions. Group differences in FA and associations with response control (e.g., reaction time variability [CVRT] and commission error rate) were examined separately within sex. Results Sex-by-diagnosis interactions were observed for FA in primary motor (M1) and medial orbitofrontal (MOFC) cortex. Post hoc tests revealed that boys with ADHD showed bilateral reductions in FA within M1, compared with TD peers; in contrast, girls with ADHD showed higher FA bilaterally within MOFC. Decreased M1 FA was associated with higher CVRT in boys and higher commission error rates in girls. For MOFC, lower FA was associated with greater CVRT and commission error rates across all participants with ADHD. Conclusion ADHD affects the white matter of boys and girls differently; boys appear to be more affected in regions responsible for control of basic actions, whereas girls show more abnormalities in regions responsible for higher-level, top–down control.

Objectives To evaluate the effectiveness of efforts to translate and disseminate evidence-based guidelines about atypical antipsychotic use to nursing homes (NHs). Design Three-arm, cluster randomized trial. Setting NHs. Participants NHs in the state of Connecticut. Measurements Evidence-based guidelines for atypical antipsychotic prescribing were translated into a toolkit targeting NH stakeholders, and 42 NHs were recruited and randomized to one of three toolkit dissemination strategies: mailed toolkit delivery (minimal intensity); mailed toolkit delivery with quarterly audit and feedback reports about facility-level antipsychotic prescribing (moderate intensity); and in-person toolkit delivery with academic detailing, on-site behavioral management training, and quarterly audit and feedback reports (high intensity). Outcomes were evaluated using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. Results Toolkit awareness of 30% (7/23) of leadership of low-intensity NHs, 54% (19/35) of moderate-intensity NHs, and 82% (18/22) of high-intensity NHs reflected adoption and implementation of the intervention. Highest levels of use and knowledge among direct care staff were reported in high-intensity NHs. Antipsychotic prescribing levels declined during the study period, but there were no statistically significant differences between study arms or from secular trends. Conclusion RE-AIM indicators suggest some success in disseminating the toolkit and differences in reach, adoption, and implementation according to dissemination strategy but no measurable effect on antipsychotic prescribing trends. Further dissemination to external stakeholders such as psychiatry consultants and hospitals may be needed to influence antipsychotic prescribing for NH residents.

Although retrieval often enhances subsequent memory (the testing effect), a negative testing effect has recently been documented in which prior retrieval harms later recall compared with restudying. The negative testing effect was predicated on the negative generation effect and the item-specific-relational framework. The present experiments examine whether the negative testing effect persists over longer delays, whether the testing manipulation interacts with retention interval, and whether the negative testing and negative generation effects respond similarly to delay. Experiment 1 demonstrated a significant negative testing effect on an immediate free-recall test but not on a delayed test (after a 2-day retention interval). Furthermore, the retrieval condition produced less forgetting than the restudy condition. Under similar conditions (Experiment 2), generation likewise produced a negative effect on an immediate free-recall test but not after a 2-day delay. In addition, the generation condition produced less forgetting over 2 days than did the read condition. The results uncover important similarities between the mnemonic effects of retrieving information from episodic (testing effect) and semantic (generation effect) memory. The pattern of forgetting across delay also has relevance for accounts of the Testing × Retention interaction, a prominent phenomenon in the literature on the testing effect.

Although memory retrieval often enhances subsequent memory, Peterson and Mulligan (2013) reported conditions under which retrieval produces poorer subsequent recall-the negative testing effect. The item-specific-relational account proposes that the effect occurs when retrieval disrupts interitem organizational processing relative to the restudy condition. Rawson et al. (2015), in contrast, failed to replicate the negative testing effect despite repeated high-powered attempts. This article examines the discrepant results, ruling out differences in procedures, and concludes that differences in participant population produced the varying outcome. Specifically, participants from the University of North Carolina (UNC) and Kent State University (KSU) completed the same version of the negative-testing paradigm and were assessed on several measures of cognitive ability (working memory capacity, Raven's progressive matrices, and SAT or ACT score). For the UNC sample, free recall scores and the amount of category clustering (a measure of organizational processing) was greater in the restudy than retrieval condition (i.e., the negative testing effect was found); for the KSU sample, there was no difference on either measure. Furthermore, in the restudy condition, recall and clustering was greater for UNC than KSU students whereas in the retrieval condition, there was no effect of site on either measure. As expected, measures of cognitive ability were greater for the UNC than KSU sample. The results indicate that the negative testing effect is replicable but is subject to limitation related to the participant population. An analysis in terms of the relationship between cognitive ability and memory predicted this pattern of results. (PsycINFO Database Record

Before and after computerized writing instruction, participants completed assessment with normed measures and DTI and fMRI connectivity scanning. Evidence-based differential diagnosis was used at time 1 to assign them to diagnostic groups: typical oral and written language (n=6), dysgraphia (impaired handwriting, n=10), dyslexia (impaired word spelling and reading, n=20), and OWL LD (impaired syntax construction, n=6). The instruction was aimed at subword letter writing, word spelling, and syntax composing. With p

Although diffusion-weighted imaging (DWI) has become a mainstay in modern brain imaging, it remains less utilized in the evaluation of the spinal cord. Many studies have shown promise in using DWI and diffusion-tensor imaging (DTI) for evaluation of the spinal cord; however, application has been stalled by technical obstacles and artifacts, and questions remain regarding its clinical utility on an individual examination level. This review discusses the background, concepts, and technical aspects of DWI and DTI, specifically for imaging of the spinal cord. The clinical and investigational applications of spinal cord DTI, as well as the practical difficulties and limitations of DWI and DTI for the evaluation of the spinal cord are examined.

Correction of echo planar imaging (EPI)-induced distortions (called “unwarping”) improves anatomical fidelity for diffusion magnetic resonance imaging (MRI) and functional imaging investigations. Commonly used unwarping methods require the acquisition of supplementary images during the scanning session. Alternatively, distortions can be corrected by nonlinear registration to a non-EPI acquired structural image. In this study, we compared reliability using two methods of unwarping: (1) nonlinear registration to a structural image using symmetric normalization (SyN) implemented in Advanced Normalization Tools (ANTs); and (2) unwarping using an acquired field map. We performed this comparison in two different test-retest data sets acquired at differing sites (N = 39 and N = 32). In both data sets, nonlinear registration provided higher test-retest reliability of the output fractional anisotropy (FA) maps than field map-based unwarping, even when accounting for the effect of interpolation on the smoothness of the images. In general, field map-based unwarping was preferable if and only if the field maps were acquired optimally.

As Diffusion Tensor Imaging (DTI) gains widespread use, many researchers have been motivated to go beyond the tensor model and fit more complex diffusion models, to gain a more complete description of white matter microstructure and associated pathology. Two such models are Diffusion Kurtosis Imaging (DKI) and Diffusion Basis Spectrum Imaging (DBSI). It is not clear which DKI parameters are most closely related to DBSI parameters, so in the interest of enabling comparisons between DKI and DBSI studies, we conducted an empirical survey of the inter-relation of these models in 12 healthy volunteers using the same diffusion acquisition. We found that Mean Kurtosis (MK) is positively associated with the DBSI Fiber Ratio, and negatively associated with the Hindered Ratio. This was primarily driven by the radial component of kurtosis. The axial component of kurtosis was strongly and specifically correlated with the Restricted Ratio. The joint spatial distributions of DBSI and DKI parameters are tissue-dependent and stable across healthy individuals. Our contribution is a better understanding of the biological interpretability of the parameters generated by the two models in healthy individuals.

Researchers have documented an intriguing phenomenon whereby simply walking through a doorway causes forgetting (the location updating effect). The Event Horizon Model is the most commonly cited theory to explain these data. Importantly, this model explains the effect without invoking the importance or reliance upon perceptual information (i.e., seeing oneself pass through the doorway). This generates the intriguing hypothesis that the effect may be demonstrated in participants who simply imagine walking through a doorway. Across two experiments, we explicitly test this hypothesis. Participants familiarised themselves with both real (Experiment 1) and virtual (Experiment 2) environments which served as the setting for their mental walk. They were then provided with an image to remember and were instructed to imagine themselves walking through the previously presented space. In both experiments, when the mental walk required participants to pass through a doorway, more forgetting occurred, consistent with the predictions laid out in the Event Horizon Model.

BACKGROUND To the authors' knowledge, few studies to date have examined adherence to recommended guidelines for follow-up and outcomes after an unsatisfactory Papanicolaou (Pap) test (UPT) with liquid-based technologies. METHODS Within 4 US health plans, the median time to follow-up and the percentage of patients with follow-up testing by 120 days was calculated after a UPT. Multivariable analyses evaluated the association between clinical factors and follow-up testing. The authors compared the risk of a diagnosis of cervical intraepithelial neoplasia of type 2 or worse (CIN2+) after a UPT with the risk after a satisfactory Pap test while controlling for study site, test year, and other covariates. RESULTS A total of 634,644 Pap tests performed between 2004 and 2010 were included in the current study. Of 1442 UPTs, 53.4% had follow-up testing within 120 days; follow-up differed across the health plans (P

Current theories of the neurobiological basis of autism spectrum disorder (ASD) posit an altered pattern of connectivity in large-scale brain networks. Here we used diffusion tensor imaging to investigate the microstructural properties of the white matter (WM) that mediates interregional connectivity in 36 high-functioning children with ASD (HF-ASD) as compared with 37 controls. By employing an atlas-based analysis using large deformation diffeometric morphic mapping registration, a widespread but left-lateralized pattern of abnormalities was revealed. The mean diffusivity (MD) of water in the WM of HF-ASD children was significantly elevated throughout the left hemisphere, particularly in the outer-zone cortical WM. Across diagnostic groups, there was a significant effect of age on left-hemisphere MD, with a similar reduction in MD during childhood in both typically developing and HF-ASD children. The increased MD in children with HF-ASD suggests hypomyelination and may reflect increased short-range cortico-cortical connections subsequent to early WM overgrowth. These findings also highlight left-hemispheric connectivity as relevant to the pathophysiology of ASD and indicate that the spatial distribution of microstructural abnormalities in HF-ASD is widespread and left-lateralized. This altered left-hemispheric connectivity may contribute to deficits in communication and praxis observed in ASD.

This article takes the demise of Christendom and what Diana Butler Bass calls the end of religion as its point of departure for a “radical” rethinking of God in fully kenotic terms. It rejects any vestige of otherworldly transcendence as a temptation to escapism, inviting us instead to seek God's complete presence among us here in the world. Going beyond Niels Gregersen's understanding of the deep incarnation of the Logos and starting instead with a complete commitment to the infra-Lutheranum, the author presents a radical Lutheran theology that embraces a total kenosis of God whose liberating and life-giving reappearance we must find implicit among us in unexpected places, not least of which might include the embers of a dying church or the crumbling of our religious institutions.

This study analyzed the role of dopamine D1 and D2 receptors in methylphenidate (MPH) conditioned place preference (CPP) in adolescent male and female rats, in addition to the role of these receptors in the effects of MPH on brain-derived neurotrophic factor (BDNF) in the dorsal striatum and nucleus accumbens. Using a nonbiased CPP procedure, the animals were conditioned from postnatal day (PD) 33 to 37. On conditioning trials, animals were first administered saline or their respective antagonist (0.1 or 0.2 mg/kg SCH-23390; 0.01 or 0.03 mg/kg eticlopride HCl), followed by MPH (5 mg/kg). Approximately 10 min after MPH administration, the rats were placed into the paired context for a 10-min trial. One day after conditioning on PD38, a preference test was administered with dividers removed. One day following the preference test on PD39, brain tissue was removed, and the nucleus accumbens and striatum were analyzed for BDNF. Results revealed that MPH conditioning resulted in an increased preference that was blocked by either dose of SCH-23390, but generally not affected by either dose of eticlopride. Further, the higher dose of SCH-23390 resulted in a conditioned place aversion in males, presumably due to an increased number of dopamine D1 receptors in adolescent males. MPH produced a significant increase of striatal and accumbal BDNF alleviated by SCH-23390 or eticlopride. These results show that MPH results in CPP in adolescent male and female rats and these effects appear to be mediated by the dopamine D1 receptor, but the effects of MPH on BDNF appear to be mediated by both dopamine receptor families.

Perhaps the most basic finding in memory research is the repetition effect-the fact that repetition enhances memory. Peterson and Mulligan (2012) recently documented a surprising negative repetition effect, in which participants who studied a list of cue-target pairs twice recalled fewer targets than a group who studied the pairs only once. Words within a pair rhymed and across pairs, the target words were drawn from a small set of categories. In the repetition condition, the pairs were initially presented in a random order and then presented a second time blocked by the category of the target words. In the single presentation condition, the pairs were presented only in the blocked order. Participants in the former condition recalled fewer target words on a free recall test despite having seen the word pairs twice (the negative repetition effect). The encoding conditions necessary to produce this effect were examined in 4 experiments. Presenting the repetitions in a single study list elicited the negative repetition effect in free and category-cued recall. However, eliminating the strong within-trial, rhyme relationship eliminated the effect in both tests. Finally, presenting a disorganized but unrelated set of rhyming word pairs as List 1 reduced recall (relative to the single-presentation condition) to the same degree as the repetition condition. The negative repetition effect is due to reduced interitem relational processing during the presentation of the organized list (or half list), a reduction that requires a competing within-target relationship but can be induced by an unrelated as well as identical set of word pairs.

Ted Peters rightly rejects, on biblical and theological grounds, the understanding of kenosis presumably endorsed by Niels Gregersen (and with him Jurgen Moltmann, John Polkinghorne and Arthur Peacocke) as divine withdrawal from creation (tsim tsum). That said, a second version of kenosis, one more consistent with Scripture and early patristic theology, meets Peters' criticism by presenting kenosis not as a creative withdrawal of divine power but as a self-negation on the part of God that results in the generation of created reality along with God's reappearance and presence in it, albeit in another form. This is the kenosis-plerosis model, one according to which God gives history its momentum and empowers finite beings as a consequence of God's own self-negation; this would make possible a way for Gregersen meaningfully to affirm God's action at higher levels of nature without violating nature's integrity, even though it does so in a heterodox way.

Stress has been reported to activate the locus coeruleus (LC)–noradrenergic system. In the present study, corticosterone (CORT) was orally administrated to rats for 21 days to mimic stress status. In situ hybridization measurements showed that CORT ingestion significantly increased mRNA levels of norepinephrine transporter (NET) and dopamine β-hydroxylase (DBH) in the LC region. Immunofluorescence staining and western blotting revealed that CORT treatment also increased protein levels of NET and DBH in the LC, as well as NET protein levels in the hippocampus, the frontal cortex and the amygdala. However, CORT-induced increase of DBH protein levels only appeared in the hippocampus and the amygdala. Elevated NET and DBH expression in most of these areas (except for NET protein levels in the LC) was abolished by simultaneous treatment with combination of corticosteroid receptor antagonist mifepristone and spironolactone (s.c. for 21 days). Also, treatment with mifepristone alone prevented CORT-induced increases of NET expression and DBH protein levels in the LC. In addition, behavioral tasks showed that CORT ingestion facilitated escape in avoidance trials using an elevated T-maze, but interestingly, there was no significant effect on the escape trial. Corticosteroid receptor antagonists failed to counteract this response in CORT-treated rats. In the open-field task, CORT treatment resulted in less activity in a defined central zone compared to controls and corticosteroid receptor antagonist treatment alleviated this increase. In conclusion, the present study demonstrates that chronic exposure to CORT results in a phenotype that mimics stress-induced alteration of noradrenergic phenotypes, but the effects on behavior are task-dependent. As the sucrose consumption test strongly suggests CORT ingestion-induced depression-like behavior, further elucidation of underlying mechanisms may improve our understanding of the correlation between stress and the development of depression.

Objective.Economic access to costly medications including biologic agents can be challenging. Our objective was to examine whether patients with rheumatoid arthritis (RA) are at particular risk for cost-related medication nonadherence (CRN) and spending less on basic needs.Methods.We identified a nationally representative sample of older adults with RA (n = 1100) in the Medicare Current Beneficiary Survey (2004–2008) and compared them to older adults with other morbidities categorized by chronic disease count: 0 (n = 5898), 1–2 (n = 30,538), and ≥ 3 (n = 34,837). We compared annual rates of self-reported CRN (skipping or reducing medication doses or not obtaining prescriptions because of cost) as well as spending less on basic needs to afford medications and tested for differences using survey-weighted logistic regression analyses adjusted for demographic characteristics, health status, and prescription drug coverage.Results.In the RA sample, the unadjusted weighted prevalence of CRN ranged from 20.7% in 2004 to 18.4% in 2008 as compared to 18.5% and 11.9%, respectively, in patients with 3 or more non-RA conditions. In adjusted analyses, having RA was associated with a 3.5-fold increase in the risk of CRN (OR 3.52, 95% CI 2.63–4.71) and almost a 2.5-fold risk of spending less on basic needs (OR 2.41, 95% CI 1.78–3.25) as compared to those without a chronic condition.Conclusion.Patients with RA experience a high prevalence of CRN and forgoing of basic needs, more than do older adults with multiple other chronic conditions. The situation did not improve during a period of policy change aimed at alleviating high drug costs.

Across 3 experiments, we investigated the factors that dictate when taking a test improves subsequent memory performance (the testing effect). In Experiment 1, participants retrieving a set of targets during a retrieval practice phase ultimately recalled fewer of those targets compared with a group of participants who studied the targets twice, a negative testing effect. In Experiments 2 and 3, theoretically motivated modifications to the basic design of Experiment 1 reversed this pattern, demonstrating the more typical positive testing effect. The results from all 3 experiments were predicted by the multifactor account, an explanatory account applied to the generation effect (improved memory for self-generated material), which details why generation typically improves memory, as well as those conditions under which generation can impair memory performance. These results suggest the testing effect and the generation effect may be understood within a common framework.

This study analyzed the interaction of adolescent methylphenidate on the behavioral response to nicotine and the effects of these drug treatments on brain-derived neurotrophic factor in the nucleus accumbens and hippocampus in male and female Sprague-Dawley rats. Animals were intraperitoneal administered 1 mg/kg methylphenidate or saline using a “school day” regimen (five days on, two days off) beginning on postnatal day (P)28 and throughout behavioral testing. In Experiment 1, animals were intraperitoneal administered 0.5 mg/kg (free base) nicotine or saline every second day for 10 days from P45–P63 and tested after a three-day drug washout on the forced swim stress task on P67–P68. Results revealed that adolescent methylphenidate blunted nicotine behavioral sensitization. However, methylphenidate-treated rats given saline during sensitization demonstrated decreased latency to immobility and increased immobility time on the forced swim stress task in males that was reduced by nicotine. In Experiment 2, a different set of animals were conditioned to nicotine (0.6 mg/kg free base) or saline using the conditioned place preference behavioral paradigm from P44–P51, and given a preference test on P52. On P53, the nucleus accumbens and hippocampus were analyzed for brain-derived neurotrophic factor. Methylphenidate enhanced nicotine-conditioned place preference in females and nicotine produced conditioned place preference in males and females pre-exposed to saline in adolescence. In addition, methylphenidate and nicotine increased nucleus accumbens brain-derived neurotrophic factor in females and methylphenidate enhanced hippocampus brain-derived neurotrophic factor in males and females. Methylphenidate adolescent exposure using a clinically relevant dose and regimen results in changes in the behavioral and brain-derived neurotrophic factor responses to nicotine in adolescence that are sex-dependent.

The contribution of this paper is to describe how we can program neuroimaging workflow using Make, a software development tool designed for describing how to build executables from source files. A makefile (or a file of instructions for Make) consists of a set of rules that create or update target files if they have not been modified since their dependencies were last modified. These rules are processed to create a directed acyclic dependency graph that allows multiple entry points from which to execute the workflow. We show that using Make we can achieve many of the features of more sophisticated neuroimaging pipeline systems, including reproducibility, parallelization, fault tolerance, and quality assurance reports. We suggest that Make permits a large step toward these features with only a modest increase in programming demands over shell scripts. This approach reduces the technical skill and time required to write, debug, and maintain neuroimaging workflows in a dynamic environment, where pipelines are often modified to accommodate new best practices or to study the effect of alternative preprocessing steps, and where the underlying packages change frequently. This paper has a comprehensive accompanying manual with lab practicals and examples (see Supplemental Materials) and all data, scripts, and makefiles necessary to run the practicals and examples are available in the "makepipelines" project at NITRC. published

The enactment effect is the phenomenon whereby carrying out a simple action phrase results in superior memory compared with listening to the phrase or observing someone else carry out the action. Several early studies suggested that action memory processing is less effortful and strategic compared with traditional verbal processing, a perspective that is still argued today. In the current study, we reexamine a particularly compelling finding in support of this view (Cohen, 1985). Contrary to Cohen’s original findings, we demonstrate that additional time to encode an action phrase leads to comparable gains in recall as seen with controls. These data fit well with a different perspective of action memory, namely that the processing of actions is guided by the same strategic, effortful processing as verbal memory.

BACKGROUND Little is known about the contribution of patient behavior to incomplete laboratory monitoring, and the reasons for patient non-completion of ordered laboratory tests remain unclear.

Histone acetyltransferase enzymes (HATs) are important therapeutic targets, but there are few cell-based assays available for evaluating the pharmacodynamics of HAT inhibitors. Here we present the application of a FRET-based reporter, Histac, in live cell studies of p300/CBP HAT inhibition, by both genetic and pharmacologic disruption. shRNA knockdown of p300/CBP led to increased Histac FRET, suggesting a role for p300/CBP in the acetylation of the histone H4 tail present. Additionally, we describe a new p300/CBP HAT inhibitor, C107, and show that it can also increase cellular Histac FRET. Taken together, these studies provide a live cell strategy for identifying and evaluating p300/CBP inhibitors.

One of the foundational principles of human memory is that repetition (i.e., being presented with a stimulus multiple times) improves recall. In the current study a group of participants who studied a list of cue-target pairs twice recalled fewer targets than a group who studied the pairs only once, a negative repetition effect. Such a demonstration is novel yet theoretically motivated. Though participants in each condition studied the same set of cue-target pairs, those who studied the pairs twice were initially presented with the pairs in a way that hindered organizational processing. Even after a 2nd presentation when the pairs were presented in a manner that should facilitate organizational processing (the same presentation given to participants who received the list only once), participants did not capitalize on the structure and consequently recalled fewer targets. The results offer compelling support for the item-specific-relational account.

Laboratory monitoring of medications is typically used to establish safety prior to drug initiation and to detect drug-related injury following initiation. It is unclear whether black box warnings (BBWs) as well as evidence- and consensus-based clinical guidelines increase the likelihood of appropriate monitoring.To determine the proportion of patients newly initiated on selected cardiovascular medications with baseline assessment and follow-up laboratory monitoring and compare the prevalence of laboratory testing for drugs with and without BBWs and guidelines.This cross-sectional study included patients aged 18 years or older from a large multispecialty group practice who were prescribed a cardiovascular medication (angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, amiodarone, digoxin, lipid-lowering agents, diuretics, and potassium supplements) between January 1 and July 31, 2008. The primary outcome measure was laboratory test ordering for baseline assessment and follow-up monitoring of newly initiated cardiovascular medications.The number of new users of each study drug ranged from 49 to 1757 during the study period. Baseline laboratory test ordering across study drugs ranged from 37.4% to 94.8%, and follow-up laboratory test ordering ranged from 20.0% to 77.2%. Laboratory tests for drugs with baseline laboratory assessment recommendations in BBWs were more commonly ordered than for drugs without BBWs (86.4% vs 78.0%, p0.001). Drugs with follow-up monitoring recommendations in clinical guidelines had a lower prevalence of monitoring (33.1% vs 50.7%, p0.001).Baseline assessment of cardiovascular medication monitoring is variable. Quality measurement of adherence to BBW recommendations may improve monitoring.