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PurposeThis study identifies effective components of a bicycle helmet promotion campaign, and mechanisms by which these components affect child helmet ownership.DesignA random telephone survey identified parents whose children did not own helmets prior to an educational campaign. A follow-up survey was conducted six months later. Regression analysis estimated the effects of four campaign components on child helmet ownership and tested for mediation by cognitive variables.SettingStudy participants were residents of a suburban community which undertook a citywide educational campaign to increase child helmet ownership.SubjectsSubjects were 210 parents with at least one school-aged child, none of whom owned helmets.InterventionA multicomponent campaign was implemented by a community coalition. In addition, random subsamples of the study participants received direct mail or direct telephone communications.ResultsOf the eligible respondents identified in the baseline sample, 39% completed the follow-up survey. Regression analysis showed that children whose parents received either helmet advice from a physician or direct telephone communications were 2.6 and 2.2 times more likely, respectively, to own helmets as children whose parents did not experience similar communication. Parental worry mediated the association, but parental beliefs about the effectiveness of helmets did not.ConclusionFuture helmet campaigns should use interpersonal strategies to increase parental worry about their children being involved in a bicycle accident. Generalization of these findings is limited by the high socioeconomic status of the study participants, and by the outcome measure, which is helmet ownership, not helmet use.

Activation of the Notch signaling pathway can inhibit retinal neuron differentiation while overexpression of the basic helix-loop-helix (bHLH) protein Xath5 can promote retinal ganglion cell differentiation. To determine how Notch and Xath5 may interact to regulate retinal neurogenesis, we have examined the ability of the Notch pathway to modulate Xath5 function. Overexpression of Xath5 and a constitutively active Notch receptor inhibits the ability of Xath5 to promote ectopic neurogenesis at neural plate stages. In addition, Xenopus Suppressor of Hairless (XSu(H)) and enhancer-of-split related 1 (ESR1), two downstream components in the Notch signaling pathway, can also block Xath5 function in this assay. However, the ability of Xath5 to promote ectopic neurons is not inhibited by co-expression of ESR1 constructs lacking the DNA binding basic domain or the conserved WRPW motif. At retinal stages, constitutively activating the Notch pathway can also block the ability of Xath5 to promote retinal ganglion cell differentiation and this effect can be mimicked by overexpression of ESR1, but not by ESR1 mutants lacking the WRPW motif. Xath5 can overcome inhibition by activated Notch at both neural plate and retinal stages when co-expressed with the zinc finger protein X-MyT1. Furthermore, Xath5 overexpression causes an increase in X-MyT1 expression. Taken together, these data imply that Notch, via the ESR genes, can control retinal neuron differentiation through the inhibition of Xath5.

In the past, occupational therapists have relied upon either indirect reports of client behavior or outcomes of standardized test paradigms to assess the efficacy of their treatment. The use of direct behavioral observations is proposed as an aid in the sensory integrative therapy process. Utilizing this method allows the therapist to quantify data, to devise and answer specific research questions, and to assess the progress of clients in treatment. Advice is given on how to best establish a behavior taxonomy to meet specific needs of the research or therapy situation. The benefits and drawbacks of computer-assisted direct behavioral observation are examined. It is concluded that computer-assisted direct behavioral observation could and should provide a valuable data collection tool in the occupational therapist's repertoire. [ABSTRACT FROM AUTHOR]

Within mental health services, persons in recovery from their own experiences of mental health challenges (peers) are increasingly being trained to provide peer support. This study describes individual and organizational outcomes related to engaging peers in a multisite demonstration project in California that sought to integrate them as cocreators throughout planning and implementation of digital mental health interventions. We collected data from key informants across 11 sites. Quarterly online surveys invited key informants to report perceived outcomes of the peer component. Biannual interviews elicited details regarding survey-reported outcomes. Quantitative data provided indications of outcome prevalence and consistency, and quotes from the interviews illustrated the complex realities underlying survey responses. One hundred three quarterly surveys and 39 biannual interviews were completed between Summer 2020 and Fall 2022. Key informants reported diverse outcomes, including integration of peer input into local decision making, mental health benefits to peers and community members, reduced workplace mental health stigma, and new cross-site collaborations. Five sites reported outcomes with greater consistency compared to the other six sites. Reports of increased peer visibility in the workplace coincided with reports of reduced stigma and increased value of peer input by mental health professionals. This study offers encouragement for the potential positive impact of engaging peers as cocreators of mental health interventions. Data suggest integrating peers does not increase mental health stigma and may instead result in various positive outcomes. The degree to which these outcomes manifest in a specific setting, however, may vary. Future research should seek to identify contextual factors that support actualization of positive outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Enteral nutrition (EN) therapy is a multistep process including evaluation, prescription, procurement, dispensing, labeling, administration, and monitoring. EN therapy is prone to human errors, but these are poorly defined in the literature. The purpose of this study was to audit EN administration practices to quantify errors of execution and identify which components of the EN order were labeled, administered, or documented incorrectly., Methods: On 2 nonconsecutive days, we identified all hospitalized patients with active EN orders and prospectively collected the following information: EN formula hanging/documented, formula hang time, infusion rate/documented rate (continuous EN), infused volume and documented schedule (intermittent EN), and EN modular documentation. Mismatches to the EN order were considered errors. We reviewed 1 month of hospital EN-related safety events for comparison., Results: Of 1045 data points collected from 160 patients, we identified 275 errors of execution: 135 labeling errors and 140 administration errors. The most common were hang time >48 h (85%), wrong number of modulars documented (48%), and wrong infusion rate (19%). We found one reported safety event (wrong formula delivered but not infused)., Conclusion: We identified a 15.9% error rate in EN order execution/documentation and 14% compliance with documentation of 48-h hang time. Errors (safety events) were grossly underreported. This highlighted several areas of opportunity to improve current EN use process, consistent with previous research on EN and oral nutrition supplement administration. Based on our findings, we plan to recommend implementation of EN barcoding at our institution, to model the familiar medication administration record., (© 2023 American Society for Parenteral and Enteral Nutrition.)

Peer support specialists ("peers") who have the lived experience of, and are in recovery from, mental health challenges are increasingly being integrated into mental health care as a reimbursable service across the US. This study describes the ways peers were integrated into Help@Hand, a multi-site innovation project that engaged peers throughout efforts to develop and offer digital mental health interventions across counties/cities ("sites") in California. Using a mixed methods design, we collected quantitative data via quarterly online surveys, and qualitative data via semi-annual semi-structured phone interviews with key informants from Help@Hand sites. Quantitative data were summarized as descriptive findings and qualitative data from interviews were analyzed using rapid qualitative analysis methods. In the final analytic phase, interview quotes were used to illustrate the complex realities underlying quantitative responses. 117 quarterly surveys and 46 semi-annual interviews were completed by key informants from 14 sites between September 2020 and January 2023. Peers were integrated across diverse activities for support and implementation of digital mental health interventions, including development of training and educational materials (78.6% of sites), community outreach (64.3%), technology testing (85.7%), technology piloting (90.9%), digital literacy training (71.4%), device distribution (63.6%), technical assistance (72.7%), and cross-site collaboration (66.7%). Peer-engaged activities shifted over time, reflecting project phases. Peer-provided digital literacy training and technology-related support were key ingredients for project implementations. This study indicates the wide range of ways peers can be integrated into digital mental health intervention implementations. Considering contextual readiness for peer integration may enhance their engagement into programmatic activities., (© 2024. The Author(s).)

Background: Behavioral medicine has made key contributions toward improving health outcomes. Engaging community partners in research is critical to addressing persistent health inequities. The aim of this scoping review was to explore how researchers engaged community partners within the field of behavioral medicine research from 2005 to 2023., Method: Publication databases and gray literature were searched for research that engaged community partners to address questions relevant to behavioral medicine. Articles were screened by title and abstract, and then by full text. Articles meeting the inclusion criteria were coded using the framework provided by the Engagement Navigator to identify engagement approaches, methods, and tools and when they were used during the research., Results: Of 1486 articles initially identified, 58 met the inclusion criteria. Most articles used well-known approaches (e.g., community-based participatory research; 67%), methods (e.g., advisory committees; 59%), and tools (e.g., interviews; 41%), and engaged with healthcare service providers (62%) and/or patients (53%). Community partners were most often included in research planning and design (79%), and less often in dissemination (45%)., Conclusion: Community engagement has considerable potential to address health inequities. Our assessment of the approaches, methods, and tools used by behavioral medicine researchers to engage with a diverse range of community partners points toward promising strategies for enhancing the impact of community engagement. Researchers should incorporate explicit descriptions of community engagement strategies in publications, an outcome that could be facilitated by clear publishing guidelines, structured reporting tools, and clear messaging from funders about the value of community engagement in behavioral medicine research., (© 2023. International Society of Behavioral Medicine.)

The solution-state structure of an amine-functionalised Cu 24 L 24 cage (MOP-15) is elucidated, enabling its direct covalent crosslinking into a series of highly tuneable organogels. These soft porous networks exhibit up to a ∼10-fold increase in capacity for iodine compared to the discrete cage precursor.

Infants exposed to Zika virus (ZIKV) prenatally may develop birth defects, developmental deficits, or remain asymptomatic. It is unclear why some infants are more affected than others, although enhancement of maternal ZIKV infection via immunity to an antigenically similar virus, dengue virus (DENV), may play a role. We hypothesized that DENV immunity may worsen prenatal ZIKV infection and developmental deficits in offspring. We utilized a translational macaque model to examine how maternal DENV immunity influences ZIKV-exposed infant macaque neurodevelopment in the first month of life. We inoculated eight macaques with prior DENV infection with ZIKV, five macaques with ZIKV, and four macaques with saline. DENV/ZIKV-exposed infants had significantly worse visual orientation skills than ZIKV-exposed infants whose mothers were DENV-naive, with no differences in motor, sensory or state control development. ZIKV infection characteristics and pregnancy outcomes did not individually differ between dams with and without DENV immunity, but when multiple factors were combined in a multivariate model, maternal DENV immunity combined with ZIKV infection characteristics and pregnancy parameters predicted select developmental outcomes. We demonstrate that maternal DENV immunity exacerbates visual orientation and tracking deficits in ZIKV-exposed infant macaques, suggesting that human studies should evaluate how maternal DENV immunity impacts long-term neurodevelopment.

The incorporation of reactive functional groups onto the exterior of metal-organic cages (MOCs) opens up new opportunities to link their well-defined scaffolds into functional porous solids. Amine moieties offer access to a rich catalogue of covalent chemistry; however, they also tend to coordinate undesirably and interfere with MOC formation, particular in the case of Cu 2 paddlewheel-based MOCs. We demonstrate that tuning the basicity of an aniline-functionalized ligand enables the self-assembly of a soluble, amine-functionalized Cu 4 L 4 lantern cage ( 1 ). Importantly, we show control over the coordinative propensity of the exterior amine of the ligand, which enables us to isolate a crystalline, two-dimensional metal-organic framework composed entirely of MOC units ( 2 ). Furthermore, we show that the nucleophilicity of the exterior amine of 1 can be accessed in solution to generate a cross-linked cage polymer ( 3 ) via imine condensation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Schneider, Markwell-Heys, Linder-Patton and Bloch.)

We report the self-sorting of a dynamic combinatorial library (DCL) of metal-organic cages composed of a rotationally isomerisable ligand. Convergence of the DCL occurs upon crystallisation and leads to low-symmetry Cu4L2L'2 cages that display differing porosities based on their overall shape and ligand configuration.

A Cu 4 L 4 metal-organic cage (MOC) composed of amine-protected ligands forms supramolecular coordination polymers (SCPs) upon covalent post-assembly deprotection. The amorphous SCPs form by virtue of aniline-copper coordination and possess a tunable porosity based on the rate of deprotection.

Postconditioning attenuates inflammation and fibrosis in myocardial infarction (MI). The aim of this study was to investigate whether postconditioning with the cytosine-phosphate-guanine (CpG)-containing Toll-like receptor-9 (TLR9) ligand 1668-thioate (CpG) can modulate inflammation and remodeling in reperfused murine MI. Thirty minutes of left descending coronary artery (LAD) occlusion was conducted in 12-wk-old C57BL/6 mice. Mice were treated with CpG intraperitoneally 5 min before reperfusion. The control group received PBS; the sham group did not undergo ischemia. M-mode echocardiography (3, 7, and 28 days) and Millar left ventricular (LV) catheterization were performed (7 and 28 days) before the hearts were excised and harvested for immunohistochemical (6 h, 24 h, 3 days, 7 days, and 28 days), gene expression (6 h, 24 h, and 3 days; Taqman RT-qPCR), protein, and FACS analysis (24 h and 3 days). Mice treated with CpG showed significantly better LV function after 7 and 28 days of reperfusion. Protein and mRNA expressions of proinflammatory and anti-inflammatory cytokines were significantly induced after CpG treatment. Histology revealed fewer macrophages in CpG mice after 24 h, confirmed by FACS analysis with a decrease in both classically M1- and alternative M2a-monocytes. CpG treatment reduced apoptosis and cardiomyocyte loss and was associated with induction of adaptive mechanisms, e.g., of heme-oxigenase-1 and β-/α-myosin heavy chain (MHC) ratio. Profibrotic markers collagen type Iα (Col-Ια) and Col-III induction was abrogated in CpG mice, accompanied by fewer myofibroblasts. This led to the formation of a smaller scar. Differential matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) expression contributed to attenuated remodeling in CpG, resulting in preserved cardiac function in a Toll-like receptor 1- and TLR9-dependent manner. Our study suggests a cardioprotective mechanism of CpG postconditioning, involving Toll-like receptor-driven modulation of inflammation. This is followed by attenuated remodeling and preserved LV function. NEW & NOTEWORTHY Cytosine-phosphate-guanine (CpG) postconditioning seems to mediate inflammation via Toll-like receptor-1 and Toll-like receptor-9 signaling. Enhanced cytokine and chemokine expressions are partly attenuated by IL-10 and matrix metalloproteinase-8 (MMP8) induction, being associated with lower macrophage infiltration and M1-monocyte differentiation. Furthermore, switch from α- to β-MHC and balanced MMP/TIMP expression led to lesser cardiomyocyte apoptosis, smaller scar size, and preserved cardiac function. Data of pharmacological postconditioning have been widely disappointing to date. Our study suggests a new pathway promoting myocardial postconditioning via Toll-like receptor activation.

Congenital Zika virus (ZIKV) exposure results in a spectrum of disease ranging from severe birth defects to delayed onset neurodevelopmental deficits. ZIKV-related neuropathogenesis, predictors of birth defects, and neurodevelopmental deficits are not well defined in people. Here we assess the methodological and statistical feasibility of a congenital ZIKV exposure macaque model for identifying infant neurobehavior and brain abnormalities that may underlie neurodevelopmental deficits. We inoculated five pregnant macaques with ZIKV and mock-inoculated one macaque in the first trimester. Following birth, growth, ocular structure/function, brain structure, hearing, histopathology, and neurobehavior were quantitatively assessed during the first week of life. We identified the typical pregnancy outcomes of congenital ZIKV infection, with fetal demise and placental abnormalities. We estimated sample sizes needed to define differences between groups and demonstrated that future studies quantifying brain region volumes, retinal structure, hearing, and visual pathway function require a sample size of 14 animals per group (14 ZIKV, 14 control) to detect statistically significant differences in at least half of the infant exam parameters. Establishing the parameters for future studies of neurodevelopmental outcomes following congenital ZIKV exposure in macaques is essential for robust and rigorous experimental design., Competing Interests: DHO is a paid consultant for Battelle, devoted to research in the areas of assisting in the design and interpretation of their nonhuman primate ZIKV studies. His relationship does not carry with it any restrictions on publication, and any associated intellectual property will be disclosed and processed according to UW-Madison policy. None of the animals used in this study are involved in any studies with Battelle.

Synthetic porous materials composed of metal-organic polyhedra (MOPs) have found application in topical areas such as gas storage, separation and catalysis. Control over their physical properties ( e.g. porosity) has typically been achieved through ligand design or judicious choice of metal ions. Here, we demonstrate pore-size control and on/off porosity in Cu 4 L 4 MOPs by exploiting their structural non-rigidity. We report an aldehyde-functionalised MOP ( 1 ) that can be isolated in five distinct solvatomorphs, each exhibiting different structural flexibility. When soaked in MeOH, two of these solvatomorphs undergo a rapid transformation to a thermodynamically favoured phase, whilst in acetone they template the crystallisation of an entirely new crystal packing. We support these findings by single and powder X-ray diffraction and rationalise the observed phase transformations by lattice energy calculations. Of the five solvatomorphs, three can be obtained as solvent-exchanged pseudo-polymorphs with distinct porosities in their activated form (SA BET = 35-455 m 2 g -1 ). Further control over the crystal packing of MOPs is achieved through covalent post-assembly modifications, which promote the crystallisation of isoreticular 2-D sheet-like structures., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Josephson junctions act as a natural spiking neuron-like device for neuromorphic computing. By leveraging the advances recently demonstrated in digital single flux quantum (SFQ) circuits and using recently demonstrated magnetic Josephson junction (MJJ) synaptic circuits, there is potential to make rapid progress in SFQ-based neuromorphic computing. Here we demonstrate the basic functionality of a synaptic circuit design that takes advantage of the adjustable critical current demonstrated in MJJs and implement a synaptic weighting element. The devices were fabricated with a restively shunted Nb/AlO x -Al/Nb process that did not include MJJs. Instead, the MJJ functionality was tested by making multiple circuits and varying the critical current, but not the external shunt resistance, of the oxide Josephson junction that represents the MJJ. Experimental measurements and simulations of the fabricated circuits are in good agreement.

Sensory processing disorder (SPD), a developmental regulatory condition characterized by marked under- or over-responsivity to non-noxious sensory stimulation, is a common but poorly understood disorder that can profoundly affect mood, cognition, social behavior and adaptive life skills. Little is known about the etiology and neural underpinnings. Clinical research indicates that children with SPD show greater prevalence of difficulties in complex cognitive behavior including working memory, behavioral flexibility, and regulation of sensory and affective functions, which are related to prefrontal cortex (PFC), striatal, and midbrain regions. Neuroimaging may provide insight into mechanisms underlying SPD, and animal experiments provide important evidence that is not available in human studies. Rhesus monkeys ( N = 73) were followed over a 20-year period from birth into old age. We focused on a single sensory modality, the tactile system, measured at 5-7 years, because of its critical importance for nourishment, attachment, and social reward in development. Positron emission tomography imaging was conducted at ages 12-18 years to quantify the availability of the D1 and D2 subtypes of the DA receptor (D1R and D2R), and the DA transporter (DAT). Heightened tactile responsivity was related to (a) elevated D1R in PFC overall, including lateral, ventrolateral, medial, anterior cingulate (aCg), frontopolar, and orbitofrontal (OFC) subregions, as well as nucleus accumbens (Acb), (b) reduced D2R in aCg, OFC, and substantia nigra/ventral tegmental area, and (c) elevated DAT in putamen. These findings suggest a mechanism by which DA pathways may be altered in SPD. These pathways are associated with reward processing and pain regulation, providing top-down regulation of sensory and affective processes. The balance between top-down cognitive control in the PFC-Acb pathway and bottom-up motivational function of the VTA-Acb-PFC pathway is critical for successful adaptive function. An imbalance in these two systems might explain DA-related symptoms in children with SPD, including reduced top-down regulatory function and exaggerated responsivity to stimuli. These results provide more direct evidence that SPD may involve altered DA receptor and transporter function in PFC, striatal, and midbrain regions. More work is needed to extend these results to humans.

The uniformity of the barriers in Josephson junctions (JJs) is a critical parameter in determining performance and operating margins for a wide variety of superconducting electronic circuits. We present an automated measurement system capable of measuring individual JJs across a 1 × 1 cm die at both ambient temperature and 4 K. This technique allows visualization of the spatial variation over a large area of the critical electrical properties of the junctions and allows for the direct correlation between room-temperature (RT) resistance and low temperature properties. The critical current variation of Nb x Si 1-x (x = 15%) barriers is found to be about 2.6% (one standard deviation) for 1024 junctions across an individual die and only weakly correlates with RT resistance measurements.

Home practice is a major component of mind-body programs, yet little is known about how to optimize the amount of prescribed home practice in order to achieve an effective "dose" of practice while minimizing participant burden. This study tested how varying the amount of home practice in a mind-body program impacts compliance and stress reduction, and whether prescribing a flexible home practice schedule increases compliance. Eighty-four stressed participants undergoing a 12-week yoga program were randomized to low, medium, and high home practice conditions. The medium condition allowed participants the flexibility to choose one of two amounts of practice each day. The low practice group exhibited the highest compliance (91%) compared to the medium and low practice groups (∼60%), but exhibited the lowest total practice time, and did not significantly reduce stress. The high practice group was the only group to achieve significant stress-reduction, which was maintained 12 weeks post program. Prescribing a flexible home practice schedule did not increase compliance. Results suggest that prescribing higher practice doses may maximize practice time and symptom reduction despite lower compliance., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: We investigated common and dissociable neural and psychological correlates of two widely used meditation-based stress reduction programs., Methods: Participants were randomized to the Relaxation Response (RR; n = 18; 56% female) or the Mindfulness-Based Stress Reduction (MBSR; n = 16; 56% female) programs. Both programs use a "bodyscan" meditation; however, the RR program explicitly emphasizes physical relaxation during this practice, whereas the MBSR program emphasizes mindful awareness with no explicit relaxation instructions. After the programs, neural activity during the respective meditation was investigated using functional magnetic resonance imaging., Results: Both programs were associated with reduced stress (for RR, from 14.1 ± 6.6 to 11.3 ± 5.5 [Cohen's d = 0.50; for MBSR, from 17.7 ± 5.7 to 11.9 ± 5.0 [Cohen's d = 1.02]). Conjunction analyses revealed functional coupling between ventromedial prefrontal regions and supplementary motor areas (p < .001). The disjunction analysis indicated that the RR bodyscan was associated with stronger functional connectivity of the right inferior frontal gyrus-an important hub of intentional inhibition and control-with supplementary motor areas (p < .001, family-wise error [FWE] rate corrected). The MBSR program was uniquely associated with improvements in self-compassion and rumination, and the within-group analysis of MBSR bodyscan revealed significant functional connectivity of the right anterior insula-an important hub of sensory awareness and salience-with pregenual anterior cingulate during bodyscan meditation compared with rest (p = .03, FWE corrected)., Conclusions: The bodyscan exercises in each program were associated with both overlapping and differential functional coupling patterns, which were consistent with each program's theoretical foundation. These results may have implications for the differential effects of these programs for the treatment of diverse conditions.

Neuromorphic computing promises to markedly improve the efficiency of certain computational tasks, such as perception and decision-making. Although software and specialized hardware implementations of neural networks have made tremendous accomplishments, both implementations are still many orders of magnitude less energy efficient than the human brain. We demonstrate a new form of artificial synapse based on dynamically reconfigurable superconducting Josephson junctions with magnetic nanoclusters in the barrier. The spiking energy per pulse varies with the magnetic configuration, but in our demonstration devices, the spiking energy is always less than 1 aJ. This compares very favorably with the roughly 10 fJ per synaptic event in the human brain. Each artificial synapse is composed of a Si barrier containing Mn nanoclusters with superconducting Nb electrodes. The critical current of each synapse junction, which is analogous to the synaptic weight, can be tuned using input voltage spikes that change the spin alignment of Mn nanoclusters. We demonstrate synaptic weight training with electrical pulses as small as 3 aJ. Further, the Josephson plasma frequencies of the devices, which determine the dynamical time scales, all exceed 100 GHz. These new artificial synapses provide a significant step toward a neuromorphic platform that is faster, more energy-efficient, and thus can attain far greater complexity than has been demonstrated with other technologies.

Neonatal sensory processing (tactile and vestibular function) was tested in 78 rhesus macaques from two experiments. At ages 4-5 years, striatal dopamine D 2 receptor binding was examined using positron emission tomography. At ages 5-7 years, adult sensory processing was assessed. Findings were: (a) prenatal stress exposure yielded less optimal neonatal sensory processing; (b) animals carrying the short rh5-HTTLPR allele had less optimal neonatal sensory scores than monkeys homozygous for the long allele; (c) neonatal sensory processing was significantly related to striatal D 2 receptor binding for carriers of the short allele, but not for animals homozygous for the long allele; and (d) there was moderate developmental continuity in sensory processing from the neonatal period to adulthood., (© 2016 The Authors. Child Development © 2016 Society for Research in Child Development, Inc.)

Background: Ulcerative colitis (UC) patients have an increased risk of developing colorectal carcinoma (CRC). In contrast to clinical and pathogenetic differences, little is known about how prognosis compares between these patients and those with sporadic CRC. The aim of this study was to compare their characteristics and prognosis and identify independent risk factors for patients with UC-associated CRC., Methods: A total of 126 patients who underwent surgery in our department (1984-2010) for UC-associated (n = 63) or sporadic (n = 63) CRC were included in this analysis. Patients were matched according to sex, tumor location, and disease stage. Clinical parameters and overall, recurrence-free, and disease-specific survival were compared. In subgroup analyses, clinical parameters of UC patients were correlated with survival., Results: Median follow-up was 129 months in the UC group and 99 months in the sporadic CRC group. UC patients were significantly younger and had more multifocal, high-grade, and mucinous carcinomas. Five-year overall survival rate for UC-associated and sporadic CRC was similar (65.7 vs. 63.2%, p = 0.98). Recurrence-free survival for International Union Against Cancer (UICC) stage II disease was superior in the sporadic CRC group (p = 0.039). In a subgroup analysis of UC patients, a shorter duration of UC (p = 0.045) and male sex (p = 0.005) were associated with a worse prognosis., Conclusions: Despite multiple clinical and histopathologic differences between UC-associated and sporadic CRC patients, overall survival and disease-specific survival are similar. In a subgroup analysis of UC patients with CRC, female sex was associated with a significantly better prognosis. This finding implies that estrogens may play a protective role in UC-associated CRC carcinogenesis.

Magnetic damping is of critical importance for devices that seek to exploit the electronic spin degree of freedom, as damping strongly affects the energy required and speed at which a device can operate. However, theory has struggled to quantitatively predict the damping, even in common ferromagnetic materials 1-3 . This presents a challenge for a broad range of applications in spintronics 4 and spin-orbitronics that depend on materials and structures with ultra-low damping 5,6 . It is believed that achieving ultra-low damping in metallic ferromagnets is limited by the scattering of magnons by the conduction electrons. However, we report on a binary alloy of cobalt and iron that overcomes this obstacle and exhibits a damping parameter approaching 10 -4 , which is comparable to values reported only for ferrimagnetic insulators 7,8 . We explain this phenomenon by a unique feature of the band structure in this system: the density of states exhibits a sharp minimum at the Fermi level at the same alloy concentration at which the minimum in the magnetic damping is found. This discovery provides both a significant fundamental understanding of damping mechanisms and a test of the theoretical predictions proposed by Mankovsky and colleagues 3 .

Background: We examined the effects of moderate prenatal alcohol exposure and/or prenatal stress exposure on (D1 R) binding in a non human primate model. The dopamine D1 R is involved in executive function, and it may play a role in cognitive behavioral deficits associated with prenatal alcohol and/or stress exposure. Little is known, however, about the effects of prenatal alcohol and/or stress exposure on the D1 R. We expected that prenatal insults would lead to alterations in D1 R binding in prefrontal cortex (PFC) and striatum in adulthood., Methods: Rhesus macaque females were randomly assigned to moderate alcohol exposure and/or mild prenatal stress as well as a control condition during pregnancy. Thirty-eight offspring were raised identically and studied as adults by noninvasive in vivo neuroimaging using positron emission tomography with the D1 antagonist radiotracer [(11) C]SCH 23390. Radiotracer binding in PFC and striatum was evaluated by 2 (alcohol) × 2 (stress) × 2 (sex) analysis of variance., Results: In PFC, a significant alcohol × sex interaction was observed with prenatal alcohol exposure leading to increased [(11) C]SCH 23390 binding in male monkeys. No main effect of prenatal alcohol or prenatal stress exposure was observed., Conclusions: These results suggest that prenatal alcohol exposure results in long-term increases in prefrontal dopamine D1 R binding in males. This may help explain gender differences in the prevalence of neurodevelopmental disorders consequent to prenatal alcohol exposure., (Copyright © 2015 by the Research Society on Alcoholism.)

Background: Previous studies have found interrelationships between the serotonin system and alcohol self-administration. The goal of this work was to directly observe in vivo effects of chronic ethanol self-administration on serotonin 5-HT1A receptor binding with [(18)F]mefway PET neuroimaging in rhesus monkeys. Subjects were first imaged alcohol-naïve and again during chronic ethanol self-administration to quantify changes in 5-HT1A receptor binding., Methods: Fourteen rhesus monkey subjects (10.7-12.8 years) underwent baseline [(18)F]mefway PET scans prior to alcohol exposure. Subjects then drank gradually increasing ethanol doses over four months as an induction period, immediately followed by at least nine months ad libidum ethanol access. A post [(18)F]mefway PET scan was acquired during the final three months of ad libidum ethanol self-administration. 5-HT1A receptor binding was assayed with binding potential (BPND) using the cerebellum as a reference region. Changes in 5-HT1A binding during chronic ethanol self-administration were examined. Relationships of binding metrics with daily ethanol self-administration were also assessed., Results: Widespread increases in 5-HT1A binding were observed during chronic ethanol self-administration, independent of the amount of ethanol consumed. A positive correlation between 5-HT1A binding in the raphe nuclei and average daily ethanol self-administration was also observed, indicating that baseline 5-HT1A binding in this region predicted drinking levels., Conclusions: The increase in 5-HT1A binding levels during chronic ethanol self-administration demonstrates an important modulation of the serotonin system due to chronic alcohol exposure. Furthermore, the correlation between 5-HT1A binding in the raphe nuclei and daily ethanol self-administration indicates a relationship between the serotonin system and alcohol self-administration., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

4-trans-[(18)F]Mefway is a PET radiotracer with high affinity for 5-HT1A receptors. Our preliminary work indicated the positional isomer, 3-[(18)F]mefway, would be suitable for PET imaging of 5-HT1A receptors. We now compare the in vivo behaviour of 3-mefway with 4-mefway to evaluate 3-[(18)F]mefway as a potential 5-HT1A PET radiotracer. Two male rhesus macaques were given bolus injections of both 3- and 4-trans-[(18)F]mefway in separate experiments. 90 minute dynamic PET scans were acquired. TACs were extracted in the mesial temporal lobe (MTL) and caudal anterior cingulate gyrus (cACg). The cerebellum (CB) was used as a reference region. In vivo behavior of the radiotracers in the CB was compared based upon the ratio of normalized PET uptake for 3- and 4-trans-[(18)F]mefway. Specific binding was compared by examining MTL/CB and cACg/CB ratios. The subject-averaged ratio of 3-[(18)F]mefway to 4-trans-[(18)F]mefway in the cerebellum was 0.96 for 60-90 minutes. MTL/CB reached plateaus of ~2.7 and ~6 by 40 minutes and 90 minutes for 3- and 4-trans-[(18)F]mefway, respectively. cACg/CB reached plateaus of ~2.5 and ~6 by 40 minutes and 70 minutes for 3- and 4-trans-[(18)F]mefway, respectively. The short pseudoequilibration times and sufficient uptake of 3-[(18)F]mefway may be useful in studies requiring short scan times. Furthermore, the similar nondisplaceable clearance in the CB to 4-trans-[(18)F]mefway suggests the lower BPND of 3-[(18)F]mefway is due to a lower affinity. The lower affinity of 3-[(18)F]mefway may make it useful for measuring changes in endogenous 5-HT levels, however, this remains to be ascertained.

Background: The precise nature of modifications to the nicotinic acetylcholine receptor (nAChR) system in response to chronic ethanol exposure is poorly understood. The present work used PET imaging to assay α4β2* nAChR binding levels of eight rhesus monkeys before and during controlled chronic ethanol intake., Methods: [(18)F]Nifene PET scans were conducted prior to alcohol exposure, and then again after at least 8 months controlled ethanol exposure, including 6 months at 1.5 g/kg/day following a dose escalation period. Receptor binding levels were quantified with binding potentials (BPND) using the cerebellum as a reference region. Alcohol self-administration was assessed as average daily alcohol intake during a 2 month free drinking period immediately following controlled alcohol., Results: Significant decreases in α4β2* nAChR binding were observed in both frontal and insular cortex in response to chronic ethanol exposure. During chronic alcohol exposure, BPND in the lateral geniculate region correlated positively with the amount of alcohol consumed during free drinking., Conclusions: The observed decreases in nAChR availability following chronic alcohol consumption suggest alterations to this receptor system in response to repeated alcohol administration, making this an important target for further study in alcohol abuse and alcohol and nicotine codependence., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

[(18)F]Nifene is an agonist PET radioligand developed to image α4β2* nicotinic acetylcholine receptors (nAChRs). This work aims to quantify the receptor density (Bmax) of α4β2* nAChRs and the in vivo (apparent) dissociation constant (KDapp) of [(18)F]nifene. Multiple-injection [(18)F]nifene experiments with varying cold nifene masses were conducted on four rhesus monkeys with a microPET P4 scanner. Compartment modeling techniques were used to estimate regional Bmax values and a global value of KDapp. The fast kinetic properties of [(18)F]nifene also permitted alternative estimates of Bmax and KDapp at transient equilibrium with the same experimental data using Scatchard-like methodologies. Averaged across subjects, the compartment modeling analysis yielded Bmax values of 4.8±1.4, 4.3±1.0, 1.2±0.4, and 1.2±0.3 pmol/mL in the regions of antereoventral thalamus, lateral geniculate, frontal cortex, and subiculum, respectively. The KDapp of nifene was 2.4±0.3 pmol/mL. The Scatchard analysis based on graphical evaluation of the data after transient equilibrium yielded Bmax estimations comparable to the modeling results with a positive bias of 28%. These findings show the utility of [(18)F]nifene for measuring α4β2* nAChR Bmax in vivo in the rhesus monkey with a single PET experiment.

Background: To determine the effects in adult offspring of maternal exposure to stress and alcohol during pregnancy, we imaged striatal and midbrain dopamine transporter (DAT) binding by positron emission tomography in rhesus monkeys (Macaca mulatta). We also evaluated the relationship between DAT binding and behavioral responses previously found to relate to dopamine D2 receptor density (responsivity to tactile stimuli, performance on a learning task, and behavior during a learning task)., Methods: Subjects were adult offspring derived from a 2 × 2 experiment in which pregnant monkeys were randomly assigned to control, daily mild stress exposure (acoustic startle), voluntary consumption of moderate-level alcohol, or both daily stress and alcohol. Adult offspring (n = 38) were imaged by positron emission tomography with the DAT ligand [(18)F]2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl)-nortropane ([(18)F]FECNT)., Results: Results showed that prenatal stress yielded an overall increase of 15% in [(18)F]FECNT binding in the striatum (p = .016), 17% greater binding in the putamen (p = .012), and 13% greater binding in the head of the caudate (p = .028) relative to animals not exposed to prenatal stress. Striatal [(18)F]FECNT binding correlated negatively with habituation to repeated tactile stimulation and positively with tactile responsivity. There were no significant effects of prenatal alcohol exposure on [(18)F]FECNT binding., Conclusions: Maternal exposure to mild daily stress during pregnancy yielded increases in striatal DAT availability that were apparent in adult offspring and were associated with behavioral characteristics reflecting tactile hyperresponsivity, a condition associated with problem behaviors in children., (© 2013 Society of Biological Psychiatry.)

Background: Prenatal alcohol exposure can contribute to a wide range of neurodevelopmental impairments in children and adults including behavioral and neuropsychiatric disorders. In rhesus monkeys, we examined whether moderate-level prenatal alcohol exposure would alter acoustic startle responses and prepulse inhibition (PPI) of the acoustic startle. PPI is a highly quantifiable measure of inhibitory neural processes or sensorimotor gating associated with neuropsychiatric disorders., Methods: Acoustic startle and PPI of the acoustic startle were tested in 37 adult rhesus monkeys (Macaca mulatta) from 4 experimental conditions: (i) moderate-level prenatal alcohol-exposed, (ii) prenatally stressed, (iii) moderate-level prenatal alcohol-exposed + prenatally stressed, and (iv) sucrose controls., Results: Prenatal alcohol-exposed monkeys showed a higher magnitude of acoustic startle response and disrupted PPI compared with monkeys not exposed to alcohol prenatally. Monkeys in all conditions showed higher hypothalamic-pituitary-adrenocortical (HPA) axis responses after undergoing the startle procedure, but HPA responses were unrelated to startle response magnitude, latency, or PPI., Conclusions: Finding altered PPI in monkeys prenatally exposed to a moderate dose of alcohol suggests that reduced sensorimotor gating is 1 effect of prenatal alcohol exposure. Because reduced sensorimotor gating is observed in many neuropsychiatric disorders, sensorimotor gating deficits could be an aspect of the comorbidity between fetal alcohol spectrum disorder and mental health conditions., (Copyright © 2013 by the Research Society on Alcoholism.)

Objectives: To further understanding of the factors influencing adolescents' motivations for physical activity, the relationship of variables derived from Self-Determination Theory to adolescents' affective response to exercise was examined., Design: Correlational., Method: Adolescents ( N = 182) self-reported psychological needs satisfaction (perceived competence, relatedness, and autonomy) and intrinsic motivation related to exercise. In two clinic visits, adolescents reported their affect before, during, and after a moderate-intensity and a hard-intensity exercise task., Results: Affective response to exercise and psychological needs satisfaction independently contributed to the prediction of intrinsic motivation in hierarchical linear regression models. The association between affective response to exercise and intrinsic motivation was partially mediated by psychological needs satisfaction., Conclusions: Intrinsic motivation for exercise among adolescents may be enhanced when the environment supports perceived competence, relatedness, and autonomy, and when adolescents participate in activities that they find enjoyable.

Unlabelled: Serotonin (5-HT) dysfunction has been implicated in neuropsychiatric illnesses and may play a pivotal role in the differential prevalence of depression between the sexes. Previous PET studies have revealed sex-based differences in 5-HT1A binding potential (BPND). The binding potential is a function of the radioligand-receptor affinity (1/KDapp), and receptor density (Bmax). In this work, we use a multiple-injection (MI) PET protocol and the 5-HT1A receptor antagonist, [(18)F]mefway, to compare sex-based differences of in vivo affinity, Bmax, and BPND in rhesus monkeys., Methods: PET [(18)F]mefway studies were performed on 17 (6m, 11f) rhesus monkeys using a 3-injection protocol that included partial saturation injections of mefway. Compartmental modeling was performed using a model to account for non-tracer doses of mefway for the estimation of KDapp and Bmax. BPND estimates were also acquired from the first injection (high specific activity [(18)F]mefway, 90-minute duration) for comparison using the cerebellum (CB) as a reference region. Regions of interest were selected in 5-HT1A binding regions of the hippocampus (Hp), dorsal anterior cingulate cortex (dACC), amygdala (Am), and raphe nuclei (RN)., Results: Female subjects displayed significantly (*p<0.05) lower KDapp in the Hp (-32%), Am (-38%), and RN (-37%). Only the Hp displayed significant differences in Bmax with females having a Bmax of -29% compared to males. Male subjects demonstrated significantly lower BPND measurements in the Am (14%) and RN (29%)., Conclusion: These results suggest that the higher BPND values found in females are the result of lower [(18)F]mefway KDapp. Although a more experimentally complex measurement, separate assay of KDapp and Bmax provides a more sensitive measure than BPND to identify the underlying differences between females and males in 5-HT1A function., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Increasing an individual's awareness and understanding of their dietary habits and reasons for eating may help facilitate positive dietary changes. Mobile technologies allow individuals to record diet-related behavior in real time from any location; however, the most popular software applications lack empirical evidence supporting their efficacy as health promotion tools., Objective: The purpose of this study was to test the feasibility and acceptability of a popular social media software application (Twitter) to capture young adults' dietary behavior and reasons for eating. A secondary aim was to visualize data from Twitter using a novel analytic tool designed to help identify relationships among dietary behaviors, reasons for eating, and contextual factors., Methods: Participants were trained to record all food and beverages consumed over 3 consecutive days (2 weekdays and 1 weekend day) using their mobile device's native Twitter application. A list of 24 hashtags (#) representing food groups and reasons for eating were provided to participants to guide reporting (eg, #protein, #mood). Participants were encouraged to annotate hashtags with contextual information using photos, text, and links. User experience was assessed through a combination of email reports of technical challenges and a 9-item exit survey. Participant data were captured from the public Twitter stream, and frequency of hashtag occurrence and co-occurrence were determined. Contextual data were further parsed and qualitatively analyzed. A frequency matrix was constructed to identify food and behavior hashtags that co-occurred. These relationships were visualized using GMap algorithmic mapping software., Results: A total of 50 adults completed the study. In all, 773 tweets including 2862 hashtags (1756 foods and 1106 reasons for eating) were reported. Frequently reported food groups were #grains (n=365 tweets), #dairy (n=221), and #protein (n=307). The most frequently cited reasons for eating were #social (activity) (n=122), #taste (n=146), and #convenience (n=173). Participants used a combination of study-provided hash tags and their own hash tags to describe behavior. Most rated Twitter as easy to use for the purpose of reporting diet-related behavior. "Maps" of hash tag occurrences and co-occurrences were developed that suggested time-varying diet and behavior patterns., Conclusions: Twitter combined with an analytical software tool provides a method for capturing real-time food consumption and diet-related behavior. Data visualization may provide a method to identify relationships between dietary and behavioral factors. These findings will inform the design of a study exploring the use of social media and data visualization to identify relationships between food consumption, reasons for engaging in specific food-related behaviors, relevant contextual factors, and weight and health statuses in diverse populations.

Disruption of the serotonin system has been implicated in anxiety and depression and a related genetic variation has been identified that may predispose individuals for these illnesses. The relationship of a functional variation of the serotonin transporter promoter gene (5-HTTLPR) on serotonin transporter binding using in vivo imaging techniques have yielded inconsistent findings when comparing variants for short (s) and long (l) alleles. However, a significant 5-HTTLPR effect on receptor binding at the 5-HT(1A) receptor site has been reported in humans, suggesting the 5-HTTLPR polymorphism may play a role in serotonin (5-HT) function. Rhesus monkeys possess a 5-HTTLPR length polymorphism similar to humans and serve as an excellent model for studying the effects of this orthologous genetic variation on behaviors and neurochemical functions related to the 5-HT system. In this study, PET imaging of [(18)F]mefway was performed on 58 rhesus monkeys (33 l/l, 25 s-carriers) to examine the relation between 5-HT(1A) receptor-specific binding and 5-HTTLPR genotypes. Significantly lower 5-HT(1A) binding was found in s-carrier subjects throughout both cortical brain regions and the raphe nuclei. These results demonstrate that the underlying 5-HT neurochemical system is influenced by this functional polymorphism and illustrate the strong potential for extending the nonhuman primate model into investigating the role of this genetic variant on behavior and gene-environment interactions.

A simple synthesis of the dopamine transporter ligand [(18)F]FECNT with high radiochemical yield and short synthesis time, suitable for routine production is reported. Reaction of 2β-carbomethoxy-3β-(4-chlorophenyl)nortropane with [(18)F]2-fluoroethyl triflate ([(18)F]FEtOTf) at room temperature for 4 min provided [(18)F]FECNT in 84% decay corrected radiochemical yield. Since [(18)F]FEtOTf was prepared from [(18)F]2-fluoroethyl bromide that was isolated from its starting material, formation of unwanted side products and the amount of expensive precursor used could be greatly reduced. The overall radiochemical yields of [(18)F]FECNT were 40% (n=29) and the total synthesis time was ca. 100 min. The average specific activity of [(18)F]FECNT was 377.4 GBq/μmol (10.2 Ci/μmol)., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Unlabelled: The PET radioligand 2-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine ((18)F-nifene) is an α4β2* nicotinic acetylcholine receptor (nAChR) agonist developed to provide accelerated in vivo equilibrium compared with existing α4β2* radioligands. The goal of this work was to analyze the in vivo kinetic properties of (18)F-nifene with both kinetic modeling and graphical analysis techniques., Methods: Dynamic PET experiments were performed on 4 rhesus monkeys (female; age range, 9-13 y) using a small-animal PET scanner. Studies began with a high-specific-activity (18)F-nifene injection, followed by a coinjection of (18)F-nifene and unlabeled nifene at 60 min. Sampling of arterial blood with metabolite analysis was performed throughout the experiment to provide a parent radioligand input function. In vivo kinetics were characterized with both a 1-tissue-compartment model (1TCM) and a 2-tissue-compartment model, Logan graphical methods (both with and without blood sampling), and the multilinear reference tissue model. Total distribution volumes and nondisplaceable binding potentials (BP(ND)) were used to compare regional binding of (18)F-nifene. Regions examined include the anteroventral thalamus, lateral geniculate body, frontal cortex, subiculum, and cerebellum., Results: The rapid uptake and binding of (18)F-nifene in nAChR-rich regions of the brain was appropriately modeled using the 1TCM. No evidence for specific binding of (18)F-nifene in the cerebellum was detected on the basis of the coinjection studies, suggesting the suitability of the cerebellum as a reference region. Total distribution volumes in the cerebellum were 6.91 ± 0.61 mL/cm(3). BP(ND) values calculated with the 1TCM were 1.60 ± 0.17, 1.35 ± 0.16, 0.26 ± 0.08, and 0.30 ± 0.07 in the anteroventral thalamus, lateral geniculate body, frontal cortex, and subiculum, respectively. For all brain regions, there was a less than 0.04 absolute difference in the average BP(ND) values calculated with each of the 1TCM, multilinear reference tissue model, and Logan methods., Conclusion: The fast kinetic properties and specific regional binding of (18)F-nifene promote extension of the radioligand into preclinical animal models and human subjects.

The goal of this work was to characterize the in-vivo behavior of [(18)F]mefway as a suitable positron emission tomography (PET) radiotracer for the assay of 5-hydroxytryptamine(1A) (5-HT(1A)) receptor density (B(max)). Six rhesus monkeys were studied using a multiple-injection (M-I) protocol consisting of three sequential bolus injections of [(18)F]mefway. Injection times and amounts of unlabeled mefway were optimized for the precise measurement of B(max) and specific binding parameters k(off) and k(on) for estimation of apparent K(D). The PET time series were acquired for 180 minutes with arterial sampling performed throughout. Compartmental analysis using the arterial input function was performed to obtain estimates for K(1), k(2), k(off), B(max), and K(Dapp) in the cerebral cortex and raphe nuclei (RN) using a model that accounted for nontracer doses of mefway. Averaged over subjects, highest binding was seen in the mesial temporal and dorsal anterior cingulate cortices with B(max) values of 42±8 and 36±8 pmol/mL, respectively, and lower values in the superior temporal cortex, RN, and parietal cortex of 24±4, 19±4, and 13±2 pmol/mL, respectively. The K(Dapp) of mefway for the 5-HT(1A) receptor sites was 4.3±1.3 nmol/L. In conclusion, these results show that M-I [(18)F]mefway PET experiments can be used for the in-vivo measurement of 5-HT(1A) receptor density.