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The basolateral amygdala (BLA) is reliably activated by psychological stress and hyperactive in conditions of pathological stress or trauma; however, subsets of BLA neurons are also readily activated by rewarding stimuli and can suppress fear and avoidance behaviours. The BLA is highly heterogeneous anatomically, exhibiting continuous molecular and connectivity gradients throughout the entire structure. A critical gap remains in understanding the anatomical specificity of amygdala subregions, circuits, and cell types explicitly activated by acute stress and how they are dynamically activated throughout stimulus exposure. Using a combination of topographical mapping for the activity-responsive protein FOS and fiber photometry to measure calcium transients in real-time, we sought to characterize the spatial and temporal patterns of BLA activation in response to a range of novel stressors (shock, swim, restraint, predator odour) and non-aversive, but novel stimuli (crackers, citral odour). We report four main findings: (1) the BLA exhibits clear spatial activation gradients in response to novel stimuli throughout the medial-lateral and dorsal-ventral axes, with aversive stimuli strongly biasing activation towards medial aspects of the BLA; (2) novel stimuli elicit distinct temporal activation patterns, with stressful stimuli exhibiting particularly enhanced or prolonged temporal activation patterns; (3) changes in BLA activity are associated with changes in behavioural state; and (4) norepinephrine enhances stress-induced activation of BLA neurons via the ß-noradrenergic receptor. Moving forward, it will be imperative to combine our understanding of activation gradients with molecular and circuit-specificity.

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No current technology can specifically target grass carp (Ctenopharyngodon idella) for control within aquatic ecosystems. Rotenone and Carbon Dioxide-Carp are currently the only available registered pesticides for grass carp; they are nonselective and typically applied throughout the water, equally exposing target and native species. A more selective control tool or pesticide application could be used by resource managers to support mitigation efforts. Development of delivery systems that exploit carp feeding strategies could increase selectivity of pesticides and minimize effects on native fishes. A pesticide with selective delivery could be less labor intensive and used within an integrative pest management strategy. The present study examined Antimycin A toxicity in juvenile and sub-adult grass carp and rainbow trout (Oncorhynchus mykiss) across two routes of exposure. Water-based toxicity studies were used to calculate the concentration to cause lethality in 50% of treated fish (LC50) at 24-h, while oral gavage toxicity studies were used to calculate the dose to cause lethality in 50% of treated grass carp and rainbow trout (LD50) 24- to 96-h. Although rainbow trout were more sensitive than grass carp to Antimycin A through water-based exposure, oral toxicity was similar between species, even with inherent gastrointestinal morphological differences. Successful delivery of a lethal dose of Antimycin A to grass carp was achieved through an oral route of exposure using the rapeseed bait and shows promise for registration as a control tool and eventual use in pest management plans. Although a lethal dose of Antimycin A could be incorporated into a single bait pellet, more bait was required to achieve desired mortality when fed to fish under laboratory conditions.

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Patients with B-cell lymphomas have altered cellular components of vaccine responses due to malignancy and therapy, and the optimal timing of vaccination relative to therapy remains unknown. Severe acute respiratory syndrome coronavirus 2 vaccines created an opportunity for new insights in vaccine timing because patients were challenged with a novel antigen across multiple phases of treatment. We studied serologic messenger RNA vaccine response in retrospective and prospective cohorts with lymphoma and chronic lymphocytic leukemia, paired with clinical and research immune parameters. Reduced serologic response was observed more frequently during active treatment, but nonresponse was also common within observation and posttreatment groups. Total immunoglobulin A and immunoglobulin M correlated with successful vaccine response. In individuals treated with anti-CD19-directed chimeric antigen receptor-modified T cells, nonresponse was associated with reduced B and T follicular helper cells. Predictors of vaccine response varied by disease and therapeutic group, and therefore further studies of immune health during and after cancer therapies are needed to individualize vaccine timing.

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OBJECTIVE: Few individuals with eating disorders (EDs) receive treatment. Innovations are needed to identify individuals with EDs and address care barriers. We developed a chatbot for promoting services uptake that could be paired with online screening. However, it is not yet known which components drive effects. This study estimated individual and combined contributions of four chatbot components on mental health services use (primary), chatbot helpfulness, and attitudes toward changing eating/shape/weight concerns ("change attitudes," with higher scores indicating greater importance/readiness). METHODS: Two hundred five individuals screening with an ED but not in treatment were randomized in an optimization randomized controlled trial to receive up to four chatbot components: psychoeducation, motivational interviewing, personalized service recommendations, and repeated administration (follow-up check-ins/reminders). Assessments were at baseline and 2, 6, and 14 weeks. RESULTS: Participants who received repeated administration were more likely to report mental health services use, with no significant effects of other components on services use. Repeated administration slowed the decline in change attitudes participants experienced over time. Participants who received motivational interviewing found the chatbot more helpful, but this component was also associated with larger declines in change attitudes. Participants who received personalized recommendations found the chatbot more helpful, and receiving this component on its own was associated with the most favorable change attitude time trend. Psychoeducation showed no effects. DISCUSSION: Results indicated important effects of components on outcomes; findings will be used to finalize decision making about the optimized intervention package. The chatbot shows high potential for addressing the treatment gap for EDs.

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OBJECTIVE: We developed a chatbot aimed to facilitate mental health services use for eating disorders (EDs) and offered the opportunity to enrol in a research study and use the chatbot to all adult respondents to a publicly available online ED screen who screened positive for clinical/subclinical EDs and reported not currently being in treatment. We examined the rates and correlates of enrolment in the study and uptake of the chatbot. METHOD: Following screening, eligible respondents (≥18 years, screened positive for a clinical/subclinical ED, not in treatment for an ED) were shown the study opportunity. Chi-square tests and logistic regressions explored differences in demographics, ED symptoms, suicidality, weight, and probable ED diagnoses between those who enroled and engaged with the chatbot versus those who did not. RESULTS: 6747 respondents were shown the opportunity (80.0% of all adult screens). 3.0% enroled, of whom 90.2% subsequently used the chatbot. Enrolment and chatbot uptake were more common among respondents aged ≥25 years old versus those aged 18-24 and less common among respondents who reported engaging in regular dietary restriction. CONCLUSIONS: Overall enrolment was low, yet uptake was high among those that enroled and did not differ across most demographics and symptom presentations. Future directions include evaluating respondents' attitudes towards treatment-promoting tools and removing barriers to uptake.

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Accessible, low-cost intervention options are necessary to address the rise in mental health problems among college students. Digital guided self-help, or coached, programs have been developed to provide such services, with many commercially available. As such, there are a large and growing number of individuals coaching these programs. However, an unmet need is to evaluate and assess best practices for training and supervising individuals in these positions. To this end, we describe how we recruited, trained, and supervised coaches as part of a large randomized controlled trial using a widely available digital commercial platform. Coaches were trained to provide digital guided self-help for depression, anxiety, and/or eating disorders for college students. Coaches initially attended three live training sessions over 2-3 weeks, viewed multiple training videos, and read a detailed coaching manual developed by our team. Thereafter, they attended weekly supervision. Following their term, coaches completed an exit survey to assess their supervision and training experiences. A total of 37 of 70 (53%) graduate-level student coaches completed the survey. The experience was reported as very positive (95%). In particular, the majority reported feeling well prepared, more confident, and felt they had developed useful skills for their own practice.

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Online surveys are routinely used in mental health screening and treatment follow-up assessment, though they can yield low response rates. We tested the effects of social psychology-informed influence strategies for increasing rates of participation in an online mental health screening survey (Experiment 1) and a treatment follow-up survey (Experiment 2). In Experiment 1 (N = 45,569), embedding one or any combination of three motivational appeals (personal gain, community gain, and inclusivity) in screening survey invitation and reminder emails unexpectedly led to lower rates of survey participation compared to when the appeals were not included (overall participation rate = 12.02%, ORs = 0.75 to 0.97, ps < .001). In Experiment 2 (N = 873), a video of a TikTok influencer encouraging survey participation embedded in treatment follow-up survey invitation and reminder emails did not significantly affect survey completion compared to a humorous gif unrelated to survey participation (overall participation rate = 47.88%, OR = 1.18, p = .200). Moderator analyses revealed that the video led to higher rates of participation than the gif among White participants (OR = 1.39, p = .031) and non-Hispanic participants (OR = 1.35, p = .029) only, whereas the video led to lower rates of participation than the gif among students who did not disclose their race (OR = 0.31, p = .010). Results suggested that efforts to improve online survey participation should be balanced with possible downsides (e.g., added email length) and should be evaluated for differential performance among population subgroups prior to widespread implementation.

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OBJECTIVE: To examine the mental health problems that college students with eating disorders (EDs) and comorbid depression and/or anxiety disorders preferred to target first in a digital treatment program and explore correlates of preferred treatment focus. METHODS: Four hundred and eighty nine college student users of a digital cognitive-behavioral guided self-help program targeting common mental health problems (76.7% female, Mage = 20.4 ± 4.4, 64.8% White) screened positive for an ED and ≥one other clinical mental health problem (i.e., depression, generalized anxiety disorder, social phobia, and/or panic disorder). Students also reported on insomnia, post-traumatic stress, alcohol use, and suicide risk. Before treatment, they indicated the mental health problem that they preferred to target first in treatment. Preferred treatment focus was characterized by diagnostic profile (i.e., ED + Depression, ED + Anxiety, ED + Depression + Anxiety), symptom severity, and demographics. RESULTS: 58% of students with ED + Anxiety, 47% of those with ED + Depression, and 27% of those with ED + Depression + Anxiety chose to target EDs first. Across diagnostic profiles, those who chose to target EDs first had more severe ED symptoms than those who chose to target anxiety or depression (ps < .05). Among students with ED + Depression + Anxiety, those who chose to target EDs first had lower depression symptoms than those who chose to target depression, lower generalized anxiety than those who chose to target anxiety, and lower suicidality than those who chose to target anxiety or depression (ps < .01). CONCLUSIONS: Students with EDs and comorbid depression and/or anxiety disorders showed variable preferred treatment focus across diagnostic profiles. Research should explore specific symptom presentations associated with preferred treatment focus. PUBLIC SIGNIFICANCE: Findings indicate that a sizable percentage of college students with depression/anxiety who also have EDs prefer to target EDs first in treatment, highlighting the importance of increasing availability of ED interventions to college students. Students with EDs and comorbid depression and/or anxiety disorders showed variable preferred treatment focus across diagnostic profiles, and preference to target EDs was associated with greater ED psychopathology across diagnostic profiles.

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The use of averaging has long been known to reduce noise in statistically independent systems that exhibit similar levels of stochastic fluctuation. This concept of averaging is general and applies to a wide variety of physical and man-made phenomena such as particle motion, shot noise, atomic clock stability, measurement uncertainty reduction, and methods of signal processing. Despite its prevalence in use for reducing statistical uncertainty, such averaging techniques so far remain comparatively undeveloped for application to light. We demonstrate here a method for averaging the frequency uncertainty of identical laser systems as a means to narrow the spectral linewidth of the resulting radiation. We experimentally achieve a reduction of frequency fluctuations from 40 Hz to 28 Hz by averaging two separate laser systems each locked to a fiber resonator. Only a single seed laser is necessary here as acousto-optic modulation is used to enable independent control of the second path. This technique of frequency averaging provides an effective solution to overcome the linewidth constraints of a single laser alone, particularly when limited by fundamental noise sources such as thermal noise, irrespective of the spectral shape of noise.

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OBJECTIVE: There is a strong association between sleep disturbance and negative affect. However, the day-to-day directional connections between sleep and negative affect remain unclear. We examined day-to-day relationships between sleep duration and negative affect in community adults. METHODS: Participants were two subsamples of the Midlife in the United States Study (Sample 1: n = 2,022; Sample 2: n = 782). Daily negative affect and previous night sleep duration were assessed via end-of-day telephone interviews for eight days. Random intercept cross-lagged panel models tested sleep duration as a predictor of next-day negative affect and vice versa, controlling for age, gender, and race. RESULTS: In both samples, shorter sleep duration predicted higher next-day negative affect, but daily negative affect was not a significant predictor of upcoming-night sleep duration. Follow-up analyses indicated that the relationship between sleep duration and negative affect was nonlinear. Sleeping fewer than 7.5 hours or more than 10.5 hours was associated with greater next-day negative affect than sleeping between 7.5 and 10.5 hours. CONCLUSIONS: In two large samples of community adults, sleep duration unidirectionally predicted higher next-day negative affect, and this relationship was nonlinear. Sleeping at least 7.5 hours and no more than 10.5 hours appeared to be an optimal range associated with lowest next-day negative affect.

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Objective: We studied current psychotherapy utilization rates among college students with mental health problems and identified characteristics associated with differential utilization. Participants: Nationwide online survey of students screening positive for at least one clinical mental health problem (N = 18,435). Methods: Rates and correlates of psychotherapy utilization were analyzed descriptively and with logistic regression. Results: Sample-wide, 19% reported receiving psychotherapy. Being male (vs. female), being Asian, Black or African American, or Multiracial (vs. White), greater financial difficulty, lower parent education, lower year in school, and attending a public (vs. private) institution were associated with lower utilization. Holding a gender minority (vs. female) identity and holding a sexual minority (vs. heterosexual) identity were associated with higher utilization. Utilization fell from Fall 2019 to Spring 2020, early during the COVID-19 pandemic, and subsequently rebounded. Conclusions: This study estimates current psychotherapy utilization among students with mental health problems and identifies possibly underserved populations.

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BACKGROUND AND PURPOSE: Endocannabinoid (eCB) signalling gates many aspects of the stress response, including the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis is controlled by corticotropin releasing hormone (CRH) producing neurons in the paraventricular nucleus of the hypothalamus (PVN). Disruption of eCB signalling increases drive to the HPA axis, but the mechanisms subserving this process are poorly understood. EXPERIMENTAL APPROACH: Using an array of cellular, endocrine and behavioural readouts associated with activation of CRH neurons in the PVN, we evaluated the contributions of tonic eCB signalling to the generation of a stress response. KEY RESULTS: The CB1 receptor antagonist/inverse agonist AM251, neutral antagonist NESS243 and NAPE PLD inhibitor LEI401 all uniformly increased Fos in the PVN, unmasked stress-linked behaviours, such as grooming, and increased circulating CORT, recapitulating the effects of stress. Similar effects were also seen after direct administration of AM251 into the PVN, while optogenetic inhibition of PVN CRH neurons ameliorated stress-like behavioural changes produced by disruption of eCB signalling. CONCLUSIONS AND IMPLICATIONS: These data indicate that under resting conditions, constitutive eCB signalling restricts activation of the HPA axis through local regulation of CRH neurons in the PVN.

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BACKGROUND: There is substantial heterogeneity in how people react to potentially traumatic events (PTEs). Although some literature has explored this heterogeneity, there are only a few studies identifying factors associated with it within the disaster literature. OBJECTIVE: The current investigation identified latent classes of post-traumatic stress disorder (PTSD) symptoms and differences between these classes after exposure to Hurricane Ike. METHODS: Adults living in Galveston and Chambers County, Texas, (n = 658) completed a battery of measures during an interview conducted two to five months after Hurricane Ike. Latent class analysis (LCA) was performed to identify latent classes of PTSD symptoms. Additionally, gender, age, racial or ethnic minority status, depression severity, anxiety severity, quality of life, perceived need for services, and disaster exposure were examined to explore class differences. RESULTS: LCA supported a 3-class model with low (n = 407, 61.9%), moderate (n = 191, 29.0%), and high PTSD symptoms (n = 60, 9.1%). Women appeared most at-risk for a moderate-severity presentation as compared to a low-severity presentation. Further, racial or ethnic minority groups appeared most at-risk for a high-severity presentation as compared to a moderate-severity presentation. Overall, the high symptom class had the poorest well-being, the most perceived need for services, and the highest exposure to the disaster, followed by the moderate symptom class, and finally the low symptom class. CONCLUSIONS: PTSD symptom classes appeared to be differentiated primarily by overall severity as well as important psychological, contextual, and demographic dimensions.

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PURPOSE: Prebiotic foods can be used to increase production of short-chain fatty acids (SCFA) in the gut. Of the SCFA, propionate is credited with the strongest anorectic activity. In previous work, a 50/50 blend of inulin and arabinoxylan was produced (I + AX) that significantly increased propionate production in an in vitro gut model. This study sought to establish whether chronic consumption of a prebiotic blend of I + AX decreases appetite and energy intake and increases intestinal propionate production in human participants. METHODS: MIXSAT (clinicaltrials.gov id: NCT02846454, August 2016) was a double-blind randomised acute-within-chronic crossover feeding trial in healthy adult men (n = 20). Treatments were 8 g per day I + AX for 21 days or weight-matched maltodextrin control. The primary outcome measure was perceived satiety and appetite during an acute study visit. Secondary outcomes were energy intake in an ad libitum meal, faecal SCFA concentration, and faecal microbiota composition. RESULTS: Perceived satiety and appetite were not affected by the intervention. I + AX was associated with a reduction in energy intake in an ad libitum meal, increased faecal SCFA concentration, and an increase in cell counts of Bifidobacteria, Lactobacilli, and other microbial genera associated with health. IMPLICATIONS: Chronic consumption of this blend of prebiotics decreased energy intake in a single sitting. Further studies are needed to confirm mechanism of action and to determine whether this might be useful in weight control.

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Fatty acid amide hydrolase (FAAH) degrades the endocannabinoid anandamide. A polymorphism in FAAH (FAAH C385A) reduces FAAH expression, increases anandamide levels, and increases the risk of obesity. Nevertheless, some studies have found no association between FAAH C385A and obesity. We investigated whether the environmental context governs the impact of FAAH C385A on metabolic outcomes. Using a C385A knock-in mouse model, we found that FAAH A/A mice are more susceptible to glucocorticoid-induced hyperphagia, weight gain, and activation of hypothalamic AMP-activated protein kinase (AMPK). AMPK inhibition occluded the amplified hyperphagic response to glucocorticoids in FAAH A/A mice. FAAH knockdown exclusively in agouti-related protein (AgRP) neurons mimicked the exaggerated feeding response of FAAH A/A mice to glucocorticoids. FAAH A/A mice likewise presented exaggerated orexigenic responses to ghrelin, while FAAH knockdown in AgRP neurons blunted leptin anorectic responses. Together, the FAAH A/A genotype amplifies orexigenic responses and decreases anorexigenic responses, providing a putative mechanism explaining the diverging human findings.

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In nutritional ecology the intake target is the diet that maximises consumer fitness. A key hypothesis of nutritional ecology is that natural selection has acted upon the behavioural and physiological traits of consumers to result in them Selectively Consuming prey to match the Intake Target (SCIT). SCIT has been documented in some herbivores and omnivores, which experience strong heterogeneity in the nutritional quality of available foods. Although carnivores experience a prey community with a much more homogeneous nutrient composition, SCIT by carnivores has nevertheless been deemed highly likely by some researchers. Here we test for SCIT for micronutrients (amino acids) in two freshwater carnivores: the river blackfish and the two-spined blackfish. Although both blackfishes exhibited non-random consumption of prey from the environment, this resulted in non-random consumption of amino acids in only one species, the river blackfish. Non-random consumption of amino acids by river blackfish was not SCIT, but instead an artefact of habitat-specific foraging. We present hypotheses to explain why wild populations of freshwater carnivores may not exhibit SCIT for amino acids. Our work highlights the need for careful, critical tests of the hypotheses and assumptions of nutritional ecology and its application to wild populations.

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Fish mortality is associated with harmful algal blooms, although whether toxicity is related directly to the presence of cyanotoxins or the prevailing water chemistry remains unclear. Similarly, while planktivorous fish may be exposed to toxin through the diet, the hazard posed by waterborne extracellular toxin to carnivorous fish is less well understood. In this study rainbow trout (Oncorhynchus mykiss) were exposed for up to 28 d to waterborne microcystin-LR at nominal concentrations of 1.5 and 50 µg L-1 (measured values 2 and 49 µg L-1, respectively). The former represents the Canadian drinking water guideline, and the latter an elevated environmental level. This study hypothesised that waterborne toxin exposure would specifically impact gill function, and given the importance of this tissue in freshwater fish ion regulation, effects on plasma ions and branchial ion transporter activity would be observed. Microcystin-LR exposure resulted in a significant and persistent hypocalcaemia at the higher exposure concentration, but plasma sodium and branchial activities of the sodium/potassium ATPase, proton ATPase and calcium ATPase enzymes remained unaffected. An in vitro assessment failed to show any effect of microcystin-LR on branchial calcium ATPase activity even at exposure concentrations as high as 1000 µg L-1. A transient increase in hepatic alkaline phosphatase activity was also observed at 49 µg L-1, but there were no effects of toxin exposure on branchial or hepatic lactate dehydrogenase activity. These results suggest that microcystin-LR exposure does not have a general effect on ion regulation, but instead produces a novel and specific impact on calcium metabolism in rainbow trout, although the mechanism underlying this effect remains unknown.

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BACKGROUND: The contrast avoidance model (CAM) proposes that persons with generalized anxiety disorder (GAD) are sensitive to sharp increases in negative emotion or decreases in positive emotion (i.e., negative emotional contrasts; NEC) and use worry to avoid NEC. Sensitivity to and avoidance of NEC could also be a shared feature of major depressive disorder (MDD) and social anxiety disorder (SAD). METHODS: In a large college sample (N = 1409), we used receiver operating characteristics analysis to examine the accuracy of a measure of emotional contrast avoidance in detecting probable GAD, MDD, and SAD. RESULTS: Participants with probable GAD, MDD, and SAD all reported higher levels of contrast avoidance than participants without the disorder (Cohen's d = 1.32, 1.62 and 1.53, respectively). Area under the curve, a measure of predictive accuracy, was 0.81, 0.87, and 0.83 for predicting probable GAD, MDD, and SAD, respectively. A cutoff score of 48.5 optimized predictive accuracy for probable GAD and SAD, and 50.5 optimized accuracy for probable MDD. CONCLUSION: A measure of emotional contrast avoidance demonstrated excellent ability to predict probable GAD, MDD, and SAD. Sensitivity to and avoidance of NEC appears to be a transdiagnostic feature of these disorders.

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Many young individuals at risk for eating disorders spend time on social media and frequently search for information related to their body image concerns. In a large randomized study, we demonstrated that a guided chat-based intervention could reduce weight and shape concerns and eating disorder pathology. The goal of the current study was to determine if a modified single session mini-course, derived from the aforementioned chat-based intervention, could reduce body image concerns among individuals using eating disorder related search terms on a social media platform. Over a two-month period of prompting individuals, 525 people followed the link to the web-based application where the intervention was hosted and subsequently completed the mini-course. This resulted in a significant improvement on the one-time body image satisfaction question pre-to post intervention (p < .001) with a moderate effect size (Cohen's d = 0.54). Additionally, individuals completing the program showed significant improvement on motivation to change their body image (p < .001) with a small effect size (Cohen's d = 0.28). Additionally, users reported that the program was enjoyable and easy to use. These results suggest that a single session micro-intervention, offered to individuals on social media, can help improve body image.

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