Density independent decline from an environmentally transmitted parasite.

Invasive environmentally transmitted parasites have the potential to cause declines in host populations independent of host density, but this is rarely characterized in naturally occurring populations. We investigated (1) epidemiological features of a declining bare-nosed wombat (Vombatus ursinus) population in central Tasmania owing to a sarcoptic mange (agent Sarcoptes scabiei) outbreak, and (2) reviewed all longitudinal wombat-mange studies to improve our understanding of when host population declines may occur. Over a 7-year period, the wombat population declined 80% (95% CI 77-86%) and experienced a 55% range contraction. The average apparent prevalence of mange was high 27% (95% CI 21-34), increased slightly over our study period, and the population decline continued unabated, independent of declining host abundance. Combined with other longitudinal studies, our research indicated wombat populations may be at risk of decline when apparent prevalence exceeds 25%. This empirical study supports the capacity of environmentally transmitted parasites to cause density independent host population declines and suggests prevalence limits may be an indicator of impending decline-causing epizootics in bare-nosed wombats. This research is the first to test effects of density in mange epizootics where transmission is environmental and may provide a guide for when apparent prevalence indicates a local conservation threat.

Association of an Advance Care Planning Video and Communication Intervention With Documentation of Advance Care Planning Among Older Adults: A Nonrandomized Controlled Trial.

Importance: COVID-19 has disproportionately killed older adults and racial and ethnic minority individuals, raising questions about the relevance of advance care planning (ACP) in this population. Video decision aids and communication skills training offer scalable delivery models. Objective: To assess whether ACP video decision aids and a clinician communication intervention improved the rate of ACP documentation during an evolving pandemic, with a focus on African American and Hispanic patients. Design, Setting, and Participants: The Advance Care Planning: Communicating With Outpatients for Vital Informed Decisions trial was a pre-post, open-cohort nonrandomized controlled trial that compared ACP documentation across the baseline pre-COVID-19 period (September 15, 2019, to March 14, 2020), the COVID-19 wave 1 period (March 15, 2020, to September 14, 2020), and an intervention period (December 15, 2020, to June 14, 2021) at a New York metropolitan area ambulatory network of 22 clinics. All patients 65 years or older who had at least 1 clinic or telehealth visit during any of the 3 study periods were included. Main Outcomes and Measures: The primary outcome was ACP documentation. Results: A total of 14 107 patients (mean [SD] age, 81.0 [8.4] years; 8856 [62.8%] female; and 2248 [15.9%] African American or Hispanic) interacted with clinicians during the pre-COVID-19 period; 12 806 (mean [SD] age, 81.2 [8.5] years; 8047 [62.8%] female; and 1992 [15.6%] African American or Hispanic), during wave 1; and 15 106 (mean [SD] 80.9 [8.3] years; 9543 [63.2%] female; and 2535 [16.8%] African American or Hispanic), during the intervention period. Clinicians documented ACP in 3587 patients (23.8%) during the intervention period compared with 2525 (17.9%) during the pre-COVID-19 period (rate difference [RD], 5.8%; 95% CI, 0.9%-7.9%; P = .01) and 1598 (12.5%) during wave 1 (RD, 11.3%; 95% CI, 6.3%-12.1%; P < .001). Advance care planning was documented in 447 African American patients (30.0%) during the intervention period compared with 233 (18.1%) during the pre-COVID-19 period (RD, 11.9%; 95% CI, 4.1%-15.9%; P < .001) and 130 (11.0%) during wave 1 (RD, 19.1%; 95% CI, 11.7%-21.2%; P < .001). Advance care planning was documented for 222 Hispanic patients (21.2%) during the intervention period compared with 127 (13.2%) during the pre-COVID-19 period (RD, 8.0%; 95% CI, 2.1%-10.9%; P = .004) and 82 (10.2%) during wave 1 (RD, 11.1%; 95% CI, 5.5%-14.5%; P < .001). Conclusions and Relevance: This intervention, implemented during the evolving COVID-19 pandemic, was associated with higher rates of ACP documentation, especially for African American and Hispanic patients. Trial Registration: ClinicalTrials.gov Identifier: NCT04660422.

Dispositional Negative Emotionality in Childhood and Adolescence Predicts Structural Variation in the Amygdala and Caudal Anterior Cingulate During Early Adulthood: Theoretically and Empirically Based Tests.

Substantial evidence implicates the amygdala and related structures in the processing of negative emotions. Furthermore, neuroimaging evidence suggests that variations in amygdala volumes are related to trait-like individual differences in neuroticism/negative emotionality, although many questions remain about the nature of such associations. We conducted planned tests of the directional prediction that dispositional negative emotionality measured at 10-17 years using parent and youth ratings on the Child and Adolescent Dispositions Scale (CADS) would predict larger volumes of the amygdala in adulthood and conducted exploratory tests of associations with other regions implicated in emotion processing. Participants were 433 twins strategically selected for neuroimaging during wave 2 from wave 1 of the Tennessee Twins Study (TTS) by oversampling on internalizing and/or externalizing psychopathology risk. Controlling for age, sex, race-ethnicity, handedness, scanner, and total brain volume, youth-rated negative emotionality positively predicted bilateral amygdala volumes after correction for multiple testing. Each unit difference of one standard deviation (SD) in negative emotionality was associated with a .12 SD unit difference in larger volumes of both amygdalae. Parent-rated negative emotionality predicted greater thickness of the left caudal/dorsal anterior cingulate cortex (ß = 0.28). Associations of brain structure with negative emotionality were not moderated by sex. These results are striking because dispositions assessed at 10-17 years of age were predictive of grey matter volumes measured 12-13 years later in adulthood. Future longitudinal studies should examine the timing of amygdala/cingulate associations with dispositional negative emotionality to determine when these associations emerge during development.

Retrospective Review of Clozapine Use in Children and Adolescents.

OBJECTIVE: Literature describing use of clozapine by children and adolescents is limited. The primary study objective was to assess the patterns of clozapine use in an inpatient child and adolescent population. METHODS: A retrospective review of child and adolescent inpatients receiving clozapine at a Canadian children's hospital from January 2000 through December 2014 was conducted. Interdisciplinary comprehensive data collection was conducted by experienced clinicians. Baseline population characteristics and psychiatric illness risk factors were captured. Illness symptoms and severity were assessed retrospectively using validated measures including the Brief Psychiatric Rating Scale (BPRS), Children's Global Assessment Scale (CGAS) and Clinical Global Impressions (CGI) scales. Estimated clozapine dosing requirements for each patient to achieve a serum level associated with response was calculated. Clozapine-related adverse events were captured. RESULTS: Twenty-eight inpatients (64% female) receiving clozapine during the study period were identified. Mean age at clozapine initiation was 15.8 years. Twenty-three patients (82%) were taking clozapine at discharge, and of these, 22 patients (96%) experienced at least minimal improvement in BPRS and CGAS scores. Patients took a mean of 33.1 days from clozapine start to reach their maximum clozapine dosage, a mean maximum of 57% of their estimated clozapine dose requirement. Mean length of stay following clozapine initiation was 60.7 days. We observed a high rate of benign hematological adverse events, but no episodes of severe neutropenia. The majority of patients were of ethnicity associated with high risk for metabolic adverse events. CONCLUSION: Most hospitalized, treatment-refractory children requiring clozapine clinically improve despite experiencing high, but largely manageable, adverse event rates.

OBJECTIF: La littérature décrivant l'utilisation de la clozapine par les enfants et les adolescents est limitée. Le premier objectif de l'étude était d'évaluer les modèles de l'utilisation de la clozapine dans une population hospitalisée d'enfants et d'adolescents. MÉTHODES: Une revue rétrospective d'enfants et d'adolescents hospitalisés recevant de la clozapine dans un hôpital canadien pour enfants de janvier 2000 à décembre 2014 a été menée. Une collection de données interdisciplinaires détaillées a été menée par des cliniciens d'expérience. Les caractéristiques de la population au départ et les facteurs de risque de maladie psychiatrique ont été captés. Les symptômes et la gravité de la maladie ont été évalués rétrospectivement à l'aide de mesures validées notamment l'échelle abrégée d'évaluation psychiatrique (BPRS), l'échelle d'évaluation globale des enfants (CGAS) et les échelles d'évaluation clinique (CGI) Les besoins de dosage estimés de clozapine pour que chaque patient obtienne un niveau sérique associé à la réponse ont été calculés. Les effets indésirables liés à la clozapine ont été captés. RÉSULTATS: Vingt-huit patients hospitalisés (64% de sexe féminin) recevant de la clozapine durant la période de l'étude ont été identifiés. L'âge moyen lors de l'initiation de la clozapine était de 15,8 ans. Vingt-trois patients (82%) prenaient de la clozapine au congé, et sur ceux-là, 22 patients (96%) connaissaient au moins un minimum d'amélioration aux scores de BPRS et CGAS. Les patients ont pris une moyenne de 33,1 jours à partir du début de la clozapine pour apprendre à connaître leur dosage maximum de clozapine, un maximum moyen de 57% de leur besoin estimé, de dose de clozapine. La durée de séjour moyenne suivant l'initiation de clozapine était de 60,7 jours. Nous avons observé un taux élevé d'effets indésirables d'hématologie bénigne mais aucun épisode de neutropénie grave. La majorité des patients étaient d'une ethnicité associée à un risque élevé d'événements métaboliques indésirables. CONCLUSION: La plupart des enfants réfractaires au traitement hospitalisés nécessitant de la clozapine s'améliorent cliniquement même s'ils connaissent des effets indésirables élevés mais largement traitables.

Differential regional decline in dopamine receptor availability across adulthood: Linear and nonlinear effects of age.

Theories of adult brain development, based on neuropsychological test results and structural neuroimaging, suggest differential rates of age-related change in function across cortical and subcortical sub-regions. However, it remains unclear if these trends also extend to the aging dopamine system. Here we examined cross-sectional adult age differences in estimates of D2-like receptor binding potential across several cortical and subcortical brain regions using PET imaging and the radiotracer [18 F]Fallypride in two samples of healthy human adults (combined N = 132). After accounting for regional differences in overall radioligand binding, estimated percent difference in receptor binding potential by decade (linear effects) were highest in most temporal and frontal cortical regions (~6-16% per decade), moderate in parahippocampal gyrus, pregenual frontal cortex, fusiform gyrus, caudate, putamen, thalamus, and amygdala (~3-5%), and weakest in subcallosal frontal cortex, ventral striatum, pallidum, and hippocampus (~0-2%). Some regions showed linear effects of age while many showed curvilinear effects such that binding potential declined from young adulthood to middle age and then was relatively stable until old age. Overall, these data indicate that the rate and pattern of decline in D2 receptor availability is regionally heterogeneous. However, the differences across regions were challenging to organize within existing theories of brain development and did not show the same pattern of regional change that has been observed in gray matter volume, white matter integrity, or cognitive performance. This variation suggests that existing theories of adult brain development may need to be modified to better account for the spatial dynamics of dopaminergic system aging.

White matter microstructure correlates of general and specific second-order factors of psychopathology.

Increasing data indicate that prevalent forms of psychopathology can be organized into second-order dimensions based on their correlations, including a general factor of psychopathology that explains the common variance among all disorders and specific second-order externalizing and internalizing factors. Nevertheless, most existing studies on the neural correlates of psychopathology employ case-control designs that treat diagnoses as independent categories, ignoring the highly correlated nature of psychopathology. Thus, for instance, although perturbations in white matter microstructure have been identified across a range of mental disorders, nearly all such studies used case-control designs, leaving it unclear whether observed relations reflect disorder-specific characteristics or transdiagnostic associations. Using a representative sample of 410 young adult twins oversampled for psychopathology risk, we tested the hypothesis that some previously observed relations between white matter microstructure properties in major tracts and specific disorders are related to second-order factors of psychopathology. We examined fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). White matter correlates of all second-order factors were identified after controlling for multiple statistical tests, including the general factor (FA in the body of the corpus callosum), specific internalizing (AD in the fornix), and specific externalizing (AD in the splenium of the corpus callosum, sagittal stratum, anterior corona radiata, and internal capsule). These findings suggest that some features of white matter within specific tracts may be transdiagnostically associated multiple forms of psychopathology through second-order factors of psychopathology rather with than individual mental disorders.

Lack of consistent sex differences in D-amphetamine-induced dopamine release measured with [18F]fallypride PET.

RATIONALE: Sex differences in the dopaminergic response to psychostimulants could have implications for drug abuse risk and other psychopathology involving the dopamine system, but human data are limited and mixed. OBJECTIVES: Here, we sought to investigate sex differences in dopamine release after oral D-amphetamine administration. METHODS: We used [18F]fallypride positron emission tomography (PET) to measure the change in dopamine D2/3 receptor availability (%ΔBPND, an index of dopamine release) between placebo and D-amphetamine sessions in two independent datasets containing a total of 39 females (on either hormonal birth control n = 18, postmenopausal n = 10, or studied in the first 10 days of their menstrual cycle n = 11) and 37 males. RESULTS: Using both a priori anatomical regions of interest based on previous findings and voxelwise analyses, we failed to consistently detect broad sex differences in D-amphetamine-induced dopamine release. Nevertheless, there was limited evidence for greater right ventral striatal dopamine release in young adult males relative to similarly aged females, but this was not consistently observed across samples. Plasma estradiol did not correlate with dopamine release and this measure did not differ in females on and off hormonal birth control. CONCLUSIONS: While our finding in young adults from one dataset of greater %ΔBPND in males is partially consistent with a previously published study on sex differences in D-amphetamine-induced dopamine release, our data do not support the presence of consistent widespread sex differences in this measure of dopamine release.

Ventral striatal dopamine transporter availability is associated with lower trait motor impulsivity in healthy adults.

Impulsivity is a transdiagnostic feature of a range of externalizing psychiatric disorders. Preclinical work links reduced ventral striatal dopamine transporter (DAT) availability with heightened impulsivity and novelty seeking. However, there is a lack of human data investigating the relationship between DAT availability, particularly in subregions of the striatum, and the personality traits of impulsivity and novelty seeking. Here we collected PET measures of DAT availability (BPND) using the tracer 18F-FE-PE2I in 47 healthy adult subjects and examined relations between BPND in striatum, including its subregions: caudate, putamen, and ventral striatum (VS), and trait impulsivity (Barratt Impulsiveness Scale: BIS-11) and novelty seeking (Tridimensional Personality Questionnaire: TPQ-NS), controlling for age and sex. DAT BPND in each striatal subregion showed nominal negative associations with total BIS-11 but not TPQ-NS. At the subscale level, VS DAT BPND was significantly associated with BIS-11 motor impulsivity (e.g., taking actions without thinking) after correction for multiple comparisons. VS DAT BPND explained 13.2% of the variance in motor impulsivity. Our data demonstrate that DAT availability in VS is negatively related to impulsivity and suggest a particular influence of DAT regulation of dopamine signaling in VS on acting without deliberation (BIS motor impulsivity). While needing replication, these data converge with models of ventral striatal functions that emphasize its role as a key interface linking motivation to action.