Hepatic Bile Formation: Developing a New Paradigm.

In 1959, Ivar Sperber contrasted bile formation with that of urine and proposed that water flow into the canalicular conduit is in response to an osmotic, not a hydrostatic, gradient. Early attempts to support the hypothesis using a bile acid, sodium taurocholate, and the hormone secretin to stimulate bile flow led to conflicting data and a moratorium on attempts to further develop the initial proposal. However, current data amplify the initial proposal and indicate both paracellular and transcellular water flow into hepatic ductules and the canalicular conduit in response to an osmotic gradient. Also, the need to further modify the initial proposal became apparent with the recognition that bile acid aggregates (micelles), which form in the canalicular conduit, generate lecithin-cholesterol vesicles that contain water unrelated to an osmotic gradient. As part of this development is the recent introduction of the fluorescent localization after photobleaching technique for direct determination of hepatic duct flow and clarification of the role of biomarkers such as mannitol and polyethylene glycol 900. With the new paradigm, these biomarkers may prove useful for quantifying paracellular and transcellular water flow, respectively. SIGNIFICANCE STATEMENT: It is essential to identify and characterize all the sites for water flow during hepatic bile formation to obtain more precision in evaluating the causes and possible therapeutic approaches to cholestatic syndromes. Updating the Sperber proposal provides a new paradigm that addresses the advances in knowledge that have occurred.

A maize semidwarf mutant reveals a GRAS transcription factor involved in brassinosteroid signaling.

Brassinosteroids (BR) and gibberellins (GA) regulate plant height and leaf angle in maize (Zea mays). Mutants with defects in BR or GA biosynthesis or signaling identify components of these pathways and enhance our knowledge about plant growth and development. In this study, we characterized three recessive mutant alleles of GRAS transcription factor 42 (gras42) in maize, a GRAS transcription factor gene orthologous to the DWARF AND LOW TILLERING (DLT) gene of rice (Oryza sativa). These maize mutants exhibited semi-dwarf stature, shorter and wider leaves, and more upright leaf angle. Transcriptome analysis revealed a role for GRAS42 as a determinant of BR signaling. Analysis of the expression consequences from loss of GRAS42 in the gras42-mu1021149 mutant indicated a weak loss of BR signaling in the mutant, consistent with its previously demonstrated role in BR signaling in rice. Loss of BR signaling was also evident by the enhancement of weak BR biosynthetic mutant alleles in double mutants of nana plant1-1 and gras42-mu1021149. The gras42-mu1021149 mutant had little effect on GA-regulated gene expression, suggesting that GRAS42 is not a regulator of core GA signaling genes in maize. Single cell expression data identified gras42 expressed among cells in the G2/M phase of the cell cycle consistent with its previously demonstrated role in cell cycle gene expression in Arabidopsis (Arabidopsis thaliana). Cis-acting natural variation controlling GRAS42 transcript accumulation was identified by expression genome-wide association study (eGWAS) in maize. Our results demonstrate a conserved role for GRAS42/SCARECROW-LIKE 28 (SCL28)/DLT in BR signaling, clarify the role of this gene in GA signaling, and suggest mechanisms of tillering and leaf angle control by BR.

Sampling pattern discrepancy in the application of compressed sensing hyperpolarized xenon-129 lung MRI.

Although hyperpolarized (HP) 129Xe ventilation MRI can be carried out within a breath hold, it is still challenging for many sick patients. Compressed sensing (CS) is a viable alternative to accelerate this approach. However, undersampled images with identical sampling ratios differ from one another. Twenty subjects (n = 10 healthy and n = 10 patients with asthma) were scanned using a GE MR750 3 T scanner, acquiring fully sampled 2D multi-slice HP 129Xe lung ventilation images (10 s breath hold, 128 × 80 (FE × PE-frequency encoding × phase encoding) and 16 slices). Using fully sampled data, 500 variable-density Cartesian random undersampling patterns were generated, each at eight different sampling ratios from 10% to 80%. The parallel imaging and compressed sensing (PICS) command from BART was employed to reconstruct undersampled data. The signal to noise ratio (SNR), structural similarity index measurement (SSIM) and sidelobe to peak ratio of each were subsequently compared. There was a high degree of variation in both SNR and SSIM results from each of the 500 masks of each sampling rate. As the undersampling increases, there is more variation in the quantifying metrics, for both healthy and asthmatic individuals. Our study shows that random undersampling poses a significant challenge when applied at sampling ratios less than 60%, despite fulfilling CS's incoherency criteria. Such low sampling ratios will result in a large variety of undersampling patterns. Therefore, skipped segments of k-space cannot be allowed to happen randomly at low sampling rates. By optimizing the sampling pattern, CS will reach its full potential and be able to be applied to a highly undersampled 129Xe lung dataset.

Hepatobiliary circulation and dominant urinary excretion of homogentisic acid in a mouse model of alkaptonuria.

Altered activity of specific enzymes in phenylalanine-tyrosine (phe-tyr) metabolism results in incomplete breakdown of various metabolite substrates in this pathway. Increased biofluid concentration and tissue accumulation of the phe-tyr pathway metabolite homogentisic acid (HGA) is central to pathophysiology in the inherited disorder alkaptonuria (AKU). Accumulation of metabolites upstream of HGA, including tyrosine, occurs in patients on nitisinone, a licenced drug for AKU and hereditary tyrosinaemia type 1, which inhibits the enzyme responsible for HGA production. The aim of this study was to investigate the phe-tyr metabolite content of key biofluids and tissues in AKU mice on and off nitisinone to gain new insights into the biodistribution of metabolites in these altered metabolic states. The data show for the first time that HGA is present in bile in AKU (mean [±SD] = 1003[±410] µmol/L; nitisinone-treated AKU mean [±SD] = 45[±23] µmol/L). Biliary tyrosine, 3(4-hydroxyphenyl)pyruvic acid (HPPA) and 3(4-hydroxyphenyl)lactic acid (HPLA) are also increased on nitisinone. Urine was confirmed as the dominant elimination route of HGA in untreated AKU, but with indication of biliary excretion. These data provide new insights into pathways of phe-tyr metabolite biodistribution and metabolism, showing for the first time that hepatobiliary excretion contributes to the total pool of metabolites in this pathway. Our data suggest that biliary elimination of organic acids and other metabolites may play an underappreciated role in disorders of metabolism. We propose that our finding of approximately 3.8 times greater urinary HGA excretion in AKU mice compared with patients is one reason for the lack of extensive tissue ochronosis in the AKU mouse model.

Decomposing the late positive potential to cannabis cues in regular cannabis users: A temporal-spatial principal component analysis.

Cannabis use disorder (CUD) is increasing in the United States, yet, specific neural mechanisms of CUD are not well understood. Disordered substance use is characterized by heightened drug cue incentive salience, which can be measured using the late positive potential (LPP), an event-related potential (ERP) evoked by motivationally significant stimuli. The drug cue LPP is typically quantified by averaging the slow wave's scalp-recorded amplitude across its entire time course, which may obscure distinct underlying factors with differential predictive validity; however, no study to date has examined this possibility. In a sample of 105 cannabis users, temporo-spatial Principal Component Analysis was used to decompose cannabis cue modulation of the LPP into its underlying factors. Acute stress was also inducted to allow for identification of specific cannabis LPP factors sensitive to stress. Factor associations with CUD severity were also explored. Eight factors showed significantly increased amplitudes to cannabis images relative to neutral images. These factors spanned early (~372 ms), middle (~824 ms), and late (>1000 ms) windows across frontal, central, and parietal-occipital sites. CUD phenotype individual differences were primarily associated with frontal, middle/late latency factor amplitudes. Acute stress effects were limited to one early central and one late frontal factor. Taken together, results suggest that the cannabis LPP can be decomposed into distinct, temporal-spatial factors with differential responsivity to acute stress and CUD phenotype variability. Future individual difference studies examining drug cue modulation of the LPP should consider (1) frontalcentral poolings in addition to conventional central-parietal sites, and (2) later LPP time windows.

Different perceptual worlds: Parent and youth perspectives on parenting outcome trajectories from a Latino family-based program.

Discrepancies between parent and youth perceptions of their relationship are a common aspect of generational acculturation gaps influencing immigrant families. Programs designed to strengthen parenting practices among immigrant Latino families commonly address immigration stresses, including differences between parent and youth perceptions, but little is known about discrepancies in their appraisals of program effects on parenting behavior. A randomized trial was conducted examining effects on parent behavior of a program for immigrant families with youth aged 10-14, developed through community-based participatory research principles. Families (346 parents and youth) were recruited by organizations serving Latino families in a Midwestern metropolitan area and randomly assigned to the eight-session psychoeducation and skill-building program or a waitlist control. Parents and youth completed self-report measures at pre-intervention, post-intervention (4 months), and a 6-month follow-up regarding parents' expression of acceptance, efforts to solicit information about the child's experiences, and consistency of discipline, key foci of the program. Based on social cognition theory, the study focused on possible differences in parents' and youths' perceptions of change in parenting behavior. Parents in the treatment group reported pre-post improved acceptance, consistent discipline, and solicitation, whereas youth reported improvement only in parental solicitation, a pattern maintained at follow-up. In the control group, the only change was youth-reported reduction in parental acceptance. Parents' perceptions of improvement are encouraging, but overall lack of improvements from the youth perspective poses a potential problem for impact on parent-child relations. Interventions may need to target both parent and youth cognitions about behavior changes directly.

Obsessive-compulsive symptoms, perceived burdensomeness, and thwarted belongingness: Associations and implications among US veterans.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is among the most debilitating psychiatric disorders worldwide, but has gone relatively unnoticed within the US veteran population. Simultaneously, suicide rates continue to remain high within this population despite the high volume of veterans who receive psychiatric care. With recent research demonstrating OCD's unique relationship with suicidality, it is imperative to explore this association and factors that may explain this association within veterans. METHODS: The present study investigated OCD symptoms and their relationship with two known risk factors of suicide, perceived burdensomeness (PB) and thwarted belongingness (TB), in two samples of veterans. RESULTS: In the first study (N = 100), OCD symptoms were found to be uniquely related to both PB and TB even after covarying for demographics, trauma exposure, and probable depression. In the second study (N = 99), these relationships were replicated longitudinally. OCD symptoms at baseline were found to be indirectly related to suicidal ideation severity at a 1-month follow-up via PB and TB at post-treatment. CONCLUSION: This study highlights the importance of assessing and addressing OCD symptoms within veterans due to the unique relationship these symptoms have with suicidal constructs. A deeper understanding of the impact of OCD within the veteran population will inform future prevention and intervention efforts.

Transcriptional responses to gibberellin in the maize tassel and control by DELLA domain proteins.

The plant hormone gibberellin (GA) impacts plant growth and development differently depending on the developmental context. In the maize (Zea mays) tassel, application of GA alters floral development, resulting in the persistence of pistils. GA signaling is achieved by the GA-dependent turnover of DELLA domain transcription factors, encoded by dwarf8 (d8) and dwarf9 (d9) in maize. The D8-Mpl and D9-1 alleles disrupt GA signaling, resulting in short plants and normal tassel floret development in the presence of excess GA. However, D9-1 mutants are unable to block GA-induced pistil development. Gene expression in developing tassels of D8-Mpl and D9-1 mutants and their wild-type siblings was determined upon excess GA3 and mock treatments. Using GA-sensitive transcripts as reporters of GA signaling, we identified a weak loss of repression under mock conditions in both mutants, with the effect in D9-1 being greater. D9-1 was also less able to repress GA signaling in the presence of excess GA3 . We treated a diverse set of maize inbred lines with excess GA3 and measured the phenotypic consequences on multiple aspects of development (e.g., height and pistil persistence in tassel florets). Genotype affected all GA-regulated phenotypes but there was no correlation between any of the GA-affected phenotypes, indicating that the complexity of the relationship between GA and development extends beyond the two-gene epistasis previously demonstrated for GA and brassinosteroid biosynthetic mutants.

Efficacy of a brief web-based tonic immobility psychoeducation intervention among trauma-exposed adults: A randomized clinical trial.

Tonic immobility (TI) is a defensive response that may occur during traumatic events. Although TI is adaptive in certain circumstances, it has been shown to contribute to increased trauma-related symptoms and poorer recovery. However, current frontline treatments for posttraumatic stress disorder (PTSD) have not focused significant attention on the experience of TI. Thus, the aim of this study was to develop and test the impact of a brief TI-focused psychoeducation (TIP) intervention on posttraumatic cognitions and PTSD symptoms relative to a health education control intervention. The sample included 46 adults with elevated PTSD symptoms who endorsed prior TI episodes. After providing informed consent, participants were randomly assigned to either the active or control intervention and completed self-report questionnaires including the tonic immobility questionnaire (TIQ-R), Life Events Checklist for DSM-5 (LEC-5), Posttraumatic Stress Checklist for DSM-5 (PCL-5), Posttraumatic Cognitions Inventory (PTCI), and Positive and Negative Affect Schedule (PANAS) at baseline, 1-week, and 1-month follow-up assessments. Results from linear mixed effects models indicated that participants in the TIP condition reported significantly larger reductions in posttraumatic cognitions and PTSD symptoms at 1-week, ds = 0.48 and 0.84, respectively, and 1-month, ds = 0.67 and 0.74. The findings suggest that TIP is a promising intervention that may be used to reduce posttraumatic cognitions and PTSD symptoms associated with TI. Given the ease of access, TIP could be used as a standalone intervention or as an add-on to existing evidence-based treatments for PTSD.

Minority stress and mental health in lesbian, gay, bisexual, transgender, and queer survivors of sexual assault.

Extant research has shown that sexual violence disproportionately affects lesbian, gay, bisexual, transgender, and queer (LGBTQ+) individuals, conferring risk for the development of posttraumatic stress symptoms (PTSS) and related mental health conditions. However, little research has focused on specific vulnerabilities among LGBTQ+-identified sexual assault (SA) survivors (e.g., minority stress) and their associations with post-SA psychopathology. To address this gap, we examined associations between experiences of minority stress and post-SA psychopathology in a sample of LGBTQ+ individuals who experienced SA (N = 92) and completed a battery of self-report measures. Results revealed significant differences in internalized stigma, community connectedness, alcohol use, and cannabis use across sexual orientation and gender modality groups, ηp 2 = .08-11. Additionally, regression analyses indicated that experiences of violence and victimization were significantly associated with higher PTSS, ß = .31, p = .020; anxiety, ß = .39, p = .003; and alcohol use severity, ß = .31, p = .027, over and above other experiences of minority stress and psychopathology risk factors. Internalized stigma was significantly associated with cannabis use severity, ß =.34, p = .011. Finally, community connectedness was significantly associated with lower anxiety symptom severity, ß = -.42, p = .001. Although longitudinal work is needed, findings indicate that experiences of minority stress may serve as risk or maintenance factors for post-SA psychopathology. These results offer important considerations for future treatment approaches tailored to LGBTQ+ survivors of SA.

Potentially traumatic pandemic stressors and anxiety-related sleep disturbance among Latinx persons.

Latinx persons have endured elevated rates of traumatic stress related to the COVID-19 pandemic. The effect of potentially traumatic pandemic stressors on anxiety-related sleep disturbances, a factor implicated in trauma-related psychopathology, is largely unexamined in this population. The present study evaluated the additive effect of potentially traumatic pandemic stressors (e.g., hospitalization) on anxiety-related sleep disturbances. Further, given within-group disparities across Latinx communities with intersectional identities and COVID-19-related risk factors, comparisons of the likelihood of pandemic stressors, by subgroup (i.e., older persons, individuals with chronic illness, and Black Latinx persons), were evaluated. Participants were 292 (29.8% female, Mage = 35.03 years, SD = 8.72) Latinx adults who completed a questionnaire battery during a period of high contagion (June 2020-July 2021). There were statistically significant differences across groups such that participants who experienced any potentially traumatic pandemic stressors reported elevated scores on indices of anxiety, depressive symptoms, and anxiety-related sleep disturbances compared to those who had not experienced these stressors, ds = 0.54-93. Hierarchical regression analysis revealed that hospitalization was associated with anxiety-related sleep disturbances after controlling for age, sex, chronic illness history, other stressors, anxiety, depressive symptoms, and somatic symptom burden, ΔR2 = .01. Black Latinx identity and chronic illness were significantly associated with potentially traumatic pandemic-related stressors. This is the first empirical work to evaluate the role of potentially traumatic pandemic stressors on sleep disturbances among Latinx persons and indicates that hospitalization in a pandemic context has an incremental effect on sleep disturbances in this minoritized group.

A replication and extension of bifactor modelling of perseverative thought in an at-risk community sample: Exploring sex differences in the structure of PT.

BACKGROUND: Perseverative thought (PT) is a transdiagnostic construct associated with internalizing disorders. Bifactor models have shown that PT can be split into a general PT factor and lower-order factors for specific forms of PT, such as rumination and worry. No bifactor study to date has investigated if the structure of PT differs across sexes. METHODS: The study consisted of 280 individuals recruited for a larger study targeting risk factors for suicidal ideation and behaviours. Participants completed a diagnostic interview and self-report questionnaires. RESULTS: A two-factor model of PT fit best in males, whereas a bifactor model fit best in females. In a structural equation model, worry was associated with generalized anxiety disorder diagnoses in females, but not males. Rumination was associated with depressive disorder diagnoses in females, but not males. CONCLUSIONS: The present study contributes to a growing literature on PT; we found that dimensionality of PT varied by sex. We also found that relations between PT factors and generalized anxiety disorder differed by sex. Sex differences in the internalizing spectrum and related risk factors need to be considered when examining the structure and function of risk factors.

Acceptability, feasibility, and utility of a safety aid reduction treatment in underserved veterans: a pilot investigation.

Access to mental health services, particularly for veterans residing in underserved communities, remain scarce. One approach to addressing availability barriers is through the use of group-based transdiagnostic or unified treatment protocols. One such protocol, Safety Aid Reduction Treatment (START), previously termed False Safety Behavior Elimination Treatment (FSET), has received increasing empirical support. However, prior research has only examined this treatment among civilians with a primary anxiety diagnosis. Thus, the purpose of the current study was to replicate and extend prior research by examining the acceptability, feasibility, and utility of START among veterans, particularly those living in underserved communities, and across a wider array of diagnoses. Veterans (n = 22) were assessed prior to, immediately after, and one month following the 8-week treatment. The majority of veterans found START useful and acceptable. Additionally, recruitment and retention rates suggest that the treatment was feasible. Notably, results revealed reductions in overall anxiety, depression, and safety aid usage, which were maintained throughout the brief follow-up period. These findings add to a growing body of literature highlighting the utility of transdiagnostic approaches in the amelioration of various anxiety and related disorders. Limitations include the small sample size and uncontrolled design.

Validating the Suicide Behavior Questionnaire-Revised among Filipino adults during the COVID-19 pandemic.

The study aimed to examine the validity of the Suicide Behavior Questionnaire-Revised (SBQ-R) among adult Filipinos experiencing severe depression symptoms during the COVID-19-related lockdowns in 2020. Results support SBQ-R's internal reliability. Confirmatory factor analyses supported SBQ-R's one-factor structure and its measurement invariance across gender and age. The SBQ-R's positive relationship with negative affect and its negative relationships with positive affect and family support demonstrate the questionnaire's criterion-related validity. The SBQ-R's cutoff of ≥8 shows that 78% of the sample were at-risk for suicide. The SBQ-R is valid in assessing suicide risk among severely depressed adults during the COVID-19 pandemic.

A review of ICT-enabled learning for schoolgirls in Asia and its impacts on education equity.

The education pathways and opportunities of schoolgirls in Asia are facing different challenges. The empirical studies have implemented Information and Communication Technology-enabled learning to expand such pathways and opportunities and promote education inclusiveness and equity. Through the Gender Analysis Framework, this review paper focuses on exploring and discussing how ICT-enabled learning may expand schoolgirls' education pathways and opportunities in Asia for inclusive and equitable education. This review covers 30 studies that adopted ICT-enabled learning, synthesizes, and presents four key ICT-enabled learning approaches: Emerging technologies-enabled learning, Digital game-based learning, Mobile-enabled learning, and Computer-assisted learning. Our result discusses about how different approaches in this review (in)directly impact on schoolgirls' access to assets, their practice and participation in learning activities, belief and perception of their own and other stakeholders', and how policies accommodate these approaches. The review further suggests several guidelines to develop an inclusive learning environment enabled by ICT to education pathways and opportunities of schoolgirls, thereby enhancing education inclusiveness and equity.

Reduced Cell Surface Levels of C-C Chemokine Receptor 5 and Immunosuppression in Long Coronavirus Disease 2019 Syndrome.

In an exploratory trial treating "long COVID" with the CCR5-binding antibody leronlimab, we observed significantly increased blood cell surface CCR5 in treated symptomatic responders but not in nonresponders or placebo-treated participants. These findings suggest an unexpected mechanism of abnormal immune downmodulation in some persons that is normalized by leronlimab. Clinical Trials Registration. NCT04678830.

Temporal adaptations in the phenylalanine/tyrosine pathway and related factors during nitisinone-induced tyrosinaemia in alkaptonuria.

BACKGROUND: Adaptations within the phenylalanine (PHE)/tyrosine (TYR) pathway during nitisinone (NIT) are not fully understood. OBJECTIVE: To characterise the temporal changes in metabolic features in NIT-treated patients with alkaptonuria. PATIENTS AND METHODS: Serum (s) and 24-urine (u) homogentisic acid (sHGA, uHGA24), TYR (sTYR, uTYR24), PHE (sPHE, uPHE24), hydroxyphenylpyruvate (sHPPA, uHPPA24), hydroxyphenyllactate (sHPLA, uHPLA24) and sNIT were measured at baseline (V1) and until month 48 (V6) in 69 NIT-treated patients, recommended to reduce protein intake. The 24-h urine urea (uUREA24), creatinine (uCREAT24) and body weight were also measured. Amounts of tyrosine metabolites in total body water (TBW) were derived by multiplying the serum concentrations by 60% body weight, and sum of TBW and urine metabolites resulted in combined values (c). RESULTS: uUREA24 and uCREAT24 decreased between V1 and V6 during NIT, whereas body weight and sNIT increased. Linear regression coefficient between uUREA24 and uCREAT24 was extremely strong (R = 0.84). sPHE, TBWPHE and cPHE24 increased gradually from V1 to V6. A decrease in cTYR24/cPHE24, sTYR/sPHE and TBWTYR/TBWPHE was seen from V2 to V6. Serum, 24-urine and combined TYR, HPPA and HPLA either remained stable or decreased from V2 to V6. DISCUSSION: The gradual increase in PHE suggests adaptation to increasing TYR during NIT therapy. The decrease in protein intake resulted in decreased muscle mass and increased weight gain. CONCLUSION: Progressive adaptation by decreasing PHE conversion to TYR occurs over time during NIT therapy. A low protein diet results in loss of muscle mass but also weight gain suggesting an increase in fat mass.

Defects in meristem maintenance, cell division, and cytokinin signaling are early responses in the boron deficient maize mutant tassel-less1.

Meristems house the stem cells needed for the developmental plasticity observed in adverse environmental conditions and are crucial for determining plant architecture. Meristem development is particularly sensitive to deficiencies of the micronutrient boron, yet how boron integrates into meristem development pathways is unknown. We addressed this question using the boron-deficient maize mutant, tassel-less1 (tls1). Reduced boron uptake in tls1 leads to a progressive impairment of meristem development that manifests in vegetative and reproductive defects. We show, that the tls1 tassel phenotype (male reproductive structure) was partially suppressed by mutations in the CLAVATA1 (CLV1)-ortholog, thick tassel dwarf1 (td1), but not by other mutants in the well characterized CLV-WUSCHEL pathway, which controls meristem size. The suppression of tls1 by td1 correlates with altered signaling of the phytohormone cytokinin. In contrast, mutations in the meristem maintenance gene knotted1 (kn1) enhanced both vegetative and reproductive defects in tls1. In addition, reduced transcript levels of kn1 and cell cycle genes are early defects in tls1 tassel meristems. Our results show that specific meristem maintenance and hormone pathways are affected in tls1, and suggest that reduced boron levels induced by tls1 are the underlying cause of the observed defects. We, therefore, provide new insights into the molecular mechanisms affected by boron deficiency in maize, leading to a better understanding of how genetic and environmental factors integrate during shoot meristem development.

Brief, interoceptive exposure focused treatment for anxiety in mild cognitive impairment.

Anxiety is common in older adults with mild cognitive impairment (MCI), and Alzheimer's disease and related dementias (ADRD). Anxiety has also been identified as a risk factor for cognitive decline. Brief interventions targeting risk mechanisms of anxiety, such as anxiety sensitivity (AS), have been effective in reducing overall anxiety in a variety of populations. This case series investigated the feasibility and efficacy of a brief AS intervention in anxious older adults with MCI (n = 9). Paired samples t-test results indicate that this intervention is capable of significantly reducing AS as measured by the Anxiety Sensitivity Index-3 (Δ = 5.11, Hedges g = 0.82, P < 0.05). Given these large AS reductions and high acceptability, further investigation of this intervention is warranted in older adults with MCI.

Perceptions of childhood unpredictability, delay discounting, risk-taking, and adult externalizing behaviors: A life-history approach.

Guided by principles from life-history theory, theories of adaptive calibration provide an overarching theoretical framework for understanding the developmental roots of impulsivity and externalizing psychopathology. The current research provides evidence for robust associations between perceptions of childhood unpredictability, delay discounting (Studies 1a and 1b), and adult externalizing traits and behaviors (Study 2). Both associations were observed while controlling for perceptions of the harshness of childhood environments, as well as a range of demographic characteristics. The association with externalizing traits and behavior was observed over and above current mood and depressive symptoms. Study 2 also replicated a previously documented association between changes in maternal employment, residence, and cohabitation during childhood and externalizing behavior and, furthermore, suggested that this association was mediated by perceptions of unpredictability. These studies provided no evidence for links between perceived childhood unpredictability and basic forms of risk-taking (Studies 1a and 1c). This research adds to a growing body of work leveraging principles from life-history theory to demonstrate links between childhood experiences, impulsivity, and potentially debilitating forms of mental illness. This work also highlights the value of assessing people's perceptions of their childhood environments.