Service users perspectives on psychosis-risk terminology: An Italian study on labeling terms preferences and stigma.

AIMS: The current range of labeling terms-at-risk mental state (ARMS), ultra-high risk for psychosis (UHR), and attenuated psychotic syndrome (APS)-used to refer to the psychosis-risk concept is varied, and their acceptability and potential stigma are not well understood. By involving Italian youth with lived experience of mental ill-health, we aimed to generate new labeling terms for psychosis-risk, and to evaluate literacy, attitudes, and preferences regarding these and the existing terms. Additionally, we investigated opinions of disclosure of the at-risk concept in clinical practice. METHODS: Through a dual-moderator focus group, novel diagnostic terms were coined for the at-risk concept: psychosis proneness (PP), change of personal reality (CPR), and hints of subjectivity dysregulation (HSD). A specifically designed questionnaire was then completed by 47 help-seeking youths, 60 relatives, and 61 clinicians to test newly generated and already established at-risk terms. RESULTS: Literacy on already established terms was significantly lower among youth (mean= 42 %) and relatives (mean= 38 %). ARMS was the preferred and least stigmatizing term among young people and clinicians. UHR was considered the most stigmatizing label. Among newly generated terms, CPR was the least stigmatizing and most informative. Disclosure of at-risk terminology was generally preferred after establishing a trusting clinician-patient relationship. CONCLUSIONS: Findings support ARMS as a useful and acceptable term in clinical practice with young people, while UHR is associated with the highest stigma. CPR is promising and should be tested in cross-cultural studies. In Italy, there is an urgent need for improving literacy on prevention in mental health.

Longitudinal associations between early post-injury serum BDNF levels and the development of post-traumatic stress disorder over two years.

BACKGROUND: This study investigated the longitudinal associations between serum BDNF (sBDNF) levels measured early after injury and the onset of post-traumatic stress disorder (PTSD) across two years. METHODS: Patients with moderate to severe physical injuries were enrolled from a trauma center. At baseline, sBDNF levels were measured and a comprehensive socio-demographic and clinical data were collected. The range of time from physical injuries to blood collection was 1-28 days, with a median (IQR) of 8.0 (6.0) days. PTSD diagnoses were determined at 3, 6, 12, and 24 months post-injury using the CAPS-5. Linear regression analyses assessed the relationship between sBDNF levels and PTSD diagnoses. RESULTS: Out of 923 patients, 112 (12.1 %) developed PTSD during the study. Prevalence rates were 8.8 % at 3 months, 7.6 % at 6 months, 4.8 % at 12 months, and 3.7 % at 24 months. Significantly, lower sBDNF levels were associated with PTSD at 12 and 24 months, after adjusting for covariates and applying Bonferroni corrections, but not at earlier assessments. LIMITATIONS: Focusing on patients with moderate to severe injuries from a single center may limit the findings' generalizability. CONCLUSION: Early post-injury sBDNF levels are predictive biomarkers for PTSD, especially significant at 12 and 24 months post-injury.

Genome-wide association study and polygenic risk score analysis for schizophrenia in a Korean population.

Although large-scale genome-wide association studies (GWASs) have revealed the genetic architecture of schizophrenia, these studies have mainly focused on populations of European ancestry. This study aimed to identify common genetic variants associated with schizophrenia in the Korean population and evaluate the performance of polygenic risk scores (PRSs) derived from large-scale GWASs across ancestries. In the Korean psychiatric GWAS project (KPGP), seven academic institutes and their affiliated hospitals across South Korea recruited a cohort of 1670 patients with DSM-IV-defined schizophrenia and 2271 healthy controls. A total of 6690,822 SNPs were tested for association with schizophrenia. We identified one previously unreported genome-wide significant locus rs2423464 (P = 2.83 × 10-11; odds ratio = 1.65; 95 % confidence interval = 1.43-1.91, minor allele frequency = 0.126). This variant was also associated with increased lysosomal-associated membrane protein family member 5 (LAMP5) gene expression. The PRS derived from the meta-analysis results of East Asian and European GWASs explained a larger proportion of the phenotypic variance in the Korean schizophrenia sample than the PRS of an East Asian or European GWAS. (R2 = 0.073 for meta-analysis; 0.028 for East Asian GWAS; 0.037 for European GWAS). GWASs involving diverse ethnic groups will expand our understanding of the genetic architecture of schizophrenia.

Interaction Effect of Childhood Abuse History and Suicidality on 12-Month Antidepressant Response in Patients With Depressive Disorder.

OBJECTIVE: We aimed to identify the individual and interactive effects of childhood abuse and suicidal ideation on antidepressant treatment response in 12 months. METHODS: In this prospective research, 1,262 depressive patients were asked about their childhood abuse history, suicidal ideation, and other clinical characteristics and socio-demographic features at baseline, and 1,015 of them were followed during 1 year of stepwise pharmacotherapy. The individual and interactive relationships of the childhood abuse history and suicidal ideation on 12-month antidepressant non-remission were explored by logistic regression with relevant covariates. RESULTS: Having a childhood abuse history and higher suicidal ideation significantly predicted a non-remission state in 12 months respectively. The interaction term of childhood abuse and suicidal ideation was also significantly related to a non-remission state at 12 months. To be specific, in the low suicidal ideation group, depressive patients with a childhood abuse history were more likely to be in a non-remission state after 12 months of medication. In the high suicidal ideation group, however, childhood abuse history was not significantly associated with the non-remission state at 12 months. CONCLUSION: The childhood abuse history and the level of suicidal ideation are informative factors predicting the long-term results of antidepressant treatment, especially when they are combined. Clinicians may consider antidepressants with a higher affinity for patients with childhood abuse history even if they don't have suicidal ideation. The cognitive intervention for suicidal ideation might be helpful in addition to pharmacological treatment.

Serum cortisol and neuroticism for post-traumatic stress disorder over 2 years in patients with physical injuries.

AIM: This study aimed to explore the relationships between serum cortisol levels, personality traits, and the development of Post-Traumatic Stress Disorder (PTSD) over 2 years among individuals with physical injuries. METHODS: Participants were consecutively recruited from a trauma center and followed prospectively for 2 years. At baseline, serum cortisol levels were measured, and personality traits were categorized into five dimensions (Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness), using the Big Five Inventory-10. The diagnosis of PTSD during follow-up (at 3, 6, 12, and 24 months post-injury) was determined using the Clinician-Administered PTSD Scale for DSM-5. Binary and multinomial logistic regression analyses were conducted to examine the interactions between cortisol levels, personality traits, and PTSD development. RESULTS: Among 923 patients analyzed, 112 (12.1%) were diagnosed with PTSD at some point during the study period, with prevalence rates decreasing from 8.8% at 3 months to 3.7% at 24 months post-injury. Direct associations between cortisol levels or personality traits and PTSD were not observed. However, a significant interaction between lower cortisol levels and higher Neuroticism in relation to PTSD risk was identified, especially during the early follow-up periods (3 to 6 months), but this association waned from the 12-month follow-up onward. CONCLUSION: Our findings reveal Neuroticism-dependent associations between serum cortisol levels and PTSD development, exhibiting temporal variations. These results suggest that PTSD development may be influenced by a complex, time-sensitive interplay of biological and psychosocial factors, underscoring the importance of considering individual differences in stress reactivity and personality in PTSD research and treatment.

Assessing the Predictive Validity of Early Post-injury CAPS-5 for Later Posttraumatic Stress Disorder Diagnosis.

Abstract.Objective: The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a widely recognized tool with exceptional reliability and validity in evaluating and diagnosing PTSD. This study aimed to determine the predictive values of CAPS-5 assessed early postinjury for subsequent development of PTSD during a 2-year follow-up period.Methods: Patients with moderate to severe physical injuries were recruited from a trauma center at a university hospital in South Korea between June 2015 and January 2021. At baseline, 1,142 patients underwent evaluations using CAPS-5 for the diagnosis of acute stress disorder (ASD) along with total scores. They were followed up for PTSD using the CAPS-5 evaluations at 3, 6, 12, and 24 months post-baseline. Area under receiver operating curve (AUROC) analyses were conducted to identify predictive values of the CAPS-5 for later PTSD development.Results: CAPS-5 diagnosis of ASD at baseline displayed fair to failed performance (AUROCs: 0.555-0.722) for predicting follow-up PTSD. However, CAPS-5 scores of ≥15 exhibited good to fair predictive accuracy (AUROCs: 0.767-0.854) for later PTSD development. Notably, for patients with intentional injuries or a history of previous trauma, a higher CAPS-5 score of ≥16 showed improved predictive accuracy.Conclusion: A CAPS-5 score of ≥15 would be an effective and practical cutoff for early prediction of PTSD following physical injuries. In cases of intentional injuries or a documented trauma history, a cutoff of ≥16 may offer enhanced predictive precision. Future research in diverse settings and populations is needed to confirm the generalizability of our findings.

Delayed effects of alcohol consumption on the association between serum BDNF levels and post-traumatic stress disorder development over two-years.

BACKGROUNDS: This study aimed to examine the individual and combined effects of serum BDNF (sBDNF) levels and alcohol consumption status, assessed shortly after a physical injury, on the development of post-traumatic stress disorder (PTSD) over two years. METHODS: Participants were consecutively recruited from a trauma center and followed prospectively for two years. At baseline, sBDNF levels and alcohol consumption history were assessed. A range of socio-demographic and clinical covariates were also collected. PTSD diagnosis during follow-up (3, 6, 12, and 24 months post-injury) was established using the Clinician-Administered PTSD Scale for DSM-5. Binary and multinomial logistic regression analyses were employed to investigate the relationships between sBDNF levels, alcohol consumption status, and PTSD onset. RESULTS: Out of 923 participants analyzed, 112 (12.1%) developed PTSD at some point during the study, with prevalence rates of 8.8% at 3 months, 7.6% at 6 months, 4.8% at 12 months, and 3.7% at 24 months. The study found no individual associations between sBDNF levels or alcohol consumption status and PTSD development. However, lower sBDNF levels significantly predicted PTSD in individuals who consumed alcohol, a relationship not observed in non-drinkers, with significant interaction terms. This pattern was consistent at later follow-up points from 12 to 24 months, but not at earlier assessments at 3 and 6 months. LIMITATIONS: The study's reliance on participants from a single trauma center with moderate to severe injuries may limit the generalizability of the findings. CONCLUSIONS: A significant interaction between sBDNF levels and alcohol consumption in relation to PTSD development was observed, particularly in the long term. These findings highlight the necessity of considering both sBDNF levels and alcohol consumption in strategies aimed at preventing PTSD among individuals with physical injuries, underscoring the need for tailored approaches based on these factors.

The Relationship Between Fast Food Consumption and Daily Lifestyle Changes During School Closures Following the COVID-19 Pandemic: A Cross-Sectional Study Among Adolescents in Korea.

OBJECTIVE: Increased fast food consumption can have adverse effects on health and well-being among adolescents, posing a significant public health concern. The school closures due to the coronavirus disease-2019 (COVID-19) pandemic have led to changes in eating patterns and disrupted a balance diet among adolescents. This study explored the factors associated with fast food consumption among adolescents during school closures due to the COVID-19 pandemic. METHODS: A total of 1,710 middle and high school students in Gwangju, South Korea participated in a cross-sectional survey. The self-administered questionnaire included items assessing dietary intake, physical activity, sleep, media use, and sociodemographic information. The Patient Health Questonnaire-9, Generalized Anxiety Disorder-7, and three item version of the UCLA Loneliness Scale were also administered. Multivariable logistic regression was used to examine the factors associated with increased fast food consumption. RESULTS: Approximately 34.6% of the surveyed adolescents reported increased fast food consumption during school closures, as well as increased sleep duration, increased sedentary behaviors including watching TV and using the internet, and reduced physical activity. Multivariable logistic regression analysis revealed that fast food consumption during school closures was associated with irregular patterns of main meals and sleep, decreased physical activity, increased internet use, and a lack of daytime adult supervision. CONCLUSION: Our results highlight the need for dietary and lifestyle monitoring and guidelines to promote health among adolescents, especially during school closures. In conclusion, nutrition intervention programs aiming to limit fast food consumption and enhance healthy dietary habits among adolescents during long-term school closures are warranted.

Clinical, cognitive, and functional characteristics of recent-onset psychosis with autistic features: A 2-year longitudinal study.

Though categorized as separate illnesses, schizophrenia and autism are known to exhibit shared characteristics. This study explored the distinctions in clinical, cognitive, and functional characteristics among individuals with recent-onset psychosis, considering the severity of their autistic symptoms, involving longitudinal examinations. We analyzed 671 patients with recent-onset psychosis from Korean Early Psychosis Cohort Study (KEPS), and used the PANSS Autism Severity Score (PAUSS) to categorize patient into 'autistic', 'moderate', and 'non-autistic' groups. The autistic group had the highest rate of schizophrenia diagnosis, and the lowest incidence of comorbid psychiatric disorders. Schizophrenia diagnosis predicted membership of the autistic group. More severe autistic symptoms correlated with worse overall symptoms and functional outcomes, which significantly predicted membership of the autistic group. Cognitive impairments and emotional recognition difficulties increased with the severity of autistic symptoms. 2-year longitudinal assessments demonstrated that group differences in autistic features and overall symptoms, and functional outcomes remained consistent, and membership of the autistic group significantly predicted symptomatic remission and functional recovery. In conclusion, the presence of autistic symptoms has a significant impact on the overall symptomatology and functional capabilities. They are enduring attributes rather than temporary state variables, and serve as a significant predictor for both symptomatic and functional recovery.

Differential predictors of early- and delayed-onset post-traumatic stress disorder following physical injury: a two-year longitudinal study.

Objectives: This study aimed to investigate the predictors of both early- and delayed-onset PTSD over a 2-year period following physical injuries. Methods: Patients were recruited from a trauma center at a university hospital in South Korea (June 2015 ~ January 2021). At baseline, 1142 patients underwent comprehensive assessments including socio-demographic, pre-trauma, trauma-related, and peri-trauma evaluations. Diagnoses of acute stress disorder (ASD) and subthreshold ASD were also determined using the Clinician-administered PTSD Scale (CAPS). Follow-up assessments at three months included diagnoses of PTSD and subthreshold PTSD using CAPS, and stressful life events (SLEs), with additional evaluations at 6, 12, and 24 months. The analyzed sample comprised 1014 patients followed up at least once after the baseline and 3-month evaluations. PTSD diagnoses were categorized into early-onset (within the first six months after trauma) and delayed-onset (more than six months after trauma). Logistic regression models identified predictors for each group. Results: Early-onset and delayed-onset PTSD were diagnosed in 79 and 35 patients, respectively. Early-onset PTSD was predicted by previous psychiatric disorders, previous traumatic events, ASD and subthreshold ASD diagnoses, and higher anxiety levels. In contrast, delayed-onset PTSD was linked to higher education, higher injury severity, and subthreshold PTSD and SLEs at 3-month follow-up. Conclusion: Distinct predictors were found for early-onset and delayed-onset PTSD. The findings underscore the heterogeneous factors influencing the temporal development of PTSD post-trauma, and may provide valuable guidance for more targeted interventions and improved patient outcomes.

Moderating role of functioning level on the association between suicidal ideation and delayed-onset post-traumatic stress disorder.

OBJECTIVES: This study aimed to investigate the relationship between suicidal ideation at baseline and the development of post-traumatic stress disorder (PTSD) in individuals who have experienced physical injuries, with a specific focus on how this relationship is moderated by the patient's functioning level. METHODS: Participants were consecutively recruited from a trauma center and prospectively followed for two years. At baseline, suicidal ideation was assessed using the Brief Psychiatric Rating Scale, and functioning level was evaluated using the Social and Occupational Functioning Assessment Scale. During the follow-up, PTSD diagnosis was established using the Clinician-Administered PTSD Scale for DSM-5. Binary and multinomial logistic regression analyses were employed to examine the associations between suicidal ideation, functioning level, and PTSD. RESULTS: Of the 1014 participants analyzed, 114 (11.2%) developed PTSD, with early-onset observed in 79 (7.8%) and delayed-onset in 35 (3.5%) cases. Suicidal ideation at baseline was significantly associated with both early- and delayed-onset PTSD. Notably, higher functioning individuals with baseline suicidal ideation had an increased likelihood of developing delayed-onset PTSD, while this association was not significant in lower functioning individuals, with significant interaction terms. Additionally, suicidal ideation was a consistent predictor of early-onset PTSD across all functioning levels. CONCLUSION: The impact of baseline suicidal ideation on PTSD varies depending on the individual's functioning level, with higher functioning individuals being more vulnerable to delayed-onset PTSD. These findings underscore the importance of considering functional status in the assessment and intervention of PTSD following physical trauma.

Understanding the Fluctuations in Korea's Suicide Rates: A Change-Point Analysis and Interrupted Time Series Analysis.

BACKGROUND: Korea has witnessed significant fluctuations in its suicide rates in recent decades, which may be related to modifications in its death registration system. This study aimed to explore the structural shifts in suicide trends, as well as accidental and ill-defined deaths in Korea, and to analyze the patterns of these changes. METHODS: We analyzed age-adjusted death rates for suicides, deaths due to transport accidents, falls, drowning, fire-related incidents, poisonings, other external causes, and ill-defined deaths in Korea from 1997 to 2021. We identified change-points using the 'breakpoints' function from the 'strucchange' package and conducted interrupted time series analyses to assess trends before and after these change-points. RESULTS: Korea's suicide rates had three change-points in February 2003, September 2008, and June 2012, characterized by stair-step changes, with level jumps at the 2003 and 2008 change-points and a sharp decline at the 2012 change-point. Notably, the 2003 and 2008 spikes roughly coincided with modifications to the death ascertainment process. The trend in suicide rates showed a downward slope within the 2003-2008 and 2008-2012 periods. Furthermore, ill-defined deaths and most accidental deaths decreased rapidly through several change-points in the early and mid-2000s. CONCLUSION: The marked fluctuations in Korea's suicide rate during the 2000s may be largely attributed to improvements in suicide classification, with potential implications beyond socio-economic factors. These findings suggest that the actual prevalence of suicides in Korea in the 2000s might have been considerably higher than officially reported.

Brain Derived Neurotrophic Factor Methylation and Long-term Outcomes after Stroke Interacting with Suicidal Ideation.

Objective: This study aimed to evaluate the unexplored relationship between BDNF methylation, long-term outcomes, and its interaction with suicidal ideation (SI), which is closely associated with both BDNF expression and stroke outcomes. Methods: A total of 278 stroke patients were assessed for BDNF methylation status and SI using suicide-related item in the Montgomery-Åsberg Depression Rating Scale at 2 weeks post-stroke. We investigated the incidence of composite cerebro-cardiovascular events (CCVEs) during an 8-14-year period after the initial stroke as long-term stroke outcome. We conducted Cox regression models adjusted for covariates to evaluate the association between BDNF methylation status and CCVEs, as well as its interaction with post-stroke SI at 2 weeks. Results: Higher methylation status of CpG 1, 3, and 5, but not the average value, predicted a greater number of composite CCVEs during 8-14 years following the stroke. The associations between a higher methylation status of CpGs 1, 3, 5, and 8, as well as the average BDNF methylation value, and a greater number of composite CCVEs, were prominent in patients who had post-stroke SI at 2 weeks. Notably, a significant interaction between methylation status and SI on composite CCVEs was observed only for CpG 8. Conclusion: The significant association between BDNF methylation and poor long-term stroke outcomes, particularly amplified in individuals who had post-stroke SI at 2 weeks, suggested that evaluating the biological marker status of BDNF methylation along with assessing SI during the acute phase of stroke can help predict long-term outcomes.

Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis.

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals.

Identification of depression in patients with acute coronary syndrome using multiple serum biomarkers.

BACKGROUND: Biomarkers for depression in patients with acute coronary syndrome (ACS) have not been identified. METHODS: This study evaluated multiple serum biomarkers for depressive disorders after ACS. Thirteen serum biomarkers associated with seven functional systems, along with sociodemographic/clinical characteristics, were evaluated in 969 patients within 2 weeks after ACS onset (acute phase). In total, 711 patients were evaluated for depressive disorder using DSM-IV criteria 1 year later (chronic phase). Logistic regression was used for the analysis. RESULTS: Depressive disorders were observed in 378 patients (39.0%) in the acute phase of ACS and 183 patients (25.7%) in the chronic phase. The weighted scores of five serum biomarkers (high-sensitivity C-reactive protein, interleukin-6, homocysteine, troponin I, and creatine kinase-MB) were significantly associated with depressive disorder diagnosis in the acute phase, and the weighted scores of three other biomarkers (tumor necrosis factor-alpha, interleukin-1 beta, and homocysteine) were significantly associated with depressive disorders in the chronic phase, in a dose-dependent manner after adjusting for relevant covariates (all P-values <0.001). CONCLUSIONS: The combination of several serum biomarkers exhibited robust associations with depressive disorders in both the acute and chronic phases of ACS.

Impact of suicidality on delayed-onset post-traumatic stress disorder is modified by age: A two-year longitudinal study.

OBJECTIVES: This study aimed to investigate the relationship between early suicidality and post-traumatic stress disorder (PTSD) onset in patients with physical injuries, focusing on age as a modifying factor. METHODS: At baseline, 1014 patients were evaluated for suicidality, age divided into younger (<60 years) vs. older (≥60 years) groups, and potential covariates. PTSD was diagnosed at follow-up at 3, 6, 12, and 24 months, and then were categorized into early-onset (within the first six months after trauma) and delayed-onset (more than six months after trauma). Logistic regression models were used after adjusting for covariates. RESULTS: Presence of suicidality at baseline was significantly associated with delayed-onset PTSD in older but not younger patients with significant interaction terms, whereas it was significantly associated with early-onset PTSD across all age groups. CONCLUSION: Age-specific associations were found between suicidality and PTSD onset. The findings highlight the importance of early suicidality assessment, especially in older patients for ongoing monitoring and support, and underscore the critical need for early PTSD identification and intervention for all ages.

Predicting suicidal ideation using multiple serum biomarkers in patients with acute coronary syndrome.

BACKGROUND: Biomarkers for suicidal behavior in patients with acute coronary syndrome (ACS) have yet to be elucidated. This study aimed to identify a panel of serum biomarkers associated with suicidal ideation (SI) in patients with ACS. METHODS: The study evaluated 969 patients within 2 weeks of ACS (acute phase) and 711 patients 12 months later (chronic phase). The evaluation included 14 serum biomarkers covering 7 functional systems, socio-demographic/clinical characteristics, and SI assessed by the "suicidal thoughts" item of the Montgomery-Åsberg Depression Rating Scale. Logistic regression models were used to analyze the data. The results showed that 195 patients (20.1 %) had SI in the acute phase, and 87 patients (12.2 %) had SI in the chronic phase. RESULTS: A combination of five serum biomarkers (tumor necrosis factor-α, interleukin-1ß, folate, troponin I, and creatine kinase-MB) was significantly associated with SI in the acute phase, and a combination of three serum biomarkers (tumor necrosis factor-α, interleukin-1ß, and folate) was significantly associated with SI in the chronic phase in a clear dose-dependent manner (all P-values < 0.001) after adjustment for relevant covariates. DISCUSSION: These findings suggest that the application of a combination of multiple serum biomarkers could improve the predictability of SI in patients with ACS at both acute and chronic phases.