A large number of studies, reviews and meta-analyses have reported cognitive deficits in ecstasy users. However most ecstasy users are polydrug users, and therefore it cannot be excluded that these deficits are (partly) the result of drugs other than ecstasy. The current study, part of the Netherlands XTC Toxicity (NeXT) study, investigates the specific sustained effects of ecstasy relative to amphetamine, cocaine and cannabis on the brain using neuropsychological examination.

A stratified sample of 67 subjects with such a variation in type and amount of drug use was included that correlations between the consumption of the various drugs were relatively low allowing stepwise linear multiple regression analyses to differentiate between the effects of ecstasy and those of other substances. Subjects were assessed with neuropsychological tests measuring attention, working memory, verbal and visuospatial memory, and visuospatial ability.

Ecstasy use [mean 327 (s.d.=364) tablets in lifetime] had a specific significant dose-related negative effect on verbal delayed recall after adjusting for the use of other drugs.

These findings strongly suggest a specific sustained negative effect of ecstasy use on verbal memory. The clinical relevance is not immediately clear, because test performance generally remained within the normal range. However the magnitude of the effect is substantial (d>0.5) and long-term consequences cannot be excluded.

Although many studies have focused on post-myocardial infarction (MI) depression, there is limited information about the evolution and determinants of depressive symptoms in the first year post-MI. Therefore we examined (1) the course of depressive symptoms during the first year post-MI and (2) the predictors of these symptom trajectories.

To assess depressive symptoms, 287 patients completed the Beck Depression Inventory during hospitalization for MI, and 2, and 12 months post-MI. Personality was assessed with the Type-D scale during hospitalization. We used latent class analysis to examine the evolution of depressive symptoms over a 1-year period and multinomial logit regression analyses to examine predictors of these symptom trajectories.

The course of depressive symptoms was stable during the first year post-MI. Four groups were identified and classified as non-depressed [40%, intercept (IC) 2.52], mildly depressed (42%, IC 6.91), moderately depressed (14%, IC 13.73) or severely depressed (4%, IC 24.54). In multivariate analysis, cardiac history (log ORsevere 2.93, p=0.02; log ORmoderate 1.81, p=0.02; log ORmild 1.46, p=0.01), history of depression (log ORsevere 4.40, p<0.001; log ORmoderate 1.97, p=0.03) and Type-D personality (log ORsevere 4.22, p<0.001; log ORmoderate=4.17, p<0.001; log ORmild 1.66, p=0.02) were the most prominent risk factors for persistence of depressive symptoms during the first year post-MI.

Symptoms of depression tend to persist during the first year post-MI. Cardiac history, prior depression and Type-D personality were identified as independent risk factors for persistence of depressive symptoms. The results of this study strongly argue for routine psychological screening during hospitalization for acute MI in order to identify patients who are at risk for chronicity of depressive symptoms and its deleterious effects on prognosis.

The personality disorders (PDs) in the ‘dramatic’ cluster B [antisocial (ASPD), histrionic (HPD), narcissistic (NPD) and borderline (BPD)] demonstrate co-morbidity. However, the degree to which genetic and/or environmental factors influence their co-occurrence is not known and, with the exception of ASPD, the relative impact of genetic and environmental risk factors on liability to the cluster B PDs has not been conclusively established.

PD traits were assessed in 1386 Norwegian twin pairs between the age of 19 and 35 years using the Structured Interview for DSM-IV Personality Disorders (SIDP-IV). Using the statistical package Mx, multivariate twin models were fitted to dimensional representations of the PDs.

The best-fitting model, which did not include sex or shared family environment effects, included common genetic and environmental factors influencing all four dramatic PD traits, and factors influencing only ASPD and BPD. Heritability was estimated at 38% for ASPD traits, 31% for HPD traits, 24% for NPD traits and 35% for BPD traits. BPD traits had the lowest and ASPD traits the highest disorder-specific genetic variance.

The frequently observed co-morbidity between cluster B PDs results from both common genetic and environmental influences. Etiologically, cluster B has a ‘substructure’ in which ASPD and BPD are more closely related to each other than to the other cluster B disorders.

Conduct disorder (CD) and peer deviance (PD) both powerfully predict future externalizing behaviors. Although levels of CD and PD are strongly correlated, the causal relationship between them has remained controversial and has not been examined by a genetically informative study.

Levels of CD and PD were assessed in 746 adult male–male twin pairs at personal interview for ages 8–11, 12–14 and 15–17 years using a life history calendar. Model fitting was performed using the Mx program.

The best-fit model indicated an active developmental relationship between CD and PD including forward transmission of both traits over time and strong causal relationships between CD and PD within time periods. The best-fit model indicated that the causal relationship for genetic risk factors was from CD to PD and was constant over time. For common environmental factors, the causal pathways ran from PD to CD and were stronger in earlier than later age periods.

A genetically informative model revealed causal pathways difficult to elucidate by other methods. Genes influence risk for CD, which, through social selection, impacts on the deviance of peers. Shared environment, through family and community processes, encourages or discourages adolescent deviant behavior, which, via social influence, alters risk for CD. Social influence is more important than social selection in childhood, but by late adolescence social selection becomes predominant. These findings have implications for prevention efforts for CD and associated externalizing disorders.

The association between the duration of untreated psychosis (DUP) and outcome of schizophrenia may be confounded by other factors such as poor pre-morbid adjustment. The aim of the present study was to examine the independent contributions of DUP and of pre-morbid adjustment to the clinical and social outcomes of schizophrenia.

A longitudinal, prospective, 2-year follow-up study of 423 patients with first-episode schizophrenia-spectrum psychosis was conducted. Patients were comprehensively assessed at entry, 1-year and 2-year follow-up. At entry, DUP was measured by IRAOS (an instrument for the assessment of onset and early course of schizophrenia) and pre-morbid adjustment was measured by the Pre-morbid Adjustment Scale (PAS) as ‘pre-morbid social adaptation’ and ‘pre-morbid school adaptation’. Outcome measures included the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), the Social Network Schedule and social information. Multiple linear regression models were used for data analysis.

The median DUP was 48 weeks, which is long compared to other studies. Longer DUP was independently associated with more psychotic symptoms at entry, 1-year and 2-year follow-up. Poorer pre-morbid social adaptation was independently associated with more negative symptoms and smaller social network at entry and 1-year follow-up. Poorer pre-morbid school adaptation was independently associated with poor vocational outcome at 1-year and 2-year follow-up.

Longer DUP is associated with poorer 2-year outcome of psychosis in schizophrenia-spectrum disorders, when pre-morbid functioning and other prognostic factors are controlled for. Impaired pre-morbid development is independently associated with more negative symptoms and poorer social outcome.

Measurement invariance of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) post-traumatic stress disorder (PTSD) criterion symptoms was tested by gender and trauma type, assaultive and non-assaultive.

Analysis was conducted using latent class analysis (LCA), based on findings that the three-class LCA model from Breslau et al. (Archives of General Psychiatry 2005, 62, 1343–1351) fits the data across the four groups best. The classes represent three levels of PTSD-related disturbance: no disturbance, intermediate disturbance and pervasive disturbance, with the last one approximating the DSM-IV PTSD diagnosis.

Analysis of measurement invariance showed that, with respect to gender, there was no evidence of differential symptom reporting within the same disturbance class. DSM-IV symptom indicators represent the latent structure of PTSD equally in males and females. We found that more female than male victims of assaultive violence experienced pervasive disturbance. In the absence of measurement variability associated with gender, the finding is likely to reflect a gender difference in susceptibility. The analysis of measurement invariance detected evidence of variability associated with trauma type. Victims of assaultive violence in the pervasive disturbance class report more severe distress (especially emotional numbing) than do victims of non-assaultive violence in the same class.

The finding of measurement bias associated with type of trauma raises questions about the applicability of a single definition for PTSD associated with assaultive violence and PTSD associated with traumatic events of lesser magnitude.

Relationships between performance on various tests of executive functions andpositive symptoms, especially delusions and hallucinations, have not beenfound consistently. This may be related to method of rating symptoms, topossible interactions between them, as well as to the low specificity of thecognitive test measures used. In this study, we have investigated therelationships between different aspects of positive symptomatology andseveral executive subprocesses.

Stable schizophrenia patients (n=96) were assessed for disorganization,delusion and hallucination symptoms rated from the Scale for Assessment ofPositive Symptoms and the Scale for Assessment of Negative Symptoms.Interference sensitivity, inhibition and flexibility were assessed using theWickens paradigm. The relationships between symptom dimensions as well aswith cognitive and other potentially confounding variables were assessedusing Pearson correlations and (simple and partial)stepwise regressions.

Generally consistent with the cognitive constructs used to account forpositive symptoms, the results indicated relationships between delusions,disorganization and inhibition, and between hallucinations and interferencesensitivity. However, these relationships appeared more complex thanexpected, with some being dependent on interactions between symptoms.

These results suggest: (i) that the globalmeasures usually employed may not be appropriate for demonstrating specificrelationships between symptoms and executive functions and(ii) that it is necessary to take into account theinteractions between positive symptoms as well as with other factors toreveal these relationships.

This study examined healthcare services used by adults diagnosed with an eating disorder (ED) in a large health maintenance organization in the Pacific Northwest.

Electronic medical records were used to collect information on all out-patient and in-patient visits and medication dispenses, from 2002 to 2004, for adults aged 18–55 years who received an ED diagnosis during 2003. Healthcare services received the year prior to, and following, the receipt of an ED diagnosis were examined. Cases were matched to five comparison health plan members who had a health plan visit close to the date of the matched case's ED diagnosis.

Incidence of EDs (0.32% of the 104 130 females, and 0.02% of the 93 628 males) was consistent with prior research employing treatment-based databases, though less than community-based samples. Most cases (50%) were first identified during a primary-care visit and psychiatric co-morbidity was high. Health services use was significantly elevated in all service sectors among those with an ED when compared with matched controls both in the year preceding and that following the receipt of the incident ED diagnosis. Contrary to expectations, healthcare utilization was found to be similarly high across the spectrum of EDs (anorexia nervosa, bulimia nervosa, and eating disorders not otherwise specified).

The elevation in health service use among women both before and after diagnosis suggests that EDs merit identification and treatment efforts commensurate with other mental health disorders (e.g. depression) which have similar healthcare impact.

Paranoia is increasingly being studied in clinical and non-clinical populations. However there is no multi-dimensional measure of persecutory ideas developed for use across the general population-psychopathology continuum. This paper reports the development of such a questionnaire: the ‘Green et al. Paranoid Thought Scales’. The aim was to devise a tool to assess ideas of persecution and social reference in a simple self-report format, guided by a current definition of persecutory ideation, and incorporating assessment of conviction, preoccupation and distress.

A total of 353 individuals without a history of mental illness, and 50 individuals with current persecutory delusions completed a pool of paranoid items and additional measures to assess validity. Items were devised from a recent definition of persecutory delusions, current assessments of paranoia, the authors' clinical experience, and incorporated dimensions of conviction, preoccupation and distress. Test–retest reliability in the non-clinical group was assessed at 2 weeks follow-up, and clinical change in the deluded group at 6 months follow-up.

Two 16-item scales were extracted, assessing ideas of social reference and persecution. Good internal consistency and validity was established for both scales and their dimensions. The scales were sensitive to clinical change. A hierarchical relationship between social reference and persecution was found. The data provide further evidence for a continuum of paranoid ideas between deluded and healthy individuals.

A reliable and valid tool for assessing paranoid thoughts is presented. It will provide an effective way for researchers to ensure consistency in research and for clinicians to assess change with treatment.

Insufficient evidence exists for a viable choice between long- and short-term psychotherapies in the treatment of psychiatric disorders. The present trial compares the effectiveness of one long-term therapy and two short-term therapies in the treatment of mood and anxiety disorders.

In the Helsinki Psychotherapy Study, 326 out-patients with mood (84.7%) or anxiety disorder (43.6%) were randomly assigned to three treatment groups (long-term psychodynamic psychotherapy, short-term psychodynamic psychotherapy, and solution-focused therapy) and were followed up for 3 years from start of treatment. Primary outcome measures were depressive symptoms measured by self-report Beck Depression Inventory (BDI) and observer-rated Hamilton Depression Rating Scale (HAMD), and anxiety symptoms measured by self-report Symptom Check List Anxiety Scale (SCL-90-Anx) and observer-rated Hamilton Anxiety Rating Scale (HAMA).

A statistically significant reduction of symptoms was noted for BDI (51%), HAMD (36%), SCL-90-Anx (41%) and HAMA (38%) during the 3-year follow-up. Short-term psychodynamic psychotherapy was more effective than long-term psychodynamic psychotherapy during the first year, showing 15–27% lower scores for the four outcome measures. During the second year of follow-up no significant differences were found between the short-term and long-term therapies, and after 3 years of follow-up long-term psychodynamic psychotherapy was more effective with 14–37% lower scores for the outcome variables. No statistically significant differences were found in the effectiveness of the short-term therapies.

Short-term therapies produce benefits more quickly than long-term psychodynamic psychotherapy but in the long run long-term psychodynamic psychotherapy is superior to short-term therapies. However, more research is needed to determine which patients should be given long-term psychotherapy for the treatment of mood or anxiety disorders.

Chronic obstructive pulmonary disease (COPD) affects 14 to 20 million Americans and is associated with increased prevalence of affective disorders, contributing significantly to disability. This study compared cognitive behavioral therapy (CBT) group treatment for anxiety and depression with COPD education for COPD patients with moderate-to-severe anxiety and/or depressive symptoms.

A randomized controlled trial (RCT) was conducted between 11 July 2002 and 30 April 2005 at the Michael E. DeBakey VA Medical Center, Houston, TX. Participants were 238 patients treated for COPD the year before, with forced expiratory value in 1 second (FEV)1/forced vital capacity (FVC)<70% and FEV1<70% predicted, and symptoms of moderate anxiety and/or moderate depression, who were being treated by a primary care provider or pulmonologist. Participants attended eight sessions of CBT or COPD education. Assessments were at baseline, at 4 and 8 weeks, and 4, 8 and 12 months. Primary outcomes were disease-specific and generic quality of life (QoL) [Chronic Respiratory Questionnaire (CRQ) and Medical Outcomes Survey Short Form-36 (SF-36) respectively]. Secondary outcomes were anxiety [Beck Anxiety Inventory (BAI)], depressive symptoms [Beck Depression Inventory-II (BDI-II)], 6-minute walk distance (6MWD) and use of health services.

Both treatments significantly improved QoL, anxiety and depression (p<0.005) over 8 weeks; the rate of change did not differ between groups. Improvements were maintained with no significant change during follow-up. Ratios of post- to pretreatment use of health services were equal to 1 for both groups.

CBT group treatment and COPD education can achieve sustainable improvements in QoL for COPD patients experiencing moderate-to-severe symptoms of depression or anxiety.

Significant associations between changes in ovarian hormones and binge eating are present across the menstrual cycle in women with bulimia nervosa. However, no study has examined these relationships in a non-clinical sample, despite the need for these data for designing risk-factor studies.

In study 1, we modified several continuous measures of binge eating and identified those that were most sensitive to menstrual-cycle fluctuations in a non-clinical sample of 10 women who completed measures for 35 days. In study 2, we explored associations between ovarian hormones and binge-eating scores in nine women who completed these same measures for 65 days and provided daily saliva samples for assays of estradiol and progesterone concentrations.

In study 1, the Emotional Eating subscale of the Dutch Eating Behavior Questionnaire exhibited superior reliability and was most sensitive to predicted menstrual-cycle changes in binge eating (i.e. increased scores in the mid-luteal/premenstrual compared with follicular/ovulatory phases). In study 2, this scale showed predicted inverse associations with estradiol and positive associations with progesterone across the menstrual cycle that could not be accounted for by changes in negative affect.

Associations between ovarian hormones and binge eating are robust and present in clinical and non-clinical samples. Findings support the ability to examine the role of ovarian hormones as risk factors for binge eating in large-scale prospective studies and twin studies.

Common fears change over development. Genetic and environmental risk factors for fears are partly shared across fears and partly fear-specific. The nature of the changes in common and fear-specific genetic and environmental risk factors over time is unknown.

Self-reported fears were obtained at ages 13–14, 16–17 and 19–20 from 2404 twins in the Swedish Twin Study of Child and Adolescent Development. A multivariate longitudinal twin analysis was conducted with Mx.

Eighteen individual items formed four fear factors: animal, blood-injury, situational, and social. The best-fit model had no quantitative or qualitative sex effects or shared environmental effects, but included a strong common factor with a stable cross-time structure with highest loadings on situational and lowest loadings on social fears. New common and fear-specific genetic risk factors emerged over development. With increasing age, genetic effects declined in overall importance and became more fear-specific. Cross-time continuity in specific genetic effects was highest for animal and lowest for social fears. Social fears had a ‘burst’ of specific genetic effects in late adolescence. Individual-specific environmental factors impacted both on the general fear factor and on specific fears. Compared to genetic effects, the impact of the unique environment was more time-specific.

Genetic and environmental risk factors for individual fears are partly mediated through a common fear factor and are partly fear-specific in their effect. The developmental pattern of these risk factors is complex and dynamic with new common and specific genetic effects arising in late adolescence and early adulthood.

Hierarchical cumulative scales are common and informative in psychology. The General Health Questionnaire (GHQ) does not appear to have been subjected to an analysis that examines the hierarchical and cumulative nature of its items. We report an analysis of data from the 30-item GHQ (GHQ-30) as part of the Health and Lifestyle Survey (HALS).

Data from 6317 participants who completed the GHQ-30 as part of the HALS were analysed using the Mokken Scaling Procedure (MSP), which is a computer program that searches polychotomous data for hierarchical and cumulative scales on the basis of a range of diagnostic criteria.

A final scale consisting of nine items from the GHQ-30 was obtained that, according to the criteria for a Mokken scale, was a reliable and very strong scale. The least difficult item in the scale is ‘been (un)able to face up to your problems?’ and the most difficult item is ‘felt that life isn't worth living?'

Items from the GHQ-30 form a short hierarchical and cumulative scale. The majority of these items also appear in the GHQ-12. The nine-item GHQ shows better distribution properties than the GHQ-30 and compares very favourably with the GHQ-12.

Both mental disorders and personality characteristics are associated with impaired work functioning, but these determinants have not yet been studied together. The aim of this paper is to examine the impairing effects that mental disorders and personality characteristics (i.e. neuroticism, locus of control and self-esteem) have on work functioning.

Data for a representative sample of 3570 working people were derived from the first two waves of the Netherlands Mental Health Survey and Incidence Study (NEMESIS), a prospective cohort study in the Dutch adult population.

Higher neuroticism, more external locus of control and lower self-esteem were each significantly associated with subsequent impairment in work functioning, independently of any effects from mental disorders. Associations between mental disorders and subsequent work impairment disappeared once personality traits were taken into account. Personality traits did not moderate the relationships between mental disorders and work functioning.

Working people with vulnerable personalities have a greater risk of impaired work functioning, independent of the risk from any mental disorder they may have.

Conduct disorder (CD) is a relatively common disorder of childhood and adolescence in the USA with substantial associated morbidity, yet little has been published on CD among Asians and Native Hawaiian/Pacific Islanders (NH/PI) in the USA.

We used the National Epidemiological Survey on Alcohol and Related Conditions (NESARC) to examine the prevalence and correlates of retrospectively reported CD within Asians and NH/PI (18 years and older). We also completed logistic regressions to explore factors associated with CD within Asians (n=1093) and, separately, NH/PI (n=139) and to explain racial differences in CD prevalence.

Asians were about a third as likely [odds ratio (OR) 0.4, 95% confidence interval (CI) 0.22–0.58] whereas NH/PI were about two and half times more likely (OR 2.6, 95% CI 1.31–5.06) to have had CD compared with Caucasian respondents. Within Asians and NH/PI, CD was strongly associated with adult antisocial behavior, substance use and affective disorders. Demographic factors, the age that subjects came to the USA, measures of family environment and family history could not explain the observed differences in prevalence of CD for NH/PI relative to Caucasians.

Asian and NH/PI youth with CD represent a subgroup of Asian youth at very high risk for a number of serious psychiatric disorders. Further investigation is needed to explain the high CD prevalence among NH/PI.

Although there have been several reports linking ecstasy use with lowered cognitive function, much previous research suffers from substantial methodological limitations. The present study aimed to examine associations between ecstasy use and higher-level cognitive functions, using a larger sample size than most previous research and better controlling for a range of potential confounds.

A cross-sectional cohort design assessed 45 currently abstinent ecstasy polydrug users (EP), 48 cannabis polydrug users (CP) and 40 legal drug users (LD). Standardized neuropsychological tests were used to measure attention, verbal, visual and working memory and executive function. Prospective memory function was also assessed.

It was not possible to discriminate between groups on the basis of the cognitive functions assessed. Regression analyses showed an inverse association between lifetime dose of ecstasy and verbal memory performance. A combination of drug-use variables, including measures of ecstasy use, contributed to prediction of attention/working memory. However, individual associations were small, explaining 1–6% of variance in cognitive scores.

Although the results suggest that heavy use of ecstasy is associated with some lowering of higher-level cognitive functions, they do not indicate a clinical picture of substantial cognitive dysfunction.

Limited information exists on the relationship between specific chronic somatic conditions and care for co-morbid depression in primary care settings. Therefore, the present prospective, general practice-based study examined this relationship.

Longitudinal data on morbidity, prescribing and referrals concerning 991 patients newly diagnosed with depression by their general practitioner (GP) were analysed. The influence of a broad range of 13 specific chronic somatic conditions on the initiation of any depression care, as well as the prescription of continuous antidepressant therapy for 180 days, was examined. Multilevel logistic regression analysis was used to control for history of depression, psychiatric co-morbidity, sociodemographics and interpractice variation.

Multilevel analysis showed that patients with pre-existing ischaemic heart disease (72.1%) or cardiac arrhythmia (59.3%) were significantly less likely to have any depression care being initiated by their GP than patients without chronic somatic morbidity (88.0%). No other specific condition had a significant influence on GP initiation of any care for depression. Among the patients being prescribed antidepressant treatment by their GP, none of the conditions was significantly associated with being prescribed continuous treatment for 180 days.

Our study indicates that patients with ischaemic heart disease or cardiac arrhythmia have a lower likelihood of GP initiation of any care for depression after being newly diagnosed with depression by their GP. This finding points to the importance of developing interventions aimed at supporting GPs in the adequate management of co-morbid depression in heart disease patients to reduce the negative effects of this co-morbidity.

Suicide is the most common cause of death among youth in China.

A case-control psychological autopsy study in 23 geographically representative disease surveillance points around China collected information from family members and close associates of 114 persons aged 15–24 years who died by suicide (cases) and 91 who died of other injuries (controls).

Among the 114 suicides 61% were female, 88% lived in rural villages, 70% died by ingesting pesticides (most commonly stored in the home), 24% previously attempted suicide, and 45% met criteria of a mental illness at the time of death. Multivariate logistic regression identified several independent risk factors: severe life events within 2 days before death (OR 31.8, 95% CI 2.6–390.6), presence of any depressive symptoms within 2 weeks of death (OR 21.1, 95% CI 4.6–97.2), low quality of life in the month before death (OR 9.7, 95% CI 2.8–34.1), and acute stress at time of death (moderate: OR 3.1, 95% CI 0.8–11.9; high: OR 9.1, 95% CI 1.2–66.8). A significant interaction between mental illness at time of death and gender indicated that diagnosis was an important predictor of suicide in males (OR 14.0, 95% CI 2.6–76.5) but not in females (OR 0.3, 95% CI 0.0–3.6). Prior suicide attempt was related to suicide in the univariate analysis (OR 57.5) but could not be included in the multivariate model because no controls had made prior attempts.

Suicide prevention efforts for youth in China must focus on restricting access to pesticides, early recognition and management of depressive symptoms and mental illnesses, improving resiliency, and enhancing quality of life.

While the role of genetic factors in self-report measures of emotion has been frequently studied, we know little about the degree to which genetic factors influence emotional facial expressions.

Twenty-eight pairs of monozygotic (MZ) and dizygotic (DZ) twins from the Minnesota Study of Twins Reared Apart were shown three emotion-inducing films and their facial responses recorded. These recordings were blindly scored by trained raters. Ranked correlations between twins were calculated controlling for age and sex.

Twin pairs were significantly correlated for facial expressions of general positive emotions, happiness, surprise and anger, but not for general negative emotions, sadness, or disgust or average emotional intensity. MZ pairs (n=18) were more correlated than DZ pairs (n=10) for most but not all emotional expressions.

Since these twin pairs had minimal contact with each other prior to testing, these results support significant genetic effects on the facial display of at least some human emotions in response to standardized stimuli. The small sample size resulted in estimated twin correlations with very wide confidence intervals.