Neurocognitive performance in the context of acute symptom reduction in OCD: Treatment effects and the impact of BDNF.

BACKGROUND: Obsessive-compulsive disorder (OCD) has been associated with neurocognitive impairments. The present study examined the effect of treatment on neurocognitive performance in OCD and the relationship between neurocognitive change and symptom change. The present study also examined polymorphisms influencing brain derived neurotrophic factor (BDNF) as predictors of neurocognitive change. METHOD: Treatment-seeking participants with OCD (N = 125) were assigned to cognitive behavioural therapy (CBT) alone, CBT combined with regular physical exercise, exercise alone, or a waitlist control group. Measures of OCD symptom severity and a neuropsychological battery were completed pre- and post-treatment. Blood or saliva samples were used to genotype the BDNF Val66Met polymorphism. RESULTS: OCD symptom severity was not cross-sectionally associated with neurocognitive performance. Several neurocognitive measures improved over treatment. The BDNF Val66Met polymorphism was significantly associated with worse performance on the Stroop test but did not significantly predict change in neurocognitive performance over time. LIMITATIONS: Limitations include lack of a healthy control group. CONCLUSION: Improvement in neurocognitive performance corresponded to symptomatic improvement and was independent of the BDNF Val66Met genotype.

The Relationship of Rumination, Worry and OCD Symptoms During Technology Supported Mindfulness Therapy for OCD.

BACKGROUND: In this study, we re-examined data from a previous randomized controlled trial investigating 'technology supported mindfulness' (TSM)-an 8-week treatment intervention for individuals experiencing OCD. The current analysis involves an examination of the longitudinal relationships between rumination, worry and OCD symptom changes during mindfulness treatment, in comparison to a waitlist control. METHODS: Participants experiencing OCD (n = 71) were randomly assigned to 8 weeks of (1) TSM or (2) waitlist control. We tested the extent to which rumination (using the Ruminative Response Scale) and worry (using the Penn State Worry Questionnaire) are associated with OCD symptom changes during the acute phase of treatment, concurrently (i.e., within the same longitudinal model). RESULTS: Generalized linear model (GLM) results indicated a significant time (week 1 vs. week 8) by condition interaction involving decreased rumination in the TSM condition: F(1, 61) = 13.37, p = 0.001, partial η2 = 0.18 and observed power = 0.94. A second GLM demonstrated decreased worry in the TSM condition: F(1, 69) = 37.34, p = 0.001, partial η2 = 0.35 and observed power = 0.83. Longitudinal 'latent difference' structural equation analyses demonstrated a cross-lagged association between worry (but not rumination) and OCD symptom changes. CONCLUSIONS: Individuals in the TSM condition experienced greater reductions in rumination and worry during 8 weeks of TSM treatment compared to the waitlist control, and reduced worry predicted subsequent OCD symptom reduction.

Online versus in-person delivery of cognitive behaviour therapy for obsessive compulsive disorder: An examination of effectiveness.

Cognitive behavioural therapy (CBT) including exposure and response prevention is the first-line psychological treatment for obsessive compulsive disorder (OCD). Given changes in the clinical landscape, there are increasing efforts to evaluate its effectiveness in online contexts. Mirroring the traditional in-person delivery, few studies have assessed the role of therapist-guided, manual-based CBT for OCD delivered in real-time via videoconferencing methods. The present study sought to fill this gap by comparing in-person and online delivery of group-based CBT for the treatment of OCD. A convenience sample of participants with moderate to severe OCD (n = 144) were recruited from a naturalistic database from two large OCD specialty assessment and treatment centres. Patients received group-based CBT that was provided in-person (pre-COVID-19 pandemic; March 2018 to March 2020) or online via videoconferencing (during the COVID-19 pandemic; March 2020 to April 2021). In both delivery methods, treatment consisted of 2-h weekly sessions led by trained clinicians. Analyses revealed that, regardless of treatment modality, both in-person and online groups demonstrated significant, reliable, and statistically equivalent improvements in OCD symptoms post-treatment. Videoconferenced, clinician-led CBT may be a promising alternative to in-person delivery for those with moderate to severe OCD symptoms.

The effect of aerobic exercise alone and in combination with cognitive behavioural therapy on obsessive compulsive disorder: A randomized control study.

PURPOSE: Cognitive behavioural therapy (CBT) has been found to be an effective treatment for OCD, but there remains a significant proportion of individuals who fail to show a treatment response. Aerobic exercise has previously been associated with decreases in anxiety and depression, as well as improvements in OCD symptoms in small-scale studies. The purpose of the present research was to use a randomized control trial design to examine the effects of exercise alone and in combination with CBT, on OCD symptoms and secondary symptoms. METHOD: 125 participants were randomly assigned to one of four treatment groups: waitlist control, exercise, CBT, and CBT with exercise. OCD symptom severity was measured at four points over the course of treatment, secondary outcome measures were gathered at three points over treatment. RESULTS: CBT alone and combined with exercise was associated with significantly greater OCD symptom reduction than exercise alone or the control groups. Total exercise frequency predicted OCD symptom reduction in the groups in which exercise was measured. Group membership did not significantly predict reductions in secondary outcome measures. CONCLUSION: Exercise frequency, rather than the presence or absence of exercise, appears to predict OCD symptom reduction, as did participation in CBT.

Is the narrative the message? The relationship between suicide-related narratives in media reports and subsequent suicides.

OBJECTIVES: When journalists report on the details of a suicide, the way that they contextualize the meaning of the event (i.e. the 'narrative') can have significant consequences for readers. The 'Werther' and 'Papageno' narrative effects refer to increases and decreases in suicides across populations following media reports on suicidal acts or mastery of crises, respectively. The goal of this study was to investigate the impact of these different narrative constructs on subsequent suicides. METHODS: This study examined the change in suicide counts over time in Toronto, Canada. It used latent difference score analysis, examining suicide-related print media reports in the Toronto media market (2011-2014). Articles (N = 6367) were coded as having a potentially harmful narrative if they described suicide in a celebrity or described a suicide death in a non-celebrity and included the suicide method. Articles were coded as having potentially protective narratives if they included at least one element of protective content (e.g. alternatives to suicide) without including any information about suicidal behaviour (i.e. suicide attempts or death). RESULTS: Latent difference score longitudinal multigroup analyses identified a dose-response relationship in which the trajectory of suicides following harmful 'Werther' narrative reports increased over time, while protective 'Papageno' narrative reports declined. The latent difference score model demonstrated significant goodness of fit and parameter estimates, with each group demonstrating different trajectories of change in reported suicides over time: (χ2[6], N = 6367) = 13.16; χ2/df = 2.19; Akaike information criterion = 97.16, comparative fit index = 0.96, root mean square error of approximation = 0.03. CONCLUSION: Our findings support the notion that the 'narrative' matters when reporting on suicide. Specifically, 'Werther' narratives of suicides in celebrities and suicides in non-celebrities where the methods were described were associated with more subsequent suicides while 'Papageno' narratives of survival and crisis mastery without depictions of suicidal behaviours were associated with fewer subsequent suicides. These results may inform efforts to prevent imitation suicides.

Longitudinal changes in intolerance of uncertainty and worry severity during CBT for generalized anxiety disorder.

Intolerance of uncertainty (IU) is a key construct in generalized anxiety disorder (GAD), but little is known about the concurrent and temporal patterns of associations between IU and GAD symptom severity during treatment. In addition, most of the extant literature focuses on IU as a unidimensional construct, whereas some researchers conceptualize IU as being comprised of two dimensions, inhibitory and prospective IU. Ninety individuals with GAD completed measures of IU and worry severity at pre-treatment, session 4, session 8, and end of treatment (session 12), during group-based cognitive behavior therapy (CBT) for GAD. Longitudinal multilevel modeling showed that IU predicted worry severity concurrently, but not prospectively over time; this pattern of associations was found with the total IUS score and the inhibitory (but not prospective) subscale score. Further, the relationship between IU total scores and worry severity became stronger over time. The relationship between inhibitory (but not prospective) IU and worry also became stronger over time. When the order of the variables in the model was reversed, worry severity also predicted concurrent but not future IU. Therefore, change in IU is associated with change in worry throughout the course of CBT, particularly as treatment progresses, though its directional association as a cause and/or effect remains unclear.

Self-critical perfectionism, dependency and entropy during cognitive behavioural therapy for depression.

OBJECTIVES: This study examined whether 'personality vulnerability' (i.e., self-critical perfectionism or dependency) predicts the trajectory of change, as well as variability and instability (i.e., entropy) of symptoms, during cognitive behaviour therapy (CBT) for depression. DESIGN: Study participants were outpatients (N = 312) experiencing a primary mood disorder. Participants received CBT for depression group sessions over 15 weeks. Self-report measures of self-critical perfectionism, dependency, and depression were collected longitudinally. METHODS: A latent growth mixture modelling (LGMM) statistical approach was used to evaluate the presence of latent classes of individuals based on their longitudinal pattern of symptom change during CBT and to evaluate whether baseline self-critical perfectionism or dependency predicts class membership. A Latent Acceleration Score (LAS) model evaluated whether perfectionism or dependency led to variability in depression symptom change (e.g., velocity) by considering changes in velocity (e.g., acceleration and/or deceleration). RESULTS: LGMM indicated the presence of two latent classes that represent symptom improvement (N = 239) or minimal symptom improvement over time (N = 73). Elevated baseline self-critical perfectionism, but not dependency, predicted a greater likelihood of membership in the class of participants who demonstrated minimal symptom improvement over time. The second analysis examined whether baseline self-critical perfectionism also predicts depression symptom variability and instability. The LAS perfectionism model demonstrated that perfectionism accelerates depression symptom change during the first seven sessions of treatment, then has a decelerating effect on depression symptom change. CONCLUSIONS: Results indicated that higher baseline self-critical perfectionism predicted higher variability and instability in depression symptoms and variability in acceleration and deceleration, over the course of treatment.

Technology supported mindfulness for obsessive compulsive disorder: The role of obsessive beliefs.

The current study examined the association of OCD symptoms and OCD belief domains, for individuals engaged in Technology Supported Mindfulness training (TSM) using an EEG-based biofeedback device (called "Muse") that permits individuals to engage in home based mindfulness meditation practices. In this randomized controlled study, treatment-seeking participants with a principal DSM-5 diagnosis of OCD (N = 71) were randomly assigned to eight weeks of: 1) a meditation program involving daily use of the "Muse" device, or 2) wait list control. At weeks 1, 4, and 8, participants completed self-report measures of OCD symptoms (YBOCS: Yale-Brown Obsessive Compulsive Scale) and OCD beliefs (OBQ; OCCWG, 2005). Latent Difference Score (LDS) models indicated that there was no significant longitudinal relationship between OBQ "Responsibility/Threat" (OBQ R/T) scores and OCD symptoms. The analysis of OBQ "Perfectionism/Certainty" (OBQ P/C) and OCD symptoms demonstrated a significant reciprocal relationship between these two variables, in which OCD symptoms predicted subsequent increases in OBQ P/C and vice versa. The analysis of OBQ "Importance/Control of Thoughts" (OBQ I/C) and OCD symptoms demonstrated a significant reciprocal relationship between these two variables, in which OCD symptoms predicted subsequent increases in OBQ I/C and vice versa. The analysis of OBQ domains and EEG derived attentional changes demonstrated a significant association between OBQ P/C and Alpha band frequencies. These results clarify the association of OBQ belief domains, OCD symptom change and EEG derived indicators of attention during TSM.

Technology supported mindfulness for obsessive compulsive disorder: Self-reported mindfulness and EEG correlates of mind wandering.

Cognitive Behavior Therapy (CBT) incorporating Exposure with Response Prevention (ERP) is the most efficacious treatment intervention for Obsessive Compulsive Disorder (OCD); however, there is a growing literature indicating that mindfulness based approaches can be beneficial in terms of managing OCD symptoms. The current study examined the potential benefits of using a consumer grade EEG-based biofeedback device (called "Muse") that permits individuals to engage in mindfulness meditation practices while at home. In this randomized controlled study, participants with a principal DSM-5 diagnosis of OCD (N = 71) were randomly assigned to eight weeks of: 1) a meditation program involving daily use of the "Muse" device, or 2) waitlist control. At weeks 1, 4, and 8, participants completed a five minute "open monitoring" practice while EEG data was recorded, and they completed self-report measures of mindfulness (FFMQ: Five Factor Mindfulness Questionnaire) and OCD symptoms (YBOCS: Yale-Brown Obsessive Compulsive Scale). Latent Difference Score (LDS) models demonstrated that the FFMQ "Non-Reactivity" facet and EEG-derived correlates of "Mind Wandering" (i.e., alpha, beta, but not delta or theta band power) were temporally associated with subsequent changes in YBOCS symptom scores. Participants in the Muse group (in comparison to the control group) experienced increased FFMQ "Non-Reactivity" and decreased mind wandering (increased alpha and beta band power), and in each case, these variables were associated with subsequent OCD symptom improvement. These results suggest that technology supported mindfulness training for OCD is associated with improvements in OCD symptoms, mindfulness and decreased mind wandering.

What Drives OCD Symptom Change During CBT Treatment? Temporal Relationships Among Obsessions and Compulsions.

Cognitive behavior therapy (CBT) is an effective treatment for obsessive-compulsive disorder (OCD). However, less is known about how obsessions and compulsions change during treatment, either in tandem, sequentially, or independently. The current study used latent difference score analysis to show path-analytic dynamic modeling of OCD symptom change during CBT. Four competing models of the temporal relationship between obsessions and compulsions were examined: no coupling (obsessions and compulsions are not dynamically related), goal directed (obsessions lead to subsequent changes in compulsions), habit driven (compulsions lead to subsequent changes in obsessions), and reciprocal. Treatment seeking participants (N = 84) with a principal diagnosis of OCD completed 12 weeks of CBT group therapy and completed measures assessing obsession and compulsion severity at pretreatment, Sessions 4 and 8, and end of treatment. Bivariate results supported the goal directed traditional CBT model, where obsession scores are temporally associated with subsequent changes in compulsion scores. These results have implications for theoretical and treatment modelling of obsessions and compulsions in OCD treatment.

The structure, correlates, and treatment related changes of mindfulness facets across the anxiety disorders and obsessive compulsive disorder.

Research with non-clinical and clinical samples has examined how mindfulness concepts relate to psychological symptom presentations. However, there is less clarity when examining treatment-seeking patients who experience DSM-diagnosed anxiety and obsessional disorders - both cross-sectionally, and following empirically-supported treatments. The Five Facet Mindfulness Questionnaire (FFMQ; Baer, Smith, Hopkins, Krietemeyer, & Toney, 2006) conceptualizes mindfulness as consisting of five facets: Observing, Describing, Acting with Awareness, Nonreactivity, and Nonjudging. The current study examines the factor structure and predictive validity of the FFMQ in a large sample of treatment-seeking individuals with obsessive compulsive disorder (OCD), panic disorder with or without agoraphobia (PD/A), social anxiety disorder (SAD), and generalized anxiety disorder (GAD). Confirmatory factor analyses (CFA) established that both four and five-factor models (i.e., with and without inclusion of the Observing factor) provided an acceptable representation of the underlying FFMQ structure, but did not support a one-factor solution. For each of these diagnostic groups, hierarchical regression analyses clarified the association between specific FFMQ facets and diagnosis specific symptom change during CBT treatment. These findings are discussed in the context of the possible transdiagnostic relevance of specific mindfulness facets, and how these facets are differentially associated with diagnosis specific symptom alleviation during CBT.

Cognitive-Behavioral Therapy for Depression Using Mind Over Mood: CBT Skill Use and Differential Symptom Alleviation.

Cognitive-behavioral therapy (CBT) for depression is highly effective. An essential element of this therapy involves acquiring and utilizing CBT skills; however, it is unclear whether the type of CBT skill used is associated with differential symptom alleviation. Outpatients (N = 356) diagnosed with a primary mood disorder received 14 two-hour group sessions of CBT for depression, using the Mind Over Mood protocol. In each session, patients completed the Beck Depression Inventory and throughout the week they reported on their use of CBT skills: behavioral activation (BA), cognitive restructuring (CR), and core belief (CB) strategies. Bivariate latent difference score (LDS) longitudinal analyses were used to examine patterns of differential skill use and subsequent symptom change, and multigroup LDS analyses were used to determine whether longitudinal associations differed as a function of initial depression severity. Higher levels of BA use were associated with a greater subsequent decrease in depressive symptoms for patients with mild to moderate initial depression symptoms relative to those with severe symptoms. Higher levels of CR use were associated with a greater subsequent decrease in depressive symptoms, whereas higher levels of CB use were followed by a subsequent increase in depressive symptoms, regardless of initial severity. Results indicated that the type of CBT skill used is associated with differential patterns of subsequent symptom change. BA use was associated with differential subsequent change as a function of initial severity (patients with less severe depression symptoms demonstrated greater symptom improvement), whereas CR use was associated with symptom alleviation and CB use with an increase in subsequent symptoms as related to initial severity.

Examining the dynamic relationships between exposure tasks and cognitive restructuring in CBT for SAD: Outcomes and moderating influences.

Meta-analyses indicate that cognitive behavioral therapy (CBT) for social anxiety disorder (SAD) leads to substantial symptom alleviation. Although there is an emphasis on engaging in exposure and cognitive restructuring during treatment, the longitudinal relationship between skill use and symptom alleviation is not well understood. Furthermore, treatment response may be attenuated by pre-existing patient vulnerabilities. This study examined the longitudinal association of skill use (i.e. exposure (EX), thought record use (TR)), symptom reduction and the potential moderating influence of perfectionism during a 12-session, manual-based CBT for SAD intervention for 100 patients (51% female) meeting DSM-IV criteria for SAD. Results obtained from Latent Difference Score (LDS) models indicated that the frequency of both EX and TR skill use led to subsequent symptom alleviation; however, this varied based on the type of skill used. Further, although both EX and TR interventions were associated with subsequent symptom reduction, the association of EX and subsequent symptom alleviation was greater than the association of TR and subsequent symptom alleviation. Finally, higher pre-treatment perfectionism was associated with greater initial skill use, followed by significantly reduced skill use in later sessions. These preliminary results suggest that perfectionistic individuals demonstrate differential engagement in EX and TR interventions during treatment.

Mindfulness and acceptance-based group therapy and traditional cognitive behavioral group therapy for social anxiety disorder: Mechanisms of change.

The present study investigated mechanisms of change for two group treatments for social anxiety disorder (SAD): cognitive behavioral group therapy (CBGT) and mindfulness and acceptance-based group therapy (MAGT). Participants were treatment completers (n = 37 for MAGT, n = 32 for CBGT) from a randomized clinical trial. Cognitive reappraisal was the hypothesized mechanism of change for CBGT. Mindfulness and acceptance were hypothesized mechanisms of change for MAGT. Latent difference score (LDS) analysis results demonstrate that cognitive reappraisal coupling (in which cognitive reappraisal is negatively associated with the subsequent rate of change in social anxiety) had a greater impact on social anxiety for CBGT than MAGT. The LDS bidirectional mindfulness model (mindfulness predicts subsequent change in social anxiety; social anxiety predicts subsequent change in mindfulness) was supported for both treatments. Results for acceptance were less clear. Cognitive reappraisal may be a more important mechanism of change for CBGT than MAGT, whereas mindfulness may be an important mechanism of change for both treatments.

Distress tolerance in OCD and anxiety disorders, and its relationship with anxiety sensitivity and intolerance of uncertainty.

There is a growing interest in the role of distress tolerance (i.e., the capacity to withstand negative emotions) in the onset and maintenance of anxiety. However, both empirical and theoretical knowledge regarding the role of distress tolerance in the anxiety disorders is relatively under examined. Accumulating evidence supports the relationship between difficulties tolerating distress and anxiety in nonclinical populations; however, very few studies have investigated distress tolerance in participants with diagnosed anxiety disorders. Individuals with social anxiety disorder (SAD), generalized anxiety disorder (GAD), panic disorder with and without agoraphobia (PD/A) and obsessive-compulsive disorder (OCD) completed measures of distress tolerance (DT), conceptually related measures (i.e., anxiety sensitivity (AS), intolerance of uncertainty (IU)), and anxiety symptom severity. Results showed that DT was negatively associated with AS and IU. DT was correlated with GAD, SAD and OCD symptoms, but not PD/A symptoms, in individuals with those respective anxiety disorders. DT was no longer a significant predictor of OCD or anxiety disorder symptom severity when AS and IU were also taken into account. There were no between group differences on DT across OCD and the anxiety disorder groups. Implications for the role of distress tolerance in anxiety pathology are discussed.

Mindfulness and acceptance-based group therapy versus traditional cognitive behavioral group therapy for social anxiety disorder: a randomized controlled trial.

UNLABELLED: Recent research has supported the use of mindfulness and acceptance-based interventions for Social Anxiety Disorder (SAD). OBJECTIVE: The purpose of the present study was to compare mindfulness and acceptance-based group therapy (MAGT) with cognitive behavioral group therapy (CBGT) with respect to outcome. It was hypothesized that MAGT and CBGT would both be superior to a control group but not significantly different from one another. METHOD: Individuals (N = 137, mean age = 34 years, 54% female, 62% White, 20% Asian) diagnosed with SAD were randomly assigned to MAGT (n = 53), CBGT (n = 53) or a waitlist control group (n = 31). The primary outcome was social anxiety symptom severity assessed at baseline, treatment midpoint, treatment completion, and 3-month follow-up. Secondary outcomes were cognitive reappraisal, mindfulness, acceptance, and rumination. Depression, valued living, and group cohesion were also assessed. RESULTS: As hypothesized, MAGT and CBGT were both more effective than the control group but not significantly different from one another on social anxiety reduction and most other variables assessed. CONCLUSIONS: The present research provides additional support for the use of mindfulness and acceptance-based treatments for SAD, and future research should examine the processes by which these treatments lead to change.

Treatment-specific changes in decentering following mindfulness-based cognitive therapy versus antidepressant medication or placebo for prevention of depressive relapse.

OBJECTIVE: To examine whether metacognitive psychological skills, acquired in mindfulness-based cognitive therapy (MBCT), are also present in patients receiving medication treatments for prevention of depressive relapse and whether these skills mediate MBCT's effectiveness. METHOD: This study, embedded within a randomized efficacy trial of MBCT, was the first to examine changes in mindfulness and decentering during 6-8 months of antidepressant treatment and then during an 18-month maintenance phase in which patients discontinued medication and received MBCT, continued on antidepressants, or were switched to a placebo. In total, 84 patients (mean age = 44 years, 58% female) were randomized to 1 of these 3 prevention conditions. In addition to symptom variables, changes in mindfulness, rumination, and decentering were assessed during the phases of the study. RESULTS: Pharmacological treatment of acute depression was associated with reductions in scores for rumination and increased wider experiences. During the maintenance phase, only patients receiving MBCT showed significant increases in the ability to monitor and observe thoughts and feelings as measured by the Wider Experiences (p < .01) and Decentering (p < .01) subscales of the Experiences Questionnaire and by the Toronto Mindfulness Scale. In addition, changes in Wider Experiences (p < .05) and Curiosity (p < .01) predicted lower Hamilton Rating Scale for Depression scores at 6-month follow-up. CONCLUSIONS: An increased capacity for decentering and curiosity may be fostered during MBCT and may underlie its effectiveness. With practice, patients can learn to counter habitual avoidance tendencies and to regulate dysphoric affect in ways that support recovery.

Predictors of sustained therapeutic change.

The authors integrate explorations by Blatt and colleagues of contributions of patient personality, therapeutic relationship, and change in mental representation to sustained therapeutic change. A pretreatment personality characteristic, self-critical perfectionism, a negative self-schema, significantly interfered with therapeutic progress in manual-directed, brief outpatient treatment for depression. The therapeutic relationship, however, facilitated changes in this negative self-representation, leading to sustained therapeutic change. The authors also explored change in the content and structural organization of representations of self and significant others in long-term, intensive inpatient treatment. A detailed clinical example elaborates the processes through which the therapeutic relationship facilitates changes in the thematic content and cognitive structural organization of patients' interpersonal schemas that appear to be the basis for sustained therapeutic gain.

The exposure hierarchy as a measure of progress and efficacy in the treatment of social anxiety disorder.

This study explored the psychometric properties and utility of the exposure hierarchy as a measure of treatment outcome for social anxiety disorder (SAD). An exposure hierarchy was created for each of 103 individuals with a diagnosis of SAD who completed a course of cognitive behavioral group therapy. Exposure hierarchy ratings were collected on a weekly basis, and a series of self-report measures were collected before and after treatment. Results indicated that the exposure hierarchy demonstrated high test-retest reliability, as well as significant convergent validity, as participants' exposure hierarchy ratings correlated positively with scores on conceptually related measures. Hierarchy ratings were significantly associated with changes in SAD symptoms over time. However, exposure hierarchy ratings were correlated to general measures of psychopathology, suggesting limited discriminant validity. The study highlights the clinical and scientific utility of the exposure hierarchy.