Codex @codex  0

Psychotherapy and Psychosomatics 83, 54–61; 57 adolescents aged 13–16, randomised treatments and twelve-month follow-up.

Child and Adolescent Mental Health 24, 242–250; randomised parent-session allocation, primary remission and follow-up.

A collection of observed variables is causally sufficient when no unobserved variable is a common cause of two or more observed variables. In a causal directed acyclic graph model, a common sufficient condition is that the observed graph includes all such common causes; independent unobserved noise affecting only one observed variable is allowed.

For example, $U\to X$ and $U\to Y$ with $U$ unobserved violates causal sufficiency for $\{X,Y\}$. Observing $U$ removes that particular hidden common cause. In contrast, $U\to X\to Y$ alone makes $U$ an ancestor of $Y$ through $X$, without supplying an additional common-cause fork outside the observed graph.

Causal sufficiency supports the use of a causal directed acyclic graph on the observed variables with independent disturbances. It does not by itself imply randomization, faithfulness of a directed acyclic graph, or identification of every causal effect. When hidden common causes remain, a latent projection may require bidirected edges to represent the induced dependence.

Primary publication: doi.org/10.3310/hta21500

Publisher, institutional or primary repository record: www.journalslibrary.nihr.ac.uk/hta/hta21500/

Relevant evidence: Abstract and Chapters 2–3; randomization, medical comorbidity, health-anxiety outcomes and economic endpoints.

Design of experiments chooses experimental units, treatments, replication, blocks in experimental design and randomization so that scientifically useful treatment contrasts can be estimated with meaningful standard errors. Allocation determines which measurements supply independent treatment information.

A randomised comparison that varies a specified treatment component while keeping the surrounding intervention appropriately similar. It is designed to separate component effects that cannot be inferred from efficacy of a multicomponent package.

Developmental Science 16, 915–925; three-arm randomised trial, Results and Discussion.

Econometrics uses statistical models to quantify economic relationships and to assess predictions or causal claims from economic data. The choice of variables and the mechanism generating observations matter as much as estimating the model coefficients.

For example, in a linear regression of log earnings on years of schooling, a slope $0.08$ corresponds to a fitted earnings ratio $e^{0.08}\approx 1.083$ for one additional year. Interpreting that ratio as a causal effect needs more than a good fit: prior attainment or family circumstances may affect both schooling and earnings, creating confounding. Randomization, suitable instrumental variables or a credible natural experiment can support causal interpretation under additional assumptions. The numerical regression coefficient alone supplies an association within its model, not those assumptions.

Egon Pearson developed the theory of statistical hypothesis testing with Jerzy Neyman. Their framework distinguishes controlling type I error under a null hypothesis from maximizing statistical power against a specified alternative hypothesis. University College London's institutional history identifies this collaboration as a central contribution.^[ref]

The Neyman-Pearson lemma makes the tradeoff precise for two simple hypotheses with densities $f_0$ and $f_1$. At a fixed allowed type I error, the most powerful test rejects where the likelihood ratio $f_1/f_0$ is largest, with boundary randomization if needed. To see the principle, compare its test function ${\varphi }_{\ast }$ with another admissible $\varphi$: the product $(\varphi -{\varphi }_{\ast })(f_1-c{f}_0)$ is nonpositive pointwise. Integrating and using the size constraint shows that $\varphi$ cannot have greater statistical power.

Eligibility criteria specify which individuals may enter a clinical trial, defining its enrolled population and excluding individuals for whom the intervention or measurements are unsuitable. Screening applies those criteria before randomization. The treatment comparison's external validity depends on how this population relates to the population of interest.

Improvement in substantially different tasks or domains, such as academic attainment after isolated working memory exercises. Randomised comparisons with credible active controls and prespecified outcome measures make the claim more informative.

A specified test for germination, recording the endpoint, conditions and observation window. For a proposed red/far-red light test, use randomization to allocate one seed lot to darkness, red, red then far-red, and red then far-red then red. Match hydration, temperature, handling and elapsed time before counting; use sham waiting periods to equalize schedules. Use dish replication, retain the dark scientific control, and record radicle emergence using an observation procedure that does not itself provide an uncontrolled light treatment. This is a proposed design, not a claim about the 1952 paper's randomization or replication.

As an original hypothetical counting example, begin with $N=40$ seeds in one dish. Suppose 12 first meet the radicle endpoint by 24 hours, eight additional seeds by 48 hours, and four additional seeds by 72 hours. These invented event counts giveand cumulative sample proportions $\hat{G}(24)=0.30$, $\hat{G}(48)=0.50$ and $\hat{G}(72)=0.60$. The 48-hour increment is $8/40=0.20$, not $0.50$; the latter includes earlier events. Counting the same emerged radicle again at each inspection would inflate the total. These numbers illustrate bookkeeping, not biological rates or treatment effects.

With a fixed denominator and irreversible classification of the first endpoint event, the set counted at an earlier inspection is a subset of the set counted later. Hence $0\le \hat{G}(t)\le 1$ and $\hat{G}(t)$ cannot decrease. This short proof applies to cumulative germination counts even if a later seedling dies. A count of currently surviving seedlings has a different definition and can decrease.

For treatment comparisons, the dish may be the experimental unit: seeds in the same dish share conditions. Forty seeds in one dish do not supply forty independent dish replicates. Report the sample size, replication, endpoint time and denominator; a sample proportion by a deadline measures this assay's outcome, not an unconditional fraction with seed viability.

Homogeneity-study measurement-order confounding occurs when container identity is associated with measurement time, so that instrumental drift can appear to be a difference between portions of a reference material. It is a sampling-design problem in a homogeneity study with replicated test portions: repeating each container twice does not by itself separate its material effect from the instrument's time dependence.

An original measurement model adds a drift term to the container and residual effects:Here $b_i$ is the container contribution, $\gamma$ a linear drift rate and $t_{ij}$ the observation time. A one-way analysis of variance that omits time can assign part of $\gamma t_{ij}$ to container variation. This is confounding, rather than evidence that the material actually changed composition.

Suppose three identical containers have true value 100 in a chosen unit, residual noise is absent, and the instrument increases by one unit per measurement interval. Measuring A twice, then B twice, then C twice at times 0 through 5 produces pairs $(100,101)$, $(102,103)$ and $(104,105)$. Their means are 100.5, 102.5 and 104.5. The within-container mean square is $M{S}_W=0.5$ and the between-container mean square is $M{S}_B=8$. The usual two-replicate estimate givesalthough the stipulated true between-container variance is zero. These are invented observations showing an omitted effect, not a fitted material certificate.

Randomization breaks the systematic link between container label and measurement order in the design, but one random sequence does not guarantee cancellation of drift. The IUPAC protocol requires randomized analytical order and inspection for suspicious trends in the resulting data.^[ref]

A deliberately balanced illustration assigns A to times 0 and 5, B to 1 and 4, and C to 2 and 3. Each mean then contains the same linear-drift contribution, $2.5\gamma$. This cancels drift from differences of those means, but does not reproduce the independent, equal-variance residual model: the within-pair differences still contain drift. Nonlinear drift would also require further assessment.

Retain timestamps, sample identities and the planned order. Suitable experimental blocks, repeated control measurements or a justified drift-aware homogeneity analysis can help distinguish instrument behaviour from material variation. A small residual scatter within adjacent duplicates is insufficient evidence that the instrument stayed stable over the full study.

Informed consent is voluntary agreement after receiving and understanding relevant information about an intervention or participation in research. In a clinical trial, the participant is informed about the study procedures, potential benefits and risks, alternatives and the option to decline or withdraw. Consent precedes randomization.

An intention-to-treat analysis compares participants according to their randomized assignment, retaining that assignment even when they do not use the assigned intervention. Its causal effect is the effect of assignment under the study's actual adherence pattern, rather than the effect of perfect adherence. Randomization protects this comparison from baseline confounding; missing data can still require assumptions or additional analysis.

Nested measurements are responses grouped inside larger units, with each measured object belonging to just one such unit. Three leaves within each pot give nested measurements; repeatedly reading one leaf gives another level of repetition. Either can yield clustered data. A common random effect can describe the shared influence of the containing experimental unit.

For the constructed pot example, label treatments by $g\in \{A,B\}$, pots within each group by $i=1,\dots ,n$, and leaves within each pot by $j=1,\dots ,m$. Consider the statistical modelHere $Y_{gij}$ is a leaf length, $\mu +{\alpha }_g$ is its group expected value, $U_{gi}$ is a pot random effect, and ${\epsilon }_{gij}$ describes remaining variation among leaves and measurement error. Assume that all pot random effects are mutually independent, all remaining errors are mutually independent, and the two collections are independent of one another and of the randomization. These are explicit modelling assumptions, conditional on the assigned treatments; no normal distribution assumption is needed for the following variance calculation.

Two distinct leaf measurements in one pot share $U_{gi}$. Their covariance is ${\tau }^2$, their individual variance is ${\tau }^2+{\sigma }^2$, and their intraclass correlation coefficient isMeasurements from different pots have zero covariance and are independent under the stated statistical model. Statistical independence therefore concerns the whole response structure, not just the fact that the measured leaves are different objects.

A concentrated intervention combining approach practice and learning about a phobic stimulus. A youth randomised trial compared this package with education-support and waiting list. Package efficacy is distinct from proof that one session is the optimal dose for all presentations.^[ref]

Parents should have a negotiated, formulation-led role that helps an adolescent undertake effective treatment while supporting increasing autonomy. Three roles must be distinguished: facilitating access and practice, changing parental responses that maintain avoidance, and receiving treatment for the parent's own difficulties. A parent being present in more sessions is not a mechanism in itself. The relevant question is which parental action changes which maintaining process, for which adolescent, beyond the effects of adolescent treatment alone.

Initial assessment should obtain both the young person's and caregiver's perspectives on feared situations, avoidance, impairment and family responses. Separate discussion with the adolescent can reveal difficulties they would not disclose in a joint meeting. A shared formulation can then identify whether parents provide repeated reassurance, take over social interactions or organise routines around avoidance. Accommodation can bring immediate relief while reducing opportunities for the adolescent to learn that uncertainty and distress are manageable. Support can instead combine recognition of distress with confidence in the young person's capacity to approach an agreed activity. These descriptions concern potentially modifiable interactions, rather than assigning parental blame for the disorder's origin.

The role should fit developmental circumstances. A thirteen-year-old dependent on a caregiver for transport may need different practical support from a seventeen-year-old arranging appointments. Parents can help implement between-session practice, notice approach rather than merely the disappearance of distress, and support school coordination. The adolescent should help decide what information is shared and which sessions are joint, within clearly explained confidentiality and safeguarding arrangements. Parent involvement can undermine treatment if it becomes surveillance, coercion or another route for excessive reassurance. Fathers, other caregivers and relevant family relationships should be considered rather than assuming that the mother is always the appropriate participant.

Adolescent-specific evidence does not support mandatory additional parent sessions for everyone. Polly Waite and colleagues randomised sixty thirteen- to eighteen-year-olds in routine services to immediate or delayed Internet CBT, with an additional random allocation of parent sessions. The parent addition did not significantly improve remission, either immediately or at follow-up, and the online programme itself did not clearly outperform waiting list on the primary remission endpoint. Confidence intervals were wide. This is evidence against assuming a reliable benefit from that particular addition, rather than proof that parental involvement is useless or that a modest targeted effect is impossible.^[ref]

Evidence from younger samples suggests hypotheses about selection. Vanessa E. Cobham and colleagues stratified families by parental anxiety before randomising sixty-seven seven- to fourteen-year-olds to child CBT with or without parental anxiety management. Their findings suggested greater benefit of the addition when a parent was anxious, but results varied across measures. The study motivates a moderator hypothesis; its small subgroups and younger participants limit a general rule for adolescent treatment.^[ref]

A larger test cautions against treating a plausible family risk factor as an established augmentation target. Cathy Creswell and colleagues studied 211 children whose mothers also had anxiety disorders. All received child CBT; additions targeted either maternal anxiety or mother–child interaction, with nonspecific contact balanced. The additions changed some maternal outcomes but did not clearly improve the primary child diagnostic outcome. Treating a parent's anxiety may be worthwhile for that parent without necessarily producing an incremental child-treatment effect. Family-risk association, target engagement and improvement in the child's disorder are separate evidential steps.^[ref]

An alternative is parent-based treatment rather than parental augmentation of child therapy. Eli R. Lebowitz and colleagues randomised 124 seven- to fourteen-year-olds to child CBT or SPACE treatment, a parent intervention reducing accommodation without direct child–therapist sessions. SPACE treatment met prespecified noninferiority criteria for anxiety outcomes and reduced accommodation. This supports the possibility that changing caregiver responses can be an effective delivery route. It does not establish that replacing adolescent-focused therapy with parent work is appropriate across the older teenage years, or that the same approach is preferred by every young person.^[ref]

Together, these studies favour flexible involvement. A useful clinical formulation can identify practical support needs, accommodation that interferes with learning, and parental anxiety requiring its own assessment. However, personalised selection rules remain hypotheses unless prospectively tested. Neither a null augmentation trial nor a successful parent-only trial settles the optimal dose of parent contact alongside a given adolescent therapy. Treatment fidelity also matters: a nominally parent-inclusive programme may differ greatly in whether it rehearses supportive responses, changes accommodation or merely provides information.

A future study should therefore recruit adolescents with diagnosed anxiety across routine services and deliver the same adequate adolescent CBT in every arm. Randomise caregivers to a brief accommodation-focused module or a credible contact-matched education condition; an additional prespecified stratum could examine parents with their own anxiety disorder. Measure accommodation and parental anxiety before allocation, and power the study for the specific treatment-by-baseline-characteristic interactions rather than searching retrospectively for successful subgroups. Include age, caregiver availability and adolescent preference in recruitment and reporting without treating chronological age as a complete measure of autonomy.

Masked diagnostic interviews, young-person-rated impairment and school or social functioning should be assessed after treatment and at six and twelve months. Parent reports should be retained as a separate perspective, not substituted for adolescent outcomes. Record what parents actually do through agreed observations or structured practice tasks, alongside session attendance and treatment fidelity. Measure changes in accommodation repeatedly before the proposed downstream improvement. Temporal mediation would constrain a mechanism, although additional mediator–outcome assumptions would still be needed for a causal mediation claim.

The trial should also measure family burden, acceptability and any deterioration in relationships, and examine families unable to attend conventional sessions. An approach that improves completer outcomes while excluding caregivers with work or language barriers may reduce practical access. Qualitative interviews can explain why a module helps or fails, while the randomised contrast estimates its incremental effect. The 2022 evidence supports parents as potential partners, change agents and recipients of care, but supports a collaboratively chosen and testable role more strongly than indiscriminate intensification of parental attendance.

Clark's cognitive account offers a plausible explanation of panic in young people when bodily sensations are interpreted as signs of imminent catastrophe. Palpitations may be understood as an impending medical disaster, dizziness as loss of control, or a strange mental sensation as “going mad”. Apprehension can increase arousal and attention to the body, generating more of the evidence that seems to confirm danger. Avoidance and safety behaviors can prevent correction. The model makes catastrophic meaning central, rather than identifying panic with bodily arousal alone.^[ref]

This distinction is developmentally important. Many children notice a rapid heartbeat after activity without fearing a panic attack. Conversely, a child may fear a sensation but lack the vocabulary to describe an adult-style medical catastrophe. Older adolescents may worry about embarrassment, losing control in public or being unable to obtain help. Assessment should therefore establish the young person's own prediction in accessible language, distinguish recurrent unexpected attacks from ordinary fear in a threatening situation, and assess persistent concern, avoidance and impairment. A parent account can add context without substituting for the young person's experience of an internal sensation.

Thalia C. Eley and colleagues studied 79 eight- to eleven-year-olds using a heartbeat mental-tracking task, anxiety sensitivity measures and panic/somatic symptom ratings. Better heartbeat perception and fear of bodily sensations were associated with higher panic/somatic symptoms. This supports examining perception and appraisal separately. It does not show that heightened perception causes panic: the sample was not a trial of diagnosed panic disorder, only a small subgroup met the study's “good perception” criterion, and heartbeat counting can reflect knowledge and estimation as well as direct perception. Symptom questionnaires and retrospective accounts also cannot establish the temporal order of a particular attack.^[ref]

Donna B. Pincus and colleagues supplied preliminary treatment evidence in adolescents. Twenty-six fourteen- to seventeen-year-olds were randomised to panic-control treatment or a self-monitoring control, thirteen per arm. The active treatment reduced clinician-rated panic severity and several self-reported outcomes, with gains maintained at follow-up. The small study supports feasibility and potential efficacy of a panic-focused package. A self-monitoring comparator does not control all expectations or therapist contact, and a multicomponent intervention cannot identify catastrophic interpretation change as its sole active ingredient.^[ref]

The evidence is consequently more secure for the usefulness of a panic-focused approach in some adolescents than for a universal cognitive explanation across childhood. Age differences in interoceptive awareness, interpretation of bodily symptoms and ability to report thoughts need direct study. An absence of a consciously recalled catastrophic thought is not decisive against a rapid or poorly articulated appraisal, but the theory must specify a testable process rather than protect itself by making every unreported appraisal invisible. Physiological or contextual influences can also contribute to sensations and threat, and changes in arousal can affect what a person later reports having thought.

An experiment should manipulate interpretation while measuring the bodily input and avoid using a treatment outcome as the only test. Recruit adolescents with diagnosed panic disorder, a comparison group with another anxiety disorder and a nonclinical comparison group. Within each group, randomly allocate participants to an age-adapted explanation of benign exercise-related sensations or a credible, contact-matched general health-information condition. Both groups would complete the same brief, developmentally appropriate mild activity under an approved protocol. The activity is a standardised source of ordinary arousal, not an instruction to provoke severe panic; medical eligibility and stopping rules would be determined beforehand with appropriate clinical oversight.

The apparatus would include ECG recording for actual heart rate and a simple respiratory measure, together with repeated short ratings of perceived sensations, expected consequences and fear. Obtain ratings before information, immediately before activity, during recovery and at a delayed follow-up. The primary contrast should be the randomised difference in panic-related fear, with baseline severity accounted for. Separately measure the catastrophic interpretation the intervention is intended to change and the actual physiological response. The key prediction is reduced fear after the benign interpretation despite comparable elicited sensations, rather than success defined merely as a smaller heartbeat increase.

The control condition should match time, adult reassurance and attention without teaching the specific reinterpretation. Assessors of diagnosis and follow-up behaviour should remain masked. Include both written and verbally supported interpretation measures, pretested for comprehension, so a developmental effect is not simply a reading test. Prespecify one primary outcome, secondary physiological and appraisal measures, meaningful effect sizes, missing-data handling and diagnostic-group interactions. Age or developmental stage should be measured and the relevant interaction adequately powered; a nonsignificant age interaction in a small trial would not establish developmental equivalence.

Several patterns would discriminate accounts. If information changes catastrophic expectations and reduces fear while the physiological input is similar, this supports a causal contribution from interpretation. If it reduces arousal as well, the overall intervention effect remains meaningful but the appraisal-specific pathway is less isolated. If the effect occurs equally for all anxiety groups, the process may be transdiagnostic rather than unique to panic. A successful manipulation with precise null effects on fear would challenge the proposed mechanism under these conditions. A failed manipulation would instead require revising the procedure or measure.

Mediation should be treated cautiously. Randomising the information identifies the effect of that information package; it does not automatically randomise appraisal scores or remove all confounding of appraisal and subsequent fear. Temporal sampling and alternative mediator measures improve the argument, but a stronger mechanistic programme would replicate with a different way of changing interpretation and test transfer to naturally occurring sensations. Follow-up should assess avoidance and impairment as well as laboratory distress, without withholding established care from participants.

By the 2022 evidence base, Clark's model provided a clear set of hypotheses and a promising adolescent treatment rationale. Associations in younger children and a small adolescent treatment trial warranted further tests, not a conclusion that every child panic presentation had already been explained. The proposed experiment would establish whether changing the meaning assigned to matched bodily sensations alters fear, and where developmental differences constrain that inference.

The Clark–Wells model is a useful, partly experimentally supported account of adolescent social anxiety, but its applicability must be assessed at the level of particular processes. It proposes that feared evaluation activates negative assumptions, self-focused attention and an internally generated impression of how one appears. safety behaviors can interfere with the interaction or make a satisfactory outcome seem dependent on protection. Anticipatory and post-event processing can perpetuate the threat interpretation. Its adult origins do not establish that all these processes operate identically at every developmental stage.^[ref]

For an adolescent, the account gives testable examples. A pupil who believes that visible hesitation will lead to rejection may monitor their voice, mentally rehearse every sentence and speak very little. Monitoring consumes attention that could be used to follow the conversation; silence changes how the interaction proceeds; afterwards, the pupil may treat their felt anxiety as evidence that their performance looked disastrous. A behavioral experiment should test the feared prediction and the effects of these strategies, rather than merely reassure the pupil that peers will approve. Actual bullying or exclusion also matters: a clinically useful account must include the social environment, not classify every negative expectation as an error.

Eleanor Leigh and colleagues provided an experimental test in 57 high- and low-social-anxiety adolescents. Participants held counterbalanced conversations while either focusing internally and using safety behaviors, or focusing externally and dropping those behaviours. The internal-focus/safety-behaviour condition increased experienced and apparent anxiety and undermined performance, using self, conversation-partner and independent ratings. This gives stronger causal evidence than a correlation between anxiety and reported strategies. But the two processes were manipulated together, participants were selected by symptom scores rather than all having a clinical diagnosis, and brief instructed behaviour need not reproduce the chronic disorder.^[ref]

Treatment evidence is consistent with clinical utility but tests a package. Jo Magne Ingul and colleagues randomised 57 thirteen- to sixteen-year-olds with primary social phobia to individual cognitive therapy, group CBT or attentional placebo. Individual cognitive therapy produced greater improvement in symptoms and impairment, with benefits assessed through twelve months. Differences in format and delivery, however, accompany the difference in formulation. Improvement cannot establish which proposed process was necessary, or exclude explanations involving individual attention, exposure opportunities or treatment competence.^[ref]

Developmental qualifications are substantive. Adolescents' models of other minds, self-description and ability to notice a mental image are still changing. A failure to articulate a distorted self-image may reflect the measure or interview demands, rather than its absence; conversely, an eloquent account elicited by an interviewer is not proof that the image drives anxiety in daily life. Peer evaluation can be particularly consequential because school interactions are repeated and difficult to leave. Parents may arrange or prevent social opportunities, while online interactions introduce different opportunities for rehearsal and concealment. These issues suggest adapting assessment and delivery while testing, rather than presuming, the proposed mechanisms.

An informative new experiment would separate the bundled processes. Recruit a multisite sample of adolescents with diagnosed social anxiety disorder, alongside an age-matched comparison sample. Within each group, randomise participants to a two-by-two design: internal versus external attention, and use versus reduction of individually identified safety behaviors during one standardised conversation. A between-participant design avoids learning and carry-over across four conversations; the required sample should be powered for prespecified interactions and meaningful effects, using pilot variability and plausible smallest effects rather than adult effect sizes alone. Diagnostic group and age are observed characteristics, so their interactions would moderate the experimental effect without being randomised causes themselves.

The conversation should use a trained, age-appropriate partner following a common script and unaware of allocation. Instructions must be comprehensible, equally credible and checked before the task. Independent coders, masked to condition and diagnostic status, would rate video-recorded performance. Record baseline anxiety and predicted evaluation before the task, self-focused attention and strategy use as manipulation checks, anxiety as the primary outcome, and partner evaluations, self–observer discrepancies and post-event processing as secondary outcomes. A physiological measure such as heart rate can characterise arousal, but should not be treated as a direct measurement of what the adolescent believes others think.

The model predicts that manipulating the proposed maintaining processes should alter anxiety and, potentially, interaction quality. Independent effects would support separating the two processes; an interaction would indicate that one changes the consequences of the other. Effects in the comparison group would not refute the model, because the clinical claim can concern habitual use and persistent feedback rather than a uniquely pathological response to the instruction. A convincing result would relate the manipulation to the specific predicted threat and self–observer gap, rather than to general distress alone.

Several controls sharpen the inference. Measure baseline social competence and verbal ability, randomise the partner/topic allocation, and use blinded coding with prespecified reliability checks. Avoid asking the partner to provide genuine humiliation: the experimental contrast concerns attention and strategies in an ordinary interaction. Obtain informed consent and assent appropriate to the participants, agree withdrawal procedures and explain the purpose afterwards. Follow participants with a new, uncoached interaction and a brief delayed assessment to examine whether any learning extends beyond immediate compliance. Prespecify exclusions, primary contrasts, missing-data handling and all subgroup analyses.

A null result is informative only if the manipulation actually changes attention and strategies, measurement is reliable, and confidence intervals rule out effects worth detecting. If only immediate self-report changes, demand characteristics remain a serious alternative. If masked performance and delayed threat beliefs change in the predicted directions, support for an adolescent maintaining mechanism becomes stronger, though not a full explanation of onset. By 2022, the model justified focused assessment and promising treatment development; the proposed factorial study would improve on treating a successful adult model or an effective treatment package as a complete developmental validation.