Survival of an HLA-mismatched, bioengineered RPE implant in dry age-related macular degeneration.

Cell-based therapies face challenges, including poor cell survival, immune rejection, and integration into pathologic tissue. We conducted an open-label phase 1/2a clinical trial to assess the safety and preliminary efficacy of a subretinal implant consisting of a polarized monolayer of allogeneic human embryonic stem cell-derived retinal pigmented epithelium (RPE) cells in subjects with geographic atrophy (GA) secondary to dry age-related macular degeneration. Postmortem histology from one subject with very advanced disease shows the presence of donor RPE cells 2 years after implantation by immunoreactivity for RPE65 and donor-specific human leukocyte antigen (HLA) class I molecules. Markers of RPE cell polarity and phagocytosis suggest donor RPE function. Further histologic examination demonstrated CD34+ structures beneath the implant and CD4+, CD68+, and FoxP3+ cells in the tissue. Despite significant donor-host HLA mismatch, no clinical signs of retinitis, vitreitis, vasculitis, choroiditis, or serologic immune response were detected in the deceased subject or any other subject in the study. Subretinally implanted, HLA-mismatched donor RPE cells survive, express functional markers, and do not elicit clinically detectable intraocular inflammation or serologic immune responses even without long-term immunosuppression.

Growth Resilience of Subarctic Rhodoliths (Lithothamnion glaciale, Rhodophyta) to Chronic Low Sea Temperature and irradiance.

Rhodolith beds are pervasive marine biological systems in the subarctic North Atlantic. Limited knowledge about effects of temperature and irradiance on rhodolith growth limits the ability to anticipate the response of rhodolith beds to this ocean's chronic low, yet changing sea temperature and irradiance regimes. We carried out a 149-d laboratory experiment with Newfoundland Lithothamnion glaciale rhodoliths to test the predictions that growth (i) is inhibited at temperatures of ~0.5°C and (ii) resumes as temperature increases above 0.5°C, albeit at a higher rate under high than low irradiances. Rhodoliths were grown in experimental tanks at near-zero (~0.7°C) seawater temperatures during the first 85 d and at temperatures increasing naturally to ~6°C for the remaining 64 d. Rhodoliths in those tanks were exposed to either low (0.02 mol photons·m-2 ·d-1 ) or high (0.78 mol photons·m-2 ·d-1 ) irradiances during the entire experiment. Rhodoliths grew at a linear rate of ~281 µm·year-1 (0.77 µm·d-1 ) throughout the experiment under both irradiance treatments despite daily seawater temperature variation of up to 3°C. Near-zero temperatures of ~0.5 to 1.0°C did not inhibit rhodolith growth. Model selection showed that PAR-day (a cumulative irradiance index) was a better predictor of growth variation than Degree-day (a cumulative thermal index). Our findings extend to ~0.5°C the lower limit of the known temperature range (~1 to at least 16°C) over which growth in L. glaciale rhodoliths remains unaffected, while suggesting that the growth-irradiance relationship in low-light environments at temperatures below 6°C is less irradiance-driven than recently proposed.

Development and Initial Psychometrics for a Therapist Competence Instrument for CBT for Youth Anxiety.

Therapist competence is an important component of treatment integrity. This article reports on the development and initial psychometric assessment of the Cognitive-Behavioral Treatment for Anxiety in Youth Competence Scale (CBAY-C), an observational instrument designed to capture therapist limited-domain competence (i.e., competence in the delivery of core interventions and delivery methods found in a specific psychosocial treatment program) in the delivery of the core practice elements in individual cognitive-behavioral treatment (ICBT) for youth anxiety. Treatment sessions (N = 744) from 68 youth participants (M age = 10.60 years, SD = 2.03; 82.3% Caucasian; 52.9% male) of the same ICBT program for youth anxiety from (a) an efficacy study and (b) an effectiveness study were independently scored by 4 coders using observational instruments designed to assess therapist competence, treatment adherence, treatment differentiation, alliance, and client involvement. Interrater reliability-intraclass correlation coefficients (2,2)-for the item scores averaged 0.69 (SD = 0.11). The CBAY-C item, scale, and subscale (Skills, Exposure) scores showed evidence of validity via associations with observational instruments of treatment adherence to ICBT for youth anxiety, theory-based domains (cognitive-behavioral treatment, psychodynamic, family, client centered), alliance, and client involvement. Important to note, although the CBAY-C scale, subscale, and item scores did overlap with a corresponding observational treatment adherence instrument independently rated by coders, the degree of overlap was moderate, indicating that the CBAY-C assesses a distinct component of treatment integrity. Applications of the instrument and future research directions discussed include the measurement of treatment integrity and testing integrity-outcome relations.

Initial development of a treatment adherence measure for cognitive-behavioral therapy for child anxiety.

The measurement of treatment adherence (a component of treatment integrity defined as the extent to which a treatment is delivered as intended) is a critical element in treatment evaluation research. This article presents initial psychometric data for scores on the Cognitive-Behavioral Therapy Adherence Scale for Youth Anxiety (CBAY-A), an observational measure designed to be sensitive to common practice elements found in individual cognitive-behavioral therapy (ICBT) for youth anxiety. Therapy sessions (N = 954) from 1 efficacy and 1 effectiveness study of ICBT for youth anxiety were independently rated by 2 coders. Interrater reliability (as gauged by intraclass correlation coefficients) for the item scores averaged 0.77 (SD = 0.15; range .48 to .80). The CBAY-A item and scale (skills, model, total) scores demonstrated evidence of convergent and discriminant validity with an observational measure of therapeutic interventions and an observational measure of the alliance. The CBAY-A item and scale scores also discriminated between therapists delivering ICBT in research and practice settings and therapists delivering nonmanualized usual clinical care. We discuss the importance of replicating these psychometric findings in different samples and highlight possible application of an adherence measure in testing integrity-outcome relations.

Sustained Implementation of Cognitive-Behavioral Therapy for Youth Anxiety and Depression: Long-term Effects of Structured Training and Consultation on Therapist Practice in the Field.

Identifying factors that promote sustained implementation of evidence-based treatments (EBTs) after therapists receive training is critical for professional psychology. To address the field's minimal knowledge in this area, we interviewed community-based therapists (N = 23) who had completed intensive training in cognitive behavioral therapy (CBT) for either anxiety or depression as part of a randomized effectiveness trial (Southam-Gerow et al., 2010; Weisz et al., 2009). Therapists were interviewed three to five years after completion of the initial trial, representing one of the longest-term follow-ups of therapist practices after training. Therapists viewed each protocol and their individual CBT strategies as effective and appropriate for the majority of their current anxiety and depression caseloads. However, therapists used parts of each protocol much more frequently than the protocol as a whole (i.e., 78.5% used parts of the Coping Cat, and 7.5% used the whole protocol; 58.6% used parts of the PASCET, and 20% used the whole protocol). Therapists reported using problem-solving the most and exposure exercises the least for current anxious cases; they used cognitive restructuring the most and homework the least for current depression cases. Interventions that were more difficult to implement in usual care settings were less likely to be sustained. Future efforts should evaluate the characteristics and structure of EBTs that are most acceptable to therapists and should investigate which kinds of ongoing learning supports will maintain therapist skills in and continued use of EBTs.

Professionals' reported provision and recommendation of psychosocial interventions for youth with autism spectrum disorder.

Children and adolescents with autism spectrum disorder (ASD) receive intervention services from multiple professionals across disciplines. Little is known about services for youth with ASD in community settings. The purpose of this study was to provide data on professionals' self-reported practices across different classes of psychosocial interventions for youth with ASD. A multidisciplinary (medicine/nursing, education, occupational/physical therapy, psychology, social work, and speech-language pathology/audiology) sample (N=709; 86% female; 86% White) of professionals who endorsed providing clinical services to youth with ASD was recruited through convenience sampling (listservs, etc.) and stratified random sampling (online provider listings). Professionals completed a survey on intervention practices with youth with ASD, specifically on their own provision of, as well as their recommendation/referral of, psychosocial interventions (focused intervention practices [FIPs], comprehensive treatment models [CTMs], and other interventions). Hierarchical multiple regression models showed discipline differences in self-reported provision and recommendation of evidence-based FIPs; training variables and unfamiliarity with FIPs predicted rates of providing and recommending. FIPs were reportedly provided and recommended at higher rates than CTMs. Descriptive data are presented on professionals' reported practice of other psychosocial interventions (e.g., cognitive-behavioral therapy). This study highlights the usefulness of examining not only provision of services but also recommendation/referral practices: professionals are important sources of information for families. Implications of the results are discussed in terms of the importance of disseminating intervention information to professionals and the need for consensus on terminology used to classify interventions and on criteria used to evaluate intervention efficacy.

Acting Locally and Globally: Dissemination and Implementation Around the World and Next Door.

Murray et al. (this issue) present a fascinating account of their international dissemination and implementation (D&I) research focused on training therapists in Thailand and Iraq to provide a modular treatment approach called Common Elements Treatment Approach to youth. In this commentary, we use Murray et al. as a springboard to discuss a few general conclusions about the current direction of D&I research. Specifically, we reflect on current D&I models, highlighting their ecological focus and their emphasis on stakeholder involvement. Next, we discuss the central importance of implementation supports such as treatment programs, training approaches, assessment and outcome monitoring tools, and organizational interventions. We conclude with a consideration of how D&I work that aims to adapt implementation supports for local needs represent a key path to our goal of sustainability.