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Although technical (quality of delivering techniques from a specific treatment) and global (general clinical expertise) competence are believed to be important ingredients of successful psychosocial treatment with youth, there have been few empirical efforts to measure both dimensions. Efforts to understand the role that each competence dimension plays in the process and outcome of youth treatment starts with determining whether the dimensions can be measured separately. This study examined whether scores from measures designed to assess technical and global competence were distinct. Treatment sessions (N = 603) from 38 youths (M age = 9.84 years, SD = 1.65; 60.5% White; 52.6% male) treated for primary anxiety problems within a randomized effectiveness trial were coded. Four coders used observational measures designed to assess technical competence, global competence, protocol adherence, and the alliance. Mean item interrater reliability was .70 (SD = .09) for technical competence and .66 (SD = .05) for global competence. While most components of global competence were distinct from technical competence scores, two components showed redundancy (r > .70). Scores on both competence measures were empirically distinct (r < .70) from scores on measures of protocol adherence and the alliance. Although the measures did not fully distinguish between technical and global competence, our findings do indicate that some components of technical and global competence may provide unique information about competence.

Though treatment integrity measurement is important for research intended to promote social and behavioral outcomes of children at risk for emotional and behavioral disorders (EBDs) in early childhood settings, measurement gaps exist in the field. This paper reports on the development and preliminary psychometric assessment of the treatment integrity measure for early childhood settings (TIMECS), an observational measure designed to address existing measurement gaps related to treatment integrity with tier 2 interventions in the early childhood field. To assess the preliminary score reliability (interrater) and validity (construct, discriminant) of the TIMECS, live observations (N = 650) in early childhood classrooms from 54 teachers (92.6% female, 7.4% male; 61.1% White) and 91 children (M age = 4.53 years, SD = .44; 45.1% female, 54.9% male; 45.1% Black) at risk for EBDs were scored by 12 coders using the TIMECS and an observational measure designed to assess teacher-child interactions. Teachers also self-reported on the quality of the teacher-child relationship. Interrater reliability (intraclass correlation coefficients, ICC [2,2]) for the quantity (i.e., adherence) item scores had a mean of .81 (SD = .07; range from .68 to .95), and the quality (i.e., competence) item scores had a mean of .69 (SD = .08; range from .52 to .80). Scores on the TIMECS Quantity and Quality items and scales showed evidence of construct validity, with the magnitude of the correlations suggesting that the quantity and quality items assess distinct components of treatment integrity. A TIMECS quantity scale also showed promise for intervention evaluation research by discriminating between teachers who had and had not been trained in a specific evidence-based intervention targeting social and behavioral skills in early childhood. The findings support the potential of the TIMECS to assess treatment integrity of teacher-delivered practices designed to address child social and behavioral outcomes of children at risk for EBDs in early childhood settings.

Δ6-Methyltestosterone was reported as the main active ingredient of the purported "dietary supplement" Jungle Warfare. This compound is structurally similar to 17α-methyltestosterone, containing an additional Δ6 double bond, and is reported to possess notable androgenic activity, raising concerns over the potential for abuse of Jungle Warfare in sport. The in vivo metabolism of Δ6-methyltestosterone in greyhounds was investigated. Urinary phase I (unconjugated) and phase II (glucuronide) metabolites were detected following oral administration using liquid chromatography-mass spectrometry. No phase II sulfate metabolites were detected. The major phase I metabolite was confirmed as 16α,17β-dihydroxy-17α-methylandrosta-4,6-dien-3-one by comparison with a synthetically-derived reference material. Minor amounts of the parent drug were also confirmed. Glucuronide conjugated metabolites were also observed, but were found to be resistant to hydrolysis using the Escherichia coli β-glucuronidase enzyme. Qualitative excretion profiles, limits of detection, and extraction recoveries were determined for the parent drug and the major phase I metabolite. These results provide a method for the detection of Jungle Warfare abuse in greyhounds suitable for incorporation into routine screening methods conducted by anti-doping laboratories.

Samples of the "dietary supplement" Furazadrol sourced through the internet have been reported to contain the designer anabolic androgenic steroids [1',2']isoxazolo[4',5':2,3]-5α-androstan-17β-ol (furazadrol F) and [1',2']isoxazolo[4',3':2,3]-5α-androstan-17β-ol (isofurazadrol IF). These steroids contain an isoxazole fused to the A-ring and were designed to offer anabolic activity while evading detection, raising concerns over the potential for abuse of this preparation in sports. The metabolism of Furazadrol (F:IF, 10:1) was studied by in vivo methods in greyhounds. Urinary phase II Furazadrol metabolites were detected as glucuronides after a controlled administration. These phase II metabolites were subjected to enzymatic hydrolysis by Escherichia coli β-glucuronidase to afford the corresponding phase I metabolites. Using a library of synthetically-derived reference materials, the identities of seven urinary Furazadrol metabolites were confirmed. Major confirmed metabolites were isofurazadrol IF, 4α-hydroxyfurazadrol 4α-HF, and 16α-hydroxy oxidised furazadrol 16α-HOF, while the minor confirmed metabolites were furazadrol F, 4β-hydroxyfurazadrol 4β-HF, 16β-hydroxyfurazadrol 16β-HF, and 16β-hydroxy oxidised furazadrol 16β-HOF. One major hydroxyfurazadrol and two dihydroxyfurazadrol metabolites remained unidentified. Qualitative excretion profiles, limits of detection, and extraction recoveries were established for furazadrol F and major confirmed metabolites. These investigations identify the key urinary metabolites of Furazadrol following oral administration, which can be incorporated into routine screening by anti-doping laboratories to aid the regulation of greyhound racing.

The purpose of this special series is to highlight how the measurement of integrity, both treatment integrity and integrity for implementation strategies, can support intervention development, evaluation, and implementation research. The seven papers and one commentary in this special series illustrate how diverse measurement approaches are used for integrity across various types of intervention research. This introductory paper provides a general overview of the themes that cut across the papers in this special series. We define key terms and discuss how the measurement of treatment integrity (i.e., extent to which the core practices of a protocol are delivered) and integrity to implementation strategies (i.e., extent to which the core practices of an implementation strategy are delivered) changes as an intervention progresses along the treatment development pipeline spanning from basic research to implementation and dissemination research. Then we discuss the ways that the measurement of integrity can change across the different steps in the pipeline to meet the goals associated with different stops along the pipeline. We finish the paper with a description of the papers in the special series and concluding thoughts.

To explore pre-doctoral faculty perceptions toward implementation of value-based care (VBC) in didactic and clinical teaching.This project was a collaborative effort between CareQuest and the University of North Carolina at Chapel Hill, Adams School of Dentistry introducing VBC to pre-doctoral dental faculty as part of a new curriculum. Following a faculty development session on VBC in June 2021, faculty and subject matter experts were invited to participate in qualitative interviews. Subject matter experts were interviewed to establish a baseline for VBC knowledge and understanding. Interviews were recorded and transcribed verbatim. Analysis was conducted by two analysts using ATLAS.ti and a thematic analysis approach.Six faculty and two subject matter experts participated in interviews. Although dental faculty demonstrated some understanding of VBC, they recognized that more training is required to build in-depth knowledge and implementation strategies for teaching dental students. Faculty discussed value-based concepts such as prevention-focused teaching, person-centered care, and disease management over invasive restoration of teeth, and how VBC is bringing about a paradigm shift in dentistry that needs to be reflected in dental education. They acknowledged a disconnect between VBC in didactic teaching versus clinical instruction. Those interviewed believed it would take time to shift faculty mindset and readiness to teach VBC, and continued efforts are needed at the leadership and faculty level for acceptance and implementation.Although dental faculty recognize that VBC can bring a shift in dental practice, more training and guidance to implement it in didactic and clinical teaching is needed.

This study evaluated the association of autistic traits (RAADS-14) with academic and social outcomes among college students using data from an online survey (N = 2,736). In the academic domain, the total trait score and all subscale scores (mentalizing deficits, social anxiety, sensory reactivity) were associated with course failure and academic difficulties independent of an autism diagnosis; the total score and mentalizing deficits also predicted lower grade point average (GPA). In the social domain, the total trait score and subscale scores were associated with lower odds of having a confidant, lower friendship quality, and higher odds of social exclusion. Subgroup analyses revealed that autistic traits had more consistently negative associations with social outcomes for students without an autism diagnosis than for students with a diagnosis. Associations were also more often significant for women than men. These results support the development of programs and services for students with autistic traits regardless of diagnostic status.

The identification and confirmation of steroid sulfate metabolites in biological samples are essential to various fields, including anti-doping analysis and clinical sciences. Ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) is the leading method for the detection of intact steroid conjugates in biofluids, but because of the inherent complexity of biological samples and the low concentration of many targets of interest, metabolite identification based solely on mass spectrometry remains a major challenge. The confirmation of new metabolites typically depends on a comparison with synthetically derived reference materials that encompass a range of possible conjugation sites and stereochemistries. Herein, energy-resolved collision-induced dissociation (CID) is used as part of UHPLC-HRMS/MS analysis to distinguish between regio- and stereo-isomeric steroid sulfate compounds. This wholly MS-based approach was employed to guide the synthesis of reference materials to unambiguously confirm the identity of an equine steroid sulfate biomarker of testosterone propionate administration.

Teacher-reported measures of treatment integrity (the extent to which prescribed practices are delivered as intended by teachers) have the potential to support efforts to evaluate and implement evidence-based interventions in early childhood settings. However, self-report treatment integrity measures have shown poor correspondence with observer-report treatment integrity measures, raising questions about score validity. This paper reports on the development and initial evaluation of the score reliability and validity of the Treatment Integrity Measure for Early Childhood Settings Teacher Report (TIMECS-TR), which is designed to address limitations of previous self-report treatment integrity measures that may have contributed to low correspondence with observer-rated measures. The TIMECS-TR includes 24 items designed to represent practices found in evidence-based interventions delivered in early childhood settings that target child social, emotional, and behavioral skills, rather than adherence to practices found in a specific evidence-based intervention. Fifty-four teachers (92.6% female, 7.4% male; 61.1% White) completed the TIMECS-TR weekly for a total of 618 times (M = 6.79 per child; SD = 2.16; range 2 to 11) about the practices they delivered with 91 children (45.1% female, 54.9% male; M = 4.53 years old; SD = 45.1% Black) who were at risk for emotional and behavioral disorders. Analyses indicated that the TIMECS-TR items evidenced mild to moderate test–retest score reliability over one week. However, analyses did not support the convergent score validity of the TIMECS-TR items or scale with observational ratings of the same practices. Teachers reported higher levels of practice delivery on the TIMECS-TR items relative to observer report. Overall, our findings raise concerns about the accuracy of teacher-report adherence measures. Lessons from this research can be used to identify possible reasons for the low correspondence between teacher- and observer-report treatment integrity measures so that future research can strive to dependably capture teacher delivery of the practices found in evidence-based interventions.

Although the alliance is a consistent predictor of treatment outcomes in psychosocial interventions, few studies have examined this association among youth with autism spectrum disorder (ASD). In particular, youth-therapist alliance has never been examined in social skills interventions (SSIs), a common modality for this population. In this study, thirty-four youth with ASD (Mage = 12.41; 79% male) participated in a community-delivered, group-based SSI in a summer camp format led by eight Head Therapists (Mage = 32.12; 50% male). Early alliance and change in alliance over the course of the treatment were assessed via self- and observer-reported measures. Both self- and observer-rated alliance were associated with positive treatment outcomes as reported by parents (decreased problem behaviors) and other peers in the group (reciprocated friendship and social preference). These results provide the first evidence of the role of the alliance in an SSI for youth with ASD and add to the growing body of literature that demonstrates the importance of assessing and addressing the alliance in treatment for this population.

Introduction Studies have found that psychological treatments produce positive clinical outcomes for many problems experienced by youth. However, there is limited research on whether therapist adherence and competence in delivering these treatments are related to differential clinical outcomes. Method We examined the relationship of therapist adherence and competence to clinical outcomes in a sample of 51 youth aged 7-14 years (M age = 10.36, SD = 1.90; 86.3% white; 60.8% male) treated for anxiety disorders with a manualized individual cognitive-behavioral therapy. Adherence and competence were measured via coding of recorded treatment session content and outcomes were measured by caregiver and youth report across multiple timepoints. We used two-level mixed-effects regression models to test the degree to which adherence and competence predicted differential youth clinical outcomes. Results Across multiple caregiver- and child-reported symptom and diagnostic outcomes, we found no statistically significant relationship between adherence or competence and clinical outcomes. Discussion Although there was variability in both treatment integrity and clinical outcome, neither adherence to nor competence in youth anxiety treatment was related to clinical outcomes for youth with anxiety disorders treated with individual cognitive-behavioral treatment (CBT) in a research clinic-based efficacy trial. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

We advance research on the association of educational expectation–attainment gaps with mental health by asking two questions that derive from the stress process and life course frameworks: (1) How does the association change over the early adult life course? and (2) To what extent is the association attributable to adult social roles and socioeconomic attainment? Using the National Longitudinal Study of Adolescent to Adult Health, we find that close to the time when the expectation would have been realized, educational attainment is associated with mental health but expectations and the interaction between expectations and attainments are not, independent of selection factors. As respondents age, expectations themselves become more consistently associated with mental health. Adult social roles and socioeconomic status contribute little to explaining these associations. We discuss the implications for the stress process framework and life course research.

While the measurement of treatment integrity is important to determine how much, and how well, interventions are delivered in schools, the science of treatment integrity is not well developed in education research. The purpose of this paper is to describe a program of research that has developed treatment integrity measures over the past 10 years to assess teacher delivery of an indicated program targeting reductions in problem behavior in early childhood and elementary school classrooms. Specifically, this paper will highlight the importance of active use of conceptual models to guide treatment integrity measure development, multidimensional assessment of treatment integrity and training procedures for observers, using several studies to illustrate the evolution and refinement of our measurement approach. Recommendations for researchers developing and evaluating interventions in schools are provided, as are recommendations to help the field move toward a more rigorous science of treatment integrity.

PurposeTo compare the effects of the Ahmed glaucoma valve (AGV; New World Medical, Rancho Cucamonga, CA) with sulcus versus anterior chamber (AC) tube placement on the corneal endothelial density and morphology over time.DesignNonrandomized, interventional study.ParticipantsThis study included 106 eyes from 101 pseudophakic patients who had the AGV tube placed in the AC (acAGV) and 105 eyes from 94 pseudophakic patients who had the AGV tube placed in the ciliary sulcus (sAGV).MethodsAll patients underwent preoperative specular microscopy, which was repeated postoperatively in 2019. The patients' demographic information, glaucoma diagnoses, and basic ocular information were obtained on chart review. Anterior segment OCT was conducted for patients who underwent sAGV to evaluate the sulcus tube position. Gonioscopy was performed to document peripheral anterior synechiae (PAS). Linear mixed-effects models were used to compare the different ocular and endothelial measurements between the 2 groups and to identify risk factors for endothelial cell density (ECD) loss over time.Main outcome measuresMonthly change in corneal endothelial measurements, including ECD and coefficient of variation (CV), calculated as the difference between preoperative and postoperative measurements divided by the number of months from the time of surgery to postoperative specular microscopy.ResultsThe acAGV and sAGV groups were comparable in all baseline characteristics except that the acAGV group had longer follow-up (37.6 vs. 20.1 months, respectively, P < 0.001). Mean monthly loss in central ECD was significantly more in the acAGV group (mean ± standard deviation: 29.3±29.7 cells/mm2) than in the sAGV group (15.3±20.7 cells/mm2, P < 0.0001). Mean monthly change in CV was similar between the 2 groups (P= 0.28). Multivariate analyses revealed that younger age and tube location in the AC were associated with faster central ECD loss (P= 0.02, P < 0.0001, respectively). For patients with sAGV, while PAS was associated with faster central ECD loss (P= 0.002), a more forward tube position tenting the iris was not (P > 0.05).ConclusionsCompared with anterior segment placement, ciliary sulcus tube implantation may be a preferred surgery approach to reduce endothelial cell loss in pseudophakic patients.

Teledentistry helped dentistry adapt to pandemic-era challenges; little is known about dental professionals' teledentistry experiences during this time. This analysis sought to understand professionals' pandemic teledentistry experiences and expectations for the modality's future.We conducted virtual individual interviews (n = 21) via Zoom to understand how federally qualified health centers (FQHCs) delivered oral care during the first year of the pandemic, including but not limited to the use of teledentistry. We independently coded each transcript, then identified themes and sub-themes.We identified three major themes: (1) Logistical and equity considerations shaped teledentistry's adoption; (2) Team-based factors influenced implementation; and (3) Teledentistry's future is as-yet undetermined.Experiences with teledentistry during the first year of COVID-19 varied substantially. Future directions should be more deliberate to counter the urgency of pandemic-style implementation and must address appropriate use, reimbursement guidance, patient and provider challenges, and customizability to each clinic's context.

Background Breast reconstruction is most frequently performed using implants or expanders. Adjunctive materials such as acellular dermal matrix and synthetic meshes are used to support the implant or expander. A paucity of large studies exist on the use of synthetic mesh for breast reconstruction. Methods A retrospective chart review of all patients over the past 7 years who had implant reconstruction with synthetic absorbable mesh at the Massachusetts General Hospital was performed. Data were collected on demographic and surgical outcomes. Statistical analysis was performed. Results A total of 227 patients (376 mastectomies) were treated with direct-to-implant subpectoral reconstruction with absorbable mesh from 2011 to 2017. The infection rate was 2.1 percent. The rate of capsular contracture was 4.8 percent. Patients who had radiation therapy either preoperatively or postoperatively had a higher rate of complications, including capsular contracture. Cost savings for using mesh instead of acellular dermal matrix surpassed $1.2 million. Conclusion Synthetic absorbable mesh is a safe alternative to acellular dermal matrix in prosthetic breast reconstruction and provides stable results along with significant cost savings. Clinical question/level of evidence Therapeutic, IV.

Mental health clinicians and administrators are increasingly asked to collect and report treatment outcome data despite numerous challenges to select and use instruments in routine practice. Measurement-based care (MBC) is an evidence-based practice for improving patient care. We propose that data collected from MBC processes with patients can be strategically leveraged by agencies to also support clinicians and respond to accountability requirements. MBC data elements are outlined using the Precision Mental Health Framework (Bickman et al. in Adm Policy Mental Health Mental Health Serv Res 43:271-276, 2016), practical guidance is provided for agency administrators, and conceptual examples illustrate strategic applications of one or more instruments to meet various needs throughout the organization.

Data from an online survey of undergraduate students at 14 colleges and universities were used to estimate the association of autism with six physical and mental health outcomes, accounting for comorbidity with other disabilities (learning disability, attention deficit hyperactivity disorder, sensory impairment, mobility impairment, mental health disorder, or other disabilities). Autism status was determined based on registration for disability accommodations based on autism and/or self-reports of an autism diagnosis. Health outcomes included self-rated physical health, self-rated mental health, depressive symptoms, symptoms of anxiety, sleep deprivation, and binge drinking. Students with autism reported poorer self-rated physical and mental health, more depressive symptoms, and more symptoms of anxiety than other students, even in the presence of controls for other disabilities. Students with autism also reported a lower likelihood of sleep deprivation and binge drinking than other students. Our results extend previous research on the health correlates of autism by considering additional indicators of health and by incorporating a direct comparison to neurotypical students. They encourage consideration of how health services for students with autism can be improved, especially for mental health problems, and argue for integrated support services that address the full constellation of physical and mental health challenges that students on the spectrum experience.Lay abstractStudies have shown that children and older adults on the autism spectrum experience more physical and mental health problems than their neurotypical peers. Less is known about the physical and mental health of college students on the spectrum. Studying college students is important because young adults on the spectrum are enrolling in college at increasing rates and because health problems can be a barrier to succeeding in college. We collected data from 2820 students at 14 colleges and universities using an online survey, some of whom had registered for accommodations based on autism and others of whom had not. We used the data to compare the physical and mental health of students on the spectrum to their neurotypical peers. Because students with autism often report other disabilities that also affect health, we accounted for whether they experienced a learning disability, attention deficit hyperactivity disorder, sensory impairment, mobility impairment, mental health disorder, or any other disabilities. We assessed health using self-reports of how healthy they were physically and mentally, and reports of depressive symptoms, symptoms of anxiety, sleep deprivation, and binge drinking. We found that students with autism reported poorer physical and mental health, more depressive symptoms, and more symptoms of anxiety even after taking into account other disabilities they may have experienced. They were also less likely to report sleep deprivation and binge drinking. Our results argue for developing specialized services to address the physical and mental health challenges of college students on the spectrum.

Hemapolin (2α,3α-epithio-17α-methyl-5α-androstan-17β-ol) is a designer steroid that is an ingredient in several "dietary" and "nutritional" supplements available online. As an unusual chemical modification to the steroid A-ring could allow this compound to pass through antidoping screens undetected, the metabolism of hemapolin was investigated by an in vivo equine drug administration study coupled with GC-MS analysis. Following administration of synthetically prepared hemapolin to a thoroughbred horse, madol (17α-methyl-5α-androst-2-en-17β-ol), reduced and dihydroxylated madol (17α-methyl-5α-androstane-2β,3α,17β-triol), and the isomeric enone metabolites 17β-hydroxy-17α-methyl-5α-androst-3-en-2-one and 17β-hydroxy-17α-methyl-5α-androst-2-en-4-one, were detected and confirmed in equine urine extracts by comparison with a library of synthetically derived reference materials. A number of additional madol derivatives derived from hydroxylation, dihydroxylation, and trihydroxylation were also detected but not fully identified by this approach. A yeast cell-based androgen receptor bioassay of available reference materials showed that hemapolin and many of the metabolites identified by this study were potent activators of the equine androgen receptor. This study reveals the metabolites resulting from the equine administration of the androgen hemapolin that can be incorporated into routine GC-MS antidoping screening and confirmation protocols to detect the illicit use of this agent in equine sports.

Student problem behaviors in early elementary school are associated with fewer learning opportunities, poor relationships with teachers, and academic and behavioral problems, including increased risk of emotional/behavioral disorders (EBDs). This study examined the effect of BEST in CLASS–Elementary (BEST in CLASS-E), a Tier 2 intervention delivered by teachers, on student problem behavior, academic achievement, teacher–student relationships, and classroom quality using a randomized controlled trial design. Participants were 45 kindergarten to grade 3 students identified at risk of development of EBDs and their 26 teachers from three elementary schools located in an urban school district. BEST in CLASS-E was found to decrease teacher-reported student problem behavior and increase teacher–student closeness; no effects were noted for academic achievement or overall classroom quality. Results suggest the promise of BEST in CLASS-E as a Tier 2 intervention delivered by teachers in elementary classrooms. Implications and limitations of the study are discussed.

The purpose of this paper is to determine how youth with anxiety recruited for a school-based randomized controlled trial (RCT) compare demographically and clinically to clinically referred youth with anxiety who participated in an RCT conducted in community mental health clinics. Youth (N = 99) with anxiety aged 12–15 years were: (a) 37 youth (M age = 13.70, SD = .89; 97.3% Norwegian; 19.0% male) from a school-based RCT and (b) 62 youth (M age = 13.8, SD = 1.0; 88.7% Caucasian; 29.5% male) from an RCT conducted in community mental health clinics. The youth were assessed for anxiety diagnoses, functional impairment, internalizing symptoms, and externalizing symptoms. Compared to the clinically referred youth who received care in community mental health clinics, the youth in the school sample met criteria for fewer anxiety diagnoses, lower severity of diagnoses, and less functional impairment caused by mental health problems. However, the school sample had significantly higher levels of youth-rated anxiety symptoms, t(95) = − 2.33, p = .02, parent-rated depression, t(94) = 4.45, p

In this exploratory study, we studied and qualitatively evaluated a prototype video data collection system to capture and analyze fish behavior in a small-scale indoor aquaculture operation. The research objective was to design and develop a hardware / software system that would have the potential to capture meaningful data from which to extract fish size, swim trajectory, and swim velocity, ultimately as information toward an assessment of fish health. The initial work presented in this paper discusses the development choices of the prototype system, including various combinations of lighting and camera positions both inside and outside of the aquaculture tanks, and several post-processing techniques to isolate fish in video, calibrate the distance from camera to fish through water, and infer fish trajectories and swim velocities. Preliminary results provided a qualitative assessment of such a system. Specific results on the system’s ability to detect fishes’ positions, trajectories, and velocities are presently limited to observational outcomes and descriptive statistics rather than large-scale quantitative analysis. The present work lays a foundation for a future commercially hardened system that would be required for the collection of larger datasets, which would in turn facilitate the future development of machine learning (ML) algorithms to begin to statistically correlate data to fish conditions and behaviors in near-real time.

Steroid sulfate esters are important metabolites for anti-doping efforts in sports, pathology and research. Analysis of these metabolites is facilitated by hydrolysis using either acid or enzymatic catalysis. Although enzymatic hydrolysis is preferred for operating at neutral pH, no known enzyme is capable of hydrolyzing all steroid sulfate metabolites. Pseudomonas aeruginosa arylsulfatase (PaS) is ideal for the hydrolysis of β-configured steroid sulfates but like other known class I sulfatases it is inefficient at hydrolyzing α-configured steroid sulfates. We have used directed evolution with liquid chromatography mass spectrometry screening to find variants capable of hydrolyzing a α-configured steroid sulfate: etiocholanolone sulfate (ECS). After targeting two regions of PaS, four residues were identified and optimized to yield a final variant with a total of seven mutations (DRN-PaS) capable of hydrolyzing ECS ~80 times faster than the best PaS variant previously available. This DRN-PaS also shows improved activity for other α-configured steroid sulfates. Simultaneous mutagenesis was essential to obtain DRN-PaS due to complementarity between targeted residues.

Objective The full phenotypic expression of non-alcoholic fatty liver disease (NAFLD) in lean subjects is incompletely characterised. We aimed to investigate prevalence, characteristics and long-term prognosis of Caucasian lean subjects with NAFLD. Design The study cohort comprises 1339 biopsy-proven NAFLD subjects from four countries (Italy, UK, Spain and Australia), stratified into lean and non-lean (body mass index (BMI) 10 483 person-years), 4.7% of lean vs 7.7% of non-lean patients reported liver-related events (p=0.37). No difference in survival was observed compared with non-lean NAFLD (p=0.069). Conclusions Caucasian lean subjects with NAFLD may progress to advanced liver disease, develop metabolic comorbidities and experience cardiovascular disease (CVD) as well as liver-related mortality, independent of longitudinal progression to obesity and PNPLA3 genotype. These patients represent one end of a wide spectrum of phenotypic expression of NAFLD where the disease manifests at lower overall BMI thresholds. Lay summary NAFLD may affect and progress in both obese and lean individuals. Lean subjects are predominantly males, have a younger age at diagnosis and are more prevalent in some geographic areas. During the follow-up, lean subjects can develop hepatic and extrahepatic disease, including metabolic comorbidities, in the absence of weight gain. These patients represent one end of a wide spectrum of phenotypic expression of NAFLD. ©

Clinician fidelity to cognitive behavioral therapy (CBT) is an important mechanism by which desired clinical outcomes are achieved and is an indicator of care quality. Despite its importance, there are few fidelity measurement methods that are efficient and have demonstrated reliability and validity. Using a randomized trial design, we compared three methods of assessing CBT adherence-a core component of fidelity-to direct observation, the gold standard. Clinicians recruited from 27 community mental health agencies (n = 126; M age = 37.69 years, SD = 12.84; 75.7% female) were randomized 1:1:1 to one of three fidelity conditions: self-report (n = 41), chart-stimulated recall (semistructured interviews with the chart available; n = 42), or behavioral rehearsal (simulated role-plays; n = 43). All participating clinicians completed fidelity assessments for up to three sessions with three different clients that were recruited from clinicians' caseloads (n = 288; M age = 13.39 years SD = 3.89; 41.7% female); sessions were also audio-recorded and coded for comparison to determine the most accurate method. All fidelity measures had parallel scales that yielded an adherence maximum score (i.e., the highest-rated intervention in a session), a mean of techniques observed, and a count total of observed techniques. Results of three-level mixed effects regression models indicated that behavioral rehearsal produced comparable scores to observation for all adherence scores (all ps gt; .01), indicating no difference between behavioral rehearsal and observation. Self-report and chart-stimulated recall overestimated adherence compared to observation (ps lt; .01). Overall, findings suggested that behavioral rehearsal indexed CBT adherence comparably to direct observation, the gold-standard, in pediatric populations. Behavioral rehearsal may at times be able to replace the need for resource-intensive direct observation in implementation research and practice.

An observational coding system was developed to track clinical change in children with autism spectrum disorder (ASD) during psychotherapy. The Pediatric Autism Spectrum Therapy Observation System (PASTOS) consists of 23 items divided into 5 subscales and is used to rate child behaviors in individual psychotherapy sessions. Manual-based cognitive behavioral therapy session transcripts of 22 children diagnosed with ASD (IQ > 70) and a concurrent anxiety disorder (M = 9.41years, SD = 1.56years) enrolled in a randomized, controlled trial were coded. Results suggested that the PASTOS exhibited promising interrater reliability, internal consistency, convergent validity at post-treatment, and treatment sensitivity. The PASTOS may be a useful tool for studying process and outcome in psychotherapy research on children with ASD.