Soluble Methane Monooxygenase.

Aerobic life is possible because the molecular structure of oxygen (O2) makes direct reaction with most organic materials at ambient temperatures an exceptionally slow process. Of course, these reactions are inherently very favorable, and they occur rapidly with the release of a great deal of energy at high temperature. Nature has been able to tap this sequestered reservoir of energy with great spatial and temporal selectivity at ambient temperatures through the evolution of oxidase and oxygenase enzymes. One mechanism used by these enzymes for O2 activation has been studied in detail for the soluble form of the enzyme methane monooxygenase. These studies have revealed the step-by-step process of O2 activation and insertion into the ultimately stable C-H bond of methane. Additionally, an elegant regulatory mechanism has been defined that enlists size selection and quantum tunneling to allow methane oxidation to occur specifically in the presence of more easily oxidized substrates.

Phylogenomic discordance is driven by wide-spread introgression and incomplete lineage sorting during rapid species diversification within rattlesnakes (Viperidae: Crotalus and Sistrurus).

Phylogenomics allows us to uncover the historical signal of evolutionary processes through time and estimate phylogenetic networks accounting for these signals. Insight from genome-wide data further allows us to pinpoint the contributions to phylogenetic signal from hybridization, introgression, and ancestral polymorphism across the genome. Here we focus on how these processes have contributed to phylogenetic discordance among rattlesnakes (genera Crotalus and Sistrurus), a group for which there are numerous conflicting phylogenetic hypotheses based on a diverse array of molecular datasets and analytical methods. We address the instability of the rattlesnake phylogeny using genomic data generated from transcriptomes sampled from nearly all known species. These genomic data, analyzed with coalescent and network-based approaches, reveal numerous instances of rapid speciation where individual gene trees conflict with the species tree. Moreover, the evolutionary history of rattlesnakes is dominated by incomplete speciation and frequent hybridization, both of which have likely influenced past interpretations of phylogeny. We present a new framework in which the evolutionary relationships of this group can only be understood in light of genome-wide data and network-based analytical methods. Our data suggest that network radiations, like seen within the rattlesnakes, can only be understood in a phylogenomic context, necessitating similar approaches in our attempts to understand evolutionary history in other rapidly radiating species.

Emerging Risk of Adolescent Depression and Suicide Detected Through Pediatric Primary Care Screening.

OBJECTIVE: The goal of the current study was to document patterns of stability and change in adolescent depression and suicide risk detected via universal depression screening in pediatric primary care and to determine who may go on to experience emerging risk. METHODS: Retrospective electronic health record information (sociodemographic data and depression screening results for 2 timepoints) was extracted for adolescents aged 12-17 who attended well-visits between November 15, 2017, and February 1, 2020, in a large pediatric primary care network. A total of 27,335 adolescents with 2 completed depression screeners were included in the current study. RESULTS: While most adolescents remained at low risk for depression and suicide across the 2 timepoints, others experienced emerging risk (i.e., low risk at time 1 but elevated risk at time 2), decreasing risk (i.e., high risk at time 1 but low risk at time 2) or stable high risk for depression or suicide. Odds of experiencing emerging depression and suicide risk were higher among adolescents who were female (compared to males), Black (compared to White), and had Medicaid insurance (compared to private insurance). Odds of experiencing emerging depression risk were also higher among older adolescents (compared to younger adolescents) as well as adolescents who identified as Hispanic/Latino (compared to non-Hispanic/Latino). CONCLUSIONS: Findings can inform symptom monitoring and opportunities for prevention in primary care.

Developmental trajectories of adolescent internalizing symptoms and parental responses to distress.

Parents' responses to their children's negative emotions are a central aspect of emotion socialization that have well-established associations with the development of psychopathology. Yet research is lacking on potential bidirectional associations between parental responses and youth symptoms that may unfold over time. Further, additional research is needed on sociocultural factors that may be related to the trajectories of these constructs. In this study, we examined associations between trajectories of parental responses to negative emotions and adolescent internalizing symptoms and the potential role of youth sex and racial identity. Adolescents and caregivers (N = 256) completed six assessments that spanned adolescent ages 13-18 years. Multivariate growth models revealed that adolescents with higher internalizing symptoms at baseline experienced increasingly non-supportive parental responses over time (punitive and distress responses). By contrast, parental responses did not predict initial levels of or changes in internalizing symptoms. Parents of Black youth reported higher minimization and emotion-focused responses and lower distress responses compared to parents of White youth. We found minimal evidence for sex differences in parental responses. Internalizing symptoms in early adolescence had enduring effects on parental responses to distress, suggesting that adolescents may play an active role in shaping their emotion socialization developmental context.

Phylogenetically diverse diets favor more complex venoms in North American pitvipers.

The role of natural selection in the evolution of trait complexity can be characterized by testing hypothesized links between complex forms and their functions across species. Predatory venoms are composed of multiple proteins that collectively function to incapacitate prey. Venom complexity fluctuates over evolutionary timescales, with apparent increases and decreases in complexity, and yet the causes of this variation are unclear. We tested alternative hypotheses linking venom complexity and ecological sources of selection from diet in the largest clade of front-fanged venomous snakes in North America: the rattlesnakes, copperheads, cantils, and cottonmouths. We generated independent transcriptomic and proteomic measures of venom complexity and collated several natural history studies to quantify dietary variation. We then constructed genome-scale phylogenies for these snakes for comparative analyses. Strikingly, prey phylogenetic diversity was more strongly correlated to venom complexity than was overall prey species diversity, specifically implicating prey species' divergence, rather than the number of lineages alone, in the evolution of complexity. Prey phylogenetic diversity further predicted transcriptomic complexity of three of the four largest gene families in viper venom, showing that complexity evolution is a concerted response among many independent gene families. We suggest that the phylogenetic diversity of prey measures functionally relevant divergence in the targets of venom, a claim supported by sequence diversity in the coagulation cascade targets of venom. Our results support the general concept that the diversity of species in an ecological community is more important than their overall number in determining evolutionary patterns in predator trait complexity.

Neoadjuvant Talazoparib in Patients With Germline BRCA1/2 Mutation-Positive, Early-Stage Triple-Negative Breast Cancer: Results of a Phase II Study.

BACKGROUND: The undetermined efficacy of the current standard-of-care neoadjuvant treatment, anthracycline/platinum-based chemotherapy, in patients with early-stage triple-negative breast cancer (TNBC) and germline BRCA mutations emphasizes the need for biomarker-targeted treatment, such as poly(ADP-ribose) polymerase inhibitors, in this setting. This phase II, single-arm, open-label study evaluated the efficacy and safety of neoadjuvant talazoparib in patients with germline BRCA1/2-mutated early-stage TNBC. PATIENTS AND METHODS: Patients with germline BRCA1/2-mutated early-stage TNBC received talazoparib 1 mg once daily for 24 weeks (0.75 mg for moderate renal impairment) followed by surgery. The primary endpoint was pathologic complete response (pCR) by independent central review (ICR). Secondary endpoints included residual cancer burden (RCB) by ICR. Safety and tolerability of talazoparib and patient-reported outcomes were assessed. RESULTS: Of 61 patients, 48 received ≥80% talazoparib doses, underwent surgery, and were assessed for pCR or progressed before pCR assessment and considered nonresponders. pCR rate was 45.8% (95% confidence interval [CI], 32.0%-60.6%) and 49.2% (95% CI, 36.7%-61.6%) in the evaluable and intent-to-treat (ITT) population, respectively. RCB 0/I rate was 45.8% (95% CI, 29.4%-63.2%) and 50.8% (95% CI, 35.5%-66.0%) in the evaluable and ITT population, respectively. Treatment-related adverse events (TRAE) were reported in 58 (95.1%) patients. Most common grade 3 and 4 TRAEs were anemia (39.3%) and neutropenia (9.8%). There was no clinically meaningful detriment in quality of life. No deaths occurred during the reporting period; 2 deaths due to progressive disease occurred during long-term follow-up (>400 days after first dose). CONCLUSIONS: Neoadjuvant talazoparib monotherapy was active despite pCR rates not meeting the prespecified threshold; these rates were comparable to those observed with combination anthracycline- and taxane-based chemotherapy regimens. Talazoparib was generally well tolerated. CLINICALTRIALS.GOV IDENTIFIER: NCT03499353.

Parent-youth convergence (and divergence) in reports about pediatric quality of life.

PURPOSE: Researchers and service providers typically assess pediatric Health-Related Quality of Life (HRQOL) by collecting independent reports from parents and youth. An emerging body of work indicates that patterns of parent-youth reports yield information germane to understanding youth outcomes. We identified patterns of HRQOL among youth and their parents seeking mental health treatment and examined links between agreement patterns and mental and physical health functioning. METHODS: Participants included 227 youth (mean age = 14.40 years, SD = 2.42; 63% female) and parent dyads presenting at a mood disorders clinic between 2013 and 2020. We assessed HRQOL using parallel youth and parent forms of the Pediatric Quality of Life Inventory Generic Core Scales. We also assessed youth clinical correlates of depression, suicidal ideation, and impairment, as well as health information via electronic health record (e.g., psychotropic medication usage, BMI). RESULTS: Latent class analysis showed three parent-youth reporting patterns: Low-Low (LL), High-High (HH), and Parent Low-Youth High (PL-YH). Relative to youth in the HH group, youth in the LL and PL-YH groups reported significantly greater depressive symptoms and had higher rates of suicidal ideation and psychotropic medication use. In addition, youth in the LL group reported significantly greater levels of impairment. CONCLUSIONS: Parent-youth patterns of HRQOL reporting can reveal clinically meaningful information and indicate poorer functioning for certain groups (LL, PL-YH) of youth. These findings have implications for improving accuracy of risk assessments that leverage HRQOL data.

Spindle Cell-Predominant Trichodiscoma With Palisading Arrangement: A Rare Variant.

ABSTRACT: Spindle cell-predominant trichodiscoma (SCPT) is a benign adnexal neoplasm, best categorized within the trichodiscoma-fibrofolliculoma continuum. SCPTs clinically present as dome-shaped papules usually on the face, particularly on the nose or the nasolabial fold. The SCPT variant has been described as a particularly cellular trichodiscoma composed of small interweaving fascicles and sheets of spindle cells. Identical lesions were previously referred to as neurofollicular hamartomas because of their predominantly fascicular stromal cellularity and focal S100 positivity. In this article, we report a rare variant of SCPT with a palisaded arrangement. The patient is a middle-aged man with no significant dermatologic history who presented with a skin-colored papule on the left nasal ala. It had been present for approximately 10 years with only minimal growth over that time. A biopsy was obtained. Histopathological analysis revealed a dermal papule composed of bland spindle cells arranged in a striking palisading pattern within a fibromyxoid stroma with associated peripheral hyperplasia of sebaceous glands. The palisaded pattern shared features reminiscent of Verocay bodies of a schwannoma. Immunohistochemical studies revealed stromal spindled cells with a strong and diffuse pattern of CD34 expression and absent S100 and SOX10 expressions. To our knowledge, only 2 cases of SCPT with a palisaded pattern have been presented. SCPT with a palisaded pattern is a rare histopathologic variant that may resemble a schwannoma but can be recognized by its strong epithelial components and immunohistochemical staining pattern.

Personalized Depression Prevention Reduces Dependent Stressors Among Adolescents: Results from a Randomized Controlled Trial.

OBJECTIVE: Depression and stressors both increase during adolescence. The stress generation model posits that depression symptoms and associated impairment contribute to the generation of dependent stressors. Adolescent depression prevention programs have been shown to reduce the risk of depression. Recently, risk-informed personalization approaches have been adopted to enhance the efficacy of depression prevention, and preliminary evidence supports the beneficial effects of personalized prevention on depression symptoms. Given the close association between depression and stress, we examined the hypothesis that personalized depression prevention programs would reduce adolescents' experience of dependent stressors (interpersonal and non-interpersonal) over longitudinal follow-up. METHOD: The present study included 204 adolescents (56% girls, 29% racial minority) who were randomized to receive either a cognitive-behavioral or an interpersonal prevention program. Youth were categorized as high or low on cognitive and interpersonal risk using a previously established risk classification system. Half of the adolescents received a prevention program that matched their risk profile (e.g., high cognitive risk randomized to cognitive-behavioral prevention); half received a mismatched program (e.g., high interpersonal risk randomized to cognitive-behavioral prevention). Exposure to dependent and independent stressors was assessed repeatedly over an 18-month follow-up period. RESULTS: Matched adolescents reported fewer dependent stressors during the post-intervention follow-up period (d = .46, p = .002) and from baseline through 18-months post-intervention (d = .35, p = .02) compared to mismatched youth. As expected, there were no differences between matched and mismatched youth on the experience of independent stressors. CONCLUSIONS: These findings further highlight the potential of personalized approaches to depression prevention and demonstrate benefits that go beyond depression symptom reduction.

Accelerating radiochemistry development: Automated robotic platform for performing up to 64 droplet radiochemical reactions in a morning.

The growing discovery and development of novel radiopharmaceuticals and radiolabeling methods requires an increasing capacity for radiochemistry experiments. However, such studies typically rely on radiosynthesizers designed for clinical batch production rather than research, greatly limiting throughput. Two general solutions are being pursued to address this: developing new synthesis optimization algorithms to minimize how many experiments are needed, and developing apparatus with enhanced experiment throughput. We describe here a novel high-throughput system based on performing arrays of droplet-based reactions at 10 µL volume scale in parallel. The automatic robotic platform can perform a set of 64 experiments in ~3 h (from isotope loading to crude product, plus sampling onto TLC plates), plus ~1 h for off-line radio-TLC analysis and radioactivity measurements, rather than the weeks or months that would be needed using a conventional system. We show the high repeatability and low crosstalk of the platform and demonstrate optimization studies for two 18F-labeled tracers. This novel automated platform greatly increases the practicality of performing arrays of droplet reactions by eliminating human error, vastly reducing tedium and fatigue, minimizing radiation exposure, and freeing up radiochemist time for other intellectually valuable pursuits.

Depression Prevention in Pediatric Primary Care: Implementation and Outcomes of Interpersonal Psychotherapy-Adolescent Skills Training.

This study evaluated the fidelity, feasibility, acceptability, and preliminary outcomes of a depression prevention program, interpersonal psychotherapy-adolescent skills training (IPT-AST), in urban pediatric primary care (PC) with a sample of primarily Black youth. Twenty-two adolescents with elevated depressive symptoms participated in this open clinical trial. Adolescents were identified through a screening questionnaire completed at well visits. Ratings of IPT-AST fidelity and session attendance were recorded. Youth and caregivers reported on their attitudes toward the intervention and completed measures of adolescents' symptoms and functioning pre- and post-intervention. Results demonstrated high levels of fidelity, attendance, and acceptability, despite some difficulties with recruitment. Adolescents and caregivers reported significant improvements in functioning. There were marginally significant reductions in self-reported depression, anxiety, and total mental health symptoms. Caregivers reported a significant decrease in total mental health symptoms. Findings provide preliminary information regarding the implementation and effects of IPT-AST when delivered in PC.

Risk and Resilience Measures Related to Psychopathology in Youth.

Childhood adversity places youth at risk for multiple negative outcomes. The current study aimed to understand how a constellation of risk and resilience factors influenced mental health outcomes as a function of adversities: socioeconomic status (SES) and traumatic stressful events (TSEs). Specifically, we examined outcomes related to psychosis and mood disorders, as well as global clinical functioning. The current study is a longitudinal follow up of 140 participants from the Philadelphia Neurodevelopmental Cohort (PNC) assessed for adversities at Time 1 (Mean age: 14.11 years) and risk, resilience, and clinical outcomes at Time 2 (mean age: 21.54 years). In the context of TSE, a limited set of predictors emerged as important; a more diverse set of moderators emerged in the context of SES. Across adversities, social support was a unique predictor of psychosis spectrum diagnoses and global functioning; emotion dysregulation was an important predictor for mood diagnoses. The current findings underscore the importance of understanding effects of childhood adversity on maladaptive outcomes within a resilience framework.

X-ray Crystal Structures of Methane Monooxygenase Hydroxylase Complexes with Variants of Its Regulatory Component: Correlations with Altered Reaction Cycle Dynamics.

Full activity of soluble methane monooxygenase (sMMO) depends upon the formation of a 1:1 complex of the regulatory protein MMOB with each alpha subunit of the (αßγ)2 hydroxylase, sMMOH. Previous studies have shown that mutations in the core region of MMOB and in the N- and C-termini cause dramatic changes in the rate constants for steps in the sMMOH reaction cycle. Here, X-ray crystal structures are reported for the sMMOH complex with two double variants within the core region of MMOB, DBL1 (N107G/S110A), and DBL2 (S109A/T111A), as well as two variants in the MMOB N-terminal region, H33A and H5A. DBL1 causes a 150-fold decrease in the formation rate constant of the reaction cycle intermediate P, whereas DBL2 accelerates the reaction of the dinuclear Fe(IV) intermediate Q with substrates larger than methane by three- to fourfold. H33A also greatly slows P formation, while H5A modestly slows both formation of Q and its reactions with substrates. Complexation with DBL1 or H33A alters the position of sMMOH residue R245, which is part of a conserved hydrogen-bonding network encompassing the active site diiron cluster where P is formed. Accordingly, electron paramagnetic resonance spectra of sMMOH:DBL1 and sMMOH:H33A complexes differ markedly from that of sMMOH:MMOB, showing an altered electronic environment. In the sMMOH:DBL2 complex, the position of M247 in sMMOH is altered such that it enlarges a molecular tunnel associated with substrate entry into the active site. The H5A variant causes only subtle structural changes despite its kinetic effects, emphasizing the precise alignment of sMMOH and MMOB required for efficient catalysis.

A Minimally Invasive Approach for Temporomandibular Joint Replacement: A Pilot Study.

Temporomandibular joint replacement (TJR) with an alloplastic (metal/ultra-high-molecular-weight polyethylene) device has proven to be a successful and predictable procedure. This paper describes a novel technique for performing TJR with an endaural incision alone. The technique we are describing uses only an endaural incision with supplemental trocar incision(s), to perform a TJR. There were 4 patients for a total of 8 temporomandibular joints that were selected. All 4 patients were assessed immediately following surgery, on postoperative days 1 and 7 and at 6 months following surgery. Maximal interincisal opening and subjective variables were assessed at each of the time points. Additionally, the total operative time was measured and compared to a previous age and diagnosis matched control group using the traditional 2 incisions TJR.There were 3 females and 1 male (ages 19-67) who underwent TJR with an endaural incision alone. There were 4 females (ages 19-68) who underwent traditional TJR surgery. None of the patients in either group had major complications and all patients were discharged on postoperative day 1. All patients in the endaural incision alone group had increased maximal interincisal opening and reported a quicker subjective decrease in pain and disability following surgery with less average time in the operating room. However, all patients in the endaural incision alone group had CN VII weakness that lasted longer than those in the traditional TJR group.The minimally invasive approach for TJR was successful in the present pilot study and could be used in specific situations to decrease the morbidity associated with additional incisions for this procedure. Ultimately, the endaural only incision approach offers promising outcomes for future patients undergoing temporomandibular joints TJR in the right patient population.

Comparison of the Accuracy of Maxillary Positioning With Interim Splints Versus Patient-Specific Guides and Plates in Executing a Virtual Bimaxillary Surgical Plan.

PURPOSE: An extension of digital technology is to provide patient-specific hardware to reposition the first jaw in a bimaxillary case without the use of an intermediate splint. The purpose of our study was to determine if there were significant differences in maxillary repositioning using interim splints versus patient-specific guides and implants (PSIs) in executing a bimaxillary virtual surgical plan (VSP). MATERIALS AND METHODS: This is a retrospective cohort study of patients who underwent bimaxillary orthognathic surgery with interim splints or PSIs planned with VSP at our institution. The difference in maxillary positions from the VSP to the postoperative cone-beam computed tomography (CBCT) was evaluated in both groups. The primary predictor variable was the method by which the maxilla was repositioned (interim splint vs PSI). The primary outcome variable was the postoperative 3D position of the maxillary incisors and right and left first molars in the anteroposterior, transverse, and vertical dimensions. Differences in the planned and postoperative positions of the above landmarks in all three planes of space between the two groups were statistically analyzed. RESULTS: A total of 82 patients were included. 13 patients had their maxillae repositioned with an interim splint between the unoperated mandible and the mobile maxilla, and 69 patients had their maxilla repositioned using custom drill/cutting guides and a PSI. The mean difference between the planned and actual position of the maxilla in the PSI group was smaller than in the splint group. In the PSI group alone, vertical changes were accurate whether the maxilla was being superiorly or inferiorly repositioned. CONCLUSION: The use of a PSI provides more accurate maxillary repositioning during bimaxillary surgery than the use of an interim splint.

Most Facial Fractures Do Not Require Surgical Intervention.

PURPOSE: Literature describing the number of patients that had a facial fracture that required surgical intervention in the United States is very limited. The purpose of this study was to evaluate the percentage of patients who required surgical intervention after presenting to a Level 1 Trauma Center with 1 or more facial fractures. MATERIALS AND METHODS: This was a retrospective cross-sectional study of all patients who presented with facial fracture(s) to University Hospital, a Level 1 Trauma Center (San Antonio, Texas), over a 5-year period from July 2015 to July 2020. Patients' charts that had 1 or more International Classification of Diseases 10 codes pertaining to facial fractures were collected. Cases were subdivided by fracture location: mandible, midface, upper face, or a combination of any of the aforementioned locations (predictor variables). After subdividing based on location, each chart was then reviewed and separated based on whether or not surgical intervention was provided (primary outcome variable). Data were tabulated and analyzed with descriptive and inferential statistics. RESULTS: Over the 5-year period, 3,416 patients presented with facial fractures. Of the 3,126 patients who survived their injuries and were not lost to follow-up, the vast majority (80.9%) did not require surgical intervention for their facial fractures. Mandible fractures required surgical intervention, whether isolated or in combination, much more frequently than in patients who did not have any type of mandible fracture (RR 8.01, 95% CI 6.92-9.27, P < .05 and RR 4.60, 95% CI 3.42-6.18, P < .05, respectively). Patients aged 50 years or less were also more likely to receive surgical intervention than those aged 51 years and more (RR 1.98 95% CI 1.63-2.41, P < .05). CONCLUSIONS: The vast majority of facial fractures that present to a Level 1 Trauma Center do not require surgical intervention. Patients who present with any type of mandible fracture and are aged 50 years or less are more likely to need surgical intervention.

Attachment and attitudes toward children: effects of security priming in parents and non-parents.

The present two-study investigation is the first to examine whether experimentally boosting attachment security (security priming) affects attitudes in the parenting domain for both parents and non-parents. Mothers (n = 72) and childless undergraduates (n = 82) were randomly assigned to a neutral or a secure prime condition and then completed measures of implicit attitudes (a child-focused version of the Go/No-Go Association Task) and explicit attitudes (self-reported) toward children. Following the priming manipulation, mothers in the secure prime condition had more positive implicit attitudes toward their child compared to mothers in the neutral prime condition. Security priming also increased mothers' positive explicit attitudes toward their children, but only among mothers who scored high on self-reported attachment-related avoidance. No priming effects emerged among non-parents. These results provide the first evidence for a causal link between parental attachment security and parental attitudes toward children.

Pathways linking attachment and depressive symptoms for Black and White adolescents: do race and neighborhood racism matter?

Decades of evidence demonstrate that insecure attachment is associated with increased risk for depressive symptoms. Yet research has focused on predominantly White samples, with little attention to whether developmental pathways vary by social-contextual factors like racial identity and neighborhood racism. This study examines whether longitudinal links between attachment style and depressive symptoms differ for White and Black American adolescents or by exposure to neighborhood racism (N = 171, Mage at Time 1 = 14 years). Multigroup measured variable path analyses controlling for gender and household income revealed that attachment avoidance predicted relative increases in depressive symptoms for White adolescents, but not for Black adolescents. Links between attachment style and depressive symptoms did not differ based on exposure to neighborhood racism. Experiences of neighborhood racism were associated with greater attachment avoidance but not anxiety. Results highlight the importance of examining attachment in different socioecological contexts to illuminate the unique pathways characterizing Black youth development.

The Depression Prevention Initiative: Trauma as a Moderator of Prevention Outcomes.

Interpersonal Psychotherapy-Adolescent Skills Training (IPT-AST) is an evidence-based indicated depression prevention program that has been shown to reduce depression symptoms. Research is needed to identify moderators of IPT-AST's effects. Although trauma history has emerged as a moderator of depression treatment outcomes, the impact of trauma on short- and long-term outcomes in the context of preventive interventions for adolescent depression is unknown. This study examines the impact of trauma on prevention outcomes in a school-based randomized controlled trial (RCT) in which 186 adolescents (mean age = 14.01 years, SD = 1.22; 67% female) were randomly assigned to IPT-AST delivered by research staff or group counseling (GC) provided by school counselors. Trauma history significantly moderated intervention outcomes during the active phase of the intervention, but not during long-term follow-up. During the active phase, youth in IPT-AST with low or no trauma exposure experienced significantly greater reductions in depression symptoms than youth in GC with low or no trauma exposure, but there were no significant differences in rates of change between the two interventions for youth with high or any trauma exposure. These findings highlight the importance of assessing trauma and investigating whether these interventions can be tailored or supplemented to enhance the effects for youth with trauma exposure.

Choices in land representation materially affect modeled biofuel carbon intensity estimates.

Estimates of biofuel carbon intensity are uncertain and depend on modeled land use change (LUC) emissions. While analysts have focused on economic and agronomic assumptions affecting the quantity of land converted, researchers have paid less attention to how models classify land into broad categories and designate some categories as ineligible for LUC. To explore the effect of these land representation attributes, we use three versions of a global human and Earth systems model, GCAM, and compute the "carbon intensity of land-use change" (CI-LUC) from increased U.S. corn ethanol production. We consider uncertainty in model parameters along with the choice of land representation and find the latter is one of the most influential parameters on estimated CI-LUC. A version of the model that protects 90% of non-commercial land reduced estimated CI-LUC by an average of 32% across Monte Carlo trials compared to our baseline model. Another version that mimics the GTAP-BIO-ADV land representation, which protects all non-commercial land, reduced CI-LUC by an average of 19%. The results of this experiment demonstrate that land representation in biofuel LUC models is an important determinant of CI-LUC.