A role for synapsin tetramerization in synaptic vesicle clustering.

Although synapsins have long been proposed to be key regulators of synaptic vesicle (SV) clustering, their mechanism of action has remained mysterious and somewhat controversial. Here, we review synapsins and their associations with each other and with SVs. We highlight the recent hypothesis that synapsin tetramerization is a mechanism for SV clustering. This hypothesis, which aligns with numerous experimental results, suggests that the larger size of synapsin tetramers, in comparison to dimers, allows tetramers to form optimal bridges between SVs that overcome the repulsive force associated with the negatively charged membrane of SVs and allow synapsins to form a reserve pool of SVs within presynaptic terminals.

Clinical and Radiographic Results After Treatment of Traumatic Syndesmotic Instability Using a Novel Screw-Suture Syndesmotic Fixation Device.

OBJECTIVES: The objective of this study was to report early outcomes of a novel screw-suture syndesmotic device compared with suture button fixation devices when treating traumatic syndesmotic instability. DESIGN: Retrospective chart review. SETTING: Single academic Level 1 Trauma Center. PATIENT SELECTION CRITERIA: All adult patients who had syndesmotic fixation with the novel device [novel syndesmotic repair implant (NSRI) group] compared with a suture button device (SB group) between January 2018 and December 2022. OUTCOME MEASURES AND COMPARISONS: Medial clear space and tibiofibular overlap measurements were compared immediately postoperatively and at the final follow-up. Patients were followed for a minimum of 1 year or skeletal healing. RESULTS: Fifty-nine patients (25 female) with an average age of 47 years (range 19-78 years) were in the NSRI group compared with 52 patients (20 female) with an average age of 41 years (range 18-73 years) in the SB group. There were no significant differences when comparing body mass index, diabetes, or smoking status between groups (P > 0.05). There was no difference when comparing the postoperative and final medial clear space measurements in the NSRI group compared with the SB group (P = 0.86; 95% confidence interval, -0.32 to 0.27). There was no difference when comparing the postoperative and final tibiofibular overlap measurements in the NSRI group compared with the SB group (P = 0.79; 95% confidence interval, -0.072 to 0.09). There were 3 cases of implant removal in the NSRI group compared with 2 in the SB group (P = 0.77). There was 1 failure in the NSRI group and none in the SB group. The remaining patients were all fully ambulatory at the final follow-up (P = 0.35). CONCLUSIONS: A novel screw-suture syndesmotic implant provides the fixation of a screw, and the flexibility of a suture had similar radiographic outcomes compared with suture button fixation devices in treating ankle syndesmotic instability. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Impact of an Integrated Human Performance Support Group: Evaluation of Air Force Special Warfare Candidate Training and Musculoskeletal Injury Outcomes Over Eight Fiscal Years.

INTRODUCTION: The Special Warfare Training Wing and Special Warfare Human Performance Support Group (HPSG; all-co-authors) were established in fiscal year (FY) 2019 to consolidate and oversee all Air Force Special Warfare (AFSPECWAR) training and provide embedded medical and human performance support to candidates with the goal of improving graduation rates and the longevity of the AFSPECWAR operator. The purpose of this manuscript is to assess the impact of the HPSG on AFSPECWAR graduation rates, musculoskeletal injury (MSKI) incidence, and cost. MATERIALS AND METHODS: Graduation rates, MSKI incidence (including incidence density and cumulative incidence probability), and MSKI-related health care costs were assessed across all AFSPECWAR training pipelines spanning 8 FYs 2015-22, including Indoctrination, Assessment, and Selection Courses (Selection); Tactical Air Control Party (TACP); Special Tactics (ST), and Guardian Angel (GA). RESULTS: A total of 5,728 distinct candidates were assessed over the time frame. There were significant decreases in attrition when comparing the HPSG era (FY 19-22) with the prior 4-year period for the ST (47% vs. 82% graduates) and TACP (34% vs. 41% graduates) training pipelines. The corresponding Selection (36% graduates) and GA (80% graduates) pipeline attrition rates remained stable. MSKI incidence rates (both incidence density and cumulative incidence probability) overall were not significantly different when comparing the pre-HPSG and HPSG time frames; however, they varied between the two time frames by course. GA candidates had a decrease in MSKI during the apprentice course in the HPSG era compared with the pre-HPSG era (2.4-1.0 cases per 100 trainee weeks; P < .001), which corresponds to a nearly 20% reduction in the cumulative incidence probability (i.e., proportion of trainees injured) after 10 weeks of course. For ST and TACP courses, however, significantly increased incidence of MSKI was observed when comparing the two time frames (P < .001), while for Selection courses, the rates remained stable. A significant reduction in the cost of MSKI-related management (62% total relative value units, 83% total costs) was observed. CONCLUSION: The impact of the HPSG on attrition, MSKI incidence, and cost-of-care was not consistent across all training pipelines; however, taken together, there were no increases in attrition, and the cost of MSKI management was significantly lower.

A specialized population of monocyte-derived tracheal macrophages promote airway epithelial regeneration through a CCR2-dependent mechanism.

Macrophages are critical for maintenance and repair of mucosal tissues. While functionally distinct subtypes of macrophage are known to have important roles in injury response and repair in the lungs, little is known about macrophages in the proximal conducting airways. Single-cell RNA sequencing and flow cytometry demonstrated murine tracheal macrophages are largely monocyte-derived and are phenotypically distinct from lung macrophages at homeostasis. Following sterile airway injury, monocyte-derived macrophages are recruited to the trachea and activate a pro-regenerative phenotype associated with wound healing. Animals lacking the chemokine receptor CCR2 have reduced numbers of circulating monocytes and tracheal macrophages, deficient pro-regenerative macrophage activation and defective epithelial repair. Together, these studies indicate that recruitment and activation of monocyte-derived tracheal macrophages is CCR2-dependent and is required for normal airway epithelial regeneration.

Estimated Financial Impact of 2021 Office-Visit Work Relative Unit Updates on Surgical Global Periods.

This cross-sectional study assesses the impact of changes to medical billing and coding work relative value units in 2021.

US-based, Prospective, Blinded Study of Thyrotropin Receptor Antibody in Autoimmune Thyroid Disease.

CONTEXT: Bioassays provide information on the functionality of thyrotropin receptor antibodies (TSH-R-Ab) and thus may offer more clinical utility than binding assays. OBJECTIVE: In this prospective, blinded, US-based study, the clinical performance of several TSH-R-Ab assays was compared. SETTING: US endocrinology clinic. SUBJECTS: One hundred sixty-two unselected, consecutive, well-documented patients with various thyroid diseases and healthy controls. INTERVENTION(S): Blinded TSH-R-Ab measurements. MAIN OUTCOME MEASURE(S): Sensitivity and specificity of 4 TSH-R-Ab assays. RESULTS: The 4 TSH-R-Ab assays were negative in all 42 patients without autoimmune thyroid disease (AITD). In 104 patients with Graves' disease (GD), irrespective of the disease duration, TSH-R-Ab positivity was present in 65 (63%), 67 (65%), and 87 (84%) for the Cobas and Immulite binding assays and stimulatory TSH-R-Ab [thyroid-stimulating immunoglobin (TSI)] bioassay, respectively (TSI vs Immulite P < .0025, TSI vs Cobas P < .0009). Fifteen newly diagnosed GD patients were all positive in the TSI bioassay, but only 11 (73%) were positive in the Cobas and Immulite binding assays. Nine GD patients with biochemical subclinical hyperthyroidism were TSI-positive but Immulite- and Cobas-negative. Two GD patients were blocking TSH-R-Ab [thyroid-blocking immunoglobin (TBI)]-positive and TSI-negative, and the Immulite and Cobas were positive in both. Additional serum samples from AITD patients that consisted of 30 TBI-positive and 10 TSI-positive samples were blindly tested in the binding assays. Only 6 of the 10 TSI-positive samples were positive in both binding assays, and 30 and 28 of the TBI-positive samples were positive in the Cobas and Immulite assays, respectively. CONCLUSION: Binding TSH-R-Ab assays are less sensitive than TSI bioassays and are not specific for stimulating antibodies. Measuring the function of TSH-R-Ab in a bioassay can provide useful information to clinicians.

Paclitaxel, Ifosfamide, and Cisplatin as Initial Salvage Chemotherapy for Germ Cell Tumors: Long-Term Follow-Up and Outcomes for Favorable- and Unfavorable-Risk Disease.

PURPOSE: Paclitaxel, ifosfamide, and cisplatin (TIP) is an established salvage regimen for germ cell tumors (GCT) on the basis of a phase II trial, but efficacy on a large patient cohort including patients with unfavorable risk features and long-term outcomes has not been reported. Herein, we report updated treatment efficacy and long-term follow-up with TIP. PATIENTS AND METHODS: Patients with GCT who received TIP after cisplatin-based chemotherapy were eligible. Favorable response (complete response or partial response with negative tumor markers), overall survival (OS) and progression-free survival (PFS) rates, relapse, and toxicity were determined. Disease was reclassified according to the International Prognostic Factor Study Group (IPFSG) score. RESULTS: Of the 104 patients, 87 had favorable risk factors and 17 had at least one unfavorable factor by Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Ten patients were treated for a second gonadal primary GCT. With a median follow-up of 8.9 years, the 5-year PFS and OS rates were 66% (95% CI, 55 to 74) and 69% (95% CI, 59 to 77), respectively. Among 87 patients with favorable-risk disease, 69 (79%) achieved a favorable response with 5-year PFS and OS rates of 67% (95% CI, 56 to 76) and 72% (95% CI, 61 to 80), respectively. Among 17 patients with MSKCC unfavorable-risk disease, 13 (76%) achieved a favorable response with 5-year PFS and OS rates of 59% (95% CI, 33 to 78) and 56% (95% CI, 28 to 76), respectively. After IPFSG reclassification, 5-year PFS and OS rates for patients with ≤intermediate-risk disease were 75% (95% CI, 50 to 89) and 73% (95% CI, 55 to 85), respectively. CONCLUSION: TIP is an effective second-line regimen for patients with GCT. Similar outcomes were observed in patients with favorable- and unfavorable-risk disease. The randomized TIGER trial (ClinicalTrials.gov identifier: NCT02375204) comparing TIP with high-dose chemotherapy will determine the optimal second-line treatment approach.

The Learning Curve for Robotic Lateral Pelvic Lymph Node Dissection for Rectal Cancer: A View from the West.

BACKGROUND: Lateral pelvic lymph-node dissection is performed for selected patients with rectal cancer with persistent lateral nodal disease after neoadjuvant therapy. This technique has been slow to be adopted in the West due to concerns regarding technical difficulty. This is the first report on the learning curve for lateral pelvic lymph node dissection in the US or Europe. OBJECTIVE: The aim of this study was to analyze the learning curve associated with robotic lateral pelvic lymph node dissection. DESIGN: Retrospective observational cohort. SETTING: Tertiary academic cancer center. PATIENTS: Consecutive patients from 2012 to 2021. INTERVENTION: All patients underwent robotic lateral pelvic lymph node dissection. MAIN OUTCOME MEASURES: The primary endpoints were the learning curves for maximum number of nodes retrieved and urinary retention which was evaluated with simple cumulative-sum and two-sided Bernoulli cumulative-sum charts. RESULTS: Fifty-four procedures were included. A single-surgeon (n = 35) and an institutional learning curve are presented in the analysis. In the single-surgeon learning curve, a turning point marking the end of a learning phase was detected at the 12th procedure for the number of retrieved nodes and at the 20th for urinary retention. In the institutional learning curve analysis, two turning points were identified at the 13th and 26th procedures indicating progressive improvements for the number of retrieved nodes and at the 27th for urinary retention. No sustained alarm signals were detected at any time point. LIMITATIONS: The retrospective nature, small sample size and the referral center nature of the reporting institution that may limit generalizability. CONCLUSIONS: In a setting of institutional experience with robotic colorectal surgery including beyond TME resections, the learning curve for robotic lateral pelvic lymph node dissection is acceptably short. Our results demonstrate feasibility of acquisition of this technique in a controlled setting, with sufficient case volume and proctoring can optimize the learning curve. See Video Abstract.

Early Postoperative Prediction of Complications and Readmission After Colorectal Cancer Surgery Using an Artificial Neural Network.

BACKGROUND: Early predictors of postoperative complications can risk-stratify patients undergoing colorectal cancer surgery. However, conventional regression models have limited power to identify complex nonlinear relationships among a large set of variables. We developed artificial neural network models to optimize the prediction of major postoperative complications and risk of readmission in patients undergoing colorectal cancer surgery. OBJECTIVE: The aim of this study was to develop an artificial neural network model to predict postoperative complications using postoperative laboratory values, and compare these models' accuracy to standard regression methods. DESIGN: This retrospective study included patients who underwent elective colorectal cancer resection between January 1, 2016, and July 31, 2021. Clinical data, cancer stage, and laboratory data from postoperative day 1 to 3 were collected. Models of complications and readmission risk were created using multivariable logistic regression and single-layer neural networks. SETTING: National Cancer Institute-Designated Comprehensive Cancer Center. PATIENTS: Adult colorectal cancer patients. MAIN OUTCOME MEASURES: Accuracy of predicting postoperative major complication, readmission and anastomotic leak using the area under the receiver-operating characteristic curve. RESULTS: Neural networks had larger areas under the curve for predicting major complications compared to regression models (neural network 0.811; regression model 0.724, p < 0.001). Neural networks also showed an advantage in predicting anastomotic leak (p = 0.036) and readmission using postoperative day 1-2 values (p = 0.014). LIMITATIONS: Single-center, retrospective design limited to cancer operations. CONCLUSIONS: In this study, we generated a set of models for early prediction of complications after colorectal surgery. The neural network models provided greater discrimination than the models based on traditional logistic regression. These models may allow for early detection of postoperative complications as soon as postoperative day 2. See Video Abstract.

A machine learning decision criterion for reducing scan time for hyperspectral neutron computed tomography systems.

We present the first machine learning-based autonomous hyperspectral neutron computed tomography experiment performed at the Spallation Neutron Source. Hyperspectral neutron computed tomography allows the characterization of samples by enabling the reconstruction of crystallographic information and elemental/isotopic composition of objects relevant to materials science. High quality reconstructions using traditional algorithms such as the filtered back projection require a high signal-to-noise ratio across a wide wavelength range combined with a large number of projections. This results in scan times of several days to acquire hundreds of hyperspectral projections, during which end users have minimal feedback. To address these challenges, a golden ratio scanning protocol combined with model-based image reconstruction algorithms have been proposed. This novel approach enables high quality real-time reconstructions from streaming experimental data, thus providing feedback to users, while requiring fewer yet a fixed number of projections compared to the filtered back projection method. In this paper, we propose a novel machine learning criterion that can terminate a streaming neutron tomography scan once sufficient information is obtained based on the current set of measurements. Our decision criterion uses a quality score which combines a reference-free image quality metric computed using a pre-trained deep neural network with a metric that measures differences between consecutive reconstructions. The results show that our method can reduce the measurement time by approximately a factor of five compared to a baseline method based on filtered back projection for the samples we studied while automatically terminating the scans.

Male rape: survivors, support and the law in late twentieth-century England and Wales.

Until 1994, men were not recognized legally as victims of rape in England and Wales. This article explores the history of male survivors of rape there, establishing the uneven patchwork of support services available to them prior to 1994. It argues that a growing psychiatric literature which studied male survivors of sexual violence was a major factor in convincing lawmakers to include men as potential victims of rape in updated sexual offence legislation. Other medical professionals played key roles in bringing male survivors to police attention, but psychiatric research was most influential in changing the policy agenda in this arena.

CD39 Is Expressed on Functional Effector and Tissue-resident Memory CD8+ T Cells.

The ecto-ATPase CD39 is expressed on exhausted CD8+ T cells in chronic viral infection and has been proposed as a marker of tumor-specific CD8+ T cells in cancer, but the role of CD39 in an effector and memory T cell response has not been clearly defined. We report that CD39 is expressed on Ag-specific CD8+ short-lived effector cells, while it's co-ectoenzyme, CD73, is found on memory precursor effector cells (MPECs) in vivo. Inhibition of CD39 enzymatic activity during in vitro T cell priming enhances MPEC differentiation in vivo after transfer and infection. The enriched MPEC phenotype is associated with enhanced tissue resident memory T cell (TRM cell) establishment in the brain and salivary gland following an acute intranasal viral infection, suggesting that CD39 ATPase activity plays a role in memory CD8+ T cell differentiation. We also show that CD39 is expressed on human and murine TRM cells across several nonlymphoid tissues and melanoma, whereas CD73 is expressed on both circulating and resident memory subsets in mice. In contrast to exhausted CD39+ T cells in chronic infection, CD39+ TRM cells are fully functional when stimulated ex vivo with cognate Ag, further expanding the identity of CD39 beyond a T cell exhaustion marker.

Adolescents With a High Burden of New-Onset Mood Symptoms After Sport-Related Concussion Benefit From Prescribed Aerobic Exercise, a Secondary Analysis of 2 Randomized Controlled Trials.

OBJECTIVE: Approximately 20% of students with sport-related concussion (SRC) report new symptoms of anxiety and depression which may be associated with delayed recovery and increased risk for developing a mood disorder. Early prescribed aerobic exercise facilitates recovery in athletes with concussion-related exercise intolerance. We studied the effect of aerobic exercise treatment on new mood symptoms early after SRC. DESIGN: Exploratory secondary analysis of 2 randomized controlled trials (RCT). SETTING: Sports medicine clinics associated with UB (Buffalo, NY), CHOP (Philadelphia, PA), and Boston Children's Hospital (Boston, MA). PARTICIPANTS: Male and female adolescents (aged 13-18 years) diagnosed with SRC (2-10 days since injury). INTERVENTIONS: Participants were randomized to individualized targeted heart rate aerobic exercise (n = 102) or to a placebo intervention designed to mimic relative rest (n = 96). MAIN OUTCOME MEASURES: Incidence of Persisting Post-Concussive Symptoms (PPCS, symptoms ≥28 days). RESULTS: First RCT recruited from 2016 to 2018 and the second from 2018 to 2020. Of 198 adolescents, 156 (79%) reported a low burden (mean 1.2 ± 1.65/24) while 42 (21%) reported a high burden (mean 9.74 ± 3.70/24) of emotional symptoms before randomization. Intervention hazard ratio for developing PPCS for low burden was 0.767 (95% CI, 0.546-1.079; P = 0.128; ß = 0.085) and for high burden was 0.290 (95% CI, 0.123-0.683; P = 0.005; ß = 0.732). CONCLUSIONS: High burden of mood symptoms early after injury increases risk for PPCS, but the sports medicine model of providing early targeted aerobic exercise treatment reduces it. Nonsports medicine clinicians who treat patients with a high burden of new mood symptoms after concussion should consider prescribing aerobic exercise treatment to reduce the risk of PPCS and a mood disorder.

Hepatoprotective potential of alpha-lipoic acid against gliclazide-induced liver injury in high-glucose-exposed human liver cells and experimental type 2 diabetic rats.

Growing clinical evidence shows that sulfonylurea therapy for patients with type 2 diabetic mellitus (T2DM) contributes to progressive worsening of their liver. The present study presents hepatotoxicity induced by gliclazide, a second-generation sulfonylurea, and alpha-lipoic acid (ALA) as a novel and promising drug for T2DM treatment. Normal human liver cells (HL-7702) were incubated with high-glucose DMEM in the presence or absence of gliclazide and ALA for 72 h, and cell viability and death were measured by flow cytometry. Next, Sprague-Dawley rats were subjected to 12 h of fasting, and fasting blood glucose was measured. The rats were randomized into four groups: HC (healthy control; n = 7), T2DM (diabetic rats without treatment; n = 9), GLC (diabetic rats with 15 mg/kg gliclazide treatment; n = 7) and GLC+ALA (diabetic rats with gliclazide and 60 mg/kg ALA treatment; n = 7). T2DM was induced by a bolus administration of 110 mg/kg nicotinamide and 55 mg/kg streptozotocin intraperitoneally. The experimental protocol lasted for 6 weeks after which the animals were sacrificed and pancreas, liver and blood samples were collected for biochemical, histological and molecular analyses. Compared to healthy control (HC) group, exposure of HL-7702 cells to high glucose induced significant cell death by 19 % (p < 0.001), which was exacerbated with gliclazide treatment by 29 % (p < 0.0001) but markedly reduced by 6 % to near HC value following ALA treatment. In vivo, GLC-treated rats had severe liver damage characterized by increased hepatocellular vacuolation, and significant expression of ED-1, iNOS and caspase-3 as well as markedly high levels of liver enzymes (aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase compared to T2DM rats. Interestingly, ALA administration prevented these pathological changes and protected the diabetic liver to levels comparable to HC rats. ALA showed hepatoprotective effect against gliclazide-induced hepatotoxicity by suppressing inflammation and apoptosis while activating antioxidant pathway in the diabetic liver. Abbreviations: ALA, Alpha-lipoic acid; ALT, Alanine aminotransferase; ALP, Alkaline phosphatase; AMPK, Adenosine monophosphate-activated protein kinase; AST, Aspartate aminotransferase; ATP, Adenosine triphosphate; DMEM, Dulbecco's Modified Eagle Medium; EDTA, ethylenediaminetetraacetic acid; FBG, Fasting blood glucose; FBS, Fetal bovine serum; GLC, Gliclazide; GLUT4, Glucose transporter type 4; GSH, Glutathione; H&E, Hematoxylin/Eosin; HbA1c, Glycosylated haemoglobin A1c; HC, Healthy control; HG, Hyperglycemic group; HOMA-ß, Homeostasis model assessment of ß-cell function; IL-1ß, Interleukin-1ß; IL-6, Interleukin-6; iNOS, Inducible nitric oxide synthase; KATP, ATP-dependent potassium channels; MDA, Malondialdehyde; MPTP, Mitochondrial permeability transition pore; NO, Nitric oxide; P/S, Penicillin/streptomycin; PAS, Periodic acid-Schiff; RIA, Radioimmunoassay; ROS, Reactive oxygen species; SOD, Superoxide dismutase; T2DM, Type 2 diabetes mellitus; TBARS, Thiobarbituric acid reactive substances; TNF-α, Tumor necrosis factor-alpha.

Para-aortic Lymph Node Dissection for Colorectal Cancer: Predicting Pathologic Lymph Node Positivity and Optimizing Outcomes.

INTRODUCTION: In colorectal cancer, the presence of para-aortic lymph nodes (PALN) indicates extraregional disease. Appropriately selecting patients for whom PALN dissection will provide oncologic benefit remains challenging. This study identified factors to predict survival among patients undergoing PALN dissection for colorectal cancer. METHODS: An institutional database was queried for patients who underwent curative-intent resection of clinically positive PALN for colorectal cancer between 2007 and 2020. Preoperative radiologic images were reviewed, and patients who did and did not have positive PALN on final pathology were compared. Survival analysis was performed to evaluate the impact of pathologically positive PALN on recurrence-free (RFS) and overall survival (OS). RESULTS: Of 74 patients who underwent PALN dissection, 51 had PALN metastasis at the time of primary tumor diagnosis, whereas 23 had metachronous PALN disease. Preoperative chemotherapy ± radiotherapy was given in 60 cases (81.1%), and 28 (37.8%) had pathologically positive PALN. Independent factors associated with positive PALN pathology included metachronous PALN disease and pretreatment and posttreatment radiographically abnormal PALN. On multivariable analysis, pathologically positive PALN was significantly associated with decreased RFS (hazard ratio 3.90) and OS (HR 4.49). Among patients with pathologically positive PALN, well/moderately differentiated histology was associated with better OS, and metachronous disease trended toward an association with better OS. CONCLUSIONS: Pathologically positive PALN are associated with poorer RFS and OS after PALN dissection for colorectal cancer. Clinicopathologic factors may predict pathologic PALN positivity. Curative-intent surgery may provide benefit, especially in patients with well-to-moderately differentiated primary tumors and possibly metachronous PALN disease.

School-Based Intervention for Adolescents With ADHD: Predictors of Effects on Academic, Behavioral, and Social Functioning.

Adolescents with attention-deficit/hyperactivity disorder (ADHD) experience significant academic, behavioral, and social skill difficulties including underachievement, risk for school dropout, poor peer relations, and emotion dysregulation. Although stimulant medication reduces ADHD symptoms, psychosocial and educational interventions are necessary to address functional impairments. We examined the nature and predictors of academic, behavioral, and social skills trajectories in response to multicomponent organizational and interpersonal skills training in 92 high school students with ADHD. Latent trajectory class analyses revealed positive treatment response ranging from 61.5% (report card grades) to 100% (inattention symptoms, organizational skills, social skills). Organizational skill and academic grade treatment response trajectories were predicted by assigned sex, pretreatment anxiety, and treatment dosage, while improvement in behavioral and social functioning was associated with better emotion regulation and family relations prior to treatment along with stronger working alliance with treatment coach at midtreatment. Multicomponent organizational and interpersonal skills training appears effective for most high school students with ADHD and the degree treatment-induced change is associated with multiple malleable factors can be leveraged to enhance intervention response.