Comparison of translation algorithms in determining maximum allowable CTV shifts for Real-Time Gated Proton Therapy (RGPT) robustness evaluation in prostate cancers.

INTRODUCTION: Real-Time Gated Proton Therapy (RGPT) is an active motion management technique that utilizes treatment gating and tumor tracking via fiducial markers. When performing RGPT treatment for prostate cancer, it is essential to account for the CTV displacement relative to the body in the clinical workflow. The workflow at the National Cancer Centre Singapore (NCCS) includes bone matching via CT-CBCT images, followed by fiducial matching via pulsed fluoroscopy (soft tissue matching), and finally, a robustness evaluation procedure to determine if the difference is within an allowable tolerance. In this study, we compare two CTV translation methods for robustness evaluation: (1) an in-house translation algorithm and (2) the RayStation "simulate organ motion" Deformable image registration (DIR) algorithm. METHODS: Nine RGPT prostate patient plans with CTV volumes ranging from 17.1 to 96.72 cm2 were included in this study. An in-house translation algorithm and "simulate organ motion" DIR RayStation algorithm were used to generate CTV shifts along R-L, I-S, and P-A axes between ± $ \pm $ 10 mm at 2 mm steps. At each step, dose metrics, which include CTV Dmax, CTV D95%, and CTV D98%, were extracted and used as comparative metrics for CTV target coverage and hot spot evaluation. RESULTS: Across all axes, there were no statistically significant differences between the two algorithms for all three dose metrics: CTV Dmax (P = 0.92, P = 0.91, and P = 0.47), CTV D95% (P = 0.97, P = 0.22, and P = 0.33), and CTV D98% (P = 0.85, P = 0.33, and P = 0.36). Further, the in-house translation algorithm evaluation time was less than 10 s, two orders of magnitude faster than the DIR algorithm. CONCLUSION: Our results demonstrate that the simpler in-house algorithm performs equivalently to the realistic DIR algorithm when simulating CTV motion in prostate cancers. Furthermore, the in-house algorithm completes the robustness evaluation two orders of magnitude faster than the DIR algorithm. This significant reduction in evaluation time is crucial especially when preparatory time efficiency is of paramount importance in a busy clinic.

A treatment-site-specific evaluation of commercial synthetic computed tomography solutions for proton therapy.

Background and purpose: Despite the superior dose conformity of proton therapy, the dose distribution is sensitive to daily anatomical changes, which can affect treatment accuracy. This study evaluated the dose recalculation accuracy of two synthetic computed tomography (sCT) generation algorithms in a commercial treatment planning system. Materials and methods: The evaluation was conducted for head-and-neck, thorax-and-abdomen, and pelvis sites treated with proton therapy. Thirty patients with two cone-beam computed tomography (CBCT) scans each were selected. The sCT images were generated from CBCT scans using two algorithms, Corrected CBCT (corrCBCT) and Virtual CT (vCT). Dose recalculations were performed based on these images for comparison with "ground truth" deformed CTs. Results: The choice of algorithm influenced dose recalculation accuracy, particularly in high dose regions. For head-and-neck cases, the corrCBCT method showed closer agreement with the "ground truth", while for thorax-and-abdomen and pelvis cases, the vCT algorithm yielded better results (mean percentage dose discrepancy of 0.6 %, 1.3 % and 0.5 % for the three sites, respectively, in the high dose region). Head-and-neck and pelvis cases exhibited excellent agreement in high dose regions (2 %/2 mm gamma passing rate >98 %), while thorax-and-abdomen cases exhibited the largest differences, suggesting caution in sCT algorithm usage for this site. Significant systematic differences were observed in the clinical target volume and organ-at-risk doses in head-and-neck and pelvis cases, highlighting the importance of using the correct algorithm. Conclusions: This study provided treatment site-specific recommendations for sCT algorithm selection in proton therapy. The findings offered insights for proton beam centers implementing adaptive radiotherapy workflows.

Unlocking Solutions: Innovative Approaches to Identifying and Mitigating the Environmental Impacts of Undocumented Orphan Wells in the United States.

In the United States, hundreds of thousands of undocumented orphan wells have been abandoned, leaving the burden of managing environmental hazards to governmental agencies or the public. These wells, a result of over a century of fossil fuel extraction without adequate regulation, lack basic information like location and depth, emit greenhouse gases, and leak toxic substances into groundwater. For most of these wells, basic information such as well location and depth is unknown or unverified. Addressing this issue necessitates innovative and interdisciplinary approaches for locating, characterizing, and mitigating their environmental impacts. Our survey of the United States revealed the need for tools to identify well locations and assess conditions, prompting the development of technologies including machine learning to automatically extract information from old records (95%+ accuracy), remote sensing technologies like aero-magnetometers to find buried wells, and cost-effective methods for estimating methane emissions. Notably, fixed-wing drones equipped with magnetometers have emerged as cost-effective and efficient for discovering unknown wells, offering advantages over helicopters and quadcopters. Efforts also involved leveraging local knowledge through outreach to state and tribal governments as well as citizen science initiatives. These initiatives aim to significantly contribute to environmental sustainability by reducing greenhouse gases and improving air and water quality.

Transcription factor condensates, 3D clustering, and gene expression enhancement of the MET regulon.

Some transcription factors (TFs) can form liquid-liquid phase separated (LLPS) condensates. However, the functions of these TF condensates in 3-Dimentional (3D) genome organization and gene regulation remain elusive. In response to methionine (met) starvation, budding yeast TF Met4 and a few co-activators, including Met32, induce a set of genes involved in met biosynthesis. Here, we show that the endogenous Met4 and Met32 form co-localized puncta-like structures in yeast nuclei upon met depletion. Recombinant Met4 and Met32 form mixed droplets with LLPS properties in vitro. In relation to chromatin, Met4 puncta co-localize with target genes, and at least a subset of these target genes is clustered in 3D in a Met4-dependent manner. A MET3pr-GFP reporter inserted near several native Met4-binding sites becomes co-localized with Met4 puncta and displays enhanced transcriptional activity. A Met4 variant with a partial truncation of an intrinsically disordered region (IDR) shows less puncta formation, and this mutant selectively reduces the reporter activity near Met4-binding sites to the basal level. Overall, these results support a model where Met4 and co-activators form condensates to bring multiple target genes into a vicinity with higher local TF concentrations, which facilitates a strong response to methionine depletion.

The Transcatheter Aortic Valve Replacement-Conduction Study: The Value of the His-Ventricular Interval in Risk Stratification for Post-TAVR Atrioventricular-Block.

Background: There is no clear consensus regarding the optimal risk stratification of high-degree atrioventricular block (HDAVB) after transcatheter aortic valve replacement (TAVR). Methods: This prospective study sought to determine the utility of the pre- and post-TAVR His-ventricular (HV) interval in the risk stratification of post-TAVR HDAVB. One hundred twenty-one patients underwent an electrophysiology study before and after TAVR. The primary outcome was HDAVB requiring pacemaker implantation within 30 days post-TAVR. A separate retrospective cohort was analyzed to determine the postoperative interval at which the risk of HDAVB is reduced to <5%. Results: HDAVB occurred in 12 (10%) patients. Baseline right bundle branch block (RBBB) (odds ratio [OR]: 13.6), implant depth >4 mm (OR: 3.9), use of mechanically- or self-expanding valves (OR: 6.3), and post-TAVR HV > 65 â€‹ms (OR: 4.9) were associated with increased risk of HDAVB, whereas PR intervals and pre-TAVR HV were not. In patients without baseline RBBB or new persistent left bundle branch block (LBBB), not one patient with post-TAVR HV < 65 â€‹ms developed HDAVB. In the separate retrospective cohort (N = 1049), the risk of HDAVB is reduced (<5%) on postoperative days 4 and 3 in patients with pre-TAVR RBBB and post-TAVR persistent LBBB, respectively. Conclusions: Baseline RBBB, new persistent LBBB, implant depth >4 mm, and a post-TAVR HV ≥ 65 â€‹ms were associated with a higher risk of post-TAVR HDAVB, whereas an HV ≤ 65 â€‹ms was associated with a lower risk. The pre-TAVR HV was not associated with our outcome, and the delta HV did not have practical incremental prognostic value. Among those without pre-TAVR RBBB or post-TAVR persistent LBBB, no patients with post-TAVR HV < 65 â€‹ms developed HDAVB.

Characterising the role of enolase in a stable Small Colony Variant of Staphylococcus aureus isolated from a diabetic foot infection patient with osteomyelitis.

The switch to alternate cell types by Staphylococcus aureus creates sub-populations even within an active population, that are highly resilient, tolerant to antibiotics and lack clinical symptoms of infection. These cells present a challenge for clinical treatment where even after initial intervention has seemingly cleared the infection, these alternate cell types persist within tissue to revert and cause disease. Small colony variants (SCV) are a cell type which facilitate persistent infection but clinically isolated SCVs are often unstable in laboratory conditions. We have isolated a pair of S. aureus isolates from an individual patient with osteomyelitis presenting with heterogenous phenotypes; a stable SCV (sSCV) and a SCV that reverts upon laboratory culturing to the usual, active and non-SCV cell type. Thus we are able use this pair to investigate and compare the genetic mechanisms that underlie the clinical variatons of SCV phenotype. The switch to the sSCV phenotype was associated with frameshift mutations in the enolase eno and the histidine kinase arlS. The phenoptye of the sSCV was an impeded growth dependent on amino acid catabolism and modulated biofilm. These mutations present potentially a new molecular mechanism which confer persistence within osteomyelitis.

A study of the relative orientation of the extraocular rectus muscles: an advanced cadaveric approach.

Purpose: The anatomy of the extraocular rectus muscle insertions is clinically relevant in the field of ophthalmology. This descriptive cadaveric study determines the relative degree orientation of the superior, lateral, and inferior rectus muscles with respect to the medial rectus and investigates the distances between the rectus muscle insertions. Method: Thirty cadavers (50% female, mean age = 81.86 years, SD 12.16) were included for a total of 60 eyes. For each eye, a lateral canthotomy and cantholysis were performed followed by a peritomy. Muscle hooks were then used to access and isolate the rectus muscles. The degree orientation was determined by marking the muscle midpoints at insertion, using the center of the cornea as the vertex, and measuring the angle with the Angle Meter 360 application (© Alexey Kozlov) (Figure 1). The distances between rectus muscles were measured from the same muscle midpoints using calipers. Results: The degree orientations with respect to the medial rectus are displayed in Figure 2 and were as follows: superior rectus (mean = 93.14, SD = 3.04, min. 82.3, max. 100.3), lateral rectus (mean = 180.21, SD = 5.65, min. 170.5, max. 190.6), and inferior rectus (mean = 90.57, SD = 4.47, min. 84.0, max. 98.9). The distances (measured in mm) between rectus muscle midpoints at insertion included medial rectus to inferior rectus (mean = 13.64, SD = 0.54), inferior rectus to lateral rectus (mean = 13.79, SD = 0.75), lateral rectus to superior rectus (mean = 13.54, SD = 0.63), and superior rectus to medial rectus (mean = 13.83, SD = 0.75). The relative distances between the midpoints of the extraocular muscles observed in males versus females showed statistically significant differences in medial rectus to inferior rectus (13.8 vs. 13.5, p = .01), inferior rectus to lateral rectus (14.1 vs. 13.5, p = .03), and superior rectus to medial rectus (14.0 vs. 13.5, p = .04), respectively (Table 1). Conclusion: This is an important study of the extraocular muscle degree orientation performed with an innovative measuring approach. The degree orientation of the insertions relative to the medial rectus may have surgical application in the field of ophthalmology.

Predicting political beliefs with polygenic scores for cognitive performance and educational attainment.

Intelligence is correlated with a range of left-wing and liberal political beliefs. This may suggest intelligence directly alters our political views. Alternatively, the association may be confounded or mediated by socioeconomic and environmental factors. We studied the effect of intelligence within a sample of over 300 biological and adoptive families, using both measured IQ and polygenic scores for cognitive performance and educational attainment. We found both IQ and polygenic scores significantly predicted all six of our political scales. Polygenic scores predicted social liberalism and lower authoritarianism, within-families. Intelligence was able to significantly predict social liberalism and lower authoritarianism, within families, even after controlling for socioeconomic variables. Our findings may provide the strongest causal inference to date of intelligence directly affecting political beliefs.

Association of Relative Left Ventricular Outflow Tract Area and Transcatheter Aortic Valve Replacement Related Paravalvular Leak.

Background: Post-transcatheter aortic valve replacement (TAVR), paravalvular leak (PVL) is a quality metric associated with worse clinical outcomes. Transcatheter heart valve (THV) sizing is based primarily on the systolic annular size without regard to the left ventricular outflow tract (LVOT), which also lies within the THV landing zone. We hypothesized that LVOT size relative to the annulus is associated with post-TAVR PVL. Methods: Data from consecutive patients undergoing TAVR in a single high-volume center from January 2018 to March 2019 were used. Pre-TAVR data from multidetector computed tomography (MDCT) were collected. Relative LVOT area was defined as LVOT area/annular area during systole. Logistic regression analysis was used to evaluate association with post-TAVR mild or greater PVL by transthoracic echocardiography before discharge. Results: Among 293 patients (median age, 81.1 years; female, 49.5%; White, 88.0%), 81.6% received SAPIEN 3 and 18.4% received CoreValve THV models. Aortic valve morphology was bicuspid in 10.9% of patients. Prevalence of mild or greater PVL was 23.5% (mild in 20.1%). Relative LVOT area had a significant inverse association such that the odds of mild or greater PVL decreased significantly with every 1% increase in relative LVOT area (adjusted odds ratio, 0.96; 95% CI, 0.93-0.98; P = .002). There was no interaction between the type of implanted valve and the relative LVOT area. Patients in the highest relative LVOT tertile had significantly lower odds of mild or greater PVL (adjusted odds ratio, 0.42; 95% CI, 0.21-0.87; P = .018 vs first tertile). Conclusions: In patients undergoing TAVR with the newer generation of THV (SAPIEN 3 and CoreValve models), a relatively narrower LVOT area vs annular area was independently associated with increased odds of mild or greater PVL before discharge.

The layered learning practice model: Ensuring accomplishment of both practice and pharmacy education.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Effect of Delayed Parathyroidectomy on Risk of Future Cardiovascular and Nephrolithiasis Interventions in Adults with Primary Hyperparathyroidism [Original Study].

OBJECTIVE: To determine whether the timing of parathyroid surgery impacts the risk of renal stone retreatment and cardiovascular interventions. SUMMARY BACKGROUND DATA: Long-term, untreated primary hyperparathyroidism is associated with significant morbidity including nephrolithiasis and cardiovascular disease. METHODS: We conducted a Population-based Cohort study of New York and California state-wide data from 2000-2020. Adult patients who underwent renal stone treatment and subsequently diagnosed with primary hyperparathyroidism (pHPT) and underwent parathyroidectomy (PTX) were included. Patients were excluded if PTX was prior to index stone procedure, they underwent second stone treatment within 6 months, with stage V CKD, with secondary or tertiary hyperparathyroidism, with prior kidney transplant or hemodialysis, or with prior cancer diagnosis. Rate of renal stone retreatment and cardiovascular interventions after PTX in pHPT patients with nephrolithiasis who underwent parathyroid surgery at ≤ 2 years and >2 years after index stone procedure was measured. RESULTS: We identified 2,093 patients who underwent first-time stone treatment and subsequent PTX. The median time to PTX was 560 days (IQR 187-1477) and follow-up was 7.4 years (IQR 4.5-13.1). Delaying PTX for more than 2 years increased the risk of renal stone retreatment by 59% (HR 1.59; P<0.001), increased the risk of experiencing coronary disease or associated interventions by 118% (HR=2.18; P=0.01), and increased the risk of experiencing an overall cardiovascular event by 52% (HR 1.52; P<0.01). CONCLUSIONS AND RELEVANCE: In symptomatic pHPT, delaying PTX significantly increases the risk of requiring future stone retreatment and cardiac/vascular surgical interventions. This highlights the importance of early surgical referral and multidisciplinary approaches to optimize outcomes and resource utilization in pHPT.

Outcomes following TAVR in patients with cardiogenic shock: A systematic review and meta-analysis.

BACKGROUND: While transcatheter aortic valve replacement (TAVR) has broadened treatment options for critically ill patients, outcomes among those with concomitant cardiogenic shock (CS) are not well-explored. METHODS: We conducted a comprehensive search of major databases for studies comparing outcomes following TAVR in patients with and without CS since inception up to October 31, 2023. Our meta-analysis included five non-randomized observational. Dichotomous outcomes were assessed using the Mantel-Haenszel method (risk ratio, 95 % CI), and continuous outcomes were evaluated using mean difference and 95 % CI with the inverse variance method. Statistical heterogeneity was determined using the inconsistency test (I2). RESULTS: Among 26,283 patients across five studies, 30-day mortality was higher in the CS group (7267 patients; 27.6 %) compared to those without CS (OR 3.41, 95 % CI [2.01, 5.76], p < 0.01), as well as 30-day major vascular complications (OR 1.72, 95 % CI [1.54, 1.92], p < 0.01). At 1-year follow-up, there was no statistically significant difference in mortality rates between the compared groups (OR 2.68, 95 % CI [0.53, 13.46], p = 0.12). No significant between-group differences were observed in the likelihood of 30-day aortic valve reintervention (OR 3.20, 95 % CI [0.63, 16.22], p = 0.09) or post-TAVR aortic insufficiency (OR 0.91, 95 % CI [0.33, 2.51], p = 0.73). Furthermore, 30-day stroke, pacemaker implantation, and in-hospital major bleeding were comparable between both cohorts. CONCLUSION: Among patients undergoing TAVR, short-term mortality is higher but one-year outcomes are similar when comparing those with, to those without, CS. Future studies should examine whether TAVR outcomes are improved when the procedure is delayed to optimize CS and when delay is not possible, whether particular management strategies lead to more favorable periprocedural outcomes.

Radiofrequency ablation of Bethesda category III thyroid nodules with benign molecular testing: Preliminary findings from a single institution.

BACKGROUND: The efficacy of radiofrequency ablation (RFA) in treating thyroid nodules with indeterminate cytology remains less studied. The objective of this study was to determine the efficacy of RFA in treating nodules with Bethesda III that have been molecularly profiled benign (BIII-MPN). METHODS: We included prospectively enrolled patients who underwent RFA for benign and BIII-MPN thyroid nodules. Primary outcome measures were volume reduction ratio (VRR), symptom score (range 0-10), and cosmetic score (range 0-3) at 1, 3, 6, and 12 months after RFA, as well as complication rates. RESULTS: A total of 258 nodules in 192 patients were included (benign: 238 in 174; BIII-MPN: 20 in 18). The median VRR differed insignificantly, whereas symptom and cosmetic score improvements were similar between two cohorts. BIII-MPN thyroid nodules were associated with lower rates of infection and temporary voice change. CONCLUSION: Our preliminary findings suggest that RFA may be a feasible management option for BIII-MPN thyroid nodules. However, appropriate will be important to address the important risk of potentially missed malignancies.

Rapid detection of blood using a novel application of RT-RPA integrated with CRISPR-Cas: ALAS2 detection as a model.

A rapid, sensitive and specific test for blood is reported based on a novel application of recombinase polymerase amplification integrated with CRISPR-Cas and lateral flow assay (LFA). The blood specific marker ALAS2 was used as the target to record the presence of blood. The assay used either RNA extracted from a body fluid as a template, or omitting this extraction step and using a direct approach where the questioned body fluid was added directly to the assay. The assay only detected blood (all peripheral blood and some menstrual blood samples) and no other body fluid (semen, saliva, or vaginal fluid). The limit of detection varied from an initial template of 0.195 ng extracted RNA (27 dilution) or 0.0218 µL (26 dilution) liquid peripheral blood. The assay gave the expected result when peripheral blood was mixed with saliva: ratios of peripheral blood/saliva at 19:1, 3:1, 1:1, 1:3 and 1:19 all gave a positive result using extracted RNA. By contrast, only three ratios of peripheral blood and saliva gave a positive result for blood (19:1, 3:1 and 1:1) when adding these two body fluids directly. When peripheral blood was mixed with semen there was a strong inhibition of the assay and ALAS2 could only be detected at ratio of 19:1 using RNA. Using reconstituted peripheral bloodstains gave comparable results to liquid peripheral blood. This is the first application of RT-RPA integrated CRISPR and combined with a LFA assay to detect body fluid-specific RNA. The proposed method opens up the potential to perform this method remote from laboratories such as at crime scenes.

3-Year Outcomes of Balloon-Expandable Valves: 20-mm vs Larger Valves (≥23 mm).

BACKGROUND: A prior Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry-based analysis reported similar 1-year clinical outcomes with small (20-mm) vs large (≥23-mm) balloon-expandable valves (BEV). OBJECTIVES: The aim of this study was to describe mid-term 3-year clinical outcomes for small vs large BEV and the relationship between discharge echocardiographic mean gradient (MG) and different definitions of prothesis-patient mismatch (PPM) with clinical outcomes. METHODS: Using the TVT Registry with Centers for Medicare and Medicaid Services linkage, a propensity-matched analysis of patients receiving 20- vs ≥23-mm BEVs was performed. Spline curves and Kaplan-Meier plots with adjusted HRs determined the relationship between MG and 3-year mortality. RESULTS: In total, 316,091 patients were analyzed; after propensity matching, 8,100 pairs of each group were compared. The 20-mm BEV was associated with higher MGs compared with ≥23-mm BEVs (16.2 ± 7.2 mm Hg vs 11.8 ± 5.7 mm Hg; P < 0.0001). At 3 years, there was no difference in mortality between 20- and ≥23-mm BEVs (31.5% vs 32.5%, respectively; HR: 0.97; 95% CI: 0.90-1.05). Compared with an MG of 10 to 30 mm Hg, an MG <10 mm Hg (HR: 1.25; 95% CI:1.22-1.27) was associated with increased 3-year mortality. Measured severe PPM and predicted no PPM were associated with increased 3-year mortality (33.5% vs 32.9% vs 32.1%; P < 0.0001) and (33.5% vs 31.1% vs 30%; P < 0.0001), respectively. Low MG and severe measured PPM were associated with lower left ventricular ejection fraction (LVEF). CONCLUSIONS: Patients with small-prosthesis BEVs (20 mm) had identical 3-year survival as those with larger (≥23-mm) BEV valves. Severe measured PPM and low MG (<10 mm Hg), but not predicted severe PPM, were associated with lower LVEF and increased mortality, suggesting that LVEF is the culprit for worse outcomes.

Supportive-leadership training to improve social connection: A cluster-randomized trial demonstrating efficacy in a high-risk occupational context.

The high, and still rising, rate of loneliness is a threat to public health (Office of the Surgeon General, 2023), with negative mental and physical health consequences (e.g., Holt-Lunstad, 2021). Given that loneliness is a risk factor for poor mental health, efforts to address loneliness are urgently needed. Workplaces can facilitate an employee's social connection through supervisor support training, which can help mitigate loneliness. Among occupational groups, the military is at higher risk for mental health disorders, suicide, and loneliness (Fikretoglu et al., 2022; Naifeh et al., 2019). This study evaluated the efficacy of an evidence-based supportive-leadership training intervention targeting active-duty U.S. Army platoon leaders and targeting both proactive support behaviors that help bolster employee social connection and responsive support behaviors, including destigmatizing mental health. Ninety-nine platoon leaders (69.7% of eligible leaders) completed the 90-min training that consisted of both in-person and computer-based components. Using a cluster-randomized controlled trial design, intervention effects were tested using an intent-to-treat approach and revealed a significant effect, whereby loneliness of service members whose leaders were randomized to the intervention group (N = 118) was significantly reduced compared to loneliness reports for service members in the control group (N = 158). Additionally, service members with higher baseline loneliness were more strongly and positively impacted by the supervisor training, reporting higher levels of supportive behaviors from their leaders at 3 months postbaseline. In sum, these results suggest how workplaces, especially those that are considered high-risk occupations, and their leaders play a critical role in a national strategy to address Americans' well-being. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The Effects of Platoon Leader Mental Health and Resilience Training on Soldier Problematic Anger.

INTRODUCTION: The DoD has prioritized programs to optimize readiness by enhancing resilience of its service members. Problematic anger in the military is an issue that impacts psychological well-being and resilience. Leader support is a potential tactic for reducing anger and its effects. Currently military resilience training is focused on individual level resilience. A gap exists in such training and there is a need to train leaders to provide mental health and resilience support to their subordinates. The present study developed and tested a theory-based training aimed at platoon leaders that focused on how to engage in proactive and responsive mental health and resilience-supportive behaviors through guided discussion, scenarios, and computer-based training with embedded quizzes. MATERIALS AND METHODS: We conducted an Institutional Review Board-approved cluster randomized controlled trial to test the effects of a leadership training with Army platoon leaders (n = 99) and soldiers (n = 276) in 2 brigades at an active duty military installation in the USA. Training was conducted in person with a computer-based component. Soldiers completed online surveys 1 month prior and again 3 months after the leader training. RESULTS: Post-training results demonstrated significant leader learning effects (Cohen's d = 1.56) and leader positive reactions to the training information, with leaders reporting the information as useful and relevant to their work. Service members in the treatment group reported significantly lower levels of anger at time 2 (b = -0.18, SE = 0.06, P = .002, pseudo ΔR2 = 0.01; d = 0.27) compared to the control group. We also found an indirect effect of the intervention on increased life satisfaction at time 2 via decreased anger (b = 0.035, SE = 0.023, 95% CI = [0.004-0.24]). CONCLUSIONS: This study provides an initial evaluation of training for platoon leaders that educates them on proactive and responsive behavioral strategies to support the mental health and resilience of their service members via decreased problematic anger and increased well-being. Further adaptations and evaluations should be conducted with other military branches and civilian occupations, as the benefits of the relatively brief and noninvasive training could be widespread.