Long-term outcomes following proton therapy for non-metastatic central nervous system germinoma in children and adolescents.

BACKGROUND/PURPOSE: Radiation is a key component in the treatment of central nervous system pure germinoma (PG) in children and adolescents. Proton therapy (PT) improves normal tissue sparing and potentially reduces adverse effects (AE). The aim of this study was to present the largest single institution experience utilizing PT for the management of PG. MATERIALS METHODS: We enrolled 35 non-metastatic patients with PG that were treated with PT at our institution between July 2007 - September 2021. Most received induction chemotherapy (n = 31, 89 %) and whole ventricular irradiation with an involved field boost (n = 29, 83 %). The most common total dose was 30 CGE (n = 18, 51.4 %). We utilized the cumulative incidence method to estimate local control (LC), freedom from distant metastases (FFDM), freedom from progression (FFP), and overall survival (OS). Treatment related toxicity was assessed per CTCAE version 5. RESULTS: Median follow-up was 6.2 years (range, 0.9---15.2). The 10-year Kaplan-Meier estimates for LC, FFDM, FFP, and OS were 100 %, 100 %, 100 %, and 94 % respectively. The most common AE were hearing impairment requiring hearing aids (n = 3), transient hypersomnia requiring medication (n = 3), and new onset endocrinopathy (n = 1). Of the 23 evaluable patients ≥ 18 years old at last follow-up, 8 were high school graduates/in college, 8 college graduates, and 7 others gainfully employed. CONCLUSIONS: When utilized in modern multimodality treatment of non-metastatic PG, the precise dosimetry of PT does not compromise disease control. Although serious radiation side effects are rare, the 100% cure rate supports further investigation into selective radiation dose and volume de-escalation.

Fire season matters for midstory hardwood control: Impacts of fire season and firing technique on plant communities.

In the southeastern USA, lack of historical fire regimes often leads to hardwood encroachment into early successional plant communities and managed pine stands, reducing wildlife value and timber yields. Land managers lack information on how firing technique interacts with fire season to influence plant communities. We designed an experiment to quantify these interactions in east-central Mississippi with pairs of 4 m × 8 m plots randomly assigned a backing and heading fire in each of three seasons: February (Feb), May-June (May/Jun), and September-October (Sep/Oct). We used thermocouples to monitor fire temperature and tagged midstory trees to monitor response. We lit heading fires with an 18-25 kph wind generated by a backpack blower and backing fires into the ambient wind. Despite backing fires producing longer residence times than heading fires and raising temperature above the lethal threshold of 60 °C an average of 54 s longer, firing technique did not influence midstory response one growing season post-fire. Backing and heading fires produced similar maximum temperatures. For both firing techniques, May/Jun resulted in the highest midstory mortality rates which were 3-fold greater than Sep/Oct and 4-fold greater than Feb. Among all three fire seasons, trees with a 2.5 cm diameter at breast height (DBH) had approximately a 75% chance of top-kill which decreased to <20% as trees approached 6.5 cm DBH. We found no effects of fire season on fire temperature, rate of spread, flame height, or percent crown scorch. We found no significant interactions between fire season and firing technique. Understory analysis revealed Sep/Oct produced the greatest increase in forb coverage, May/Jun resulted in the most grass coverage, and Feb produced the most brambles (Rubus spp.). On sites with similar species, weather, and fuel conditions to ours, land managers should emphasize fire season over firing technique for midstory control and understory manipulation. Where midstory hardwood control with fire is a priority, fire return intervals should be frequent enough to prevent trees from exceeding 2.5 cm DBH to avoid trees escaping fire's reach. These data can help managers reduce midstory competition with crop trees and promote understory development for wildlife.

Axillary Surgery for Chemoresidual (ypN-Positive) Nodal Disease.

This cohort study using pooled data from 2 randomized clinical trials examines whether removing more lymph nodes with axillary lymph node dissection improved outcomes over sentinel lymph node biopsy when most patients received adjuvant radiation therapy or regional nodal irradiation.

Effects on Lung Tissue After Breast Cancer Radiation: Comparing Photon and Proton Therapies.

Purpose: In breast cancer, improved treatment approaches that reduce injury to lung tissue and early diagnosis and intervention for lung toxicity are increasingly important in survivorship. The aims of this study are to (1) compare lung tissue radiographic changes in women treated with conventional photon radiation therapy and those treated with proton therapy (PT), (2) assess the volume of lung irradiated to 5 Gy (V5) and 20 Gy (V20) by treatment modality, and (3) quantify the effects of V5, V20, time, and smoking history on the severity of tissue radiographic changes. Patients and Methods: A prospective observational study of female breast cancer patients was conducted to monitor postradiation subclinical lung tissue radiographic changes. Repeated follow-up x-ray computed tomography scans were acquired through 2 years after treatment. In-house software was used to quantify an internally normalized measure of pulmonary tissue density change over time from the computed tomography scans, emphasizing the 6- and 12-month time points. Results: Compared with photon therapy, PT was associated with significantly lower lung V5 and V20. Lung V20 (but not V5) correlated significantly with increased subclinical lung tissue radiographic changes 6 months after treatment, and neither correlated with lung effects at 12 months. Significant lung tissue density changes were present in photon therapy patients at 6 and 12 months but not in PT patients. Significant lung tissue density change persisted at 12 months in ever-smokers but not in never-smokers. Conclusion: Patients treated with PT had significantly lower radiation exposure to the lungs and less statistically significant tissue density change, suggesting decreased injury and/or improved recovery compared to photon therapy. These findings motivate additional studies in larger, randomized, and more diverse cohorts to further investigate the contributions of treatment modality and smoking regarding the short- and long-term radiographic effects of radiation on lung tissue.

Consolidative Proton Radiotherapy for Pediatric Extramedullary Ocular Acute Myeloid Leukemia.

Purpose: Pediatric acute myeloid leukemia (AML) often involves extramedullary sites, which can be resistant to standard induction chemotherapy. Consolidative radiation therapy can be used in select cases to improve local control rates and help bridge patients to curative stem cell transplants. However, there is no previously published data to support the use of proton radiotherapy (PT) in this setting. We present radiographic findings and pathologic outcomes of the first reported patient with extramedullary ocular AML to be treated with PT. Patients and Methods: Details regarding diagnostic evaluation and treatment were obtained from the electronic medical records at the University of Florida Proton Therapy Institute, Nemours Children's Health, and St. Joseph's Children's Hospital. Results: This 7-month-old patient presented with biopsy-proven relapsed AML in the bilateral anterior chambers of the eyes, which did not resolve with induction chemotherapy. The patient then received PT to a dose of 24 cobalt gray equivalent to both eyes and was found to have no evidence of disease following treatment. Conclusion: This case provides further evidence that consolidative radiotherapy may be considered for select patients with extramedullary AML who have limited response to induction chemotherapy. Given the increased prevalence of extramedullary AML in pediatric patients, it is worth considering the utilization of PT to mitigate damage to nearby organs and the risk of secondary malignancies.

What drives wild pig (Sus scrofa) movement in bottomland and upland forests?

BACKGROUND: The wild pig (Sus scrofa) is an exotic species that has been present in the southeastern United States for centuries yet continues to expand into new areas dominated by bottomland and upland forests, the latter of which are less commonly associated with wild pigs. Here, we aimed to investigate wild pig movement and space use attributes typically used to guide wild pig management among multiple spatiotemporal scales. Our investigation focused on a newly invaded landscape dominated by bottomland and upland forests. METHODS: We examined (1) core and total space use using an autocorrelated kernel density estimator; (2) resource selection patterns and hot spots of space use in relation to various landscape features using step-selection analysis; and (3) daily and hourly differences in movement patterns between non-hunting and hunting seasons using generalized additive mixed models. RESULTS: Estimates of total space use among wild pigs (n = 9) were smaller at calculated core (1.2 ± 0.3 km2) and 90% (5.2 ± 1.5 km2) isopleths than estimates reported in other landscapes in the southeastern United States, suggesting that wild pigs were able to meet foraging, cover, and thermoregulatory needs within smaller areas. Generally, wild pigs selected areas closer to herbaceous, woody wetlands, fields, and perennial streams, creating corridors of use along these features. However, selection strength varied among individuals, reinforcing the generalist, adaptive nature of wild pigs. Wild pigs also showed a tendency to increase movement from fall to winter, possibly paralleling increases in hard mast availability. During this time, there were also increases in anthropogenic pressures (e.g. hunting), causing movements to become less diurnal as pressure increased. CONCLUSIONS: Our work demonstrates that movement patterns by exotic generalists must be understood across individuals, the breadth of landscapes they can invade, and multiple spatiotemporal scales. This improved understanding will better inform management strategies focused on curbing emerging invasions in novel landscapes, while also protecting native natural resources.

Regulation of Mertk Surface Expression via ADAM17 and γ-Secretase Proteolytic Processing.

Mertk, a type I receptor tyrosine kinase and member of the TAM family of receptors, has important functions in promoting efferocytosis and resolving inflammation under physiological conditions. In recent years, Mertk has also been linked to pathophysiological roles in cancer, whereby, in several cancer types, including solid cancers and leukemia/lymphomas. Mertk contributes to oncogenic features of proliferation and cell survival as an oncogenic tyrosine kinase. In addition, Mertk expressed on macrophages, including tumor-associated macrophages, promotes immune evasion in cancer and is suggested to act akin to a myeloid checkpoint inhibitor that skews macrophages towards inhibitory phenotypes that suppress host T-cell anti-tumor immunity. In the present study, to better understand the post-translational regulation mechanisms controlling Mertk expression in monocytes/macrophages, we used a PMA-differentiated THP-1 cell model to interrogate the regulation of Mertk expression and developed a novel Mertk reporter cell line to study the intracellular trafficking of Mertk. We show that PMA treatment potently up-regulates Mertk as well as components of the ectodomain proteolytic processing platform ADAM17, whereas PMA differentially regulates the canonical Mertk ligands Gas6 and Pros1 (Gas6 is down-regulated and Pros1 is up-regulated). Under non-stimulated homeostatic conditions, Mertk in PMA-differentiated THP1 cells shows active constitutive proteolytic cleavage by the sequential activities of ADAM17 and the Presenilin/γ-secretase complex, indicating that Mertk is cleaved homeostatically by the combined sequential action of ADAM17 and γ-secretase, after which the cleaved intracellular fragment of Mertk is degraded in a proteasome-dependent mechanism. Using chimeric Flag-Mertk-EGFP-Myc reporter receptors, we confirm that inhibitors of γ-secretase and MG132, which inhibits the 26S proteasome, stabilize the intracellular fragment of Mertk without evidence of nuclear translocation. Finally, the treatment of cells with active γ-carboxylated Gas6, but not inactive Warfarin-treated non-γ-carboxylated Gas6, regulates a distinct proteolytic itinerary-involved receptor clearance and lysosomal proteolysis. Together, these results indicate that pleotropic and complex proteolytic activities regulate Mertk ectodomain cleavage as a homeostatic negative regulatory event to safeguard against the overactivation of Mertk.

Seroreactivity of antibodies to hepatitis B core antigen among hepatitis B surface antigen-screened negative blood donors and its implications for blood safety in a resource-constrained country.

BACKGROUND AND OBJECTIVES: Transfusion-related hepatitis B infections have been reduced significantly with the implementation of blood screening using both serology and nucleic acid amplification technology (NAT) in developed countries. However, in resource-constrained countries, where NAT is inaccessible, the risk persists from early acute and occult cases. This study aimed to determine the antibodies to hepatitis B core antigen (anti-HBc) reactive rate among hepatitis B surface antigen (HBsAg)-screened negative blood donors and its impact on blood safety in the Philippines. MATERIALS AND METHODS: A total of 1602 HBsAg-negative samples, randomly collected from nine leading blood service facilities representative of each region in the Philippines, were tested for anti-HBc immunoglobulin M (IgM), Total and antibodies to HBsAg (anti-HBs) using the Architect i2000SR Immunoassay Analyser (Abbott Laboratories, IL). Anti-HBc IgM and/or Total repeat reactive were further tested for hepatitis B virus (HBV) NAT using the Cobas TaqScreen MPX v2.0 (Roche Diagnostics, Basel). RESULTS: Overall, 19.16% HBsAg-negative samples (n = 307/1602) were reactive for either anti-HBc IgM or Total or a combination of both, of which 1.3% (n = 4/307) had detectable HBV-DNA and 80.5% (n = 247/307) were anti-HBs positive. About the anti-HBs titres, 30.27% (n = 485/1602) were positive (≥10 IU/L) with 55.67% (n = 270/485) having titres ≥100 IU/L. Anti-HBs-only-positive samples were 14.85% (n = 238/1602). CONCLUSION: We observed a high anti-HBc reactive rate (19.16%) with 3.7% anti-HBc-only reactive (anti-HBs negative) and 1.3% HBV-DNA positive. This warrants the need to reconsider existing screening practices to improve blood safety in the country.

Environmental predictors for the restoration of a critically endangered coral, Acropora palmata, along the Florida reef tract.

The population decline and lack of natural recovery of multiple coral species along the Florida reef tract have instigated the expanding application of coral restoration and conservation efforts. Few studies, however, have determined the optimal locations for the survival of outplanted coral colonies from restoration nurseries. This study predicts the optimal locations for Acropora palmata colonies along the Florida reef tract using a boosted-regression-tree model to examine the relationships between the occurrence of wild A. palmata and ten environmental variables. Our model results predicted A. palmata was most likely to occur in shallow reef habitats with (i) generally low mean chlorophyll-a concentrations (< 1 mg m-3), (ii) moderate fetch (3 kJ m-2), (iii) salinities between 20 and 37.5 ppt, (iv) temperatures between 20 and 32°C, (vi) low mean concentrations of total nitrogen (0.16 ppm), and (iv) irradiance between 26.5 and 53.5 mol m-2 s-1. The most suitable habitats for A. palmata were disproportionately allocated to reefs in Biscayne Bay, the Upper Keys, the western-lower Florida Keys, the Marquesas, and the Dry Tortugas. The middle Florida Keys had unfavorable environmental conditions for A. palmata habitat. Results from this study inform where A. palmata, outplanted as part of restoration and conservation efforts, would have suitable environmental conditions to persist over time. This study also provides decision-making support for management focused on the conservation and restoration of the endangered species A. palmata along the Florida reef tract.

Outcomes following proton therapy for pediatric esthesioneuroblastoma.

BACKGROUND: Pediatric esthesioneuroblastoma (EN) can infiltrate skull base anatomy, presenting challenges due to high radiation doses and pediatric tissue sensitivity. This study reports outcomes of pediatric EN treated with proton radiotherapy (PT). PROCEDURE: Using an IRB-approved prospective outcomes registry, we evaluated patient, tumor, and treatment-related variables impacting disease control and toxicity in pediatric nonmetastatic EN treated with modern multimodality therapy, including PT. RESULTS: Fifteen consecutive patients (median age 16) comprising Kadish stage B (n = 2), C (n = 9), and D (n = 4) tumors were assessed, including six with intracranial involvement, four with cranial nerve deficits, and four with cervical lymphadenopathy. Before radiation, two had subtotal and 13 had gross total resections (endoscopic or craniofacial). Two underwent neck dissection. Eleven received chemotherapy before radiation (n = 5), concurrent with radiation (n = 4), or both (n = 2). Median total radiation dose (primary site) was 66 Gy/CGE for gross disease and 54 Gy/CGE (cobalt Gray equivalent) for microscopic disease. Median follow-up was 4.8 years. No patients were lost to follow-up. Five-year disease-free and overall survival rates were 86% (no local or regional recurrences). Two patients developed vertebral metastases and died. Two required a temporary feeding tube for oral mucositis/dysphagia. Late toxicities included symptomatic retinopathy, major reconstructive surgery, cataracts, chronic otitis media, chronic keratoconjunctivitis, hypothyroidism, and in-field basal cell skin cancer. CONCLUSIONS: A multimodality approach for pediatric EN results in excellent local control. Despite the moderate-dose PT, serious radiation toxicity was observed; further dose and target volume reductions may benefit select patients. Longer follow-up and comparative data from modern photon series are necessary to fully characterize any relative PT advantage.

Proton Therapy in the Treatment of Men with Breast Cancer.

Purpose: Male breast cancer treatment involves multimodality therapy, including radiation therapy; nevertheless, few men have received proton therapy (PT) for it. Further, heart disease is an established leading cause of death in men, and radiation therapy heart dose correlates with cardiac toxicity, highlighting the need for cardiac-sparing radiation techniques. Thus, we provide a descriptive analysis of PT in a male breast cancer cohort. Patients and Methods: Men who received PT for localized breast cancer between 2012 and 2022 were identified from a prospective database. Toxicities were prospectively recorded by using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Results: Five male patients were identified. All had estrogen receptor (ER)-positive, Her2neu-negative disease and received adjuvant endocrine therapy. One had genetic testing positive for BRCA2, one had a variant of unknown significance (VUS) in the APC gene, and one had a VUS in MSH2. Median age was 73 years (range, 41-80). Baseline comorbidities included obesity (n = 1), diabetes (n = 1), hypertension (n = 4), history of deep vein thrombosis (n = 1), personal history of myocardial infarction (n = 3; 1 with a pacemaker), and a history of lung cancer (n = 1). All received PT to the left chest wall and comprehensive regional lymphatics. One received passive-scattering PT, and 4 received pencil beam scanning. One patient received a boost to the mastectomy incision via electrons. Median heart dose was 1 GyRBE (range, 0-1.0), median 0.1-cm3 dose to the left anterior descending artery was 7.5 GyRBE (range, 0-14.2), and median follow-up was 2 years (range, 0.75-6.5); no patient experienced a new cardiac event, and all remain free from breast cancer recurrence and progression. Conclusion: In a small case series for a rare diagnosis, PT to the chest wall and regional lymphatics, including internal mammary nodes, resulted in low cardiac exposure, high local regional disease control rates, and minimal toxicity. Proton therapy should be considered for treating men with breast cancer to achieve cardiac sparing.

Racial and Ethnic Demographic Reporting in Phase 2 Proton Therapy Clinical Trials: A Review.

Purpose: Equitable inclusion of racial and ethnic participation in clinical trials is crucial to improving disparities in health care, especially for historically marginalized populations. Our study aims to describe the racial and ethnic demographics of patients enrolled in published phase 2 clinical trials involving proton therapy in the United States. Materials and Methods: Published manuscripts were identified in PubMed, Embase, World of Science, and Cochrane. Phase 2 trials evaluating proton therapy for US patients were included. For each article in the study, data were collected comprising authors, title, and publication year, and clinical trial numbers were verified. Additional data included tumor site, primary institution, sample size, reported race/ethnicity, and raw number/percentile of race/ethnicity. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were used. Results: Overall, 970 titles were identified; 636 remained after duplicate screening, and 75 full-text articles were assessed. We identified 38 eligible manuscripts for inclusion comprising 2648 patients. Only 15 (39%) of the publications reported race/ethnicity. Of these, 8 (21%) and 10 (26%) documented Hispanic or Black trial participants, respectively; however, only 6 (16%) documented trial participation for both Hispanic and Black patients. Of the 1409 patients with a documented race/ethnicity, 89.0% (n = 1254) were non-Hispanic white, 5.3% (n = 75) were Black, and 2.2% (n = 31) were Hispanic. Other and unknown race/ethnicity comprised the remaining patients (3.5%; n = 49). Conclusion: We identified underreporting of demographic data in published phase 2 proton therapy trials, which unfortunately mirrored underreporting for cancer drug clinical trials. We also noted dramatic Black and Hispanic patient underrepresentation across the trials in which race and ethnicity are reported. Findings highlight the urgent need to identify and address barriers to proton therapy trials for Black and Hispanic patients ensuring clinical trials in radiation oncology are representative of the patients seen in clinical practice.

Epicardial placement of human placental membrane protects from heart injury in a swine model of myocardial infarction.

Cardiac ischemic reperfusion injury (IRI) is paradoxically instigated by reestablishing blood-flow to ischemic myocardium typically from a myocardial infarction (MI). Although revascularization following MI remains the standard of care, effective strategies remain limited to prevent or attenuate IRI. We hypothesized that epicardial placement of human placental amnion/chorion (HPAC) grafts will protect against IRI. Using a clinically relevant model of IRI, swine were subjected to 45 min percutaneous ischemia followed with (MI + HPAC, n = 3) or without (MI only, n = 3) HPAC. Cardiac function was assessed by echocardiography, and regional punch biopsies were collected 14 days post-operatively. A deep phenotyping approach was implemented by using histological interrogation and incorporating global proteomics and transcriptomics in nonischemic, ischemic, and border zone biopsies. Our results established HPAC limited the extent of cardiac injury by 50% (11.0 ± 2.0% vs. 22.0 ± 3.0%, p = 0.039) and preserved ejection fraction in HPAC-treated swine (46.8 ± 2.7% vs. 35.8 ± 4.5%, p = 0.014). We present comprehensive transcriptome and proteome profiles of infarct (IZ), border (BZ), and remote (RZ) zone punch biopsies from swine myocardium during the proliferative cardiac repair phase 14 days post-MI. Both HPAC-treated and untreated tissues showed regional dynamic responses, whereas only HPAC-treated IZ revealed active immune and extracellular matrix remodeling. Decreased endoplasmic reticulum (ER)-dependent protein secretion and increased antiapoptotic and anti-inflammatory responses were measured in HPAC-treated biopsies. We provide quantitative evidence HPAC reduced cardiac injury from MI in a preclinical swine model, establishing a potential new therapeutic strategy for IRI. Minimizing the impact of MI remains a central clinical challenge. We present a new strategy to attenuate post-MI cardiac injury using HPAC in a swine model of IRI. Placement of HPAC membrane on the heart following MI minimizes ischemic damage, preserves cardiac function, and promotes anti-inflammatory signaling pathways.

Complete genome sequence of Vibrio parahaemolyticus strain PH1273, isolated from aquacultured shrimp in the Philippines.

We announce the complete genome sequence of Vibrio parahaemolyticus strain PH1273. This strain was collected from a Penaeus vannamei pond in the Philippines in 2015. Genome analysis revealed that it lacks the gene pirAB responsible for causing acute hepatopancreatic necrosis disease but encode multiple secretion systems and the associated effectors.

The biased M3 mAChR ligand PD 102807 mediates qualitatively distinct signaling to regulate airway smooth muscle phenotype.

Airway smooth muscle (ASM) cells attain a hypercontractile phenotype during obstructive airway diseases. We recently identified a biased M3 muscarinic acetylcholine receptor (mAChR) ligand, PD 102807, that induces GRK-/arrestin-dependent AMP-activated protein kinase (AMPK) activation to inhibit transforming growth factor-ß-induced hypercontractile ASM phenotype. Conversely, the balanced mAChR agonist, methacholine (MCh), activates AMPK yet does not regulate ASM phenotype. In the current study, we demonstrate that PD 102807- and MCh-induced AMPK activation both depend on Ca2+/calmodulin-dependent kinase kinases (CaMKKs). However, MCh-induced AMPK activation is calcium-dependent and mediated by CaMKK1 and CaMKK2 isoforms. In contrast, PD 102807-induced signaling is calcium-independent and mediated by the atypical subtype protein kinase C-iota and the CaMKK1 (but not CaMKK2) isoform. Both MCh- and PD 102807-induced AMPK activation involve the AMPK α1 isoform. PD 102807-induced AMPK α1 (but not AMPK α2) isoform activation mediates inhibition of the mammalian target of rapamycin complex 1 (mTORC1) in ASM cells, as demonstrated by increased Raptor (regulatory-associated protein of mTOR) phosphorylation as well as inhibition of phospho-S6 protein and serum response element-luciferase activity. The mTORC1 inhibitor rapamycin and the AMPK activator metformin both mimic the ability of PD 102807 to attenuate transforming growth factor-ß-induced α-smooth muscle actin expression (a marker of hypercontractile ASM). These data indicate that PD 102807 transduces a signaling pathway (AMPK-mediated mTORC1 inhibition) qualitatively distinct from canonical M3 mAChR signaling to prevent pathogenic remodeling of ASM, thus demonstrating PD 102807 is a biased M3 mAChR ligand with therapeutic potential for the management of obstructive airway disease.

Characteristics of International Assaultive Psychiatric Patients: Review of Published Findings, 2017-2022.

Since the 1960s, empirical research has focused on a better understanding of the characteristics of assaultive psychiatric patients. International research from 1960 to 2017 indicated that male and female patients with schizophrenia and substance use disorder presented the greatest risk for assault with nursing personnel being at higher risk. This present review of studies sought to assess the latest research findings on assaultive patients for the most recent five-year period, 2017-2022. It was hypothesized that patients with schizophrenia and substance use disorders would present the greatest assault risk for nursing personnel. The studies in this review supported this hypothesis. Assaults by patients with schizophrenia and substance abuse has been a consistent finding worldwide for 62 years of published research. Explanations for these findings, the possible role of posttraumatic stress disorder (PTSD) in assaultive patients, and an updated methodological review are presented.