Stabilization of ß-Catenin Directs HEB to Limit Thymic Selection.

Activation of ß-catenin in CD4+CD8+ double-positive (DP) thymocytes halts development before the thymic selection stage and predisposes to transformation. Leukemogenesis, but not the developmental block, depends on TCF-1, ß-catenin's DNA-binding partner. In this study, we show that ß-catenin activation directs the DNA-binding protein HEB to block DP thymocyte development. Conditional loss of HEB in DP thymocytes with stabilized ß-catenin restores the frequencies of postselection TCRßhi/CCR7+ and TCRßhi/CD69+ DPs and their cell-cycle profile. This recovery is associated with significant reversal of ß-catenin-induced expression changes, particularly those related to the CD69+ DP cell signature and to cell-cycle pathways. Stabilizing ß-catenin in DP thymocytes directs HEB binding to ≈11,000 novel DNA sites throughout the genome. Novel HEB sites mark most CD69+ DP cell signature genes that change expression upon activation of ß-catenin and then revert after loss of HEB. Moreover, many of the novel HEB sites occupy promoter regions of genes enriched in mitotic cell cycle pathways. HEB binding to those regions correlates with downregulation of the associated genes, and HEB inactivation restores expression to physiologic levels. These findings highlight a molecular interplay between HEB and ß-catenin that can impair thymic development.

Tcf-1 promotes genomic instability and T cell transformation in response to aberrant ß-catenin activation.

Understanding the mechanisms promoting chromosomal translocations of the rearranging receptor loci in leukemia and lymphoma remains incomplete. Here we show that leukemias induced by aberrant activation of ß-catenin in thymocytes, which bear recurrent Tcra/Myc-Pvt1 translocations, depend on Tcf-1. The DNA double strand breaks (DSBs) in the Tcra site of the translocation are Rag-generated, whereas the Myc-Pvt1 DSBs are not. Aberrantly activated ß-catenin redirects Tcf-1 binding to novel DNA sites to alter chromatin accessibility and down-regulate genome-stability pathways. Impaired homologous recombination (HR) DNA repair and replication checkpoints lead to retention of DSBs that promote translocations and transformation of double-positive (DP) thymocytes. The resulting lymphomas, which resemble human T cell acute lymphoblastic leukemia (T-ALL), are sensitive to PARP inhibitors (PARPis). Our findings indicate that aberrant ß-catenin signaling contributes to translocations in thymocytes by guiding Tcf-1 to promote the generation and retention of replication-induced DSBs allowing their coexistence with Rag-generated DSBs. Thus, PARPis could offer therapeutic options in hematologic malignancies with active Wnt/ß-catenin signaling.

Maternal exposure to zolpidem and risk of specific birth defects.

Zolpidem is a non-benzodiazepine agent indicated for treatment of insomnia. While zolpidem crosses the placenta, little is known about its safety in pregnancy. We assessed associations between self-reported zolpidem use 1 month before pregnancy through to the end of the third month ("early pregnancy") and specific birth defects using data from two multi-site case-control studies: National Birth Defects Prevention Study and Slone Epidemiology Center Birth Defects Study. Analysis included 39,711 birth defect cases and 23,035 controls without a birth defect. For defects with ≥ 5 exposed cases, we used logistic regression with Firth's penalised likelihood to estimate adjusted odds ratios and 95% confidence intervals, considering age at delivery, race/ethnicity, education, body mass index, parity, early-pregnancy antipsychotic, anxiolytic, antidepressant use, early-pregnancy opioid use, early-pregnancy smoking, and study as potential covariates. For defects with three-four exposed cases, we estimated crude odds ratios and 95% confidence intervals. Additionally, we explored differences in odds ratios using propensity score-adjustment and conducted a probabilistic bias analysis of exposure misclassification. Overall, 84 (0.2%) cases and 46 (0.2%) controls reported early-pregnancy zolpidem use. Seven defects had sufficient sample size to calculate adjusted odds ratios, which ranged from 0.76 for cleft lip to 2.18 for gastroschisis. Four defects had odds ratios > 1.8. All confidence intervals included the null. Zolpidem use was rare. We could not calculate adjusted odds ratios for most defects and estimates are imprecise. Results do not support a large increase in risk, but smaller increases in risk for certain defects cannot be ruled out.

Associations between maternal periconceptional alcohol consumption and risk of omphalocele among offspring, National Birth Defects Prevention Study, 1997-2011.

OBJECTIVE: Previous studies of alcohol consumption during pregnancy and omphalocele have produced mixed results. We updated an earlier analysis of National Birth Defects Prevention Study (NBDPS) data, adding six years of participants, to examine associations between maternal alcohol consumption and omphalocele. METHODS: NBDPS was a multi-site, population-based case-control study in the United States. Cases were identified from birth defect surveillance programs in 10 states; controls were liveborn infants without a birth defect randomly selected from the same catchment areas. Mothers self-reported alcohol consumption during the periconceptional period (one month before through the third gestational month) via telephone interview. Our study included mothers of 410 omphalocele cases and 11,219 controls with estimated dates of delivery (EDDs) during 1997-2011. We used logistic regression to estimate adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for periconceptional alcohol consumption and omphalocele. We performed a probabilistic bias analysis to evaluate the impact of alcohol exposure misclassification on our results. RESULTS: Overall, 44% of case and 38% of control mothers reported periconceptional alcohol consumption; 22% and 17%, respectively, reported binge drinking. Any maternal periconceptional alcohol consumption was associated with modestly increased odds of omphalocele (AOR 1.35, 95% CI 1.09, 1.68), as was binge drinking (AOR 1.47, 95% CI 1.08, 2.01). Our bias analysis yielded estimates further from the null. CONCLUSIONS: We observed modest associations between maternal periconceptional alcohol consumption and omphalocele. Based on our bias analysis, studies of alcohol and birth defects not accounting for exposure misclassification may underestimate associations.

G-Computation and Agent-Based Modeling for Social Epidemiology: Can Population Interventions Prevent Posttraumatic Stress Disorder?

Agent-based modeling and g-computation can both be used to estimate impacts of intervening on complex systems. We explored each modeling approach within an applied example: interventions to reduce posttraumatic stress disorder (PTSD). We used data from a cohort of 2,282 adults representative of the adult population of the New York City metropolitan area from 2002-2006, of whom 16.3% developed PTSD over their lifetimes. We built 4 models: g-computation, an agent-based model (ABM) with no between-agent interactions, an ABM with violent-interaction dynamics, and an ABM with neighborhood dynamics. Three interventions were tested: 1) reducing violent victimization by 37.2% (real-world reduction); 2) reducing violent victimization by100%; and 3) supplementing the income of 20% of lower-income participants. The g-computation model estimated population-level PTSD risk reductions of 0.12% (95% confidence interval (CI): -0.16, 0.29), 0.28% (95% CI: -0.30, 0.70), and 1.55% (95% CI: 0.40, 2.12), respectively. The ABM with no interactions replicated the findings from g-computation. Introduction of interaction dynamics modestly decreased estimated intervention effects (income-supplement risk reduction dropped to 1.47%), whereas introduction of neighborhood dynamics modestly increased effectiveness (income-supplement risk reduction increased to 1.58%). Compared with g-computation, agent-based modeling permitted deeper exploration of complex systems dynamics at the cost of further assumptions.

Managing Ischemic Heart Disease in Women: Role of a Women's Heart Center.

PURPOSE OF REVIEW: Heart centers for women (HCW) were developed due to the rising cardiovascular morbidity and mortality in women in the United States in the early 1990s. Our review encompasses the epidemiology, risk factors, diagnostic strategies, treatments, and the role of HCW in managing women with ischemic heart disease (IHD). RECENT FINDINGS: HCW use a multidisciplinary team to manage women with IHD. Due to the paucity of randomized controlled trials investigating various manifestations of IHD, some treatments are not evidence-based such as those for coronary microvascular dysfunction and spontaneous coronary artery dissection. Sex-specific risk factors have been identified and multimodality cardiac imaging is improving in diagnosing IHD in women. Treatments are being studied to help improve symptoms and outcomes in women with IHD. There has been progress in the care of women with IHD. HCW can be instrumental in treating women with IHD, doing research, and being a source of research study participants.

Health Literacy Among In-Care Older HIV Diagnosed Persons with Multimorbidity: MMP NYS (Excluding NYC).

Older persons living with diagnosed HIV (PLWDH) are also at risk for age-related chronic conditions. With conflicting results on studies assessing health literacy and durable viral suppression, this study is the first in assessing this relationship using representative data on older in-care HIV-diagnosed persons with multimorbidity. Weighted data collected 2009-2014 from the Medical Monitoring Project (MMP) was used. Health literacy was assessed using the three-item Brief Health Literacy Screen (BHLS). The mean health literacy score was 11.22 (95% CI 10.86-11.59), and the mean multimorbidity was 4.75 (SE = 0.32). After adjusting, health literacy (OR 0.87, 95% CI 0.77-0.99) was found to be significantly associated with durable viral suppression. Adequate health literacy can help with achieving durable viral suppression. For these persons, addressing health literacy might increase their ability to access and navigate the healthcare system, thereby helping them stay engaged and maintain adherence to HIV care.

Knowledge and attitudes towards ambulatory treatment of tuberculоsis in Kazakhstan.

BACKGROUND: Ambulatory based treatment of tuberculosis has been recently introduced in Kazakhstan. We sought to assess the attitudes of the general population, TB patients and their household members towards ambulatory TB treatment and identify how knowledge of TB is associated with these attitudes. METHODS: New pulmonary TB cases and their household and community controls were recruited from three regions of Kazakhstan in 2012-2014. 1083 participants completed audio computer-assisted self interviews to assess their knowledge of TB and attitudes towards ambulatory care. Mixed effects logistic regression models were used to identify factors associated with attitudes toward ambulatory TB treatment. RESULTS: The proportion of people who considered ambulatory TB treatment as appropriate was very low (24.9%). Positive attitudes towards ambulatory TB treatment were significantly associated with region of residence, higher level of education, family support and experience with TB. The association between sufficient tuberculosis knowledge and favorable attitude toward ambulatory treatment was stronger among community controls compared to TB patients and their family members. CONCLUSIONS: This study provides insight into attitudes toward ambulatory TB treatment among different groups and the specific influence of TB knowledge on these attitudes. Our findings can inform the process of integration of new TB treatment strategies and the development of appropriate education and advocacy programs in the general population.

Limiting Alcohol Outlet Density to Prevent Alcohol Use and Violence: Estimating Policy Interventions Through Agent-Based Modeling.

Increasing alcohol outlet density is well-documented to be associated with increased alcohol use and problems, leading to the policy recommendation that limiting outlet density will decrease alcohol problems. Yet few studies of decreasing problematic outlets and outlet density have been conducted. We estimated the association between closing alcohol outlets and alcohol use and alcohol-related violence, using an agent-based model of the adult population in New York City. The model was calibrated according to the empirical distribution of the parameters across the city's population, including the density of on- and off-premise alcohol outlets. Interventions capped the alcohol outlet distribution at the 90th to the 50th percentiles of the New York City density, and closed 5% to 25% of outlets with the highest levels of violence. Capping density led to a lower population of light drinkers (42.2% at baseline vs. 38.1% at the 50th percentile), while heavy drinking increased slightly (12.0% at baseline vs. 12.5% at the 50th percentile). Alcohol-related homicides and nonfatal violence remained unchanged. Closing the most violent outlets was not associated with changes in alcohol use or related problems. Results suggest that focusing solely on closing alcohol outlets might not be an effective strategy to reduce alcohol-related problems.

Simulating the Suicide Prevention Effects of Firearms Restrictions Based on Psychiatric Hospitalization and Treatment Records: Social Benefits and Unintended Adverse Consequences.

Objectives. To estimate the number of lives saved from firearms suicide with expansions of gun restrictions based on mental health compared with the number who would be unnecessarily restricted. Methods. Agent-based models simulated effects on suicide mortality resulting from 5-year ownership disqualifications in New York City for individuals with any psychiatric hospitalization and, more broadly, anyone receiving psychiatric treatment. Results. Restrictions based on New York State Office of Mental Health-identified psychiatric hospitalizations reduced suicide among those hospitalized by 85.1% (95% credible interval = 36.5%, 100.0%). Disqualifications for anyone receiving psychiatric treatment reduced firearm suicide rates among those affected and in the population; however, 244 820 people were prohibited from firearm ownership who would not have died from firearm suicide even without the policy. Conclusions. In this simulation, denying firearm access to individuals in psychiatric treatment reduces firearm suicide among those groups but largely will not affect population rates. Broad and unfeasible disqualification criteria would needlessly restrict millions at low risk, with potential consequences for civil rights, increased stigma, and discouraged help seeking.

Trajectories of childhood adversity and the risk of depression in young adulthood: Results from the Avon Longitudinal Study of Parents and Children.

BACKGROUND: The significance of the timing and chronicity of childhood adversity for depression outcomes later in life is unclear. Identifying trajectories of adversity throughout childhood would allow classification of children according to the accumulation, timing, and persistence of adversity, and may provide unique insights into the risk of subsequent depression. METHODS: Using data from the Avon Longitudinal Study of Parents and Children, we created a composite adversity score comprised of 10 prospectively assessed domains (e.g., violent victimization, inter-parental conflict, and financial hardship) for each of eight time points from birth through age 11.5 years. We used semiparametric group-based trajectory modeling to derive childhood adversity trajectories and examined the association between childhood adversity and depression outcomes at the age of 18 years. RESULTS: Among 9,665 participants, five adversity trajectories were identified, representing stable-low levels (46.3%), stable-mild levels (37.1%), decreasing levels (8.9%), increasing levels (5.3%), and stable-high levels of adversity (2.5%) from birth through late childhood. Approximately 8% of the sample met criteria for probable depression at 18 years and the mean depression severity score was 3.20 (standard deviation = 3.95, range 0-21). The risk of depression in young adulthood was elevated in the decreasing (odds ratio [OR] = 1.72, 95% confidence interval [CI] = 1.19-2.48), increasing (OR = 1.81, 95% CI = 1.15-2.86), and stable-high (OR = 1.80, 95% CI = 1.00-3.23) adversity groups, compared to those with stable-low adversity, when adjusting for potential confounders. CONCLUSIONS: Children in trajectory groups characterized by moderate or high levels of adversity at some point in childhood exhibited consistently greater depression risk and depression severity, regardless of the timing of adversity.

Takotsubo cardiomyopathy in a man with no trigger and multiple cardioembolic complications-A rare constellation.

Takotsubo Cardiomyopathy (TC) is an uncommon, transient, reversible cardiomyopathy, with a classic pattern of wall-motion abnormalities, usually seen in women after an emotional stressor. Despite its increased recognition, there remain gaps in the exact mechanisms, predisposing factors, and predictors of recovery; this is particularly true for males where the condition occurs far less frequently than in females. TC typically resolves within weeks, and the prognosis is favorable compared to acute coronary syndromes. Nonetheless, about 1% of cases may be complicated by left ventricular (LV) thrombus and embolism. Herein we describe an atypical case of a man with no obvious trigger, who developed TC with left ventricular thrombus and multiple embolic complications, but subsequently showed complete and full resolution. Multimodality imaging including echocardiography, cardiac CT and cardiac MRI was instrumental in this diagnostic dilemma, as well as useful in guiding treatment options and informing prognosis.

Use of ultrasound enhancing agents in transesophageal echocardiography to improve interpretive confidence of left atrial appendage thrombus.

BACKGROUND: The value of ultrasound enhancing agents (UEA) in patients undergoing transesophageal echocardiography (TEE) for the exclusion of left atrial appendage (LAA) thrombi prior to direct current cardioversion (DCCV) is evolving. METHODS: We retrospectively identified 88 consecutive TEEs, where a commercial UEA was used during LAA interrogation. De-identified non-enhanced (pre-UEA) and enhanced cine loop images (post-UEA) from the same subjects were randomly reviewed by four expert readers in a blinded fashion. RESULTS: In 33% of the cases, UEA use was associated with a statistically insignificant improvement in physician confidence (scale, 0-3) in determining the presence or absence of a LAA thrombus (P = 0.071). In instances where non-enhanced images yielded an uncertain interpretation or when the left atrium contained spontaneous echo contrast (SEC), UEA use was associated with an improvement in interpretive confidence in 49% (P < 0.001) and 41% of the cases (P = 0.001), respectively. Overall, the absolute rate of hypothetical decision to proceed with DCCV rose by 9% with the application of UEA (P = 0.004). In instances where non-enhanced images were interpreted with limited confidence or when SEC was present, there were absolute increases of 16% (P < 0.001) and 21% (P < 0.001) in hypothetical procession to DCCV, respectively. In cases of a combination of limited interpretive confidence and SEC, UEA use was associated with a 29% absolute increase in the rate of procession to DCCV (P < 0.001). CONCLUSIONS: In patients undergoing TEE interrogation of the LAA, the use of UEA is associated with an increase in the level of interpretive confidence and higher rates of theoretical procession to DCCV.

Agent-Based Modeling in Public Health: Current Applications and Future Directions.

Agent-based modeling is a computational approach in which agents with a specified set of characteristics interact with each other and with their environment according to predefined rules. We review key areas in public health where agent-based modeling has been adopted, including both communicable and noncommunicable disease, health behaviors, and social epidemiology. We also describe the main strengths and limitations of this approach for questions with public health relevance. Finally, we describe both methodologic and substantive future directions that we believe will enhance the value of agent-based modeling for public health. In particular, advances in model validation, comparisons with other causal modeling procedures, and the expansion of the models to consider comorbidity and joint influences more systematically will improve the utility of this approach to inform public health research, practice, and policy.

Reducing Urban Violence: A Contrast of Public Health and Criminal Justice Approaches.

BACKGROUND: Cities are investing millions in Cure Violence, a public health approach to reduce urban violence by targeting at-risk youth and redirecting conflict to nonviolent responses. The impact of such a program compared with criminal justice responses is unknown because experiments directly comparing criminal justice and public health approaches to violence prevention are infeasible with observational data. We simulated experiments to test the influence of two interventions on violence: (1) Cure Violence and (2) directed police patrol in violence hot spots. METHODS: We used an agent-based model to simulate a 5% sample of the New York City (NYC) adult population, with agents placed on a grid representing the land area of NYC, with neighborhood size and population density proportional to land area and population density in each community district. Agent behaviors were governed by parameters drawn from city data sources and published estimates. RESULTS: Under no intervention, 3.87% (95% CI, 3.84, 3.90) of agents were victimized per year. Implementing the violence interrupter intervention for 10 years decreased victimization by 13% (to 3.35% [3.32, 3.39]). Implementing hot-spots policing and doubling the police force for 10 years reduced annual victimization by about 11% (to 3.46% [3.42, 3.49]). Increasing the police force by 40% combined with implementing the violence interrupter intervention for 10 years decreased violence by 19% (to 3.13% [3.09, 3.16]). CONCLUSIONS: Combined investment in a public health, community-based approach to violence prevention and a criminal justice approach focused on deterrence can achieve more to reduce population-level rates of urban violence than either can in isolation. See video abstract at, http://links.lww.com/EDE/B298.

Monitoring suPAR levels in post-kidney transplant focal segmental glomerulosclerosis treated with therapeutic plasma exchange and rituximab.

BACKGROUND: Therapeutic plasma exchange (TPE) is an important therapy for recurrent focal segmental glomerulosclerosis (rFSGS) post kidney transplant. suPAR has been causally implicated in rFSGS, and shown to be a unique biomarker for the occurrence and progression of chronic kidney disease. This study was targeted to evaluate the application of monitoring suPAR in TPE treated rFSGS. METHODS: A retrospective (n = 19) and a prospective (n = 15) cohort of post transplant FSGS patients treated with TPE and rituximab were enrolled. We measured serum suPAR levels before and after the combined therapies, and assessed the role of suPAR changes on proteinuria reduction and podocyte ß3- integrin activity. RESULTS: Treatment with TPE and rituximab resulted in significant decrease in proteinuria and suPAR levels. Among the variables including baseline suPAR, serum creatinine, proteinuria, eGFR, age at diagnosis, age at transplantation, transplantation numbers, time to recurrence, and TPE course numbers, only the reduction in suPAR levels and baseline proteinuria significantly correlated with the changes in proteinuria after treatment, with the former performed better in predicting proteinuria alteration. Additionally, the mean podocyte ß3 integrin activity significantly decreased after TPE and rituximab treatment (1.10 ± 0.08) as compared to before treatment (1.34 ± 0.08), p < 0.05. Only the reduction in suPAR predicted the response to therapies with an odds ratio of 1.43, 95% CI (1.02, 2.00), p < 0.05. CONCLUSIONS: Serum suPAR levels reduced significantly after TPE and rituximab treatment in post transplant FSGS patients. The reduction in suPAR levels may be utilized to assess the changes in proteinuria and monitor the response to the therapies. Larger, multi-centered prospective studies monitoring serum suPAR levels in TPE managed post transplant FSGS are warranted.

Social Support Moderates Effects of Natural Disaster Exposure on Depression and Posttraumatic Stress Disorder Symptoms: Effects for Displaced and Nondisplaced Residents.

Social support is a known protective factor against the negative psychological impact of natural disasters. Most past research has examined how the effects of exposure to traumatic events influences whether someone meets diagnostic criteria for depression and posttraumatic stress disorder (PTSD); it has also suggested sequelae of disaster exposure depends on whether survivors are displaced from their homes. To capture the full range of the psychological impact of natural disasters, we examined the buffering effects of social support on depressive symptoms and cluster-specific PTSD symptoms, with consideration of displacement status. In a survey conducted 18 to 24 months after Hurricane Katrina, 810 adults exposed to the disaster reported the number of Katrina-related traumatic events experienced, perceived social support 2 months post-Katrina, and cluster-specific PTSD and depressive symptoms experienced since Katrina. Analyses assessed the moderating effects of social support and displacement and the conditional effects of displacement status. Social support significantly buffered the negative effect of Katrina-related traumatic events on depressive symptoms, B = -0.10, p = .001, and avoidance and arousal PTSD symptoms, B = -0.02, p = .035 and B = -0.02, p = .042, respectively. Three-way interactions were nonsignificant. Conditional effects indicated social support buffered development of depressive symptoms across all residents; however, the moderating effects of support on avoidance and arousal symptoms only appeared significant for nondisplaced residents. Results highlight the protective effects of disaster-related social support among nondisplaced individuals, and suggest displaced individuals may require more formal supports for PTSD symptom reduction following a natural disaster.

Invited Commentary: Agent-Based Models-Bias in the Face of Discovery.

Agent-based models (ABMs) have grown in popularity in epidemiologic applications, but the assumptions necessary for valid inference have only partially been articulated. In this issue, Murray et al. (Am J Epidemiol. 2017;186(2):131-142) provided a much-needed analysis of the consequence of some of these assumptions, comparing analysis using an ABM to a similar analysis using the parametric g-formula. In particular, their work focused on the biases that can arise in ABMs that use parameters drawn from distinct populations whose causal structures and baseline outcome risks differ. This demonstration of the quantitative issues that arise in transporting effects between populations has implications not only for ABMs but for all epidemiologic applications, because making use of epidemiologic results requires application beyond a study sample. Broadly, because health arises within complex, dynamic, and hierarchical systems, many research questions cannot be answered statistically without strong assumptions. It will require every tool in our store of methods to properly understand population dynamics if we wish to build an evidence base that is adequate for action. Murray et al.'s results provide insight into these assumptions that epidemiologists can use when selecting a modeling approach.

Measuring Childhood Adversity in Life Course Cardiovascular Research: A Systematic Review.

OBJECTIVE: Identifying the life course health effects of childhood adversity is a burgeoning area of research, particularly in relation to cardiovascular disease (CVD). However, adversity measurement varies widely across studies, which may hamper our ability to make comparisons across studies and identify mechanisms linking adversity to CVD. The purposes of this review are to summarize adversity measurement approaches in the context of CVD, identify gaps, and make recommendations for future research. METHODS: PubMed and PsycINFO searches were conducted through June 2016. Studies were selected if CVD end point or predisease risk markers were investigated in association with a measure of childhood adversity. Forty-three studies were reviewed. A meta-analysis was not conducted because of the variation in exposures and outcomes assessed. RESULTS: Adversity measurement was heterogeneous across studies. Metrics included different sets of adverse events, relational factors, and socioeconomic indicators. Thirty-seven percent measured childhood adversity prospectively, 23% examined a CVD end point, and 77% treated adversity as an unweighted summary score. Despite the heterogeneity in measurement, most studies found a positive association between childhood adversity and CVD risk, and the association seems to be dose-response. CONCLUSIONS: The literature on childhood adversity and CVD would benefit from improving consistency of measurement, using weighted adversity composites, modeling adversity trajectories over time, and considering socioeconomic status as an antecedent factor instead of a component part of an adversity score. We suggest conceptual and analytic strategies to enhance, refine, and replicate the observed association between childhood adversity and CVD risk.

The Transmission of Gun and Other Weapon-Involved Violence Within Social Networks.

Fatal and nonfatal injuries resulting from gun violence remain a persistent problem in the United States. The available research suggests that gun violence diffuses among people and across places through social relationships. Understanding the relationship between gun violence within social networks and individual gun violence risk is critical in preventing the spread of gun violence within populations. This systematic review examines the existing scientific evidence on the transmission of gun and other weapon-related violence in household, intimate partner, peer, and co-offending networks. Our review identified 16 studies published between 1996 and 2015 that suggest that exposure to a victim or perpetrator of violence in one's interpersonal relationships and social networks increases the risk of individual victimization and perpetration. Formal network analyses find high concentrations of gun violence in small networks and that exposure to gun violence in one's networks is highly correlated with one's own probability of being a gunshot victim. Physical violence by parents and weapon use by intimate partners also increase risk for victimization and perpetration. Additional work is needed to better characterize the mechanisms through which network exposures increase individual risk for violence and to evaluate interventions aimed at disrupting the spread of gun and other weapon violence in high-risk social networks.