Cardiovascular impact of near complete estrogen deprivation in premenopausal women with breast cancer: The CROWN study.

Survival with operable breast cancer has improved markedly in recent decades, however, treatment-related cardiovascular toxicities threaten to offset these gains. Ovarian function suppression paired with aromatase inhibition, for premenopausal women with hormone receptor (HR)-positive breast cancer, is a newer widely adopted therapy with the potential for significant long-term cardiovascular toxicity. Abrupt estrogen deprivation for non-cancer reasons is associated with accelerated coronary artery disease. Women with breast cancer treated with aromatase inhibition in addition to ovarian function suppression experience a dual hit with regards to estrogen exposure. The CaRdiac Outcomes With Near-complete estrogen deprivation (CROWN) study seeks to understand the early, subclinical natural history of cardiovascular compromise in young women undergoing near-complete estrogen deprivation (NCED) therapy. It is critical to understand the early subclinical development of cardiovascular disease to identify a window for therapeutic intervention before overt cardiovascular events occur. This three-site regional study (Atrium Health Wake Forest, Duke, and Virginia Commonwealth University) uses serial stress cardiac magnetic resonance (CMR) imaging and cardiac computed tomography angiography (CCTA) obtained during the initial two years of NCED therapy to study myocardial prefusion reserve (MPR), large cardiovascular vessel changes, left ventricular function, and other cardiovascular parameters. The CROWN cohort will consist of 90 premenopausal women with breast cancer, 67 with HR-positive disease receiving NCED and 23 comparators with HR-negative disease. Participants will undergo three annual CMR scans and 2 CCTA scans during the 2-year study period. After initial activation hurdles, accrual has been brisk, and the study is expected to complete accrual in December 2024. Efforts are in place to encourage participant retention with the study primary outcome, change in MPR between the two groups, to be reported in 2026 to 2027. The results of this study will enable premenopausal women with breast cancer to balance the health burdens of cancer at a young age and treatment-related cardiovascular morbidity. Finally, the tools developed here can be utilized to study cardiovascular risk across a range of cancer types and cancer therapies with the ultimate goals of both developing generalizable risk stratification tools as well as validating interventions which prevent overt cardiovascular compromise.

Treatment Options for Brain Metastases.

OPINION STATEMENT: Therapies for brain metastasis continue to evolve as the life expectancies for patients have continued to prolong. Novel advances include the use of improved technology for radiation delivery, surgical guidance, and response assessment, along with systemic therapies that can pass through the blood brain barrier. With increasing complexity of treatments and the increased need for salvage treatments, multi-disciplinary management has become significantly more important.

Cumulative stressors reduce the self-regulating capacity of coastal ecosystems.

Marine ecosystems are prone to tipping points, particularly in coastal zones where dramatic changes are associated with interactions between cumulative stressors (e.g., shellfish harvesting, eutrophication and sediment inputs) and ecosystem functions. A common feature of many degraded estuaries is elevated turbidity that reduces incident light to the seafloor, resulting from multiple factors including changes in sediment loading, sea-level rise and increased water column algal biomass. To determine whether cumulative effects of elevated turbidity may result in marked changes in the interactions between ecosystem components driving nutrient processing, we conducted a large-scale experiment manipulating sediment nitrogen concentrations in 15 estuaries across a national-scale gradient in incident light at the seafloor. We identified a threshold in incident light that was related to distinct changes in the ecosystem interaction networks (EIN) that drive nutrient processing. Above this threshold, network connectivity was high with clear mechanistic links to denitrification and the role of large shellfish in nitrogen processing. The EIN analyses revealed interacting stressors resulting in a decoupling of ecosystem processes in turbid estuaries with a lower capacity to denitrify and process nitrogen. This suggests that, as turbidity increases with sediment load, coastal areas can be more vulnerable to eutrophication. The identified interactions between light, nutrient processing and the abundance of large shellfish emphasizes the importance of actions that seek to manage multiple stressors and conserve or enhance shellfish abundance, rather than actions focusing on limiting a single stressor.

An Exploratory Study of the Prosecution of Fatal Child Maltreatment: Criminal Charges Filed Against Presumed Perpetrators in the United States in 2017.

In the United States child maltreatment fatalities (CMFs) do not usually meet the standard for manslaughter or murder, resulting in convictions of lesser crimes and little jail time. This exploratory study examined the charges brought against suspected CMF perpetrators in 2017. Univariate and bivariate analyses were conducted using data obtained from the Nexis Uni newspaper database, that has over 40,000 high quality media sources, for the year 2017. We found that the most frequently used charges were endangering the welfare of a child and murder, the former of which was more related to neglect-deaths and the latter to physical abuse-deaths. There was no difference between charges for male and female perpetrators. Practical implications for research, policy, and practice are discussed.

Mapping the estuarine ecosystem service of pollutant removal using empirically validated boosted regression tree models.

Humans rely on the natural environment and benefit from the goods and services provided by natural ecosystems. Quantification and mapping of ecosystem services (ES) is required to better protect valued ES benefits under pressure from anthropogenic activities. The removal of excess nitrogen, a recognized catchment-derived pollutant, by biota in estuarine soft sediments is an important ES that potentially ameliorates the development of eutrophication symptoms. Here, we quantified estuarine benthic sediment characteristics and denitrification enzyme activity (DEA), a proxy of inorganic N removal, at 109 sites in four estuaries to develop a general ("global") model for predicting DEA. Our initial global model for linking DEA and environmental characteristics had good explanatory power, with sediment mud content having the strongest influence on DEA (60%), followed by sediment organic matter content (≈35%) and sediment chlorophyll a content (≈5%). Predicted and empirically evaluated DEA values in a fifth estuary (Whitford, n = 90 validation sites) were positively correlated (r = 0.77), and the fit and certainty of the model (based on two types of uncertainty measures) increased further after the validation sites were incorporated into it. The model tended to underpredict DEA at the upper end of its range (at the muddier, more organically enriched sites), and the relative roles of the three environmental predictors differed in Whitford relative to the four previously sampled estuaries (reducing the explained deviance relative to the initial global model). Our detailed quantification of DEA and methodological description for producing empirically validated maps, complete with uncertainty information, represents an important first step in the construction of nutrient pollution removal ES maps for use in coastal marine spatial management. This technique can likely be adapted to map other ecosystem functions and ES proxies worldwide.

Male Victims of Female-Perpetrated Partner Violence: A Qualitative Analysis of Men's Experiences, the Impact of Violence, and Perceptions of Their Worth.

There has been a recent increase in the amount of research on male victims of female-perpetrated partner violence (PV) but research needs to be conducted to understand how the patterns of abuse persist in these relationships. In the current study, the experiences of 59 male PV victims in the USA, recruited through online advertisements in professional networks and websites (e.g., agencies that specialize in male victims of PV), were explored through a thematic analysis. Analyses suggested that the help seeking process of male PV victims is complex and heterogeneous and can often lead to further negative consequences due to various structural, cultural, social, and organizational factors. The findings also highlight the potential societal issues that male victims perceived as contributing to male victimization and lack of available resources for them. The results are discussed in terms of its implications for agencies, service providers, and general societal attitudes that are relevant to raising awareness about this phenomenon.

An exploratory analysis of the notable activities of U.S. child death review teams.

Child death review teams (CDRTs) focus on the prevention of child deaths, but a comprehensive understanding of their activities is lacking. This exploratory study addressed this gap through a qualitative analysis of reported CDRT activities using the "spectrum of prevention" framework. We collected state-level CDRT reports published 2006-2015, recorded their activities (n = 193), and coded them using the "spectrum of prevention" framework. The highest percentage (64.2%) of activities was categorized under "fostering coalitions and networks." We recommend that CDRTs increase their reporting of activities so others can better understand their potential impact on preventing child deaths.

Influence of Intimate Terrorism, Situational Couple Violence, and Mutual Violent Control on Male Victims.

The goal of the current study is to test - among samples of men - some previous findings relative to Johnson's (2008) typology of partner violence (PV). Among samples of exclusively women, Johnson has found that the frequency and severity of PV - and victims' mental health - are worse for female victims of intimate terrorism (IT) than of situational couple violence (SCV). However, such findings have rarely been tested in male victims of PV. Furthermore, although Johnson posits that mutual violent control (MVC) is relatively rare, other research suggests that it is about as common as IT and may be associated with worse PV and health. We examined the relative frequency and severity of various forms of PV, and the relative health and mental health between men who (a) experienced IT versus SCV, and (b) experienced IT versus MVC. Our two samples were 611 men who sought help for PV victimization and 1,601 men from a population-based sample. Our analyses showed that across samples, men who were victims of IT had significantly worse mental health than men who experienced SCV, and IT victims experienced more severe and frequent PV, including physical, sexual, and non-physical forms of PV. Male victims of IT had worse mental and physical health than either men who perpetrated IT or experienced MVC, but men involved in MVC were involved in relationships with more types of PV than either male IT perpetrators or victims. Results are discussed in terms of their implications for Johnson's typology, future research, and service providers.

Changes in the location of biodiversity-ecosystem function hot spots across the seafloor landscape with increasing sediment nutrient loading.

Declining biodiversity and loss of ecosystem function threatens the ability of habitats to contribute ecosystem services. However, the form of the relationship between biodiversity and ecosystem function (BEF) and how relationships change with environmental change is poorly understood. This limits our ability to predict the consequences of biodiversity loss on ecosystem function, particularly in real-world marine ecosystems that are species rich, and where multiple ecosystem functions are represented by multiple indicators. We investigated spatial variation in BEF relationships across a 300 000 m2 intertidal sandflat by nesting experimental manipulations of sediment pore water nitrogen concentration into sites with contrasting macrobenthic community composition. Our results highlight the significance of many different elements of biodiversity associated with environmental characteristics, community structure, functional diversity, ecological traits or particular species (ecosystem engineers) to important functions of coastal marine sediments (benthic oxygen consumption, ammonium pore water concentrations and flux across the sediment-water interface). Using the BEF relationships developed from our experiment, we demonstrate patchiness across a landscape in functional performance and the potential for changes in the location of functional hot and cold spots with increasing nutrient loading that have important implications for mapping and predicating change in functionality and the concomitant delivery of ecosystem services.

Sexual Aggression Experiences Among Male Victims of Physical Partner Violence: Prevalence, Severity, and Health Correlates for Male Victims and Their Children.

Although research has documented the prevalence and health correlates of sexual aggression among women who have experienced severe partner violence (PV), no research has documented the parallel issues among male victims of severe PV. Research also suggests that children of female victims of both physical and sexual PV have worse mental health than children of female victims of physical PV only, but no research has assessed the mental health of children whose fathers experienced both physical and sexual PV. We surveyed 611 men who experienced physical PV from their female partners and sought help. We assessed the types and extent of various forms of PV, the men's mental and physical health, and the mental health of their oldest child. Results showed that almost half of the men experienced sexual aggression in their relationship, and 28 % severe sexual aggression. Increasing levels of severity of sexual aggression victimization was associated with greater prevalence and types of other forms of PV. In addition, greater levels of severity of sexual aggression victimization among the men was significantly associated with depression symptoms, post-traumatic stress disorder symptoms, physical health symptoms, and poor health, and attention deficit and affective symptoms among their children. These associations held after controlling for demographics and other violence and trauma exposure. Discussion focused on the importance of broadening our conceptualization of PV against men by women to include sexual aggression as well.

The mental health of male victims and their children affected by legal and administrative partner aggression.

The authors recently developed a psychometrically valid measure of legal and administrative (LA) intimate partner violence (IPV) victimization (Hines, Douglas, & Berger, 2014). The current article explores the impact of actual and threatened LA aggression on the mental health of male physical IPV victims and their children. In the current study, a sample of 611 men who sought help after experiencing physical IPV from their female partners completed a survey assessing the types and extent of IPV that occurred in their relationship, including LA aggression, their own mental health outcomes, and the mental health of their oldest child. A series of OLS regressions indicated that after controlling for covariates, actual LA aggression was associated with more symptoms of PTSD and depression in male victims, and that both threatened and actual LA aggression were associated with higher levels of affective and oppositional defiant symptoms in the men's school age children. The current findings suggest that it is important to screen couples for the presence of LA aggression and male partners and their children should be referred for mental health treatment if LA aggression is occurring in the relationship. Aggr. Behav. 42:346-361, 2016. © 2015 Wiley Periodicals, Inc.

Relative Influence of Various Forms of Partner Violence on the Health of Male Victims: Study of a Helpseeking Sample.

Researchers argue that partner violence (PV) is a multidimensional and heterogeneous phenomenon that needs to be measured in multiple ways to capture its range, extent, severity, and potential consequences. Several large scale, population-based studies show that about 40%-50% of PV victims in a one-year time period are men; this finding is consistent whether the study focuses on physical PV or a combination of several forms of PV. However, no one has investigated how the different forms of PV contribute to male victims' poor mental health, although research suggests that physical, psychological, and sexual PV contribute unique variance to female victims' poor health. The current study investigated how six forms of PV - physical, sexual, severe psychological, controlling, legal/administrative (LA), and injury - contributed to the poor health of 611 male victims of PV who sought help. We found that the combination of PV contributed significant unique variance to men's depression, post-traumatic stress disorder, physical health, and poor health symptoms, after controlling for demographic and other traumatic experiences. The common variance among the forms of PV victimization was the strongest contributor to victims' poor health; the types of PV that contributed the most unique variance were controlling behaviors, LA aggression, sexual aggression, and injury. Discussion focuses on the research and practice implications of these findings.

Children Whose Fathers Seek Help for Partner Violence Victimization: Descriptive Characteristics and Their Behavioral Health as Compared to a Population-Based Sample.

Children whose parents seek help for partner violence (PV) victimization are at an increased risk for internalizing and externalizing behavioral health problems. The literature has examined this phenomenon primarily among children of battered women. This study examines the sociodemographic characteristics and behavioral health of children whose fathers have sought help for PV victimization and compares them to children of men from the general population. Children whose fathers sought help for PV victimization were less likely to live with their fathers. Bivariate analyses showed that children of male victims had elevated scores in Diagnostic and Statistical Manual of Mental Disorders (DSM)-related areas of behavioral health; many of these findings remain in multivariate analyses, especially among older children. The implications of the results are discussed for researchers and social service practitioners.

A self-report measure of legal and administrative aggression within intimate relationships.

Although experts agree that intimate partner violence (IPV) is a multidimensional phenomenon comprised of both physical and non-physical acts, there is no measure of legal and administrative (LA) forms of IPV. LA aggression is when one partner manipulates the legal and other administrative systems to the detriment of his/her partner. Our measure was developed using the qualitative literature on male IPV victims' experiences. We tested the reliability and validity of our LA aggression measure on two samples of men: 611 men who sustained IPV and sought help, and 1,601 men in a population-based sample. Construct validity of the victimization scale was supported through factor analyses, correlations with other forms of IPV victimization, and comparisons of the rates of LA aggression between the two samples; reliability was established through Cronbach's alpha. Evidence for the validity and reliability of the perpetration scale was mixed and therefore needs further analyses and revisions before we can recommend its use in empirical work. There is initial support for the victimization scale as a valid and reliable measure of LA aggression victimization among men, but work is needed using women's victimization's experiences to establish reliability and validity of this measure for women. An LA aggression measure should be developed using LGBTQ victims' experiences, and for couples who are well into the divorce and child custody legal process. Legal personnel and practitioners should be educated on this form of IPV so that they can appropriately work with clients who have been victimized or perpetrate LA aggression.

A longitudinal, multilevel analysis of homicide against children aged 0-9 years using state-level characteristics: 1979-2007.

Annually, over a thousand children are the victims of homicide in the United States Homicide among younger children, 0-9 years of age, is usually perpetrated by parents and caregivers. Researchers neither have tracked changes in the homicide rate among young children over time nor have they used theory to understand what factors may drive these changes. In this analysis of state-level data, we used longitudinal growth modeling and ecological theory to examine changes in homicide rate against children aged 0-9 years from 1979 to 2007. Our results indicate that states are relatively consistent, over time, in their homicide rates. Furthermore, a cultural context of criminal and risky behavior is positively associated with homicide against children. We discuss implications for future research and prevention.

Climatic, oceanic, freshwater, and local environmental drivers of New Zealand estuarine macroinvertebrates.

Understanding the responses of organisms to different environmental drivers is critical for improving ecosystem management and conservation. Estuarine ecosystems are under pressure from multiple anthropogenic stressors (e.g. increasing sediment and nutrient loads, pollution, climate change) that are affecting the functions and services these ecosystems provide. Here, we used long-term estuarine benthic invertebrate monitoring data (∼30 year time-series) to evaluate the responses of macrobenthic invertebrate communities and indicator species to climatic, oceanic, freshwater, and local environmental drivers in New Zealand estuaries. We aimed to improve our ability to predict ecosystem change and understand the effects of multiple environment drivers on benthic communities. Our analyses showed that the abundance and richness of macrobenthic fauna and four indicator taxa (bivalves known to have differing tolerances to sediment mud content: Austrovenus stutchburyi, Macomona liliana, Theora lubrica, and Arthritica bifurca) responded to unique combinations of multiple environmental drivers across sites and times. Macrobenthic responses were highly mixed (i.e., positive and negative) and site-dependent. We also show that responses of macrobenthic fauna were lagged and most strongly related to climatic and oceanic drivers. The way the macrobenthos responded has implications for predicting and understanding the ecological consequences of a rapidly changing environment and how we conserve and manage coastal ecosystems.

Impact of Anti-Estrogen Therapy on Early Cardiovascular Referrals, Tests and Medications in Premenopausal Women with Operable Breast Cancer.

INTRODUCTION: Premenopausal women with high-risk hormone receptor (HR)-positive breast cancer often receive ovarian function suppression (OFS) and anti-estrogen therapy which induces near complete estrogen deprivation (NCED). This treatment improves recurrence-free survival but may increase cardiovascular risk. We sought to identify patterns of cardiovascular care and outcomes in premenopausal women with operable breast cancer. METHODS: Premenopausal women ≤ 50 years of age with stage I-III HR-positive or triple negative breast cancer (TNBC) were identified by retrospective review. We categorized women into 3 groups based on anti-estrogen therapy approach: NCED (HR + OFS), anti-estrogen therapy without OFS (HRnoOFS), and no anti-estrogen therapy (TNBC). Baseline characteristics, post-diagnosis cardiovascular events and cardiovascular actions (tests, referrals and medications) were recorded. Categorical variables were compared among the groups using chi-square and Fisher's exact tests; continuous outcomes were compared using ANOVA. RESULTS: 82, 83, and 52 women were identified in the HR + OFS, HRnoOFS, and TNBC groups respectively; mean follow-up was 5.0 years. Mean number of cardiovascular actions per year were highest in the HR + OFS group compared with HRnoOFS and TNBC groups (0.35 vs. 0.20 and 0.27, respectively; P = .036). The HR + OFS group had significantly more referrals and tests per year than the other groups. Cardiovascular medication initiation did not differ among groups. CONCLUSIONS: In this early follow-up period, there were meaningful numbers of cardiovascular actions, with women on NCED experiencing the most per year. Future work should seek to further understand the impact of anti-estrogen therapy on the cardiovascular health of premenopausal women and test strategies to mitigate cardiotoxicity.

Predicting potentially life-threatening partner violence by women toward men: a preliminary analysis.

Researchers have documented predictors of life-threatening violence by men toward women. Little research has assessed predictors of life-threatening violence toward men by women. We investigated such predictors in a sample of 302 men who sustained partner violence (PV) and sought help. Based on prior research on women as victims, we examined the following as potential predictors: demographics of the participant, his female partner, and their relationship; relationship power imbalances; her use of various forms of PV; her alcohol/drug use; his use of various forms of PV; his mental health and substance abuse; and his help seeking and social support. Logistic regressions indicated that there were 2 consistent predictors: the female partner's frequency of physical PV and the number of sources from which the participant sought help.

Metaplastic Breast Cancer: Current Understanding and Future Directions.

Metaplastic breast cancers (MBC) encompass a group of highly heterogeneous tumors which share the ability to differentiate into squamous, mesenchymal or neuroectodermal components. While often termed rare breast tumors, given the relatively high prevalence of breast cancer, they are seen with some frequency. Depending upon the definition applied, MBC represents 0.2% to 1% of breast cancers diagnosed in the United States. Less is known about the epidemiology of MBC globally, though a growing number of reports are providing information on this. These tumors are often more advanced at presentation relative to breast cancer broadly. While more indolent subtypes exist, the majority of MBC subtypes are associated with inferior survival. MBC is most commonly of triple-negative phenotype. In less common hormone receptor positive MBCs, hormone receptor status appears not to be prognostic. In contrast, relatively rare HER2-positive MBCs are associated with superior outcomes. Multiple potentially targetable molecular features are overrepresented in MBC including DNA repair deficiency signatures and PIK3/AKT/mTOR and WNT pathways alterations. Data on the prevalence of targets for novel antibody-drug conjugates is also emerging. While chemotherapy appears to be less active in MBC than in other breast cancer subtypes, efficacy is seen in some MBCs. Disease-specific trials, as well as reports of exceptional responses, may provide clues for novel approaches to this often hard-to-treat breast cancer. Strategies which harness newer research tools, such as large data and artificial intelligence hold the promise of overcoming historic barriers to the study of uncommon tumors and could markedly advance disease-specific understanding in MBC.

Alcohol and drug abuse in men who sustain intimate partner violence.

Extensive work has documented an association between sustaining intimate partner violence (IPV) and alcohol/drug abuse among women, yet little research has documented the same association in men, even though men comprise 25-50% of all IPV victims in a given year. This study investigates the associations among sustaining IPV and alcohol/drug abuse among both a clinical and community sample of men. The clinical sample is comprised of 302 men who sustained intimate terrorism-a form of IPV that is characterized by much violence and controlling behavior-from their female partners and sought help. The community sample is composed of 520 men, 16% of whom sustained common couple violence, a lower level of more minor reciprocal IPV. Analyses showed that among both groups of men who sustained IPV, the prevalence and frequency of alcohol/drug abuse was significantly higher than in men who did not sustain IPV. However, a dose-response relationship between sustaining IPV and alcohol/drug abuse was found only among men in the community sample. Path modeling showed that, for the community sample, the best fitting models were ones that showed that the alcohol/drug abuse predicted IPV victimization, an association that was fully mediated by their use of IPV.