A complex systems model of breast cancer etiology: The Paradigm II Model.

BACKGROUND: Complex systems models of breast cancer have previously focused on prediction of prognosis and clinical events for individual women. There is a need for understanding breast cancer at the population level for public health decision-making, for identifying gaps in epidemiologic knowledge and for the education of the public as to the complexity of this most common of cancers. METHODS AND FINDINGS: We developed an agent-based model of breast cancer for the women of the state of California using data from the U.S. Census, the California Health Interview Survey, the California Cancer Registry, the National Health and Nutrition Examination Survey and the literature. The model was implemented in the Julia programming language and R computing environment. The Paradigm II model development followed a transdisciplinary process with expertise from multiple relevant disciplinary experts from genetics to epidemiology and sociology with the goal of exploring both upstream determinants at the population level and pathophysiologic etiologic factors at the biologic level. The resulting model reproduces in a reasonable manner the overall age-specific incidence curve for the years 2008-2012 and incidence and relative risks due to specific risk factors such as BRCA1, polygenic risk, alcohol consumption, hormone therapy, breastfeeding, oral contraceptive use and scenarios for environmental toxin exposures. CONCLUSIONS: The Paradigm II model illustrates the role of multiple etiologic factors in breast cancer from domains of biology, behavior and the environment. The value of the model is in providing a virtual laboratory to evaluate a wide range of potential interventions into the social, environmental and behavioral determinants of breast cancer at the population level.

Trends and Variation in the Gap Between Current and Anticipated Life Satisfaction in the United States, 2008-2020.

Objectives. To describe national- and county-level trends and variation in a novel measure of hope. Methods. Using data from the Gallup National Health and Well-Being Index (n = 2 766 728), we summarized the difference between anticipated life satisfaction (ALS) and current life satisfaction (CLS), measured by the Cantril Self-Anchoring Scale, for each year from 2008 to 2020 and by county over two 5-year periods in the United States. Results. Across all years, there was a significant positive trend in the difference between ALS and CLS for the nation (P = .024), which remained positive but not significant when we excluded 2020. Maintenance of ALS with a decrease in CLS drove the 2020 increase. From 2008-2012 to 2013-2017, 14.5% of counties with 300 or more responses (n = 599) experienced an increase in the difference of more than 1 SD, whereas 13.9% experienced a more than 1 SD decrease. Fifty-two counties experienced decreases in ALS and CLS. Conclusions. Responding to trends in the gap between ALS and CLS at national and local levels is essential for the collective well-being of our nation, especially as we navigate and emerge from crisis.

Project Earthrise: Proceedings of the Ninth Annual Conference of inVIVO Planetary Health.

The "Earthrise" photograph, taken on the 1968 Apollo 8 mission, became one of the most significant images of the 20th Century. It triggered a profound shift in environmental awareness and the potential for human unity-inspiring the first Earth Day in 1970. Taking inspiration from these events 50 years later, we initiated Project Earthrise at our 2020 annual conference of inVIVO Planetary Health. This builds on the emergent concept of planetary health, which provides a shared narrative to integrate rich and diverse approaches from all aspects of society towards shared solutions to global challenges. The acute catastrophe of the COVID-19 pandemic has drawn greater attention to many other interconnected global health, environmental, social, spiritual, and economic problems that have been underappreciated or neglected for decades. This is accelerating opportunities for greater collaborative action, as many groups now focus on the necessity of a "Great Transition". While ambitious integrative efforts have never been more important, it is imperative to apply these with mutualistic value systems as a compass, as we seek to make wiser choices. Project Earthrise is our contribution to this important process. This underscores the imperative for creative ecological solutions to challenges in all systems, on all scales with advancing global urbanization in the digital age-for personal, environmental, economic and societal health alike. At the same time, our agenda seeks to equally consider our social and spiritual ecology as it does natural ecology. Revisiting the inspiration of "Earthrise", we welcome diverse perspectives from across all dimensions of the arts and the sciences, to explore novel solutions and new normative values. Building on academic rigor, we seek to place greater value on imagination, kindness and mutualism as we address our greatest challenges, for the health of people, places and planet.

Parental Alcohol Problems, Parental Divorce, and Type 2 Diabetes in Adulthood: A Longitudinal Prospective Cohort Study in Middle-Aged Men.

OBJECTIVE: Type 2 diabetes is a chronic disease and a serious global public health concern increasing both mortality and morbidity. Previous studies have found evidence for an association between early psychological stress and diabetes later in life. METHODS: This study examined the association between parental alcohol problems and parental divorce and the incidence of type 2 diabetes in Finnish men aged 42 to 61 years (n = 754) in a prospective setting. Information on parental alcohol problems and parental divorce was derived from school records and subjective experiences of the same events from self-rated questionnaires. The average follow-up time for the participants until the first type 2 diabetes diagnosis was 23.3 years (25th-75th percentile, 21.2-27.9 years). RESULTS: Cox regression analyses revealed that parental alcohol problems (hazard ratio = 3.09, 95% confidence interval = 1.38-6.88) were associated with an increased risk of type 2 diabetes during the follow-up, even after adjustment for age, marital status, education, Human Population Laboratory Depression Scale scores, smoking, alcohol consumption, body mass index, and serum high-sensitivity C-reactive protein. In a similar model, parental divorce (hazard ratio = 1.69, 95% confidence interval = 0.40-7.05) was not associated with an increased risk of type 2 diabetes during the follow-up. CONCLUSIONS: Our findings suggest that not all adverse childhood experiences contribute equally to the risk of type 2 diabetes. Parental alcohol problems, but not parental divorce, were associated with an increased risk of type 2 diabetes in men. These findings highlight the need for early interventions targeting parents with excessive alcohol consumption to reduce their offspring's risk of life-style-related disorders.

Current Practice for Cryptorchidism: Survey of Pediatric Urologists.

INTRODUCTION: We evaluated current practice patterns in the management and screening of cryptorchidism among pediatric urologists and compared them to the 2014 AUA (American Urological Association) guidelines on cryptorchidism. METHODS: A 14-question survey was disseminated to members of the SPU (Society for Pediatric Urology) to assess their current practice patterns. RESULTS: There were 187 responses (38.4% response rate) with a notable bimodal distribution in respondent practice years, with 39.3% in practice for 10 years or less and 41.4% in practice for more than 20 years. Despite guideline recommendations against the use of ultrasound, the majority of respondents will use it in cases of obesity or bilateral nonpalpable testes (greater than 50%). In the evaluation for bilateral nonpalpable testes most respondents (greater than 80%) perform an endocrine workup. Nevertheless, 55.1% will proceed with surgical exploration even if the workup indicates absence of testicular tissue. Subgroup analysis revealed those in practice for 10 years or less vs greater than 20 years were more likely to perform 2-stage Fowler-Stephens in cases of short vessels (80.8% vs 58.1%) and to perform transscrotal orchiopexy in cases amenable to that approach (79.5% vs 52%). If examination under anesthesia reveals the testicle in the scrotum, 46.5% still perform orchiopexy, citing concerns the testicle will ascend or parental concerns about the diagnosis. CONCLUSIONS: Based on the responses some discordance exists between practice patterns and guideline recommendations. Although surgery may be avoided with endocrine evaluation for suspected anorchia, many respondents will still perform exploration. The evaluation, management and surgical approach in cryptorchidism may be influenced by years in practice.

Socioeconomic position, John Henryism, and incidence of acute myocardial infarction in Finnish men.

Previous cross-sectional studies examining whether John Henryism (JH), or high-effort coping with socioeconomic adversity, potentiates the inverse association between socioeconomic position (SEP) and cardiovascular health have focused mainly on hypertension in African Americans. We conducted the first longitudinal test of this hypothesis on incident acute myocardial infarction (AMI) using data from the Kuopio Ischemic Heart Disease Risk Factor Study in Finland (N = 1405 men, 42-60 years). We hypothesized that the expected inverse gradient between SEP and AMI risk would be stronger for men scoring high on JH than for those scoring low. John Henryism was measured by a Finnish version of the JH Scale for Active Coping. Four different measures of SEP were used: childhood SEP, education, income, and occupation. AMI hazard ratios (HR) by SEP and JH were estimated using COX proportional hazard models, before and after adjustment for study covariates. 205 cases of AMI occurred over a median of 14.9 years. Men employed in lower rank (farmer, blue-collar) occupations who scored high on JH had significantly higher age-adjusted risks of AMI than men in higher rank (white-collar) occupations (HR = 3.14, 95% CI: 1.65-5.98 for blue collar; HR = 2.33, 95% CI: 1.04-5.22 for farmers) who also scored high on JH. No socioeconomic differences in AMI were observed for men who scored low on JH (HR = 1.36, 95% CI: 0.74-2.47 for blue collar; HR = 0.93, 95% CI: 0.59-1.48 for farmers; p = 0.002 for the SEP × JH interaction). These findings persisted after adjustment for sociodemographic, behavioral, and biological factors. Results for other SEP measures were in the same direction, but did not reach statistical significance. Repetitive high-effort coping with adversity (John Henryism) was independently associated with increased risk for AMI in Finnish men, underscoring the potential relevance of the John Henryism hypothesis to CVD outcomes other than hypertension and to populations other than African Americans.

Neighbourhood food, physical activity, and educational environments and black/white disparities in obesity: a complex systems simulation analysis.

BACKGROUND: Multiple approaches that can contribute to reducing obesity have been proposed. These policies may share overlapping pathways, and may have unanticipated consequences, creating considerable complexity. Aiming to illuminate the use of agent-based models to explore the consequences of key policies, this paper simulates the effects of increasing neighbourhood availability of good food stores, physical activity infrastructure and higher school quality on the reduction of black/white disparities in body mass index (BMI) in the USA. METHODS: We used an agent-based model, with parameters derived from the empirical literature, which included individual and neighbourhood characteristics over the life course as determinants of behaviours thought to impact BMI. We systematically varied the strength of the 3 policy interventions, examining the impact of 125 different policy scenarios on black/white BMI disparities. RESULTS: In the absence of any of these policies, black/white BMI disparities generally increased over time. However, we found that some combinations of these policies resulted in reductions in BMI, yielding decreases in the black/white BMI disparity as large as a 90%. CONCLUSIONS: Within the structure of relationships captured in this simulation model, there is support for the further use of agent-based simulation models to explore upstream policies as plausible candidates for the reduction of black/white disparities in BMI. These results highlight the potential insights into important public health problems, such as obesity, that can come from uniting the systems science approach with policy analysis.

Hypospadias repair with onlay preputial graft: a 25-year experience with long-term follow-up.

OBJECTIVE: To evaluate the long-term outcomes of hypospadias repair using an onlay preputial graft. PATIENTS AND METHODS: Patient records from 1989 to 2013 were retrospectively reviewed. One surgeon performed all cases and surgical technique was the same for all patients. RESULTS: There were 62 patients in the cohort, with a mean (range) follow-up of 47.4 (1-185) months. The meatal location was separated into distal (one patient), midshaft (19) and proximal (42). In all, 22 (35.5%) patients had complications. There were three main types of complications, including meatal stenosis in three (4.8%), stricture in three (4.8%), and fistula in 21 (33.9%). The mean (range) timing of presentation with a complication after surgery was 24.9 (1-127) months. In all, 54.5% of the patients with complications presented at ≥1 year after the initial surgery and 31.8% presented at ≥3 years. On univariable analysis age at the time of surgery, length of the graft, presence of chordee or meatal location (proximal or midshaft) did not predict a complication. The width of the graft was associated with a complication, with each 1 mm increase in width decreasing the odds of a complication by 56%. On multivariable analysis width remained statistically significant (odds ratio 0.44, 95% confidence interval 0.230-0.840; P = 0.013) for predicting a complication. CONCLUSION: Hypospadias repair with onlay preputial graft is an option for single-stage repair, especially in cases of proximal hypospadias or where the urethral plate width and/or the glanular groove is insufficient for other types of repair. Compared with flaps, the use of grafts may decrease the risk of penile torsion and prevent less bulk around the urethra, improving skin and glans closure.