Optimal-order exit point bounds in exponential last-passage percolation via the coupling technique

We develop a new probabilistic method for deriving deviation estimates in directed planar polymer and percolation models. The key estimates are for exit points of geodesics as they cross transversal down-right boundaries. These bounds are of optimal cubic-exponential order. We derive them in the context of last-passage percolation with exponential weights with near-stationary boundary conditions. As a result, the probabilistic coupling method is empowered to treat a variety of problems optimally, which could previously be achieved only via inputs from integrable probability. As applications in the bulk setting, we obtain upper bounds of cubic-exponential order for transversal fluctuations of geodesics, and cube-root upper bounds with a logarithmic correction for distributional Busemann limits and competition interface limits. Several other applications are already in the literature.Comment: Accepted version. Two main corrections: Added to Prop. 3.6 a missing assumption that was used in its proof. (The z-parameter must be close to zeta). Also added a related assumption to Thm. 4.4(b) (previously Prop. C.1), which relies on Prop. 3.6. Some further minor corrections and edits. Slightly improved Thm. 3.4 and Prop. B.6. Significantly revised introduction. New reference

Structural Racism and the Workplace: Impacts of Racial Diversity and Segregation on Cardiovascular Mortality in the United Autoworkers-General Motors Cohort

The main objective of this dissertation was to investigate the cardiovascular disease (CVD) consequences of structural racism operating implicitly as discriminatory employment and labor policies and practices. Public health interventions targeting proximal risk factors such as health behavior have effectively reduced overall morbidity and mortality; yet, disparities in CVD mortality between Black and white populations persist even with a focus on working populations, which would presumably have similar baseline education, health, and healthcare access within skill levels. The American Heart Association has stated that structural racism is a fundamental cause of disparities in CVD risk as it creates mutually reinforcing systems of unequal distribution of wealth, resources, opportunities, and power. First, we provide a background on the relationship between structural racism and cardiovascular health wherein ongoing interactions between macrosystems and institutions constrain the opportunities, resources, and power of socially racialized groups. This functions to prevent the elimination of Black-white cardiovascular health gaps. In the first chapter, we make explicit how structural racism is posited to function through the workplace in the form of labor and employment organizational practices and norms that impact CVD mortality. Next, we assess structural racism’s influence on workforce policies and practices, particularly workplace racial diversity, which may present upstream targets for assessing and reducing racial health disparities in CVD. We evaluate whether a more racially balanced workforce would be protective against CVD mortality in a retrospective study of nearly 40,000 hourly Michigan autoworkers. We found that there was a protective effect of increasing exposure to racial diversity that was strongest and most consistent among Black workers. In this first chapter, our findings provided evidence that workplace practices encouraging diverse hiring and retention have the potential to improve all workers’ health, particularly the socially racialized groups in that workforce. Work as a social determinant of cardiovascular health and workplace exposures to particulate matter both remain understudied among Black working populations. In the next chapter, we aimed to assess the risk of CVD mortality among Black autoworkers from the United Autoworkers – General Motors (GM) cohort study under several hypothetical scenarios: increasing exposure to workplace racial diversity, reduced metalworking fluid exposures, and both. Using longitudinal data from Black workers from the Detroit GM plant, we applied the parametric g-formula to assess the risk of CVD mortality under hypothetical scenarios with set values for plantwide racial diversity, and selected exposure limits for metalworking fluid, separately and jointly. Our findings were consistent with the hypothesis that interventions to increase racial diversity and decrease metalworking fluid would reduce CVD mortality risk. Our study underscored the importance of a racially diverse workplace in addition to reducing occupational hazard concerns for the prevention of CVD deaths among racialized populations. Structural racism not only influences racial diversity, but also the ongoing racial segregation of Black Americans which has been associated with several cardiovascular outcomes. In recent decades, racial segregation has focused almost exclusively on measures of dissimilarity in residential spaces; however, little research has explored segregation beyond the residence. We present an analysis on the occupational structures and organization of work by examining the impact of job-based racial segregation and job mobility. This analysis used the index of dissimilarity to measure segregation and estimated exposure to cumulative job trajectories. We found that the relationship between increasing segregation and CVD mortality risk was highest among Black workers with lower job mobility. Black workers with higher job trajectories also experienced the harmful impacts of racial segregation, though at a lower magnitude. Among white workers, increasing racial segregation was harmful only for those with higher job mobility. Importantly, the higher-grade job assignments also have the most exposure to the GM occupational hazard of interest, metalworking fluid. Thus making our interaction between segregation and job mobility a cruicial method which can isolate pathways from segregation to CVD mortality via occupational hazards and psychosocial stress. Our findings provided evidence that workplace racial segregation may increase CVD mortality risk among Black workers, regardless of their career growth, and that addressing workplace racial segregation in concert with increasing opportunities for job mobility may be important to improving the long-term health of racialized working populations. The hypotheses addressed in this dissertation are of public health importance considering the persistent racial disparities in CVD mortality and the gaps in the literature regarding the long-term health impacts of structural racism in the workplace. These studies provide information on the relationships between racial discrimination, occupational hazards, and CVD mortality, adding to the scientific literature that informs workplace policies and practices that aim to reduce racial disparities in preventable chronic disease

KEYNOTE-859: a Phase III study of pembrolizumab plus chemotherapy in gastric/gastroesophageal junction adenocarcinoma

Adenocarcinoma; Gastroesophageal junction cancer; PembrolizumabAdenocarcinoma; Cáncer de la unión gastroesofágica; PembrolizumabAdenocarcinoma; Càncer de la unió gastroesofàgica; PembrolizumabCurrent guidelines recommend two-drug cytotoxic chemotherapy with a fluoropyrimidine (fluorouracil or capecitabine) and a platinum-based agent (oxaliplatin or cisplatin) as first-line treatment for advanced gastric cancer. Pembrolizumab monotherapy has demonstrated durable antitumor activity in patients with advanced programmed death ligand 1-positive (combined positive score ≥1) gastric/gastroesophageal junction adenocarcinoma. Accumulating evidence indicates that combining pembrolizumab with standard-of-care chemotherapy for the treatment of advanced or metastatic cancer improves clinical outcomes. We describe the rationale for and the design of the randomized, double-blind, placebo-controlled, Phase III KEYNOTE-859 study, which is investigating pembrolizumab in combination with chemotherapy as first-line treatment for patients with human epidermal growth factor receptor 2-negative advanced unresectable or metastatic gastric/gastroesophageal junction adenocarcinoma. The planned sample size is 1542 patients, and the primary end point is overall survival