The spatial structure of an evolving population affects which mutations become fixed. Some structures amplify selection, increasing the likelihood that beneficial mutations become fixed while deleterious mutations do not. Other structures suppress selection, reducing the effect of fitness differences and increasing the role of random chance. This phenomenon can be modeled by representing spatial structure as a graph, with individuals occupying vertices. Births and deaths occur stochastically, according to a specified update rule. We study death-Birth updating: An individual is chosen to die and then its neighbors compete to reproduce into the vacant spot. Previous numerical experiments suggested that amplifiers of selection for this process are either rare or nonexistent. We introduce a perturbative method for this problem for weak selection regime, meaning that mutations have small fitness effects. We show that fixation probability under weak selection can be calculated in terms of the coalescence times of random 1 arXiv:1906.01036v1 [q-bio.PE] 3 Jun 2019 walks. This result leads naturally to a new definition of effective population size. Using this and other methods, we uncover the first known examples of transient amplifiers of selection (graphs that amplify selection for a particular range of fitness values) for the death-Birth process. We also exhibit new families of "reducers of fixation", which decrease the fixation probability of all mutations, whether beneficial or deleterious.
6557 Background: Recent advances in oncology treatment present an expanding spectrum of cancer-treatment-related emergencies.Many aspects of healthcare utilization, specifically emergency department (ED) visits, are not well studied in this population. The purpose of this study is to determine (1) what proportion of cancer patients visit the ED with an oncology drug-related side effect and are admitted and (2) what factors impact the probability of inpatient admission among these patients. Methods: This study evaluated ED visits by adult patients undergoing active drug treatment for cancer insured by a large commercial and Medicare health plan in the United States between January 1, 2018, and September 30, 2019. Among cancer-related ED visits, logistic regression was used to determine the marginal effect of demographic and clinical characteristics of patients on acute inpatient admission. Results: There were 39,921 total ED visits among patients undergoing drug treatment for cancer; of these, 76% presented with an oncology drug-related side-effect. 36% of all ED visits resulted in admission, 5% resulted in an observation stay. After adjusting, age was not a significant predictor of inpatient admission. Being male (p < 0.01) and living in urban (p < 0.01) or suburban (p < 0.01) zip codes significantly increased the likelihood of admission. Patients with colorectal (p = 0.019), gastrointestinal (p < 0.01), blood (p < 0.01), lung (p < 0.01), metastatic (p < 0.01) cancers, or Hodgkin’s lymphoma (p < 0.01) had significantly increased risk of admission. Patients with prostate (p < 0.01) cancer had a significantly reduced risk of admission. The primary complaint upon presentation to the ED was the most important predictor of inpatient admission; sepsis, pneumonia, medical complications, white cell disorders, metastatic cancer, and fractures were all associated with a significantly higher (all p < 0.001) risk of admission. Patients with comorbid heart failure (p < 0.001), those taking ulcer medications (p < 0.01), or inflammatory bowel disease (p = 0.03) had a significantly increased risk of admission. Results were consistent regardless of payer (Medicare or commercial health plan). Conclusions: This study identified cancer patients for whom acute inpatient admission from an ED presentation is more likely. Future studies identifying cancer patients who may be at risk of making an ED presentation based on demographic, clinical and disease-related characteristics are needed and may help inform targeted follow up of patients to mitigate potentially avoidable ED presentation and subsequent inpatient admission.
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