A comparison of random vs. chemotaxis-driven contacts of T cells with dendritic cells during repertoire scanning.

Generating adaptive immunity after infection or immunization requires physical interactions within a lymph node (LN) T-zone between antigen-bearing dendritic cells (DCs) that arrive from peripheral tissues and rare cognate T cells entering via high endothelial venules (HEVs). This interaction results in activation of cognate T cells, expansion of that T cell lineage and their exit from the LN T-zone via efferent lymphatics (ELs). How antigen-specific T cells locate DCs within this complex environment is controversial, and both random T cell migration and chemotaxis have been proposed. We developed an agent-based computational model of a LN that captures many features of T cell and DC dynamics observed by two-photon microscopy. Our simulations matched in vivo two-photon microscopy data regarding T cell speed, short-term directional persistence of motion and cell motility. We also obtained in vivo data regarding density of T cells and DCs within a LN and matched our model environment to measurements of the distance from HEVs to ELs. We used our model to compare chemotaxis with random motion and showed that chemotaxis increased total number of T cell DC contacts, but decreased unique contacts, producing fewer activated T cells. Our results suggest that, within a LN T-zone, a random search strategy is optimal for a rare cognate T cell to find its DC match and maximize production of activated T cells.

Contemporary Primary Prevention Aspirin Use by Cardiovascular Disease Risk: Impact of US Preventive Services Task Force Recommendations, 2007-2015: A Serial, Cross-sectional Study.

BACKGROUND: No previous study has evaluated the impact of past US Preventive Services Task Force statements on primary prevention (PP) aspirin use in a primary care setting. The aim of this study was to evaluate temporal changes in PP aspirin use in a primary care population, stratifying patients by their 10-year global cardiovascular disease risk, in response to the 2009 statement. METHODS AND RESULTS: This study estimated biannual aspirin use prevalence using electronic health record data from primary care clinics within the Fairview Health System (Minnesota) from 2007 to 2015. A total of 94 270 patient encounters had complete data to estimate a 10-year cardiovascular disease risk score using the 2013 American College of Cardiology/American Heart Association global risk estimator. Patients were stratified into low- (<10%), intermediate- (10-20%), and high- (≥20%) risk groups. Over the 9-year period, PP aspirin use averaged 43%. When stratified by low, intermediate and high risk, average PP aspirin use was 41%, 63%, and 73%, respectively. Average PP aspirin use decreased after the publication of the 2009 US Preventive Services Task Force recommendation statement: from 45% to 40% in the low-risk group; from 66% to 62% in the intermediate-risk group; and from 76% to 73% in the high-risk group, before and after the guideline. CONCLUSIONS: Publication of the 2009 US Preventive Services Task Force recommendation was not associated with an increase in aspirin use. High risk PP patients utilized aspirin at high rates. Patients at intermediate risk were less intensively treated, and patients at low risk used aspirin at relatively high rates. These data may inform future aspirin guideline dissemination.