; (ii) pathophysiological changes over time, including pathogen persistence profiles for patients with differing treatment histories; (iii) activation and deactivation of immune system processes; and (iv) whether, and what species of, Bartonella are transmitted by ticks. (B) Clinical outcomes research The Secretary shall conduct or support clinical outcomes research to— (i) establish epidemiological research objectives to determine the long-term course of illness for Lyme disease and other tick-borne diseases and disorders; (ii) establish patient-centered treatment outcome objectives to allow for the comparative effectiveness of different treatment modalities; and (iii) establish patient-centered research objectives to help elucidate promising treatment protocols for individuals suspected of harboring coinfections with more than one tick-transmitted pathogen. (C) Collaborative, multidisciplinary research The Secretary shall encourage the solicitation of proposals for collaborative, multidisciplinary research that would— (i) result in innovative approaches to study emerging scientific opportunities or eliminate gaps in research to improve the research portfolio, including application of successful and promising advances in the study of other types of diseases, such as upregulating or downregulating immune system cells or processes; (ii) outline key research questions, methodologies, and knowledge gaps; (iii) expand the number of research proposals that involve collaboration between 2 or more national research institutes or national centers of the National Institutes of Health, including proposals for research through the Common Fund pursuant to section 402(b)(7) of the Public Health Service Act ( 42 U.S.C. 282(b)(7) ) to improve the research portfolio; (iv) expand the number of collaborative multi-institutional research grants related to tick-borne disease