OBJECTIVES/GOALS: The Mayo Clinic Clinical and Translational Science (CTS) Predoctoral program aims to develop independent researchers capable of leading multi-disciplinary teams to accelerate the translation of discovery to application. Here, we detail the outcomes of our graduates over the past ten years (2010-2019). METHODS/STUDY POPULATION:): A survey was fielded with all CTS graduates whose degrees were conferred since the program’s inception to 2019. Items addressed their current position, whether they were still involved in research, what type of research they were involved in, and whether they stayed involved with education. They also submitted a recent CV, from which data were collected about publications and grants. A subset were then contacted for a semi-structured interview. Items included questions addressing motivation for pursuing a PhD in CTS, whether the program prepared them for their current work, gaps they felt they had in training, and whether they felt they were making a difference in the lives of patients. RESULTS/ANTICIPATED RESULTS: Of the 41 alumni, 34 responded (83% response rate). Of these, 19 (56%) are at Mayo Clinic, 9 (26%) work for other academic institutions, and 6 (21%) do not work for an academic institution. Most have remained in research (33/34, 97%). The majority (22/33, 67%) are involved in clinical research, 30% (10/33) in basic science, and 24% (8/33) in healthcare delivery research. Most (23/34, 68%) are engaged in educational activities. When asked about changes they have led, 67% (18/27) led quality improvement projects and 44% (12/27) designed a new research method. Several hold leadership positions either in their organization (12/16, 75%) or in a professional organization (10/16, 63%). DISCUSSION/SIGNIFICANCE OF IMPACT: The CTS Predoctoral program successfully prepares scholars for careers involving clinical and translational research; furthermore, alumni remain in research-oriented careers after graduation. We will continue to gather longitudinal data alumni move forward in their careers.

Because individuals develop dementia as a manifestation of neurodegenerative or neurovascular disorder, there is a need to develop reliable approaches to their identification. We are undertaking an observational study (Ontario Neurodegenerative Disease Research Initiative [ONDRI]) that includes genomics, neuroimaging, and assessments of cognition as well as language, speech, gait, retinal imaging, and eye tracking. Disorders studied include Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, and vascular cognitive impairment. Data from ONDRI will be collected into the Brain-CODE database to facilitate correlative analysis. ONDRI will provide a repertoire of endophenotyped individuals that will be a unique, publicly available resource.

Schistosomes are parasitic flatworms that cause schistosomiasis, a neglected tropical disease that affects hundreds of millions worldwide. Treatment and control of schistosomiasis relies almost entirely on the single drug praziquantel (PZQ), making the prospect of emerging drug resistance particularly worrisome. This review will survey reports of PZQ (and other drug) resistance in schistosomes and other platyhelminths, and explore mechanisms by which drug resistance might develop. Newer genomic and post-genomic strategies that offer the promise of better understanding of how drug resistance might arise in these organisms will be discussed. These approaches could also lead to insights into the mode of action of these drugs and potentially provide markers for monitoring the emergence of resistance.

A new book by Stephen Engstrom repeats a criticism of Bruce Aune's of Kant's derivation of the universalizability formula of the categorical imperative. The criticism is that Kant omitted at least one substantive premise in the derivation of the formula: ‘Act only on that maxim through which you can at the same time will that it become a universal law.’ The grounds for the formula that are given in the Groundwork of the Metaphysics of Morals, however, are said to support only a weaker requirement, namely, that a maxim conform to a universal law. Hence, Kant omits at least one necessary substantive premise of the derivation. This paper attempts to show that nothing substantive is omitted from the argument. It only needs two principles of inference that it is assumed add nothing substantive to the premises.

This study identified profiles of 13 risk factors across child, family, school, and neighborhood domains in a diverse sample of children in kindergarten from four US locations (n = 750; 45% minority). It then examined the relation of those early risk profiles to externalizing problems, school failure, and low academic achievement in Grade 5. A person-centered approach, latent class analysis, revealed four unique risk profiles, which varied considerably across urban African American, urban White, and rural White children. Profiles characterized by several risks that cut across multiple domains conferred the highest risk for negative outcomes. Compared to a variable-centered approach, such as a cumulative risk index, these findings provide a more nuanced understanding of the early precursors to negative outcomes. For example, results suggested that urban children in single-parent homes that have few other risk factors (i.e., show at least average parenting warmth and consistency and report relatively low stress and high social support) are at quite low risk for externalizing problems, but at relatively high risk for poor grades and low academic achievement. These findings provide important information for refining and targeting preventive interventions to groups of children who share particular constellations of risk factors.

Gauss-Seidel is a general method for solving a system of equations (possibly nonlinear). It makes repeated sweeps through the variables; within a sweep as each new estimate for a variable is computed, the current estimate for that variable is replaced with the new estimate immediately, instead of on completion of the sweep. The idea is to use new data as soon as it is computed. Gauss- Seidel is often efficient for computing the invariant measure of a Markov chain (especially if the transition matrix is sparse), and for computing the value function in optimal control problems. In many applications the computation can be significantly improved by appropriately ordering the variables within each sweep. A simple heuristic is presented here for computing an ordering that quickens convergence. In parallel processing, several variables must be computed simultaneously, which appears to work against Gauss-Seidel. Simple asynchronous parallel Gauss-Seidel methods are presented here. Experiments indicate that the methods retain the benefit of a good ordering, while further speeding up convergence by a factor of P if P processors participate.

In this paper, we focus on the optimal stopping problem. A probabilistic interpretation of the Gauss-Seidel (and the Jacobi) method for computing the value function is given, which motivates our ordering heuristic. However, the ordering heuristic and parallel processing methods apply in a broader context, in particular, to the important problem of computing the invariant measure of a Markov chain.

The status of the Serbian standard language in the years since the breakup of Yugoslavia has been controversial. Serbian linguists were ill prepared for the demise of the unified Serbo-Croatian language in 1991 and found themselves scrambling to create a new linguistic order. While die Croatian linguists in socialist Yugoslavia had long advocated a separate literary language called Croatian, rather than Croato-Serbian, the Serbs had continued to insist on the joint language and readily accepted the term Serbo-Croatian. With the disintegration of Yugoslavia, the Serbs finally had to recognize that given Croatian and Bosnian-Muslim linguistic separatism, a joint literary language was no longer possible. In this paper, I examine the consequences of the breakup of Serbo-Croatian for Serbs in the Yugoslav successor states, especially in the Federal Republic of Yugoslavia (FRY). I discuss the emergence of three ideologically opposed factions of Serbian linguists. The debate among Serbian linguists has been heated and acrimonious, reflecting broader political struggles within the FRY. I suggest that politically motivated turmoil in Serbian linguistic circles has put the New Serbian on a chaotic, unstable, and unpredictable path into the future.