Work in Progress: Rigorously Assessing the Anecdotal Evidence of Increased Student Persistence in an Active, Blended, and Collaborative Mechanical Engineering Environment

This work in progress describes an ongoing study of an active, blended, and collaborative (ABC) course environment used in a core mechanical engineering course. This course has built on the growing body of literature citing active learning (Freeman et al., 2014), blended structures (Bowen & Ithaka, 2012), and collaborative engagement (Jeong & Chi, 2007) as positive influences on college and university science, technology, engineering, and math (STEM) outcomes. For the last six years, “Dynamics”, a core mechanical engineering course at a large public university, has utilized in-class activities, frequently-watched problem-solving videos, and a collaborative blog space to realize an ABC environment. On one key metric of course success, the rate of students who drop, fail, or withdraw from (DFW), the course has experienced near-constant improvements since the ABC structures were introduced. In this study, the authors utilize rigorous longitudinal methods to determine whether this drop in DFW rates can be directly attributed to increased implementation of ABC features. The authors hypothesize that as instructors become accustomed to the ABC environment and increase the level of in-class activity, use of blended resources, and collaboration, the likelihood of DFW in each subsequent year would drop. However, in the same time period, each subsequent class entered with higher levels of performance on proxy measures for prior knowledge. We therefore build a logistic regression model to predict individual-level DFW and determine whether the anecdotal drops in DFW that we observe can be attributed to the expansion of the ABC environment. More specifically, we predict likelihood of DFW based on students’ prior knowledge (grade in the preceding course, SAT math score), key demographics (gender, race/ethnicity), the semester and year they took Dynamics, their instructor, their year in school, and their major. We test for year fixed effects {year_t, t = 1, 2, ..., 7} to determine whether odds ratios for DFW consistently and significantly decrease over time. We also test for instructor effects, in particular for differences between the instructors who were involved in the design and development of the ABC environment and more independent instructors who only partially implemented the ABC course components. We anticipate results that will provide more rigorous, less biased, and efficient estimates for the individual- and class-level components that explain variance in DFW rates. These results would provide immediate implications for the next phase of our work, as we assess the next on-term implementation of the course in 2016. Our findings would also have long-term significance for other classes in mechanical engineering and related disciplines and for classes at other institutions that are considering implementing a comprehensive ABC learning environment

Analyzing an Abbreviated Dynamics Concept Inventory and Its Role as an Instrument for Assessing Emergent Learning Pedagogies

The Dynamics Concept Inventory (DCI) is a validated assessment tool commonly used to evaluate student growth within core, gateway-level mechanics courses. This research explored the evaluative use of this tool within the context of Freeform – an emergent course system that buttresses active class meetings with blended and collaborative virtual learning environments, themselves founded upon extensive multimedia content and interactive forums – at Purdue University. The paper specifically considers a number of related issues including: (i) the thoughtful development (via expert content validation) and statistical reliability of an abbreviated DCI instrument, which is more amenable to in-class implementation than the much longer full DCI; (ii) the correlation of abbreviated-DCI performance with exam scores and final course grades for a dynamics course using the Freeform framework with an emphasis on both conceptual understanding and traditional problem-solving skills; and (iii) various inter-section performance metrics in a preliminary study on how an implementation of the abbreviated-DCI may help elucidate the impact of the instructor within the Freeform framework. The results of these analyses supported the validity and reliability of the abbreviated DCI tool, and demonstrated its usefulness in a formal research setting. The preliminary study suggested that the Freeform framework might normalize differences in instructor pedagogical choices and student performance across class sections. These findings indicate that the abbreviated DCI holds promise as a research instrument and lay the groundwork for future inquiry into the impact of the Freeform instructional framework on students and instructors alike

Transforming a Dynamics Course to an Active, Blended, and Collaborative Format: Focus on the Faculty

Mechanical engineering programs are increasingly applying educational research by transforming courses to be more interactive and to use a blend of online and face-to-face materials. However, the process of an existing course adopting these new practices is not well studied, and even less is understood about the faculty experience from on-boarding to delivery of a new curriculum or pedagogy. In this study, we follow the translation of an active, blended, and collaborative (ABC) curriculum for a core dynamics course from a large public university (where the ABC curriculum was developed) to a small private university. We use interpretive phenomenology to focus on the lived experience of the instructor newly implementing these course materials, format, and pedagogical approach. Specifically, we address the following research questions: (1) What is the lived experience of a mechanical engineering instructor at a different institution as she adopts and adapts the provided materials and format? (2) How does the experience of this instructor evolve throughout the semester? We use rich qualitative data to understand the experience of the instructor, who taught this course in its prior format and, in Fall 2015, taught the “off-term” core dynamics course via the new ABC structure. Through weekly reflection prompts, pre- and post-semester interviews, and supplementary process data (e.g., notes of weekly meetings between the new implementer and ABC team at the large public university), we describe and characterize the multi-faceted instructor experience. This includes her experience learning about the curriculum and online tools, implementing the class and adjusting her teaching practices, and assessing her students’ engagement with the course and understanding of dynamics concepts. Our findings suggest further areas of inquiry for studies of faculty practices around curriculum adoption, including probing opportunities for cross-institutional collaborations to share materials and transform courses, interrogating variation in mechanical engineering department and student cultures, and studying sources of faculty development and support throughout the course transformation process

Genome-wide characterization of pancreatic adenocarcinoma patients using next generation sequencing

Pancreatic adenocarcinoma (PAC) is among the most lethal malignancies. While research has implicated multiple genes in disease pathogenesis, identification of therapeutic leads has been difficult and the majority of currently available therapies provide only marginal benefit. To address this issue, our goal was to genomically characterize individual PAC patients to understand the range of aberrations that are occurring in each tumor. Because our understanding of PAC tumorigenesis is limited, evaluation of separate cases may reveal aberrations, that are less common but may provide relevant information on the disease, or that may represent viable therapeutic targets for the patient. We used next generation sequencing to assess global somatic events across 3 PAC patients to characterize each patient and to identify potential targets. This study is the first to report whole genome sequencing (WGS) findings in paired tumor/normal samples collected from 3 separate PAC patients. We generated on average 132 billion mappable bases across all patients using WGS, and identified 142 somatic coding events including point mutations, insertion/deletions, and chromosomal copy number variants. We did not identify any significant somatic translocation events. We also performed RNA sequencing on 2 of these patients' tumors for which tumor RNA was available to evaluate expression changes that may be associated with somatic events, and generated over 100 million mapped reads for each patient. We further performed pathway analysis of all sequencing data to identify processes that may be the most heavily impacted from somatic and expression alterations. As expected, the KRAS signaling pathway was the most heavily impacted pathway (P<0.05), along with tumor-stroma interactions and tumor suppressive pathways. While sequencing of more patients is needed, the high resolution genomic and transcriptomic information we have acquired here provides valuable information on the molecular composition of PAC and helps to establish a foundation for improved therapeutic selection

Genome evolution in the allotetraploid frog Xenopus laevis

To explore the origins and consequences of tetraploidy in the African clawed frog, we sequenced the Xenopus laevis genome and compared it to the related diploid X. tropicalis genome. We characterize the allotetraploid origin of X. laevis by partitioning its genome into two homoeologous subgenomes, marked by distinct families of ???fossil??? transposable elements. On the basis of the activity of these elements and the age of hundreds of unitary pseudogenes, we estimate that the two diploid progenitor species diverged around 34 million years ago (Ma) and combined to form an allotetraploid around 17-18 Ma. More than 56% of all genes were retained in two homoeologous copies. Protein function, gene expression, and the amount of conserved flanking sequence all correlate with retention rates. The subgenomes have evolved asymmetrically, with one chromosome set more often preserving the ancestral state and the other experiencing more gene loss, deletion, rearrangement, and reduced gene expression.ope

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Theoretical analysis reveals a role for RAF conformational autoinhibition in paradoxical activation

RAF kinase inhibitors can, under certain conditions, increase RAF kinase signaling. This process, which is commonly referred to as ‘paradoxical activation’ (PA), is incompletely understood. We use mathematical and computational modeling to investigate PA and derive rigorous analytical expressions that illuminate the underlying mechanism of this complex phenomenon. We find that conformational autoinhibition modulation by a RAF inhibitor could be sufficient to create PA. We find that experimental RAF inhibitor drug dose–response data that characterize PA across different types of RAF inhibitors are best explained by a model that includes RAF inhibitor modulation of three properties: conformational autoinhibition, dimer affinity, and drug binding within the dimer (i.e., negative cooperativity). Overall, this work establishes conformational autoinhibition as a robust mechanism for RAF inhibitor-driven PA based solely on equilibrium dynamics of canonical interactions that comprise RAF signaling and inhibition

A mechanism for the response of KRASG13D expressing colorectal cancers to EGFR inhibitors

Previous analysis of Phase 3 clinical trial data for colorectal cancer patients treated with cetuximab revealed that patients harboring a KRAS mutation did not benefit from treatment. This finding set the stage for one of the first examples of cancer personalized medicine. Confusingly, patients with a Glycine to Aspartic Acid mutation at amino acid 13 of KRAS (KRASG13D) appeared to respond positively to cetuximab, suggesting this mutation is an exception to the rule that KRAS mutations confer resistance to Epidermal Growth Factor Receptor (EGFR) inhibitors. Oncologists have stated that the mechanism that explains why the KRASG13D mutation is an exception should be identified before KRASG13D colorectal cancer patients should be treated differently. We have recently elucidated this mechanism using mathematical modeling of the KRAS biochemical system coupled with experimental biology. The mechanism we revealed involves a cetuximab-mediated reduction in HRAS and NRAS signaling within KRASG13D cancer cells, owing to impaired binding of KRASG13D to the tumor suppressor, Neurofibromin (NF1)

How often is each gene mutated within the cancer patient population?

Genome sequenced samples from cancer patients helped identify roles of different mutation types and enabled targeted therapy development. However, critical questions like what are the gene mutation rates among the patients? or what genes are most commonly mutated, pan-cancer? have only been recently answered. Here, we highlight this recent advance