Dartmouth Institute for Health Policy and Clinical Practice
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From Chaos to Cohesion: Building a Brand Kit
No full textFrom Chaos to Cohesion: Building a Brand Kit is a lesson designed for undergraduate students to show how a strong visual identity supports an organization’s mission and goals. Utilizing interactive instruction, guided exercises, individual exploration, and peer discussions, students will learn how elements, such as typography, logos, and color can shape public perception and align with audience expectations. By the end of the lesson, students will have created a sample brand kit and graphic to reflect an organization’s purpose and tone.
This lesson integrates marketing theory, real-life examples, and independent hands-on learning to encourage creativity, collaboration, and strategic thinking. Students will be able to reflect on how cohesive design can enhance an organization. Ultimately, this lesson empowers students to not only understand marketing decisions, but also empower them to craft professional, mission-oriented brand identities for their own clubs and organizations on campus. Therefore, this lesson is applicable to their academic, social, and professional lives
Bridging Bench to Bedside: Developing Sup2-IL-33 armored CAR T cells for translational immunotherapy
No full textDespite some promising results, CAR T cell therapy elicits limited responses in most patients with solid tumors. Armoring CAR T cells with immunomodulatory cytokines improves efficacy in solid tumors. We previously reported that administering IL-2 superkine (Sup2) and IL-33 cytokine armored CAR T cells without host pre-conditioning is sufficient to broadly activate host immunity to delay growth of B16F10 melanoma in immunocompetent B6 mice. However, lymphodepleting pre-conditioning prior to CAR T cell infusion is routinely utilized to enable engraftment of adoptively transferred cells. Here we assess the efficacy TRP1-specific CAR T cells with or without Sup2 and IL-33 armoring following local or systemic pre-conditioning regimens. CAR T cell expansion kinetics and phenotype were evaluated with luminescence imaging, flow cytometry, and single-cell RNA sequencing. We found that systemically pre-conditioned mice treated with Sup2-IL33 CAR T cells exerted substantially greater tumor control and extended overall survival compared to non- or locally pre-conditioned mice. Pre-conditioning with total body irradiation (TBI) increased expression of IFN stimulated genes promoting the emergence of novel Tox- effector phenotypes following Sup2-IL33 CAR T cell treatment. Durable responsiveness and extended survival following combined therapy required continued CAR T cell persistence despite the ability of Sup2-IL33 armoring to induce endogenous tumor immunity.
Limitations in mouse tumor models can hinder clinical translation of novel immunotherapeutic treatments. Bone, liver, and thymus (BLT) humanized mice recapitulate many components of the human immune system, allowing pre-clinical therapies to be assessed in the context of human immune cells during development. We evaluated the efficacy of Sup2-IL33 armored TIM-1 specific CAR T cells against Caki-1 renal cell carcinoma tumors in BLT humanized mice. Human immune reconstitution, tumor antigen expression, and CAR T cell phenotype were evaluated with flow cytometry and luminescence imaging. Despite effective in vitro killing of Caki-1 tumor cells, Sup2-IL33 CAR T cells did not improve in vivo tumor control. However, cytokine armoring increased the expansion of adoptively transferred CD8 T cells, suggesting that Sup2-IL33 armoring may be beneficial for proliferation of human T cells. Together, these studies aim to advance Sup2-IL33 CAR T cell therapy through evaluation in more clinically relevant models
Safer, More Useable 3D Printers For Schools
No full textWith recent technological advances, 3D printing has become widely accessible. This has allowed for greater ease in producing and obtaining machine gun conversion devices (MCDs). MCDs have the capacity to turn semi-automatic rifles and handguns into fully automatic machine guns. Even though it is illegal to print, own, or sell MCDs, print files for these devices are freely available on file sharing websites and easy to produce via 3D printing. It naturally follows that this increase in access to MCDs increases the potential risk for mass shootings. Additionally, 3D printing technologies are becoming increasingly prevalent in educational settings, such as makerspaces. This further increases students\u27 access to MCDs. This project thus seeks to produce a safer, more usable 3D printer that both prevents the printing of MCDs and is more appealing for use in educational settings. There are three main components of this project that will be developed simultaneously. First, for the software end, current market software companies (such as Materialise) are working on MCD detection. To this end, they are developing a slicing software that is able to detect potential MCDs in 3D print files based on key object geometries. The slicing software then outputs a G-code file along with a binary flag indicating whether or not an MCD was detected by the slicing software. This project will extend upon the MCD detection output by developing a software routine which will be embedded in the slicing software. This software routine will secure the G-Code and ensure that the G-Code produced by the slicing software with MCD detection capabilities is the same G-Code that is provided to the 3D printer. This will be accomplished by computing an encrypted signature only on G-Code files for prints in which an MCD was not detected. This project will also thus need to modify an existing 3D printer\u27s firmware such that verification of the encrypted signature becomes possible. The firmware will need to ensure that the G-Code is signed and that neither the signature nor G-Code have been modified since they were produced by the slicing software. Only if the G-Code file is signed and both the signature and G-Code are found to be unaltered will the print proceed. Second, the hardware component involves constructing a 3D printer from an open-source kit and designing a cost-effective (compared to current market solutions) enclosure using particle board, MDF, and polycarbonate panels. The enclosure will feature an integrated ventilation and carbon filter system for heat and VOC management, along with a secure locking mechanism to enhance safety. Our MCD detection software will be integrated into the printer’s firmware. Our MCD detection software will then be integrated into the firmware of our constructed printer. Finally, the UI/UX component is centered around a user-focused approach to create an intuitive and effective training experience for young 3D printer users. Our work is divided into two main segments: user research and user testing. Initial research has identified slicing software as a key pain point, driving our goal to design a new, simplified interface tailored for educational use. In the second phase, we will conduct usability testing with local elementary and middle school students, utilizing tools like Maze and Amplitude to gather both qualitative and quantitative data
Engineering the Microenvironment of the Human Heart to Mature Human Stem Cell-Derived Cardiomyocytes
No full textDespite being the leading cause of death globally, cardiovascular diseases are still subject to controversial pharmacological intervention as the majority of cardiac drug failures and post-approval withdrawals are attributed to unforeseen cardiovascular toxicity. The current standard methods of cardiovascular research based on static two-dimensional cell cultures and animal models have significant translational limitations to overcome unsuccessful drug development. To that end, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have shown to be promising as an alternative personalized cell source. However, a key bottleneck in the current applications of hiPSC-CMs lies in their structural and functional immaturity and thus, to what extent the intact hiPSC-CMs are predictive of clinical drug effects or disease models is unclear.
Understanding the single cell population dynamics and probabilities that a hiPSC-CM cell will evolve towards a mature adult CM structurally, functionally, and genetically is necessary for making predictions and directing decisions to achieve a desired final cell type or population. By employing developmental biology, biochip design, tissue engineering, and machine learning, this thesis builds the foundation for overcoming this obstacle and develops methodologies and design approaches to understand cardiac single cell-cell and cell-matrix interaction dynamics needed in enhancing maturity of hiPSC-CMs and ultimately treating heart diseases. The goal of this thesis is to establish a paired experimental process and guiding computational model using on-chip dynamic cell culture with spatiotemporal image recordings and RNA sequencing measurements to predict both the outcome of hiPSC-CM maturation level and the process parameters that should be adjusted to achieve the desired result.
The research methodology and design approaches developed through the final microphysiological chip will enable a granular understanding of the microenvironmental effects on the developmental biology of fetal to adult human cardiomyocytes - in particular, the mechanical properties of the matrix and cellular network interactions with respect to hiPSC-CM performance. Modular matrix design approaches and insights derived from this study have the potential to extend to other cellular systems to understand the cell-cell and cell-matrix relationships in complex microenvironmental contexts
This Is How You Can Be a COOL Adult
No full text“This Is How You Can Be a COOL Adult” is an interactive and self-reflective lesson designed to help high school juniors through college seniors practice being more compassionate, open-minded, optimistic, and laughing-out-loud (humorous) in their everyday lives. By the end of this lesson, students will be able to describe and explore research-based strategies that foster compassion, open-mindedness, optimism, and humor, and create a personalized “COOL Action Plan” with self-reflection logs to track progress. The lesson takes place in an unconventional classroom setting (outdoors) and includes mini-lectures, meditation, collaborative games, creative role-play, personal reflection, and practical methods for applying these qualities in real-life contexts. Ultimately, this lesson encourages students to cultivate greater humility and civic engagement
EEG Processing Pipeline for Objective ASD Diagnosis
No full text15-20% of the world\u27s population exhibit some form of neurodivergence. One neurodivergent disorder, Autism spectrum disorder (ASD), affecting 1 in 36 children, relies on subjective behavioral assessments for diagnosis. This is because modern screening tools have high false positive and false negative rates. Accurately diagnosing ASD early leads to significant improvements in cognitive, language, and social-emotional functioning in children. Early diagnosis enables earlier entry into specialized education programs, improving academic outcomes. Socially, early diagnosis leads to greater independence in adulthood, reducing healthcare costs and the need for intensive interventions. Currently, one biomarker has been accepted into the FDA’s Biomarker Qualification Program for ASD diagnosis via EEG. Additionally, many studies have found differences in EEG data between ASD and non-ASD patients. However, due to high heterogeneity in study results, one consistent method has yet to be adopted as an objective ASD EEG diagnostic. Our sponsor is a healthy tech startup committed to creating an objective autism diagnosis process from EEG analysis. This functional healthcare tool will utilize well-researched processing methods to revolutionize neurodivergence diagnosis
THE IMPLEMENTATION AND MINIATURIZATION OF A NEW CURRENT SOURCE INTO THE CONSOLIDATED LAYOUT OF AN ELECTRICAL IMPEDANCE TOMOGRAPHY PROBE WITH A NOVEL APPROACH TO ELECTRODE LAYOUT
No full textProstate cancer is the most highly diagnosed form of cancer in male subjects in the United States. As a result, over 100,000 radical prostatectomies are performed annually in the US [1]. However, it is currently very difficult for surgeons to confirm that all impacted tissues have been effectively removed from the patient. Positive surgical margins are an independent risk factor for the recurrence of cancer, yet currently there is no method to efficiently, intraoperatively assess the status of surgical margins during a radical prostatectomy. There is a need for a new tool that is small enough to fit into a laparoscopic port, images the tissues in real time, is ideally radiation-free, and is cost-effective. Electrical impedance tomography is a strong option for filling this void. Yet currently developed EIT probes have limitations. This thesis focuses on combatting these limiting factors and producing a novel, more accurate, miniaturized EIT probe design. Building upon previous EIT designs, a more stable, constant current source was implemented into the system to attempt to improve accuracy, the number of electrodes used for voltage measurement was increased and their arrangement re-designed for added resolution, and the circuitry was simplified to reduce the possible introduction of parasitic impedances. High impedance buffers and low noise components were also implemented for this reason. Additionally, noise and stray capacitance were combatted by moving all analog circuitry onto the device PCB close to the electrodes to eliminate the need for long leads which can introduce distortion of signals. In the process of implementing these improvements, previous EIT probe designs were evaluated, a new electrode layout was designed, improved current sources were analyzed, extensive component evaluation was performed, PCB prototypes of a system layout with the above changes were produced, a calibration scheme for these new designs was developed, these calibrated systems were evaluated, this improved design was miniaturized, and the final, miniaturized, probe layout was analyzed. This research has been another step towards the development of a small scale, clinically implementable, low noise, high accuracy, high precision EIT probe which could provide vital, real-time information to surgeons during radical prostatectomies
Developing Real-time, Online Beam Control of UHDR Irradiators to Facilitate FLASH Translational Investigations
No full textThe field of radiation oncology seeks novel techniques to increase the therapeutic ratio to treat malignancies while minimizing damage and toxicities in healthy tissues. While it was observed that delivering therapeutic doses at high dose rate could elicit lower biological effects over a half-century ago, the field of ultra-high dose rate (UHDR) radiation therapy (colloquially known as FLASH RT) has seen a resurgence in recent years due to an alignment of accelerator capability, dosimetric advances, and improved biotechnological techniques. This has opened the door to studying potential underlying mechanisms such that we may leverage the effects of FLASH tissue sparing in the near future. Collaboration of Dartmouth College with the Dartmouth Cancer Center established a leading FLASH development platform with two linacs currently being used for preclinical studies while preparing for an early clinical study.
Patient safety is a core tenet; however, FLASH RT has the potential to cause immense harm if radiation is improperly applied. Modern linear accelerators can produce UHDR fluences but safely delivering a precise amount of dose and verifying what was delivered are two of the biggest challenges to FLASH RT. Under UHDR operation, desired doses can be achieved in a small number of pulses delivered over several milliseconds so a single unwanted pulse can result in a significant deviation from the therapy plan. This work developed critical dosimetry and control systems of electron clinical irradiators to produce clinically usable, safe UHDR beams. Specifically: Linac modification and beam controller (clinical Varian C-arm linac and an IntraOp Mobetron intraoperative unit) Dosimeters viable under UHDR conditions (including diamond, semiconductor, and current transfer dosimeters) New calibration methods, QA procedures, and experimental workflows Real-time dose monitoring and output control of a novel irradiator, towards meeting state regulatory requirements for human FLASH trials at Dartmouth
BEHAVIORAL AND NEURAL EFFECTS OF DISTRIBUTING VISUAL ATTENTION ACROSS LOCATION AND FEATURE SPACE
Get PDFVisual attention refers to the mechanisms by which relevant visual information, such as location, simple features (e.g., color, orientation), and objects, is selected and prioritized for further processing. The current dissertation investigates capacity limitations on spatial and feature–based attention in early visual processing and behavioral performance. Specifically, I examined whether attention could be efficiently tuned across narrow and broad ranges of locations and colors, or even be split across noncontiguous locations in the case of spatial attention. I used several behavioral paradigms and frequency–tagging methods in electroencephalography (EEG) to illustrate the effects of narrowing or broadening the attentional focus on performance and early visual processing. My findings indicate that the spatial focus of attention can modulate the neural gain of early visual processing across varying ranges of locations but cannot be split into discrete spotlights within a visual quadrant. Furthermore, I found that feature–based attention can flexibly ‘zoom’ in and out across continuous narrow and broad ranges in color space with no performance cost. Interestingly, measures of early visual-cortical processing indicated a cost in neural gain when attention was directed to broader ranges of colors — drawing parallels to the previously reported processing cost in spatial attention. However, this cost at early processing stages appears to be compensated for at later stages, leading to overall no cost in behavioral performance. In sum, the current dissertation provides novel evidence for how spatial and feature–based attention can be tuned across varying ranges in location and feature space and demonstrates that each type of attention is constrained by the unique format of the sensory representations over which it operates
