Dartmouth Institute for Health Policy and Clinical Practice
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Over the Influence: Considering Scenarios Sponsored Adventure Influencers Find Themselves In
Get PDFAn experienced mountain guide sketches three situations—promoting clothing, going fast with minimal gear, and making the reaching of an iconic scene look easy—where social media influencers could misinform the public
Having a Cow: Exploring the Economic and Mental Health Challenges of Dairying in the Upper Valley
Get PDFUntil late in the 20th century, the dairyman was an influential actor in the fabric of the Upper Valley consisting of Grafton, Orange, Sullivan and Windsor counties (Rozwenc, 1981 & Weld, 1905). Dairy farmers were critical to both the economic growth of the region and the construction of a local identity centered around distinctive high quality dairy products. However, the dairy farmers responsible for the bucolic feel and scrappy independence unique to the Upper Valley are being traded in for massive operations lacking both quality of milk and the cultural intricacy specific to local dairies. In 1905 there were 4,173 dairy farms in Grafton county and 1,833 in Sullivan county (Weld, 1905). In 2022, there were 19 and 11 respectively. In addition to the decline in the quantity of farms, the mental health of farmers has significantly deteriorated. Suicide rates across the country have increased by 40% since the turn of the century, and farmers represent one of the five industries with suicide rates accelerating significantly faster than the national average (CDC, 2020). In 2018, Agri-Mark, the region’s largest milk cooperative, announced a milk price so low they pre-empted the letter with a list of suicide hotlines (Wellington, 2018). My thesis works to 1) identify the economic and political conditions that allowed for this collapse and 2) build an oral history based on semi-structured interviews regarding the importance of dairy farming to the Upper Valley and the mental health struggles these farmers face. Through literature research and interviews, the unique conditions of the dairy farmer are primarily 1) the constant flow of perishable product inherent to cow biology, 2) the leverage of processors due to the complex handling/distribution schemes, and 3) the misalignment between governmental regulation and small farmers\u27 needs. The oral histories revealed dairy farmers are expressing 1) burnout from responsibility, 2) anxiety of uncertain market conditions and 3) the pressure of maintaining a farm inherited by generations
Tôi and Moi: The Ambivalence of the Self in Lưu Trọng Lư and Proust
No full textMuch scholarship has discussed the prevalence of the first-person pronoun tôi (‘I’) in the New Poetry movement in 1930s Vietnam during the French colonization and the nature of the individual agency that accompanies the word. Yet, despite bearing visible marks of the Cartesian self, the Vietnamese subjectivity portrayed in Lưu Trọng Lư’s poetry resists essentialist categorization, engendering what Bhabha calls mimicry. But what does the colonial subject mimic? This essay looks closely at arguably the most canonical French author that precedes the rise of the New Poetry movement in Vietnam, Marcel Proust, whose La Recherche reveals the elusive ideal of the self even within the French subject. Tracing the oscillation between metaphor and metonymy in both Proust’s prose and Lưu’s poetry as deconstructed by Paul de Man, the essay drifts from textual literariness to ontological questions on subjectivity. It further examines the intricacies of the colonial subject who dwells in the space of ambivalence along the axis of metonymy of presence
Upward Mobility of First-Generation Low-Income Dartmouth Students
Get PDFThe most promising way for young people to achieve upward mobility, which at the most basic level means making more money than their parents, is to attend the best college possible. From its inception, Dartmouth College has been an institution set up to educate the children of the wealthiest and most powerful families. Over the last few decades, more and more promising students have come from families whose parents and grandparents did not attend college. When First-Generation Low-Income (FGLI) students arrive at Dartmouth, they encounter an institution set up for wealthy students. I aimed to discover how well Dartmouth supports FGLI students to graduation, allows them to thrive, and prepares them for upward mobility after graduation. I interviewed three students and five alums who completed the First Year Summer Enrichment Program (FYSEP) run through the First-Generation Office—and six staff members who work closely with FGLI students. I recorded the interviews using Dartmouth-supported Zoom software and sent them to a company to have them transcribed. I used another Dartmouth-supported coding software to code the interviews using a coding scheme I developed. I coded the data into several categories. As I coded, I added more code categories. Once the data was coded, I analyzed it. I found the three main themes that arose: the adjustment to Dartmouth, challenges that threaten successful graduation in four years, and the alums’ views on upward mobility and building social capital. I found that my interviewees experienced culture shock, feelings of impostor syndrome, and self-doubt. They encountered challenges and hidden barriers. Some FGLI students struggle to build social capital and utilize resources at Dartmouth. Furthermore, alums who did not build a good social capital base found it more challenging to obtain high-paying employment. They all struggled at some level with navigating life, having achieved financial upward mobility
Modeling Glaciers to Infer Paleoclimate Conditions During and Following the Last Glacial Maximum in Chirripó National Park, Costa Rica
No full textThe tropics are a critical part of Earth’s climate system, yet their role in global climate changes such as Quaternary glacial-interglacial cycles is poorly understood. Determining the timing, magnitude and spatial distribution of tropical cooling during the Last Glacial Maximum (LGM; ~26-19 ka) and Termination 1 (19-11.7 ka) is important for understanding the mechanisms that caused the global transition from glacial to interglacial conditions. There is a discrepancy between low-elevation records in the tropics which suggest only moderate cooling during the LGM, and high-elevation tropical records which suggest larger temperature decreases. This discrepancy may highlight an important role of water vapor in glacial-interglacial climate change, however there is a lack of quantitative records of high-elevation tropical temperature during the LGM and Termination 1. Glaciers in the humid inner tropics (~10°N-10°S) respond sensitively to temperature and past tropical glacier extents can provide valuable information about past climate conditions at high elevation. Here, I use past glacial extents to quantify the magnitude of high-elevation temperature change during the LGM and Termination 1 at a site in Costa Rica.
I simulate the extents of past glaciers in Chirripó National Park (9.48°N, 83.48°W) in the Cordillera de Talamanca Range of Costa Rica using a two-dimensional numerical glacier model that incorporates surface energy balance and ice-flow models. I input modern climate variables including temperature, precipitation, lapse rate, short-wave radiation and wind speed, and alter these variables to grow glaciers to mapped and dated extents. My results provide quantitative estimates of temperature, precipitation, and lapse-rates relative to modern during the LGM and Termination 1.
I show that LGM glacial extents require a temperature decrease of 8.2-9.7°C relative to modern with a range of precipitation changes (+100% to -80% relative to modern). Simulations with a temperature decrease of ~7.6°C relative to modern and no change in precipitation result in a completely ice-free landscape, suggesting that this landscape was only marginally glaciated. I compare the results with climate conditions inferred at similar high-elevation sites in the humid inner tropics and show that there was a relatively uniform and large magnitude of LGM cooling and Termination 1 warming
URBAN HORIZONS: NAVIGATING SUSTAINABLE PRACTICES IN 15-MINUTE CITIES
Get PDFClimate change poses a pressing challenge of the modern age. With wide-ranging implications for society, many fields play a role in shaping public policy and fostering awareness about the environmental crisis. One approach, the 15-minute city, aims to ensure that all essential services and amenities are accessible within a 15-minute walk or bike ride. This vision reflects a shift toward more sustainable and resilient urban environments. Cities such as Amsterdam, Boston, and Oxford, in adopting key elements of this concept, present diverse case studies for understanding how 15- minute city frameworks can effectively maximize socioeconomic interests. The analysis of Amsterdam’s level of spatial accessibility reveals disparities in tailoring solutions for different demographics. Boston’s approaches to adapting public infrastructure provide a model for understanding the policy mechanisms that can work toward 15-minute city goals. Oxford’s vision, which emphasizes the need for community engagement, presents a balanced approach to development. Through examining these cases, this thesis project explores how social policy mechanisms (e.g., public policies, zoning laws, and infrastructure investments) contribute to the realization of 15-minute cities in Western Europe and the United States.
This thesis also investigates the cultural factors that influence these initiatives and evaluates how demographic variations impact their effectiveness. The landscape of media, policy review, and relevant literature provides a platform for the various narratives. Due to the differing perspectives on climate solutions, this project explores the varied coverage in the pertinent literature. In order to understand the effects of “15-minute cities,” this project also works to introduce factors that impact urbanization and human stabilit
Advances Toward Prion Therapeutics Using Genome-Wide Discovery
No full textPrion diseases are rapidly progressing, invariably fatal neurodegenerative diseases that affect humans and animals. At the core of all prion diseases is a single protein, the mammalian prion protein (PrP). The conformational change of PrP from its cellular conformation (PrPC), into a misfolded conformation (PrPSc) is central to prion pathogenesis.
There are currently no effective therapies for any type of prion disease. The search for anti-prion therapeutics has faced numerous challenges, including prion strain specificity, drug resistance, delivery to the brain, limited efficacy against human disease despite favorable outcomes in rodent models, and efficacy that is highly dependent on the timing of administration. Despite these challenges, substantial advancements have been achieved. Specifically, therapies that reduce PrPC levels have demonstrated significant potential and successfully circumvent many of these obstacles. PrPC is required at the cell surface for initial prion infection, to sustain infection, and for prion-induced neurotoxicity. Therefore, therapies that reduce the amount of PrPC at the cell surface could be clinically relevant.
I performed genome-wide CRISPR-Cas9 knockout screens to identify regulators of cell surface PrPC in the prion-susceptible neuronal-like cell line, CAD5. These screens identified core genes involved in cell surface PrPC expression, revealed differences based on cellular differentiation state, and suggested potential therapeutic targets for prion disease. These genome-wide discovery efforts identified the oligosaccharyltransferase complex (OST), an enzyme complex essential for N-linked glycosylation, as a novel therapeutic target for prion disease. Inhibition of OST effectively treats rodent and human prions in culture, illustrating how genetic discovery can enhance our understanding of complex disease.
Creative strategies may be necessary to treat prion diseases. Therefore, we tested alternating treatment regimens with existing anti-prion therapeutics to avoid the emergence of drug-resistant prions. Additionally, I developed a method to perform FACS-based screening for genetic modifiers of prion infection in cultured cells. This will enable future genetic discovery experiments in prion-infected cells. The studies detailed herein aim to contribute to the progression of therapeutic development for prion diseases
Novel combination therapies for estrogen receptor-positive breast cancer driven by rational molecular mechanisms
Get PDFBreast cancer (BC) is the most common non-keratinocyte cancer diagnosed in women in the United States with approximately 300,000 new cases diagnosed each year. Despite a myriad of treatment options, BC remains the second-most deadly cancer. Estrogen receptor-positive (ER+) BC comprises 60-70% of BC diagnoses and is treated with endocrine therapies that limit ER signaling. Despite endocrine therapy options, ~1/3 of patients experience recurrence within 10-20 years of diagnosis. Novel therapeutic strategies are required to limit BC recurrence-related morbidity and mortality.
Radiotherapy is used as an adjuvant treatment for ER+ BC patients prior to the use of endocrine therapy. Radiation and endocrine therapies individually induce oxidative stress in cancer cells, tumors grown in mice, and human tumors. To investigate the potential to exploit this oxidative stress phenomenon through combination therapy, we tested a panel of ER+ breast cell line models in vitro and in vivo. Endocrine therapy was mimicked using hormone and estrogen deprivation. Radiation therapy was administered with a clinical irradiator. We demonstrated that concurrent treatment with radiation and endocrine therapy induces DNA damage, exacerbates oxidative stress, and significantly slows tumor growth across model systems.
Estrogen therapy was shown to be as effective as anti-estrogen therapy in 1981. It remains under-utilized because of the paradoxical method of promoting ER signaling with therapeutic levels of estrogen and the corresponding lack of mechanistic understanding of its therapeutic action. Estrogen therapy is only effective in ~30% of patients with advanced disease, and lack of a predictive biomarker and rational combination therapies to increase treatment efficacy have limited estrogen use. Our team’s previous work showed that overexpression of ER triggers response to estrogen therapy. When cells overexpressing ER are treated with physiological levels of estrogen, ER drives a hypertranscriptional phenotype that results in increased DNA damage and cell death. I demonstrate how this phenomenon can be exploited by chromatin-modifying agents. Co-treatment with the histone deacetylase inhibitor (HDACi) entinostat and 17beta-estradiol induced DNA damage, acetylation, chromatin accessibility, growth suppression, and synergistically delayed time to tumor recurrence. These collective studies provide pre-clinical evidence for combination therapies that have potential to improve outcomes in patients with ER+ BC