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Use of Public Research and Manufacturing Enterprises to Lower Prescription Drug Prices and Increase Innovation
Get PDFThis article proposes building on the success of publicly funded drug research and development and expanding the model to include the full cycle development, testing, manufacture and distribution of innovative and affordable new drugs
An Appalachian Perspective on Suicide: A Focus on West Virginia’s Unique Context
No full textINTRODUCTION: The Appalachian region, spanning 13 states from New York to northern Mississippi, experiences the suicide rates in the United States (U.S.), underscoring a public health crisis exacerbated by persistent socioeconomic challenges. West Virginia (WV), the only state entirely within Appalachia, serves as a focal point for understanding the broader suicide crisis in the region, as WV has the highest suicide rates in the region. Moreover, the state has several unique socioeconomic factors, like increased poverty, lower educational attainment, limited access to healthcare, and a high prevalence of chronic pain and substance that may contribute to elevated rates of suicide. This dissertation addresses gaps in understanding suicide in WV by: (1) identifying and discussing the discrepancies in suicide risk measures used in state-based and national population-based surveys (2) examining the relationship between socioeconomic deprivation and suicide rates in WV (3) exploring socioeconomic and related factors of lifetime suicide risk in WV.
METHODS: This dissertation employed a mixed-methods approach. First, a two-part systematic review was conducted to identify suicide risk measures used across large state-based and national population-health surveys. Second, negative binomial regression models were used to assess the relationship between socioeconomic deprivation, using three preestablished indices, and suicide rates. Lastly, logistic regression models were used to examine the factors associated with suicide risk among WV adults using data collected from the 2021 MATCH survey.
RESULTS: The results from the systematic review revealed significant variability in how suicide risk is measured, with implications for surveillance, policy, and targeted prevention strategies. Aim two analyses demonstrated a strong association between deprivation indices and suicide rates, highlighting several key index items that have particular relevance when examining suicide rates in WV. Aim three analyses identified rural-urban disparities in risk factors, emphasizing the need for region-specific prevention efforts.
CONCLUSION: The findings from this dissertation underscore the importance of enhancing surveillance methods to better capture suicide incidence and prevalence, informing long-term prevention strategies. Findings also highlighted key socioeconomic factors which may contribute to suicide risk in WV, underscoring the urgent need for tailored, region-specific interventions. By addressing gaps in measurement and examining the influence of socioeconomic deprivation and rural-urban disparities, this work provides actionable insights to inform targeted interventions and improve suicide prevention efforts in Appalachia, particularly in W
Examining the Online Marketing of Sport Psychology Services by Certified Mental Performance Consultants: A Rhetorical Analysis
Get PDFIn recent years, Certified Mental Performance Consultants (CMPCs) have increased their footprint in social media to connect with those that seek sport psychology services (Cotterill & Symes, 2014). The aim of this study was to identify what social media platforms are most used among CMPCs and what persuasive elements are used to draw in potential clients. All active CMPCs from 1992 to 2023 were examined to determine the most popular social media platforms used, followed by an analysis of 219 CMPCs based on their ownership of a LinkedIn account and professional website. Results indicated that LinkedIn and the consultants’ custom professional website were the most popular online platforms used. The most common rhetorical strategies used included authority, ethos, and pathos to market the benefits of their consulting services to the public. Lastly, master’s level CMPCs used reciprocity and social proof in greater volume, whereas doctoral level CMPCs leaned more on authority to establish persuasiveness. Future research could explore short video content produced by CMPCs on social media platforms to gain new insights into consumer engagement with sport psychology services
SARS-CoV-2 immunogenicity models inform novel strategies that can improve mRNA vaccines
Get PDFThe onset of the 2020 COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, issued a call to action in the fields of biomedical science and public health to implement strategies to contain and protect against the viral threat. In record times, pharmaceutical companies produced antiviral therapies and novel mRNA vaccines that were approved by the FDA for human use. With time, these vaccines were able to assist in ending the pandemic. However, time also showed the limits of mRNA vaccine induced immunity. Despite antibody responses being initially robust, titers dramatically wane with time and are limited in cross-neutralizing ability. As SARS-CoV-2 viral variants of concern continued to emerge across the globe with mutations that enabled increased pathogenicity as well as greater transmission rates, strategies to improve the protective capacity of vaccines became urgently needed. Due to differences between the mouse and human ACE2 receptors, authentic SARS-CoV-2 virus causes limited disease in mice. To model viral pathogenesis in preclinical small animal models, the K18-hACE2 transgenic mouse in which human ACE2 is expressed under the cytokeratin 18 promoter, was returned to research use after its initial implementation for modeling SARS-CoV infection. We worked to characterize the pathology and disease phenotypes of emerging variant of concern (VOC) strains to prepare translatable preclinical models for the evaluation of new vaccination strategies. The Alpha (B.1.1.7) and Beta (B.1.351) variants caused differential phenotypes compared to the ancestral variant and lowered the lethal dose of virus in K18-hACE2 mice. Here, we describe the efforts to characterize the mouse challenge model for the SARS-CoV-2 Delta variant (B.1.617). In a comparison against the Alpha variant administered at the same dose, Delta caused delayed onset of morbidity phenotypes. Despite this, Delta-challenged animals showed equal viral burden in the lung and nasal wash to Alpha animals which were approaching humane endpoint criteria. Interestingly, the lung tissues of Delta-challenged animals showed increased inflammation by histopathological analysis, and high expression of proinflammatory genes in transcriptomic analyses. With these data, we determined that the K18-hACE2 mouse model of Delta challenge develops high pulmonary inflammation compared to prior models. With an understanding of the severe Delta challenge model, we aimed to develop another preclinical mouse model to better understand a prominent COVID-19 comorbidity: obesity. Individuals with obesity and metabolic disease were determined early in the pandemic to be at greater risk of developing severe disease. With the understanding that obesity predisposes to more severe infections due to dysregulated inflammatory responses, and clinical reports that persons with high body mass index (BMI) experience more dramatic antibody waning, establishing a model to evaluate vaccines in an immunodeficient host was critical. We used the diet-induced obesity (DIO) approach to accomplish metabolic disease phenotypes in K18-hACE2 animals and observed that DIO animals after SARS-CoV-2 Alpha challenge experience a shortened time to morbidity. DIO female animals had higher lung viral burden than lean animals post-challenge. Female DIO animals also showed greater expression of antiviral genes and interferon gamma in the lungs. Male DIO animals showed a decrease in antibody related genes compared to lean animals. With an understanding of the unique immune responses in healthy and comorbid hosts, we moved to use them to evaluate the correlates of protection of known and novel vaccine strategies. Intranasal vaccines are hypothesized to generate superior immunity to muscular vaccines for respiratory pathogens due to the elicitation of immunity in the respiratory mucosa. We vaccinated K18-hACE2 mice with two doses of an intranasal virus like particle expressing RBD proteins adjuvanted with a bacterial enzymatic combinatorial chemistry adjuvant (BECC470). Compared to intramuscular mRNA vaccinated mice, intranasal mice developed higher anti-RBD IgA responses. Despite showing lower in vitro virus neutralization, nasal vaccinated animals were protected against lethal Delta variant challenge and exhibited less lung inflammation than mRNA vaccinated mice. Unfortunately, the cross protection from nasal vaccination was limited, and only mRNA vaccinated animals were protected in a follow up experiment using the Omicron variant. Next, mRNA vaccination was evaluated in the DIO K18-hACE2 comorbidity model. Despite hypotheses that DIO animals would be poorly protected after vaccination, DIO male and female animals developed high titers of anti-RBD IgG. Single cell RNA sequencing suggested differences in naïve B cell and macrophage populations between lean and DIO animals after Omicron challenge. Still, this was accompanied by limited viral burden was detected in the lung tissue. These experiments demonstrated the efficacy of mRNA vaccines against multiple viral variants and in immunocompromised individuals. Still, mRNA vaccines demonstrate limitations in immune breadth and durability. Finally, we designed experiments to characterize the immune response to mRNA vaccination to identify targets for novel immune-potentiating adjuvants. First, we identified the minimum protective dose of an mRNA COVID-19 vaccine for mice that provided protection against Omicron challenge six months after vaccination. With a known dose, we then profiled the early immunological events that occur post-vaccination and identified a correlative relationship between the chemokines CXCL10 and CXCL13, and protective antibody levels. We hypothesized that exploiting expression of these chemokines using mRNA genetic adjuvants administered with the vaccine could support better antibody responses. Cxcl13-mRNA administered with a low dose of mRNA vaccine increased antibody levels to match a higher dose of vaccine alone. These data provide exciting proof of concept to the use of mRNA genetic adjuvants that can improve vaccine immunity but may also have applications across human diseases, through tailoring of the host immune response. We hypothesize that the emergence of mRNA technology during the COVID-19 pandemic introduced a new approach to solving problems in human health and has near-boundless potential
Evaluation of Rare Earth Element Hydraulic Preconcentrate Material Characteristics and Instrumentation Design
No full textAbstract
Evaluation of Rare Earth Element Hydraulic Preconcentrate Material Characteristics and Instrumentation Design
Michael King
Manufacturing rare earth element (REE) hydraulic preconcentrate (HPC) by the West Virginia University Water Resources Institute (WRI) requires dewatering of high-water content low solids material. The HPC is hydraulically placed and stored in geotextile tubes with an incoming total solids of 2% and a desired passively dewatered solids content of 30%. The identification of the different material characteristics from two field HPC production sites is (one coal based and one hardrock based) required for identification. For the one coal based, the HPC material was tested and classified based on ASTM protocols. From these tests, the material was classified as a poorly graded sand (SP). Field observations indicated a high percentile of fines while also maintaining larger clumps due to metals contained within the material and polymer additives used for flocculation. For the hardrock site, the HPC material tested as a ML-silt and consolidation tests performed indicated that HPC elastic phase of consolidation is entirely absent as primary consolidation occurs immediately followed by a slow secondary consolidation phase. The coefficient of consolidation (cv) average values were determined to be 0.01628, 0.02827, and 0.03326 in2/min. These cv values coincide with previous research on acid mine drainage treatment precipitates.An instrumentation selection process undertaken with the objective to track the total solids developing within a Geobag under passive dewatering with volumetric change to determine an average timeframe to reach the 30% total solids target value. From tests and analysis conducted on different instruments, it was found that most conventional soil moisture probes are not adequate for use with the HPC sludge-like materials due to high volumetric reductions of the material during dewatering. Reliance on a manual field testing was implemented. The first Geobag experienced a decrease of 1 to 2% total solids over a three-month period. The Marcy Scale device showed a percent difference of 148.52% in its measurements compared to lab results for influent total solids. Differences are attributed to the influent’s low total solids content not being able to be precisely measured using the Marcy Scale device
