A Process Improvement Study on a Military System of Clinics to Manage Patient Demand and Resource Utilization Using Discrete-Event Simulation, Sensitivity Analysis, and Cost-Benefit Analysis

Inefficiencies in the healthcare system are a growing concern. Long wait-times are a concern at military clinics because it takes servicemembers away from performing their duties. Managing wait-times are particularly challenging due to frequent relocations of servicemembers and variable patient demands that are less likely to be experienced by civilian clinics. Military clinics must be capable to meet increasing demand when servicemembers require a Deployment Health Assessment; it also needs to be capable of handling an instantaneous surge of walk-ins when a medical incident occurs in the local area. It must be able to meet these demands in a fiscally austere environment. Existing research primarily focuses on stand-alone clinics, whereas this research takes a novel approach of examining a system of clinics, in which some resources are shared. This research evaluates the impacts of variable staffing levels on total wait-time for the system of clinics at baseline demand and when demand increases, using discrete-event simulation, sensitivity analysis, and cost-benefit analysis. This research finds misallocated resources; the wait-time of alternative systems are sensitive to deployment and medical incident demands; and hiring an optometrist while removing an occupational medicine doctor provides the highest savings in baseline, deployment, and medical incident demand environments

Is Income Growth Enough to Reduce Total Fertility Rate in the Philippines? Empirical Evidence from Regional Panel Data

The population debate in the country has been dynamic and contentious. On the one hand, proponents of population management say that the rapid population growth in the Philippines has hindered the country’s economic development. On the other hand, others are saying that population growth is uncorrelated with economic growth. The core idea behind the link between population and economic growth is the demographic transition. Demographic transition is a change from a situation of high fertility and high mortality to one of low fertility and low mortality. Advocates of speeding the demographic transition placed emphasis on the need of public efforts to speed up the voluntary reduction in fertility rates as rapidly as possible, arguing that demographic transitions, where they have occurred, have typically been accelerated and even triggered, by proactive government policies. Those that are against direct government intervention argue that fertility rates fall when income rises and therefore, policies to increase income should be the main concern. This paper looks at the relationship between per capita income and total fertility rate (TFR), controlling for other factors, using a regional panel econometric model using data from the National Demographic and Health Survey (NDHS), Family Planning Survey (FPS), Family Income and Expenditure Survey (FIES), Labor Force Survey (LFS) and the Regional Gross Domestic Product (RGDP). The results show that increasing per capita income indeed reduces TFR but its impact is minimal and given that the country average per capita growth is low, it will take some time before the country benefits from the demographic transition through the income effect alone. The results of the analysis can also explain why the decline in fertility rate in the Philippines has been slower in recent times, lagging behind the significant changes in the international scene

Final design report: Spoiler Alert! Active aero for Formula SAE, Senior Design Spring 2022

The purpose of this Senior Design Project was to design and build an actively actuated front wing for the Oklahoma State Formula SAE competition car. This was accomplished using multiple engineering analysis and design methods, as well as multiple methods of product manufacturing and testing. The Aerodynamics, Mechanical, Electrical, and Testing sub-teams worked together to design and build a carbon fiber multi-tier actively actuated front wing. The results of testing showed that the wing decreased overall lap time, translating to up to an 8-place improvement in the skid pad competition, as well as up to a 12-place improvement in the autocross competition

A Low Concentration of Ethanol Impairs Learning but Not Motor and Sensory Behavior in Drosophila Larvae

Drosophila melanogaster has proven to be a useful model system for the genetic analysis of ethanol-associated behaviors. However, past studies have focused on the response of the adult fly to large, and often sedating, doses of ethanol. The pharmacological effects of low and moderate quantities of ethanol have remained understudied. In this study, we tested the acute effects of low doses of ethanol (∼7 mM internal concentration) on Drosophila larvae. While ethanol did not affect locomotion or the response to an odorant, we observed that ethanol impaired associative olfactory learning when the heat shock unconditioned stimulus (US) intensity was low but not when the heat shock US intensity was high. We determined that the reduction in learning at low US intensity was not a result of ethanol anesthesia since ethanol-treated larvae responded to the heat shock in the same manner as untreated animals. Instead, low doses of ethanol likely impair the neuronal plasticity that underlies olfactory associative learning. This impairment in learning was reversible indicating that exposure to low doses of ethanol does not leave any long lasting behavioral or physiological effects

Characterization of a novel alpha-conotoxin TxID from Conus textile that potently blocks rat alpha3/beta4 nicotinic acetylcholine receptors

The alpha 3 beta 4 nAChRs are implicated in pain sensation in the PNS and addiction to nicotine in the CNS. We identified an alpha-4/6-conotoxin (CTx) TxID from Conus textile. The new toxin consists of 15 amino acid residues with two disulfide bonds. TxID was synthesized using solid phase methods, and the synthetic peptide was functionally tested on nAChRs heterologously expressed in Xenopus laevis oocytes. TxID blocked rat alpha 3 beta 4 nAChRs with a 12.5 nM IC50, which places it among the most potent alpha 3 beta 4 nAChR antagonists. TxID also blocked the closely related alpha 6/alpha 3 beta 4 with a 94 nM IC50 but showed little activity on other nAChR subtypes. NMR analysis showed that two major structural isomers exist in solution, one of which adopts a regular alpha-CTx fold but with different surface charge distribution to other 4/6 family members. alpha-CTx TxID is a novel tool with which to probe the structure and function of alpha 3 beta 4 nAChRs

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Essential Role of Loop Dynamics in Type II NRPS Biomolecular Recognition.

Non-ribosomal peptides play a critical role in the clinic as therapeutic agents. To access more chemically diverse therapeutics, non-ribosomal peptide synthetases (NRPSs) have been targeted for engineering through combinatorial biosynthesis; however, this has been met with limited success in part due to the lack of proper protein-protein interactions between non-cognate proteins. Herein, we report our use of chemical biology to enable X-ray crystallography, molecular dynamics (MD) simulations, and biochemical studies to elucidate binding specificities between peptidyl carrier proteins (PCPs) and adenylation (A) domains. Specifically, we determined X-ray crystal structures of a type II PCP crosslinked to its cognate A domain, PigG and PigI, and of PigG crosslinked to a non-cognate PigI homologue, PltF. The crosslinked PCP-A domain structures possess large protein-protein interfaces that predominantly feature hydrophobic interactions, with specific electrostatic interactions that orient the substrate for active site delivery. MD simulations of the PCP-A domain complexes and unbound PCP structures provide a dynamical evaluation of the transient interactions formed at PCP-A domain interfaces, which confirm the previously hypothesized role of a PCP loop as a crucial recognition element. Finally, we demonstrate that the interfacial interactions at the PCP loop 1 region can be modified to control PCP binding specificity through gain-of-function mutations. This work suggests that loop conformational preferences and dynamism account for improved shape complementary in the PCP-A domain interactions. Ultimately, these studies show how crystallographic, biochemical, and computational methods can be used to rationally re-engineer NRPSs for non-cognate interactions

Dynamic visualization of type II peptidyl carrier protein recognition in pyoluteorin biosynthesis.

Using a covalent chemical probe and X-ray crystallography coupled to nuclear magnetic resonance data, we elucidated the dynamic molecular basis of protein recognition between the carrier protein and adenylation domain in pyoluteorin biosynthesis. These findings reveal a unique binding mode, which contrasts previously solved carrier protein and partner protein interfaces

Dynamic visualization of type II peptidyl carrier protein recognition in pyoluteorin biosynthesis.

Using a covalent chemical probe and X-ray crystallography coupled to nuclear magnetic resonance data, we elucidated the dynamic molecular basis of protein recognition between the carrier protein and adenylation domain in pyoluteorin biosynthesis. These findings reveal a unique binding mode, which contrasts previously solved carrier protein and partner protein interfaces