Molecular Infectious Disease Epidemiology: Survival Analysis and Algorithms Linking Phylogenies to Transmission Trees

Recent work has attempted to use whole-genome sequence data from pathogens to reconstruct the transmission trees linking infectors and infectees in outbreaks. However, transmission trees from one outbreak do not generalize to future outbreaks. Reconstruction of transmission trees is most useful to public health if it leads to generalizable scientific insights about disease transmission. In a survival analysis framework, estimation of transmission parameters is based on sums or averages over the possible transmission trees. A phylogeny can increase the precision of these estimates by providing partial information about who infected whom. The leaves of the phylogeny represent sampled pathogens, which have known hosts. The interior nodes represent common ancestors of sampled pathogens, which have unknown hosts. Starting from assumptions about disease biology and epidemiologic study design, we prove that there is a one-to-one correspondence between the possible assignments of interior node hosts and the transmission trees simultaneously consistent with the phylogeny and the epidemiologic data on person, place, and time. We develop algorithms to enumerate these transmission trees and show these can be used to calculate likelihoods that incorporate both epidemiologic data and a phylogeny. A simulation study confirms that this leads to more efficient estimates of hazard ratios for infectiousness and baseline hazards of infectious contact, and we use these methods to analyze data from a foot-and-mouth disease virus outbreak in the United Kingdom in 2001. These results demonstrate the importance of data on individuals who escape infection, which is often overlooked. The combination of survival analysis and algorithms linking phylogenies to transmission trees is a rigorous but flexible statistical foundation for molecular infectious disease epidemiology.Comment: 28 pages, 11 figures, 3 table

An exploratory randomized controlled trial of assisted practice for improving sit-to-stand in stroke patients in the hospital setting

Objectives: To evaluate the amount of practice achieved and assess potential for effects on performance of 30 minutes of daily training in sit-to-stand. Design: Randomized controlled pilot study. Setting: Stroke rehabilitation unit, UK. Participants: Eighteen stroke patients needing 'stand by' help to sit-to-stand. Interventions: In addition to usual rehabilitation the experimental group (n=9) practised sit-to-stand and leg strengthening exercises for 30 minutes, on weekdays for two weeks, with a physiotherapy assistant. The control group received arm therapy. Main outcome measures: Frequency of sit-to-stands per day. Performance measures: rise time, weight taken through the affected foot at 'thighs off', number of attempts needed to achieve three successful sit-to-stands and the number of sit-to-stands performed in 60 seconds. Outcome was measured one and two weeks after baseline assessment. Results: Sit-to-stand frequency averaged 18 per day. Thirty minutes of practice in sit-to-stand resulted in a mean of 50 (SD 17.2) extra stands per day. There was a significant mean difference of 10% body weight taken through the affected foot after one week of intervention: The control group had reduced weight through the affected leg while the training group increased weight (F1,16 = 11.1, P=0.004, 95% confidence interval (CI) - 16.61 to - 3.72). No significant differences between groups were found on other measures. Results two weeks after baseline were inconclusive due to loss of five participants. Conclusions: Task-specific practice given for 30 minutes a day appears promising for patients learning to sit-to-stand. © SAGE Publications 2008

Is Feeding Algae to Lab- Grown Chicken the Future of Agriculture?

The goal of this ongoing research is to develop a more cost-effective process for culturing cells to produce synthetic or lab grown meat. Cellular agriculture is an emerging technology with potential to have a smaller energy footprint and decrease in land used for livestock compared to traditional meat production. Cellular agriculture will allow Utah to experience continued population growth without hampering the meat production of the state. However, currently the cost of producing synthetic meat is a constraint for expanding production and availability. This project is focused on testing various combinations of hydrolysates to determine a cost-effective alternative to current growth media. Yeast, wheat, soy, and algal hydrolysates are being tested in various combinations and cell growth is being monitored. The use of algal hydrolysates sets this work apart from contemporary research. Algal hydrolysates demonstrate a potential to be cheaper than current hydrolysates while still providing the cells with the needed nutrients. This research involves several phases of cell culturing. The first phase has involved the passaging of Human Embryonic Kidney (HEK) cells. These cells were selected due to their availability and stability for culture testing as well as the rapid growth they undergo in cultures. The HEK cells were used as a precursor to other mammalian cell types for the purpose of developing a protocol for the passaging and maintenance of mammalian cells. The second phase of the project will include analysis of the yield, confluency, cytotoxicity, and morphology of HEK cells after being cultured on various combinations of hydrolysates. These cultures will be repeated in triplicate to ensure accuracy in the results. Once the data from the cultures has been analyzed, chicken cells will be tested in the five hydrolysates with the most promising outcomes in HEK cultures

Studies to investigate the role of free radicals and low density lipoprotein oxidation in the development of atherosclerosis in human subjects with diabetes mellitus

The oxidation of low density lipoprotein (LDL) by free radicals (FR) may be one of the early events in the production of atheroma. I have taken several approaches to test the overall hypothesis that more FR oxidation of LDL occurs in diabetes explaining its associated excess risk of atherosclerosis. Before embarking on the body of the work a methodological problem was first clarified. Diene conjugated fatty acids (DCFA) are one of the products of FR attack on lipids, and are used as markers of FR activity however dietary fat also contains DCFA. Therefore a study was designed to test the hypothesis that diet is an important source of DCFA in human serum and tissues, thereby questioning the use of DCFA as a marker of FR activity. The results suggest that diabetes per se is not associated with a lower TRAP but that an interaction may exist between diabetes and smoking which would help explain the even greater risk that smoking poses to diabetics and suggests that smoking diabetics would be more vulnerable to FR damage in circumstances of increased FR load such as following ischaemic episodes. Many explanations for the lack of correlation between peroxidisability and TRAP are discussed in the text. One possibility is that peroxidisability is influenced by the balance between lipid soluble antioxidants and the availability of oxidisable substrate and that TRAP is chiefly contributed to by water soluble antioxidants. Vitamin E is the major lipid soluble antioxidant and this balance can be represented by the ratio of the concentrations of vitamin E to cholesterol plus triglyceride termed the vitamin E status. A study was undertaken to test the hypothesis that:- individuals suffering from diabetes have lower vitamin E levels relative to levels of oxidisable lipids than do non-diabetics; or in other words, have lower vitamin E status which is in turn associated with evidence of greater lipid peroxidation in diabetes. Plasma vitamin E status and TEARS concentration were determined in thirty five diabetic and twenty nine non-diabetic subjects. Vitamin E status was not significantly different in the diabetic and non-diabetic subjects. TEARS concentrations were significantly higher in diabetics than nondiabetics but did not correlate with vitamin E status. This study confirmed reports that increased lipid peroxidation occurs in diabetes but suggest that this is little influenced by vitamin E status. Epidemiological evidence suggests an inverse correlation between dietary antioxidants and the risk of atherosclerotic disease. Ten diabetics and non-diabetics took part in a study aimed at testing the hypothesis that vitamin C and vitamin E dietary supplementation increase the TRAP and vitamin E status of plasma respectively, and reduces lipid peroxidation in diabetics and non-diabetics. In addition to the effect of vitamin supplementation upon plasma TEARS the effect on copper stimulated oxidation of LDL isolated by ultracentrifugation was also assesed. Vitamin C, 1g per day, was associated with a rise in TRAP, a reduction in vitamin E status and possibly with a delayed rise in TEARS. These findings could be explained by a pro-oxidant effect of high dose vitamin C in individuals on a normal diet containing iron. Vitamin E, 300mg per day, was associated with a rise in vitamin E status, no change in TRAP, no change in several parameters of LDL oxidation but with a fall in TEARS. Although the latter result is consistent with a reduction in FR lipid oxidation in response to vitamin E supplementation several other explanations are discussed in the text. The presence of diabetes did not alter the response to vitamin supplementation. Overall the studies in this thesis do not provide evidence for the contention that diabetes might be a state of excess FR lipid oxidation thus explaining its associated high risk of atherosclerotic disease. (Abstract shortened by ProQuest.)

SOCIODEMOGRAPHIC, COGNITIVE, AND AFFECTIVE ANTECEDENTS TO PREGNANCY PLANNING AMONG WOMEN WITH DIABETES

The prevalence of diabetes mellitus is increasing among women of reproductive age and can elevate risk during pregnancy of fetal malformation, perinatal loss, preeclampsia, preterm birth, and macrosomia. Those risks can be reduced by use of contraception until blood glucose is lowered, but current data suggests that women with diabetes are not consistently engaging in family planning practices. To facilitate the improvement of family planning services for women with diabetes, the goal of this three-paper dissertation was to describe the prevalence, racial and ethnic health disparities, contraceptive behaviors, and contraceptive attitudes of women with diabetes. Aim 1 was to estimate the prevalence of diagnosed diabetes, undiagnosed diabetes, suboptimal preconception glycemic control, and prediabetes among women of reproductive age by race and ethnicity. Aim 2 was to distinguish the effectiveness of contraception used by women with diabetes and evaluate the hypothesis that women with diabetes used less effective contraception than women without diabetes. Aim 1 and Aim 2 were conducted using data from the National Longitudinal Study of Adolescent to Adult Health (Add Health), which contained biological and survey data from women aged 24−32 in 2007−2008. Aim 3 was to describe the attitudes of women with diabetes towards using contraception (including attitudes about the benefits, barriers, and self-efficacy related to contraception use), for which primary data collection was conducted at a high-risk obstetrics clinic with postpartum women. In Aim 1, our data supported the hypothesis that diabetes prevalence varied by race and ethnicity. The highest rates of total diabetes, undiagnosed diabetes, prediabetes, and suboptimal preconception glycemic control were found among non-Hispanic black women. In Aim 2, our data supported the hypothesis that women with diabetes would be more likely to use no contraception than their normoglycemic peers. In Aim 3, we found support for the hypothesis that women with diabetes who had a greater perception of contraception’s benefits had greater odds of using procedure/prescription contraception in the postpartum period. Together, the findings from the three papers in this dissertation identified priority populations and promising targets for future intervention development to improve family planning service delivery to women with diabetes.Doctor of Philosoph

Indirect effects of a competitor on life history and reproductive traits in a cavity nesting bird

Research on life history evolution in birds has revealed both direct and indirect effects of predation. Increased levels of nest predation favor reproductive behaviors that reduce the threat of predators on offspring or allow parents to bet hedge for future reproductive attempts. In this study, I investigate whether the presence of a competitor, the house wren (Troglodytes aedon), results in similar indirect effects on life history and reproductive behaviors of Carolina chickadees (Poecile carolinensis). House wrens compete for nesting cavities and will kill Carolina chickadee eggs and nestlings. I monitored nest boxes in Western North Carolina where exposure to house wrens varies. I surveyed house wren presence at active Carolina chickadee nests and measured clutch size and mass, incubation, provisioning rates, nestling growth rates, development, and fledging success of chickadees. House wren takeover accounted for 35% of nesting failures, more than any other cause of failure in our study. I found smaller clutch sizes in areas where house wrens were present. However, I did not detect any effects of house wren presence on chickadee egg size, incubation, provisioning, growth, or development. These results suggest that house wren presence affects a narrow range of life history traits early in the nesting period, possibly because this is when house wrens are the biggest threat. Reducing clutch size may be a strategy used by Carolina chickadees to decrease reproductive investment in an environment where early nest failure is probable, allowing adults to reserve energy for survival to the next breeding season

The Relationship Between Alternative Fieldwork Approaches and Student Competence and Confidence for Occupational Therapy in Behavioral Health

Purpose: The purpose of this case-series study was to assess the relationship between three instructional methods that fall within the parameters of the revised Accreditation Council for Occupational Therapy Education fieldwork objective C.1.9 and perceived student competence and confidence in providing therapy services in a behavioral health setting. Methods: The study included a convenience sample of (n=49) graduate students enrolled in an entry-level Doctor of Occupational Therapy program and a Doctor of Physical Therapy program in the Midwest. The participants attended a presentation on bipolar disorder and were randomly assigned to engage in one of three instructional methods: (a) lived experience academics, (b) problem-based learning, and (c) standardized patients to further learn about bipolar disorder. Results: Analyses revealed no significant interaction effects on competence across instructional methods but did reveal significant main effects of group and time on confidence. Confidence increased across all instructional methods and exhibited a significant difference between the lived experience academics and standardized patient. Significance: The study results demonstrate a need for further research on how to best prepare occupational therapy students for behavioral health settings

Administrators Matter in NGSS Implementation (2019): Updated Findings on How School and District Leaders Are Making Science Happen

Administrators need learning opportunities if they are to adequately understand the substantial shifts of the Next Generation Science Standards (NGSS) and support teachers in implementing them. Accordingly, the K-8 NGSS Early Implementers Initiative has consistently expanded the professional learning it provides for administrators, particularly for site administrators, who generally have the most contact with teachers. This tenth evaluation report in the series, intended for site and district administrators and state leaders, highlights:- The professional learning strategies used by the Initiative to engage and empower administrators to support NGSS implementation (includes two district vignettes)- The impact of the professional learning on administrator understanding and actions- The challenges experienced by the Initiative in trying to involve administrators- Recommendations for increasing administrator help with science implementatio

Eating As Treatment (EAT): A Stepped-Wedge, Randomized Controlled Trial of a Health Behavior Change Intervention Provided by Dietitians to Improve Nutrition in Patients With Head and Neck Cancer Undergoing Radiation Therapy (TROG 12.03)

Purpose: Malnutrition in head and neck cancer (HNC) treatment is common and associated with poorer morbidity and mortality outcomes. This trial aimed to improve nutritional status during radiation therapy (RT) using a novel method of training dietitians to deliver psychological techniques to improve nutritional behaviors in patients with HNC. Methods and Materials: This trial used a stepped-wedge, randomized controlled design to assess the efficacy of the Eating As Treatment (EAT) program. Based on motivational interviewing and cognitive behavioral therapy, EAT was designed to be delivered by oncology dietitians and integrated into their clinical practice. During control steps, dietitians provided treatment as usual, before being trained in EAT and moving into the intervention phase. The training was principles based and sought to improve behavior-change skills rather than provide specific scripts. Patients recruited to the trial (151 controls, 156 intervention) were assessed at 4 time points (the first and the final weeks of RT, and 4 and 12 weeks afterward). The primary outcome was nutritional status at the end of RT as measured by the Patient-Generated Subjective Global Assessment. Results: Patients who received the EAT intervention had significantly better scores on the primary outcome of nutritional status at the critical end-of-treatment time point (β = −1.53 [−2.93 to −.13], P =.03). Intervention patients were also significantly more likely than control patients to be assessed as well-nourished at each time point, lose a smaller percentage of weight, have fewer treatment interruptions, present lower depression scores, and report a higher quality of life. Although results were not statistically significant, patients who received the intervention had fewer and shorter unplanned hospital admissions. Conclusions: This trial is the first of its kind to demonstrate the effectiveness of a psychological intervention to improve nutrition in patients with HNC who are receiving RT. The intervention provides a means to ameliorate malnutrition and the important related outcomes and consequently should be incorporated into standard care for patients receiving RT for HNC