Cerebellar mechanisms for motor learning: Testing predictions from a large-scale computer simulation

The cerebellum is the major brain structure that contributes to our ability to improve movements through learning and experience. We have combined computer simulations with behavioral and lesion studies to investigate how modification of synaptic strength at two different sites within the cerebellum contributes to a simple form of motor learning—Pavlovian conditioning of the eyelid response. These studies are based on the wealth of knowledge about the intrinsic circuitry and physiology of the cerebellum and the straightforward manner in which this circuitry is engaged during eyelid conditioning. Thus, our simulations are constrained by the well-characterized synaptic organization of the cerebellum and further, the activity of cerebellar inputs during simulated eyelid conditioning is based on existing recording data. These simulations have allowed us to make two important predictions regarding the mechanisms underlying cerebellar function, which we have tested and confirmed with behavioral studies. The first prediction describes the mechanisms by which one of the sites of synaptic modification, the granule to Purkinje cell synapses (gr → Pkj) of the cerebellar cortex, could generate two time-dependent properties of eyelid conditioning—response timing and the ISI function. An empirical test of this prediction using small, electrolytic lesions of the cerebellar cortex revealed the pattern of results predicted by the simulations. The second prediction made by the simulations is that modification of synaptic strength at the other site of plasticity, the mossy fiber to deep nuclei synapses (mf → nuc), is under the control of Purkinje cell activity. The analysis predicts that this property should confer mf → nuc synapses with resistance to extinction. Thus, while extinction processes erase plasticity at the first site, residual plasticity at mf → nuc synapses remains. The residual plasticity at the mf → nuc site confers the cerebellum with the capability for rapid relearning long after the learned behavior has been extinguished. We confirmed this prediction using a lesion technique that reversibly disconnected the cerebellar cortex at various stages during extinction and reacquisition of eyelid responses. The results of these studies represent significant progress toward a complete understanding of how the cerebellum contributes to motor learning. ^

Comparison of two strategies for the treatment of acute myocardial infarction: In-hospital outcomes analysis

A strategy of pre-hospital reduced dose fibrinolytic administration coupled with urgent coronary intervention (PCI) for patients with STEMI (FAST-PCI) has been found to be superior to primary PCI (PPCI) alone. A coordinated STEMI system-of-care that includes FAST-PCI might offer better outcomes than pre-hospital diagnosis and STEMI team activation followed by PPCI alone. We compared the in-hospital outcomes for patients treated with the FAST-PCI approach with outcomes for patients treated with the PPCI approach during a pause in the FAST-PCI protocol. In-hospital data for 253 STEMI patients (03/2003–12/2009), treated with FAST-PCI protocol were compared to 124 patients (12/2009–08/2011), treated with PPCI strategy alone. In-hospital mortality was the primary endpoint. Stroke, major bleeding, and reinfarction during index hospitalization were secondary endpoints. Comparing the strategies used during the two time intervals, in-hospital mortality was significantly lower with FAST-PCI than with PPCI (2.77% vs. 10.48%, p = 0.0017). Rates of stroke, reinfarction and major bleeding were similar between the two groups. There was a lower frequency of pre- PCI TIMI 0 flow (no patency) seen in patients treated with FAST-PCI compared to the PPCI patients (26.7% vs. 62.7%, p<0.0001). Earlier infarct related artery patency in the FAST-PCI group had a favorable impact on the incidence of cardiogenic shock at hospital admission (FAST-PCI- 3.1% vs. PPCI- 20.9%, p<0.0001). The FAST-PCI strategy was associated with earlier infarct related artery patency and the lower incidence of cardiogenic shock on hospital arrival, as well as with reduced in-hospital mortality among STEMI patients.^

Longitudinal categorical data analysis: A continuous -time Markov chain approach

In this dissertation, we propose a continuous-time Markov chain model to examine the longitudinal data that have three categories in the outcome variable. The advantage of this model is that it permits a different number of measurements for each subject and the duration between two consecutive time points of measurements can be irregular. Using the maximum likelihood principle, we can estimate the transition probability between two time points. By using the information provided by the independent variables, this model can also estimate the transition probability for each subject. The Monte Carlo simulation method will be used to investigate the goodness of model fitting compared with that obtained from other models. A public health example will be used to demonstrate the application of this method. ^

First Trimester Screening and its Impact on Uptake of Diagnostic Testing

Introduction: First Trimester Screening (FTS) combines maternal age with fetal nuchal translucency (NT) and maternal analytes to identify pregnancies at an increased risk for Down syndrome and trisomy 18. Though the accuracy of this screening is high, it cannot replace the conclusive accuracy of prenatal diagnostic testing (PDT). Since FTS has been available, a decrease in the number of women who pursue PDT has been observed. This study sought to determine if there has been a significant change in the amount of PDT performed in our clinics, if the type of FTS result affects the patient’s decision regarding PDT, and what the patient’s intentions are regarding PDT. Material and Methods: A database review was performed for the two years prior and the two years after the January 2007 American College of Obstetricians and Gynecologists (ACOG) guidelines regarding FTS were issued. We compared the number of women who were AMA and the number of women who were AMA and had PDT between those time periods. We also determined the number of positive and negative FTS results, and determined how many of those patients had PDT. Finally, we surveyed our patients and referring physicians to determine: what the patient understands about FTS, what the patient’s intentions are regarding FTS, and how physicians present the option of FTS to their patients. Results: We determined that there was a 19.6% decrease in the amount of PDT performed when we compared the two time periods at our three specified clinics. Many of our patients were against having PDT prior to their genetic counseling session, but after they received genetic counseling, 76% of our population became open to the possibility of having PDT. Conclusion: Similar to previous studies, we determined that there has been a significant decrease in the number of PDT procedures performed at our clinics, which coincides with the release of the January 2007 ACOG statement regarding FTS. While our patients regarded FTS as a way to gain early information about their pregnancy in a non-invasive manner, they also stated they would use their results as a way to aid in their decision regarding PDT.

Does the choice of bottle nipple affect the oral feeding performance of very-low-birthweight (VLBW) infants?

BACKGROUND: There is a continuous debate regarding the best bottle nipple to be used to enhance the bottle-feeding performance of a preterm infant. Aim: To verify that feeding performance can be improved by using the bottle nipple with the physical characteristics that enhance infants' sucking skills. METHODS: Ten "healthy" VLBW infants (941+/-273 g) were recruited. Feeding performance was monitored at two time periods, when taking 1-2 and 6-8 oral feedings/d. At each time and within 24 h, performance was monitored using three different bottle nipples offered in a randomized order. Rate of milk transfer (ml/min) was the primary outcome measure. The sucking skills monitored comprised stage of sucking, suction amplitude, and duration of the generated negative intraoral suction pressure. RESULTS: At both times, infants demonstrated a similar rate of milk transfer among all three nipples. However, the stage of sucking, suction amplitude, and duration of the generated suction were significantly different between nipples at 1-2, but not 6-8 oral feedings/d.CONCLUSION: We did not identify a particular bottle nipple that enhanced bottle feeding in healthy VLBW infants. Based on the notion that afferent sensory feedback may allow infants to adapt to changing conditions, we speculate that infants can modify their sucking skills in order to maintain a rate of milk transfer that is appropriate with the level of suck-swallow-breathe coordination achieved at a particular time. Therefore, it is proposed that caretakers should be more concerned over monitoring the coordination of suck-swallow-breathe than over the selection of bottle nipples.

The association of food sources of calcium with weight class in adolescent girls

To determine the association of food sources of calcium with weight class in adolescent girls, the major food sources of calcium were determined for 718 sixth grade girls at three different time periods during an 18 month school-based health intervention program using a FFQ. To determine weight class, the BMI of each girl was stratified using CDC age and gender specific criteria at each time period. The percent contribution of the major food sources of calcium to total calcium intake was compared among the different weight classes at each time period, among those girls who had changed weight class at the different time periods and for those girls who did not change weight class at the different time periods. The mean total calcium intake increased by 20% between the first two time periods and by 12% between the first and last time periods with the intervention despite baseline total calcium intake already being greater than the recommended 1300 mg/day. The percent contribution of the major food sources of calcium were highly correlated among the weight classes that were compared throughout the study. Those girls who remained in the normal weight class throughout the study had the most consistent intake of food sources of calcium. Their top four food sources of calcium were different types of milk which provided greater than 50% of their total calcium intake. Despite there being no significant differences in the major food sources of calcium among the different weight classes, these data show a successful intervention for increasing calcium intake among adolescent girls. ^

Assessment of the performance of 3m 3500 organic vapor monitors over extended sampling durations

The purpose of this study was to assess the accuracy and precision of airborne volatile organic compound (VOC) concentrations measured using passive air samplers (3M 3500 organic vapor monitors) over extended sampling durations (9 and 15 days). A total of forty-five organic vapor monitor samples were collected at a State of Texas air monitoring site during two different sampling periods (July/August and November 2008). The results of this study indicate that for most of the tested compounds, there was no significant difference between long-term (9 or 15 days) sample concentrations and the means of parallel consecutive short-term (3 days) sample concentrations. Biases of 9 or 15-day measurements vs. consecutive 3-day measurements showed considerable variability. Those compounds that had percent bias values of <10% are suggested as acceptable for long-term sampling (9 and 15 days). Of the twenty-one compounds examined, 10 compounds are classified as acceptable for long-term sampling; these include m,p-xylene, 1,2,4-trimethylbenzene, n-hexane, ethylbenzene, benzene, toluene, o-xylene, d-limonene, dimethylpentane and methyl tertbutyl ether. The ratio of sampling procedure variability relative to variability within days was approximately 1.89 for both sampling periods for the 3-day vs. 9-day comparisons and approximately 2.19 for both sampling periods for the 3-day vs. 15-day comparisons. Considerably higher concentrations of most VOCs were measured during the November sampling period compared to the July/August period. These differences may be a result of varying meteorological conditions during these two time periods, e.g., the differences in wind direction, and wind speed. Further studies are suggested to further evaluate the accuracy and precision of 3M 3500 organic vapor monitors over extended sampling durations. ^

Has the development of a New Urbanist community affected the physical activity levels of residents in surrounding neighborhoods?

Study Aims. The neighborhood environment has been shown to influence physical activity levels, but little is known about how far-reaching these effects are. This study sought to determine whether or not the development of a New Urbanist community in Austin, Texas affected the physical activity levels of residents in surrounding neighborhoods. The results were stratified by demographic characteristics, residential distance from the New Urbanist community, and type of physical activity to determine if any observed changes varied by these factors.^ Methods. Self-report questionnaires were mailed to a random sample of households located within one mile of the New Urbanist development. The questionnaire included questions about physical activity behaviors before and after the community was constructed in 2006. Changes in reported levels of physical activity between the two time points were examined.^ Results. The prevalence and average minutes per week of total physical activity did not change. Significant increases in the frequency and quantity of moderate-intensity leisure-time physical activity were observed. The amount of time spent walking and biking for recreation outside of the neighborhood increased significantly among those living close to Mueller. The weekly time spent in vigorous-intensity activity increased significantly, especially among those living closer to Mueller. There were significant decreases in the prevalence of and time spent walking for transport. The use of Mueller parks and trails was highest among participants living close to Mueller.^ Conclusions. The nearby Mueller development does not appear to have encouraged sedentary members of the surrounding population to become physically active, but might be associated with increased weekly physical activity among those who were already active. The increase in vigorous-intensity physical activity and recreational walking/biking outside of the neighborhood among those subjects living closer to Mueller may be attributed to the use of Mueller parks and trails, which was also considerably higher among this group. People may be substituting the time they spent walking for transport before the Mueller development with moderate-intensity leisure-time physical activity. Future research should seek to identify barriers that may be preventing more nearby residents from using Mueller facilities for physical activity. ^

Examining seasonal variations in physical activity among low-income Hispanic walk-trail users living in the Cameron Park Colonia

This study examines variations in physical activity by season, and within seasons by age and gender among park users living in the Cameron Park Colonia, a low-income Hispanic community along the Texas-Mexico border. This is the first study of its kind to evaluate seasonal variations by physical activity among a Hispanic population. We hypothesized that (1) there are no differences in overall physical activity by season; (2) youth engage in more sport-related physical activity compared to adults, (3) males engage in more physical activity than females, and (4) there are differences in physical activity between walk-trail users compared to non walk-trail users in the park.^ Physical activity behavioral data was collected (males n=2,093; females n=1,014) at two time periods (winter 2007; summer 2007) via direct observations and assessed park use, walking trail use, and physical activity (moderate-to-vigorous physical activity (MVPA) by seasons. Frequencies for physical activities were calculated for gender, age groups, and season. Separate Pearson's chi-square analyses were used to address variations in physical activity, age, gender, intensity level of physical activity by season, between walk-trails users and non walk-trail users.^ People visiting the park engaged in more sedentary behavior in winter than summer and a higher percentage engaged in MVPA in the summer than winter (p<.05). More females engaged in light activity compared to males (p<.05). Walk-trail users consisted mostly of females and engaged in more light activity than non walk-trail users (p<.05) who participated in more MVPA.^ Increasing access to parks and walk-trails may be an intervention strategy to increase physical activity among Hispanics. More research is needed to assess promoting trail use and determining long-term effects on physical activity among minority/ethnic groups at greater risk of a sedentary lifestyle and reasons for trail use and non-use. Future studies should focus on the types of activities Hispanics engage in at different parks particularly between men and women. As a result of this study city officials and planners may use this information to build and design parks that cater to the types of activities that Hispanics engage in and may use to meet physical activity guidelines.^

Impact of environmental regulations on lead concentrations in Texas ambient air and water: 1970--1990

In the last two decades, the significance of lead has been addressed in a number of environmental regulations at the national and state levels. This project investigated the environmental regulations (Clean Air Act and Amendments, 1970-1990 and Clean Water Act of 1977) and their cumulative effects on lead in ambient air and water in the state of Texas. For this purpose, historical records from the Texas Water Development Board, Texas Natural Resources Conservation Commission, and the United States Geological Survey have been assembled and analyzed for temporal and spatial trends. These trends might correspond to the phase out of lead in gasoline and other regulations.^ This study concluded that there is a significant correlation (p $\leq$.001) between environmental regulations of lead in gasoline and the concentration of lead in ambient air. Lead concentrations in ambient air have been reduced by over 90 percent in the past twenty years. An overall significant difference (p $\leq$.001) was found in mean (94, 15 respectively) lead concentrations in surface water between two time periods, one at the beginning of the twenty year period and one at the end of the study period. There has been an overall reduction of lead concentrations in surface water in Texas of approximately 84 percent. However, this reduction cannot be statistically associated with any one regulation. Groundwater data could not be analyzed for lead concentrations because of limitations of reporting data as "less than". Approximately two percent of the groundwater data was analyzed by Oneway ANOVA and no significant difference was found between the means (18, 19 respectively) of two time periods, 1977-1979 and 1988-1990. This data is consistent with the regulations having a contributory affect on declining concentrations, but other factors cannot be ruled out as having added to these declines. This study can also serve as a starting point for a more in-depth study of environmental regulations and their impact on the environment. ^

LIFE SATISFACTION: A COMPARISON OF RETIRED AND EMPLOYED WOMEN

This research addressed the question of life satisfaction for retired and employed women with long-term employment in a typically female occupational setting. Questions of how women's retirement is related to life satisfaction have been largely neglected because of cultural assumptions about the relative unimportance of the work role in women's lives. It is generally believed that the major source of satisfaction for women is in traditional family roles. Therefore, it follows that retirement from work is not experienced as a loss for women.^ The actual consequences of women's retirement have not been examined systematically. Descriptive data about their lives are inadequate. It is not known what patterns and resources result from a lifetime of work for women.^ The objectives of the study were to test assumptions from role and continuity theory regarding life satisfaction for retired women and women employed late in life and to describe the retirement and work experiences of the women.^ Life satisfaction was measured by the Neugarten, Havighurst and Tobin Life Satisfaction Index. Perceptions of appropriate roles for females and males were assessed through an attitudinal sex-role instrument. A composite index, derived from perceptions of health, social participation, and income at two time periods, measured level of continuity. These indices and demographic information, attitudinal items about work and retirement, and social network data comprised the mailed, self-administered survey and the personal interviews.^ The study population included 91 retired and 53 employed women, 55 years or older with a minimum of 20 years continuous employment, who were enrolled in the pension program of a large retail store.^ The retired women's perceptions of their health and social participation were more positive than the employed women's. Traditional retired women demonstrated higher life satisfaction than nontraditional retired women. Both retired and employed women who perceived continuity in life patterns scored statistically higher on life satisfaction than women who perceived discontinuity. Financial planning was the area of greatest retirement concern for retired and employed women.^

RESPIRATORY COMPENSATION MECHANISMS IN THE UPPER AND LOWER RESPIRATORY TRACTS OF AN ANIMAL MODEL AFTER SUBCHRONIC INHALATION EXPOSURE TO FORMALDEHYDE: IMPLICATIONS FOR TOXICOLOGY RISK ASSESSMENT (DEPOSITION, DOSE RECEIVED, RESPONSE)

The potential for significant human populations to experience long-term inhalation of formaldehyde and reports of symptomatology due to this exposure has led to a considerable interest in the toxicologic assessment of risk from subchronic formaldehyde exposures using animal models. Since formaldehyde inhalation depresses certain respiratory parameters in addition to its other forms of toxicity, there is a potential for the alteration of the actual dose received by the exposed individual (and the resulting toxicity) due to this respiratory effect. The respiratory responses to formaldehyde inhalation and the subsequent pattern of deposition were therefore investigated in animals that had received subchronic exposure to the compound, and the potential for changes in the formaldehyde dose received due to long-term inhalation evaluated. Male Sprague-Dawley rats were exposed to either 0, 0.5, 3, or 15 ppm formaldehyde for 6 hours/day, 5 days/week for up to 6 months. The patterns of respiratory response, deposition and the compensation mechanisms involved were then determined in a series of formaldehyde test challenges to both the upper and to the lower respiratory tracts in separate groups of subchronically exposed animals and age-specific controls (four concentration groups, two time points). In both the control and pre-exposed animals, there was a characteristic recovery of respiratory parameters initially depressed by formaldehyde inhalation to at or approaching pre-exposure levels within 10 minutes of the initiation of exposure. Also, formaldehyde deposition was found to remain very high in the upper and lower tracts after long-term exposure. Therefore, there was probably little subsequent effect on the dose received by the exposed individual that was attributable to the repeated exposures. There was a diminished initial minute volume response in test challenges of both the upper and lower tracts of animals that had received at least 16 weeks of exposure to 15 ppm, with compensatory increases in tidal volume in the upper tract and respiratory rate in the lower tract. However, this dose-related effect was probably not relevant to human risk estimation because this formaldehyde dose is in excess of that experienced by human populations. ^

International comparison of wait times and quality of care: A pilot study

During the healthcare reform debate in the United States in 2009/2010, many health policy experts expressed a concern that expanding coverage would increase waiting times for patients to obtain care. Many complained that delays in obtaining care in turn would compromise the quality of healthcare in the United States. Using data from The Commonwealth Fund 2010 International Health Policy Survey in Eleven Countries, this study explored the relationship between wait times and quality of care, employing a wait time scale and several quality of care indicators present in the dataset. The impact of wait times on quality was assessed. Increased wait time was expected to reduce quality of care. However, this study found that wait times correlated with better health outcomes for some measures, and had no association with others. Since this is a pilot study and statistical significance was not achieved for any of the correlations, further research is needed to confirm and deepen the findings. However, if future studies confirm this finding, an emphasis on reducing wait times at the expense of other health system level performance variables may be inappropriate. ^

POPULATION CODING IN LAMINAR CORTICAL CIRCUITS

One of the fundamental questions in neuroscience is to understand how encoding of sensory inputs is distributed across neuronal networks in cerebral cortex to influence sensory processing and behavioral performance. The fact that the structure of neuronal networks is organized according to cortical layers raises the possibility that sensory information could be processed differently in distinct layers. The goal of my thesis research is to understand how laminar circuits encode information in their population activity, how the properties of the population code adapt to changes in visual input, and how population coding influences behavioral performance. To this end, we performed a series of novel experiments to investigate how sensory information in the primary visual cortex (V1) emerges across laminar cortical circuits. First, it is commonly known that the amount of information encoded by cortical circuits depends critically on whether or not nearby neurons exhibit correlations. We examined correlated variability in V1 circuits from a laminar-specific perspective and observed that cells in the input layer, which have only local projections, encode incoming stimuli optimally by exhibiting low correlated variability. In contrast, output layers, which send projections to other cortical and subcortical areas, encode information suboptimally by exhibiting large correlations. These results argue that neuronal populations in different cortical layers play different roles in network computations. Secondly, a fundamental feature of cortical neurons is their ability to adapt to changes in incoming stimuli. Understanding how adaptation emerges across cortical layers to influence information processing is vital for understanding efficient sensory coding. We examined the effects of adaptation, on the time-scale of a visual fixation, on network synchronization across laminar circuits. Specific to the superficial layers, we observed an increase in gamma-band (30-80 Hz) synchronization after adaptation that was correlated with an improvement in neuronal orientation discrimination performance. Thus, synchronization enhances sensory coding to optimize network processing across laminar circuits. Finally, we tested the hypothesis that individual neurons and local populations synchronize their activity in real-time to communicate information about incoming stimuli, and that the degree of synchronization influences behavioral performance. These analyses assessed for the first time the relationship between changes in laminar cortical networks involved in stimulus processing and behavioral performance.