Gain of function of cardiac voltage-gated sodium channel (Nav1.5) leads to Long QT Syndrome Type 3 (LQT3). LQT3 phenotype can be exacerbated by expanding the perinexus, which is an intercellular nanodomain with high density of Nav1.5 in the intercalated disc. Following this finding, we found that elevating extracellular sodium and widening the perinexus synergistically exacerbated LQT3 phenotype, Importantly, we also found that perinexal expansion increases the susceptibility to cardiac arrest in aged LQT3, which demonstrated that perinexal expansion is an arrhythmogenic risk especially in aged LQT3 patients. Furthermore, we observed that the perinexus narrows with aging and conceals LQT3 phenotype, which suggests that perinexal narrowing may have a cardio-protective role during aging in LQT3. Surprisingly, following the finding of the synergistic effect of extracellular sodium elevation and perinexal widening on LQT3 phenotype in drug-induced LQT3 guinea pig hearts, we found that this synergistic effect was not observed in genetically-modified LQT3 mouse hearts, which is due to high sodium also increasing transient outward potassium current (Ito). In summary, the whole project investigated the role of the perinexus in LQT3 from different conditions including sodium, aging and species. The findings in this project discovered the importance of perinexal expansion in LQT3 and also the involvement of Ito in sodium regulating LQT3 phenotype in hearts which functionally express Ito channels. Therefore, a LQT3 animal model which has similar electrophysiology close to human may be a great option for translational purpose. / Doctor of Philosophy / Long QT Syndrome Type 3 (LQT3) is an inherited heart disease with the phenotype of long QT interval in ECG. It has been found that LQT3 phenotype gets worse when a very tiny space in the heart, termed as the perinexus, is wide due to cardiac edema. Following this finding, we also found that increasing sodium concentration together with wide perinexus can further exacerbate LQT3 phenotype in guinea pig hearts. Furthermore, we found that widening the perinexus in aged LQT3 hearts causes cardiac death but not in adult, which suggests that perinexal widening worsens LQT3 phenotype and even leads to cardiac death in aged hearts. Besides, we found that the perinexus narrows with aging and there is no difference in LQT3 phenotype between adult and aged hearts, which suggests that the narrow perinexus during aging may protect the hearts from cardiac death in LQT3. Surprisingly, we discovered that increasing sodium and widening the perinexus together fails to exacerbate LQT3 phenotype when compared with widening the perinexus alone in LQT3 mouse hearts, which is due to high sodium increasing transient outward potassium current (Ito). Notably, Ito channels are not functionally expressed in guinea pig hearts. In summary, the whole project investigated the role of the perinexus in LQT3 from different conditions including sodium, aging and species. The findings in this project discovered the importance of perinexal expansion in LQT3 and also the involvement of Ito in sodium regulating LQT3 phenotype in hearts. Therefore, a LQT3 animal model which has similar electrophysiology close to human may be a great option for translational purpose.

The first study investigates the factors that impact the duration of U.S. fresh fruit and vegetable imports. We employ both survival analysis (Kaplan Meier estimates and Cox proportional hazards model) as well as count data models. Our results indicate that SPS treatment requirements positively impact the duration of trade while new market access has the opposite effect. Other factors typically included in trade duration models (such as: GDP, transportation costs, tariff rates, etc.) were also investigated. We also employ a probit model to understand the factors impacting the probability that a country selects into exporting fresh fruits and vegetables to the United States. The second study estimates the goods-time elasticity of substitution for Food Stamp/SNAP participants versus non participants. We find that the elasticity of substitution for SNAP participants is not statistically different from zero. This indicates that SNAP participants have Leontief production function in household food production, implying that increasing the amount of SNAP benefits paid to participants will not lead to more food production if the time households dedicate to food preparation remains unchanged. This finding extends the analysis done by Baral, Davis and You (2011) and offers insights for policies related to the SNAP program. / Master of Science

Yes / Evidence has shown that older adults have lower accuracy in Theory-of-Mind (ToM) tasks compared to young adults, but we are still unclear whether the difficulty in decoding mental states in older adults stems from not looking at the critical areas, and more so from the ageing Asian population. Most ToM studies use static images or short vignettes to measure ToM but these stimuli are dissimilar to everyday social interactions. We investigated this question using a dynamic task that measured both accuracy and error types, and examined the links between accuracy and error types to eye gaze fixation at critical areas (e.g. eyes, mouth, body). A total of 82 participants (38 older, 44 young adults) completed the Movie for the Assessment of Social Cognition task on the eye tracker. Results showed that older adults had a lower overall accuracy with more errors in the ipo-ToM (under-mentalising) and no-ToM (lack of mentalisation) conditions compared to young adults. We analysed the eye gaze data using principal components analysis and found that increasing age and looking less at the face were related to lower MASC accuracy in our participants. Our findings suggest that ageing deficits in ToM are linked to a visual attention deficit specific to the perception of socially relevant nonverbal cues. / This study was funded by the Ministry of Higher Education Malaysia (FRGS/1/2016/SS05/SYUC/03/2) awarded to M.H.Y.

Many common statistical techniques for modeling multidimensional dynamic data sets can be seen as variants of one (or multiple) underlying linear/nonlinear model(s). These statistical techniques fall into two broad categories of supervised and unsupervised learning. The emphasis of this dissertation is on unsupervised learning under multiple generative models. For linear models, this has been achieved by collective observations and derivations made by previous authors during the last few decades. Factor analysis, polynomial chaos expansion, principal component analysis, gaussian mixture clustering, vector quantization, and Kalman filter models can all be unified as some variations of unsupervised learning under a single basic linear generative model. Hidden Markov modeling (HMM), however, is categorized as an unsupervised learning under multiple linear/nonlinear generative models. This dissertation is primarily focused on hidden Markov models (HMMs). On the first half of this dissertation we study enhancements on the theory of hidden Markov modeling. These include three branches: 1) a robust as well as a closed-form parameter estimation solution to the expectation maximization (EM) process of HMMs for the case of elliptically symmetrical densities; 2) a two-step HMM, with a combined state sequence via an extended Viterbi algorithm for smoother state estimation; and 3) a duration-dependent HMM, for estimating the expected residency frequency on each state. Then, the second half of the dissertation studies three novel applications of these methods: 1) the applications of Markov switching models on the Bifurcation Theory in nonlinear dynamics; 2) a Game Theory application of HMM, based on fundamental theory of card counting and an example on the game of Baccarat; and 3) Trust modeling and the estimation of trustworthiness metrics in cyber security systems via Markov switching models. As a result of the duration dependent HMM, we achieved a better estimation for the expected duration of stay on each regime. Then by robust and closed form solution to the EM algorithm we achieved robustness against outliers in the training data set as well as higher computational efficiency in the maximization step of the EM algorithm. By means of the two-step HMM we achieved smoother probability estimation with higher likelihood than the standard HMM. / Ph. D.

Introduction: Adverse Childhood Experiences (ACEs) are known to increase risk of mental health challenges throughout development, and sleep is known to decrease risk of mental health challenges. These have not been studied in tandem in younger cohorts. We investigated whether interactions between sleep duration and sleep regularity would moderate the impact of ACE exposure on risk for the development of mental health disorders. Methods: We conducted secondary cross-sectional analyses on the 2020-2021 waves of the National Survey of Children's Health (NSCH) (n = 92,669). We used logistic and ordinal regression to replicate known main effects of ACEs (total, household, community, and single) and sleep (duration and irregularity) on mental health diagnostic status and symptom severity, and we examined the interaction of ACEs and sleep on mental health diagnostic status. To correct for multiple comparisons, all original models were performed with one half of the dataset and then replicated in the second half. Follow-up analyses by age cohort (0-5, 6-11, 12-17 years) further examined interaction effects across development. Poverty level, parental education status, child age, child sex, neighborhood safety, neighborhood support, and race/ethnicity were included as covariates, as indicated in a priori acyclic graph (DAG) modeling. Results: Known main effects for ACE and sleep on mental health diagnoses were replicated across all models. Interactions between ACE exposure and adequate sleep duration or increased sleep irregularity were not clinically significant, although some were statistically significant due to large sample size, such that adequate sleep duration was associated with marginally increased risk of mental health diagnosis (Omnibus B = 0.048, p < 0.0001) and greater bedtime irregularity was associated with marginally decreased risk of mental health diagnosis (Omnibus B = -0.030, p < 0.001). Discussion: Main effects in this analysis are consistent with previous literature on ACEs, sleep, and mental health. However, interaction effects were largely small and clinically insignificant. Dichotomous and categorical parent-report items assessing sleep health may not be sensitive to interaction effects, compared with continuous data or physiological measurements. Further, examining mental health symptoms (rather than diagnosis status) may also allow for more nuanced understanding of potential interaction effects.

Words in utterance-final positions are often pronounced more slowly than utterance-medial words, as previous studies on individual languages have shown. This paper provides a systematic cross-linguistic comparison of relative durations of final and penultimate words in utterances in terms of the degree to which such words are lengthened. The study uses time-aligned corpora from 10 genealogically, areally, and culturally diverse languages, including eight small, under-resourced, and mostly endangered languages, as well as English and Dutch. Clear effects of lengthening words at the end of utterances are found in all 10 languages, but the degrees of lengthening vary. Languages also differ in the relative durations of words that precede utterance-final words. In languages with on average short words in terms of number of segments, these penultimate words are also lengthened. This suggests that lengthening extends backwards beyond the final word in these languages, but not in languages with on average longer words. Such typological patterns highlight the importance of examining prosodic phenomena in diverse language samples beyond the small set of majority languages most commonly investigated so far.

Previous research indicates that women prefer orgasms triggered by penile-vaginal intercourse (PVI) as compared to those triggered by direct manual stimulation of the clitoris. However, for reasons that are not well understood, most women are unable to reach PVI orgasms as often as they desire. In addition, it is unclear why many women prefer PVI orgasms to those triggered by direct clitoral stimulation. This study developed a more precise measure of PVI orgasm frequency and evaluated key predictors of this frequency, including duration of intercourse, physical and psychological health, and partner traits with implications for either mating quality or relationship quality. The present study also measured PVI orgasm importance and investigated why it is important for many women. The sample consisted of 835 adult women with experience in PVI. Mean PVI orgasm frequency was 50%, with 39.4% of women never or rarely having PVI orgasms, 37.1% sometimes having PVI orgasms, and 23.5% almost always or always having PVI orgasms. As a median response, women believed that PVI orgasm was “very important” and perceived importance was correlated with orgasm frequency (r = .31, p < .001), as were reasons for importance. Duration of intercourse showed a linear relationship with PVI orgasm frequency, but this finding was qualified for women at the low and high extremes of the orgasm frequency distribution. Body esteem, anxiety during intercourse, exercise, and general pain predicted PVI orgasm frequency. Sensitive male traits, although valued by women even more highly than alpha male traits, showed notably weaker relationships with PVI orgasm than did male alpha traits. This is consistent with evolutionary theories of orgasm, and it supports the view that the female orgasm may function to favor some males over others in terms of sire choice. Clinical and theoretical implications of the present findings are discussed.

No description available.

The expanding irrigated acreage in the Mississippi Delta has resulted in increased withdrawals that exceed the recharge rate of the Mississippi River Valley Alluvial Aquifer (MRVAA), leading to a decline in water levels. This trend poses a threat of rapid depletion, potentially resulting in deteriorating water quality and increased pumping costs in the region. Water-conserving irrigation practices are a key component to any potential solution, promising enhanced water use efficiency and sustainable agricultural practices. Nonetheless, farmers adopt these practices at different times. This study used a duration model to identify the factors that influence the timing of adoption of computerized hole selection (CHS) and center pivot (CP) practices. We found that farmers who attended extension meetings and held the belief that CHS would lower their input costs adopted it more promptly. Also, participation in conservation programs facilitated the quicker adoption of CP. Conversely, greater farming experience and a higher cumulative number of adopters were associated with slower adoption times for both CHS and CP.

No / The first purpose of this paper is to assess the short-run forecasting capabilities of two competing financial duration models. The forecast performance of the Autoregressive Conditional Multinomial–Autoregressive Conditional Duration (ACM-ACD) model is better than the Asymmetric Autoregressive Conditional Duration (AACD) model. However, the ACM-ACD model is more complex in terms of the computational setting and is more sensitive to starting values. The second purpose is to examine the effects of market microstructure on the forecasting performance of the two models. The results indicate that the forecast performance of the models generally decreases as the liquidity of the stock increases, with the exception of the most liquid stocks. Furthermore, a simple filter of the raw data improves the performance of both models. Finally, the results suggest that both models capture the characteristics of the micro data very well with a minimum sample length of 20 days.