Methods in Hypothesis Testing, Markov Chain Monte Carlo and Neuroimaging Data Analysis

This thesis presents three distinct topics: a modified K-S test for autocorrelated data, improving MCMC convergence rate with residual augmentations, and resting state fMRI data analysis. In Chapter 1, we present a modified K-S test to adjust for sample autocorrelation. We first demonstrate that the original K-S test does not have the nominal type one error rate when applied to autocorrelated samples. Then the notion of mixing conditions and Billingsley's theorem are reviewed. Based on these results, we suggest an effective sample size formula to adjust sample autocorrelation. Extensive simulation studies are presented to demonstrate that this modified K-S test has the nominal type one error as well as reasonable power for various autocorrelated samples. An application to an fMRI data set is presented in the end. In Chapter 2 of this thesis, we present the work on MCMC sampling. Inspired by a toy example of random effect model, we find there are two ways to boost the efficiency of MCMC algorithms: direct and indirect residual augmentations. We first report theoretical investigations under a class of normal/independece models, where we find an intriguing phase transition type of phenomenon. Then we present an application of the direct residual augmentations to the probit regression, where we also include a numerical comparison with other existing algorithms.Statistic

Thank God That Regressing Y on X is Not the Same as Regressing X on Y: Direct and Indirect Residual Augmentations

What does regressing Y on X versus regressing X on Y have to do with MCMC? It turns out that many strategies for speeding up data-augmentation type algorithms can be understood as fostering independence or “de-correlation” between a regression function and the corresponding residual, thereby reducing or even eliminating dependence among MCMC iterates. There are two general classes of algorithms, those corresponding to regressing parameters on augmented data/auxiliary variables and those that operate the other way around. The interweaving strategy (Yu and Meng, 2011, JCGS) provides a general recipe to automatically take advantage of both, and it is the existence of two different types of residuals that makes the interweaving strategy seemingly magical in some cases and promising in general. The concept of residuals—which depends on actual data—also highlights the potential for substantial improvements when data augmentation schemes are allowed to depend on the observed data. At the same time, there is an intriguing phase transition type of phenomenon regarding choosing (partially) residual augmentation schemes, reminding us once more of the prevailing issue of trade-off between robustness and efficiency. This article reports on these latest theoretical investigations (using a class of normal/independence models) and empirical findings (using a posterior sampling for a Probit regression) in the search for effective residual augmentations—and ultimately more MCMC algorithms—that meet the 3-S criterion: simple, stable, and speedy.Statistic

Induction of heartwood formation in young Indian sandalwood (Santalum album L.) by gas elicitors

Induction of heartwood formation in 6-year-old Indian sandalwood (Santalum album L.) trees by treatment with carbon dioxide, ethylene, nitrogen, and wounding was investigated. All treatments induced fragrant heartwood formation upward and downward from the drill hole. The amount of heartwood formed above and below the drill hole depended on the treatment in the order nitrogen>carbon dioxide>ethylene>wounding, whereas the radial extension proportion was, in order, nitrogen>carbon dioxide>ethylene=wounding. Based on the chemical analysis (GC–MS) and evaluation of the essential oil quality and heartwood properties, heartwood induced by carbon dioxide showed the maximum similarities to naturally formed heartwood, which included the same color, similar chemical composition, reasonable oil content, and quality essential oil, whereas ethylene, nitrogen, and wounding treatment showed fewer similarities to natural heartwood. The results suggest that carbon dioxide is a promising candidate gas elicitor for inducing heartwood formation in young S. album

Genetic diversity and selection of three nuclear genes in Schistosoma japonicum populations

Background: The blood fluke, Schistosoma japonicum still causes severe disease in China, the Philippines and Indonesia. Although there have been some studies the molecular epidemiology of this persistent and harmful parasite, few have explored the possibility and implications of selection in S. japonicum populations. Methods: We analyzed diversity and looked for evidence of selection at three nuclear genes (SjIpp2, SjFabp and SjT22.6) in 13 S. japonicum populations. Results: SjT22.6 was found to exhibit high nucleotide diversity and was under positive selection in the mountainous region of mainland China. As a tegumental protein, its secondary and tertiary structure differed between S. japonicum strains from the mountainous and lakes regions. In contrast, SjIpp2 and SjFabp had relatively low levels of nucleotide diversity and did not show significant departure from neutrality. Conclusions: As a tegument-associated antigen-encoding gene of S. japonicum, SjT22.6 has high nucleotide diversity and appears to be under positive selection in the mountainous region of mainland China

EST analysis of gene expression in the tentacle of Cyanea capillata

AbstractJellyfish, Cyanea capillata, has an important position in head patterning and ion channel evolution, in addition to containing a rich source of toxins. In the present study, 2153 expressed sequence tags (ESTs) from the tentacle cDNA library of C. capillata were analyzed. The initial ESTs consisted of 198 clusters and 818 singletons, which revealed approximately 1016 unique genes in the data set. Among these sequences, we identified several genes related to head and foot patterning, voltage-dependent anion channel gene and genes related to biological activities of venom. Five kinds of proteinase inhibitor genes were found in jellyfish for the first time, and some of them were highly expressed with unknown functions

The associations of economic growth and anaemia for school-aged children in China

Economic growth has brought improvements in many areas of child health, but its effects on anaemia among school-aged children remain unknown. However, this is important because iron deficiency anaemia is common and is the main cause of disability-adjusted life years for school-aged children. In this study, we included 429,222 Chinese children aged 7–17 years from five consecutive national cross-sectional surveys during 1995–2014. Using altitude-adjusted haemoglobin concentration measured from capillary blood samples, we defined anaemia status according to World Health Organization's recommendation. We used logistic regressions weighted by provincial population to examine the association between provincial gross domestic product (GDP) per capita and anaemia, adjusting for sex, age, urban–rural location, regional socio-economic status (SES), fixed effect of province, and clustering of schools. We used generalised additive mixed models to evaluate a potentially non-linear relationship. For each 100% growth in GDP per capita, there was a 40% (odds ratio [OR] = 0.60; 95% confidence interval [CI; 0.56, 0.65]) reduction in anaemia. However, the association was weaker for girls and in cities with a lower SES. The association was weaker across 2005–2014 (OR = 0.75, 95% CI [0.62, 0.90]) compared with 1995–2005 (OR = 0.52; 95% CI [0.44, 0.61]), reflecting a weaker association when GDP per capita reaches around $2,000. The results were similar for moderate-to-severe anaemia. We concluded that economic growth has been associated with reductions in anaemia among school-aged children in China but with fewer benefits for girls and those in poorer settings. Further economic development in China is unlikely to bring similar reductions in anaemia, suggesting that additional population level and targeted interventions will be needed

Dual RNA-Seq Unveils Pseudomonas plecoglossicida htpG Gene Functions During Host-Pathogen Interactions With Epinephelus coioides

Pseudomonas plecoglossicida is a temperature-dependent opportunistic pathogen which is associated with a variety of diseases in fish. During the development of “white nodules” disease, the expression of htpG in P. plecoglossicida was found to be significantly up-regulated at its virulent temperature of 18°C. The infection of htpG-RNAi strain resulted in the onset time delay, reduction in mortality and infection symptoms in spleen of Epinephelus coioides, and affected the bacterial tissue colonization. In order to reveal the effect of htpG silencing of P. plecoglossicida on the virulence regulation in P. plecoglossicida and immune response in E. coioides, dual RNA-seq was performed and a pathogen-host integration network was constructed. Our results showed that infection induced the expression of host genes related to immune response, but attenuated the expression of bacterial virulence genes. Novel integration was found between host immune genes and bacterial virulence genes, while IL6, IL1R2, IL1B, and TLR5 played key roles in the network. Further analysis with GeneMANIA indicated that flgD and rplF might play key roles during the htpG-dependent virulence regulation, which was in accordance with the reduced biofilm production, motility and virulence in htpG-RNAi strain. Meanwhile, IL6 and IL1B were found to play key roles during the defense against P. plecoglossicida, while CELA2, TRY, CPA1, CPA2, and CPB1 were important targets for P. plecoglossicida attacking to the host

Effects of N-G-monomethyl-L-arginine (NMMA) and catalase on intracellular survival of Vibrio alginolyticus in macrophages of large yellow croaker Pseudosciaena crocea

The intracellular survival of Vibrio alginolyticus and Vibrio parahaemolyticus in large yellow croaker macrophages of Pseudosciaena crocea was investigated. In addition, the effects of N-G-monomethyl-L-arginine (NMMA) and catalase on the interaction of V. alginolyticus with macrophages from head kidney and on macrophages reactive nitrogen intermediate (RNI) and reactive oxygen intermediate (ROI) in vitro were determined. V. alginolyticus ND-01 was able to survive in macrophages from head kidney of large yellow croakers for at least 3 h, while V. paraheamolyticus 1.1614 could not survive in the macrophages for 1 h. Intracellular bacterial survival was affected by the addition of specific inhibitors of macrophage oxidative function. Exposure of macrophages to NMMA and catalase decreased the number of viable cells of V. alginolyticus inside large yellow croaker macrophages. Furthermore, a close correlation was observed between the number of intracellular survival bacteria with the amount of NO and H2O2 produced by macrophages.National Department Public Benefit Research Foundation of China [200903029]; Natural Science Foundation of Fujian Province [2011J06014

Role of ST-Segment Resolution Alone and in Combination With TIMI Flow After Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction

BACKGROUND: To evaluate the role of ST-segment resolution (STR) alone and in combination with Thrombolysis in Myocardial Infarction (TIMI) flow in reperfusion evaluation after primary percutaneous coronary intervention (PPCI) for ST-segment– elevation myocardial infarction by investigating the long-term prognostic impact.METHODS AND RESULTS: From January 2013 through September 2014, we studied 5966 patients with ST-segment–elevation myocardial infarction enrolled in the CAMI (China Acute Myocardial Infarction) registry with available data of STR evaluated at 120 minutes after PPCI. Successful STR included STR ≥50% and complete STR (ST-segment back to the equipotential line). After PPCI, the TIMI flow was assessed. The primary outcome was 2-year all-cause mortality. STR &lt; 50%, STR ≥50%, and complete STR occurred in 20.6%, 64.3%, and 15.1% of patients, respectively. By multivariable analysis, STR ≥50% (5.6%; adjusted hazard ratio [HR], 0.45 [95% CI, 0.36–0.56]) and complete STR (5.1%; adjusted HR, 0.48 [95% CI, 0.34–0.67]) were significantly associated with lower 2-year mortality than STR &lt;50% (11.7%). Successful STR was an independent predictor of 2-year mortality across the spectrum of clinical variables. After combining TIMI flow with STR, different 2-year mortality was observed in subgroups, with the lowest in successful STR and TIMI 3 flow, intermediate when either of these measures was reduced, and highest when both were abnormal.CONCLUSIONS: Post-PPCI STR is a robust long-term prognosticator for ST-segment–elevation myocardial infarction, whereas the integrated analysis of STR plus TIMI flow yields incremental prognostic information beyond either measure alone, support-ing it as a convenient and reliable surrogate end point for defining successful PPCI.</p

Role of ST-Segment Resolution Alone and in Combination With TIMI Flow After Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction

BACKGROUND: To evaluate the role of ST-segment resolution (STR) alone and in combination with Thrombolysis in Myocardial Infarction (TIMI) flow in reperfusion evaluation after primary percutaneous coronary intervention (PPCI) for ST-segment– elevation myocardial infarction by investigating the long-term prognostic impact.METHODS AND RESULTS: From January 2013 through September 2014, we studied 5966 patients with ST-segment–elevation myocardial infarction enrolled in the CAMI (China Acute Myocardial Infarction) registry with available data of STR evaluated at 120 minutes after PPCI. Successful STR included STR ≥50% and complete STR (ST-segment back to the equipotential line). After PPCI, the TIMI flow was assessed. The primary outcome was 2-year all-cause mortality. STR &lt; 50%, STR ≥50%, and complete STR occurred in 20.6%, 64.3%, and 15.1% of patients, respectively. By multivariable analysis, STR ≥50% (5.6%; adjusted hazard ratio [HR], 0.45 [95% CI, 0.36–0.56]) and complete STR (5.1%; adjusted HR, 0.48 [95% CI, 0.34–0.67]) were significantly associated with lower 2-year mortality than STR &lt;50% (11.7%). Successful STR was an independent predictor of 2-year mortality across the spectrum of clinical variables. After combining TIMI flow with STR, different 2-year mortality was observed in subgroups, with the lowest in successful STR and TIMI 3 flow, intermediate when either of these measures was reduced, and highest when both were abnormal.CONCLUSIONS: Post-PPCI STR is a robust long-term prognosticator for ST-segment–elevation myocardial infarction, whereas the integrated analysis of STR plus TIMI flow yields incremental prognostic information beyond either measure alone, support-ing it as a convenient and reliable surrogate end point for defining successful PPCI.</p