Methods for longitudinal data measured at distinct time points

For longitudinal data where the response and time-dependent predictors within each individual are measured at distinct time points, traditional longitudinal models such as generalized linear mixed effects models or marginal models cannot be directly applied. Instead, some preprocessing such as smoothing is required to temporally align the response and predictors. In Chapter 2, we propose a binning method, which results in equally spaced bins of time for both the response and predictor(s). Hence, after incorporating binning, traditional models can be applied. The proposed binning approach was applied on a longitudinal hemodialysis study to look for possible contemporaneous and lagged effects between occurrences of a health event (i.e., infection) and levels of a protein marker of inflammation (i.e., C-reactive protein). Both Poisson mixed effects models and zero-inflated Poisson (ZIP) mixed effects models were applied to the subsequent binned data, and some important biological findings about contemporaneous and lagged associations were uncovered. In addition, a simulation study was conducted to investigate various properties of the binning approach. In Chapter 3, asymptotic properties have been derived for the fixed effects association parameter estimates following binning, under different data scenarios. In addition, we propose some leave-one-subject-out cross-validation algorithms for bin size selection. In Chapter 4, in order to identify levels of a predictor that might be indicative of recently occurred event(s), we propose a generalized mixed effects regression tree (GMRTree) based method which estimates the tree by standard tree method such as CART and estimates the random effects by a generalized linear mixed effects model. One of the main steps in this method was to use a linearization technique to change the longitudinal count response into a continuous surrogate response. Simulations have shown that the GMRTree method can effectively detect the underlying tree structure in an applicable longitudinal dataset, and has better predictive performance than either a standard tree approach without random effects or a generalized linear mixed effects model, assuming the underlying model indeed has a tree structure. We have also applied this method to two longitudinal datasets, one from the aforementioned hemodialysis study and the other from an epilepsy study

COMPATIBILITY EVALUATION OF BZ25-1 CRUDE OILS IN BOHAI BAY, CHINA

ABSTRACT BZ25-1 oilfield is located in the southeast of Bohai bay which geographically lies between 119 o 00′to 119 o 15′east longitude and 38 o 10′to 38 o 20′north latitude. It has two oil blocks, including Shahejie (SHJ) waxy oil and Minghuazhen (MHZ) heavy oil, with six wellhead platforms WHPA~WHPF and six submarine pipelines. Therein, the WHPC-WHPB and WHPB-SPM (Single Point Mooring) pipelines transport the mixture of the two produced crude oils. However, the mixing of the two oils will certainly bring out a change in their components and properties, which directly affects the safe operation of the submarine pipelines and offshore production facilities. Therefore, this paper compounds three kinds of MHZ/SHJ mixed oils with blending ratios of 1:1, 3:1 and 9:1, mainly studies how the components, rheological and thermophysical properties of the oil mixtures change with the blending ratio. The major objective of this study is to evaluate the compatibility of the two crude oils and provide a theoretical basis for the production optimization and risk elusion of the oilfield. The results of the study show that the components and properties of SHJ crude oil are quite different from those of MHZ oil, the flow behavior of SHJ oil is more sensitive to temperature. As MHZ oil in the compounds increases, the contents of asphaltene, resin, sulfur and carbon residue will increase except wax contents, their viscosities, densities and flash points will also increase, but their pour points, yield stresses, calorific values and other major thermophysical parameters will decrease. A blending ratio of 2~7:1 for MHZ to SHJ crude oil can be concluded to make the properties of the compounds meet the safe and economic requirements of the subsea pipeline and offshore facility operations and ensure the compatibility of the mixed oils. In actuality, the field operations have confirmed that the recommended blending ratio is reasonable and practicable

Fatty acid 2-hydroxylation inhibits tumor growth and increases sensitivity to cisplatin in gastric cancer

Background: Most gastric cancers are diagnosed at an advanced or metastatic stage with poor prognosis and survival rate. Fatty acid 2-hydroxylase (FA2H) with high expression in stomach generates chiral (R)-2-hydroxy FAs ((R)-2-OHFAs) and regulates glucose utilization which is important for cell proliferation and invasiveness. We hypothesized that FA2H impacts gastric tumor growth and could represent a novel target to improve gastric cancer therapy. Methods: FA2H level in 117 human gastric tumors and its association with tumor growth, metastasis and overall survival were examined. Its roles and potential mechanisms in regulating tumor growth were studied by genetic and pharmacological manipulation of gastric cancer cells in vitro and in vivo. Findings: FA2H level was lower in gastric tumor tissues as compared to surrounding tissues and associated with clinicopathologic status of patients, which were confirmed by analyses of multiple published datasets. FA2H depletion decreased tumor chemosensitivity, partially due to inhibition of AMPK and activation of the mTOR/S6K1/Gli1 pathway. Conversely, FA2H overexpression or treatment with (R)-2-OHFAs had the opposite effects. In line with these in vitro observations, FA2H knockdown promoted tumor growth with increased level of tumor Gli1 in vivo. Moreover, (R)-2-OHFA treatment significantly decreased Gli1 level in gastric tumors and enhanced tumor chemosensitivity to cisplatin, while alleviating the chemotherapy-induced weight loss in mice. Interpretation: Our results demonstrate that FA2H plays an important role in regulating Hh signaling and gastric tumor growth and suggest that (R)-2-OHFAs could be effective as nontoxic wide-spectrum drugs to promote chemosensitivity. Fund: Grants of NSF, NIH, and PAPD. Keywords: Fatty acid 2-hydroxylation, Gastric cancer, Lipid metabolism, mTOR, Chemotherapy, Hedgehog pathwa

Genetically predicted C-reactive protein mediates the association between rheumatoid arthritis and atlantoaxial subluxation

ObjectiveInvestigating the causal relationship between rheumatoid arthritis (RA) and atlantoaxial subluxation (AAS) and identifying and quantifying the role of C-reactive protein (CRP) as a potential mediator.MethodsUsing summary-level data from a genome-wide association study (GWAS), a two-sample Mendelian randomization (MR) analysis of genetically predicted rheumatoid arthritis (14,361 cases, and 43,923 controls) and AAS (141 cases, 227,388 controls) was performed. Furthermore, we used two-step MR to quantitate the proportion of the effect of c-reactive protein-mediated RA on AAS.ResultsMR analysis identified higher genetically predicted rheumatoid arthritis (primary MR analysis odds ratio (OR) 0.61/SD increase, 95% confidence interval (CI) 1.36-1.90) increased risk of AAS. There was no strong evidence that genetically predicted AAS had an effect on rheumatoid arthritis risk (OR 1.001, 95% CI 0.97-1.03). The proportion of genetically predicted rheumatoid arthritis mediated by C-reactive protein was 3.7% (95%CI 0.1%−7.3%).ConclusionIn conclusion, our study identified a causal relationship between RA and AAS, with a small proportion of the effect mediated by CRP, but a majority of the effect of RA on AAS remains unclear. Further research is needed on additional risk factors as potential mediators. In clinical practice, lesions of the upper cervical spine in RA patients need to be given more attention

Incorporation size of lymph node metastasis focus and pre-ablation stimulated Tg could more effectively predict clinical outcomes in differentiated thyroid cancer patients without distant metastases

BackgroundThe size of lymph node metastasis (LNM) and pre-ablation stimulated Tg (ps-Tg) were key predictors of clinical prognosis in differentiated thyroid cancer (DTC) patients, however, very few studies combine the above two as predictors of clinical prognosis of DTC patients.MethodsPersistent/recurrent disease and clinicopathologic factors were analyzed in 543 DTC patients without distant metastases who underwent LN dissection, near-total/total thyroidectomy, and radioiodine ablation.ResultsIn the multivariate analysis, size of LNM, ps-Tg, and the activity of 131I significantly correlated with long-term remission. The optimal cutoff size of LNM 0.4 cm-1.4 cm (intermediate-risk patients) and >1.4cm (high-risk patients) increased the recurrence risk (hazard ratio [95% CI], 4.674 [2.881-7.583] and 13.653 [8.135–22.913], respectively). Integration of ps-Tg into the reclassification risk stratification showed that ps-Tg ≤ 10.1 ng/mL was relevant to a greatly heightened possibility of long-term remission (92.2%–95.4% in low-risk patients, 67.3%–87.0% in intermediate-risk patients, and 32.3%–57.7% in high-risk patients).ConclusionThe cutoff of 0.4 cm and 1.4 cm for a definition of size of LNM in DTC patients without distant metastases can reclassify risk assessment, and incorporating ps-Tg could more effectively predict clinical outcomes and modify the postoperative management plan

Separation of the Sound Power Spectrum of Multiple Sources by Three-Dimensional Sound Intensity Decomposition

The identification and separation of sources are the prerequisite of industrial noise control. Industrial machinery usually contains multiple noise sources sharing same-frequency components. There are usually multiple noise sources in mechanical equipment, and there are few effective methods available to separate the spectrum intensity of each sound source. This study tries to solve the problem by the radiation relationship between three-dimensional sound intensity vectors and the power of the sources. When the positions of the probe and the sound source are determined, the sound power of the sound source at each frequency can be solved by the particle swarm optimization algorithm. The solution results at each frequency are combined to obtain the sound power spectrum of each sound source. The proposed method is first verified by a simulation on two point sources. The experiment is carried out on a fault simulation test bed in an ordinary laboratory; we used three three-dimensional sound intensity probes to form a line array and conducted spectrum separation of the nine main noise sources. The sound intensity on the main frequency band of each sound source was close to the result of the near-field measurement of the one-dimensional sound intensity probe. The proposed spectral separation method of the sound power of multiple sound sources provides a new method for accurate noise identification in industrial environments

Comparative Developmental Toxicity and Stress Protein Responses of Dimethyl Sulfoxide to Rare Minnow and Zebrafish Embryos/Larvae

Dimethyl sulfoxide ( DMSO), a widely used carrier solvent, can be toxic to test organisms and has species-specific sensitivity. In this study, the developmental toxicity and stress protein responses of DMSO to rare minnow (Gobiocypris rarus) and zebrafish ( Danio rerio) with two tests were compared in the early life stage. In the first test, fertilized eggs were exposed to 0%, 0.0001%, 0.001%, 0.01%, 0.1%, 1.0%, 1.5%, and 2.0% v/v of DMSO until 3 days post hatching. In the second test, larvae from 0 to 8 d were exposed to 2% DMSO until 4 days. Our results showed that DMSO was toxic to rare minnow and zebrafish on multiple indexes, and the no-observed-effect concentrations of DMSO in both species were 1.0% and 0.001% for developmental toxicity analysis and stress protein analysis, respectively. Furthermore, rare minnow larvae were more sensitive than zebrafish to DMSO for spinal malformation. The sensitive period for induction of spinal malformation by DMSO was 0-7 d after hatch (dah) for rare minnow and 0-4 dah for zebrafish. Together, these results will provide support to the use of DMSO in ecotoxicological studies using rare minnow and will contribute to a better understanding of the toxicity of DMSO