Estimation of Parameters in Replicated Time Series Regression Models

The time series regression model was widely studied in the literature by several authors. However, statistical analysis of replicated time series regression models has received little attention. In this thesis, we study the application of quasi-least squares, a relatively new method, to estimate the parameters in replicated time series models with general ARMA( p, q) correlation structure. We also study several established methods for estimating the parameters in those models, including the maximum likelihood, method of moments, and the GEE method. Asymptotic comparisons of the methods are made bV fixing the number of repeated measurements in each series, and letting the number of replications n go to infinity. Our theoretical as well as some simulation results show that the quasi-least squares estimates are undoubtedly better than the moment estimates, and are good competitors and more robust than the maximum likelihood estimates. Examples are presented to illustrate the application of the quasi-least squares method to analyze real life data situations

Chemosensitivity of radioresistant cells in the multicellular spheroids of A549 lung adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>The relapse of cancer after radiotherapy is a clinical knotty problem. Previous studies have demonstrated that the elevation of several factors is likely in some way to lead to the development of treatment tolerance, so it is necessary to further explore the problem of re-proliferated radioresistant cells to chemotherapeutic agents. In the present study, we aimed to investigate the chemosensitivity of radioresistant cells originated from the multicellular spheroids of A549 lung adenocarcinoma.</p> <p>Methods</p> <p>After irradiated with 25 Gy of 6 MV X-ray to A549 multicellular spheroids, whose 10th re-proliferated generations were employed as radioresistant cells, and the control groups were A549 parental cells and MCF7/VCR resistant cells. The chemo-sensitivity test was made by six kinds of chemotherapeutic drugs which were DDP, VDS, 5-Fu, HCP, MMC and ADM respectively, while verapamil (VPL) was used as the reversal agent. Then the treatment effect was evaluated by MTT assay, and the multidrug resistant gene expressions of <it>mdr1 </it>and <it>MRP </it>were measured by RT-PCR.</p> <p>Results</p> <p>Both A549 parental cells and A549 derived radioresistant cells were resistant to DDP, but sensitive to VDS, 5-Fu, HCP, MMC and ADM. The inhibitory rates of VPL to these two types of cell were 98% and 25% respectively (P < 0.001). In addition, without drugs added, the absorbance value (A value) of A549 parental cells was 2-folds higher than that of their radioresistant cells (P < 0.001). As to the MCF7/VCR cells, they were resistant to DDP and VDS, but slight sensitive to MMC, ADM, 5-Fu, and HCP with 80% of inhibitory rate to VPL. The subsequent RT-PCR demonstrated that the <it>Mdr1</it>/β2-MG and <it>MRP</it>/β2-MG of all A549 cells were about 0 and 0.7 respectively, and those of MCF7/VCR cells were 35 and 4.36.</p> <p>Conclusion</p> <p>The chemosensitivity of A549 radioresistant cells had not changed markedly, and the decreased sensitivity to VPL could not be explained by the gene expression of <it>mdr1 </it>and <it>MRP</it>. It is possible that the changes in the cell membrane and decreased proliferate ability might be attributed to the resistance. Unlike multidrug resistance induced by chemotherapy, VPL may be not an ideal reverser to radioresistant cells. Therefore, the new biological strategy needs to be developed to treat recurring radioresistant tumor in combination with chemotherapy.</p

Uncovering the spatial heterogeneity of Ediacaran carbon cycling

Author Posting. © The Author(s), 2016. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Geobiology 15 (2017): 211–224, doi:10.1111/gbi.12222.Records of the Ediacaran carbon cycle (635 to 541 million years ago) include the Shuram excursion (SE), the largest negative carbonate-carbon isotope excursion in Earth history (down to -12 ‰). The nature of this excursion remains enigmatic given the difficulties of interpreting a perceived extreme global decrease in the δ13C of seawater dissolved inorganic carbon (DIC). Here, we present carbonate and organic carbon isotope (δ13Ccarb and δ13Corg) records from the Ediacaran Doushantuo Formation along a proximal-to-distal transect across the Yangtze Platform of South China as a test of the spatial variation of the SE. Contrary to expectations, our results show that the magnitude and morphology of this excursion and its relationship with coexisting δ13Corg are highly heterogeneous across the platform. Integrated geochemical, mineralogical, petrographic, and stratigraphic evidence indicates that the SE is a primary marine signature. Data compilations demonstrate that the SE was also accompanied globally by parallel negative shifts of δ34S of carbonate-associated sulfate (CAS) and increased 87Sr/86Sr ratio and coastal CAS concentration, suggesting elevated continental weathering and coastal marine sulfate concentration during the SE. In light of these observations, we propose a heterogeneous oxidation model to explain the high spatial heterogeneity of the SE and coexisting δ13Corg records of the Doushantuo, with likely relevance to the SE in other regions. In this model, we infer continued marine redox stratification through the SE but with increased availability of oxidants (e.g., O2 and sulfate) limited to marginal near-surface marine environments. Oxidation of limited spatiotemporal extent provides a mechanism to drive heterogeneous oxidation of subsurface reduced carbon mostly in shelf areas. Regardless of the mechanism driving the SE, future models must consider the evidence for spatial heterogeneity in δ13C presented in this study.We thank the National Key Basic Research Program of China (Grant 2013CB955704) and the State Key R&D project of China (Grant 2016YFA060104) as well as the NSF-ELT program and the NASA Astrobiology Institute (TWL) for funding

Radio Location of Partial Discharge Sources: A Support Vector Regression Approach

Partial discharge (PD) can provide a useful forewarning of asset failure in electricity substations. A significant proportion of assets are susceptible to PD due to incipient weakness in their dielectrics. This paper examines a low cost approach for uninterrupted monitoring of PD using a network of inexpensive radio sensors to sample the spatial patterns of PD received signal strength. Machine learning techniques are proposed for localisation of PD sources. Specifically, two models based on Support Vector Machines (SVMs) are developed: Support Vector Regression (SVR) and Least-Squares Support Vector Regression (LSSVR). These models construct an explicit regression surface in a high dimensional feature space for function estimation. Their performance is compared to that of artificial neural network (ANN) models. The results show that both SVR and LSSVR methods are superior to ANNs in accuracy. LSSVR approach is particularly recommended as practical alternative for PD source localisation due to it low complexity

Application of Quasi-Least Squares to Analyse Replicated Autoregressive Time Series Regression Models

Time series regression models have been widely studied in the literature by several authors. However, statistical analysis of replicated time series regression models has received little attention. In this paper, we study the application of the quasi-least squares method to estimate the parameters in a replicated time series model with errors that follow an autoregressive process of order p. We also discuss two other established methods for estimating the parameters: maximum likelihood assuming normality and the Yule-Walker method. When the number of repeated measurements is bounded and the number of replications n goes to infinity, the regression and the autocorrelation parameters are consistent and asymptotically normal for all three methods of estimation. Basically, the three methods estimate the regression parameter efficiently and differ in how they estimate the autocorrelation. When p=2, for normal data we use simulations to show that the quasi-least squares estimate of the autocorrelation is undoubtedly better than the Yule-Walker estimate. And the former estimate is as good as the maximum likelihood estimate almost over the entire parameter space.Autoregression, quasi-least squares, relative efficiency, repeated measurements, time series regression models,

Overweight and Obesity Difference of Chinese Population Between Different Urbanization Levels

Purpose: To determine the difference of Body Mass Index (BMI), the prevalence of overweight and obesity, and their predictors among residents of different urbanization levels in China. Methods: A stratified, multistage, random cluster sampling method was used to select a representative sample aged 18-60 years in metropolitan, prefecture, and rural areas in 4 provinces and Beijing City in China. A total of 6,159 residents were interviewed. Multiple logistic regression was used to evaluate the association between urbanization levels and the prevalence of overweight/obesity adjusted for sociodemographic characteristics and lifestyle factors. Findings: The prevalence of overweight and obesity was 21.0% and 2.5%, respectively. Compared to metropolitan residents (BMI = 22.76 ± 3.20 kg/m2), rural and prefecture residents had a higher BMI, 23.17 ± 3.49 kg/m2 (P \u3c001) and 23.06 ± 3.31 kg/m2 (P =.004), respectively. Multiple logistic regression showed that, compared to the rural residents, those in prefecture and metropolitan areas were less likely to be overweight and obese (OR = 0.80 [95% CI: 0.68-0.94] and OR = 0.68 [95% CI: 0.57-0.80], respectively). The prevalence of overweight/obesity was higher in males (OR = 1.68 [95% CI: 1.43-1.97]) and patients with noncommunicable chronic diseases (NCD; OR = 2.50 [95% CI: 2.16-2.89]). Less frequency of physical activity was associated with a higher prevalence of overweight/obesity (OR: 0.85, [95% CI: 0.74, 0.97]). Conclusions: The rural population had an increased prevalence of overweight/obesity compared to both the prefecture and metropolitan populations. Male gender, older age, and NCD were positively associated with the prevalence of overweight/obesity. Policies are urgently needed to combat the overweight and obesity challenge in rural China

510 - Dupilumab is efficacious in patients with prurigo nodularis regardless of stable use of topical corticosteroids and topical calcineurin inhibitors: pooled results from two phase 3 trials (LIBERTY-PN PRIME and PRIME2)

Abstract Introduction Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by severely itchy skin nodules, which substantially affects quality of life. Although topical treatments are frequently prescribed, these therapies are limited by insufficient demonstrated evidence for efficacy, and/or associated side effects. Objectives This study reports the effect of dupilumab on pruritus, skin lesions, and quality of life in patients with PN, with or without stable use of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI), in an analysis of pooled data from two phase 3 trials. Materials & Methods LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679) were two randomized, double-blind, placebo-controlled, 24-week studies. Adults with PN inadequately controlled by topical prescription therapies, or for whom those therapies are inadvisable, were randomized 1:1 to dupilumab 300 mg every 2 weeks or matched placebo. “Stable use” was defined as maintaining the same medicine (low-to-medium potency TCS and/or TCI) during the study, with the same frequency of treatment (once or twice daily) as from 2 weeks prior to screening. Efficacy was assessed from baseline to Week 24 through the Worst Itch Numerical Rating Scale (WI-NRS; scored 0–10; high scores represent a poorer outcome), and the Investigator’s Global Assessment for PN-Stage score (IGA PN-S; scored 0–4; high scores represent a poorer outcome). Impact on Health-Related Quality of Life (HRQoL) was assessed through the Dermatology Life Quality Index questionnaire (DLQI; 10 questions scored 0–3 with a maximum score of 30; high scores represent poorer HRQoL). Results 311 patients were randomized (dupilumab/placebo n = 153/158), including 182 patients with stable use of TCI/TCS (dupilumab/placebo N = 91/91) and 129 patients without (dupilumab/placebo N = 62/67). Baseline demographics and disease characteristics were well balanced in both subgroups. At Week 24, significantly more patients treated with dupilumab with or without stable use of TCI/TCS achieved a ≥ 4-point improvement in WI-NRS (59.3%/58.1%) vs placebo (13.2%/26.9% [nominal P < 0.0001/P < 0.0001]). The proportion of patients achieving an IGA PN-S score of 0 or 1 at Week 24 was also significantly higher in the dupilumab group for patients with or without stable use of TCI/TCS (48.4%/43.5%), vs placebo (11.0%/25.4% [nominal P < 0.0001/P = 0.0319]). The positive impact of dupilumab treatment on HRQoL was greater, for patients with and without a stable use of TCI/TCS vs placebo, as suggested by the mean change from baseline in DLQI at Week 24 (−12.9/−11.9 vs −5.5/−7.1 [nominal P < 0.0001/P < 0.0001], respectively). Although the placebo response was higher for patients without stable use of TCI/TCS, the effect of dupilumab treatment was comparable in the two subgroups. Treatment-emergent adverse events (TEAEs) occurred with similar rates in dupilumab-treated patients with or without stable use of TCI/TCS (59.3%/60.7%), compared with placebo (53.3%/47.8%). Patients with or without stable use of TCI/TCS had similar rates of severe TEAEs in the dupilumab groups (2.2%/4.9%) and placebo groups (3.3%/4.5%). Conclusion Dupilumab treatment improves itch, skin lesions, and quality of life in patients with PN, with an acceptable safety profile, with little to no influence from concomitant treatment with topical therapies (TCI/TCS)

The Jenkyns Event (early Toarcian OAE) in the Ordos Basin, North China

The early Toarcian (Early Jurassic) Oceanic Anoxic Event (T-OAE) or Jenkyns Event (~183 Ma) was marked by a globally synchronous negative carbon-isotope excursion, large-scale organic carbon burial and widespread oxygen depletion in the oceans. These features have been associated with volcanic activity of the Karoo and Ferrar large igneous provinces. The Jenkyns Event is well investigated in the Tethyan Ocean, but its expression in continental settings outside of Europe are still poorly understood. Here, the lacustrine Anya (AY) section in the NE Ordos Basin, North China, is studied for carbon-isotope geochemistry and palynology. Palynostratigraphy constrains the age of the section to the Pliensbachian-Toarcian transition, and a positive trend in \u3b413C, interrupted by a pronounced negative carbon-isotope excursion, has been identified in bulk organic matter and long-chain n-alkanes. The negative excursion is the expression of the Jenkyns Event, and coincides with variable total organic carbon (TOC) content in lake sediments. The maximum TOC (~21.5%) values precede the most negative carbon isotopes. A turnover from spore and seed fern-dominated palynological assemblages to Classopollis superabundance is coincident with the isotopic excursion and indicates clearly environmental perturbation. Biomarker data suggest that the organic matter was mainly sourced from higher plants. The magnitude of the Toarcian excursion in the bulk organic matter of this section (~ 12 12.5\u2030) is much larger compared to that typically observed in marine and lake strata. Humidity-related fractionation effects in land plants and changes in plant groups might have contributed to the recorded magnitude. This magnitude is also larger than that of other terrestrial records, and casts doubt on the use of terrestrial C-isotope data to constrain deep time pCO2. Nevertheless, our findings show that the Jenkyns Event is well-recorded in lacustrine facies of the Ordos Basin