This book presents some recent developments in correlated data analysis. It utilizes the class of dispersion models as marginal components in the formulation of joint models for correlated data. This ...enables the book to handle a broader range of data types than those analyzed by traditional generalized linear models. One example is correlated angular data. This book provides a systematic treatment for the topic of estimating functions. Under this framework, both generalized estimating equations (GEE) and quadratic inference functions (QIF) are studied as special cases. In addition to marginal models and mixed-effects models, this book covers topics on joint regression analysis based on Gaussian copulas and generalized state space models for longitudinal data from long time series. Various real-world data examples, numerical illustrations and software usage tips are presented throughout the book. This book has evolved from lecture notes on longitudinal data analysis, and may be considered suitable as a textbook for a graduate course on correlated data analysis. This book is inclined more towards technical details regarding the underlying theory and methodology used in software-based applications. Therefore, the book will serve as a useful reference for those who want theoretical explanations to puzzles arising from data analyses or deeper understanding of underlying theory related to analyses.
Summary
The paper presents an incremental updating algorithm to analyse streaming data sets using generalized linear models. The method proposed is formulated within a new framework of renewable ...estimation and incremental inference, in which the maximum likelihood estimator is renewed with current data and summary statistics of historical data. Our framework can be implemented within a popular distributed computing environment, known as Apache Spark, to scale up computation. Consisting of two data‐processing layers, the rho architecture enables us to accommodate inference‐related statistics and to facilitate sequential updating of the statistics used in both estimation and inference. We establish estimation consistency and asymptotic normality of the proposed renewable estimator, in which the Wald test is utilized for an incremental inference. Our methods are examined and illustrated by various numerical examples from both simulation experiments and a real world data analysis.
•The SS biochar produced at 450°C is the most suitable one for garlic cultivation.•The favourable C:S ratio drifted when the biochar production temperature changed.•General heavy metal accumulation ...in the garlic root & bulb occurred for the most enriched Zn and Cu in the biochar.•Heavy metal bioaccumulation increased with heavy metal leaching from biochars but did not increase with increased C:S ratio.
Applying biochar products from sewage sludge (SS) pyrolysis as soil amendment for plant cultivation was investigated in this study with special attention paid to heavy metal accumulation in the plants when pyrolysis temperature and biochar-to-soil mass ratio (C:S) were changed. Biochar obtained at four different temperatures were adopted as soil amendment for Allium sativum L. garlic plant cultivation. Experimental results revealed that biochars were rich in nutrient contents and they improved garlic yields. Although contents of heavy metals including As, Zn, Pb, Ni, Cd, Cr and Cu, etc. were elevated in the biochars compared to local soil, they fell within the acceptable limits for land application and SS is a suitable biochar resource, especially biochar produced at 450°C had rich micropores, relatively stable functional groups in structure and rugged surface to contact well with soil, conducive to its usage as a biochar. The garlic grew faster when planted in the biochar-amended soil and had higher final dry matter yields than those planted in the reference soil, especially biochar produced at 450°C corresponding to the highest final yields. The C:S ratio related to the highest garlic yields changed when the pyrolysis temperature was changed and this ratio was 1:4 for the biochar produced at 450°C. General heavy metal accumulation in the garlic occurred only for the most enriched Zn and Cu, and mainly in the roots & bulbs; in addition this bioaccumulation was increasing as leaching from biochar increased but not increasing with C:S ratio. The garlic planted in soil amended with biochar of 450°C contained the lowest level of heavy metals compared to other biochars. Those results indicated that heavy metal accumulation in plants can be inhibited through proper pyrolysis temperature choice and prevention of heavy metal leaching from the SS biochar.
Background and aims:Infliximab is an effective treatment for ulcerative colitis with over 60% of patients responding to treatment and up to 30% reaching remission. The mechanism of resistance to ...anti-tumour necrosis factor α (anti-TNFα) is unknown. This study used colonic mucosal gene expression to provide a predictive response signature for infliximab treatment in ulcerative colitis.Methods:Two cohorts of patients who received their first treatment with infliximab for refractory ulcerative colitis were studied. Response to infliximab was defined as endoscopic and histological healing. Total RNA from pre-treatment colonic mucosal biopsies was analysed with Affymetrix Human Genome U133 Plus 2.0 Arrays. Quantitative RT-PCR was used to confirm microarray data.Results:For predicting response to infliximab treatment, pre-treatment colonic mucosal expression profiles were compared for responders and non-responders. Comparative analysis identified 179 differentially expressed probe sets in cohort A and 361 in cohort B with an overlap of 74 probe sets, representing 53 known genes, between both analyses. Comparative analysis of both cohorts combined, yielded 212 differentially expressed probe sets. The top five differentially expressed genes in a combined analysis of both cohorts were osteoprotegerin, stanniocalcin-1, prostaglandin-endoperoxide synthase 2, interleukin 13 receptor alpha 2 and interleukin 11. All proteins encoded by these genes are involved in the adaptive immune response. These markers separated responders from non-responders with 95% sensitivity and 85% specificity.Conclusion:Gene array studies of ulcerative colitis mucosal biopsies identified predictive panels of genes for (non-)response to infliximab. Further study of the pathways involved should allow a better understanding of the mechanisms of resistance to infliximab therapy in ulcerative colitis.ClinicalTrials.gov number, NCT00639821.
Summary
Multi‐compartment models have been playing a central role in modelling infectious disease dynamics since the early 20th century. They are a class of mathematical models widely used for ...describing the mechanism of an evolving epidemic. Integrated with certain sampling schemes, such mechanistic models can be applied to analyse public health surveillance data, such as assessing the effectiveness of preventive measures (e.g. social distancing and quarantine) and forecasting disease spread patterns. This review begins with a nationwide macromechanistic model and related statistical analyses, including model specification, estimation, inference and prediction. Then, it presents a community‐level micromodel that enables high‐resolution analyses of regional surveillance data to provide current and future risk information useful for local government and residents to make decisions on reopenings of local business and personal travels. r software and scripts are provided whenever appropriate to illustrate the numerical detail of algorithms and calculations. The coronavirus disease 2019 pandemic surveillance data from the state of Michigan are used for the illustration throughout this paper.
Icotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small-cell lung cancer patients when given as second- or further-line treatment. In this open-label, ...randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation.
Eligible participants were adults with stage IIIB/IV lung adenocarcinoma and exon 19/21 EGFR mutations. Participants were randomly allocated (1 : 1) to receive oral icotinib or 3-week cycle of cisplatin plus pemetrexed for up to four cycles; non-progressive patients after four cycles were maintained with pemetrexed until disease progression or intolerable toxicity. The primary end point was progression-free survival (PFS) assessed by independent response evaluation committee. Other end points included overall survival (OS) and safety.
Between January 2013 and August 2014, 296 patients were randomized, and 285 patients were treated (148 to icotinib, 137 to chemotherapy). Independent response evaluation committee-assessed PFS was significantly longer in the icotinib group (11.2 versus 7.9 months; hazard ratio, 0.61, 95% confidence interval 0.43-0.87; P = 0.006). No significant difference for OS was observed between treatments in the overall population or in EGFR-mutated subgroups (exon 19 Del/21 L858R). The most common grade 3 or 4 adverse events (AEs) in the icotinib group were rash (14.8%) and diarrhea (7.4%), compared with nausea (45.9%), vomiting (29.2%), and neutropenia (10.9%) in the chemotherapy group. AEs (79.1% versus 94.2%; P < 0.001) and treatment-related AEs (54.1% versus 90.5%; P < 0.001) were significantly fewer in the icotinib group than in the chemotherapy group.
First-line icotinib significantly improves PFS of advanced lung adenocarcinoma patients with EGFR mutation with a tolerable and manageable safety profile. Icotinib should be considered as a first-line treatment for this patient population.
Ferroptosis: process and function Xie, Y; Hou, W; Song, X ...
Cell death and differentiation,
03/2016, Volume:
23, Issue:
3
Journal Article
Peer reviewed
Open access
Ferroptosis is a recently recognized form of regulated cell death. It is characterized morphologically by the presence of smaller than normal mitochondria with condensed mitochondrial membrane ...densities, reduction or vanishing of mitochondria crista, and outer mitochondrial membrane rupture. It can be induced by experimental compounds (e.g., erastin, Ras-selective lethal small molecule 3, and buthionine sulfoximine) or clinical drugs (e.g., sulfasalazine, sorafenib, and artesunate) in cancer cells and certain normal cells (e.g., kidney tubule cells, neurons, fibroblasts, and T cells). Activation of mitochondrial voltage-dependent anion channels and mitogen-activated protein kinases, upregulation of endoplasmic reticulum stress, and inhibition of cystine/glutamate antiporter is involved in the induction of ferroptosis. This process is characterized by the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS) derived from iron metabolism and can be pharmacologically inhibited by iron chelators (e.g., deferoxamine and desferrioxamine mesylate) and lipid peroxidation inhibitors (e.g., ferrostatin, liproxstatin, and zileuton). Glutathione peroxidase 4, heat shock protein beta-1, and nuclear factor erythroid 2-related factor 2 function as negative regulators of ferroptosis by limiting ROS production and reducing cellular iron uptake, respectively. In contrast, NADPH oxidase and p53 (especially acetylation-defective mutant p53) act as positive regulators of ferroptosis by promotion of ROS production and inhibition of expression of SLC7A11 (a specific light-chain subunit of the cystine/glutamate antiporter), respectively. Misregulated ferroptosis has been implicated in multiple physiological and pathological processes, including cancer cell death, neurotoxicity, neurodegenerative diseases, acute renal failure, drug-induced hepatotoxicity, hepatic and heart ischemia/reperfusion injury, and T-cell immunity. In this review, we summarize the regulation mechanisms and signaling pathways of ferroptosis and discuss the role of ferroptosis in disease.
A direct regeneration of cathode materials from spent LiFePO
4
batteries using a solid phase sintering method has been proposed in this article. The spent battery is firstly dismantled to separate ...the cathode and anode plate, and then the cathode plate is soaked in DMAC organic solvent to separate the cathode materials and Al foil at optimal conditions of 30 min at 30 °C and solid liquid ratio of 1 : 20 g ml
−1
. XRD and SEM results of the spent LiFePO
4
after separation show that there are some impurity phase components and irregular morphologies with many agglomerations. The spent materials are regenerated at appropriate temperatures with doping of new LiFePO
4
at different ratios. Battery capacities from regenerated LiFePO
4
can reach over 120 mA h g
−1
at 0.1C discharge conditions, especially with the highest value of 144 mA h g
−1
with a doping ratio of 3 : 7 at 700 °C. The rate capabilities and cycling performance of batteries made from regenerated LiFePO
4
with doping at 600 °C and 700 °C are generally better than those at 800 °C. All the performances of batteries made from regenerated LiFePO
4
with pure phase and uniform morphology can meet the basic requirements for reuse.
A direct regeneration of cathode materials from spent LiFePO
4
batteries using a solid phase sintering method has been proposed in this article.
We examined whether mucosal melanomas are different in their clinical course and patterns of metastases when arising from different anatomic sites. Our hypothesis was that metastatic behavior would ...differ from primary mucosal melanomas at different anatomical sites.
Clinical and pathological data from 706 patients were compared for their stage distribution, patterns of metastases, CKIT/BRAF mutation status, and overall survival for different anatomical sites.
The anatomic sites of the primary mucosal melanomas were from the lower GI tract (26.5%), nasal cavity and paranasal sinuses (23%), gynecological sites (22.5%), oral cavity (15%), urological sites (5%), upper GI tract (5%), and other sites (3.0%). At initial diagnosis, 14.5% were stage I disease, 41% Stage II, 21.5% Stage III, and 23.0% stage IV. Predominant metastatic sites were regional lymph nodes (21.5%), lung (21%), liver (18.5%), and distant nodes (9%). Oral cavity mucosal melanoma had a higher incidence of regional nodal metastases (31.7% versus 19.8%,P = 0.009), and a higher incidence of lung metastases (32.5% versus 18.5%,P = 0.007) compared to other primary mucosal melanomas. There was a 10% incidence of CKIT mutation and 12% BRAF mutation. Mucosal melanomas from nasal pharyngeal and oral, gastrointestinal, gynecological, and urological had a similar survival with a 1-year survival rate (88%, 83%, 86%), 2-year survival rate (66%, 57%, 61%), 5-year survival rate (27%, 16%, 20%), respectively.
The largest sample size allows, for the first time, a comparison of primary melanoma stage and patterns of metastases across anatomical sites. With few exceptions, the presenting stages, incidence of nodal and distant metastases, the site of predilection of distant metastases, or overall survival were similar despite different primary anatomic sites. These findings suggest that clinical trials involving mucosal melanomas and the administration of systemic therapy can be applied equally to mucosal melanomas regardless of their primary anatomic site.
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