bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concise Drug Review: Pazopanib and Axitinib
Authors: van Geel Robin M.J.M. , Beijnen Jos H. , Schellens Jan H.M. 
Published: June 2012

Abstract

Learning Objectives
After completing this course, the reader will be able to: Identify the current indications for pazopanib and axitinib.Describe the mechanism of action and the pharmacokinetics of pazopanib and axitinib.Enumerate the clinical benefits of pazopanib and axitinib, and describe the position of these drugs in the treatment paradigm of metastatic renal cell cancer.
CME This article is available for continuing medical education credit at CME.TheOncologist.com
Pazopanib and axitinib are both U.S. Food and Drug Administration approved ATP-competitive inhibitors of the vascular endothelial growth factor receptor. Pazopanib and axitinib have been shown to be effective and tolerable treatment options for patients with metastatic renal cell cancer and therefore have enlarged the armamentarium for this disease. This concise drug review discusses the clinical benefits, clinical use, mechanism of action, bioanalysis, pharmacokinetics, pharmacogenetics, pharmacodynamics, drug resistance, toxicity, and patient instructions and recommendations for supportive care for these two drugs.
Relationships Among Self-Efficacy, Social Support, Social Problem Solving, and Self-Management in a Rural Sample Living With Type 2 Diabetes Mellitus
Authors: Hunt Caralise W. , Wilder Barbara , Steele Michael M. , Grant Joan S. , Pryor Erica R. , Moneyham Linda 
Published: July 2012

Self-management behaviors are important for control of type 2 diabetes mellitus. Therefore, determining factors that promote effective self-management behaviors may be significant for improving the well-being of patients with type 2 diabetes mellitus. This study examined relationships among self-efficacy, social support, social problem solving, and diabetes self-management behaviors. Further, this study evaluated whether social support and social problem solving were mediators of the relationship between self-efficacy and diabetes self-management behaviors in those living with type 2 diabetes mellitus.Using a cross-sectional, descriptive correlational design, data from a convenience sample of 152 rural people living with type 2 diabetes mellitus were examined. Findings indicated that self-efficacy was a strong predictor of diabetes self-management. The effect of social support on diabetes self-management differed among men and women in the sample. Social support and social problem solving were significantly associated with diabetes self-management in men. Neither social support nor social problem solving were mediators of the relationship between self-efficacy and diabetes self-management in this sample. These findings suggest that nurses need to consider implementing interventions to improve patients’ self-efficacy and potentially influence diabetes self-management.
Graeber Companies, Inc.: Examining Impairment of Equity-Owned Investments
Authors: Needles Belverd E 
Published: June 2012

ABSTRACT
The Graeber Companies, Inc. case illustrates the implications of the Fair Value Measurements Standard (FASB ASC 820 or IFRS 13) and the Fair Value Option for Financial Assets and Financial Liabilities (FASB ASC 825 or IAS 39) on the accounting and auditing issues regarding fair value accounting. Based on an actual company's experience, the case provides an application of the new standards on fair value measurement, which is one major achievement of the FASB/IASB convergence project. Graeber Companies, Inc. is a 100-year-old financial boutique firm that, through its wholly owned and partially owned subsidiaries, is engaged in financial service activities. One of Graeber's proprietary investments is an equity investment in Advisor Group, Inc. (AGI)—an early stage development company. Students evaluate AGI's financial performance and strategic activities, including operating losses, issuance of preferred stock and proposed acquisitions by another investor company relative to its materiality, and potential impairment of Graeber Companies' equity-owned investment. The case study requires a determination of materiality of the equity investment and introduces students to the different valuation techniques such as Discounted Cash Flow Analysis, Public Market Analysis, Precedent Transaction Analysis, and the waterfall schedule method. The usefulness of these methods is then analyzed in determining the fair value of an investment in the situation where there have been no recent market transactions. Through analysis of the financial statements, relevant footnotes, and obtaining/obtained fair market value using different valuation approaches, students make a recommendation on materiality and on the fairness of the Graeber Companies management conclusion that no impairment of its investment in Advisor Group has taken place.
Primary Endoscopic Dacryocystorhinostomy with or without Silicone Tubing: A Prospective Randomized Study
Authors: Al-Qahtani Ali S. 
Published: June 2012

Background Endoscopic dacryocystorhinostomy (DCR) is an effective surgical procedure to treat saccal and postsaccal stenosis or nasolacrimal duct obstruction. The use of silicone tube after endoscopic DCR is still controversial. A prospective randomized study was conducted to compare the success rate between the use of silicone stent and no use of silicone stent in endoscopic DCR. Methods A prospective randomized study was conducted at Aseer Central Hospital and Abha Private Hospital, Abha, Kingdom of Saudi Arabia, on all patients undergoing endoscopic DCR between July 1, 2006 and 30 June 30, 2010. Patients were allocated randomly for endoscopic DCR with or without stent. The data collection included age, sex, diagnosis, method, and duration of surgery. Patients were followed up postoperatively at 1 week, 1 month, and then every 3 months for 1 year. Results During the period of the study a total of 173 cases of postsaccal stenosis underwent endoscopic DCR (67 male and 106 female subjects). The mean age was 51.8 years (range, 18–72 years). A stent was used in 92 patients (53.2%) and not used in 81 patients (46.8%). With silicone tubing the success rate was 96%, and without silicone tubing it was 91%, an overall success rate of 94%. The odds ratio of failure without a silicone tube was 3.25 but confidence interval was from 0.84 to 12.60 and the difference between these two groups was statistically not significant (p = 0.117). Conclusion In this study, there was no statistically significant advantage of using endoscopic DCR with stent over the endoscopic DCR without stent.
A Population-Based 5-Year Follow-Up of Allergic Rhinitis in Chinese Children
Authors: Kong Weijia , Chen Jianjun , Wang Yanjun , Xiang Jisheng , Zhang Xujing , Wang Jinghui , Yin Xiaoyan 
Published: June 2012

Background There have been few longitudinal investigations of allergic rhinitis (AR) in Chinese children. We previously conducted an investigation of the prevalence of AR in 3- to 6-year old children for the year of 2005–2006. The aim of this study was to observe the natural course of AR in children in the previously investigated population during a cohort study for 5 years. Methods A total of 1211 children in the previously investigated population were included in this study. Telephone interviews were conducted three times during the 1st, 3rd, and 5th year from the previous study. 14 Questions including duration, severity of nasal symptoms, asthma, and related problems of allergy were examined. Skin-prick tests (SPTs) were performed again on those children who had done SPTs in the previous study 14 after the last follow-up (i.e., after 5 years). Results Of the 1211 children, 870 (71.8%) completed the 5-year observation period. In the 5th year, the prevalence of positive sal symptoms was 29.4% (256 of the 870 children), including 64/70 (91.4%) of those who were formerly symptom positive and SPT+, 45/104 (43.3%) of those who were formerly symptom positive and SPT−, 40/66 (60.6%) of those who were formerly symptom positive with SPTs not performed (SPTs[x]), and 107/630 (17.0%) of those who were formerly symptom negative. SPT results showed that 96.1% (73/76) of previous SPT+ children remained SPT+; only 3.9% (6/154) became SPT+ in previous SPT− children. Conclusion We concluded that the natural course of AR (symptom positive and SPT+) and non-AR (symptom positive and SPT−) children were quite different.
Spatial distribution and packing of xylem conduits
Authors: Martínez‐Vilalta Jordi , Mencuccini Maurizio , Álvarez Xavier , Camacho Juan , Loepfe Lasse , Piñol Josep 
Published: June 2012

• Premise of the study: The hydraulic properties of the xylem determine the ability of plants to transport water from the soil to the leaves and to cope with important stress factors such as frost and drought. Hydraulic properties have usually been studied as a function of the anatomy of xylem conduits and their pits, but recent studies have proposed that system‐level properties, related to the topology of the xylem network, may also play a role. Here we study how the spatial arrangement of conduits in xylem cross sections affects the relationship between mean conduit lumen area and conduit density (packing function) across species.• Methods: Point pattern analysis was used to describe the spatial distribution of xylem conduits in 97 woody species. The effect of conduit aggregation on the packing function was tested using phylogenetic generalized least squares. A hydraulic model with an explicit description of the topology of the xylem network was used to interpret the functional significance of our findings.• Key results: The spatial arrangement of conduits affected the packing function across species, so that species with aggregated distributions tended to have lower conduit densities for a given conduit size and lower conduit lumen fractions. According to our modeling results, the higher conduit‐to‐conduit connectivity of species with aggregated distributions allows them to achieve higher hydraulic conductivity. Species with aggregated conduits, however, pay a cost in terms of increased vulnerability to embolism.• Conclusions: The spatial arrangement of conduits affects the fundamental structural and functional attributes of the xylem.
Development of indel markers from Citrus clementina (Rutaceae) BAC‐end sequences and interspecific transferability in Citrus
Authors: Ollitrault Frédérique , Terol Javier , Martin Alena Alonso , Pina Jose Antonio , Navarro Luis , Talon Manuel , Ollitrault Patrick 
Published: June 2012

• Premise of the study: Indel markers were developed from BAC‐end sequences of Citrus clementina cv. Nules. Transferability and polymorphism were tested in the Citrus genus to estimate the potential of indel markers mined from a single genotype for use in genetic studies.• Methods and Results: Using polyacrylamide gel electrophoresis and DNA silver staining, 89 indel markers were tested for their transferability and polymorphism. Thirty‐eight markers were selected. Heterozygosity in C . clementina cv. Nules was confirmed for 33 of these indel pairs. A preliminary diversity study using a capillary electrophoresis fragment analyzer was conducted with 21 indels using 45 accessions representing Citrus genus diversity. Intraspecific and interspecific polymorphisms were observed.• Conclusions: These results indicate the utility of indel markers developed from sequence data of a single genotype of interspecific origin. In Citrus, these markers will be useful for genetic mapping, germplasm characterization, and phylogenetic assignment of DNA fragments.
Development and characterization of nine highly polymorphic microsatellite primers for Platycladus orientalis (Cupressaceae)
Authors: Zhu Lin , Lou Anru 
Published: June 2012

• Premise of the study: Microsatellite primers were developed and characterized for the long‐lived tree species Platycladus orientalis for further investigation of its population characteristics.• Methods and Results: Nine polymorphic microsatellites were identified for P. orientalis. The number of alleles per locus ranged from four to 22 (average = 11) for 94 individual specimens examined from four populations. The observed and expected heterozygosities ranged from 0.208 to 1.000 and 0.555 to 0.931, respectively.• Conclusions: These nine markers can be used in future studies examining population genetics and the reproductive biology of P. orientalis, thereby revealing the importance of old‐growth populations for the retention of genetic diversity, and providing useful insights into the maintenance of the potential genetic resource of this species.
Development of microsatellite markers in a riparian shrub, Spiraea thunbergii (Rosaceae)
Authors: Ashizawa Kazuya , Kimura Megumi K. , Takahashi Akiko , Lian Chunlan , Kuramoto Noboru 
Published: June 2012

• Premise of the study: Microsatellite primers in the deciduous shrub Spiraea thunbergii were developed to investigate genetic diversity and population genetic structure. Cross‐species transferability was assayed in four congeneric species.• Methods and Results: Using a compound simple sequence repeat (SSR) marker method, 10 primer sets were identified in Japanese populations of S. thunbergii. The primers amplified compound SSRs with two to five alleles per locus. More than half of the primers were also amplified in S. prunifolia, S. nipponica var. nipponica, and S. japonica.• Conclusions: These markers might be useful for future studies of population genetics of S. thunbergii and congeneric species.
Microsatellite markers for Vellozia gigantea (Velloziaceae), a narrowly endemic species to the Brazilian campos rupestres
Authors: Martins Ana Paula V. , Proite Karina , Kalapothakis Evanguedes , Santos Fabrício R. , Chaves Anderson V. , Borba Eduardo L. 
Published: June 2012

• Premise of the study: Microsatellite primers were developed for the first time in Velloziaceae, in the endangered species Vellozia gigantea.• Methods and Results: Using two different protocols, seven primer sets were characterized in three populations of V. gigantea. The primers amplified di‐ and trinucleotide repeats with six to 12 alleles per locus. These revealed high levels of genetic variation, presenting an average observed heterozygosity of 0.508 in V. gigantea. The seven primers were tested for cross‐amplification in three Vellozia species. All primers successfully amplified in V. auriculata. Six primers amplified in V. compacta and three in V. hirsuta.• Conclusions: The new marker set described here will be useful for studies of population genetics of V. gigantea. The cross‐amplification results indicate the utility of primers for studies in other Vellozia species.
Substrate Rigidity Regulates Human T Cell Activation and Proliferation
Authors: O’Connor Roddy S. , Hao Xueli , Shen Keyue , Bashour Keenan , Akimova Tatiana , Hancock Wayne W. , Kam Lance C. , Milone Michael C. 
Published: June 2012

AbstractAdoptive immunotherapy using cultured T cells holds promise for the treatment of cancer and infectious disease. Ligands immobilized on surfaces fabricated from hard materials such as polystyrene plastic are commonly employed for T cell culture. The mechanical properties of a culture surface can influence the adhesion, proliferation, and differentiation of stem cells and fibroblasts. We therefore explored the impact of culture substrate stiffness on the ex vivo activation and expansion of human T cells. We describe a simple system for the stimulation of the TCR/CD3 complex and the CD28 receptor using substrates with variable rigidity manufactured from poly(dimethylsiloxane), a biocompatible silicone elastomer. We show that softer (Young’s Modulus [E] &lt; 100 kPa) substrates stimulate an average 4-fold greater IL-2 production and ex vivo proliferation of human CD4+ and CD8+ T cells compared with stiffer substrates (E &gt; 2 MPa). Mixed peripheral blood T cells cultured on the stiffer substrates also demonstrate a trend (nonsignificant) toward a greater proportion of CD62Lneg, effector-differentiated CD4+ and CD8+ T cells. Naive CD4+ T cells expanded on softer substrates yield an average 3-fold greater proportion of IFN-γ–producing Th1-like cells. These results reveal that the rigidity of the substrate used to immobilize T cell stimulatory ligands is an important and previously unrecognized parameter influencing T cell activation, proliferation, and Th differentiation. Substrate rigidity should therefore be a consideration in the development of T cell culture systems as well as when interpreting results of T cell activation based upon solid-phase immobilization of TCR/CD3 and CD28 ligands.
Subcongenic Analyses Reveal Complex Interactions between Distal Chromosome 4 Genes Controlling Diabetogenic B Cells and CD4 T Cells in Nonobese Diabetic Mice
Authors: Stolp Jessica , Chen Yi-Guang , Cox Selwyn L. , Henck Vivien , Zhang Wenyu , Tsaih Shirng-Wern , Chapman Harold , Stearns Timothy , Serreze David V. , Silveira Pablo A. 
Published: June 2012

Abstract
Autoimmune type 1 diabetes (T1D) in humans and NOD mice results from interactions between multiple susceptibility genes (termed Idd) located within and outside the MHC. Despite sharing ∼88% of their genome with NOD mice, including the H2g7 MHC haplotype and other important Idd genes, the closely related nonobese resistant (NOR) strain fails to develop T1D because of resistance alleles in residual genomic regions derived from C57BLKS mice mapping to chromosomes (Chr.) 1, 2, and 4. We previously produced a NOD background strain with a greatly decreased incidence of T1D as the result of a NOR-derived 44.31-Mb congenic region on distal Chr. 4 containing disease-resistance alleles that decrease the pathogenic activity of autoreactive B and CD4 T cells. In this study, a series of subcongenic strains for the NOR-derived Chr. 4 region was used to significantly refine genetic loci regulating diabetogenic B and CD4 T cell activity. Analyses of these subcongenic strains revealed the presence of at least two NOR-origin T1D resistance genes within this region. A 6.22-Mb region between rs13477999 and D4Mit32, not previously known to contain a locus affecting T1D susceptibility and now designated Idd25, was found to contain the main NOR gene(s) dampening diabetogenic B cell activity, with Ephb2 and/or Padi2 being strong candidates as the causal variants. Penetrance of this Idd25 effect was influenced by genes in surrounding regions controlling B cell responsiveness and anergy induction. Conversely, the gene(s) controlling pathogenic CD4 T cell activity was mapped to a more proximal 24.26-Mb region between the rs3674285 and D4Mit203 markers.
Interchangeability of Themis1 and Themis2 in Thymocyte Development Reveals Two Related Proteins with Conserved Molecular Function
Authors: Lesourne Renaud , Zvezdova Ekaterina , Song Ki-Duk , El-Khoury Dalal , Uehara Shoji , Barr Valarie A. , Samelson Lawrence E. , Love Paul E. 
Published: June 2012

Abstract
Themis1, a recently identified T cell protein, has a critical function in the generation of mature CD4+CD8− and CD4−CD8+ (CD4 and CD8 single-positive [SP]) thymocytes and T cells. Although Themis1 has been shown to bind to the adaptor proteins LAT and Grb2, previous studies have yielded conflicting results regarding whether thymocytes from Themis1−/− mice exhibit TCR-mediated signaling defects. In this study, we demonstrate that, in the absence of Themis1, TCR-mediated signaling is selectively impaired in CD4 SP and CD8 SP thymocytes but is not affected in CD4+CD8+ double-positive thymocytes despite high expression of Themis1 in double-positive thymocytes. Like Themis1, Themis2, a related member of the Themis family, which is expressed in B cells and macrophages, contains two conserved cysteine-based domains, a proline-rich region, and a nuclear localization signal. To determine whether Themis1 and Themis2 can perform similar functions in vivo, we analyzed T cell development and TCR-mediated signaling in Themis1−/− mice reconstituted with either Themis1 or Themis2 transgenes. Notably, Themis1 and Themis2 exhibited the same potential to restore T cell development and TCR-mediated signaling in Themis1−/− mice. Both proteins were tyrosine phosphorylated and were recruited within Grb2 signaling complexes to LAT following TCR engagement. These results suggest that conserved molecular features of the Themis1 and Themis2 proteins are important for their biological activity and predict that Themis1 and Themis2 may perform similar functions in T and B cells, respectively.
μ-Chain–Deficient Mice Possess B-1 Cells and Produce IgG and IgE, but Not IgA, following Systemic Sensitization and Inhalational Challenge in a Fungal Asthma Model
Authors: Ghosh Sumit , Hoselton Scott A. , Schuh Jane M. 
Published: June 2012

Abstract
Allergic bronchopulmonary aspergillosis is often difficult to treat and results in morbidity associated with chronic airway changes. This study assessed the requirement for B cells and their products in the allergic pulmonary phenotype in a murine model of fungal allergic asthma that mimics allergic bronchopulmonary aspergillosis. C57BL/6 and μMT mice (assumed to lack peripheral B cells) were sensitized with Aspergillus fumigatus extract and challenged with two inhalation exposures of live conidia to induce airway disease. Airway hyperresponsiveness after methacholine challenge, peribronchovascular inflammation, goblet cell metaplasia, and fibrotic remodeling of the airways was similar between μMT mice and their wild-type counterparts (C57BL/6). Surprisingly, even in the absence of the μ-chain, these μMT mice produced IgE and IgG Abs, although the Abs induced did not have specificity for A. fumigatus Ags. In contrast, IgA was not detected in either the lavage fluid or serum of μMT mice that had been exposed to A. fumigatus. Our findings also reveal the existence of CD19+CD9+IgD+ B-1 cells in the lungs of the μMT animals. These data show the μMT mice to have a developmental pathway independent of the canonical μ-chain route that allows for their survival upon antigenic challenge with A. fumigatus conidia, although this pathway does not seem to allow for the normal development of Ag-specific repertoires. Additionally, this study shows that IgA is not required for either clearance or containment of A. fumigatus in the murine lung, as fungal outgrowth was not observed in the μMT animals after multiple inhalation exposures to live conidia.