bluuebunny/crossref_metadata_2025 huggingface dataset:
Catechin prevents the calcium oxalate monohydrate induced renal calcium crystallization in NRK-52E cells and the ethylene glycol induced renal stone formation in rat
Authors: Zhai Wei , Zheng Junhua , Yao Xudong , Peng Bo , Liu Min , Huang Jianhua , Wang Guangchun , Xu Yunfei
Published: September 2013

Background

Reactive oxygen species play important roles in renal calcium crystallization. In this study, we examined the effects of catechin, which have been shown to have antioxidant properties on the renal calcium crystallization.

Methods

In the vitro experiment, the changes of the mitochondrial membrane potential, expression of superoxide dismutase (SOD), 4-hydroxynonenal (4-HNE), cytochrome c, and cleaved caspase 3 were measured to show the effects of catechin treatment on the NRK-52E cells induced by calcium oxalate monohydrate (COM). In the vivo study, Sprague–Dawley rats were administered 1% ethylene glycol (EG) to generate a rat kidney stone model and then treated with catechin (2.5 and 10 mg/kg/day) for 14 days. The urine and serum variables were dected on 7 and 14 days after EG administration. The expression of cytochrome c, cleaved caspase 3, SOD, osteopontin (OPN), malondialdehyde (MDA), 8-hydroxy-2′-deoxyguanosine (8-OHdG) in kidney were measured. Furthermore, the mitochondrial microstructure in the kidney was also examined by transmission electron microscopy.

Results

Catechin treatment could prevent the changes in mitochondrial membrane potential and expression of SOD, 4-HNE, cytochrome c, and cleaved caspase 3 in NRK-52E cells induced by the COM. For the in vivo experiments, the EG administration induced renal calcium crystallization was also prevented by the catechin. The expression of SOD, OPN, MDA, OPN and 8-OHdG, were increased after EG administration and this increase was diminished by catechin. Moreover, catechin also prevented EG induced mitochondrial collapse in rat.

Conclusions

Catechin has preventive effects on renal calcium crystallization both in vivo and in vitro, and provide a potential therapeutic treatment for this disease.
Susceptibility to myocardial ischemia reperfusion injury at early stage of type 1 diabetes in rats
Authors: Li Haobo , Liu Zipeng , Wang Junwen , Wong Gordon T , Cheung Chi-Wai , Zhang Liangqing , Chen Can , Xia Zhengyuan , Irwin Michael G
Published: September 2013

Background

Large body of evidences accumulated in clinical and epidemiological studies indicate that hearts of diabetic subjects are more sensitive to ischemia reperfusion injury (IRI), which results in a higher rate of mortality at post-operation than that of non-diabetes. However, experimental results are equivocal and point to either increased or decreased susceptibility of the diabetic hearts to IRI, especially at the early stage of the disease. The present study was designed to test the hypothesis that the duration/severity of the indexed ischemia is a major determinant of the vulnerability to myocardial IRI at early stage of diabetes.

Methods

Four weeks streptozotocin (STZ)-induced diabetic (D) and non-diabetic (C) Sprague–Dawley rats were randomly assigned to receive 30 or 45 min of left anterior descending artery ligation followed by 2 or 3 hours of reperfusion, respectively. Cardiac function was recorded by using Pressure-Volume (PV) conduction system. Myocardial infarct size was determined with triphenyltetrazolium chloride staining. Plasma Creatine kinase-MB (CK-MB), Lactate dehydrogenase (LDH) release, myocardial nitric oxide(NO) content and nitrotyrosine formation, 15-F2t-Isoprostane and plasma superoxide dismutase (SOD) were measured with colorimetric assays. Cardiomyocyte apoptosis was assessed by TUNEL staining. Myocardial TNFα, Caspase-3, STAT3, Akt, and GSK-3β were determined by Western blotting.

Results

Prolongation of ischemia but not reperfusion from 30 min to 45 min significantly increased infarct size in D compared to C rats (P < 0.05), accompanied with significantly increased plasma CK-MB (P < 0.05). Prolongation of the duration of either ischemia or reperfusion significantly increased plasma LDH release and myocardial 15-F2t-Isoprostane and reduced plasma SOD activity, with concomitant reduction of myocardial NO and increase of nitrotyrosine formation in D relative to C (P < 0.05). Prolongation of ischemia and reperfusion significantly reduced left ventricular ejection fraction and increased the peak rate of pressure, accompanied with increased end systolic pressure in D relative to C rats (P < 0.05) but reduced phosphorylations of myocardial STAT3 at site Ser727 and Akt at site Ser473 as well as GSK-3β at Ser 9 (P < 0.05).

Conclusions

Diabetic hearts, even at early stage of the disease are more sensitive to IRI, and this increased severity of post-ischemic myocardial injury depends more on the duration of ischemia than that of reperfusion.
Lipid peroxidation and antioxidant enzymes activity in Plasmodium vivax malaria patients evolving with cholestatic jaundice
Authors: Fabbri Camila , de Cássia Mascarenhas-Netto Rita , Lalwani Pritesh , Melo Gisely C , Magalhães Belisa ML , Alexandre Márcia AA , Lacerda Marcus VG , Lima Emerson S
Published: September 2013

Background

Plasmodium vivax infection has been considered a benign and self-limiting disease, however, recent studies highlight the association between vivax malaria and life-threatening manifestations. Increase in reactive oxygen species has already been described in vivax malaria, as a result of the increased metabolic rate triggered by the multiplying parasite, and large quantities of toxic redox-active byproducts generated. The present study aimed to study the oxidative stress responses in patients infected with P. vivax, who developed jaundice (hyperbilirubinaemia) in the course of the disease, a common clinical complication related to this species.

Methods

An evaluation of the lipid peroxidation and antioxidant enzymes profile was performed in 28 healthy individuals and compared with P. vivax infected patients with jaundice, i.e., bilirubin < 51.3 μmol/L (8 patients) or without jaundice (34 patients), on day 1 (D1) and day 14 (D14) after anti-malarial therapy.

Results

Hyperbilirubinaemia was more frequent among women and patients experiencing their first malarial infection, and lower haemoglobin and higher lactate dehydrogenase levels were observed in this group. Malondialdehyde levels and activity of celuroplasmin and glutathione reductase were increased in the plasma from patients with P. vivax with jaundice compared to the control group on D1. However, the activity of thioredoxin reductase was decreased. The enzymes glutathione reductase, thioredoxin reductase, thiols and malondialdehyde also differed between jaundiced versus non-jaundiced patients. On D14 jaundice and parasitaemia had resolved and oxidative stress biomarkers were very similar to the control group.

Conclusion

Cholestatic hyperbilirubinaemia in vivax malaria cannot be totally disassociated from malaria-related haemolysis. However, significant increase of lipid peroxidation markers and changes in antioxidant enzymes in patients with P. vivax-related jaundice was observed. These results suggest oxidative processes contributing to malaria pathogenesis, what may be useful information for future anti-oxidant therapeutical interventions in these patients.
Molecular-guided therapy predictions reveal drug resistance phenotypes and treatment alternatives in malignant peripheral nerve sheath tumors
Authors: Peacock Jacqueline D , Cherba David , Kampfschulte Kevin , Smith Mallory K , Monks Noel R , Webb Craig P , Steensma Matthew
Published: September 2013

Background

Malignant peripheral nerve sheath tumors (MPNST) are rare highly aggressive sarcomas that affect 8-13% of people with neurofibromatosis type 1. The prognosis for patients with MPNST is very poor. Despite TOP2A overexpression in these tumors, doxorubicin resistance is common, and the mechanisms of chemotherapy resistance in MPNST are poorly understood. Molecular-guided therapy prediction is an emerging strategy for treatment refractory sarcomas that involves identification of therapy response and resistance mechanisms in individual tumors. Here, we report the results from a personalized, molecular-guided therapy analysis of MPNST samples.

Methods

Established molecular-guided therapy prediction software algorithms were used to analyze published microarray data from human MPNST samples and cell lines, with benign neurofibroma tissue controls. MPNST and benign neurofibroma-derived cell lines were used for confirmatory in vitro experimentation using quantitative real-time PCR and growth inhibition assays. Microarray data was analyzed using Affymetrix expression console MAS 5.0 method. Significance was calculated with Welch’s t-test with non-corrected p-value < 0.05 and validated using permutation testing across samples. Paired Student’s t-tests were used to compare relative EC50 values from independent growth inhibition experiments.

Results

Molecular guided therapy predictions highlight substantial variability amongst human MPNST samples in expression of drug target and drug resistance pathways, as well as some similarities amongst samples, including common up-regulation of DNA repair mechanisms. In a subset of MPNSTs, high expression of ABCC1 is observed, serving as a predicted contra-indication for doxorubicin and related therapeutics in these patients. These microarray-based results are confirmed with quantitative, real-time PCR and immunofluorescence. The functional effect of drug efflux in MPNST-derived cells is confirmed using in vitro growth inhibition assays. Alternative therapeutics supported by the molecular-guided therapy predictions are reported and tested in MPNST-derived cells.

Conclusions

These results confirm the substantial molecular heterogeneity of MPNSTs and validate molecular-guided therapy predictions in vitro. The observed molecular heterogeneity in MPNSTs influences therapy prediction. Also, mechanisms involving drug transport and DNA damage repair are primary mediators of MPNST chemotherapy resistance. Together, these findings support the utility of individualized therapy in MPNST as in other sarcomas, and provide initial proof-of concept that individualized therapy prediction can be accomplished.
Are morphological criteria sufficient for the identification of circulating tumor cells in renal cancer?
Authors: El-Heliebi Amin , Kroneis Thomas , Zöhrer Evelyn , Haybaeck Johannes , Fischereder Katja , Kampel-Kettner Karin , Zigeuner Richard , Pock Hannelore , Riedl Regina , Stauber Rudolf , Geigl Jochen Bernd , Huppertz Berthold , Sedlmayr Peter , Lackner Carolin
Published: September 2013

Background

Single circulating tumor cells (CTCs) or circulating tumor microemboli (CTMs) are potential biomarkers of renal cell cancer (RCC), however studies of CTCs/CTMs in RCC are limited. In this pilot study we aimed to evaluate a novel blood filtration technique suited for cytomorphological classification, immunocytochemical and molecular characterization of filtered, so called circulating non-hematologic cells (CNHCs) - putative CTCs/CTMs - in patients with RCC.

Methods

Blood of 40 patients with renal tumors was subjected to ScreenCell® filtration. CNHCs were classified according to cytomorphological criteria. Immunocytochemical analysis was performed with antibodies against CD45, CD31 and carbonic anhydrase IX (CAIX, a RCC marker). DNA of selected CNHCs and respective primary tumors was analysed by array-CGH.

Results

CNHC-clusters with malignant or uncertain malignant cytomorphological features - putative CTMs - were negative for CD45, positive for CD31, while only 6% were CAIX positive. Array-CGH revealed that 83% of malignant and uncertain malignant cells did represent with a balanced genome whereas 17% presented genomic DNA imbalances which did not match the aberrations of the primary tumors. Putative single CTCs were negative for CD45, 33% were positive for CD31 and 56% were positive for CAIX.

Conclusions

The majority of CNHC-clusters, putative CTMs, retrieved by ScreenCell® filtration may be of endothelial origin. Morphological criteria seem to be insufficient to distinguish malignant from non-malignant cells in renal cancer.
Regional consensus opinion for the management of Beta thalassemia major in the Arabian Gulf area
Authors: Qari Mohamad H , Wali Yasser , Albagshi Muneer H , Alshahrani Mohammad , Alzahrani Azzah , Alhijji Ibrahim A , Almomen Abdulkareem , Aljefri Abdullah , Al Saeed Hussain H , Abdullah Shaker , Al Rustumani Ahmad , Mahour Khoutir , Mousa Shaker A
Published: September 2013

Thalassemia syndrome has diverse clinical presentations and a global spread that has far exceeded the classical Mediterranean basin where the mutations arose. The mutations that give rise to either alpha or beta thalassemia are numerous, resulting in a wide spectrum of clinical severity ranging from carrier state to life-threatening, inherited hemolytic anemia that requires regular blood transfusion. Beta thalassemia major constitutes a remarkable challenge to health care providers. The complications arising due to the anemia, transfusional iron overload, as well as other therapy-related complications add to the complexity of this condition. To produce this consensus opinion manuscript, a PubMed search was performed to gather evidence-based original articles, review articles, as well as published work reflecting the experience of physicians and scientists in the Arabian Gulf region in an effort to standardize the management protocol.
Female physicians: trends and likely impacts on healthcare in Israel
Authors: Haklai Ziona , Applbaum Yael , Tal Orna , Aburbeh Myriam , Goldberger Nehama F
Published: September 2013

Background

Female physicians have become an increasing proportion of the medical workforce in Israel. This study investigates this trend and discusses its likely impact on the quantity and quality of medical care available.

Method

Data on licensed physicians and new licenses issued to physicians were taken from a Ministry of Health database, and analyzed by gender, age, academic origin (Israeli graduates, immigrants, Israeli-born who studied abroad), and specialty for the years 1999–2011.

Data on employed physicians, their population group, and work hours were taken from the Central Bureau of Statistics (CBS) annual Labour Force Survey for the years 2009–2011.

Results

The proportion of women amongst physicians aged under 65 rose from 38% in 1999 to 42% in 2011, and was even higher for younger physicians. The highest proportion of females is found amongst new immigrant physicians who studied abroad. The corresponding proportion has been rising steadily amongst Israeli-educated physicians, and is lowest amongst Israeli-born physicians who studied abroad.

Similarly, among newly licensed physicians, the proportion of females has traditionally been highest among immigrants who studied abroad and lowest among Israeli-born graduates who studied abroad. Among newly-licensed physicians who studied in Israel, the proportion of females has historically been intermediate between the other two groups, but it has recently risen to 54% and now parallels the proportion of females among immigrants who studied abroad. In recent years, the mix of academic origins among newly licensed physicians has changed dramatically, with important implications for the proportion of women among newly licensed physicians.

The highest percentage of females was found in family medicine followed by oncology, pediatrics and psychiatry. The greatest increase over the years in this percentage was for gynecology and internal medicine.

Female physicians worked shorter hours than males, particularly at younger ages. The proportion of females among employed Arab physicians is much lower than among Jewish physicians.

Conclusions

The proportion of female physicians has been steadily rising, although in recent years the increase has leveled off. This has been due, in part, to the decline in the flow of immigrant physicians and the increase in the number of Israelis studying abroad. Future developments in medical education options and immigration will determine whether their proportion will continue rising. Planning for future medical personnel must take these results into consideration.
Recruitment and functionality traits as bioindicators of ecological restoration success in the Lurg Hills district, Victoria, Australia
Authors: Monie Kristin , Florentine Singarayer , Palmer Grant
Published: September 2013

Introduction

The Regent Honeyeater Project commenced ecological restoration in the Lurg district in 1994, with an aim to restore habitats for the critically endangered Regent Honeyeater Anthochaera phrygia and a range of other threatened and declining species. Within this context, our study aimed to explore whether plant reproduction can be an effective measure of ecological restoration success.

Methods

Evaluation involved comparing attributes at unrestored, restored and remnant sites to establish whether sites displayed evidence of a clear restoration trajectory. Five age classes (unrestored, 4–6 years old, 8–10 years old, 12–14 years old and remnant areas) and two landforms (upper hills and lower hills) were considered. The diversity of woody plant species—which have easily recognisable reproductive material and which all recruit seedlings—provides easily measured parameters that have the potential to allow the determination of early establishment success and long-term ecological development of restored ecosystems.

Results

Restoration plantings developed in a hybrid state towards a benchmark in the lower hills; seedling species composition differed significantly among age classes, increasing in similarity with time since restoration, with some divergence from the target pathway. Composition of functional groups with reproductive outputs was also significantly different among age classes; however, a restoration trajectory was only evident in the upper hills where sites converged towards the target goal.

Conclusions

Divergence or deviation from the restoration trajectory was not deemed to be a restoration failure, as the variety of functional groups with fruits and diversity of seedlings recruiting indicated a potential increase in resilience in the future due to greater variability across the landscape. Plant recruitment was effective in detecting development trends towards a restoration target in this study and therefore may be a useful measure that contributes to determining ecological restoration success.
Dynamic pressurization induces transition of notochordal cells to a mature phenotype while retaining production of important patterning ligands from development
Authors: Purmessur Devina , Guterl Clare C , Cho Samuel K , Cornejo Marisa C , Lam Ying W , Ballif Bryan A , Laudier Damien M , Iatridis James C
Published: September 2013

Introduction

Notochordal cells (NCs) pattern aneural and avascular intervertebral discs (IVDs), and their disappearance, is associated with onset of IVD degeneration. This study induced and characterized the maturation of nucleus pulposus (NP) tissue from a gelatinous NC-rich structure to a matrix-rich structure populated by small NP cells using dynamic pressurization in an ex vivo culture model, and also identified soluble factors from NCs with therapeutic potential.

Methods

Porcine NC-rich NP tissue was cultured and loaded with hydrostatic pressure (0.5 to 2 MPa at 0.1 Hz for 2 hours) either Daily, for 1 Dose, or Control (no pressurization) groups for up to eight days. Cell phenotype and tissue maturation was characterized with measurements of cell viability, cytomorphology, nitric oxide, metabolic activity, matrix composition, gene expression, and proteomics.

Results

Daily pressurization induced transition of NCs to small NP cells with 73.8%, 44%, and 28% NCs for Control, 1 Dose and Daily groups, respectively (P < 0.0002) and no relevant cell death. Dynamic loading matured NP tissue by significantly increasing metabolic activity and accumulating Safranin-O-stained matrix. Load-induced maturation was also apparent from the significantly decreased glycolytic, cytoskeletal (Vimentin) and stress-inducible (HSP70) proteins assessed with proteomics. Loading increased the production of bioactive proteins Sonic Hedgehog (SHH) and Noggin, and maintained Semaphorin3A (Sema3A).

Discussion

NP tissue maturation was induced from dynamic hydrostatic pressurization in a controlled ex vivo environment without influence from systemic effects or surrounding structures. NCs transitioned into small nonvacuolated NP cells probably via differentiation as evidenced by high cell viability, lack of nitric oxide and downregulation of stress-inducible and cytoskeletal proteins. SHH, Sema3A, and Noggin, which have patterning and neurovascular-inhibiting properties, were produced in both notochordal and matured porcine NP. Results therefore provide an important piece of evidence suggesting the transition of NCs to small NP cells is a natural part of aging and not the initiation of degeneration. Bioactive candidates identified from young porcine IVDs may be isolated and harnessed for therapies to target discogenic back pain.
Joint migration velocity analysis of PP- and PS-waves for VTI media
Authors: Cai Pengfei , Tsvankin Ilya
Published: September 2013

Combining PP-waves with mode-converted PS reflections in migration velocity analysis (MVA) can help build more accurate VTI (transversely isotropic with a vertical symmetry axis) velocity models. To avoid problems caused by the moveout asymmetry of PS-waves and take advantage of efficient MVA algorithms designed for pure modes, here we generate pure SS-reflections from PP and PS data using the [Formula: see text] method. Then the residual moveout in both PP and SS common-image gathers is minimized during iterative velocity updates. The model is divided into square cells, and the VTI parameters [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] are defined at each grid point. The objective function also includes the differences between the migrated depths of the same reflectors on the PP and SS sections. Synthetic examples confirm that 2D MVA of PP- and PS-waves may be able to resolve all four relevant parameters of VTI media if reflectors with at least two distinct dips are available. The algorithm is also successfully applied to a 2D line from 3D ocean-bottom seismic data acquired at Volve field in the North Sea. After the anisotropic velocity model has been estimated, accurate depth images can be obtained by migrating the recorded PP and PS data.
Prediction of Survival by [18F]Fluorodeoxyglucose Positron Emission Tomography in Patients With Locally Advanced Non–Small-Cell Lung Cancer Undergoing Definitive Chemoradiation Therapy: Results of the ACRIN 6668/RTOG 0235 Trial
Authors: Machtay Mitchell , Duan Fenghai , Siegel Barry A. , Snyder Bradley S. , Gorelick Jeremy J. , Reddin Janet S. , Munden Reginald , Johnson Douglas W. , Wilf Larry H. , DeNittis Albert , Sherwin Nancy , Cho Kwan Ho , Kim Seok-ki , Videtic Gregory , Neumann Donald R. , Komaki Ritsuko , Macapinlac Homer , Bradley Jeffrey D. , Alavi Abass
Published: September 2013

Purpose

In this prospective National Cancer Institute–funded American College of Radiology Imaging Network/Radiation Therapy Oncology Group cooperative group trial, we hypothesized that standardized uptake value (SUV) on post-treatment [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) correlates with survival in stage III non–small-cell lung cancer (NSCLC).

Patients and Methods

Patients received conventional concurrent platinum-based chemoradiotherapy without surgery; postradiotherapy consolidation chemotherapy was allowed. Post-treatment FDG-PET was performed at approximately 14 weeks after radiotherapy. SUVs were analyzed both as peak SUV (SUVpeak) and maximum SUV (SUVmax; both institutional and central review readings), with institutional SUVpeak as the primary end point. Relationships between the continuous and categorical (cutoff) SUVs and survival were analyzed using Cox proportional hazards multivariate models.

Results

Of 250 enrolled patients (226 were evaluable for pretreatment SUV), 173 patients were evaluable for post-treatment SUV analyses. The 2-year survival rate for the entire population was 42.5%. Pretreatment SUVpeak and SUVmax (mean, 10.3 and 13.1, respectively) were not associated with survival. Mean post-treatment SUVpeak and SUVmax were 3.2 and 4.0, respectively. Post-treatment SUVpeak was associated with survival in a continuous variable model (hazard ratio, 1.087; 95% CI, 1.014 to 1.166; P = .020). When analyzed as a prespecified binary value (≤ v > 3.5), there was no association with survival. However, in exploratory analyses, significant results for survival were found using an SUVpeak cutoff of 5.0 (P = .041) or 7.0 (P < .001). All results were similar when SUVmax was used in univariate and multivariate models in place of SUVpeak.

Conclusion

Higher post-treatment tumor SUV (SUVpeak or SUVmax) is associated with worse survival in stage III NSCLC, although a clear cutoff value for routine clinical use as a prognostic factor is uncertain at this time.
Economic Burden of Cancer Survivorship Among Adults in the United States
Authors: Guy Gery P. , Ekwueme Donatus U. , Yabroff K. Robin , Dowling Emily C. , Li Chunyu , Rodriguez Juan L. , de Moor Janet S. , Virgo Katherine S.
Published: September 2013

Purpose

To present nationally representative estimates of the impact of cancer survivorship on medical expenditures and lost productivity among adults in the United States.

Methods

Using the 2008 to 2010 Medical Expenditure Panel Survey, we identified 4,960 cancer survivors and 64,431 individuals without a history of cancer age ≥ 18 years. Direct medical costs were measured using annual health care expenditures and examined by source of payment and service type. Indirect morbidity costs were estimated from lost productivity as a result of employment disability, missed work days, and lost household productivity. We evaluated the economic burden of cancer survivorship by estimating excess costs among cancer survivors, stratified by time since diagnosis (recently diagnosed [≤ 1 year] and previously diagnosed [> 1 year]), compared with individuals without a history of cancer using multivariable regression models stratified by age (18 to 64 and ≥ 65 years), controlling for age, sex, race/ethnicity, education, and comorbidities.

Results

In 2008 to 2010, the annual excess economic burden of cancer survivorship among recently diagnosed cancer survivors was $16,213 per survivor age 18 to 64 years and $16,441 per survivor age ≥ 65 years. Among previously diagnosed cancer survivors, the annual excess burden was $4,427 per survivor age 18 to 64 years and $4,519 per survivor age ≥ 65 years. Excess medical expenditures composed the largest share of the economic burden among cancer survivors, particularly among those recently diagnosed.

Conclusion

The economic impact of cancer survivorship is considerable and is also high years after a cancer diagnosis. Efforts to reduce the economic burden caused by cancer will be increasingly important given the growing population of cancer survivors.
Revised Staging Classification Improves Outcome Prediction for Small Intestinal Neuroendocrine Tumors
Authors: Kim Michelle Kang , Warner Richard R.P. , Roayaie Sasan , Harpaz Noam , Ward Stephen C. , Itzkowitz Steven , Wisnivesky Juan P.
Published: September 2013

Purpose

Small intestinal (SI) neuroendocrine tumors (NETs) have heterogeneous outcomes. The NET societies have recently proposed a TNM staging classification. In this study, we used population-based data to assess the validity of the staging system.

Patients and Methods

We identified patients with SI-NETS diagnosed between 1988 and 2009 from the Surveillance, Epidemiology, and End Results registry. We used Kaplan-Meier analysis to assess disease-specific survival according to TNM status. Cox models were constructed to evaluate differences in prognosis after controlling for potential confounders.

Results

We identified 6,792 patients with SI-NET. Although the current staging system was predictive of prognosis, there was overlap among some groups (stage I/IIA, P = .36; stage IIB/IIIB, P = .70). Additionally, stage IIIB patients had better survival than stage IIIA patients (P < .001). Adjusted analyses showed similar outcomes for T1 versus T2 disease (hazard ratio [HR], 1.02; 95% CI, 0.63 to 1.66). Patients with T3 (HR, 3.60; 95% CI, 2.28 to 5.69) and T4 (HR, 5.50; 95% CI, 3.42 to 8.86) tumors had significantly worse survival than patients with T1 disease. N1 involvement conferred worse survival in T1 (HR, 3.08; 95% CI, 1.75 to 5.44) and T2 disease (HR, 2.73; 95% CI, 1.84 to 4.07) but not in T3 (HR, 0.99; 95% CI, 0.76 to 1.30) or T4 (HR, 0.98; 95% CI, 0.71 to 1.35) disease. A revised classification showed no overlap in survival across groups.

Conclusion

Progressively more advanced T status is associated with worse SI-NET prognosis. Regional lymph node involvement is a marker of worse survival only among patients with T1 or T2 status. These results suggest that revisions to the current staging classification may be helpful.
Baseline Blood Work Before Initiation of Chemotherapy: What Is Safe in the Real World?
Authors: Warr Julia , Hird Amanda E. , DeAngelis Carlo , Giotis Angie , Ko Yoo-Joung
Published: September 2013

This study describes the incidence of clinically significant changes in laboratory values before chemotherapy administration in a large cohort at a tertiary cancer center.
An Automated System for Detecting Nonadherence in Laboratory Testing and Monitoring for Myelosuppression in Patients Receiving Self-Administered Oral Chemotherapy
Authors: Morrell Robert M. , Tooze Janet A. , Harmon Michele S. , Carter Annette F. , DeTroye Alisha T. , Lesser Glenn J.
Published: September 2013

The authors sought to assess monitoring lapses and incidents of myelosuppression in patients undergoing self-administered chemotherapy for glioblastoma, as well as test software designed to detect and alert clinicians to lapses in monitoring.
Impact of Chemotherapy-Induced Peripheral Neuropathy on Treatment Delivery in Nonmetastatic Breast Cancer
Authors: Speck Rebecca M. , Sammel Mary D. , Farrar John T. , Hennessy Sean , Mao Jun J. , Stineman Margaret G. , DeMichele Angela
Published: September 2013

The authors found that oncologists limited the dosing of chemotherapy because of chemotherapy-induced peripheral neuropathy events in a significant proportion of paclitaxel recipients, most frequently in those who received a weekly regimen.
Documenting the Benefits and Cost Savings of a Large Multistate Cancer Pathway Program From a Payer's Perspective
Authors: Kreys Eugene D. , Koeller Jim M.
Published: September 2013

Broadly implemented clinical pathways can achieve reasonable physician compliance, resulting in substantial cost savings.
Helping Patients Quit Tobacco: ASCO's Efforts to Help Oncology Care Specialists
Authors: Hanna Nasser
Published: September 2013

In a time of continuing changes in oncology practice, such as more complex health care and communication systems, few initiatives will have as great an impact on societal health and well-being as reducing tobacco use.
Pretreatment Patient Comorbidity and Tobacco Use Increase Cost and Risk of Postoperative Complications After Esophagectomy at a High-Volume Cancer Center
Authors: Murphy Caitlin C. , Incalcaterra James R. , Albright Heidi W. , Correa Arlene M. , Swisher Stephen G. , Hofstetter Wayne L.
Published: September 2013

Although direct cost comparisons between institutions may not yet be possible, the model and methods the authors used to assess variance in cost of esophagectomy could be adopted for use in different clinical settings.
The Black Skyscraper
Authors: Brown Adrienne
Published: September 2013

Brown’s essay explores how black modernists W. E. B. DuBois and Wallace Thurman used the skyscraper’s abstracted view of the masses to envision raced models of democracy and difference. As urban identity in the 1920s became increasingly associated with ethnic identity, writers used the view from the skyscraper’s apex to imagine both utopian and dystopian designs of modern sociality. While lynching and minstrelsy have previously been the primary vehicles for thinking about race, crowds, and visions during the early twentieth century, Thur man and DuBois insist on the significance of skyscraper architecture in creating new racial imaginaries for modern modes of vision.
Frederick Douglass in 1848
Authors: Marrs Cody
Published: September 2013

When revolutions rocked Europe in 1848, Frederick Douglass responded almost immediately by framing these movements across the Atlantic in global terms, connecting class strife in the Old World to the struggle over slavery in the New. Yet he also used the revolts of 1848 long after they had ended to discern other, related patterns of protest and repression in the slavery crisis of the 1850s, in the Civil War, and in the rise and fall of Radical Reconstruction. His reflections on these rebellions thereby shuttle between times and locations, weaving together disparate places and events in ways that advance a multilinear sense of historical time. The manner in which Douglass writes through 1848— connecting Europe to the United States and integrating those failed rebellions into a capacious philosophy of history—thus suggests that transnationalism itself inheres in a particular kind of temporal, and even literary, transport.
The Climates of Liberty: Natural Rights in theCreoleCase and “The Heroic Slave”
Authors: Hyde Carrie
Published: September 2013

Hyde reassesses the relationship between natural and civil rights by tracking the climatological metaphors that shape representations of the 1841 slave revolt aboard the Creole, in which 135 slaves obtained freedom by redirecting a US ship to the British territory of Nassau, Bahamas. Reading Frederick Douglass’s fictional reconstruction of the revolt in “The Heroic Slave” (1853) in conjunction with the diplomatic letters it revises, Hyde shows how the conceit of natural law allowed writers to portray national statutes as mere “local fictions.” Whereas Secretary of State Daniel Webster symptomatically invoked the rhetoric of weather and natural disaster to negate the agency of the slaves on the Creole, Douglass uses natural phenomena to portray emancipation as a force of nature that controverts the geopolitical partitioning of freedom. Douglass’s objective, however, is not ultimately postnational or cosmopolitan, as critics have suggested. Instead, “The Heroic Slave” uses the universalizing rhetoric of natural law to denaturalize exclusionary laws within the United States, even as it attempts to salvage the potential of US democracy. Douglass never forfeits the idea that rights ought to be inalienable by nature, but by recognizing that rights are alienable in practice—not simply that they are often divested and withheld, but that they can be transferred to those who do not already possess them—he narrates the extralegal drama of political legitimation.
Aztlán’s Asians: Forging and Forgetting Cross-Racial Relations in the Chicana/O Literary Imagination
Authors: Sae-Saue Jayson Gonzales
Published: September 2013

Using José Villarreal’s Pocho, Luis Valdez’s Vietnam Campesino, Américo Paredes’s “Ichiro Kikuchi,” and Rolando Hinojosa’s Korean Love Songs as its primary examples, Sae-Saue’s essay shows that crossracial relations between Chicana/os and Asians reverberate consistently in narratives that articulate Chicana/o political identities. In these texts, Asia and Asians provoke powerful political awakenings because transnational and interracial ideas about Asia and Asians factor significantly in the political emergence of their respective Chicana/o protagonists. However, by relegating Asia and Asians to the margins of a larger narrative structure, the texts repress these transnational and cross-racial encounters after their having precipitated intense political thinking. In this manner, these important Chicana/o writings communicate a political culture in which transnational and interracial thinking about Asia and Asians exists in a complementary and conflicted relationship with a need to articulate local community problems without extra-ethnic distractions. Sae-Saue argues that the marginalization of Asia and Asians in early Chicana/o literature symbolizes the historical tensions of a political culture committed to communicating local community concerns on one hand, and the development of transnational and interracial political thinking on the other.
A global pattern of mechanical stress polarizes cell divisions and cell shape in the growing Drosophila wing disc
Authors: LeGoff Loïc , Rouault Hervé , Lecuit Thomas
Published: September 2013

Organismal development is under genetic control. Ultimately, mechanical forces shape embryos. If we want to understand the precise regulation of size and shape in animals, we must dissect how forces are distributed in developing tissues, and how they drive cell behavior to shape organs. This has not been addressed fully in the context of growing tissues. As cells grow and divide, they exert a pressure on their neighbors. How these local stresses add up or dissipate as the tissue grows is an unanswered question. We address this issue in the growing wing imaginal disc of Drosophila larvae, the precursor of the adult wing. We used a quantitative approach to analyze the strains and stresses of cells of the wing pouch, and found a global pattern of stress whereby cells in the periphery of the tissue are mechanically stretched and cells in the center are compressed. This pattern has important consequences on cell shape in the wing pouch: cells respond to it by polarizing their acto-myosin cortex, and aligning their divisions with the main axis of cell stretch, thereby polarizing tissue growth. Ectopic perturbations of tissue growth by the Hippo signaling pathway reorganize this pattern in a non-autonomous manner, suggesting a synergy between tissue mechanics and growth control during wing disc morphogenesis.
Celebrity Endorsements, Firm Value, and Reputation Risk: Evidence from the Tiger Woods Scandal
Authors: Knittel Christopher R. , Stango Victor
Published: September 2013

We estimate the stock market effects of the Tiger Woods scandal on his sponsors and sponsors' competitors. In the 10–15 trading days after the onset of the scandal, the full portfolio of sponsors lost more than 2% of market value, with losses concentrated among the core three sponsors: Electronic Arts, Nike, and PepsiCo (Gatorade). Sponsors' day-by-day losses correlate strongly with Google search intensity regarding the endorsement-related impact of the scandal, as well as with qualitative indicators of “endorsement-related news.” At least some sponsors' losses were competitors' gains, suggesting that endorsement deals are partially a business-stealing strategy. However, competitors who were themselves celebrity endorsement intensive fared relatively worse than those who were not endorsement intensive, and that difference also correlates day by day with news/search intensity regarding the scandal. It appears that the scandal sent a negative marketwide signal about the reputation risk associated with celebrity endorsements.

This paper was accepted by Pradeep Chintagunta, marketing.
Pareto Efficiency in Robust Optimization
Authors: Iancu Dan A. , Trichakis Nikolaos
Published: September 2013

This paper formalizes and adapts the well-known concept of Pareto efficiency in the context of the popular robust optimization (RO) methodology for linear optimization problems. We argue that the classical RO paradigm need not produce solutions that possess the associated property of Pareto optimality, and we illustrate via examples how this could lead to inefficiencies and suboptimal performance in practice. We provide a basic theoretical characterization of Pareto robustly optimal (PRO) solutions and extend the RO framework by proposing practical methods that verify Pareto optimality and generate solutions that are PRO. Critically important, our methodology involves solving optimization problems that are of the same complexity as the underlying robust problems; hence, the potential improvements from our framework come at essentially limited extra computational cost. We perform numerical experiments drawn from three different application areas (portfolio optimization, inventory management, and project management), which demonstrate that PRO solutions have a significant potential upside compared with solutions obtained using classical RO methods.

This paper was accepted by Gérard P. Cachon, optimization.
Horizontal Mergers in Multitier Decentralized Supply Chains
Authors: Cho Soo-Haeng
Published: September 2013

The well-known economic theory predicts that consumer price will fall after a horizontal merger when the amount of marginal cost reduction from operating synergies exceeds the premerger markup of a merging firm. However, when a horizontal merger occurs in a multitier decentralized supply chain where a finite number of firms compete at each tier, we show that this result holds only when a merger occurs at the tier that acts as the leader in the supply chain. In this supply chain, a horizontal merger at any other tier will decrease consumer price when the cost reduction exceeds a certain threshold that is larger than the premerger markup. Moreover, this threshold is increasing as the supply chain gets longer and can be substantially larger than the premerger markup. When accounting for subsequent entry after a merger in long-run equilibrium, contrary to a common belief, a larger synergy from a merger does not necessarily benefit consumers more.

This paper was accepted by Yossiv Aviv, operations management.
Cannabinoids in Exhaled Breath following Controlled Administration of Smoked Cannabis
Authors: Himes Sarah K , Scheidweiler Karl B , Beck Olof , Gorelick David A , Desrosiers Nathalie A , Huestis Marilyn A
Published: September 2013

BACKGROUND

Δ9-Tetrahydrocannabinol (THC), 11-nor-9-carboxy-THC (THCCOOH), and cannabinol (CBN) were measured in breath following controlled cannabis smoking to characterize the time course and windows of detection of breath cannabinoids.

METHODS

Exhaled breath was collected from chronic (≥4 times per week) and occasional (<twice per week) smokers before and after smoking a 6.8% THC cigarette. Sample analysis included methanol extraction from breath pads, solid-phase extraction, and liquid chromatography–tandem mass spectrometry quantification.

RESULTS

THC was the major cannabinoid in breath; no sample contained THCCOOH and only 1 contained CBN. Among chronic smokers (n = 13), all breath samples were positive for THC at 0.89 h, 76.9% at 1.38 h, and 53.8% at 2.38 h, and only 1 sample was positive at 4.2 h after smoking. Among occasional smokers (n = 11), 90.9% of breath samples were THC-positive at 0.95 h and 63.6% at 1.49 h. One occasional smoker had no detectable THC. Analyte recovery from breath pads by methanolic extraction was 84.2%–97.4%. Limits of quantification were 50 pg/pad for THC and CBN and 100 pg/pad for THCCOOH. Solid-phase extraction efficiency was 46.6%–52.1% (THC) and 76.3%–83.8% (THCCOOH, CBN). Matrix effects were −34.6% to 12.3%. Cannabinoids fortified onto breath pads were stable (≤18.2% concentration change) for 8 h at room temperature and −20°C storage for 6 months.

CONCLUSIONS

Breath may offer an alternative matrix for identifying recent driving under the influence of cannabis, but currently sensitivity is limited to a short detection window (0.5–2 h).
Understanding and Supporting Triple Transitions of International Doctoral Students: ELT And SuReCom Models
Authors: Jindal-Snape Divya , Ingram Richard
Published: September 2013

This paper presents two original conceptual models to explain the triple transitions ofinternational doctoral students and how these can be facilitated better through effective supervisory relationships. These models are based on primary data collected by authors and well known theories, namely the ABC model, Emotional Intelligence and Resilience. The data suggest that when international doctoral students moved to the UK,they had to deal with not only a new educational system and different level of studies; they also had to deal with the daily life issues of being in a new country. These educational and daily life issues were not mutually exclusive and had an impact on each other. However, if one was going exceptionally well,it could act as a buffer for any problems in the other area. Transparent supervisory relationships, where mutual expectations were clear, were seen tobe an effective way of enhancing the transition experience of international doctoral students. This study is the first to explore the triple transitions ofinternational students. The Educational and Life Transitions (ELT) andSupervision Remit Compatibility (SuReCom) models are significant in ensuring successful transition and well-being of international doctoral students.
Effect of Tin on Hot Ductility and High-temperature Oxidation Behavior of 20CrMnTi Steel
Authors: Peng Hong-bing , Chen Wei-qing , Chen Lie , Guo Dong
Published: September 2013

The hot ductility and high-temperature oxidation behavior of 20CrMnTi steel with 0.02% Cu and x% Sn (0.004 ⩽ x ⩽ 0.049) were investigated. The results show that tin has no significant effect on tensile strength of sample with less than 0.049% Sn. The critical temperature where the hot ductility reduces dramatically rises with the increase of tin content while the hot ductility decreases with its increase. The average tin content at austenite grain boundaries (GB) and substrate is 0.108% and 0.045% respectively in the specimen containing 0.049% tin quenched after heated to 1223 K and held for 600 s. Sn-segregation at the GB deteriorates the hot ductility. There is no direct relationship between the cause of the ductility trough and tin. However, Sn-segregation at the GB causes it to deepen a lot. The tin content should be controlled below 0.021%, which would not deteriorate the hot ductility significantly. There is no tin-enrichment at the scale/substrate interface when tin content is less than 0.049%. Moreover, although Sn is enriched under the steel surface, any liquid Sn-enrichment wasn't observed at the oxide/steel interface even in as high as 0.45% Sn-bearing steel with 0.02% Cu.
Solubility of Bismuth in Liquid Bi-S Based Free Cutting Steel
Authors: Liu Haitao , Chen Weiqing , Li Wenying , Yu Yanchong
Published: September 2013

Solubility of bismuth in liquid Bi-S based free cutting steel was measured using a vapor-liquid equilibration method at 1540–1600 °C, and the recovery rate of bismuth in the steel with different temperatures under an atmospheric pressure was also measured. The results showed that the solubility of bismuth in liquid Bi-S based free cutting steel from experiment under a constant volume at 1540, 1560, 1580, and 1600 °C were 0.174, 0.181, 0.205, and 0.220 mass%, respectively, and the relationship of bismuth solubility vs. temperature could be expressed as lg[%Bi] = −6049/T + 2.572. Meanwhile, the solubility of bismuth increased with the increase of Mn content, but decreased with the increase of C content. The recovery of bismuth in this experiment reached a maximum when the temperature was at bismuth boiling point or so, and then it was decreased with the increase of temperature when the temperature was above 1560 °C, which might be attributed to the accelerating of bismuth evaporation that were caused by the increase of bismuth equilibrium partial pressure above the surface of the molten steel with increasing temperature.
Defect Structure of the NiS2 Disulphide
Authors: Poczekajlo A. , Grzesik Z. , Mrowec S.
Published: September 2013

Defect structure of NiS2 disulphide has been studied using marker technique and sulphidation rate measurements of NiS to NiS2, as a function of temperature and sulphur vapor pressure. It has been found that cation sublattice of the discussed compound is predominantly disordered and the prevailing defects are doubly ionized interstitial cations and quasi-free electrons. Using kinetic results, the self-diffusion coefficient of cations in NiS2 has been calculated basing on Wagner's theory of metal oxidation.