bluuebunny/crossref_metadata_2025 huggingface dataset:
Genotype-Guided Dosing Study of FOLFIRI plus Bevacizumab in Patients with Metastatic Colorectal Cancer
Authors: Toffoli Giuseppe , Sharma Manish R. , Marangon Elena , Posocco Bianca , Gray Elizabeth , Mai Quan , Buonadonna Angela , Polite Blase N. , Miolo Gianmaria , Tabaro Gianna , Innocenti Federico
Published: August 2016

Purpose: UGT1A1*28 confers a higher risk of toxicity in patients treated with irinotecan. Patients with *1/*1 and *1/*28 genotypes might tolerate higher than standard doses of irinotecan. We aimed to identify the MTD of irinotecan in patients with metastatic colorectal cancer (mCRC) with *1/*1 and *1/*28 genotypes treated with FOLFIRI plus bevacizumab, and to determine whether bevacizumab alters irinotecan pharmacokinetics.

Experimental Design: Previously untreated patients with mCRC (25 *1/*1; 23 *1/*28) were given FOLFIRI plus bevacizumab every 2 weeks. The irinotecan dose was escalated using a 3 + 3 design in each genotype group as follows: 260, 310, and 370 mg/m2. The MTD was the highest dose at which <4/10 patients had a dose-limiting toxicity (DLT). Pharmacokinetics of irinotecan and SN-38 were measured on days 1 to 3 (without bevacizumab) and 15 to 17 (with bevacizumab).

Results: For *1/*1 patients, 2 DLTs were observed among 10 patients at 310 mg/m2, while 370 mg/m2 was not tolerated (2 DLTs in 4 patients). For *1/*28 patients, 2 DLTs were observed among 10 patients at 260 mg/m2, while 310 mg/m2 was not tolerated (4 DLTs in 10 patients). Neutropenia and diarrhea were the most common DLTs. Changes in the AUCs of irinotecan and SN-38 associated with bevacizumab treatment were marginal.

Conclusions: The MTD of irinotecan in FOLFIRI plus bevacizumab is 310 mg/m2 for UGT1A1 *1/*1 patients and 260 mg/m2 for *1/*28 patients. Bevacizumab does not alter the pharmacokinetics of irinotecan. The antitumor efficacy of these genotype-guided doses should be tested in future studies of patients with mCRC treated with FOLFIRI plus bevacizumab. Clin Cancer Res; 23(4); 918–24. ©2016 AACR.
Knockdown of Apolipoprotein E Enhanced Sensitivity of Hep3B Cells to Cardiac Steroids via Regulating Na+/K+-ATPase Signalosome
Authors: Liu Miao , Feng Li-Xing , Sun Peng , Liu Wang , Mi Tian , Lei Min , Wu Wanying , Jiang Baohong , Yang Min , Hu Lihong , Guo De-An , Liu Xuan
Published: August 2016

This study compared the sensitivity of human hepatoma Hep3B, SK-HEP-1, SMMC-7721, and BEL-7402 cells to cardiac steroids, including bufalin (BF), a bufalin derivative (BF211), ouabain (OUA), and digitoxin (DIG). Hep3B cells exhibited relatively low sensitivity to cardiac steroids. Expression levels of subunits of Na+/K+-ATPase were high in Hep3B cells. However, colocalization of Na+/K+-ATPase and caveolin was nearly undetectable in Hep3B cells. By using RNA-Seq technology, we found a total of 36 genes to be differentially expressed between Hep3B cells and SK-HEP-1 cells, which are highly sensitive to cardiac steroids. Our bioinformatics analysis determined that these genes were mostly comprised of extracellular space, protein binding, and extracellular region. Among these 36 genes, apolipoprotein E (APOE) played a critical role, as knockdown APOE expression induced colocalization of Na+/K+-ATPase and caveolin and increased sensitivity of Hep3B cells to both proliferation-inhibiting and cytotoxic effects of BF or BF211. Also, the effects of BF on PI3K/AKT/GSK3β and apoptosis signal cascades were enhanced in APOE knockdown cells. The results of our study confirmed the role of Na+/K+-ATPase signalosome in cytotoxicity of cardiac steroids and suggested that APOE regulated the sensitivity of cells to cardiac steroids by affecting formation and function of Na+/K+-ATPase signalosome. In addition, intercellular interaction with high level of Na+/K+-ATPase β1 subunit may be also a factor in the low sensitivity of Hep3B cells to cardiac steroids. Mol Cancer Ther; 15(12); 2955–65. ©2016 AACR.
EGFR and RB1 as Dual Biomarkers in HPV-Negative Head and Neck Cancer
Authors: Beck Tim N. , Georgopoulos Rachel , Shagisultanova Elena I. , Sarcu David , Handorf Elizabeth A. , Dubyk Cara , Lango Miriam N. , Ridge John A. , Astsaturov Igor , Serebriiskii Ilya G. , Burtness Barbara A. , Mehra Ranee , Golemis Erica A.
Published: August 2016

Clinical decision making for human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is predominantly guided by disease stage and anatomic location, with few validated biomarkers. The epidermal growth factor receptor (EGFR) is an important therapeutic target, but its value in guiding therapeutic decision making remains ambiguous. We integrated analysis of clinically annotated tissue microarrays with analysis of data available through the TCGA, to investigate the idea that expression signatures involving EGFR, proteins regulating EGFR function, and core cell-cycle modulators might serve as prognostic or drug response–predictive biomarkers. This work suggests that consideration of the expression of NSDHL and proteins that regulate EGFR recycling in combination with EGFR provides a useful prognostic biomarker set. In addition, inactivation of the tumor suppressor retinoblastoma 1 (RB1), reflected by CCND1/CDK6-inactivating phosphorylation of RB1 at T356, inversely correlated with expression of EGFR in patient HNSCC samples. Moreover, stratification of cases with high EGFR by expression levels of CCND1, CDK6, or the CCND1/CDK6-regulatory protein p16 (CDKN2A) identified groups with significant survival differences. To further explore the relationship between EGFR and RB1-associated cell-cycle activity, we evaluated simultaneous inhibition of RB1 phosphorylation with the CDK4/6 inhibitor palbociclib and of EGFR activity with lapatinib or afatinib. These drug combinations had synergistic inhibitory effects on the proliferation of HNSCC cells and strikingly limited ERK1/2 phosphorylation in contrast to either agent used alone. In summary, combinations of CDK and EGFR inhibitors may be particularly useful in EGFR and pT356RB1-expressing or CCND1/CDK6-overexpressing HPV-negative HNSCC. Mol Cancer Ther; 15(10); 2486–97. ©2016 AACR.
Evaluation of Cardiovascular Risk Factors, Haematological and Biochemical Parameters, and Serum Endocan Levels in Patients with Lichen Planus
Authors: Ozlu Emin , Karadag Ayse Serap , Toprak Aybala E. , Uzuncakmak Tugba K. , Gerin Fethullah , Aksu Feyza , Ozakpınar Ozlem , Akdeniz Necmettin
Published: August 2016

Background and Objective: The current study aimed to evaluate cardiovascular risk factors, haematological and biochemical parameters, and serum endocan concentrations in lichen planus (LP) patients. Methods: This study was conducted with 86 cases, including 43 LP patients and 43 healthy controls. Cardiovascular risk factors, haematological and biochemical parameters, and endocan levels were evaluated. Results: The serum endocan concentrations of LP patients were not significantly different from those of the healthy controls (p > 0.05). There were no significant differences in the serum endocan levels according to classification by cardiovascular risk factors and smoking history (p > 0.05). In the LP group, white blood cell count, platelet distribution width and monocyte count/high-density lipoprotein cholesterol ratios were significantly higher when compared to the healthy controls (p < 0.05). The LP group had a lower mean platelet volume than the healthy controls (p < 0.05). Conclusions: Serum endocan levels did not change significantly in patients with LP, and there were significant differences in haematological and biochemical parameters.
Factors Associated with the Use of Gene Expression Profiles in Estrogen Receptor-Positive Early-Stage Breast Cancer Patients: A Nationwide Study
Authors: Kuijer Anne , Schreuder Kay , Elias Sjoerd G. , Smorenburg Carolien H. , Rutgers Emiel J.T. , Siesling Sabine , van Dalen Thijs
Published: August 2016

Background: Breast cancer guidelines suggest the use of gene expression profiles (GEPs) in estrogen receptor-positive (ER+) breast cancer patients in whom controversy exists regarding adjuvant chemotherapy benefit based on traditional prognostic factors alone. We evaluated the current use of GEPs in these patients in the Netherlands. Patients and Methods: Primary breast cancer patients treated between January 1, 2011 and December 31, 2014 and eligible for GEP use according to the Dutch national breast cancer guideline were identified in the Netherlands Cancer Registry: ER+ patients <70 years with grade 1 tumors >2 cm or grade 2 tumors 1-2 cm without overt lymph node metastases (pN0-Nmi). Mixed-effect logistic regression analysis was performed to associate characteristics of patients, tumors and hospitals with GEP use. Results: GEPs were increasingly deployed: 12% of eligible patients received a GEP in 2011 versus 46% in 2014. Lobular versus ductal morphology (OR 0.58, 95% CI 0.47-0.72), pN1mi status (versus pN0, OR 0.52, 95% CI 0.40-0.68), and tumor size (>3 cm vs. >2 cm, OR 0.33, 95% CI 0.14-0.88) were inversely associated with GEP use. High socioeconomic status (SES) (OR 1.32, 95% CI 1.06-1.64) and younger age (OR 0.96/year increasing age, 95% CI 0.95-0.96) were positively associated with GEP use. GEP use per hospital did vary, but no predefined institutional factors remained independently associated with GEP use. Conclusion: GEP use increased over time and was influenced by patient- and tumor-associated factors as well as by SES.
Effectiveness of Phosphodiesterase 5 Inhibitors in the Treatment of Erectile Dysfunction in Patients with Spinal Cord Trauma: Systematic Review and Meta-Analysis
Authors: García-Perdomo Herney Andrés , Echeverría-García Fernando , Tobías Aurelio
Published: August 2016

Objective: To determine the effectiveness of the Phosphodiesterase 5 (PDE5) Inhibitors for the treatment of erectile dysfunction in patients with spinal trauma. Methods: A systematic review and meta-analysis comparing PDE5 inhibitors versus placebo were carried out for clinical trials conducted between 1980 and 2014 that evaluated male patients older than 18 years, diagnosed with spinal cord trauma and erectile dysfunction. We designed a search strategy for Medline, CENTRAL, EMBASE and other electronic sources. Two investigators independently and blindly screened the studies for inclusion. A random effect meta-analysis was performed. Results: Six studies involving 963 patients were included. Male patients over 18 years with ED attributable or subsequent to traumatic spinal cord injury (SCI) were included from these studies. In 4 of these studies, patients were randomized to the treatment group receiving sildenafil and the comparison group was placebo. Out of the remaining 2 trials, one compared tadalafil against the placebo and the other vardenafil versus placebo. The improvement on SCIs with PDE5 inhibitors was found to be large (standardized mean difference 0.71; 95% CI 0.39-1.03), with a high heterogeneity (I2 = 74.4%). Conclusions: PDE5 inhibitors are effective for the treatment of erectile dysfunction secondary to SCI.
Paisagens como panorama e ritmos audiovisuais: percepção ambiental na pesca da Tainha
Authors: Devos Rafael , Vedana Viviane , Barbosa Gabriel Coutinho
Published: August 2016

O artigo desenvolve uma abordagem audiovisual para o estudo dos saberes, fazeres e interações envolvidos na prática da vigia de cardumes durante a temporada de pesca da tainha com rede de cerco, em Florianópolis. Através de fotos panorâmicas, narrativas em vídeo e montagens em hipermídia, provocamos o leitor/espectador a “ver peixe”, ampliando suas habilidades perceptuais na compreensão da formação da paisagem litorânea entre coletivos de pesca.
Formation of Contract under the Islamic Majallah and unidroit Principles of 2010
Authors: Dodeen Mahmoud M.
Published: August 2016

This article focuses on the rules for creating contracts under the Islamic Majallah and unidroit Principles of 2010. The research uses an analytical approach and comparative Arab jurisprudence. To compare the Majallah and unidroit Principles academically, this article’s focus is especially on countries where the civil law originated from the Majallah. Such countries include Jordan, Kuwait, and the United Arab Emirates. Here we show that the Majallah generally agrees with the unidroit Principles regarding the rules of contract formation. The main points of disagreement between the two are seen in a very limited number of concepts.
DNA barcodes unite two problematic taxa: the meiobenthic Boreohydra simplex is a life-cycle stage of Plotocnide borealis (Hydrozoa: Aplanulata)
Authors: PYATAEVA SOFIA V. , HOPCROFT RUSSELL R. , LINDSAY DHUGAL J. , COLLINS ALLEN G.
Published: August 2016

Genetic barcodes of arctic medusae and meiobenthic cnidarians have uncovered a fortuitous connection between the medusa Plotocnide borealis Wagner, 1885 and the minute, mud-dwelling polyp Boreohydra simplex Westblad, 1937. Little to no sequence differences exist among independently collected samples identified as Boreohydra simplex and Plotocnide borealis, showing that the two different forms represent a single species that is henceforth known by the older name Plotocnide borealis Wagner, 1885. The polyp form has been observed to produce bulges previously hypothesized to be gonophores, and the results here are consistent with that view. Interestingly, the polyp has also been reported to produce egg cells in the epiderm, a surprising phenomenon that we document here for only the second time. Thus, P. borealis produces eggs in two different life stages, polyp and medusa. This is the first documented case of a metagenetic medusozoan species being able to produce gametes in both the medusa and polyp stage. It remains unclear what environmental/ecological conditions modulate the production of eggs and/or medusa buds in the polyp stage. Similarly, sperm production, fertilization and development are unknown, warranting further studies.
Comparisons of Modeled and Observed Reflectivities and Fall Speeds for Snowfall of Varied Riming Degrees during Winter Storms on Long Island, New York
Authors: Molthan Andrew L. , Colle Brian A. , Yuter Sandra E. , Stark David
Published: August 2016

Derived radar reflectivities and fall speeds for four Weather Research and Forecasting (WRF) Model bulk microphysical parameterizations (BMPs) run at 1.33-km grid spacing are compared with ground-based, vertically pointing Ku-band radar, scanning S-band radar, and in situ measurements at Stony Brook, New York. Simulations were partitioned into periods of observed riming degree as determined manually using a stereo microscope and camera during nine winter storms. Simulations were examined to determine whether the selected BMPs captured the effects of varying riming intensities, provided a reasonable match to the vertical structure of radar reflectivity or fall speed, and whether they produced reasonable surface fall speed distributions. Schemes assuming nonspherical mass–diameter relationships yielded reflectivity distributions closer to observed values. All four schemes examined in this study provided a better match to the observed, vertical structure of reflectivity during moderate riming than light riming periods. The comparison of observed and simulated snowfall speeds had mixed results. One BMP produced episodes of excessive cloud water at times, resulting in fall speeds that were too large. However, most schemes had frequent periods of little or no cloud water during moderate riming periods and thus underpredicted the snowfall speeds at lower levels. Short, 1–4-h periods with relatively steady snow conditions were used to compare BMP and observed size and fall speed distributions. These limited data suggest the examined BMPs underpredict fall speeds of cold-type snow habits and underrepresent aggregates larger than 4-mm diameter.
Carotid Stenting Versus Carotid Endarterectomy: What Did the Carotid Revascularization Endarterectomy Versus Stenting Trial Show and Where Do We Go From Here?
Authors: Lal Brajesh K. , Meschia James F. , Howard George , Brott Thomas G.
Published: August 2016

Although rapidly expanding in its use, carotid artery stenting remains a relatively new procedure. Its growth is due, at least in part, to the perceived advantages of a less invasive technique. However, the clinical effectiveness and specific role for stenting in the treatment of carotid occlusive disease are still under evaluation. The primary aim of the randomized clinical trial, Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), was to contrast the relative efficacy of carotid stenting versus carotid endarterectomy in preventing stroke, myocardial infarction, or death during a 30-day periprocedural period or ipsilateral stroke over the follow-up period in patients with symptomatic and asymptomatic extracranial carotid stenosis. The secondary goals were to describe the differential efficacy of the 2 procedures in men and women, contrast periprocedural (30-day) morbidity and postprocedural morbidity and mortality, estimate and contrast the restenosis rates of the 2 procedures, evaluate differences in measures of health-related quality of life and cost-effectiveness, and identify subgroups of participants at differential risk of stenting or surgery. This report summarizes the results obtained from CREST with respect to its primary and secondary aims.
MCMC Z-G
Authors: Wang Wei , Lee Philseok , Joo Seang-Hwane , Stark Stephen , Louden Robert
Published: August 2016

In recent years, there has been a surge of interest in measuring noncognitive constructs in educational and managerial/organizational settings. For the most part, these noncognitive constructs have been and continue to be measured using Likert-type (ordinal response) scales, which are susceptible to several types of response distortion. To deal with these response biases, researchers have proposed using forced-choice format, which requires respondents or raters to evaluate cognitive, affective, or behavioral descriptors presented in blocks of two or more. The workhorse for this measurement endeavor is the item response theory (IRT) model developed by Zinnes and Griggs (Z-G), which was first used as the basis for a computerized adaptive rating scale (CARS), and then extended by many organizational scientists. However, applications of the Z-G model outside of organizational contexts have been limited, primarily due to the lack of publicly available software for parameter estimation. This research effort addressed that need by developing a Markov chain Monte Carlo (MCMC) estimation program, called MCMC Z-G, which uses a Metropolis-Hastings-within-Gibbs algorithm to simultaneously estimate Z-G item and person parameters. This publicly available computer program MCMC Z-G can run on both Mac OS® and Windows® platforms.
Voice Outcomes following a Single Office‐Based Steroid Injection for Vocal Fold Scar
Authors: Young William G. , Hoffman Matthew R. , Koszewski Ian J. , Whited Chad W. , Ruel Brienne N. , Dailey Seth H.
Published: August 2016

Objective

Persistent dysphonia from vocal fold scar remains a clinical challenge, with current therapies providing inconsistent outcomes. We evaluated voice outcomes after a single office‐based steroid injection.

Study Design

Case series with chart review.

Setting

Academic medical center.

Subjects and Methods

This study was based on pre‐ and postoperative analysis of patient‐reported, perceptual, acoustic, aerodynamic, and videostroboscopic parameters. The sample comprised 25 patients undergoing office‐based dexamethasone injection into the superficial lamina propria for mild/moderate vocal fold scar. Average follow‐up was 13.7 ± 4.4 weeks; patients completed 3.5 ± 2.3 sessions of voice therapy between assessments. Complete data sets were not available for each parameter; sample size is noted with results.

Results

Voice handicap index (n = 24; P <. 001) and glottal function index (n = 22; P <. 001) decreased after injection. Total GRBAS score (grade, roughness, breathiness, asthenia, strain) decreased (n = 25; P <. 001). Fundamental frequency range increased (n = 24; P =. 024). Phonation threshold pressure decreased (n = 14; P =. 017). Videostroboscopic parameters of vocal fold edge (P =. 004), glottic closure (P =. 003), and right mucosal wave (P =. 016) improved after injection.

Conclusions

Office‐based steroid injection combined with voice therapy for mild/moderate vocal fold scar is associated with improved patient‐reported and functional voice measures. These findings provide preliminary support for this approach. Importantly, the procedure is low risk and can be performed in the office, thus offering a simple treatment alternative to patients with a disorder that has traditionally been difficult to manage. Prospective studies evaluating the effects of multiple injections are warranted.
Curcumin improves atorvastatin-induced myotoxicity in rats: Histopathological and biochemical evidence
Authors: Elshama Said Said , El-Kenawy Ayman El-Meghawry , Osman Hosam-Eldin Hussein
Published: August 2016

Atorvastatin is considered to be one of the most commonly used of all statins anti-hyperlipidemic drugs despite the fact that there is much controversy about its safety. Its therapeutic use becomes severely limited by the hazards of inducing myotoxicity. Curcumin is one of the safe spices that have chemoprotection and cytoprotection effects against endogenous and exogenous noxious stimuli. This study investigates the effect of curcumin on atorvastatin sub-chronic use-induced myotoxicity in rats by the assessment of serum creatinine phosphokinase, lactic acid dehydrogenase, myoglobin, troponin, potassium, creatinine, and histopathological changes of skeletal, smooth, and cardiac muscles by light and electron microscope examination. Eighty adult albino rats were divided into four groups; each group consists of 20 rats. The control group received water, the second group received atorvastatin, the third group received curcumin, and the fourth group received curcumin with atorvastatin for 90 days by gastric gavage. The prolonged use of atorvastatin induced significant abnormalities of all myotoxicity biomarkers associated with histopathological and ultrastructural changes in the different types of the muscles. Co-administration of curcumin with sub-chronic use of atorvastatin led to an improvement in myotoxicity manifestations.
Mapping Gender Segregation in Pre-Primary and Primary Education in Cyprus
Authors: Rentzou Konstantina
Published: August 2016

Although great emphasis is given on the quality of early childhood education, the demographics of the teaching personnel attract limited attention even though those characteristics are linked to the quality of education. The present study aims at exploring gender segregation in pre-primary and primary education in Cyprus, using the statistical lenses through which feminization can be understood. The article presents the number of male and female undergraduate students enrolled in pre-primary and primary education programs. Employment data are also presented. This article sets out to discuss statistical data and literature to find out which research needs to be undertaken to ensure the inclusion of more men in pre-primary and primary education in Cyprus. Statistics highlight the need to critically examine existing literature, to conduct research with both males and females and to start the process of recruiting and supporting more males moving into pre-primary and primary education.
A Gateway Deployment Heuristic for Enhancing the Availability of Sensor Grids
Authors: Hussain Majid , Kim Ki-Hyung , Akbar Ali Hammad , Khalid Shehzad , Bang Seung-Jin , Javed Mohsin , Amjad Madiha
Published: August 2016

Wireless sensor grids form a special class of sensor networks that find more applicability than their randomly deployed counterparts in many commercial applications due to innate regularity in their design and operation. In contemporary wireless sensor grids, primarily single gateway sensor grids, each node senses the information and follows a relay relationship with gateway forming a multisource single receiver paradigm and pursues an added energy consumption pattern that serves as a premier bottleneck in wireless sensor grid environment. This research focuses on statistically modeling the energy consumption of single gateway sensor grids in terms of network availability by analyzing different energy consumption phenomena with communication as a grid-wide routing problem. On the basis of our findings and results in conjunction with Moor's law of semiconductors and batteries, we propose a linear programming heuristic for multiple gateway deployment to reduce network survivability costs and optimize communication for wireless sensor grids. We then present a case study using the proposed heuristic that is augmented through a node scheduler for nearest gateway connectivity, collision avoidance, and fairness, to show the performance gain that presents an ultimate cut-through energy paradigm.
Proper Global Shared Preference Detection Based on Golden Section and Genetic Algorithm for Affinity Propagation Clustering
Authors: Jiao Libin , Bie Rongfang , Zhang Guangzhi , Wang Shenling , Mehmood Rashid
Published: August 2016

Affinity propagation (AP) clustering is a well-known effective clustering algorithm that outperforms other traditional clustering algorithms. However, the quality of clustering results depends considerably on related sensitive parameters (i.e., preferences and the damping factor). Thus, a feasible procedure based on golden section (GS) and the genetic algorithm (GA) is proposed. This procedure, called the “GS/GA-AP” algorithm, can perform proper global shared preference detection, including identifying a suitable number of clusters. A global shared preference is provided using the GS value between the minimum and maximum of similarities for AP as a default option, and the unsatisfactory clustering result becomes robust when the parameter with GA is selected. Finally, satisfactory experiments using one simulation data set and eight benchmark data sets are performed to verify the effectiveness of the proposed algorithm. The results indicate that GS/GA-AP clearly outperforms the original AP clustering algorithm.
Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Combination With Fludarabine and Cytarabine, in Pediatric Relapsed or Refractory Acute Leukemia
Authors: Alexander Thomas B. , Lacayo Norman J. , Choi John K. , Ribeiro Raul C. , Pui Ching-Hon , Rubnitz Jeffrey E.
Published: August 2016

Purpose

To characterize the toxicity, pharmacokinetics, and pharmacodynamics of selinexor, a selective inhibitor of nuclear export, when combined with fludarabine and cytarabine, in children with relapsed or refractory leukemia.

Patients and Methods

Eighteen patients with relapsed or refractory acute leukemia were enrolled in the SELHEM (Selinexor With Fludarabine and Cytarabine for Treatment of Refractory or Relapsed Leukemia or Myelodysplastic Syndrome) clinical trial (NCT02212561). Selinexor, initially at 30 mg/m2 per dose, was given orally on days 1, 3, 8, 10, 22, and 24 and was escalated according to a rolling-six design. Fludarabine 30 mg/m2 and cytarabine 2 g/m2 were administered on days 15 to 19. Pharmacokinetic and pharmacodynamic studies were performed on days 1 and 22. Response evaluations were performed on day 15 and at the completion of course 1.

Results

Among the 17 patients who were evaluable for toxicity, three were treated at 30 mg/m2, three at 40 mg/m2, six at 55 mg/m2, and five at 70 mg/m2. The most common grade 3 nonhematologic toxicity was asymptomatic hyponatremia. Two patients who were treated at 70 mg/m2 experienced reversible cerebellar toxicity, thereby defining the dose-limiting toxicity. Pharmacokinetic parameters demonstrated that plasma exposure was dose proportional. Fifteen of 16 patients demonstrated at least a twofold increase of XPO1 mRNA, indicating inhibition of the XPO1 protein. In this group of heavily pretreated, relapsed, and refractory patients, seven of 15 evaluable patients (47%) achieved complete response or complete response with incomplete count recovery.

Conclusion

Selinexor, in combination with fludarabine and cytarabine, is tolerable at doses up to 55 mg/m2 in pediatric patients with relapsed or refractory leukemia. All patients who received selinexor at ≥ 40 mg/m2 demonstrated XPO1 target inhibition. Response rates are promising and will be further explored in a phase II trial.
The Effect of Combined Spinal–Epidural Versus Epidural Analgesia in Laboring Women on Nonreassuring Fetal Heart Rate Tracings: Systematic Review and Meta-analysis
Authors: Hattler Judith , Klimek Markus , Rossaint Rolf , Heesen Michael
Published: August 2016

BACKGROUND:

Combined spinal–epidural labor analgesia has gained popularity, but it is unclear whether this technique is associated with a higher incidence of nonreassuring fetal heart rate (FHR) tracings compared with epidural analgesia. Our meta-analysis aimed at comparing the incidence of nonreassuring FHR tracings between the 2 neuraxial techniques.

METHODS:

Databases were searched to identify randomized controlled trials that compared the incidence of nonreassuring FHR tracings, as defined in the individual studies, after combined spinal–epidural versus epidural analgesia in laboring women. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using the random-effects model. We performed a subgroup analysis for studies using low-dose epidural bupivacaine concentrations (≤0.125%) for epidural analgesia.

RESULTS:

Seventeen trials including 3947 parturients were retrieved that compared the 2 neuraxial techniques. All trials used intrathecal opioids in 1 study arm. The pooled effect estimate of low- and high-dose epidural bupivacaine studies together showed a significantly increased risk of nonreassuring FHR tracings with the combined technique (RR 1.31, 95% CI 1.02–1.67, P = .03, I
2 = 18%). A subgroup analysis of 10 trials using low-dose epidural bupivacaine found a RR for nonreassuring FHR tracings between combined spinal–epidural and epidural analgesia of 1.12, 95% CI 0.93–1.34, P = .18. In a sensitivity analysis of those low-dose epidural bupivacaine studies that ensured blinding of the outcome assessor, the RR was 1.41, 95% CI 0.99–2.02, P = .06.

CONCLUSIONS:

Combined spinal–epidural labor analgesia was associated with a higher risk of nonreassuring FHR tracings than epidural analgesia alone. In the subgroup analysis comparing combined spinal–epidural with low-dose epidural labor analgesia, the 95% CI contains a clinically significant difference between groups; moreover, the 95% CI overlaps with the 95% CI of the comparison of the combined low- and high-dose epidural techniques. Therefore, it cannot be concluded that there was no difference between combined spinal–epidural and low-dose epidural techniques.
Correspondence between the ULF wave power spatial distribution and auroral oval boundaries
Authors: Козырева Ольга , Kozyreva Olga , Пилипенко Вячеслав , Pilipenko Vyacheslav , Энгебретсон Марк , Engebretson Mark , Климушкин Дмитрий , Klimushkin Dmitriy , Магер Павел , Mager Pavel
Published: August 2016

The world-wide spatial distribution of the wave power in the Pc5 band during magnetic storms has been compared with auroral oval boundaries. The poleward and equatorward auroral oval boundaries are estimated using either the British Antarctic Survey database containing IMAGE satellite UV observations of the aurora or the OVATION model based on the DMSP particle data. The “epicenter” of the spectral power of broadband Pc5 fluctuations during the storm growth phase is mapped inside the auroral oval. During the storm recovery phase, the spectral power of narrowband Pc5 waves, both in the dawn and dusk sectors, is mapped inside the auroral oval or around its equatorward boundary. This observational result confirms previously reported effects: the spatial/temporal variations of the Pc5 wave power in the morning/pre-noon sector are closely related to the dynamics of the auroral electrojet and magnetospheric field-aligned currents. At the same time, narrowband Pc5 waves demonstrate typical resonant features in the amplitude-phase latitudinal structure. Thus, the location of the auroral oval or its equatorward boundary is the preferred latitude for magnetospheric field-line Alfven resonator excitation. This effect is not taken into account by modern theories of ULF Pc5 waves, but it could be significant for the development of more adequate models.
Total knee arthroplasty at a crossroads
Authors: Sehat Khosrow
Published: August 2016

Anatomical total knee arthroplasty alignment versus conventional mechanical alignment; or a combination?
Determination of Recent Growth Hormone Abuse Using a Single Dried Blood Spot
Authors: Reverter-Branchat Gemma , Bosch Jaume , Vall Jessica , Farré Magí , Papaseit Esther , Pichini Simona , Segura Jordi
Published: August 2016

BACKGROUND

Although it is being increasingly applied, blood collection for drug testing in sport presents some logistic issues that complicate full applicability on a large scale. The use of dried blood spots (DBS) could benefit compliant blood testing considerably owing to its simplicity, minimal invasiveness, analyte stability, and reduced costs. The aim of this study was to evaluate the applicability of DBS to the methodology approved by the World Anti-Doping Agency (WADA) for detection of doping by recombinant human growth hormone (rhGH) in serum.

METHODS

A protocol for a single DBS analysis using the hGH isoforms differential immunoassays (kit 1 and kit 2) was developed and validated. A clinical study with healthy volunteers injected for 3 consecutive days with a low subcutaneous dose (0.027 mg · kg−1 · day−1 · person−1) of rhGH was conducted. Finger prick DBS and paired-time serum samples from arm venipuncture were compared.

RESULTS

The analysis of the DBS-based protocol indicated that with only a single blood spot it was possible to detect positivity for growth hormone abuse. In spite of the low rhGH dose administered and independently of the kit used, the window of detection for DBS was confirmed in all analyzed samples up to 8 h after rhGH administration and extended up to 12 h in 50% of the cases. Serum positivity was detected in all studied samples for 12 h after administration.

CONCLUSIONS

These results support the usefulness of DBS as a biological matrix for testing recent growth hormone abuse.
The poetic reactivation of historical time: Eija-Liisa Ahtila’s Where is Where?
Authors: Walsh Maria
Published: August 2016

In this article, I argue that Eija-Liisa Ahtila’s techniques of narration in her six-screen film installation Where is Where? (2008) generate an affective, lived relation to historical time that counters its reduction in contemporary news media to a series of easily consumed and forgotten instants. Ahtila’s multi-screen film, based in part on Frantz Fanon’s account of the murder by two Algerian boys of their European playmate as revenge for the massacre of Meftah in 1956 during the Algerian War, conjures a different kind of remembering and embodying of historical events. To elaborate this claim, I perform a rereading of Guy Debord’s concept of historical time and argue that Ahtila’s work orchestrates an image of historical time transformed into ‘use’ rather than collected in the archive. This form of time, which incorporates historical agency and cyclical temporalities, connects with Julia Kristeva’s concept of ‘women’s time’ as well as Irish poet Eavan Boland’s writing on history and the past in relation to oppression, colonialism and violence. Film examples looked at include Alain Resnais’ Hiroshima, Mon Amour (1959) and I consider Maya Deren’s notion of the poetic in film. Through an evocation of the ‘vertical register’ of the latter, Where is Where? shows us the incommensurability of war crime and trauma as well as the necessity to forge a relation to this incommensurability.
Threshold faces: The physiognomy of Comédie
Authors: Foster David
Published: August 2016

Since its re-emergence in 2000, and its re-exhibition as a gallery film as opposed to a piece of cinema, Marin Karmitz’s film adaptation of Samuel Beckett’s Comédie – filmed in 1966 in close collaboration with Beckett himself – has been recognized as an important and even canonical work of avant-garde film. Along with Beckett’s other work for the screen, it foreshadowed some prominent aesthetic tendencies that emerged in artists’ film and video in the decades that followed. This article focuses on Comédie’s use of close-ups of the human face, and discusses this medium-specific trope as a threshold image that ‘auto-expressively’ both conceals and reveals its subject. This dichotomy of simultaneous concealment and revelation is shown to manifest through the ‘threshold space’ of the close-up being occupied but never transcended by the film’s protagonists. The figures are deprived of the intersubjectivity that would be engendered through interfacing with another, a notion developed by exploring the dynamic between the virtual face/s we see on-screen, and the face of the viewer. It is posited that the ambiguity of the faces’ directness of address comes to inscribe a perpetual process of unveiling, perpetually towards a state of transcendence, of ontological totality; such absoluteness only arriving inasmuch as it is constituted by the formless presence of the black screen. The article argues that Comédie’s faces represent an abyssal, reflexive awareness of an incarceration inside the process of becoming, and thus inside the very process of their representation.
Exhibiting Cinema in Contemporary Art, Erika Balsom (2013)
Authors: Jacobs Steven
Published: August 2016

Amsterdam: Amsterdam University Press, 256 pp., ISBN: 9789089644718, paperback, € 39.95
Gender and politics: The relevance of gender on judgements about the merit of candidates and the fairness of quotas
Authors: Santos Maria Helena , Amâncio Lígia , Alves Hélder
Published: August 2016

Drawing on the conceptualization of meritocracy as an illusion, we argue that perceptions of merit and fairness of sex quotas in politics are influenced by gender ideology, specifically gender symbolical asymmetry, which equates men with individuals and the universal reference of ‘person’, and women with a sexed category. A total of 311 Portuguese participants read one of eight scenarios manipulating the sex and political competence of two candidates for an electoral list where only one would be selected. According to the experimental condition, either the female or the male candidate was presented as more competent or both candidates were presented as equally competent. In the control condition no such information was provided. Participants rated the merit of the selected candidate and the fairness of quotas. Results show that men take mostly only the candidates’ competence information into consideration. Reflecting gender symbolic asymmetry women were also influenced by the fact that the selected candidate was male or female. Results are discussed in the light of the gender symbolic asymmetry model.
O mundo é um palco: a teatralidade em 'Depois do Ensaio', de Ingmar Bergman
Authors: Ramos de Souza Gustavo
Published: August 2016

Quando os teóricos de vanguarda reivindicaram a pureza do cinema em oposição aos excessos de teatralidade que contaminavam a nova arte, ignoravam que o cinema, arte de natureza intermidiática, só teria a enriquecer ao dialogar com o teatro – ainda que fosse preciso esperar que o cinema moderno renovasse a linguagem cinematográfica ao entrelaçar as potências de cada linguagem. Assim, o objetivo deste artigo é analisar o telefilme Depois do ensaio (1984), de Ingmar Bergman, visando, a partir de uma discussão sobre a teatralidade no cinema, demonstrar em que medida Bergman promove um amálgama entre cinema e teatro e dialoga constantemente com a obra do dramaturgo August Strindberg.
Tiradentes, festival de cinema e opiniões
Authors: Guimarães Pedro Maciel
Published: August 2016

Relato da minha experiência como curador de curtas da Mostra de Cinema de Tiradentes há 5 anos. Criado em 1998, o festival foca no cinema brasileiro independente e autoral e se tornou uma das grandes plataformas de exibição e discussão do cinema brasileiro contemporâneo.
Targeting Molecular Aberrations in Breast Cancer: Is It about Time?
Authors: Esserman Laura , Benz Christopher , DeMichele Angela
Published: August 2016

Overview:

Breast cancer is not one homogeneous disease; it is a heterogeneous cancer with remarkable genomic variation and variable risk for systemic spread, time to recurrence, and response to treatment. Although it is increasingly clear that a substantial proportion of newly diagnosed patients with breast cancer carry only minimal risk of developing metastatic disease, our inability to accurately prognosticate leads to systemic overtreatment. The recent introduction of multigene predictors for baseline risk assessment and treatment response in breast cancer subsets heralds the beginning of personalized cancer care and the transition to precision medicine. At the same time, rapid clinical adoption of these predictors illustrates the voracious unmet need for better and more finely tuned prognostic and predictive tools. Recent advances in clinical trial designs have enabled the testing of novel agents in combination with standard therapy in the neoadjuvant setting, with a goal of identifying the specific biomarker-drug pairs that should be advanced for confirmatory trials and accelerated approval on the basis of response to therapy.
The FEM Analysis of Stress Distribution in front of the Crack Tip and Fracture Process in the Elements of Modified and Unmodified Cast Steel G17CrMo5-5
Authors: Pała Robert , Dzioba Ihor
Published: August 2016

The article presents influence of modification of the low-alloy cast steel G17CrMo5-5 by rare earth metals on stress distribution in front of the crack at the initial moment of the crack extension. Experimental studies include determination of strength and fracture toughness characteristics for unmodified (UM) and modified (M) cast steel. In the numerical computations, experimentally tested specimens SEN(B) were modelled. The true stress–strain curves for the UM and M cast steel are used in the calculation. The stress distributions in front of the crack were calculated at the initial moment of the crack extension. On the basis of data on the particle size inclusions in the UM and M cast steel, and the calculated stress distributions was performed an assessment of the possibility of the occurrence of cleavage fracture. The analysis results indicate that at room temperature for the UM cast steel, there is a possibility of cleavage fracture, while for the M cast steel occurrence of cleavage fracture is negligible.
Comparative Evaluation of the Different Data Mining Techniques Used for the Medical Database
Authors: Kasperczuk Anna , Dardzińska Agnieszka
Published: August 2016

Data mining is the upcoming research area to solve various problems. Classification and finding association are two main steps in the field of data mining. In this paper, we use three classification algorithms: J48 (an open source Java implementation of C4.5 algorithm), Multilayer Perceptron - MLP (a modification of the standard linear perceptron) and Naïve Bayes (based on Bayes rule and a set of conditional independence assumptions) of the Weka interface. These classifiers have been used to choose the best algorithm based on the conditions of the voice disorders database. To find association rules over transactional medical database first we use apriori algorithm for frequent item set mining. These two initial steps of analysis will help to create the medical knowledgebase. The ultimate goal is to build a model, which can improve the way to read and interpret the existing data in medical database and future data as well.
Observations of MR Fluid Clumping Behaviour in a Squeeze-Mode Damper
Authors: Sapiński Bogdan
Published: August 2016

The study summarises the results of quasistatic experimental tests of an MR squeeze-mode damper prototype (MRSQD) performed at the MTS testing machine. Of particular interests was the influence of MR fluid clumping behaviour in the MRSQD working gap on the force output of the device. The MRSQD tests were assessed by measuring the damping force output at prescribed sinusoidal displacement inputs and at various (fixed) voltage levels resulting in the respective average current levels in the control coil. The influence of piston position offset on the damping force was also investigated. The collected data were shown in the form of damping force time histories and damping force-piston displacements loops and discussed with respect to MR fluid clumping behaviour.
Oxy-combustion of biomass in a circulating fluidized bed
Authors: Kosowska-Golachowska Monika , Kijo-Kleczkowska Agnieszka , Luckos Adam , Wolski Krzysztof , Musiał Tomasz
Published: August 2016

The objective of this study was to investigate combustion characteristics of biomass (willow, Salix viminalis) burnt in air and O2/CO2 mixtures in a circulating fluidized bed (CFB). Air and oxy-combustion characteristics of wooden biomass in CFB were supplemented by the thermogravimetric and differential thermal analyses (TGA/DTA). The results of conducted CFB and TGA tests show that the composition of the oxidizing atmosphere strongly influences the combustion process of biomass fuels. Replacing N2 in the combustion environment by CO2 caused slight delay (higher ignition temperature and lower maximum mass loss rate) in the combustion of wooden biomass. The combustion process in O2/CO2 mixtures at 30% and 40% O2 is faster and shorter than that at lower O2 concentrations.
A note on the generic nature of Pringsheim functions
Authors: Darji Udayan B. , Swanson David
Published: August 2016

We prove that the power series of a generic function
Pseudo-slant submanifolds in cosymplectic space forms
Authors: Dirik Süleyman , Atçeken Mehmet
Published: August 2016

In this paper, we study the geometry of the pseudo-slant submanifolds of a cosymplectic space form. Necessary and sufficient conditions are given for a submanifold to be a pseudo-slant submanifold, pseudo-slant product, mixed geodesic and totally geodesic in cosymplectic manifolds. Finally, we give some results for totally umbilical pseudo-slant submanifold in a cosymplectic manifold and cosymplectic space form.
Some vector inequalities for two operators in Hilbert spaces with applications
Authors: Dragomir Sever S.
Published: August 2016

In this paper we establish some vector inequalities for two operators related to Schwarz and Buzano results. We show amongst others that in a Hilbert space H we have the inequality

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$${1 \over 2}\left[ {\left\langle {{{\left| {\rm{A}} \right|^2 + \left| {\rm{B}} \right|^2 } \over 2}{\rm{x}},{\rm{x}}} \right\rangle ^{1/2} \left\langle {{{\left| {\rm{A}} \right|^2 + \left| {\rm{B}} \right|^2 } \over 2}{\rm{y}},{\rm{y}}} \right\rangle ^{1/2} + \left| {\left\langle {{{\left| {\rm{A}} \right|^2 + \left| {\rm{B}} \right|^2 } \over {\rm{2}}}} {\rm{x}},{\rm{y}}\right\rangle } \right|} \right] \ge \left| {\left\langle {{\mathop{\rm Re}\nolimits} ({\rm{B}}*{\rm{A}})\,{\rm{x}},{\rm{y}}} \right\rangle } \right|$$

for A, B two bounded linear operators on H such that Re (B*A) is a nonnegative operator and any vectors x, y ∈ H.

Applications for norm and numerical radius inequalities are given as well.
The time-varying shortest path problem with fuzzy transit costs and speedup
Authors: Rezapour Hassan , Shirdel Gholamhassan
Published: August 2016

In this paper, we focus on the time-varying shortest path problem, where the transit costs are fuzzy numbers. Moreover, we consider this problem in which the transit time can be shortened at a fuzzy speedup cost. Speedup may also be a better decision to find the shortest path from a source vertex to a specified vertex.
Some common random fixed point theorems for contractive type conditions in cone random metric spaces
Authors: Saluja Gurucharan S. , Tripathi Bhanu Pratap
Published: August 2016

In this paper, we establish some common random fixed point theorems for contractive type conditions in the setting of cone random metric spaces. Our results unify, extend and generalize many known results from the current existing literature.