bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurochemical effect of lead exposure: A study on catecholamine metabolism
Authors: Ong C.N. , Chia K.S. , Koh D. , Saijoh K.
Published: October 2013

In an attempt to examine the neurochemical changes of lead exposure, a study was conducted on 106 lead workers and a control group of 25 nonexposed workers. The urinary excretion of major catecholamine metabolites, homovanillic acid (HVA), and vanillylmandellic acid (VMA) were measured. Workers exposed to lead had a mean blood lead concentration of 43.2 μg/100 ml, whereas the concentration for workers not exposed to lead was 12.7 μg/100 ml. Urinary HVA was significantly elevated in the exposed group when compared with controls (p<0.01). HVA was also found to be associated with an increase of lead in blood. Although not statistically significant, the VMA excretion was also noted to be moderately elevated; however, it is recognized that the present study was unable to establish a highly significant dose‐response relationship between lead exposure and HVA excretion, as has been reported earlier in lead‐poisoned children.
Dose‐excretion relationship in tetrachloroethylene‐exposed workers and the effect of tetrachloroethylene co‐exposure on trichloroethylene metabolism
Authors: Seiji Kazunori , Inoue Osamu , Jin Chui , Liu Yu‐Tang , Cai Shi‐Xiong , Ohashi Mariko , Watanabe Takao , Nakatsuka Haruo , Kawai Toshio , Ikeda Masayuki
Published: October 2013

Personal monitoring of 8‐hour time‐weighted average intensity of exposure with diffuse samplers and analysis of shift‐end urine for total trichloro‐compounds (TTC) and other metabolites were conducted in two groups of workers in China, one (121 subjects) exposed to tetrachloroethylene (TETRA) alone, and the other (38 subjects) exposed to a mixture of TETRA and trichloroethylene (TRI). Urinalysis was also performed on samples from 103 non‐exposed controls. A linear exposure‐excretion relationship could be observed in both groups of workers. Comparison of these results with those of Japanese TETRA‐workers suggested the presence of ethnic difference in TETRA metabolism. Urinary metabolite levels were markedly lower in the mixed (TETRA + TRI) exposure group as compared to previous findings in a group exposed to TRI alone. The observation indicates that metabolism of TRI is suppressed by the co‐exposure to TETRA in humans.
Lung cancer in motor exhaust‐related occupations
Authors: Hayes Richard B. , Thomas Terry , Silverman Debra T. , Vineis Paolo , Blot William J. , Mason Thomas J. , Pickle Linda W. , Correa Pelayo , Fontham Elizabeth T.H. , Schoenberg Janet B.
Published: October 2013

The association between employment in motor exhaust‐related occupations and the risk for lung cancer was examined in 2,291 male cases of lung cancer and 2,570 controls in data pooled from three U.S. case control studies carried out by the National Cancer Institute between 1976 and 1983. Most analyses were limited to subjects providing direct, in‐person interviews, including 1,444 cases and 1,893 controls. For those providing direct interviews and employed 10 years or more in motor exhaust‐related (MER) occupations, the age, smoking, and study area adjusted odds ratio (OR) for lung cancer was 1.5 (95% CI = 1.2–1.9). Risk was elevated for truck drivers (OR = 1.5; 95% CI = 1.1–1.9) and for other MER occupations (OR = 1.4; 95% CI = 1.1–2.0). The odds ratios associated with MER employment of 10+ years were 1.6 (95% CI = 1.2–2.1) for whites and 1.4 (95% CI = 0.9–2.1) for nonwhites; 0.9 (95% CI = 0.6–1.2) for those with possible exposure to other recognized or reported lung carcinogens; and 1.6 (95% CI 1.2–2.1) for those without such exposure. The 50% excess risk for lung cancer associated with employment in motor exhaust‐related occupations could not be explained by greater use of cigarettes or by other occupational exposures among these workers.
Inflammation in organic dust‐induced lung disease: New approaches for research into underlying mechanisms
Authors: Holt Patrick G.
Published: October 2013

The application of new technology to the study of lung inflammation is providing fresh insight into the nature of the underlying reactions. This review highlights the impact of modern cell biological and molecular biological techniques on current research in this area.
Bronchial hyperreactivity among pig and dairy farmers
Authors: Rylander Ragnar , Essie Nils , Donham Kelley J.
Published: October 2013

The presence of work‐related symptoms, pulmonary functions, and bronchial reactivity were studied in farmers working with dairy animals or pigs. An increased incidence of the organic dust toxic syndrome, cough, and throat irritation was found. Pulmonary function baseline values were close to normal, and no significant decreases occurred over the work period. Bronchial reactivity was increased.
Carbon disulfide exposure and neurotoxic sequelae among viscose rayon workers
Authors: Aaserud Olaf , Hommeren Ole Jörgen , Tvedt Björn , Nakstad Per , Mowé Gunnar , Efskind Jon , Russell David , Jörgensen Eva B. , Nyberg‐Hansen Rolf , Rootwelt Kjell , Gjerstad Leif
Published: October 2013

In Norway's only viscose rayon plant, carbon disulfide (CS2) concentrations in ambient air usually were between 30 and 50 mg/m3 during the first 23 years of production. From 1970/1971 until the factory was closed in 1982, corresponding values were 10–25 mg/m3. Through all of these years, high peak exposures of CS2 and H2S occurred. In 1986, 16 of the 24 men still at work in 1982 and with at least 10 years' experience in the spinning room agreed to participate in this study. Clinical neurological examination demonstrated abnormalities in 15; neuropsychological tests showed impairments of probable organic origin in 14. Thirteen had cerebral atrophy demonstrated by cerebral computed tomography (CT). Electromyography (EMG) was abnormal in six, neurography in 11. Regional cerebral blood flow measurements indicated flow asymmetries in eight, whereas Doppler investigation of the extracranial carotid and vertebral arteries, electroencephalography (EEG), and evoked response investigations were mostly normal. Based on these results and the exposure data, a diagnosis of CS2‐induced encephalopathy was reached in eight workers; another six had an encephalopathy in which CS2 exposure was regarded as a partial cause. Correspondingly, seven had a neuropathy probably caused by CS2 exposure alone; in three others, CS2 was found to be the partial cause of a neuropathy. This indicates that long‐term, relatively moderate exposure to CS2 in association with high peak exposures to CS2 and H2S involves a substantial risk of developing neurotoxic disease.
Simpson‐golabi‐behmel syndrome: An X‐linked encephalo‐tropho‐schisis syndrome
Authors: Neri G. , Marini R. , Cappa M. , Borrelli P. , Opitz J.M.
Published: October 2013

Introduction

The following paper by Professor Giovanni Neri and colleagues was originally published in 1988, American Journal of Medical Genetics 30:287–299. This paper represented a seminal work at the time of publication as it not only reported a new family with a disorder that had been called the “gigantism‐dysplasia syndrome”, but also suggested naming the condition the Simpson‐Golabi‐Behmel syndrome. This eponym has clearly stood “the test of time”, and that designation is now widely accepted. This paper is graciously republished by Wiley‐Blackwell in the Special Festschrift issue honoring Professor Neri.

John C. Carey

Editor‐in‐Chief

We report on another family with the so‐called “gigantism‐dysplasia syndrome”, an X‐linked condition characterized by pre‐and postnatal overgrowth, characteristic face with apparent coarseness, dysplastic changes in several tissues, and mild intellectual impairment. This condition has been called the Golabi–Rosen syndrome; however, we agree that is the same entity as that described, in a milder form, by Simpson et al. in 1975 and by Behmel et al. in 1984. Therefore, we suggest that this entity be designated the Simpson‐Golabi‐Behmel syndrome. The manifestations in affected individuals suggest that this condition represents an X‐linked encephalo‐tropho‐schisis syndrome. © 2013 Wiley Periodicals, Inc.
Influence of lignin on rheological behaviors and electrospinning of polysaccharide solution
Authors: Ahn Yongjun , Kang Youngwoong , Park Beomsu , Ku Min Kyung , Lee Sang Hyun , Kim Hyungsup
Published: October 2013

The effect of lignin is a key issue in various cellulose processes. To study the effects of lignin state and content on cellulose electrospinning and fiber properties, two different types of cellulose solutions were prepared and electrospun under several different conditions. One was mixture of cellulose and lignin and the other one was hemp cellulose in which cellulose is naturally combined with lignin. In both the cases, the solutions were stably electrospun when the lignin concentration was lower than 5%. The lignin in the cellulose/lignin mixture resulted in film‐like fiber and bimodal distribution of the fiber diameter, while the lignin in the hemp cellulose mainly increased the fiber diameter. It is originated from the different phase separation behaviors of the two solutions. The results can give the fundamental understandings for the roles and action of lignin in cellulose process. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40031.
Elaboration and characterization of bioblends based on PVC/PLA
Authors: Hachemi Razika , Belhaneche‐Bensemra Naima , Massardier Valérie
Published: October 2013

With the aim to develop new biomaterials (bioblends) to be used in the field of waste elimination, this contribution focuses on the elaboration and characterization of new materials based on poly (vinyl chloride) (PVC) and poly (lactic acid) (PLA). The bioblends based on PVC/PLA were prepared by melt mixing in the absence and presence of maleic anhydride (MAH). The binary blends were first characterized in terms of thermal (glass transition temperature) and mechanical properties (tensile and micro‐hardness). Their thermal stability was investigated by thermogravimetric analysis (TGA). The results showed that this pair of polymers is not miscible and exhibited lower properties than those of the separated polymers. The in situ compatibilization was then performed using MAH and dicumyl peroxide (DCP) as an initiator. The presence of MAH enhanced the processability of the bioblends by decreasing the temperature of mixing. The properties of subsequent PVC/PLA bioblends were investigated through tensile and micro‐hardness testing, thermal analysis (DSC and TGA), and SEM. From the mechanical results, high level of compatibility was found when introducing MAH. The TGA studies indicated that the incorporation of PLA in PVC (matrix) increased thermal stability of the bioblend. Microscopic observations revealed uniformly dispersed PLA in the PVC matrix, confirming that phase separation has disappeared in the presence of MAH. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40045.
Antimicrobial properties and thermal stability of polycarbonate modified with 1‐alkyl‐3‐methylimidazolium tetrafluoroborate ionic liquids
Authors: Rogalsky Sergiy , Fatyeyeva Kateryna , Lyoshina Lyudmila , Tarasyuk Oksana , Bulko Olga , Lobok Sofiia
Published: October 2013

Four water immiscible ionic liquids (ILs): 1‐hexyl‐3‐methylimidazolium tetrafluoroborate, 1‐heptyl‐3‐methylimidazolium tetrafluoroborate, 1‐octyl‐3‐methylimidazolium tetrafluoroborate and 1‐dodecyl‐3‐methylimidazolium tetrafluoroborate have been synthesized. Polycarbonate (PC) films containing ILs were prepared by solvent casting from methylene chloride solutions. Scanning electron microscopy measurements showed the high homogeneity of PC/IL films with the IL content up to 4 wt %. The tendency to IL aggregation was observed for polymeric films with higher IL content (5%). PC/IL composites were found to have the reduced thermal decomposition temperature under both an air and a nitrogen atmosphere in comparison with the neat PC. The effect of IL content on the antimicrobial activity of PC films against Escherichia coli bacteria was studied. Pronounced antimicrobial efficacy was revealed for PC/IL films for all studied ILs starting from 3 wt % of IL. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40050.
Synthesis and antibacterial activity of alkylated chitosan under basic ionic liquid conditions
Authors: Pei Lijun , Cai Zhaosheng , Shang Shibin , Song Zhanqian
Published: October 2013

A novel method to synthesize alkylated chitosan with [Bmim]OH basic ionic liquid as alkaline reagent is reported for the first time. Chitosan was alkalized by [Bmim]OH basic ionic liquid before it was reacted with various alkyl halides, and a series of alkylated chitosans with different carbon chain substituents were prepared. The structure of alkylated product was characterized by IR, 1H‐NMR, and XRD. The reusability of the ionic liquid was also investigated, and the experimental results indicated that there was no noticeable change for the degree of substitution (DS) of alkylated chitosan after the ionic liquid was reused for three times. The antibacterial activities of the target products were investigated according their minimum inhibitory concentration (MIC) against K. pneumoniae, P. aeruginosa, E. aerogenes, E. coil, S. epidermidis, and S. aureus, and the results indicated that E‐CTS, B‐CTS, and D‐CTS could exhibit excellent antibacterial activities against P. aeruginosa, and their MIC were 128, 128, and 256 μg mL−1, respectively. Meanwhile, the antibacterial activities of alkylted chitosans were decreased with the growth of the DS or the growth of the carbon chain. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40052.
Fluidity improvement of semiaromatic polyamides: Modification with oligomers
Authors: Zhang Chuanhui , Huang Xianbo , Zeng Xiangbin , Cao Min , Cai Tongmin , Jiang Sujun , Yi Qingfeng
Published: October 2013

Poly(decamethylene terephthalamide) PA10T with different relative viscosities (RV) were successfully produced by the reaction of 1,10‐decanediamine and terephthalic acid through molecular weight regulator benzoic acid (BA). RV was shown to be decreased linearly with increasing BA concentrations and detailed structures of PA10Ts were characterized by 13C‐NMR. Fluidity of PA10T with varying molecular weight was tested and low RV PA10Ts were used as modifiers to improve fluidity behaviors of high RV PA10Ts, meanwhile mechanical properties were maintained. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40058.
A prospective intravascular ultrasound investigation of the necessity for and efficacy of postdilation beyond nominal diameter of 3 current generation DES platforms for the percutaneous treatment of the left main coronary artery
Authors: Shand James A. , Sharma Divyesh , Hanratty Colm , McClelland Anthony , Menown Ian B.A. , Spence Mark S. , Richardson Geoffrey , Herity Niall A. , Walsh Simon J.
Published: October 2013

Objectives

To define the size of the left mainstem coronary artery (LMS) in the Northern Irish population and investigate the clinical feasibility, safety, and efficacy of post dilation beyond nominal diameter of current generation Drug eluting stent (DES) when treating the LMS.

Background

There is no prospective data examining the need, feasibility, and safety of over‐expansion of current generation DES beyond nominal diameter.

Methods

Patients with flow‐limiting coronary atheroma requiring IVUS assessment of the LMS were recruited. Standardized measurements of the distal LMS were made. Subsequently, patients requiring post dilation of current generation DES within the LMS were entered into a PCI registry.

Results

Overall, 125 patients were recruited into the initial study. Mean cross‐sectional area (CSA) of the distal LMS was 22.6 mm2(SD ± 5.4 mm2). Mean maximal vessel diameter was 5.7 mm (SD ± 0.7 mm). Increasing plaque burden was associated with reduced CSA (P < 0.001). In 31 consecutive patients undergoing IVUS guided PCI of the LMS with 5.5 and 6.0 mm balloon catheters, mean maximal stent diameters were >5.0 mm with the Biomatrix Flex 9 crown and Promus Element Large vessel platforms. No intraprocedural complications occurred. Mean follow up was 13.4 months. Clinical restenosis rate was 3.2%, with 2 deaths unrelated to index procedure.

Conclusions

The majority of patients with angiographic coronary atheroma have a mean LMS diameter of >4 mm indicating the requirement for post dilation beyond nominal diameter all of current generation DES in almost all patients when treating the LMS. This is achievable with current DES platforms with no intraprocedural complication. Clinical follow up indicates excellent short‐term efficacy. © 2013 Wiley Periodicals, Inc.
Decomposition of Epoxy Model Compounds in Near‐Critical Water
Authors: Liu Y. , Wei H. , Wu S. , Guo Z.
Published: October 2013

Two tpyes of epoxy resin model compounds, one containing an ether bond and bisphenol‐A structure (compound I) and the other comprising ether and tertiary amine bonds (compound II), were prepared and then decomposed in near‐critical water (NCW). In the case of model compound I, at low temperatures the water molecules behave as nucleophilic reagent reacting with the terminal ether group of the model compound. When the temperature is increased, the middle ether bond of the model compound molecule can be broken down. As to model compound II, at lower temperatures, cleavage of the ether bond happens more easily than that of the tertiary amine bond because of higher positive charge density centered at the carbon atom in the ether group. At higher temperatures, the energy required to break down the ether bond is reduced dramatically after being protonated by H+, and therefore, the bond can be cleaved more readily than the tertiary amine bond. The decomposition products in both model compounds were found unstable and could react with each other to generate other compounds. Decomposition mechanisms were also proposed based on the decomposition products for the model compounds.
Optimizing Established Processes like Sugar Extraction from Sugar Beets – Design of Experiments versus Physicochemical Modeling
Authors: Both S. , Eggersglüß J. , Lehnberger A. , Schulz T. , Schulze T. , Strube J.
Published: October 2013

Extraction of sugar from sugar beets is a process optimized over decades based on experience gathered during production. This process improvement is achieved without any systematic approach for optimization which raised the question whether such a mature process can be further optimized effectively, applying methods developed in the last decade like statistical experiment design or physicochemical modeling. Viable areas of operation for the respective approaches will be assessed and discussed using the example of sucrose extraction from sugar beet. Operating conditions are optimized regarding extraction kinetics and equilibrium behavior. Physicochemical modeling, however, requires detailed information on phase equilibria, fluid dynamics, and mass transfer effects. Here, the phase ratio can be identified as a sensitive parameter and process performance like the HETP (high equivalent of a theoretical plate) value can be enhanced. Therefore, the volumetric productivity serves as indicator. Potentials of process design and process optimization by a combination of statistical design of experiments and physicochemical modeling approaches are assessed, and respective possibilities and limitations are discussed.
Influence of Emulsifiers on the Formation and Crystallization of Solid Lipid Nanoparticles
Authors: El Kinawy O. S. , Petersen S. , Bergt K. , Ulrich J.
Published: October 2013

The production of solid lipid nanoparticles by means of hot homogenization uses two different techniques: emulsification (liquid state) and crystallization (solid state). Both these processes depend on many parameters, such as composition, energy input, or geometry of the emulsification device. In former investigations known from the literature, the influence of the emulsifier concentration and the potential of controlling the polymorphic forms of the solidified particles were not investigated in detail. Here, these two factors were analyzed on the example of palm oil particles stabilized with emulsifiers suitable for foods. The influence of the emulsifier concentration on the resulting droplet and particle sizes is very high, up to a certain level. However, beside this influence, the polymorphic form of the solidified particles can be controlled by the right choice of emulsifier type and concentration.
Wood identification using pressure DSC data
Authors: Tarrío‐Saavedra Javier , Francisco‐Fernández Mario , Naya Salvador , López‐Beceiro Jorge , Gracia‐Fernández Carlos , Artiaga Ramón
Published: October 2013

This work addresses the problem of supervised classification of industrial wood species (seven different types in the present study) through their thermo‐oxidative stability. This is evaluated by pressure differential scanning calorimetry (PDSC) using the ASTM E2009. The maximization of the ratio of correct classification and the reduction of the costs of this activity are intended. This supervised classification problem was carried out using two different proposals: applying novel nonparametric functional data analysis techniques, based on kernel estimation, to the original PDSC curves, and using machine learning classification approaches applied to different multivariate data sets. The multivariate data sets were obtained, on the one hand, by estimating the fractal (Hausdorff) dimension of the PDSC curves by several methods, jointly with selecting the parameters from fitting a nonlinear model to the PDSC curves and, on the other hand, applying principal component analysis or partial linear squares to the thermograms. The results obtained show that the PDSC curves can be used to discriminate wood samples when these innovative and traditional statistical techniques are applied. In the best of the cases, a probability of correct classification that equals to 0.92 was obtained. PDSC represents a new alternative to the use of images, spectra, and other thermal signals as thermogravimetric analysis for classification purposes.Copyright © 2013 John Wiley & Sons, Ltd.
Patterns of cancer screening in primary care from 2005 to 2010
Authors: Martires Kathryn J. , Kurlander David E. , Minwell Gregory J. , Dahms Eric B. , Bordeaux Jeremy S.
Published: October 2013

BACKGROUND

Cancer screening recommendations vary widely, especially for breast, prostate, and skin cancer screening. Guidelines are provided by the American Cancer Society, the US Preventive Services Task Force, and various professional organizations. The recommendations often differ with regard to age and frequency of screening. The objective of this study was to determine actual rates of screening in the primary care setting.

METHODS

Data from the National Ambulatory Medical Care Survey were used. Only adult visits to non–federally employed, office‐based physicians for preventive care from 2005 through 2010 were examined. Prevalence rates for breast, pelvic, and rectal examinations were calculated, along with the rates for mammograms, Papanicolaou smears, and prostate‐specific antigen tests. Factors associated with screening, including age, race, smoking status, and insurance type, were examined using t tests and chi‐square tests.

RESULTS

In total, 8521 visits were examined. The rates of most screening examinations and tests were stable over time. Clinical breast examinations took place significantly more than mammography was ordered (54.8% vs 34.6%; P < .001). White patients received more mammography (P = .031), skin examinations (P < .010), digital rectal examinations (P < .010), and prostate‐specific antigen tests (P = .003) than patients of other races. Patients who paid with Medicare or private insurance received more screening than patients who had Medicaid or no insurance (P < .010).

CONCLUSIONS

Current cancer screening practices in primary care vary significantly. Cancer screening may not follow evidence‐based practices and may not be targeting patients considered most at risk. Racial and socioeconomic disparities are present in cancer screening in primary care. Cancer 2014;120:253–261. © 2013 American Cancer Society.
Nomograms for preoperative prediction of prognosis in patients with oral cavity squamous cell carcinoma
Authors: Montero Pablo H. , Yu Changhong , Palmer Frank L. , Patel Purvi D. , Ganly Ian , Shah Jatin P. , Shaha Ashok R. , Boyle Jay O. , Kraus Dennis H. , Singh Bhuvanesh , Wong Richard J. , Morris Luc G. , Kattan Michael W. , Patel Snehal G.
Published: October 2013

BACKGROUND

This study sought to develop prognostic tools that will accurately predict overall and cancer‐related mortality and risk of recurrence in individual patients with oral cancer based on host and tumor characteristics. These tools would take into account numerous prognosticators beyond those covered by the traditional TNM (tumor–node–metastasis) staging system.

METHODS

Demographic, host, and tumor characteristics of 1617 patients with cancer of the oral cavity, who were treated primarily with surgery at a single‐institution tertiary care cancer center between 1985 and 2009, were reviewed from a preexisting database. Recurrent disease was recorded in 509 patients (456 locoregional and 116 distant); 328 patients died of cancer‐related causes, and 542 died of other causes. The median follow‐up was 42 months (range, 1‐300 months). The following variables were analyzed as predictors of prognosis: age, sex, race, alcohol and tobacco use, oral cavity subsite, invasion of other structures, comorbidity, tumor size, and clinical nodal status. The stepdown method was used to select the statistically most influential predictors for inclusion in the final nomogram for each outcome of interest.

RESULTS

The most influential predictors of both recurrence and cancer‐specific mortality probability (CSMP) were tumor size, nodal status, subsite, and bone invasion. Nomograms were generated for prediction of overall survival (OS), CSMP, and locoregional recurrence‐free probability (LRRFP). The nomograms were internally validated with an overfit‐corrected predictive discrimination metric (concordance index) for OS of 67%, CSMP of 66%, and LRRFP of 60%.

CONCLUSIONS

Nomograms have been developed that can reasonably estimate OS, CSMP, and LRRFP based on specific tumor and host characteristics in patients with oral cancer. Cancer 2014;120:214–221. © 2013 American Cancer Society.
Molecular determinants of outcome with mammalian target of rapamycin inhibition in endometrial cancer
Authors: Mackay Helen J. , Eisenhauer Elizabeth A. , Kamel‐Reid Suzanne , Tsao Ming , Clarke Blaise , Karakasis Katherine , Werner Henrica M. J. , Trovik Jone , Akslen Lars A. , Salvesen Helga B. , Tu Dongsheng , Oza Amit M.
Published: October 2013

BACKGROUND

Targeting the phosphatidylinositol 3‐kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is of increasing interest as a therapeutic strategy in many tumors. The aim of this study was to identify molecular markers associated with mTOR inhibitor activity in women with metastatic endometrial cancer.

METHODS

Archival tumor samples were collected from 94 women with recurrent or metastatic endometrial cancer who participated in 3 National Cancer Insitute of Canada Clinical Trials Group phase 2 trials investigating single‐agent mTOR inhibitors: IND160A and IND160B (temsirolimus) and IND192 (ridaforolimus). Analyses included mutational profiling using the OncoCarta Panel version 1.0 and immunohistochemical expression of the tumor suppressor gene PTEN (phosphatase and tensin homologue) and stathmin, a marker of PI3K activation. Associations between biomarker results and clinical outcomes were assessed.

RESULTS

Mutations were found in 32 of 73 analyzed tumors, PIK3CA (21 patients) was the most common mutated gene. Co‐mutations were seen in 8 tumors, most frequently KRAS and PIK3CA (4 cases). PTEN loss was observed in 46 of 85 samples analyzed and increased stathmin expression was observed in 15 of 65 analyzed samples. No correlation was observed between biomarkers and response or progression. In patients taking concurrent metformin, there was a trend toward lower progression, of 11.8% versus 32.5% (P = .14).

CONCLUSIONS

No predictive biomarker or combination of biomarkers for mTOR inhibitor activity were identified in this study. Restriction and enrichment of study entry, especially based on archival tumor tissue, should be undertaken with caution in trials using these agents. Cancer 2014;120:603–610. © 2013 American Cancer Society.
Efficacy and safety of bevacizumab in recurrent sex cord‐stromal ovarian tumors: Results of a phase 2 trial of the Gynecologic Oncology Group
Authors: Brown Jubilee , Brady William E. , Schink Julian , Van Le Linda , Leitao Mario , Yamada S. Diane , de Geest Koen , Gershenson David M.
Published: October 2013

BACKGROUND

The Gynecologic Oncology Group conducted this phase 2 trial to estimate the antitumor activity of bevacizumab and to determine the nature and degree of toxicity in patients with recurrent sex cord‐stromal tumors of the ovary.

METHODS

A prospective, multi‐institutional cooperative group trial was performed in women with recurrent, measurable ovarian stromal tumors. Patients were allowed to have unlimited prior therapy, excluding bevacizumab. Bevacizumab 15 mg/kg was administered intravenously on day 1 of every 21‐day cycle until patients developed disease progression or adverse effects that prohibited further treatment. The primary endpoint was the response rate (RR). Inhibin A and B levels were measured before each cycle, and the values were examined in relation to response and progression.

RESULTS

Thirty‐six patients were enrolled, and all were eligible and evaluable. Patients received a median of 9 cycles of treatment (range, 2‐37 cycles). Six patients (16.7%) had partial responses (90% confidence interval, 7.5%‐30.3%), 28 patients (77.8%) had stable disease, and 2 patients (5.6%) had progressive disease. This met the criterion for declaring the regimen active. The median progression‐free survival was 9.3 months, and the median overall survival was not reached in during reporting period. Two grade 4 toxicities occurred, including hypertension and proteinuria; and the most common grade 3 toxicities were hypertension (n = 5) and pain (n = 5). Inhibin A and B values were lower in patients who responded to treatment.

CONCLUSIONS

Bevacizumab has activity in the treatment of recurrent sex cord‐stromal tumors of the ovary, and its toxicity is acceptable. Further investigation is warranted. Cancer 2014;120:344–351. © 2013 American Cancer Society.
Costs and outcomes evaluation of patient navigation after abnormal cancer screening: Evidence from the Patient Navigation Research Program
Authors: Bensink Mark E. , Ramsey Scott D. , Battaglia Tracy , Fiscella Kevin , Hurd Thelma C. , McKoy June M. , Patierno Steven R. , Raich Peter C. , Seiber Eric E. , Warren‐Mears Victoria , Whitley Elizabeth , Paskett Electra D. , Mandelblatt S. ,   Patient Navigation Research Program
Published: October 2013

BACKGROUND

Navigators can facilitate timely access to cancer services, but to the authors' knowledge there are little data available regarding their economic impact.

METHODS

The authors conducted a cost‐consequence analysis of navigation versus usual care among 10,521 individuals with abnormal breast, cervical, colorectal, or prostate cancer screening results who enrolled in the Patient Navigation Research Program study from January 1, 2006 to March 31, 2010. Navigation costs included diagnostic evaluation, patient and staff time, materials, and overhead. Consequences or outcomes were time to diagnostic resolution and probability of resolution. Differences in costs and outcomes were evaluated using multilevel, mixed‐effects regression modeling adjusting for age, race/ethnicity, language, marital status, insurance status, cancer, and site clustering.

RESULTS

The majority of individuals were members of a minority (70.7%) and uninsured or publically insured (72.7%). Diagnostic resolution was higher for navigation versus usual care at 180 days (56.2% vs 53.8%;P = .008) and 270 days (70.0% vs 68.2%;P < .001). Although there were no differences in the average number of days to resolution between the 2 groups (110 days vs 109 days;P = .63), the probability of ever having diagnostic resolution was higher for the navigation group versus the usual‐care group (84.5% vs 79.6%;P < .001). The added cost of navigation versus usual care was $275 per patient (95% confidence interval, $260‐$290;P < .001). There was no significant difference in stage distribution among the 12.4% of patients in the navigation group vs 11% of the usual‐care patients diagnosed with cancer.

CONCLUSIONS

Navigation adds costs and modestly increases the probability of diagnostic resolution among patients with abnormal screening test results. Navigation is only likely to be cost‐effective if improved resolution translates into an earlier cancer stage at the time of diagnosis.Cancer2014;120:570–578. ©2013 American Cancer Society.
Automated tobacco assessment and cessation support for cancer patients
Authors: Warren Graham W. , Marshall James R. , Cummings K. Michael , Zevon Michael A. , Reed Robert , Hysert Pat , Mahoney Martin C. , Hyland Andrew J. , Nwogu Chukwumere , Demmy Todd , Dexter Elisabeth , Kelly Maureen , O'Connor Richard J. , Houstin Teresa , Jenkins Dana , Germain Pamela , Singh Anurag K. , Epstein Jennifer , Dobson Amato Katharine A. , Reid Mary E.
Published: October 2013

BACKGROUND

Tobacco assessment and cessation support are not routinely included in cancer care. An automated tobacco assessment and cessation program was developed to increase the delivery of tobacco cessation support for cancer patients.

METHODS

A structured tobacco assessment was incorporated into the electronic health record at Roswell Park Cancer Institute to identify tobacco use in cancer patients at diagnosis and during follow‐up. All patients who reported tobacco use within the past 30 days were automatically referred to a dedicated cessation program that provided cessation counseling. Data were analyzed for referral accuracy and interest in cessation support.

RESULTS

Between October 2010 and December 2012, 11,868 patients were screened for tobacco use, and 2765 were identified as tobacco users and were referred to the cessation service. In referred patients, 1381 of those patients received only a mailed invitation to contact the cessation service, and 1384 received a mailing as well as telephone contact attempts from the cessation service. In the 1126 (81.4%) patients contacted by telephone, 51 (4.5%) reported no tobacco use within the past 30 days, 35 (3.1%) were medically unable to participate, and 30 (2.7%) declined participation. Of the 1381 patients who received only a mailed invitation, 16 (1.2%) contacted the cessation program for assistance. Three questions at initial consult and follow‐up generated over 98% of referrals. Tobacco assessment frequency every 4 weeks delayed referral in < 1% of patients.

CONCLUSIONS

An automated electronic health record‐based tobacco assessment and cessation referral program can identify substantial numbers of smokers who are receptive to enrollment in a cessation support service. Cancer 2014;120:562–569. © 2013 American Cancer Society.
Autophagy and enhanced chemosensitivity in experimental pancreatic cancers induced by noninvasive radiofrequency field treatment
Authors: Koshkina Nadezhda V. , Briggs Katrina , Palalon Flavio , Curley Steven A.
Published: October 2013

BACKGROUND

Patients with pancreatic ductal adenocarcinoma (PDAC) have limited therapeutic options and poor response to the standard gemcitabine (GCB)‐based chemotherapy. In the current study, the authors investigated the feasibility of noninvasive short‐wave radiofrequency (RF) electric fields to improve the cytotoxic effect of GCB on PDAC cells and determined its mechanism of action.

METHODS

The cytotoxicity of RF alone and in combination with GCB was studied in vitro on normal pancreatic human pancreatic ductal epithelial cells and different PDAC cell lines by flow cytometry, and in vivo on ectopic and orthotopic human PDAC xenograft models in mice. The mechanism of RF activity was studied by Western blot analysis and immunohistochemistry. Toxicity was determined by histopathology.

RESULTS

Exposure of different PDAC cells to 13.56‐megahertz radio waves resulted in a substantial cytotoxic effect, which was accompanied by the induction of autophagy but not apoptosis. These effects of RF were found to be absent in normal cells. Excessive numbers of autophagosomes in cancer cells persisted 24 to 48 hours after RF exposure and then declined. The addition of a subtoxic dose of GCB to RF treatment inhibited the recovery of cancer cells from the RF‐induced autophagy and enhanced the cytotoxic effect of the latter on cancer cells. The treatment of PDAC in situ in mice with the combination of noninvasive RF and GCB was found to have a superior antitumor effect compared with the use of RF or GCB alone, yet there was no evidence of systemic toxicity.

CONCLUSIONS

Noninvasive RF treatment induced autophagy but not apoptosis in cancer cells and demonstrated potential as an enhancer of chemotherapy for treating patients with pancreatic cancer without toxicity to normal cells. Cancer 2014;120:480–491. © 2013 American Cancer Society.
Distinct physiological and developmental properties of hippocampal CA2 subfield revealed by using anti‐Purkinje cell protein 4 (PCP4) immunostaining
Authors: San Antonio Andrew , Liban Kristopher , Ikrar Taruna , Tsyganovskiy Eugene , Xu Xiangmin
Published: October 2013

The hippocampal CA2 subfield was initially identified by Lorente de Nó as an anatomically distinct region based on its cytoarchitectural features. Although there is an enormous body of literature on other hippocampal subfields (CA1 and CA3), relatively little is known about the physiological and developmental properties of CA2. Here we report identification of the CA2 region in the mouse by immunostaining with a Purkinje cell protein 4 (PCP4) antibody, which effectively delineates CA3/CA2 and CA2/CA1 borders and agrees well with previous cytoarchitectural definitions of CA2. The PCP4 immunostaining–delineated CA2 neurons have distinguishable differences in cell morphology, physiology, and synaptic circuit connections compared with distal CA3 and proximal CA1 regions. The average somatic sizes of excitatory cells differ across CA1–3, with the smallest to largest somatic size being CA1<CA2<CA3. CA2 excitatory cells have dense dendritic spines, but do not have thorny excrescences associated with bordering CA3 neurons. Photostimulation functional circuit mapping shows that CA2 excitatory neurons receives extensive synaptic input from CA3, but no detectable input from the dentate gyrus. CA2 excitatory cells also differ significantly from CA3 cells in intrinsic electrophysiological parameters, such as membrane capacitance and spiking rates. Although CA2 neurons differ from CA1 neurons for PCP4 and other marker expressions, these neurons have less distinct neurophysiological and morphological properties. Developmental examination revealed that PCP4 immunostaining first appears at postnatal day 4–5 and becomes successively more refined around CA2 until reaching adult form by postnatal day 21. J. Comp. Neurol. J. Comp. Neurol. 522:1333–1354, 2014. © 2013 Wiley Periodicals, Inc.
Hybrid biogeography based optimization for constrained optimal spot color matching
Authors: Lin Jian , Xu Li , Zhang Huiyuan
Published: October 2013

Biogeography‐based optimization (BBO) is a new evolutionary algorithm which mimics the immigration and emigration of species among islands. Used widely in packaging and printing to obtain a colorful appearance, the spot color matching (SCM) is formulated as a complex multi‐dimensional optimization problem. In this article, BBO is combined with the harmony search (HS) and opposition‐based learning (OBL) approaches to construct an effective hybrid algorithm for solving the SCM problem. HS is used to enhance the local searching ability of BBO, and OBL is employed to increase the diversity of initial population; consequently, the exploration and exploitation abilities of the hybrid algorithm are enhanced and well balanced. Experiment results are presented to show the effectiveness of the proposed scheme. © 2013 Wiley Periodicals, Inc. Col Res Appl, 39, 607–615, 2014
Factors contributing to high ThinPrep® Pap test unsatisfactory rates in an academic medical center laboratory
Authors: Selvaggi Suzanne M.
Published: October 2013

Specimen adequacy is a key component in the cytologic evaluation of cervical Pap tests. At our institution, yearly unsatisfactory rates continue to be high, placing our laboratory in the 95th percentile for CAP benchmark data for unsatisfactory Pap test rates. Using the 2001 Bethesda System criteria, unsatisfactory Pap test rates were calculated over a ten year period (January 2002 to December 2011) and contributing factors were analyzed. Of the 124,457 ThinPrep Pap tests performed, 4,163 (3.3%) were unsatisfactory for evaluation, the majority (90%) due to too few squamous epithelial cells. Peri/postmenopausal women and those who had received radiation/chemotherapy had the highest unsatisfactory rates; 55% and 25%, respectively. Higher unsatisfactory Pap test rates are related to the patient population served. Defined, reproducible adequacy criteria need to be defined for Pap tests from patients in certain clinical conditions. Diagn. Cytopathol. 2014;42:380–383. © 2013 Wiley Periodicals, Inc.
Comparison of diagnostic accuracy between CellprepPlus® and ThinPrep® liquid‐based preparations in effusion cytology
Authors: Lee Yong‐Moon , Hwang Ji‐Yong , Son Seung‐Myoung , Choi Song‐Yi , Lee Ho‐Chang , Kim Eun‐Joong , Han Hye‐Suk , An Jin young , Han Joung‐Ho , Lee Ok‐Jun
Published: October 2013

Liquid‐based cytology (LBC) is being increasingly used for body fluid specimens and has improved diagnostic accuracy when compared to conventional smears. We compared the diagnostic accuracy and cellular morphologic features between CellprepPlus® LBC and ThinPrep® LBC in effusion cytology.

One hundred and eighty body fluid specimens, consisting of 119 pleural fluid specimens, 59 peritoneal fluid specimens, and 2 pericardial fluid specimens, were obtained from 166 patients. Equal volumes of body fluid from each specimen were used in the CellprepPlus® and ThinPrep® preparations. Sensitivity, specificity, and positive and negative predictive values were evaluated. In addition, we selected 16 specimens from patients with metastatic adenocarcinoma, confirmed them by both LBC preparations, and measured the size of the nucleus in the tumor cells in these specimens.

The sensitivity of the CellprepPlus® and ThinPrep® methods was 73.1% and 50.0%, respectively. The specificity and positive predictive values were 100% for both LBC methods, and the negative predictive values of the CellprepPlus® and ThinPrep® methods were 90.9% and 83.3%, respectively. The average nuclear size of the tumor cells was calculated as 20.87 μm using the CellprepPlus® method and 15.08 μm using the ThinPrep® method (P < 0.05).

The CellprepPlus® method provided better diagnostic accuracy of effusion cytology compared to the ThinPrep® method and revealed the characteristic morphological features of tumor cells, including large and hypochromatic nuclei, prominent nucleoli, distinct nuclear membranes, and high cellularity. Diagn. Cytopathol. 2014;42:384–390. © 2013 Wiley Periodicals, Inc.
Inconclusive or erroneous fine‐needle aspirates of breast with adequate and representative material: A cytologic/histologic study
Authors: Shabb Nina S. , Boulos Fouad I. , Chakhachiro Zaher , Abbas Jaber , Abdul‐Karim Fadi W.
Published: October 2013

Adequately cellular and representative fine‐needle aspirates (FNAs) of breast have a high diagnostic accuracy. There is, however, a recognized category designated as “gray zone” where a definitive diagnosis cannot be reached. We reviewed our experience in this category to identify useful diagnostic parameters.

Twenty‐four such FNAs with surgical follow‐up were retrieved from AUBMC files (2003–2009). Cytology slides were reviewed blindly.

All cases were females, 29–73 years. There were three erroneous and 21 inconclusive diagnoses. The majority (15) was invasive adenocarcinomas: two cribriform, four tubular, one lobular, and eight not otherwise specified. The remaining cases were papillary and fibroepithelial tumors (three each), ductal carcinoma in situ, cribriform (two), and one adenomyoepithelioma (AME). Useful diagnostic features included: (1) Biphasic cell population with focal nuclear atypia and intranuclear and cytoplasmic vacuolar inclusions (AME). (2) Complex clusters of epithelial cells with cribriform architecture (cribriform carcinoma). (3) Rigid tubular epithelial structures with abrupt change in diameter, ending in pointed tips with abnormal branching (tubular carcinoma). (4) Cellular stromal fragments (fibroepithelial tumors). (5) Papillary fibrovascular cores, columnar cells, and three‐dimensional papillary epithelial fragments (papillary tumors). Myoepithelial cells classically described in benign aspirates were not always a discriminatory factor.

The “gray zone” in breast FNA is usually due to overlapping cytologic features of some benign and malignant lesions. Useful distinguishing cytologic features are described. Diagn. Cytopathol 2014;42:405–415. © 2013 Wiley Periodicals, Inc.
Morphological divergence and flow‐induced phenotypic plasticity in a native fish from anthropogenically altered stream habitats
Authors: Franssen Nathan R. , Stewart Laura K. , Schaefer Jacob F.
Published: October 2013

Understanding population‐level responses to human‐induced changes to habitats can elucidate the evolutionary consequences of rapid habitat alteration. Reservoirs constructed on streams expose stream fishes to novel selective pressures in these habitats. Assessing the drivers of trait divergence facilitated by these habitats will help identify evolutionary and ecological consequences of reservoir habitats. We tested for morphological divergence in a stream fish that occupies both stream and reservoir habitats. To assess contributions of genetic‐level differences and phenotypic plasticity induced by flow variation, we spawned and reared individuals from both habitats types in flow and no flow conditions. Body shape significantly and consistently diverged in reservoir habitats compared with streams; individuals from reservoirs were shallower bodied with smaller heads compared with individuals from streams. Significant population‐level differences in morphology persisted in offspring but morphological variation compared with field‐collected individuals was limited to the head region. Populations demonstrated dissimilar flow‐induced phenotypic plasticity when reared under flow, but phenotypic plasticity in response to flow variation was an unlikely explanation for observed phenotypic divergence in the field. Our results, together with previous investigations, suggest the environmental conditions currently thought to drive morphological change in reservoirs (i.e., predation and flow regimes) may not be the sole drivers of phenotypic change.