bluuebunny/crossref_metadata_2025 huggingface dataset:
Recombinant Lucilia Sericata chymotrypsin in a topical hydrogel formulation degrades human wound eschar ex vivo
Authors: Britland Stephen , Smith Annie , Finter Wayne , Eagland Donald , Vowden Kath , Vowden Peter , Telford Gary , Brown Alan , Pritchard David
Published: March 2011

Larval biotherapy is a debridement tool used in wound management. The mechanism of action involves degradation of eschar by serine proteases including chymotrypsin within the alimentary fluids of first instar Lucilia sericata. With the rationale of obviating some limitations of biotherapy, including cost, complexity of use, and patient reticence, the present study describes a mobile hydrogel formulation containing freeze‐dried recombinant L. sericata chymotrypsin designed for topical application. Neither freeze‐drying nor formulation into the hydrogel significantly attenuated the measured activity of released enzyme compared to fresh‐frozen enzyme in aqueous solution. Gel electrophoresis confirmed qualitatively that the chymotrypsin/hydrogel formulation both with and without supplementary urea at 10% w/v degraded human chronic wound eschar ex vivo. Mindful that the hallmark of intractability of chronic wounds is aberrant biochemistry, the pH activity profile for the enzyme/hydrogel formulation was compared with exudate pH in chronic wounds of mixed aetiology in a cohort of 48 hospital in‐patients. Five patients' wounds were acidic, however, the remainder were predominantly alkaline and coincided with the pH optimum for the insect enzyme. Thus, a recombinant L. sericata chymotrypsin and hydrogel formulation could represent a pragmatic alternative to larval therapy for the management of chronic wounds. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Determination of robustness and optimal work conditions for a purification process of a therapeutic recombinant protein using response surface methodology
Authors: Amadeo Ignacio , Mauro Laura V. , Ortí Eduardo , Forno Guillermina
Published: March 2011

A typical chromatographic purification step has numerous operating parameters that can impact its performance. As it is not feasible to evaluate the influence of each one, the current practice in biopharmaceutical industry is to apply risk analysis approach to identify process parameters that should be examined during process characterization. Once these parameters are identified, a response surface study can be run to help understand the relationship between critical inputs and outputs. We performed a study comprising optimization and robustness determination for a Blue‐Sepharose purification step of rhEPO, a well‐known therapeutic glycoprotein. Initially, risk analysis was fulfilled to identify key parameters. A small‐scale model was created and qualified before its use in experimental studies, given by a Box–Behnken design with three factors. This method proved to be a very useful tool in bioprocess validation studies in which many input variables can affect product quality and safety. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
A model‐based method for investigating bioenergetic processes in autotrophically growing eukaryotic microalgae: Application to the green algae Chlamydomonas reinhardtii
Authors: Cogne Guillaume , Rügen Marco , Bockmayr Alexander , Titica Mariana , Dussap Claude‐Gilles , Cornet Jean‐François , Legrand Jack
Published: March 2011

A constraint‐based modeling approach was developed to investigate the metabolic response of the eukaryotic microalgae Chlamydomonas reinhardtii under photoautotrophic conditions. The model explicitly includes thermodynamic and energetic constraints on the functioning metabolism. A mixed integer linear programming method was used to determine the optimal flux distributions with regard to this set of constraints. It enabled us, in particular, to highlight the existence of a light‐driven respiration depending on the incident photon flux density in photobioreactors functioning in physical light limitation. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
The evolution of institutional effectiveness in the community college
Authors: Head Ronald B.
Published: March 2011

The origins of institutional effectiveness are traced, its evolution within community colleges is described, the use of the term institutional effectiveness is analyzed, and a practical, operational definition of the term is presented.
Institutional effectiveness as process and practice in the American community college
Authors: Manning Terri Mulkins
Published: March 2011

Institutional effectiveness is defined in light of the requirements of the six regional accrediting agencies, common terms are delineated, and the processes and practice of institutional effectiveness in community colleges is explored.
Accountability and institutional effectiveness in the community college
Authors: Ewell Peter T.
Published: March 2011

Heightened national goals for degree attainment in the United States means increasing prominence for community colleges, which entails greater scrutiny in the form of accountability. Technology and a new generation of accountability measures appropriate to the distinctive community college mission are available to meet this challenge.
Accreditation and its influence on institutional effectiveness
Authors: Head Ronald B. , Johnson Michael S.
Published: March 2011

Effective community colleges use the accreditation process to provide a framework for strengthening the effectiveness of programs and services.
The community college IR shop and accreditation: A case study
Authors: Johnston George
Published: March 2011

The office of institutional research (IR) at a community college can provide valuable assistance in supporting accreditation and institutional effectiveness using this proven model.
Program review and institutional effectiveness
Authors: Bers Trudy
Published: March 2011

Program reviews have multiple purposes and designs. While focused on units within the college, the compilation of reviews also provides evidence of institutional effectiveness.
Measuring student success
Authors: Baldwin Christopher , Bensimon Estela Mara , Dowd Alicia C. , Kleiman Lisa
Published: March 2011

This chapter presents commonly used measures of student success, analyzes their strengths and weaknesses, and discusses innovative measures being used to benchmark community colleges throughout the United States.
The future of institutional effectiveness
Authors: Alfred Richard L.
Published: March 2011

Forces inside and outside community colleges are changing the context for performance and mandating new conceptions of effectiveness.
1,4‐Dialkynylbutatrienes: Synthesis, Stability, and Perspectives in the Chemistry of carbo‐Benzenes
Authors: Maraval Valérie , Leroyer Léo , Harano Aya , Barthes Cécile , Saquet Alix , Duhayon Carine , Shinmyozu Teruo , Chauvin Remi
Published: March 2011

The π‐electron‐rich C8‐conjugated sequence of 1,4‐dialkynylbutatrienes is identified as a fragile and fascinating motif occurring in carbo‐benzene derivatives, and in Diederich’s 1,4‐bis(arylethynyl)‐ or 1,4‐bis(triisopropylsilylethynyl)butatriene “capped” representatives, in particular, in tetraalkynylbutatriene. The family of symmetrical 1,4‐dialkynylbutatrienes (ECC)RCCCCR(CCE) is extended to functional caps (E=H, CH3, CCPh, CPhCHBr, or CPhCBr2) with non‐alkynyl substituents at the sp2 vertices (R=Ph or CF3). The targets were selected for their potential in appealing retrosynthetic routes to carbo‐benzenes, in which the aromatic C18 macrocycle would be directly generated by sequential metathesis or reductive coupling processes. The functional 1,4‐dialkynylbutrienes were synthesized by either classical methods used for the preparation of generic butatrienes (R′Li/CuX‐mediated reductive coupling of gem‐dihaloenynes or SnCl2/HCl‐mediated reduction of 3,6‐dioxy‐octa‐1,4,7‐triyne precursors). Their spectroscopic and electrochemical properties are compared and analyzed on the basis of the relative extent of total conjugation.
Controlled Supramolecular Oligomerization of C3‐Symmetrical Molecules in Water: The Impact of Hydrophobic Shielding
Authors: Besenius Pol , van den Hout Kelly P. , Albers Harald M. H. G. , de Greef Tom F. A. , Olijve Luuk L. C. , Hermans Thomas M. , de Waal Bas F. M. , Bomans Paul H. H. , Sommerdijk Nico A. J. M. , Portale Giuseppe , Palmans Anja R. A. , van Genderen Marcel H. P. , Vekemans Jef A. J. M. , Meijer E. W.
Published: March 2011

The supramolecular oligomerization of three water‐soluble C3‐symmetrical discotic molecules is reported. The compounds all possess benzene‐1,3,5‐tricarboxamide cores and peripheral GdIII–DTPA (diethylene triamine pentaacetic acid) moieties, but differ in their linker units and thus in their propensity to undergo secondary interactions in H2O. The self‐assembly behavior of these molecules was studied in solution using circular dichroism, UV/Vis spectroscopy, nuclear magnetic resonance, and cryogenic transmission electron microscopy. The aggregation concentration of these molecules depends on the number of secondary interactions and on the solvophobic character of the polymerizing moieties. Hydrophobic shielding of the hydrogen‐bonding motif in the core of the discotic is of paramount importance for yielding stable, helical aggregates that are designed to be restricted in size through anti‐cooperative, electrostatic, repulsive interactions.
Kinetics and Mechanism of Hydrogen‐Atom Abstraction from Rhodium Hydrides by Alkyl Radicals in Aqueous Solutions
Authors: Pestovsky Oleg , Veysey Stephen W. , Bakac Andreja
Published: March 2011

The kinetics of the reaction of benzyl radicals with [L1(H2O)RhH{D}]2+ (L1=1,4,8,11‐tetraazacyclotetradecane) were studied directly by laser‐flash photolysis. The rate constants for the two isotopologues, k=(9.3±0.6) × 107 M−1 s−1 (H) and (6.2±0.3) × 107 M−1 s−1 (D), lead to a kinetic isotope effect kH/kD=1.5±0.1. The same value was obtained from the relative yields of PhCH3 and PhCH2D in a reaction of benzyl radicals with a mixture of rhodium hydride and deuteride. Similarly, the reaction of methyl radicals with {[L1(H2O)RhH]2+ + [L1(H2O)RhD]2+} produced a mixture of CH4 and CH3D that yielded kH/kD=1.42±0.07. The observed small normal isotope effects in both reactions are consistent with reduced sensitivity to isotopic substitution in very fast hydrogen‐atom abstraction reactions. These data disprove a literature report claiming much slower kinetics and an inverse kinetic isotope effect for the reaction of methyl radicals with hydrides of L1Rh.
Serial Angioscopic Evaluation of Neointimal Coverage and Incidence of Thrombus Formation After Paclitaxel‐Eluting Stent Implantation: Comparison Between 6‐ and 18‐Month Follow‐Up
Authors: Hara Masahiko , Nishino Masami , Taniike Masayuki , Makino Nobuhiko , Kato Hiroyasu , Egami Yasuyuki , Shutta Ryu , Tanouchi Jun , Yamada Yoshio
Published: March 2011

Background:

Long‐term serial angioscopic follow‐up data after paclitaxel‐eluting stent (PES) implantation has not previously been published. The aim of this study is to compare the angioscopic parameters such as neointimal coverage grade and prevalence of red mural thrombus at 6‐ and 18‐month follow‐up after PES implantation.

Hypothesis:

Neointimal formation continues to grow and prevalence of angioscopic thrombus formation becomes low over time after PES implantation.

Methods:

We retrospectively enrolled 17 patients with 19 stents who underwent both 6‐ and 18‐month follow‐up coronary angioscopy after PES implantation. We evaluated the minimum and maximum neointimal coverage grade within 1 stent using coronary angioscopy by classifying neointimal coverage grade into 4 categories. Neointimal coverage grade and incidence of angioscopic red mural thrombus were compared between 6‐ and 18‐month follow‐up groups.

Results:

Minimum neointimal coverage grade at 18 months become lower than that at the 6‐month follow‐up (0.95 ± 0.62 at 6 mo vs 0.58 ± 0.51 at 18 mo, P = 0.035), whereas maximum grade was not significantly different (2.16 ± 0.83 at 6 mo vs 2.37 ± 0.76 at 18 mo, P = 0.248). High incidence of angioscopic red mural thrombus at 6 months was maintained even at 18‐month follow‐up (68% at 6 mo vs 84% at 18 mo, P = 0.224).

Conclusions:

Long‐term serial angioscopic follow‐up demonstrated persistent high incidence of red mural thrombus formation at 18 months after PES implantation. © 2011 Wiley Periodicals, Inc.

The authors have no funding, financial relationships, or conflicts of interest to disclose.
Hepatocellular carcinoma with extrahepatic metastasis
Authors: Uchino Koji , Tateishi Ryosuke , Shiina Shuichiro , Kanda Miho , Masuzaki Ryota , Kondo Yuji , Goto Tadashi , Omata Masao , Yoshida Haruhiko , Koike Kazuhiko
Published: March 2011

BACKGROUND:

Despite significant advances in the treatment of intrahepatic lesions, the prognosis for patients with hepatocellular carcinoma (HCC) who have extrahepatic metastasis remains poor. The objective of this study was to further elucidate the clinical course and prognostic determinants of patients with this disease.

METHODS:

In total, 342 patients who had HCC with extrahepatic metastasis were enrolled. The metastases were diagnosed at initial presentation with HCC in 28 patients and during follow‐up in the remaining patients. The authors analyzed clinical features, prognoses, and treatments and established a scoring system to predict prognosis using a split‐sample method with a testing set and a training set.

RESULTS:

The most frequent site of extrahepatic metastasis was the lung followed by lymph nodes, bone, and adrenal glands. These metastases were related directly to death in only 23 patients (7.6%). The median survival after diagnosis of extrahepatic metastasis was 8.1 months (range, 0.03‐108.7 months). In univariate analysis of the training set (n = 171), performance status, Child‐Pugh classification, the number and size of intrahepatic lesions, macroscopic vascular invasion, symptomatic extrahepatic metastases, α‐fetoprotein levels, and complete responses to treatment were associated significantly with prognosis. On the basis of multivariate analysis, a scoring system was developed to predict prognosis that assessed uncontrollable intrahepatic lesions, extent of vascular invasion, and performance status. This scoring system was validated in the testing set (n = 171) and produced a concordance index of 0.73.

CONCLUSIONS:

The controllability of intrahepatic lesions and performance status were identified as important prognostic factors in patients with advanced HCC who had extrahepatic metastasis. Cancer 2011. © 2011 American Cancer Society.
Salvage radiation in men after prostate‐specific antigen failure and the risk of death
Authors: Cotter Shane E. , Chen Ming Hui , Moul Judd W. , Lee W. Robert , Koontz Bridget F. , Anscher Mitchell S. , Robertson Cary N. , Walther Philip J. , Polascik Thomas J. , D'Amico Anthony V.
Published: March 2011

BACKGROUND:

A survival benefit has been observed with salvage radiation therapy (RT) for prostate‐specific antigen (PSA) failure after radical prostatectomy (RP) in men with rapid rises in PSA doubling time (DT, <6 months). Whether such a benefit exits in men with a protracted PSA rise in DT (≥6 months) is unclear and was examined in the current study.

METHODS:

Of 4036 men who underwent RP at Duke University between 1988 and 2008, 519 experienced a PSA failure, had complete data, and were the subjects of this study. Univariate and multivariate Cox regression analyses were performed to evaluate whether salvage RT in men with either a rapid (<6 months) or a protracted (≥6 months) PSA DT was associated with the risk of all‐cause mortality adjusting for age at the time of PSA failure, known prostate cancer prognostic factors, and cardiac comorbidity.

RESULTS:

After a median follow‐up of 11.3 years after PSA failure, 195 men died. Salvage RT was associated with a significant reduction in all‐cause mortality for men with either a PSA DT of <6 months (adjusted hazard ratio [AHR], 0.53; P = .02) or a PSA DT of ≥6 months (AHR, 0.52; P = .003). In a subset of patients with comorbidity data at the time of PSA failure, salvage RT remained associated with a significant reduction in all‐cause mortality for both men with a PSA DT of <6 months (AHR, 0.35; P = .042) or a PSA DT of ≥6 months (AHR, 0.60; P = .04).

CONCLUSIONS:

Salvage RT for PSA DTs less than or in excess of 6 months is associated with a decreased risk in all‐cause mortality. Cancer 2011. © 2011 American Cancer Society.
Solitary plasmacytomas
Authors: Reed Valerie , Shah Jatin , Medeiros L. Jeffery , Ha Chul S. , Mazloom Ali , Weber Donna M. , Arzu Isidora Y. , Orlowski Robert Z. , Thomas Sheeba K. , Shihadeh Ferial , Alexanian Raymond , Dabaja Bouthaina S.
Published: March 2011

BACKGROUND:

The objective of this study was to review the outcome of patients with solitary plasmacytoma (SP) after definitive radiation therapy.

METHODS:

The authors retrospectively reviewed 84 patients with SP who were diagnosed and treated at The University of Texas MD Anderson Cancer Center during 1988 to 2008. The impact of tumor anatomic site, tumor size, and the presence of serum and urinary paraprotein at diagnosis was assessed on local control, survival, and the risk of developing multiple myeloma (MM).

RESULTS:

Fifty‐nine patients (70%) had bone SP, and 25 patients (30%) had extramedullary SP. Serum paraprotein was present in 39 patients (46%). The median radiation dose was 45 grays (Gy) (range, 36‐53.4 Gy). Local control was achieved in 77 patients (92%). Neither radiation dose nor tumor size predicted local control. The 5‐year rate of progression to MM was 47% and was higher for patients with bone SP (56% vs 30% for extramedullary SP; P = .021), and patients who had serum paraprotein detected at diagnosis (60% vs 39%; P = .016). On univariate analysis, patients aged <60 years and men had higher rates of progression to MM, although the differences were not significant (P = .048 and P = .29, respectively). Multivariate analysis revealed that bone location and serum protein at diagnosis were associated statistically with progression to MM. The 5‐year overall survival rate for the entire patient cohort was 78%, and no difference was observed between patients who had bone SP versus extramedullary SP (76% vs 85%, respectively; P = .274).

CONCLUSIONS:

The current results indicated that definitive radiation therapy for SP can provide excellent local control. Progression to MM remains the main problem and is more common among patients with bone SP and those who have serum paraprotein detected at diagnosis. Cancer 2011;. © 2011 American Cancer Society.
Intraoperative molecular assay for sentinel lymph node metastases in early stage breast cancer
Authors: Osako Tomo , Iwase Takuji , Kimura Kiyomi , Yamashita Kyoko , Horii Rie , Yanagisawa Akio , Akiyama Futoshi
Published: March 2011

BACKGROUND:

Conventional histopathological examination is limited in measuring accurate total metastatic volume in a lymph node. Recently, a molecular‐based procedure to detect lymph node metastases, one‐step nucleic acid amplification (OSNA) assay, has been developed. OSNA assay can assess a whole lymph node and yields semiquantitative results. The authors compared the performance in intraoperative detection of sentinel lymph node metastases with OSNA assay using a whole lymph node versus routine frozen section (FS) histology with a 2 mm‐sectioned lymph node.

METHODS:

Subjects comprised 531 consecutive patients diagnosed with OSNA assay and 618 consecutive patients diagnosed with FS histological examination. The authors compared the sentinel lymph node‐positive rate between the OSNA and FS cohorts, and investigated characteristics of patients for whom OSNA could detect metastases but FS could not. OSNA (+) was defined as micrometastasis, and OSNA (++) and (+I) were defined as macrometastasis.

RESULTS:

OSNA assay detected more cases of sentinel lymph node metastases than FS histology (OSNA 121 of 531, 22.8% vs FS 109 of 618, 17.6%; P = .036), particularly micrometastases (46 of 531, 8.7% vs 28 of 618, 4.5%; P = .0064). There was no difference in macrometastasis detection between OSNA and FS (75 of 531, 14.1% vs 81 of 618, 13.1%; P = .68). OSNA detected more metastases than FS in postmenopausal patients (77 of 302, 25.5% vs 43 of 351, 12.3%; P < .0001), and in tumors without fat invasion (23 of 156, 14.7% vs 6 of 151, 4.0%; P = .012) or lymphovascular invasion (67 of 395, 17.0% vs 45 of 458, 9.8%; P = .042).

CONCLUSIONS:

Intraoperative OSNA assay detects more sentinel lymph node metastases, particularly micrometastases, than does FS histology. OSNA assay can also detect more metastases in postmenopausal patients or from less aggressive primary tumors compared with FS histology. Cancer 2011. © 2011 American Cancer Society.
Steroid receptor expression in thymomas and thymic carcinomas
Authors: Mimae Takahiro , Tsuta Koji , Takahashi Fumiaki , Yoshida Akihiko , Kondo Tadashi , Murakami Yoshinori , Okada Morihito , Takeuchi Masahiro , Asamura Hisao , Tsuda Hitoshi
Published: March 2011

BACKGROUND:

Although protein expressions of glucocorticoid receptor (GR), estrogen receptors (ERα and ERβ), progesterone receptor A (PgR‐A), and androgen receptor (AR) were shown to play roles in the growth and differentiation of normal thymus and thymic tumors, to the authors' knowledge their association with patient characteristics and prognosis has yet to be determined.

METHODS:

A series of 140 thymic epithelial tumors (57 type A + AB thymomas, 40 type B1 + B2 thymomas, 6 type B3 thymomas, and 37 thymic carcinomas) were examined for GR, ERα, ERβ, PgR‐A, and AR expression using immunohistochemistry. In addition, the correlation between expression of these hormone receptors and clinicopathologic factors and overall survival (OS) was assessed.

RESULTS:

GR and ERβ demonstrated a high rate of expression in thymomas and thymic carcinomas (82.9% and 76.4%, respectively), whereas rates of ERα, PgR‐A, and AR expression were low (13.6%, 0.71%, and 23.6%, respectively). A significant correlation (P < .05) was found between ERα expression and tumor size and between ERβ expression and tumor stage. Multivariate analyses revealed that histologic subtype (P = .0039), tumor stage (P = .0012), and GR expression (P = .0025) were significantly correlated with the 10‐year OS rate.

CONCLUSIONS:

GR and ERβ demonstrated high rates of expression in thymomas and thymic carcinomas. Furthermore, multivariate analysis revealed that GR expression was associated with better prognosis in patients with surgically resected thymomas and thymic carcinomas. Cancer 2011;. © 2011 American Cancer Society.
Examination of laryngoesophageal dysfunction‐free survival as an endpoint in nonsurgical treatment of squamous cell carcinomas of the larynx and hypopharynx
Authors: Caudell Jimmy J. , Carroll William R. , Spencer Sharon A. , Bonner James A.
Published: March 2011

BACKGROUND:

A recently published consensus guideline suggested a new endpoint for clinical trials involving cancer of the larynx and hypopharynx: laryngoesophageal dysfunction‐free survival (LEDFS). The authors of this report examined LEDFS in the context of definitive radiotherapy alone (RT) or with concurrent chemoradiotherapy (CRT).

METHODS:

Patients with a stage III to IVB squamous cell carcinomas of the larynx or hypopharynx who received definitive radiotherapy were included. Consensus guidelines also suggested analysis of the following: tumor classification, lymph node status, pretreatment tracheotomy, pretreatment swallowing dysfunction, and subsite. LEDFS was assessed using Kaplan‐Meier survival analyses.

RESULTS:

Eighty‐five patients (73.9%) received CRT, and 30 patients (26.1%) received RT. For the entire cohort, the 3‐year LEDFS rate was 28.9%. CRT was associated with an improved LEDFS at 3 years (32.2% vs 20%; P = .02). Pretreatment dysphagia (P = .06) and N2 or N3 lymph node status (P = .09) demonstrated a trend toward poorer LEDFS, but patients who had T4 tumors had an LEDFS similar to that of patients who had T2 and T3 tumors.

CONCLUSIONS:

LEDFS was superior in patients who received CRT compared with patients who received RT alone. T4 status was not associated with a worse LEDFS. Cancer 2011. © 2011 American Cancer Society.
Plasma Epstein‐Barr virus DNA screening followed by 18F‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography in detecting posttreatment failures of nasopharyngeal carcinoma
Authors: Wang Wen‐Yi , Twu Chih‐Wen , Lin Wan‐Yu , Jiang Rong‐San , Liang Kai‐Li , Chen Kuan‐Wen , Wu Ching‐Te , Shih Yi‐Ting , Lin Jin‐Ching
Published: March 2011

BACKGROUND:

The authors investigated the clinical implication of plasma Epstein‐Barr virus (EBV) DNA assay and 18F‐fluoro‐2‐deoxy‐D‐glucose (18F‐FDG) positron emission tomography (PET) in the detection of recurrent nasopharyngeal carcinoma (NPC).

METHODS:

Two hundred forty‐five patients with NPC who had previously received treatment and were in a state of remission were monitored prospectively using a plasma EBV DNA assay every 3 to 6 months. 18F‐FDG PET studies were obtained when abnormal EBV DNA or clinically suggestive signs of recurrence were noted.

RESULTS:

Thirty‐six of 245 patients (14.7%) patients had abnormal EBV DNA tests and underwent PET scans. In the remaining 209 patients, 3658 blood tests were negative. PET scans also were obtained in 5 patients who had undetectable EBV DNA levels but signs that were clinically suggestive of disease recurrence. Subsequent analyses focused on 41 patients who had PET studies. In lesion‐based analyses, the sensitivity, specificity, and accuracy of PET by visual interpretation were 81.8%, 77.1%, and 79.2%, respectively, for all 125 lesions. In patient‐based analyses, the accuracy of PET by visual interpretation was 51.2%. All 36 patients who had detectable plasma levels of EBV DNA had demonstrable NPC recurrences, whereas no recurrences were noted in 5 patients who had undetectable EBV DNA levels but signs that clinically mimicked a recurrence. Compared with annual PET, the annual cost of blood tests every 3 to 6 months per patient saved approximately 77% ∼ 88% in expenses.

CONCLUSIONS:

The plasma EBV DNA assay correctly predicted all NPC recurrences, and PET had high capacity to localize potential lesion sites. The authors concluded that applying the strategy of EBV DNA screening followed by PET scanning may guide appropriate further treatment planning in a cost‐effective manner. Cancer 2011;. © 2011 American Cancer Society.
Rising incidence of second cancers in patients with low‐risk (T1N0) thyroid cancer who receive radioactive iodine therapy
Authors: Iyer N. Gopalakrishna , Morris Luc G. T. , Tuttle R. Michael , Shaha Ashok R. , Ganly Ian
Published: March 2011

BACKGROUND:

American Thyroid Association guidelines currently recommend the selective use of radioactive iodine (RAI) therapy in patients with well differentiated thyroid cancer (WDTC). Despite these guidelines, RAI ablation has been used routinely in all but the very lowest risk patients with thyroid cancer over the last 30 years. The objective of this study was to evaluate patterns of RAI use and elevated risk of secondary primary malignancies (SPM) in patients with low‐risk (T1N0) WDTC.

METHODS:

The Surveillance, Epidemiology, and End Results (SEER) database was used to analyze trends in RAI use over time in the United States. To determine the excess risk of SPM, the standardized incidence ratio (SIR) and excess absolute risk (EAR) of various cancers were calculated in the 2 cohorts. Between 1973 and 2007, 37,176 patients with WDTC were followed in the SEER Program, equating to 408,750 person‐years at risk (PYR). In total, 14,589 patients received RAI, and SPMs were observed in 3223 patients.

RESULTS:

During the study period, the rate of RAI use in patients with low‐risk (T1N0) WDTC increased from 3.3% to 38.1%. For low‐risk patients, the SIR of SPM was 1.21 (95% confidence interval [CI], 0.93‐1.54), and the EAR was 4.6 excess cases per 10,000 PYR. SPM with significantly elevated risk because of RAI were salivary gland malignancies (SIR = 11.13; 95% CI, 1.35‐40.2) and leukemia (SIR = 5.68; 95% CI, 2.09‐12.37). The excess risk of leukemia was significantly greater in patients aged <45 years (SIR = 5.32; 95% CI, 2.75‐9.30) compared with the excess risk in older patients (SIR = 2.26; 95% CI, 1.43‐3.39).

CONCLUSIONS:

The increased risk of a SPM in patients with low‐risk (T1N0) WDTC, along with a lack of data demonstrating improved survival outcomes with adjuvant RAI, provide a compelling argument in favor of rationing the use of RAI in this patient population. Cancer 2011;. © 2011 American Cancer Society.
Phase 2 study of high‐dose proton therapy with concurrent chemotherapy for unresectable stage III nonsmall cell lung cancer
Authors: Chang Joe Y. , Komaki Ritsuko , Lu Charles , Wen Hong Y. , Allen Pamela K. , Tsao Anne , Gillin Michael , Mohan Radhe , Cox James D.
Published: March 2011

BACKGROUND:

The authors sought to improve the toxicity of conventional concurrent chemoradiation therapy for stage III nonsmall cell lung cancer (NSCLC) by using proton‐beam therapy to escalate the radiation dose to the tumor. They report early results of a phase 2 study of high‐dose proton therapy and concurrent chemotherapy in terms of toxicity, failure patterns, and survival.

METHODS:

Forty‐four patients with stage III NSCLC were treated with 74 grays (radiobiologic equivalent) proton therapy with weekly carboplatin (area under the curve, 2 U) and paclitaxel (50 mg/m2). Disease was staged with positron emission tomography/computed tomography (CT), and treatments were simulated with 4‐dimensional (4D) CT to account for tumor motion. Protons were delivered as passively scattered beams, and treatment simulation was repeated during the treatment process to determine the need for adaptive replanning.

RESULTS:

Median follow‐up time was 19.7 months (range, 6.1‐44.4 months), and median overall survival time was 29.4 months. No patient experienced grade 4 or 5 proton‐related adverse events. The most common nonhematologic grade 3 toxicities were dermatitis (n = 5), esophagitis (n = 5), and pneumonitis (n = 1). Nine (20.5%) patients experienced local disease recurrence, but only 4 (9.1%) had isolated local failure. Four (9.1%) patients had regional lymph node recurrence, but only 1 (2.3%) had isolated regional recurrence. Nineteen (43.2%) patients developed distant metastasis. The overall survival and progression‐free survival rates were 86% and 63% at 1 year.

CONCLUSIONS:

Concurrent high‐dose proton therapy and chemotherapy are well tolerated, and the median survival time of 29.4 months is encouraging for unresectable stage III NSCLC. Cancer 2011;. © 2011 American Cancer Society
Sentinel lymph node biopsy in breast cancer patients treated with neoadjuvant chemotherapy
Authors: Pecha Vaclav , Kolarik Dusan , Kozevnikova Renata , Hovorkova Karolina , Hrabetova Petruse , Halaska Michael , Sottner Oldrich , Trnkova Marketa , Petruzelka Lubos , Kolarova Hana
Published: March 2011

BACKGROUND:

Sentinel lymph node biopsy (SLNB) is a widely used staging method for patients with early breast cancer. Neoadjuvant chemotherapy modifies the anatomical conditions in the breast and axilla, and thus SLNB remains controversial in patients treated preoperatively. The aim of this study was to demonstrate the reliability and accuracy of this procedure in this particular group of patients.

METHODS:

The retrospective study analyzed medical records of patients diagnosed with primary breast cancer between the years 2005 and 2009. Of the patients treated by neoadjuvant therapy, 343 underwent lymphatic mapping to identify sentinel lymph nodes, and these were included in the analysis.

RESULTS:

The overall detection rate of sentinel lymph nodes was 80.8%. It was strongly influenced by clinical lymph node status (significantly higher success rate in lymph node‐negative patients); higher detection rates were also associated with age <50 years, estrogen receptor positivity, lower proliferation index, and absent lymphovascular space invasion. The false‐negative rate was 19.5% and was only marginally significantly dependent on lymphovascular space invasion. The overall accuracy of the method was 91.5%.

CONCLUSIONS:

By using the present technique, sentinel lymph node biopsy cannot be recommended as a reliable predictor of axillary lymph node status when performed at the authors' institution after neoadjuvant chemotherapy. Infrequent use of blue dye for lymphatic mapping, low number of resected sentinel lymph nodes, and absence of any selection among patients included in the study could be the main factors responsible for the low detection rate and high false‐negative rate. Cancer 2011;. © 2011 American Cancer Society.
Biospecimen reporting for improved study quality (BRISQ)
Authors: Moore Helen M. , Kelly Andrea B. , Jewell Scott D. , McShane Lisa M. , Clark Douglas P. , Greenspan Renata , Hayes Daniel F. , Hainaut Pierre , Kim Paula , Mansfield Elizabeth A. , Potapova Olga , Riegman Peter , Rubinstein Yaffa , Seijo Edward , Somiari Stella , Watson Peter , Weier Heinz‐Ulrich , Zhu Claire , Vaught Jim
Published: March 2011

Human biospecimens are subjected to collection, processing, and storage that can significantly alter their molecular composition and consistency. These biospecimen preanalytical factors, in turn, influence experimental outcomes and the ability to reproduce scientific results. Currently, the extent and type of information specific to the biospecimen preanalytical conditions reported in scientific publications and regulatory submissions varies widely. To improve the quality of research that uses human tissues, it is crucial that information on the handling of biospecimens be reported in a thorough, accurate, and standardized manner. The Biospecimen Reporting for Improved Study Quality (BRISQ) recommendations outlined herein are intended to apply to any study in which human biospecimens are used. The purpose of reporting these details is to supply others, from researchers to regulators, with more consistent and standardized information to better evaluate, interpret, compare, and reproduce the experimental results. The BRISQ guidelines are proposed as an important and timely resource tool to strengthen communication and publications on biospecimen‐related research and to help reassure patient contributors and the advocacy community that their contributions are valued and respected. Cancer (Cancer Cytopathol) 2011. Published 2011 by the American Cancer Society.
Semantic middleware for e‐Science knowledge spaces
Authors: Futrelle Joe , Gaynor Jeff , Plutchak Joel , Myers James D. , McGrath Robert E. , Bajcsy Peter , Kastner Jason , Kotwani Kailash , Lee Jong Sung , Marini Luigi , Kooper Rob , McLaren Terry , Liu Yong
Published: March 2011

The Tupelo semantic content management middleware implements Knowledge Spaces that enable scientists to integrate information into a comprehensive research record as they work with existing tools and domain‐specific applications. Knowledge Spaces combine approaches that have demonstrated success in automating parts of this integration activity, including content management systems for domain‐neutral management of data, workflow technologies for management of computation and analysis, and semantic web technologies for extensible, portable, citable management of descriptive information and other metadata. Tupelo's ‘Context’ facility and its associated semantic operations both allow existing data representations and tools to be plugged in, and also provide a semantic ‘glue’ of important associative relationships that span the research record, such as provenance, social networks, and annotation. Tupelo has enabled the recent work creating e‐Science cyberenvironments to serve distributed, active scientific communities, allowing researchers to develop, coordinate and share datasets, documents, and computational models, while preserving process documentation and other contextual information needed to produce an integrated research record suitable for distribution and archiving. Copyright © 2011 John Wiley & Sons, Ltd.
Power‐aware provisioning of virtual machines for real‐time Cloud services
Authors: Kim Kyong Hoon , Beloglazov Anton , Buyya Rajkumar
Published: March 2011

Reducing power consumption has been an essential requirement for Cloud resource providers not only to decrease operating costs, but also to improve the system reliability. As Cloud computing becomes emergent for theAnything as a Service(XaaS) paradigm, modern real‐time services also become available through Cloud computing. In this work, we investigate power‐aware provisioning of virtual machines for real‐time services. Our approach is (i) to model a real‐time service as a real‐time virtual machine request; and (ii) to provision virtual machines in Cloud data centers using dynamic voltage frequency scaling schemes. We propose several schemes to reduce power consumption by hard real‐time services and power‐aware profitable provisioning of soft real‐time services. Copyright © 2011 John Wiley & Sons, Ltd.
Cooperative multitasking for GPU‐accelerated grid systems
Authors: Ino Fumihiko , Ogita Akihiro , Oita Kentaro , Hagihara Kenichi
Published: March 2011

This paper presents a cooperative multitasking method for concurrent execution of scientific and graphics applications on the graphics processing unit (GPU). Our method is designed to accelerate compute unified device architecture‐based applications using idle GPU cycles in the office. To prevent significant slow‐down of graphics applications, the method divides scientific tasks into smaller pieces, which are then sequentially executed at the appropriate intervals. The method also has flexibility in finding the best tradeoff point between scientific applications and graphics applications. Experimental results show that the proposed method is useful to control the frame rate of the graphics application and the throughput of the scientific application. For example, biological sequence alignment can be processed at approximately 30% of the dedicated throughput while achieving interactive rendering at 58 frames per second. We also show that matrix multiplication can be efficiently processed at 60% of the dedicated throughput during word processing and web browsing. Copyright © 2011 John Wiley & Sons, Ltd.
Monitoring CD4 in whole blood with an opto‐fluidic detector based on spatially modulated fluorescence emission
Authors: Kiesel Peter , Beck Markus , Johnson Noble
Published: March 2011

We describe a new optical detection technique, termed “spatially modulated fluorescence emission,” that delivers high signal‐to‐noise discrimination without precision optics to enable a flow cytometer that can combine high performance, robustness, compactness, low cost, and ease of use. The detection technique is demonstrated with measurements of absolute CD4+ and percentage CD4 counts in human blood. Benchmarking against a commonly used commercial instrument for this test yields excellent agreement for both absolute CD4 and percentage CD4. © 2011 International Society for Advancement of Cytometry
Evolution of transthoracic fine needle aspiration and core needle biopsy practice: A comparison of two time periods, 1996–1998 and 2003–2005
Authors: Minot Douglas M. , Jaben Elizabeth , Aubry Marie‐Christine , Voss Jesse S. , Vine Roanna L. , Lee Peter U. , Carlson Stephanie K. , Clayton Amy C.
Published: March 2011

To examine the performance of our large pulmonary transthoracic fine needle aspiration/core biopsy (FNA/CB) practice over time, we performed a retrospective analysis of data from 333 consecutive procedures performed in 1996–1998 and 568 consecutive procedures performed in 2003–2005. Fluoroscopic guidance was performed more frequently in the earlier cohort, while a larger majority of procedures in the later cohort were by computed tomography (CT‐guidance). A follow‐up histologic diagnosis of cancer or clinical evidence of disease was considered the gold‐standard. FNA/CB procedures during the later time period were performed on smaller lesions overall (3.60 cm versus 2.97 cm; P = 0.003) and malignant lesions also tended to be smaller (3.87 cm versus 3.14 cm; P = 0.006). Minimal improvements in sensitivity (94% versus 91%), specificity (99% versus 95%), diagnostic accuracy (95% versus 92%), negative predictive value (NPV) (80% versus 74%), and positive predictive value (PPV) (100% versus 99%) were noted during 2003–2005 when compared with 1996–1998 in all lesions. Larger improvements in sensitivity (94% versus 73%), diagnostic accuracy (95% versus 79%), and NPV (79% versus 50%) were identified in very small lesions (<1 cm) in the later patient cohort in comparison to the earlier patient cohort, as well as a significant decrease in total procedure complications. CT‐guided transthoracic FNA/CB continues to be a very effective tool in our practice assessing lung lesions and performance has improved considerably at our institution for very small lesions. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.
Fascin as an identifier of metastatic urothelial carcinoma: A retrospective study of fine‐needle aspiration cell blocks and histologic tissue microarrays
Authors: Vogt Adam P. , Cohen Cynthia , Siddiqui Momin T.
Published: March 2011

Fascin, a marker of invasiveness in urothelial carcinoma, has not been correlated with metastatic disease. To enhance diagnostic accuracy and correctly identify primary site for appropriate patient management, fascin may be a useful marker in metastatic urothelial carcinoma. In this study, we evaluated twenty five cases with adequate cell block material for immunohistochemistry (IHC) staining in patients with either concurrent or previously resected urothelial carcinoma between 2005 and 2010. Fascin, thrombomodulin, uroplakin, cytokeratin 7, and cytokeratin 20 IHC were performed on paraffin‐embedded cell block serial sections. Fascin was over‐expressed in the majority (23/25, 92%) of metastatic urothelial carcinomas. We found concordant results in 22 of 25 (88%) cases for fascin and thrombomodulin IHC staining. Either fascin and/or thrombomodulin demonstrated positive staining in 25 of 25 (100%) cases. Histologic tissue microarrays of 72 genitourinary (GU) carcinomas of the kidney and prostate were stained with fascin to reveal all cases to be negative in the cells of interest. In comparing fascin with the traditional markers of urothelial carcinoma, fascin expression is of greater frequency and intensity than thrombomodulin. The combination of fascin and/or thrombomodulin identified all 25 (100%) cases of urothelial carcinoma. Fascin IHC staining is equivalent in frequency and intensity to cytokeratin 7. Fascin is an advantageous diagnostic complement, to thrombomodulin and/or cytokeratin 7, in the setting of metastatic urothelial carcinoma, and is highly specific and sensitive relative to GU malignancies. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.
Cytopathologic features and differential diagnostic considerations of primary lymphoepithelioma‐like carcinoma of the lung
Authors: Hayashi Toshitetsu , Haba Reiji , Tanizawa Junko , Katsuki Naomi , Kadota Kyuichi , Miyai Yumi , Bando Kenji , Shibuya Shinsuke , Nakano Masayuki , Kushida Yoshio
Published: March 2011

Primary lymphoepithelioma‐like carcinoma (LELC) of the lung is an extremely rare disease that occurs more commonly in Asians, and is composed of undifferentiated carcinoma with prominent lymphoid stroma. LELC is reported to be closely associated with Epstein‐Barr virus (EBV) infection. A case is presented here in which bronchial brushing smears in a 70‐year‐old man, revealed large clusters of neoplastic cells with scant cytoplasm. The nuclei were large, hyperchromatic, of irregular contour and with prominent nucleoli. Also identified were prominent intratumoral lymphoid infiltration and brisk mitotic figures. We detected EBV‐coded small RNA in situ hybridization in smears. A cytologic diagnosis of a LELC was suggested. Further evaluation and immunohistochemical studies were conducted on formalin‐fixed, paraffin‐embeddedmaterial. Cords or nests of large neoplastic cells with enlarged nuclei and prominent nucleoli with marked lymphoid infiltration and lymphoid stroma were identified on H&E sections. Immunohistochemically, the tumor cells showed diffuse and strong membranous staining for CK(AE1/AE3), CK5/6, CK34βE12, Napsin A and Bcl‐2 but were negative for CK7, CK14, CK20, EMA, TTF‐1, chromogranin A, synaptophysin and CD56. The proliferative index with MIB‐1 was around 60%, and the p53 positive cells around 20%. The diagnosis of primary LELC of the lung was confirmed based on cytopathologic, histopathologic, immunohistochemical and EBER results, and a detailed systemic examination to exclude possible extrapulmonary (nasopharyngeal) origin. We report the cytopathological features of LELC of the lung and demonstrate here for the first time the positivity of the EBER with RNA‐ISH method in smears with emphasis on differential diagnostic considerations. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.
Sex and experience influence behavioral responses of adult rats to potentiated and nonpotentiated ultrasonic vocalizations of pups
Authors: Rohitsingh Shelly‐Ann , Smith Jonathan A. , Shair Harry N.
Published: March 2011

Responsiveness of adult rodent caretakers to infant rodents is necessary for their survival and proper development. Both olfactory and auditory cues are known to influence adult behavior toward the young. In the present study, we found that adults respond differentially to a recording of potentiated vs. non‐potentiated ultrasound vocalizations of a 12‐day‐old rat pup, either in the presence or absence of olfactory cues. The combination of olfactory and potentiated ultrasonic vocalization produced the greatest effect. Adult behavior was also affected by the adults' sex and parental experience in an interaction. Parental experience of females made them more responsive to the type of ultrasonic vocalization; males were little affected. Female experience, of course, includes the hormonal changes due to pregnancy and lactational state. The results are consistent with a communicatory function for isolation‐induced ultrasonic vocalization. © 2011 Wiley Periodicals, Inc. Dev Psychobiol 53:677–684, 2011.
Changes in object‐oriented arm movements that precede the transition to goal‐directed reaching in infancy
Authors: Lee Mei‐Hua , Ranganathan Rajiv , Newell Karl M.
Published: March 2011

The emergence of prehensile skills in infancy is one of the central issues in motor development. The objective of this longitudinal study was to quantitatively describe the changes in the object‐oriented arm movements that precede the transition to goal‐directed reaching movements in infancy. Arm kinematics in 10 full‐term infants were recorded biweekly from the age of 10 to 28 weeks while objects were presented for prehension. The kinematics were analyzed across three progressive phases of object‐oriented arm movements (early, before, and after onset of reaching movements). As infant age increased through the stage of object‐oriented movements, the distinguishing feature was that there was a decrease in movement jerk (when normalized to a dimensionless quantity), which reflects the increasing ability to adaptively modulate arm movements. This change in the dynamic characteristics of the object‐oriented arm movements precedes the onset of goal‐directed reaching movements and is hypothesised to reflect a critical variable in the infant developmental process of learning to reach in prehension. © 2011 Wiley Periodicals, Inc. Dev Psychobiol 53:685–693, 2011.