bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifications of FIRST radio sources in the NOAO Deep Wide‐Field Survey
Authors: El Bouchefry K. , Cress C.M.
Published: June 2007

In this paper we present the results of an optical and near infrared identification of 514 radio sources from the FIRST survey (Faint Images of the Radio Sky Survey at Twenty centimetres) with a flux‐density limit of 1 mJy in the NOAO Deep Wide‐Field Survey (NDWFS) Boötes field. Using optical (Bw, R, I) and K band data with approximate limits of Bw ∼ 25.5 mag, R ∼ 25.8 mag, I ∼ 25.5 mag and K ∼ 19.4 mag, optical counterparts have been identified for 378 of 514 FIRST radio sources. This corresponds to an identification rate of 34% in four bands (BwRIK), 60% in optical bands (BwRI) and 74% in the I band. Photometric redshifts for these sources have been computed using the hyperz code. The inclusion of quasar template spectra in hyperz is investigated. We note that the photometric data are, in many cases, best matched to templates with very short star‐formation timescales and the inferred ages of identified galaxies depend strongly on the assumptions about the star‐formation timescale. The redshifts obtained are fairly consistent with those expected from the K ‐z relation for brighter radio sources but there is more scatter in the K ‐z diagram at z < 1. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Contribution to the study of composite spectra: XII. Spectroscopic orbits of eight southern stars
Authors: Carquillat J.‐M. , Prieur J.‐L.
Published: June 2007

We present the results of a radial‐velocity study of eight southern SB1 spectroscopic binaries with composite spectra: HD 34318‐9, HD 47579‐80, HD 70442‐3, HD 74946‐7, HD 102171‐2, HD 120901‐2, HD 168701‐2, and HD 174191‐2. The observations were made at Haute‐Provence observatory with the CORAVEL instrument between 1982 and 2006. From the radial‐velocity measurements of the cool components, we derive the orbital elements of those spectroscopic binaries. Using all the available data, we obtain an estimation of the orbital inclination and the angular separation of the two components. Finally we discuss the rotation‐revolution synchronism of the cool components. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Absolute bioavailability of sitagliptin, an oral dipeptidyl peptidase‐4 inhibitor, in healthy volunteers
Authors: Bergman Arthur , Ebel David , Liu Fang , Stone Julie , Wang Amy , Zeng Wei , Chen Li , Dilzer Stacy , Lasseter Kenneth , Herman Gary , Wagner John , Krishna Rajesh
Published: June 2007

The purpose of this study was to determine the absolute bioavailability of sitagliptin, an orally active, potent and highly selective dipeptidyl peptidase‐4 inhibitor recently approved in the United States for the treatment of type 2 diabetes. The effect of a high fat meal on sitagliptin pharmacokinetics was also assessed. The study was performed in two parts. Intravenous doses (2 h infusion) of 25, 50 and 100 mg were administered double‐blind to 10 (8 active, 2 placebo) subjects in a fixed‐sequence manner in Part I. In Part II, 12 subjects were randomized to each of three open‐label treatments: an intravenous 100 mg dose; a single oral 100 mg final market image tablet administered following a high fat meal and a single oral 100 mg final market image tablet administered fasted. Following each dose, plasma and urine were collected at pre‐specified times for evaluation of sitagliptin pharmacokinetics. All doses were generally well tolerated in both parts of the study. Following rising intravenous doses of sitagliptin, AUC0−∞ increased dose‐proportionally, indicating that plasma clearance is independent of dose over the dose range evaluated. Renal clearance of unchanged sitagliptin accounted for approximately 70% of the total plasma clearance of sitagliptin, indicating that sitagliptin is primarily cleared via renal excretion. Averaged across doses, the mean total plasma clearance was 416 ml/min. The mean absolute bioavailability of sitagliptin was 87% with a 90% CI of (81%, 93%). The AUC0−∞ and Cmax geometric mean ratios (fed/fasted) and 90% CIs were 1.03 (0.97, 1.11) and 0.94 (0.86, 1.03), respectively, and were contained within the bounds of (0.80, 1.25). Additionally, the high‐fat meal had no significant effect on Tmax or apparent terminal t1/2. Thus, food does not affect the pharmacokinetics of sitagliptin and therefore can be administered without regard to food. Copyright © 2007 John Wiley & Sons, Ltd.
Pharmacokinetics and dose proportionality of three Tramadol Contramid®OAD tablet strengths
Authors: Karhu David , El‐Jammal Ali , Dupain Thibaut , Gaulin Delphine , Bouchard Sylvie
Published: June 2007

A three‐way crossover study in 27 human volunteers was conducted to characterize the pharmacokinetics and to assess the dose proportionality of 100 mg, 200 mg and 300 mg strengths of a novel once‐a‐day tramadol controlled‐release tablet (Tramadol Contramid®OAD) following single‐dose administration. Serial blood samples were collected at predefined timepoints over a 48 h period and racemic tramadol and O‐desmethyltramadol concentrations in plasma were determined using a validated LC‐MS/MS method. Pharmacokinetic parameters were derived using noncompartmental methods. Following dose normalization and logarithmic transformation of concentration‐dependent parameters, the results were compared using analysis of variance (ANOVA). The residual variability thereby obtained was used to construct 90% classical confidence intervals. The two one‐sided tests procedure was used for all pairwise comparisons. Dose proportionality was concluded since the 90% CI for the ratio of geometric means was included in the acceptance range of 0.80–1.25 for all comparisons. Copyright © 2007 John Wiley & Sons, Ltd.
Fitting Semiparametric Additive Hazards Models using Standard Statistical Software
Authors: Schaubel Douglas E. , Wei Guanghui
Published: June 2007

The Cox proportional hazards model has become the standard in biomedical studies, particularly for settings in which the estimation covariate effects (as opposed to prediction) is the primary objective. In spite of the obvious flexibility of this approach and its wide applicability, the model is not usually chosen for its fit to the data, but by convention and for reasons of convenience. It is quite possible that the covariates add to, rather than multiply the baseline hazard, making an additive hazards model a more suitable choice. Typically, proportionality is assumed, with the potential for additive covariate effects not evaluated or even seriously considered. Contributing to this phenomenon is the fact that many popular software packages (e.g., SAS, S‐PLUS/R) have standard procedures to fit the Cox model (e.g., proc phreg, coxph), but as of yet no analogous procedures to fit its additive analog, the Lin and Ying (1994) semiparametric additive hazards model. In this article, we establish the connections between the Lin and Ying (1994) model and both Cox and least squares regression. We demonstrate how SAS's phreg and reg procedures may be used to fit the additive hazards model, after some straightforward data manipulations. We then apply the additive hazards model to examine the relationship between Model for End‐stage Liver Disease (MELD) score and mortality among patients wait‐listed for liver transplantation. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Evaluating Health Care Performance: Strengths and Limitations of Multilevel Analysis
Authors: Tan Alai , Freeman Jean L. , Freeman Daniel H.
Published: June 2007

An increasing number of health services researchers are using multilevel analysis for evaluating health care performance. This method has the distinct advantage of accounting for within‐provider correlation among patients. Alternatively, in a similar manner, estimators based on cluster sampling can also adjust for within‐provider correlation. Cluster sampling methods do not require assumptions about error distribution as multilevel analysis does. To our knowledge, no comparison has been made between multilevel analysis and cluster sampling estimators in evaluating health care performance using either a simulated or real dataset. In this paper, we compare the cluster sampling estimators to multilevel estimators in evaluating screening mammography performance using Medicare claims data. We also discuss the strengths and limitations of multilevel analysis in profiling health care providers with small caseloads. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Risk factors for faecal incontinence after rectal cancer treatment
Authors:   cooperative clinical investigators of the Dutch Total Mesorectal Excision trial, Lange M M , den Dulk M , Bossema E R , Maas C P , Peeters K C M J , Rutten H J , Klein Kranenbarg E , Marijnen C A M , van de Velde C J H
Published: June 2007

Background

Low anterior resection (LAR) may result in faecal incontinence. This study aimed to identify risk factors for long-term faecal incontinence after total mesorectal excision (TME) with or without preoperative radiotherapy (PRT).

Methods

Between 1996 and 1999, patients with operable rectal cancer were randomized to TME with or without PRT. Eligible patients who underwent LAR were studied retrospectively at 2 years (399 patients) and 5 years (339) after TME.

Results

At 5 years after surgery faecal incontinence was reported by 61·5 per cent of patients who had PRT and 38·8 per cent of those who did not (P < 0·001). Excessive blood loss and height of the tumour were associated with long-term faecal incontinence, but only in patients treated with PRT.

Conclusion

Faecal incontinence is likely to occur after PRT and TME, especially when the perineum is irradiated.
Island roots, global reach: A case study in internationalizing Kapi'olani Community College
Authors: Richards Leon , Franco Robert W.
Published: June 2007

This chapter offers a case study of Kapi'olani Community College, an institution that initiated its Asia‐Pacific emphasis in 1988, strengthened the emphasis throughout the 1990s, and expanded it to an integrated international emphasis in 2007.
Comparison of drug‐eluting stents with bare metal stents in unselected patients with acute myocardial infarction
Authors: Kupferwasser L. Iri , Amorn Allen M. , Kapoor Nikhil , Lee Michael S. , Kar Saibal , Cercek Bojan , Dohad Suhail , Mirocha James , Forrester James S. , Shah Prediman K. , Makkar Raj R.
Published: June 2007

Objectives:

The aim of this study was to compare the procedural characteristics and outcomes of patients with acute myocardial infarction treated with drug‐eluting stents (DES) vs. bare metal stents (BMS).

Background:

DES have been shown to reduce the incidence of restenosis and target vessel revascularization (TVR) in clinical randomized studies when compared with BMS in patients undergoing elective percutaneous intervention. Limited data are available with the use of DES in patients with acute ST‐segment elevation myocardial infarction.

Methods:

Two hundred and sixty‐one consecutive patients who presented with myocardial infarction between 7/2001 and 8/2005 were studied. The procedural characteristics, 30‐day and 12‐month outcomes of 131 patients treated with DES were compared with 130 patients treated with BMS.

Results:

At 12‐months follow‐up DES therapy was associated with a substantial decrease in major adverse cardiovascular events (MACE) (HR 0.33; P =0.002), TVR (HR 0.19; P =0.002), and recurrent myocardial infarction (HR 0.23; P =0.051) vs. BMS therapy. Coronary interventions utilizing DES were characterized by a marked increase in the number of stent per target vessel (DES: 1.9 ± 0.9 vs. BMS: 1.38 ± 0.6, P < 0.0001), treatment of bifurcation (DES: 21% vs. BMS: 5%, P =0.0004), and multivessel intervention (DES: 22% vs. BMS: 8%, P =0.003).

Conclusion:

The routine use of DES in acute myocardial infarction is associated with reduced rates of MACE at 12 months vs BMS, despite a higher rate of complex procedures in the DES treated patients. In addition to its anti‐restenosis effect, the improved outcome of patients treated with DES may be linked to a more complete revascularization in association with prolonged clopidogrel therapy. © 2007 Wiley‐Liss, Inc.
Tryptophan‐to‐Dye Fluorescence Energy Transfer Applied to Oxygen Sensing by Using Type‐3 Copper Proteins
Authors: Zauner Gerhild , Lonardi Emanuela , Bubacco Luigi , Aartsma Thijs J. , Canters Gerard W. , Tepper Armand W. J. W.
Published: June 2007

A fluorescence‐based system to sense oxygen in solution is described. The method exploits the sensitivity of the endogenous fluorescence of type‐3 copper proteins towards the presence of oxygen by translating the near‐UV emission of the protein to label fluorescence in the visible range through a FRET mechanism. The main protein in this study, a recombinant tyrosinase from the soil bacterium Streptomyces antibioticus, has been covalently labeled with a variety of fluorescent dye molecules with emission maxima spanning the whole visible wavelength range. In all cases, the emission of the label varied considerably between O2‐bound and O2‐free protein with a contrast exceeding that of the Trp emission for some labels. It is shown that different constructs may be simultaneously observed using a single excitation wavelength. Next to the described application in oxygen sensing, the method may be applicable to any protein showing variations in tryptophan fluorescence, for example as a function of ligand binding or catalysis.
Tetraazaperopyrenes: A New Class of Multifunctional Chromophores
Authors: Riehm Till , De Paoli Gabriele , Konradsson Asgeir E. , De Cola Luisa , Wadepohl Hubert , Gade Lutz H.
Published: June 2007

Tetraazaperopyrene and a range of derivatives have been synthesised and their photophysical and redox‐chemical properties studied. The parent compound, 1,3,8,10‐tetraazaperopyrene (1), was prepared by treating 4,9‐diamino‐3,10‐perylenequinone diimine with triethyl orthoformate, whereas the 2,9‐disubstituted derivatives of 1 were obtained after treatment with the corresponding carboxylic acid chloride or anhydride (2 mol equiv). The 1,3,8,10‐tetraazaperopyrene core structure was established by X‐ray diffraction of 2,9‐bis(2‐bromophenyl)‐1,3,8,10‐tetraazaperopyrene (6). The UV‐visible absorption spectra of the compounds have a characteristic visible π*←π absorption band at 440 nm (log εmax=4.80) with a strong vibrational progression (Δν≈1450 cm−1). Diprotonation of the nitrogen atoms induces a bathochromic shift of this band from 430–440 to 470–480 nm and all four nitrogen atoms are protonated when pure H2SO4 is used as the solvent. The first and second as well as the third and fourth protonations occur concomitantly, which implies that they have very similar pKa values and, consequently, similar proton affinities. A theoretical study of the proton affinities in the gas phase and in solution attributes this behaviour to the effects of polar solvents, which dampen the charge of a protonated site at the other end of the molecule and thus effectively decouple the two opposite pyrimidine units in the polycondensed aromatic compound. The photophysical data were modelled in a time‐dependent DFT study of 1, 1H22+ and 1H44+ in both the gas phase and in a polar solvent. All the dyes show weak fluorescence in organic solvents, however, their protonated conjugate acids show dramatically increased fluorescence intensity. All of the dyes undergo two electrochemically reversible one‐electron reductions with cyclovoltammetric half‐wave potentials at Ered1≈−0.9 V and Ered2≈−1.3 V (vs. SCE), which are associated with characteristic spectral changes.
Heavy Grignard Reagents: Challenges and Possibilities of Aryl Alkaline Earth Metal Compounds
Authors: Westerhausen Matthias , Gärtner Martin , Fischer Reinald , Langer Jens , Yu Lian , Reiher Markus
Published: June 2007

Compounds of the type arylMX, with M=Ca, Sr, Ba and X as any kind of ligand (such as halide, phosphanide, amide, aryl), are presented. The low reactivity of the heavy alkaline earth metals calcium, strontium, and barium enforces an activation prior to use for the direct synthesis. The insertion of these metals into CI bonds of aryl iodides (direct synthesis) yields aryl metal iodides and has to be performed at low temperatures and in THF. Aryl alkaline‐earth‐metal compounds show some characteristics: 1) the ease of ether cleavage enforces low reaction temperatures, 2) for Sr and Ba the Schlenk equilibrium is shifted towards homoleptic MI2 and MPh2, 3) high solubility of diaryl alkaline‐earth‐metal derivatives in THF even at low temperatures initiated quantum chemical investigations on the aggregation behavior, and 4) a strong low field shift of the 13C resonances of the ipso carbon atoms in NMR spectra was observed. First results from quantum chemical calculations on diaryl dicalcium(I) suggest a long CaCa bond with a considerable CaCa bond dissociation energy. Initial results on a selection of applications such as metallation, metathesis, and addition reactions of aryl calcium compounds are presented as well.
Rapid screening of enzymes for the enzymatic hydrolysis of chiral esters in drug discovery
Authors: Petucci Chris , Di Li , McConnell Oliver
Published: June 2007

Thirty‐five enzymes were rapidly screened for their ability to selectively hydrolyze chiral esters to their corresponding carboxylic acids for the efficient generation of chiral intermediates in drug discovery. Optimization of the enzymatic reactions at various incubation times was performed using a robotic liquid handler. Enantiomeric pairs of chiral esters and carboxylic acids were then analyzed simultaneously by chiral GC/MS in a single analysis. This analytical approach is particularly useful for compounds that do not possess a conjugated chromophore or are volatile and difficult to analyze by chiral HPLC/UV or HPLC/MS. The resulting data was used to determine enantiomeric excesses and percent conversions to the desired enantiomer of the carboxylic acid for the selection of efficient enzymes for bioconversions in drug discovery in a pharmaceutical company. Chirality, 2007. © 2007 Wiley‐Liss, Inc.
Linked claims and medical records for cancer case management
Authors: Eberl Margaret M. , Watroba Nancy , Reinhardt Marc , Pomerantz Jay , Serghany Joseph , Broffman Gregory , Fox Chester H. , Mahoney Martin C. , Edge Stephen B.
Published: June 2007

BACKGROUND.

Failure to obtain the requisite follow‐up of patients with abnormal mammograms may delay cancer diagnosis and impact outcome. Up to 20% of women do not receive timely recommended follow‐up. The current study tested the accuracy of the linkage of payer claims and clinical data to identify the appropriate treatment for patients with abnormal mammograms.

METHODS.

Electronic medical records in a staff model practice that was affiliated with a single health payer were scanned to identify the Breast Imaging Reporting and Data System (BI‐RADS®) code for all mammograms. For each woman with a BI‐RADS code 0, 3, 4, or 5 mammogram, the payer claims were searched for follow‐up breast procedures (imaging, biopsy, and surgery) occurring within 2 months for BI‐RADS code 0, 4, and 5 mammograms and within 8 months for BI‐RADS code 3 mammograms. For women with >1 abnormal mammogram during the study period, only follow‐up for the first abnormal mammogram was examined. The medical records of cases defined by claims as not having recommended follow‐up care were reviewed to determine the accuracy of claims analyses.

RESULTS.

A total of 17,329 women underwent 23,721 mammograms between January 1, 2001 and December 31, 2003. BI‐RADS codes 0, 3, 4, or 5 occurred in 1490 mammograms (6.3%). Among 1206 women with a first abnormal mammogram who were eligible for claims follow‐up, 16% did not receive recommended follow‐up care. Medical record review demonstrated that the claims search accurately identified follow‐up care in 97% of these cases.

CONCLUSIONS.

Administrative claims supplemented with BI‐RADS data were found to accurately identify the follow‐up care of patients with abnormal mammograms. Case management using this method may assist physicians in ensuring that all patients receive appropriate care. Cancer 2007. © 2007 American Cancer Society.
Gemcitabine‐based combinations for inoperable pancreatic cancer: Have we made real progress?
Authors: Bria Emilio , Milella Michele , Gelibter Alain , Cuppone Federica , Pino Maria Simona , Ruggeri Enzo Maria , Carlini Paolo , Nisticò Cecilia , Terzoli Edmondo , Cognetti Francesco , Giannarelli Diana
Published: June 2007

BACKGROUND.

Several attempts have been made at improving the efficacy of gemcitabine in advanced pancreatic cancer by combining it with other chemotherapeutic or molecularly targeted agents. However, randomized trials have produced conflicting results.

METHODS.

All prospective, randomized, phase 3 trials that compared single‐agent gemcitabine with gemcitabine‐based combinations were considered eligible for the current analysis. A literature‐based meta‐analysis was performed, event‐based relative risk ratios with 95% confidence intervals were derived through both a fixed‐effect model approach and a random‐effect model approach, and overall survival (OS) was explored as the primary endpoint. To estimate the magnitude of the eventual benefit, absolute differences and the number of patients needed to treat (NNT) for 1 patient to benefit were calculated. A sensitivity analysis for OS was performed according to the type of agent used in combination with gemcitabine.

RESULTS.

Twenty trials that involved 6296 patients were identified. No significant differences in the primary endpoint were observed in the overall population or in the sensitivity analysis. Conversely, a significant advantage was evident with regard to both progression‐free survival (PFS) and the overall response rate (ORR) in the overall population, with an absolute benefit of 2.6% (NTT = 39 patients) and 3.0% (NNT = 33 patients). Platinum combinations led to the greatest absolute benefits for PFS and ORR compared with single‐agent gemcitabine (10% and 6.5%, respectively), but this did not result in an OS benefit. Improvement in PFS, but not in the ORR, was correlated with an improvement in OS.

CONCLUSIONS.

Single‐agent gemcitabine remains the standard of care for patients with advanced pancreatic cancer. However, platinum/gemcitabine combinations appeared to improve PFS and the ORR and, thus, may be considered in selected patients. Cancer 2007. © 2007 American Cancer Society.
Long‐term outcomes after treatment with brachytherapy and supplemental conformal radiation for prostate cancer patients having intermediate and high‐risk features
Authors: Dattoli Michael , Wallner Kent , True Lawrence , Cash Jennifer , Sorace Richard
Published: June 2007

BACKGROUND.

This study summarizes long‐term outcomes from treatment of prostate cancer with increased risk of extracapsular cancer extension (ECE) using brachytherapy‐based treatment.

METHODS.

A total of 282 consecutive patients were treated from 1992–1996 by 1 author (M.D.). Two hundred forty‐three patients had at least 1 higher risk feature for ECE including Gleason Score 7–10 (172), prostate‐specific antigen (PSA) above 10 (166), and clinical stages T2c (109) and T3 (107). Using National Comprehensive Cancer Network (NCCN) guidelines, 119 patients had intermediate‐risk disease and 124 had high‐risk disease. Patients received pelvic 3‐dimensional conformal external beam radiation followed by a palladium (Pd)‐103 boost. Generous brachytherapy margins were utilized. Biochemical failure was defined using ASTRO Consensus Definition, nadir +2 and PSA >0.2 ng/mL at last follow‐up. The nonfailing patient follow‐up period was 1–14 years (median, 9.5 years). Biochemical data and original biopsy slides were independently re‐reviewed at the University of Washington (by K.W. and L.T., respectively).

RESULTS.

Overall actuarial freedom from biochemical progression at 14 years was 81%, including 87% and 72% having intermediate and high‐risk disease, respectively. Absolute risk of failure decreased progressively, falling to 1% beyond 6 years after treatment. All failing patients had prostate biopsies without evidence of local recurrence. The strongest predictor of failure was Gleason score (P = .03) followed by PSA (P = .041). Treatment morbidity was limited to temporary RTOG grade 1–2 urinary and gastrointestinal symptoms.

CONCLUSIONS.

High tumor control rates are possible with beam radiation followed by Pd‐103 brachytherapy. Despite perceptions that brachytherapy is inappropriate for patients at higher risk for ECE, this series strengthens the rationale that brachytherapy‐based treatment may be a desirable modality for such patients. Cancer 2007. © 2007 American Cancer Society.
The Nature and Efficiency of Neurotransmitter Exocytosis also Depend on Physicochemical Parameters
Authors: Amatore Christian , Arbault Stéphane , Guille Manon , Lemaître Frédéric
Published: June 2007

Exocytosis is an important biological process used by cells to deliver messengers or effectors to target cells with high spatial, quantitative, and kinetic precision. This process occurs by interaction and fusion of vesicles containing the (bio)chemical information with the cell membrane to release their contents into the surrounding medium. Because of its importance for life, this mechanism underlies many biological controlling factors, including different families of proteins and enzymes. Tremendous efforts have been made over the last decade toward their determination. However, in parallel, many studies have also shown that the physical and chemical characteristics of the exocytosis actors (vesicle, membrane, and extracellular medium) could directly affect the quantitative or kinetic features of secretion. The major pieces evidence for this influence, which have been reported in the literature, are reviewed herein. It demonstrates undoubtedly that pure biological aspects cannot be segregated from the physicochemical context of living mechanisms.
Liquid‐based endometrial cytology in the management of sonographically thickened endometrium
Authors: Buccoliero Anna M. , Gheri Chiara F. , Castiglione Francesca , Garbini Francesca , Fambrini Massimiliano , Bargelli Gianni , Barbetti Alfredo , Pappalardo Salvatore , Taddei Antonio , Boddi Vieri , Scarselli Gian F. , Marchionni Mauro , Taddei Gian L.
Published: June 2007

Liquid‐based cytology represents an opportunity to re‐evaluate endometrial cytology. We evaluated the accuracy of liquid‐based endometrial cytology as compared to biopsy in 670 women scheduled for histeroscopy because of thickened endometrium (>4 mm), as evaluated by transvaginal sonography. Endometrial biopsy detected pathology in 41 (6%) of cases (21 of which were adenocarcinomas). Cytologic study found pathology in 62 (9%) cases (19 of which were adenocarcinomas). Two hundred ninety‐one biopsies (43%) and 28 (4%) cytologies were inadequate. The sensitivity and the specificity were estimated, respectively, at 95% and 98%; the positive and negative predictive values were estimated, respectively, at 83% and 99%. Cytology provided sufficient material more often than biopsy (P < 0.01). We consider endometrial cytology an efficacious diagnostic opportunity. It could be usefully applied in association with transvaginal sonography. The combination of these procedures might reduce more invasive and expensive diagnostic procedures. Diagn. Cytopathol. 2007;35:398–402. © 2007 Wiley‐Liss, Inc.
Pseudoangiosarcomatous features in medullary thyroid carcinoma spindle‐cell variant. Report of a case studied by FNA and immunohistochemistry
Authors: Laforga Juan B. , Aranda F. Ignacio
Published: June 2007

We report a case of medullary thyroid carcinoma (MTC), spindle cell variant, which exhibited striking histological pseudovascular clefts and abortive lumina, closely mimicking an angiosarcoma. The patient is a 72‐yr‐old‐man who presented facial rash and a solid nodule in the right lobe of the thyroid gland. The fine‐needle aspiration (FNA) showed bloody background containing loosely groups of fusiform and plasmocytoid cells with coarse chromatin and eosinophilic granular cytoplasms. Microscopically, the tumor exhibited spindle‐cell pattern intermingled with a striking angiosarcoma‐like pattern characterized by the presence of abortive lumen and clefts containing erythrocytes. Dense hyaline extracellular amyloid was present. The tumor cells were strongly positive for cytokeratin, chromogranine‐A, synaptophysine, serotonin, calcitonin, and CEA. TTF‐1 was weakly positive. Stains for CD34 and CD31 were negative. This case illustrates that the spindle cell variant of MTC may exhibit an infrequent angiosarcoma‐like appearance which may be misdiagnosed as angiosarcoma. Diagn. Cytopathol. 2007;35:424‐428. © 2007 Wiley‐Liss, Inc.
ThinPrep Pap tests in patients with endometrial cancer: A histo‐cytological correlation
Authors: Zhou Jianhong , Tomashefski Joseph F. , Khiyami Amer
Published: June 2007

The aim of this retrospective study was to correlate cytological diagnoses of endometrial cancers in ThinPrep Pap tests with the histological diagnoses. ThinPrep specimens from 67 patients within 12 mo of the histological diagnosis of endometrial cancer were studied. Of this study sample, 89.6% had abnormal Pap tests. Abnormal Pap tests occurred in 96.8, 68.4, and 100% of patients with grades 1, 2, or 3 endometrial cancers, respectively. Of patients with endocervical involvement, 88.9% had positive or suspicious Pap tests, compared with 41.1% without endocervical involvement (LR = 7.85, P < 0.01). Of patients with ≥50% myometrial invasion, 78.9% had positive or suspicious Pap tests, compared with 34.8% with less than 50% invasion (LR = 10.97, P < 0.01). Positive or suspicious Pap tests were found in 59.5 and 32.1% of those with tumors ≥3 cm or <3cm, respectively (LR = 4.85, P < 0.05). Diagn. Cytopathol. 2007;35:448–453. © 2007 Wiley‐Liss, Inc.
Estimated cardiac vagal tone predicts fetal responses to mother's and stranger's voices
Authors: Smith Laura S. , Dmochowski Pawel A. , Muir Darwin W. , Kisilevsky Barbara S.
Published: June 2007

Heart rate responses of 84 near‐term fetuses to recorded female voices were examined in 166 trials of auditory stimulation. Each fetus was presented with a 2‐min recording of their mother's voice and a 2‐min recording of a female stranger's voice, in counterbalanced order, with a 10‐min rest period between trials. High frequency heart rate variability during a 2‐min baseline period was used to estimate cardiac vagal tone for each trial. Differential heart rate responses to familiar and unfamiliar voice recordings were observed during a 2‐min poststimulus period, only when estimated cardiac vagal tone was high. This finding suggests that vagal tone plays a moderating role in the cardiac responses of term fetuses to familiar and unfamiliar stimuli. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 543‐547, 2007.
Measuring salivary cortisol in studies of child development: Watch out—what goes in may not come out of saliva collection devices
Authors: Harmon Amanda G. , Hibel Leah C. , Rumyantseva Olga , Granger Douglas A.
Published: June 2007

Technical advances that enable the noninvasive measurement of biomarkers in saliva have spawned a generation of investigations that integrate biological variables into behavioral and developmental research. This study examines whether the collection of saliva, using common absorbent devices compromises the measurement of cortisol when saliva specimens have low sample volume. Within subjects (n = 20), saliva samples were prepared to experimentally represent a gradient of lower to higher sample volumes. One aliquot was immediately frozen (no treatment control) and the remaining aliquots were absorbed (“collected”) using one of three collection techniques employed in studies of child development (e.g., braided cotton dental rope, Salivette cotton pledget, or hydrocellulose microsponge). The sample volume recovered from each device relative to the initial volume available to be absorbed, and cortisol level recovered from each device relative to the untreated‐control condition were measured. Results reveal that for certain collection devices (1) the percent volume recovered is related to the initial volume available to be absorbed, (2) a substantial percentage of cortisol in saliva specimens can remain in absorbent material, and (3) the percent of cortisol recovered can be associated with the initial sample volume available to be absorbed. When research participants, such as young children, produce low volume saliva specimens, some absorbent devices may have the potential to introduce error variance in the measurement of salivary cortisol. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 495‐500, 2007.
Differential enhancement of neural and photoreceptor cell differentiation of cultured pineal cells by FGF‐1, IGF‐1, and EGF
Authors: Araki Masasuke , Suzuki Haruno , Layer Paul
Published: June 2007

There are several common features between the pineal organ and the lateral eye in their developmental and evolutionary aspects. The avian pineal is a photoendocrine organ that originates from the diencephalon roof and represents a transitional type between the photosensory organ of lower vertebrates and the endocrine gland of mammals. Previous cell culture studies have shown that embryonic avian pineal cells retain a wide spectrum of differentiative capacities, although little is known about the mechanisms involved in their fate determination. In the present study, we investigated the effects of various cell growth factors on the differentiation of photoreceptor and neural cell types using pineal cell cultures from quail embryos. The results show that IGF‐1 promotes differentiation of rhodopsin‐immunoreactive cells, but had no effect on neural cell differentiation. Simultaneous administration of EGF and IGF‐1 further enhanced differentiation of rhodopsin‐immunoreactive cells, although the mechanism of the synergistic effect is unknown. FGF‐1 did not stimulate proliferation of neural progenitor cells, but intensively promoted and maintained expression of a neural cell phenotype. FGF‐1 appeared to lead to the conversion from an epithelial (endocrinal) to a neuronal type. It also enhanced phenotypic expression of retinal ganglion cell markers but rather suppressed expression of an amacrine cell marker. These results indicate that growth factors are important regulatory cues for pineal cell differentiation and suggest that they play roles in determining the fate of the pineal organ and the eye. It can be speculated that the differences in environmental cues between the retina and pineal may result in the transition of the pineal primordium from a potentially ocular (retinal) organ to a photoendocrine organ. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007
EphA4 misexpression alters tonotopic projections in the auditory brainstem
Authors: Huffman Kelly J. , Cramer Karina S.
Published: June 2007

Auditory pathways contain orderly representations of frequency selectivity, which begin at the cochlea and are transmitted to the brainstem via topographically ordered axonal pathways. The mechanisms that establish these tonotopic maps are not known. Eph receptor tyrosine kinases and their ligands, the ephrins, have a demonstrated role in establishing topographic projections elsewhere in the brain, including the visual pathway. Here, we have examined the function of these proteins in the formation of auditory frequency maps. In birds, the first central auditory nucleus, n. magnocellularis (NM), projects tonotopically to n. laminaris (NL) on both sides of the brain. We previously showed that the Eph receptor EphA4 is expressed in a tonotopic gradient in the chick NL, with higher frequency regions showing greater expression than lower frequency regions. Here we misexpressed EphA4 in the developing auditory brainstem from embryonic day 2 (E2) through E10, when NM axons make synaptic contact with NL. We then evaluated topography along the frequency axis using both anterograde and retrograde labeling in both the ipsilateral and contralateral NM‐NL pathways. We found that after misexpression, NM regions project to a significantly broader proportion of NL than in control embryos, and that both the ipsilateral map and the contralateral map show this increased divergence. These results support a role for EphA4 in establishing tonotopic projections in the auditory system, and further suggest a general role for Eph family proteins in establishing topographic maps in the nervous system. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007
REREa/Atrophin‐2 interacts with histone deacetylase and Fgf8 signaling to regulate multiple processes of zebrafish development
Authors: Plaster Nikki , Sonntag Carmen , Schilling Thomas F. , Hammerschmidt Matthias
Published: June 2007

The transcriptional regulator RERE/Atrophin‐2 (RERE) is required for the normal patterning of the early vertebrate embryo, including the central nervous system, pharyngeal arches, and limbs. Consistent with a role as a transcriptional corepressor, RERE binds histone deacetylase 1 and 2 (HDAC1/2), and orphan nuclear receptors such as Tlx. Here, we identify the zebrafishbabyface(bab) as a mutant inrereaand show that it interacts genetically withfibroblast growth factor 8(fgf8). We suggest that this finding is largely due to its interactions with HDAC, because genetic or pharmacological disruptions of HDAC phenocopy many features of thebabmutant. Furthermore, removing the functions of either REREa or HDAC synergizes with loss of Fgf8 function to disrupt posterior mesoderm formation during somitogenesis, midbrain–hindbrain boundary maintenance, and pharyngeal cartilage development. Together, these results reveal novel in vivo roles for REREa in HDAC‐mediated regulation of Fgf signaling. We present a model for RERE‐dependent patterning in which tissue‐specific transcriptional repression, by means of an REREa‐HDAC complex, modulates growth factor signaling during embryogenesis. Developmental Dynamics 236:1891–1904, 2007. © 2007 Wiley‐Liss, Inc.
Transgenic analysis of the anterior eye‐specific enhancers of the zebrafish gelsolin‐like 1 (gsnl1) gene
Authors: Yoshikawa Shunichi , Norcom Evan , Nakamura Hisashi , Yee Richard W. , Zhao Xinping C.
Published: June 2007

The anterior segment of the eye includes such structures as the cornea, lens, iris, and ciliary body and is essential for many visual and physiological functions of the eye. The zebrafish gelsolin‐like 1 (gsnl1) gene encodes an actin regulatory protein and is expressed in the anterior segment of the eye. We report the transgenic analyses of the gsnl1 promoter and enhancer that are required for expression in the anterior segment of the eye. A 6.4‐kb genomic fragment upstream from the translation initiation site (ATG) was capable of driving green fluorescent protein (GFP) expression in transient transgenic embryos and stable transgenic adult fish, which mimics the endogenous gsnl1 expression. The GFP expression was localized in the corneal epithelium (CE) and the annular ligament (AL) at the iridocorneal angle. A unique enhancer for each of these two tissues was identified at 3.7‐kb upstream from the ATG. The 60‐bp AL and 25‐bp CE enhancers were separated by 100‐bp and functioned independently from each other. Deletion analysis indicated that the proximal promoter was located 1.6‐kb upstream from the ATG. Stable GFP transgenic lines were established for future studies of genetic regulation in the anterior segment of the fish eye. Developmental Dynamics 236:1929–1938, 2007. © 2007 Wiley‐Liss, Inc.
Expression of Frizzled5, Frizzled7, and Frizzled10 during early mouse development and interactions with canonical Wnt signaling
Authors: Kemp Caroline R. , Willems Erik , Wawrzak Danuta , Hendrickx Marijke , Agbor Agbor Terence , Leyns Luc
Published: June 2007

Wnt signaling has been shown to be important in the patterning of the gastrulating mouse embryo, especially in axis formation. To this date, there is no clear indication that the Wnt receptors, Frizzleds (Fzds), are involved in such early specification. Moreover, at the gastrulation stage, the only Fzd with a known characterized expression pattern is Fzd8, which is expressed in the anterior visceral endoderm (aVE) (Lu et al. [2004] Gene Expr Patterns 4:569–572). Following a real time RT‐PCR study to evaluate Fzd expression in the gastrulating embryo, we used whole‐mount in situ hybridization to reveal new expression domains for Fzd5, Fzd7, and Fzd10. Fzd5 is expressed in the aVE and Fzd7 expression is restricted to the epiblast of the gastrulating embryo. The expression pattern of Fzd10 in the primitive streak of the gastrula suggests it has a role in mesoderm induction. We also show that the purified, secreted forms of the extracellular cysteine‐rich domains (CRDs) of FZD5, Fzd7, and Fzd8 can antagonize Wnt3a‐induced β‐Catenin accumulation in L‐cells, whereas in mouse embryonic stem cells, these CRDs can inhibit spontaneous mesoderm formation and promote neural differentiation. Our data demonstrate that Fzd5, Fzd7, and Fzd10 are expressed in distinct domains of the gastrulating embryo, and that the CRDs of FZD5, Fzd7, and Fzd8 can regulate Wnts, indicating that Fzds interpret Wnt signals during embryonic mesoderm and neural induction. Developmental Dynamics 236:2011–2019, 2007. © 2007 Wiley‐Liss, Inc.
Lymphatic development in mouse small intestine
Authors: Kim Kyung Eun , Sung Hoon‐Ki , Koh Gou Young
Published: June 2007

Lymphatic vessels in the small intestine serve as essential conduits for the absorption and transport of lipids from the intestine to the thoracic duct. Although the morphology and function of the intestinal lymphatic vasculature are well known, little is known about the embryonic development of these vessels. In this study, we examined development of lymphatic and blood vasculatures in the intestinal tube during mouse embryonic development by immunostaining with recently discovered molecular markers for lymphatic endothelial cells: LYVE‐1, VEGFR3, Prox‐1, and podoplanin. Immature lymphatics became detectable in mesentery, but not in intestinal tube, around E13.5–E14.5, while organized lymphatic vessel plexuses and capillaries were observed in intestinal tube and villi around E17.5. These lymphatic plexuses and capillaries in the intestinal tube appeared to be formed through an active branching process associated with activation of VEGFR3 and involvement of LYVE‐1+ macrophages. Our data also reveal that the lymphatic vessels in the intestinal tube, unlike the blood vessels, have not originated from the mesoderm of intestine. All lymphatic vessels in the intestinal tube originated by extension of mesenteric lymphatic vessels through an active branching process. Although the formation of lymphatic vessels follows the formation of blood vessels in the intestine, a mature lymphatic vasculature is formed before birth. Together, our study reveals the temporal and spatial windows of intestinal lymphatic development during embryonic development in mouse. Developmental Dynamics 236: 2020–2025, 2007. © 2007 Wiley‐Liss, Inc.
Prochondrogenic signals induce a competence for Runx2 to activate hypertrophic chondrocyte gene expression
Authors: Kempf Hervé , Ionescu Andreia , Udager Aaron M. , Lassar Andrew B.
Published: June 2007

Whereas Runx2 is necessary for bone formation and cartilage hypertrophy, it is unclear why Runx2 induces markers of chondrocyte hypertrophy only in chondrocytes. We document that chondrocytes either contain a cofactor, which can be induced in somitic cells by prochondrogenic signals, that is necessary for Runx2 to induce chondrocyte hypertrophy or, alternatively, lack a repressor of this maturation program. Sequential Shh and bone morphogenetic protein (BMP) signals or forced expression of either Nkx3.2 or Sox9 (plus BMP signals) induces chondrogenesis in presomitic mesoderm and simultaneously induces a competence for Runx2 to activate the chondrocyte maturation program. The ability of either sequential Shh and BMP signals or retrovirus‐encoded Nkx3.2 or Sox9 to induce this competence correlates with their ability to activate chondrogenesis in various embryonic tissues. Consistent with these findings in embryonic tissues, we have found that cotransfected Runx2 and Smad1 are able to induce the expression of a reporter construct driven by the collagen X regulatory sequences in chondrocytes but not in fibroblasts. In contrast, both Runx2 and Smad1 are competent to activate reporters driven by either reiterated Runx or Smad binding sites, respectively, in both cell types. As Sox9 and Nkx3.2 have previously been shown to block chondrocyte maturation in vivo, our findings suggest that these transcription factors can, in addition, either induce the expression or activity of a factor in chondrocytes that is required for Runx2 to activate the chondrocyte maturation program, or alternatively that these transcription factors block the expression or activity of a repressor of this maturation program. Developmental Dynamics 236:1954–1962, 2007. © 2007 Wiley‐Liss, Inc.
Culture of Ciona intestinalis in closed systems
Authors: Joly Jean‐Stéphane , Kano Shungo , Matsuoka Terumi , Auger Helene , Hirayama Kazuko , Satoh Nori , Awazu Satoko , Legendre Laurent , Sasakura Yasunori
Published: June 2007

A virtual image showing ascidian Ciona intestinalis larvae swimming to "corals" located at the bottom of the picture. On top right is a tailbud embryo still in the chorion before hatching. Swimming larvae are carrying constructs driving the expression of green fluorescent proteins in epidermis. Larvae become juveniles through metamorphosis (lower right). Juveniles and adult neural complex pictures derive from a transgenic line with Ror‐b regulatory sequences, which drives yellow fluorescent protein expression at the top of endostyles in juveniles and at the margins of the so‐called ciliated funnels in neural complexes. The corals were reconstructed from details of two adult neural gland complexes artificially merged. Our ascidian facilities in closed‐systems contribute to the maintenance of such transgenic lines. See Joly et al., Developmental Dynamics 236:1832–1840.
Phosphane and Phosphite Unsymmetrically Disubstituted Diiron Complexes Related to the Fe‐Only Hydrogenase Active Site
Authors: Li Ping , Wang Mei , He Chengjiang , Liu Xiaoyang , Jin Kun , Sun Licheng
Published: June 2007

A series of unsymmetrically disubstituted diiron complexes [(μ‐pdt){Fe(CO)2L1}{Fe(CO)2L2}] [pdt = 1,3‐propanedithiolato; L1 = PMe3, L2 = PMe2Ph, 4; PPh3, 5; PCy3, 6; P(OEt)3, 7; L1 = PMe2Ph, L2 = PPh3, 8; P(OEt)3, 9; L1 = P(OEt)3, L2 = PPh3, 10; PCy3, 11] and [(μ‐edt){Fe(CO)2PMe3}{Fe(CO)2PPh3}] (edt = 1,2‐ethanedithiolato, 12) were prepared by means of stepwise CO displacements of [(μ‐pdt)Fe2(CO)6] and [(μ‐edt)Fe2(CO)6] by different tertiary phosphane and phosphite ligands. The interconversion of the irondithiacyclohexane ring and the rotation of the [Fe(CO)2PR3] subunit were studied using by variable‐temperature 31P{1H} NMR spectroscopy of 4, 6 and 12 in solution. The molecular structures of 4–6, 8–10 and 12 show that complexes 4–6, 8, 9 and 12 possess an apical/basal coordination mode and complex 10 has an apical/apical conformation. The X‐ray analyses indicate that the PMe2Ph ligand in the apical position of the starting complex [(μ‐pdt){Fe(CO)3}{FeCO2(PMe2Ph)}] rotates to the basal position on conversion to the products 8 and 9. Cyclic voltammograms of 4–11 were studied both under argon and CO. The influences of the phosphane and phosphite ligands on the redox properties of the unsymmetrically disubstituted diiron complexes are discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)