bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase I Study of Bryostatin 1 and Gemcitabine
Authors: El-Rayes Basil F. , Gadgeel Shirish , Shields Anthony F. , Manza Stephanie , Lorusso Patricia , Philip Philip A.
Published: December 2006

Purpose: Bryostatin 1 is a macrocyclic lactone with protein kinase C inhibitory activity. Gemcitabine is a nucleotide analogue with a broad spectrum of anticancer activity. Bryostatin 1 enhanced the activity of antitumor agents including gemcitabine in preclinical models. The primary objective of this phase I study was to determine the recommended doses for phase II trials of bryostatin 1 and gemcitabine.

Experimental Design: Eligible patients had histologic or cytologic diagnosis of nonhematologic cancer refractory to conventional treatment; life expectancy of >3 months; normal renal, hepatic, and bone marrow function; and a Southwest Oncology Group performance status of 0 to 2. Gemcitabine was administered i.v. over 30 minutes and was followed by bryostatin 1 by i.v. infusion over 24 hours on days 1, 8, and 15 of a 28-day cycle. Bryostatin 1 (μg/m2) and gemcitabine (mg/m2) doses were escalated as follows: 25/600, 25/800, 25/1,000, 30/1,000, 35/1,000, and 45/1,000, respectively.

Results: Thirty-six patients (mean age, 57 years; male/female 15:21) were treated. The median number of treatment cycles per patient was 3 (range, 0-24). Four patients developed dose limiting toxicities: myalgia, 2; myelosuppression, 1; and elevation of serum alanine aminotransferase levels, 1. Ten grade 3 toxicities were observed (anemia, 2; neutropenia, 5; thrombocytopenia, 3). No treatment-related death was seen. The recommended doses for phase II trials for bryostatin 1 and gemcitabine were 35 μg/m2 and 1,000 mg/m2, respectively. Two heavily pretreated patients with breast and colon cancer experienced partial responses lasting 22 and 8 months, respectively. Eight patients had stable disease.

Conclusion: The combination of bryostatin 1 and gemcitabine seemed to be well tolerated with limited grade 3 toxicity. The recommended dose of bryostatin 1 in combination with full doses of gemcitabine was 35 μg/m2.
Antiestrogenic Glyceollins Suppress Human Breast and Ovarian Carcinoma Tumorigenesis
Authors: Salvo Virgilo A. , Boué Stephen M. , Fonseca Juan P. , Elliott Steven , Corbitt Cynthia , Collins-Burow Bridgette M. , Curiel Tyler J. , Srivastav Sudesh K. , Shih Betty Y. , Carter-Wientjes Carol , Wood Charles E. , Erhardt Paul W. , Beckman Barbara S. , McLachlan John A. , Cleveland Thomas E. , Burow Matthew E.
Published: December 2006

Purpose: We have identified the phytoalexin compounds glyceollins I, II, and III, which exhibit marked antiestrogenic effects on estrogen receptor function and estrogen-dependent tumor growth in vivo. The purpose of this study was to investigate the interactions among the induced soy phytoalexins glyceollins I, II, and III on the growth of estrogen-dependent MCF-7 breast cancer and BG-1 ovarian cancer cells implanted in ovariectomized athymic mice.

Experimental Design: Four treatment groups for each cell line were used: vehicle control, 20 mg/kg/mouse/d glyceollin mixture injection, 0.72 mg estradiol (E2) implant, and E2 implant + 20 mg/kg/mouse/d glyceollin injection.

Results: Treatment with glyceollin suppressed E2-stimulated tumor growth of MCF-7 cells (−53.4%) and BG-1 cells (−73.1%) in ovariectomized athymic mice. These tumor-inhibiting effects corresponded with significantly lower E2-induced progesterone receptor expression in the tumors. In contrast to tamoxifen, the glyceollins had no estrogen-agonist effects on uterine morphology and partially antagonized the uterotropic effects of estrogen.

Conclusions: These findings identify glyceollins as antiestrogenic agents that may be useful in the prevention or treatment of breast and ovarian carcinoma.
Tumor-Selective Gene Expression in a Hepatic Metastasis Model after Locoregional Delivery of a Replication-Competent Retrovirus Vector
Authors: Hiraoka Kei , Kimura Takahiro , Logg Christopher R. , Kasahara Noriyuki
Published: December 2006

Purpose: Replication-competent retrovirus (RCR) vectors have been shown to achieve highly efficient and tumor-restricted replicative spread and gene transfer in vivo after direct intratumoral injection in a variety of primary cancer models. In this setting, the intrinsic inability of retroviruses to infect postmitotic normal cells, combined with their unique ability to persist through stable integration, allow further transduction of ectopic tumor foci as the infected cancer cells migrate. However, i.v. delivery of RCR vectors has never been tested previously, particularly in an immunocompetent tumor model.

Experimental Design: We combined optical imaging, flow cytometry, and molecular analysis to monitor RCR vector spread after administration via locoregional infusion in a hepatic metastasis model of colorectal cancer.

Results: Robust RCR replication was first confirmed in both human WiDr and murine CT26 colorectal cancer cells in vitro, with transduction levels reaching >90% in <12 days after virus inoculation at multiplicities of infection of 0.01 to 0.1. In vivo, infusion of RCR supernatant into the portal circulation resulted in progressive and significant transduction of multifocal intrahepatic CT26 tumors in syngeneic mice, averaging about 30% but with up to 60% transduction in some tumors within 4 weeks. However, immunohistochemistry and quantitative PCR analysis showed no evidence of RCR spread to adjacent normal liver or to any other normal tissues.

Conclusions: Our results thus show that locoregional infusion of RCR vectors can be used to deliver therapeutic genes selectively to tumor cells in the liver while sparing normal hepatocytes and without dissemination to extrahepatic normal tissues.
Second Hand Smoke Exposure and Survival in Early-Stage Non–Small-Cell Lung Cancer Patients
Authors: Zhou Wei , Heist Rebecca S. , Liu Geoffrey , Asomaning Kofi , Miller David P. , Neuberg Donna S. , Wain John C. , Lynch Thomas J. , Christiani David C.
Published: December 2006

Purpose: Second hand smoke (SHS) exposure is associated with higher risk of lung cancer. However, the role of SHS in lung cancer survival is not clear.

Experimental Design: We examined the association between self-reported SHS exposure before diagnosis and overall survival and recurrence-free survival in 393 early-stage non–small-cell lung cancer patients. SHS exposure was analyzed by both duration and location of exposure using log-rank test and Cox proportional hazard models, adjusting for covariates including pack-years of smoking.

Results: The median follow-up time was 66 months (range, 0.2-140 months). There were 135 recurrences and 213 deaths. The 5-year overall survival rates were 71% [95% confidence interval (95% CI), 62-81%], 61% (51-72%), 49% (38-60%), and 47% (37-58%), respectively, for patients with the lowest to highest quartile of SHS exposure durations (P < 0.001, log-rank test), with the adjusted hazard ratio (AHR) of 1.57 (95% CI, 1.02-2.41) for the highest versus lowest quartile of SHS exposure durations (Ptrend = 0.04). For different SHS exposure locations, a stronger association was found for SHS exposure at work (AHR of the highest versus lowest quartile, 1.71; 95% CI, 1.12-2.61; Ptrend = 0.03) than for exposure at home (AHR, 1.26; 95% CI, 0.86-1.86; Ptrend = 0.20) or leisure places (AHR, 1.28; 95% CI, 0.83-1.95; Ptrend = 0.16). Similar associations were observed when SHS exposure durations were dichotomized into two or three groups and between SHS exposure and recurrence-free survival.

Conclusions: SHS exposure is associated with worse survival in early-stage non–small-cell lung cancer patients, especially for SHS exposure at the work.
Molecular and Biochemical Analyses of Platelet-Derived Growth Factor Receptor (PDGFR) B, PDGFRA, and KIT Receptors in Chordomas
Authors: Tamborini Elena , Miselli Francesca , Negri Tiziana , Lagonigro M. Stefania , Staurengo Samantha , Dagrada Gian Paolo , Stacchiotti Silvia , Pastore Elisa , Gronchi Alessandro , Perrone Federica , Carbone Antonino , Pierotti Marco A. , Casali Paolo G. , Pilotti Silvana
Published: December 2006

Purpose: We have previously shown the presence of an activated platelet-derived growth factor (PDGF) receptor (PDGFR) B and its ligand PDGFB in a limited number of patients with clinical and radiological responses to imatinib mesylate treatment. This article describes the results of comprehensive molecular/biochemical analyses of the three receptors targeted by the drug (PDGFRB, PDGFRA, and KIT) in a series of 31 chordoma patients.

Experimental Design: The presence and activation status of PDGFRB, PDGFRA, and KIT receptors were investigated by means of immunoprecipitation and Western blot analyses complemented by immunohistochemistry, their expression level was analyzed by means of real-time PCR, and the occurrence of activating point mutations was investigated by means of cDNA sequencing. The PDGFB, PDGFA, and stem cell factor cognate ligands were investigated by reverse transcription-PCR, and gene status was assessed by fluorescence in situ hybridization.

Results: The results show that PDGFRB was highly expressed and phosphorylated, whereas PDGFRA and KIT were less expressed but phosphorylated and thus activated. These findings, together with the absence of gain-of-function mutations and the presence of the cognate ligands, strongly support the hypothesis that the activation mechanism is the autocrine/paracrine loop. No role seems to be played by gene amplification.

Conclusions: In the light of our findings, the clinical benefit observed in chordoma patients treated with imatinib seems to be attributable to the switching off of all three receptors.
Expression of Matrix Metalloproteinase-7 on Cancer Cells and Tissue Endothelial Cells in Renal Cell Carcinoma: Prognostic Implications and Clinical Significance for Invasion and Metastasis
Authors: Miyata Yasuyoshi , Iwata Takahisa , Ohba Kojiro , Kanda Shigeru , Nishikido Masaharu , Kanetake Hiroshi
Published: December 2006

Purpose: The expression of matrix metalloproteinase-7 (MMP-7) correlates with the malignant potential of various tumors and patient survival. We investigated the clinical and prognostic significance of MMP-7 expression in cancer cells and endothelial cells in human renal cell carcinoma (RCC).

Experimental Design: We reviewed tissue samples of 156 patients with RCC who had undergone radical operation. MMP-7 expression was examined by immunohistochemistry. Sections containing MMP-7-positive vessels were also stained for CD34. The density of MMP-7-positive vessels was determined by a computer-aided image analysis system. Multivariate analysis was done to assess relevant variables for invasion, metastasis, and cause-specific survival.

Results: The proportion of MMP-7-expressing tumor cells were significantly higher (P < 0.001) than that of normal cells. MMP-7-positive vessels were considered blood vessels based on staining for CD34, and their density was increased in tumor areas. The proportion of MMP-7-expressing cancer cells and density of MMP-7-positive vessels correlated with grade, pathologic tumor stage, and metastasis. Multivariate analysis showed that MMP-7 expression on cancer cells correlated with pathologic tumor stage only, whereas MMP-7-positive vessel density correlated with metastasis only. The elevated status of MMP-7 in cancer tissues was an independent predictor for cause-specific survival (odds ratio, 8.61; P = 0.040) by multivariate analysis.

Conclusions: Our results showed that MMP-7 influences tumor progression by regulating invasion and angiogenesis. Multivariate analysis showed that MMP-7 status of cancer tissues was strong predictor of poor prognosis. Our results suggest that MMP-7 targeting treatment may be a potential target against RCC.
Genetic and Epigenetic Analysis of CHEK2 in Sporadic Breast, Colon, and Ovarian Cancers
Authors: Williams Louise H. , Choong David , Johnson Sandra A. , Campbell Ian G.
Published: December 2006

Purpose: Germ-line variants in CHEK2 have been associated with increased breast, thyroid, prostate, kidney, and colorectal cancer risk; however, the prevalence of somatic inactivation of CHEK2 in common cancer types is less clear. The aim of this study was to determine if somatic mutation and/or epigenetic modification play a role in development of sporadic breast, colon, or ovarian cancers.

Experimental Design: We undertook combined genetic and epigenetic analysis of CHEK2 in sporadic primary breast, ovarian, and colon tumors [all exhibiting chromosome 22q loss of heterozygosity (LOH)] and cancer cell lines. Expression of Chk2 was assessed by immunohistochemistry in 119 ovarian tumors.

Results: Two novel germ-line variants were identified; however, none of the primary tumors harbored somatic mutations. Two CpG clusters previously implicated in CHEK2 silencing were investigated for evidence of hypermethylation. No methylation was detected at the distal CpG island. The proximal CpG cluster was methylated in all tumor and normal DNA, suggesting that this might not represent a true CpG island and is not relevant in the control of CHEK2 expression. Twenty-three percent of ovarian tumors were negative for Chk2 protein by immunohistochemistry, but there was no significant correlation between LOH across the CHEK2 locus and intensity of Chk2 staining (P = 0.12).

Conclusions: LOH across the CHEK2 locus is common in sporadic breast, ovarian, and colorectal cancers, but point mutation or epigenetic inactivation of the retained allele is uncommon. Loss of Chk2 protein in ovarian cancer was not associated with allelic status, suggesting that inactivation does not occur as a consequence of haploinsufficiency.
Pathways Targeting Tumor Lymphangiogenesis
Authors: Wissmann Christoph , Detmar Michael
Published: December 2006

Tumor metastasis to sentinel lymph nodes represents the first step of tumor dissemination in most human cancers and serves as a major prognostic indicator for disease progression. Recent studies have revealed that tumors can actively induce the formation of lymphatic vessels, and that tumor lymphangiogenesis is correlated with lymph node metastasis in experimental cancer models and in several types of human cancers. Metastatic tumor cells may continue to promote lymphatic vessel growth even after their metastasis to sentinel lymph nodes, likely promoting further cancer spread. Vascular endothelial growth factor-C (VEGF-C) and VEGF-D were the first specific lymphangiogenesis factors identified, acting predominantly via VEGF receptor-3 (VEGFR-3) that is expressed by lymphatic endothelial cells, and a large number of clinical studies have shown a correlation between tumor expression of VEGF-C or VEGF-D and lymph node metastasis. VEGFR-3 activation promotes lymphatic endothelial cell proliferation, migration, and survival via the extracellular signal-regulated kinase 1/2, the phosphatidylinositol 3-kinase/AKT, and the c-Jun NH2-terminal kinase 1/2 pathways. Additional tumor lymphangiogenesis factors have been recently identified, including VEGF-A. Importantly, blockade of the VEGFR-3 pathway by specific antibodies, by soluble receptor constructs, and by small molecule kinase inhibitors efficiently inhibits experimental tumor lymphangiogenesis and metastasis and might also represent a novel therapeutic avenue for the treatment of human cancers.
Free DNA and Carcinoembryonic Antigen Serum Levels: An Important Combination for Diagnosis of Colorectal Cancer
Authors: Flamini Emanuela , Mercatali Laura , Nanni Oriana , Calistri Daniele , Nunziatini Roberta , Zoli Wainer , Rosetti Paola , Gardini Nice , Lattuneddu Arturo , Verdecchia Giorgio Maria , Amadori Dino
Published: December 2006

Purpose: The identification of new molecular markers for the early detection of colorectal cancer has become an important objective. We compared the sensitivity and specificity of free circulating DNA with that of the more conventional carcinoembryonic antigen (CEA) and evaluated the two markers in combination.

Experimental Design: The study was carried out on 75 healthy donors and 75 colorectal cancer patients. Free DNA was determined in serum with quantitative PCR analysis. The diagnostic accuracy of each assay was calculated using receiver operating characteristic (ROC) curves. The diagnostic relevance of the two-marker combination was analyzed by the logistic regression model.

Results: Median free DNA concentration was ∼5-fold higher in patients than in healthy donors (P < 0.001). The area under the ROC curve was 0.86, and when 12.5 ng/mL was used as cutoff, 81.3% sensitivity and 73.3% specificity were observed for the overall series. As CEA and free DNA provided independent diagnostic information, they were also considered in combination. ROC curve analysis of the combined CEA and free DNA algorithms showed a higher diagnostic capacity (area under the ROC curve, 0.92) than that of markers considered singly, with 84% sensitivity and 88% specificity.

Conclusions: Free circulating DNA, especially when used in combination with CEA, represents a potentially useful tool for the diagnosis of early-stage colorectal cancer.
The Evolution of Sex Chromosomes and Sex Determination in Vertebrates and the Key Role of DMRT1
Authors: Ferguson-Smith M.
Published: December 2006

Mechanisms of vertebrate sex determination are reviewed in the light of what is known about the origin and evolution of sex chromosomes. All vertebrate males have testes that are similar in anatomy and in spermatogenesis. Despite a variety of sex chromosome systems, the same cascade of genes operate in the differentiation of testes and male genitalia. Only the primary signal or switch that initiates the cascade may be different. Genetic sex determination (GSD) occurs in most species, although temperature-dependent sex determination (TSD) is the switch in some reptiles without GSD. SRY is the genetic switch in eutherians (placental mammals) and DMRT1 may have that function in birds and at least one species of fish. The switch in all other groups of vertebrates with either male or female heterogamety is unknown. DMRT1 is an ancient sex determining gene, found first in invertebrates, and is one of several genes expressed in higher levels in the vertebrate embryonic testis than in the embryonic ovary. It is singled out in this review because of its likely key role in sex determination both in birds and in reptiles with TSD. DMRT1 is one of the few sex genes that have been mapped in representative species of fish, turtles, crocodiles, amphibians, birds and mammals. Greater effort in comparative mapping, sequencing and expression studies is required to discover the other primary switch genes in vertebrates and to answer questions about their evolution.
Involvement of Homeobox Genes in Mammalian Sexual Development
Authors: Svingen T. , Koopman P.
Published: December 2006

In eutherian mammals, sexual development hinges on the differentiation of the gonadal primordia into either testes or ovaries, in turn determined by the activity of the Y-linked gene Sry. Organogenesis of the gonads requires input from a complex network of morphogenetic signals, many of which are still uncharacterised. Homeobox genes are known to play important roles in embryo morphogenesis and organogenesis in a number of systems. Here, we review current data relating to possible roles of the extended homeobox gene family on gonad development, sex-specific morphogenesis and gametogenesis, and speculate that these genes may play a broader role in these processes than is currently suspected.
Extended Pedigree with Multiple Cases of XX Sex Reversal in the Absence of SRY and of a Mutation at the SOX9 Locus
Authors: Temel S.G. , Gulten T. , Yakut T. , Saglam H. , Kilic N. , Bausch E. , Jin W.J. , Leipoldt M. , Scherer G.
Published: December 2006

It is well established that testicular differentiation of the human embryonic gonad depends on the action of the Y-chromosomal gene SRY. However, exceptional cases such as SRY-negative cases of 46,XX testicular disorder of sexual development (DSD), and of 46,XX ovotesticular DSD document that testicular tissue can develop in the absence of the SRY gene. These SRY-negative XX sex reversal cases are very rare and usually sporadic, but a few familial cases have been reported. We present a large, consanguineous family with nine affected individuals with phenotypes ranging from 46,XX testicular DSD to 46,XX ovotesticular DSD, with predominance of male characteristics. Absence of SRY in peripheral blood was documented by fluorescence in situ hybridization (FISH) and PCR analysis in all nine affected individuals, and by FISH analysis on gonadal sections with testicular tissue in four affected individuals. By quantitative PCR, a duplication of the SOX9 gene was excluded. In addition, as linkage analysis showed that the nine affected members of the family do not share a common SOX9 haplotype, any mutation at the SOX9 locus could be ruled out. Together, these findings implicate a mutation at a sex-determining locus other than SRY and SOX9 as the cause for the XX sex reversal trait in this family.
Familial Translocation t(1;9) Associated with Macromastia: Molecular Cloning of the Breakpoints
Authors: Wieacker P. , Apeshiotis N. , Jakubiczka S. , Volleth M. , Wieland I.
Published: December 2006

A familial reciprocal translocation associated with severe macromastia has been characterized by molecular cytogenetic and molecular analysis. Cloning of the translocation breakpoints revealed that no known gene has been disrupted by this translocation. Therefore, a position effect compromising the regulation of a still to be identified gene in the vicinity of the breakpoints can be assumed.
mRNA Expression Analysis and the Molecular Basis of Neonatal Testis Defects in Dmrt1 Mutant Mice
Authors: Fahrioglu U. , Murphy M.W. , Zarkower D. , Bardwell V.J.
Published: December 2006

Transcriptional regulators containing the DM domain DNA binding motif have been found to control sexual differentiation in a diverse group of metazoan animals including vertebrates, insects, and nematodes, suggesting that these proteins may comprise a very ancient group of sexual regulators. Dmrt1, 1 of 7 mammalian DM domain genes, is essential for several aspects of testicular differentiation in mice. The Dmrt1 mutant phenotype becomes apparent shortly after birth, and culminates in severe testicular dysgenesis. To better understand the roles of Dmrt1 in testicular development we have performed a more detailed analysis of its mutant phenotypes, and we have used mRNA expression profiling to identify genes misregulated in the neonatal Dmrt1 mutant testis. We find that Dmrt1 mutant germ cells fail to undergo several of the normal postnatal events of germ cell development, including radial movement, mitotic proliferation, differentiation into spermatogonia, and initiation of meiosis, and they die by P14. During this period Dmrt1 mutant Sertoli cells fail to polarize and form tight junctions, and fail to cease proliferation, eventually filling the seminiferous tubules. Expression profiling at P1 and P2 in Dmrt1 mutant testes indicates defects in several important testicular signaling pathways (Gdnf, retinoic acid, TGFβ, FSH), and detects elevated expression of the pluripotency marker Stella/Dppa3/Pgc7, providing insight into the molecular basis of Dmrt1 testis defects. This work also identifies a number of new candidate testicular regulators for further investigation.
A Diploid-Triploid (60,XX/90,XXY) Intersex in a Holstein Heifer
Authors: Meinecke B. , Drögemüller C. , Kuiper H. , Bürstel D. , Wohlsein P. , Ebeling S. , Wehrend A. , Meinecke-Tillmann S.
Published: December 2006

The diploid/triploid (60,XX/90,XXY) condition in Bos taurus is very rare and only three cases have been published previously. The present animal exhibited an aplastic vulva, penis and clitoris agenesis, a male-like urethra located in a pseudoprepuce opening between the mammary complexes and a well developed M. rectipeninus. A normal (60,XX) female karyotype was detected in lymphocyte cultures whereas uterus and tendon cells revealed a 60,XX/90,XXY mixoploidy. Quantification of X and Y chromosome-specific sequences using RT-PCR revealed extraordinary high Y chromosome equivalents in the sample recovered from the male-like transformed vestibulum vaginae suggesting a causative relationship. The pathogenesis of the missing clitoris and penis, which is contrasted by the concomitant presence of a well developed M. rectipeninus, remains difficult to explain. A chimeric origin is suggested despite the fact that microsatellite analysis of the animal’s blood cells displayed no un- usual allele accumulation.
Testosterone Stimulates Mounting Behavior and Arginine Vasotocin Expression in the Brain of both Sexual and Unisexual Whiptail Lizards
Authors: Hillsman K.D. , Sanderson N.S. , Crews D.
Published: December 2006

In nonmammalian vertebrates the abundance of arginine vasotocin (AVT) neurons in the brain is sexually dimorphic, a pattern that is modulated by testicular androgen. This peptide is thought to be involved in the control of male-typical mounting behaviors. The all-female desert-grasslands whiptail (Cnemidophorus uniparens) reproduces by obligate parthenogenesis and in nature no males exist, but eggs treated with aromatase inhibitor hatch into individuals (called virago C. uniparens) having testes, accessory sex structures, high circulating concentrations of androgens, and exhibiting only male-like copulatory behavior. To examine the ‘sexual’ dimorphism of AVT-containing neurons in these animals, we compared AVT immunoreactivity in gonadectomized control and virago C. uniparens, with that of gonadectomized male and female Cnemidophorus inornatus, a sexual species that is the maternal ancestor to the parthenogenetic species. Mounting behavior is elicited in both species and both sexes by testosterone, and it was predicted that the distribution and abundance of AVT cell bodies and fibers would reflect the propensity of males and females of the two species to display male-typical copulatory behavior. Since both this propensity and AVT abundance are controlled by androgens, we compared testosterone-implanted and control animals within each group. Testosterone treatment generally increased AVT abundance, except in lab-reared parthenoforms, in which testosterone treatment was the least effective in inducing male-like copulatory behavior.
Circulating ICAM-1 and VCAM-1 Levels in Patients with Obstructive Sleep Apnea Syndrome
Authors: Ursavaş Ahmet , Karadağ Mehmet , Rodoplu Erkan , Yılmaztepe Arzu , Oral Haluk Barbaros , Gözü R. Oktay
Published: December 2006

Background: Obstructive sleep apnea syndrome (OSAS)-induced hypoxic stress modulates circulating inflammatory mediators causing accelerated atherogenesis. Objectives: We hypothesized that OSAS-induced hypoxia might result in cardiovascular disease due to increased expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the endothelial surface. Methods: Thirty-nine subjects with moderate-to-severe OSAS and 34 non-apneic controls matched for age, gender, body mass index (BMI), smoking history, and cardiovascular disease were included in this prospective study. Overnight polysomnography was performed. Circulating ICAM-1 and VCAM-1 levels in the serum were measured by enzyme-linked immunosorbent assay. Results: Circulating levels of both ICAM-1 (480.1 ± 216.7 vs. 303.4 ± 98.6 ng/ml, p < 0.0001) and VCAM-1 (1,156.6 ± 79.8 vs. 878.8 ± 71.1 ng/ml, p = 0.002) were significantly increased in the OSAS group compared to the control group. For an ICAM-1 cutoff level of 375 ng/ml, predictive sensitivity and specificity for OSAS were 69.2% (95% confidence interval, CI: 52.4–83.0%) and 82.4% (95% CI: 65.5–93.2%), respectively. For a VCAM-1 cutoff level of 859 ng/ml, predictive sensitivity and specificity for OSAS were 74.4% (95% CI: 57.9–86.9%) and 64.7% (95% CI: 46.5–80.2%), respectively. There was a significant positive correlation between circulating levels of ICAM-1 and ln of AHI (r = 0.276, p = 0.018). Multiple logistic regression analyses showed that OSAS was associated with high ICAM-1 and high VCAM-1 levels independent of age, gender, BMI, smoking status and cardiovascular disease. Conclusion: We conclude that OSAS can independently increase circulating levels of adhesion molecules.
Breathing Pattern Adopted by Children with Cystic Fibrosis with Mild to Moderate Pulmonary Impairment during Exercise
Authors: Keochkerian David , Chlif Mehdi , Delanaud Stéphane , Gauthier Rémi , Maingourd Yves , Ahmaidi Said
Published: December 2006

Background: It is well known that severe lung impairment in cystic fibrosis (CF) may compromise respiratory muscle function at rest. Even though patients with CF and severe obstructive lung disease exhibit an abnormal breathing pattern during exercise (due to expiratory flow limitation), patients with CF and normal lung function reportedly have a normal breathing pattern. Objectives: The aim of the study was to assess the precise characteristics of the ventilatory pattern adopted during exercise by children with CF and mild to moderate lung disease. Methods: Nine children diagnosed as having mild to moderate CF and 9 healthy children with a similar age distribution participated in this study. Both groups performed a continuous incremental cycling protocol. Breathing and timing components were assessed during exercise. Results: Differences in the breathing pattern between children with CF and controls during exercise are illustrated in Hey plot which described a rapid shallow breathing pattern in children with CF. During exercise, children with CF showed a significantly lower mean inspiratory flow than healthy children (p < 0.001), whereas the mean expiratory flow was higher (p < 0.001). Children with CF also showed a significant increase in the end-tidal carbon dioxide pressure, which may indicate the emergence of hypercapnia. Conclusions: During exercise, children with CF (even those not suffering from advanced disease) showed signs of rapid, shallow breathing and an increase in the ventilatory response. This was essentially due to an increase in the mean inspiratory flow, which in turn suggests an expiratory flow limitation. The children were also predisposed to hypercapnia.
Evaluation of Auditory and Visual Feedback on Task Performance in a Virtual Assembly Environment
Authors: Zhang Ying , Fernando Terrence , Xiao Hannan , Travis Adrian R. L
Published: December 2006

This paper presents the creation of an assembly simulation environment with multisensory feedback (auditory and visual), and the evaluation of the effects of auditory and visual feedback on the task performance in the context of assembly simulation in a virtual environment (VE). This VE experimental system platform brings together complex technologies such as constraint-based assembly simulation, optical motion tracking technology, and real time 3D sound generation technology around a virtual reality workbench and a common software platform. A peg-in-a-hole and a Sener electronic box assembly task have been used as the task cases to conduct the human factor experiment, using sixteen participants. Both objective performance data (i.e., task completion time, TCT; and human performance error rate, HPER) and subjective opinions (i.e., questionnaires) on the utilization of auditory and visual feedback in a virtual assembly environment (VAE) have been gathered from the experiment. Results showed that the introduction of auditory and/or visual feedback into VAE did improve the assembly task performance. They also indicated that integrated feedback (auditory plus visual) offered better assembly task performance than either feedback used in isolation. Most participants preferred integrated feedback to either individual feedback (auditory or visual) or no feedback. The participants' comments demonstrated that nonrealistic or inappropriate feedback had a negative effect on the task performance, and easily made them frustrated.
Three Levels of Metric for Evaluating Wayfinding
Authors: Ruddle Roy A , Lessels Simon
Published: December 2006

Three levels of virtual environment (VE) metric are proposed, based on: (1) users' task performance (time taken, distance traveled, and number of errors made), (2) physical behavior (locomotion, looking around, and time and error classification), and (3) decision making (i.e., cognitive) rationale (think aloud, interview, and questionnaire). Examples of the use of these metrics are drawn from a detailed review of research into VE wayfinding. A case study from research into the fidelity that is required for efficient VE wayfinding is presented, showing the unsuitability in some circumstances of common metrics of task performance such as time and distance, and the benefits to be gained by making fine-grained analyses of users' behavior. Taken as a whole, the paper highlights the range of techniques that have been successfully used to evaluate wayfinding and explains in detail how some of these techniques may be applied.
The Usability of Collaborative Virtual Environments and Methods for the Analysis of Interaction
Authors: Schroeder Ralph , Heldal Ilona , Tromp Jolanda
Published: December 2006

This paper describes two methods for analyzing interactions in collaborative virtual environments (CVEs): one whereby quantitative data are captured, interaction is categorized into a number of activities, and statistical analysis can be performed on frequencies and sequences of events. The other is based on the transcription of individual fragments of interaction, which are analyzed in terms of their key dynamics. The two methods each have their strengths and weaknesses, especially in terms of generalizability and the lessons we can derive from them. Both also point to different problems that need to be addressed in methods for analyzing interaction—such analysis being, in turn, a precondition for improving the usability of CVEs. The paper concludes with an argument for a combination of the two methods, and some reflections about the relationship between the analysis of interaction and the usability of CVEs.
The Place Probe: Exploring a Sense of Place in Real and Virtual Environments
Authors: Benyon David , Smyth Michael , O'Neill Shaleph , McCall Rod , Carroll Fiona
Published: December 2006

This paper describes the design, application, and refinement of a qualitative tool designed to study sense of place. The Place Probe incorporates a range of stimuli and techniques aimed at articulating a person's sense of place. It has been developed, used, and undergone three revisions. The paper describes the background to the choice of measures that were included in the Place Probe and describes its application in both a physical place and a virtual representation of that place. This enables a comparison of the experiences. An analysis of the results reveals a similarity of reported experience, however the extremes experienced in the physical place were less pronounced in the virtual representation. The Place Probe has been refined in light of the results of the empirical work and now incorporates both qualitative and quantitative data on the experience of place.
Virtual Fitness: Stimulating Exercise Behavior through Media Technology
Authors: IJsselsteijn W. A , Kort Y. A. W. de , Westerink J , Jager M. de , Bonants R
Published: December 2006

The current paper describes research that is aimed at elucidating our understanding of media technology factors that may help users of exercise equipment to stay motivated for doing regular workouts. In particular, we investigated the effects of immersion and coaching by a virtual agent on intrinsic motivation and the sense of presence of participants cycling on a stationary home exercise bike. A basic two-by-two within-subjects experimental design was employed whereby participants were presented with a virtual racetrack with two levels of immersion (high vs. low) and two levels of a virtual coach (with vs. without). Results indicate a clear positive effect of immersion on both motivation and presence. The virtual coach significantly lowered the perceived control and pressure/tension dimensions of intrinsic motivation, but did not affect the enjoyment dimension. The presence of the virtual coach also reduced negative effects associated with VEs, such as feeling dizzy or nauseated.
A Longitudinal Study of Task Performance, Head Movements, Subjective Report, Simulator Sickness, and Transformed Social Interaction in Collaborative Virtual Environments
Authors: Bailenson Jeremy N , Yee Nick
Published: December 2006

Empirical research on human behavior in collaborative virtual environments (CVEs) is in its infancy. Historically, one of the more valuable tools social scientists have used to evaluate new forms of media is longitudinal studies that examine user behavior over an extended period of time. In the current study, three triads of participants came to the lab for 15 sessions over a ten week period to collaborate for approximately 45 minutes per session. We examined nonverbal behavior, task performance on verbal tasks, and subjective ratings of presence, copresence, simulator sickness, and entitativity over time. Furthermore, we examined two types of transformed social interaction: nonverbal mimicry and facial similarity. Results demonstrated substantial changes in task performance, subjective ratings, nonverbal behavior, and simulator sickness over time as participants became familiar with the system. Furthermore, transforming avatar appearance to increase facial similarity sometimes improved task performance. We discuss implications for research on CVEs.
Automating the Display of Third Person/Stealth Views of Virtual Environments
Authors: Kalawsky Roy , Simpkin Graeme
Published: December 2006

In order to gain a greater insight into the relationships that exist between entities in three-dimensional (3D) datasets, the scientific, engineering, and arts communities are increasingly using interactive visualization and virtual reality (VR) techniques. They have realized that interactively visualizing 3D datasets from different viewpoints makes it possible to achieve a better understanding of the underlying dataset structure. Viewpoints can be either static or dynamic as in an interactive fly-through. However, unskilled users often select flight paths (or viewing situations) that cause nauseous effects that detrimentally distract the user from the task at hand. Interactions between multiple users or virtual agents in a virtual environment present further challenges because it is necessary for the user to monitor multiple activities concurrently.

If the user has to make decisions based on what is taking place in a complex virtual environment, then it is very important that correct and appropriate viewpoints are maintained. For example, flight simulator debriefing tools require first and third person viewing so that the actions that have taken place can be understood. In these situations there is a need to select multiple viewpoints for each participant. Consequently (because of the high cognitive load), maintaining control over a number of different viewpoints is very challenging.

Within this paper the authors describe the real-time automatic display controller they have developed for third person/stealth views of a multi-participant virtual environment—where it is important for users to gain a global and localized understanding of the tasks being performed. They discuss important cinematic conventions and how these are set in the context of characterizing a 3D communication medium, as well as determining their role for optimal viewing parameters. The real time automatic display controller is of particular benefit to applications such as scientific visualization, flight simulation, engineering/architectural modeling, scene of accident reconstruction/analysis, and other complex human-system behavior analysis applications.
The Duty of Diplomatic Dissent
Authors: Kiesling John Brady
Published: December 2006

The poor outcome of the Iraq War has highlighted the usefulness of 'reality-based' foreign policy. Yet the personal and professional consequences of dissent remain high in the US (and every other) diplomatic service. The Dissent Channel, currently underutilized, was designed to protect both the US State Department and its employees from bureaucratic retaliation for unwelcome real-world expertise. It should be reinvigorated. However, the unimpressive policy impact of dissent, whether through institutional channels or public resignations, makes it clear that effective dissent requires mobilizing the domestic political process as a force multiplier. Good dissent raises the political price of foreign policy blunders, and only through turning a bureaucratic system painfully against itself can blunders actually be prevented.
Managing Blurred Environments
Authors: Sementelli Arthur J.
Published: December 2006

Scholars often offer ideas for public administration focusing on the changing relationships between public and private sectors. These ideas have grown into discourses including the new public management and others. Scholars also tend to differ in their view of what public administration should be, fostering conflict. If one considers these discourses collectively through the lens of managing resources in a blurred environment, it can provide a space for meaningful discussions to emerge. One then might reshape a civic space that engages new public management, governance, and others collaboratively employing usufruct to focus this discussion given the emergence of postmodern conditions.
Public Administration and the Life Sciences
Authors: Meyer-Emerick Nancy
Published: December 2006

Biopolitics applies methodology from the life sciences to study human behavior and policy related to living things. Although Gulick introduced the concept to public administration more than 25 years ago, it remains nearly absent in the public administration literature. This article reintroduces the origin, concepts, and methodology of biopolitics and explores its application to public administration but also suggests that a public administration perspective would be a valuable contribution in return.
Six Normative Principles for the Contracting-Out Debate
Authors: Goodsell Charles T.
Published: December 2006

Six normative principles are developed for consideration in the debate as to when and how government should directly administer its activities versus contract them out. These differ from the inherently governmental and economic efficiency criteria commonly espoused. The principles are inspired by the purposes of government stated in the Preamble to the Constitution and are developed according to Friedrich’s concept of public administration as a disciplined taking of measures. Even though illustrative rather than comprehensive, the principles collectively show how public administration has moral, legal, and economic obligations.
Citizen Evaluations of Local Police
Authors: Orr Marion , West Darrell M.
Published: December 2006

The sources of public assessments of government policy long have been the object of controversy between those proposing personal experience versus a symbolic attitudes model based on more general political and social beliefs. However, much of the research focuses on national policy issues that are not concrete and are removed from the daily experiences of many Americans. The authors use attitudes about local police to examine whether public assessments are linked more to people’s direct experience with crime and the police or whether such impressions are associated with more abstract attitudes about politics and law enforcement. They find that personal experience mattered more than symbolic attitudes when it came to views about police courtesy and fairness. However, both personal experience and symbolic attitudes were important in regard to opinions about crime seriousness and assessments of overall police performance. These results have important implications for how citizens evaluate local government services.
Single Mothers, Social Capital, and Work–Family Conflict
Authors: Ciabattari Teresa
Published: December 2006

The purpose of this article is to examine work–family conflict among low-income, unmarried mothers. Analyzing the Fragile Families and Child Wellbeing Study, a national sample of nonmarital births, I examine how social capital affects work–family conflict and how both social capital and work–family conflict affect employment. Results show that social capital reduces unmarried mothers' reports of work–family conflict, especially for low-income women. In addition, mothers who report high levels of conflict are less likely to be employed; this pattern holds for women who are looking for work and those who are not. However, even at high levels of conflict, low-income women are more likely to be employed. The results suggest that work–family conflict has two consequences for unmarried women: It keeps them out of the labor force and makes it more difficult for women who want to work to maintain employment stability.
Talking About Family
Authors: Goldberg Abbie E.
Published: December 2006

Although a growing literature exists on children of lesbian, gay, and bisexual (LGB) parents, little is known about these children's experiences as adults. Of interest is how these individuals negotiate disclosure of their parents' sexual orientation. This qualitative study of 42 adults raised by LGB parents explores this issue. Participants grew up in a diverse range of contexts: Some were always aware of their family's nontraditional status, some were told in childhood, and others were never explicitly told. As adults, participants described a number of reasons for coming out about their family, including a desire to educate, a desire to “screen out” homophobic individuals, and a need for openness in their relationships. Several participants did not disclose about their families at all, and several told only when necessary. Findings are discussed in terms of the diversity inherent among adult children of LGB parents and implications for practice, policy, and research.
Minority Youths and Juvenile Justice
Authors: Kempf-Leonard Kimberly
Published: December 2006

This article describes the current status of minority youths in juvenile justice systems. With nearly 20 years of federal support, there has been considerable research attention to identifying, explaining, and reducing the disproportionate minority contact with juvenile justice systems. Although progress is evident, the achievements of the Disproportionate Minority Contact (DMC) initiative have made it clear that the questions are more complicated than initially appeared. The answers do not appear in simple comparisons of youths by race but require “similarly situated” youths who differ only by minority status. Assuring that youths are similarly situated requires knowing their status on many complex and interrelated factors that exist across multiple levels of individuals, families, communities, and juvenile justice systems. The ways in which DMC can be reduced also require addressing parity in opportunities and expectations, both in the community and throughout juvenile justice systems.
Determinants of Disruption
Authors: Trulson Chad R.
Published: December 2006

With a few exceptions, most of the empirical research on institutional misconduct has focused on adult prison inmates. As a result, little is known about the factors related to misconduct among state-committed delinquents. This article examined the institutional misconduct of 4,684 state-committed delinquents released from a large Southern juvenile correctional system. Males, non-Whites, gang members and/or those with gang-related family members, and those with earlier, more serious, and more extensive delinquent histories were significantly more likely to engage in serious forms of institutional misconduct. These predictors were consistent for the model examining a less serious but disruptive form of institutional misconduct, with the exception that race, sex, and gang membership failed to be significant. The analyses also indicate that the determinants of misconduct for males may differ for state-committed females. This article concludes with suggestions for future research on institutional misconduct involving state-committed delinquents.