bluuebunny/crossref_metadata_2025 huggingface dataset:
Instant-messaging Shiva, flying taxis, Bil Klinton and more: children's narratives from rural India
Authors: Arora Payal
Published: March 2008

In this article, story (re)productions by children in rural India are seen as a potential tool for addressing current `participatory' issues facing development practitioners. A project was implemented to involve children from a rural village in South India in e-literary storybook productions. The intention was to foster online representations of the rural voice through the lens of the child. Drawing on the material of children's stories, multiple subjectivities are revealed that compel us to reconsider relations of the 'rural' with technology and current social contexts. An analysis of these narratives highlights children's appropriation capabilities as they weave the 'urbanness' and 'global' with the 'rural' fabric, moving beyond the traditional discourse of the urban—rural dichotomy. This effort capitalizes on current theorizations of territory as scapes, making the case to harness children's stories to enlighten the adult, well-intentioned development practitioner who seeks genuine understanding of territory and practice.
Ordering sex in cyberspace: a content analysis of escort websites
Authors: Castle Tammy , Lee Jenifer
Published: March 2008

Research studies on prostitution, more specifically escort services, have neglected the use of the internet as a method of solicitation and advertisement. The current study is an exploratory analysis of the content of 76 escort websites, located using online search engines. The purpose of this study was to uncover information about the escort agencies and escorts that utilize the internet for advertisement purposes. One of the goals of this research study was to describe the `typical' escort website from the potential customer perspective and includes information on individual escorts, prices, payment options and reviews.
Thermal fatigue properties and grain boundary character distribution in Sn–x Ag–0˙5Cu (x = 1, 1˙2 and 3) lead free solder interconnects
Authors: Terashima S. , Tanaka M. , Tatsumi K.
Published: March 2008

Thermal fatigue properties of Sn–x Ag–0˙5Cu (x = 1, 1˙2 and 3, mass%) lead free solder interconnects were discussed from the viewpoints of both morphology and grain boundary character distribution. 3Ag showed the longer thermal fatigue life than 1Ag and 1˙2Ag. Both cracks, which were initiated by thermal strain, and grain boundary damage due to grain boundary sliding degraded the thermal fatigue lives. From a microstructural observation using orientation imaging microscopy, recrystallisation of tin grains was observed, and 3Ag suppressed coarsening of tin grains after further thermal fatigue as compared with 1Ag and 1˙2Ag. Moreover, 3Ag showed a larger amount of coincidence site lattice boundaries than 1Ag and 1˙2Ag. It is suggested that in 3Ag not only smaller tin grains but also larger amount of coincidence site lattice boundaries suppressed crack propagation and grain boundary sliding.
Phosphatidylinositol 3-kinase signaling in proliferating cells maintains an anti-apoptotic transcriptional program mediated by inhibition of FOXO and non-canonical activation of NFκB transcription factors
Authors: Terragni Jolyon , Graham Julie R , Adams Kenneth W , Schaffer Michael E , Tullai John W , Cooper Geoffrey M
Published: March 2008

Background

Phosphatidylinositol (PI) 3-kinase is activated by a variety of growth factor receptors and the PI 3-kinase/Akt signaling pathway is a key regulator of cell proliferation and survival. The downstream targets of PI 3-kinase/Akt signaling include direct regulators of cell cycle progression and apoptosis as well as a number of transcription factors. Growth factor stimulation of quiescent cells leads to robust activation of PI 3-kinase, induction of immediate-early genes, and re-entry into the cell cycle. A lower level of PI 3-kinase signaling is also required for the proliferation and survival of cells maintained in the presence of growth factors, but the gene expression program controlled by PI 3-kinase signaling in proliferating cells has not been elucidated.

Results

We used microarray analyses to characterize the changes in gene expression resulting from inhibition of PI 3-kinase in proliferating cells. The genes regulated by inhibition of PI 3-kinase in proliferating cells were distinct from genes induced by growth factor stimulation of quiescent cells and highly enriched in genes that regulate programmed cell death. Computational analyses followed by chromatin immunoprecipitations demonstrated FOXO binding to both previously known and novel sites in promoter regions of approximately one-third of the up-regulated genes, consistent with activation of FOXO1 and FOXO3a in response to inhibition of PI 3-kinase. NFκB binding sites were similarly identified in promoter regions of over one-third of the down-regulated genes. RelB was constitutively bound to promoter regions in cells maintained in serum, however binding decreased following PI 3-kinase inhibition, indicating that PI 3-kinase signaling activates NFκB via the non-canonical pathway in proliferating cells. Approximately 70% of the genes targeted by FOXO and NFκB regulate cell proliferation and apoptosis, including several regulators of apoptosis that were not previously known to be targeted by these transcription factors.

Conclusion

PI 3-kinase signaling in proliferating cells regulates a novel transcriptional program that is highly enriched in genes that regulate apoptosis. At least one-third of these genes are regulated either by FOXO transcription factors, which are activated following PI 3-kinase inhibition, or by RelB, which is activated by PI 3-kinase via the non-canonical pathway in proliferating cells.
Intergeneric transfer of ribosomal genes between two fungi
Authors: Xie Jiatao , Fu Yanping , Jiang Daohong , Li Guoqing , Huang Junbin , Li Bo , Hsiang Tom , Peng Youliang
Published: March 2008

Background

Horizontal gene transfer, also called lateral gene transfer, frequently occurs among prokaryotic organisms, and is considered an important force in their evolution. However, there are relatively few reports of transfer to or from fungi, with some notable exceptions in the acquisition of prokaryotic genes. Some fungal species have been found to contain sequences resembling those of bacterial genes, and with such sequences absent in other fungal species, this has been interpreted as horizontal gene transfer. Similarly, a few fungi have been found to contain genes absent in close relatives but present in more distantly related taxa, and horizontal gene transfer has been invoked as a parsimonious explanation. There is a paucity of direct experimental evidence demonstrating the occurrence of horizontal gene transfer in fungi.

Results

We found a fungal field isolate from rice (Oryzae sativa) that contains ribosomal DNA sequences from two species of fungal rice pathogens (Thanatephorus cucumeris and Ceratobasidium oryzae-sativae). This field isolate has four types of ribosomal DNA internal transcribed spacers (ITS), namely pure ITS of C. oryzae-sativae, which was dominant in this field isolate, pure ITS of T. cucumeris, and two chimeric ITS, with ITS1 derived from C. oryzae-sativae and ITS2 from T. cucumeris, or ITS1 from T. cucumeri s and ITS2 from C. oryzae-sativae. The presence of chimeric forms indicates that the intergeneric hybrid was not merely composed of nuclei from the parental species, but that nuclear fusion and crossing over had taken place.

Conclusion

Hyphae of T. cucumeris and C. oryzae-sativae are vegetatively incompatible, and do not successfully anastomose. However, they parasitize the same host, and perhaps under the influence of host enzymes targeted to weaken pathogen cells or in dying host plant tissue, the fungal hyphae lost their integrity, and normal vegetative incompatibility mechanisms were overcome, allowing the hyphae to fuse. Based on the presence of other similarly anomalous isolates from the field, we speculate that these types of intergeneric hybridization events and occurrences of horizontal gene transfer may not be so rare in the field.
Screening of functional and positional candidate genes in families with common variable immunodeficiency
Authors: Salzer Ulrich , Neumann Carla , Thiel Jens , Woellner Cristina , Pan-Hammarström Qiang , Lougaris Vassilis , Hagena Tina , Jung Johannes , Birmelin Jennifer , Du Likun , Metin Ayse , Webster David A , Plebani Alessandro , Moschese Viviana , Hammarström Lennart , Schäffer Alejandro A , Grimbacher Bodo
Published: March 2008

Background

Common variable immunodeficiency (CVID) comprises a heterogeneous group of primary antibody deficiencies with complex clinical and immunological phenotypes. The recent discovery that some CVID patients show monogenic defects in the genes encoding ICOS, TACI or CD19 prompted us to investigate several functional candidate genes in individuals with CVID.

Results

The exonic, protein coding regions of the genes encoding: APRIL, BCMA, IL10, IL10Rα, IL10Rβ, IL21, IL21R, and CCL18, were analyzed primarily in familial CVID cases, who showed evidence of genetic linkage to the respective candidate gene loci and CVID families with a recessive pattern of inheritance. Two novel SNPs were identified in exon 5 and exon 8 of the IL21R gene, which segregated with the disease phenotype in one CVID family. Eleven additional SNPs in the genes encoding BCMA, APRIL, IL10, IL10Rα, IL21 and IL21R were observed at similar frequencies as in healthy donors.

Conclusion

We were unable to identify obvious disease causing mutations in the protein coding regions of the analyzed genes in the studied cohort.
Agreement between a self-administered questionnaire on musculoskeletal disorders of the neck-shoulder region and a physical examination
Authors: Perreault Nathalie , Brisson Chantal , Dionne Clermont E , Montreuil Sylvie , Punnett Laura
Published: March 2008

Background

In epidemiological studies on neck-shoulder disorders, physical examination by health professionals, although more expensive, is usually considered a better method of data collection than self-administered questionnaires on symptoms. However, little is known on the comparison of these two methods of data collection. The agreement between self-administered questionnaires and the physical examination on the presence of neck-shoulders disorders was assessed in the present study.

Methods

This study was conducted among clerical workers using video display units. Prevalent cases were workers for whom neck-shoulder symptoms were present for at least 3 days during the previous 7 days and for whom pain intensity was greater than 50 mm on a 100 mm visual analogue scale. All 85 workers meeting this definition and a random sample of 102 workers who did not meet this definition were selected. Physical examination included measures of active range of motion and musculoskeletal strength. Cohen's kappa and global percent agreement were calculated to compare the two methods of data collection. The effect on the agreement of different question and physical examination definitions and the importance of the time interval elapsed between the administrations of the tests were also evaluated.

Results

Kappa coefficients ranged from 0.19 to 0.54 depending on the definitions used to ascertain disorders. The agreement was highest when the two instruments were administered 21 days apart or less (Kappa = 0.54, global agreement = 77%). It was not substantially improved by the addition of criteria related to functional limitations or when comparisons were made with alternative physical examination definitions. Pain intensity recorded during physical examination maneuvers was an important element of the agreement between questionnaire and physical examination findings.

Conclusion

These results suggest a fair to good agreement between the presence of musculoskeletal disorders ascertained by self-administered questionnaire and physical examination that may reflect differences in the constructs measured. Shorter time lags result in better agreement. Investigators should consider these results before choosing a method to measure the presence of musculoskeletal disorders in the neck-shoulder region.
Oral Health Care Reform in Finland – aiming to reduce inequity in care provision
Authors: Niiranen Teija , Widström Eeva , Niskanen Tapani
Published: March 2008

Background

In Finland, dental services are provided by a public (PDS) and a private sector. In the past, children, young adults and special needs groups were entitled to care and treatment from the public dental services (PDS). A major reform in 2001 – 2002 opened the PDS and extended subsidies for private dental services to all adults. It aimed to increase equity by improving adults' access to oral health care and reducing cost barriers. The aim of this study was to assess the impacts of the reform on the utilization of publicly funded and private dental services, numbers and distribution of personnel and costs in 2000 and in 2004, before and after the oral health care reform. An evaluation was made of how the health political goals of the reform: integrating oral health care into general health care, improving adults' access to care and lowering cost barriers had been fulfilled during the study period.

Methods

National registers were used as data sources for the study. Use of dental services, personnel resources and costs in 2000 (before the reform) and in 2004 (after the reform) were compared.

Results

In 2000, when access to publicly subsidised dental services was restricted to those born in 1956 or later, every third adult used the PDS or subsidised private services. By 2004, when subsidies had been extended to the whole adult population, this increased to almost every second adult. The PDS reported having seen 118 076 more adult patients in 2004 than in 2000. The private sector had the same number of patients but 542 656 of them had not previously been entitled to partial reimbursement of fees.

The use of both public and subsidised private services increased most in big cities and urban municipalities where access to the PDS had been poor and the number of private practitioners was high. The PDS employed more dentists (6.5%) and the number of private practitioners fell by 6.9%. The total dental care expenditure (PDS plus private) increased by 21% during the study period. Private patients who had previously not been entitled to reimbursements seemed to gain most from the reform.

Conclusion

The results of this study indicate that implementation of a substantial reform, that changes the traditionally defined tasks of the public and private sectors in an established oral health care provision system, proceeds slowly, is expensive and probably requires more stringent steering than was the case in Finland 2001 – 2004. However, the equity and fairness of the oral health care provision system improved and access to services and cost-sharing improved slightly.
The barriers to smoking cessation in Swiss methadone and buprenorphine-maintained patients
Authors: Wapf Victoria , Schaub Michael , Klaeusler Beat , Boesch Lukas , Stohler Rudolf , Eich Dominique
Published: March 2008

Background

Smoking rates in methadone-maintained patients are almost three times higher than in the general population and remain elevated and stable. Due to the various negative health effects of smoking, nicotine dependence contributes to the high mortality in this patient group. The purpose of the current study was to investigate Swiss methadone and buprenorphine-maintained patients' willingness to stop smoking and to clarify further smoking cessation procedures.

Methods

Substance abuse history, nicotine dependence, and readiness to stop smoking were assessed in a sample of 103 opiate-dependent patients in the metropolitan area of Zurich, Switzerland. Patients were asked to document their smoking patterns and readiness to quit.

Results

Only a small number of patients were willing to quit smoking cigarettes (10.7%) and, even though bupropione or nicotine replacement therapy was included in the fixed daily treatment care, only one patient received nicotine replacement therapy for smoking cessation. A diagnosis of depression in patients' clinical records was associated with readiness to stop smoking. No significant associations were found between readiness to quit smoking and age, methadone treatment characteristics, and presence of co-dependencies.

Conclusion

The current prescription level of best medicine for nicotine dependence in Swiss methadone and buprenorphine-maintained patients is far from adequate. Possible explanations and treatment-relevant implications are discussed.
Homoplasy in genome-wide analysis of rare amino acid replacements: the molecular-evolutionary basis for Vavilov's law of homologous series
Authors: Rogozin Igor B , Thomson Karen , Csürös Miklós , Carmel Liran , Koonin Eugene V
Published: March 2008

Background

Rare genomic changes (RGCs) that are thought to comprise derived shared characters of individual clades are becoming an increasingly important class of markers in genome-wide phylogenetic studies. Recently, we proposed a new type of RGCs designated RGC_CAMs (after Conserved Amino acids-Multiple substitutions) that were inferred using genome-wide identification of amino acid replacements that were: i) located in unambiguously aligned regions of orthologous genes, ii) shared by two or more taxa in positions that contain a different, conserved amino acid in a much broader range of taxa, and iii) require two or three nucleotide substitutions. When applied to animal phylogeny, the RGC_CAM approach supported the coelomate clade that unites deuterostomes with arthropods as opposed to the ecdysozoan (molting animals) clade. However, a non-negligible level of homoplasy was detected.

Results

We provide a direct estimate of the level of homoplasy caused by parallel changes and reversals among the RGC_CAMs using 462 alignments of orthologous genes from 19 eukaryotic species. It is shown that the impact of parallel changes and reversals on the results of phylogenetic inference using RGC_CAMs cannot explain the observed support for the Coelomata clade. In contrast, the evidence in support of the Ecdysozoa clade, in large part, can be attributed to parallel changes. It is demonstrated that parallel changes are significantly more common in internal branches of different subtrees that are separated from the respective common ancestor by relatively short times than in terminal branches separated by longer time intervals. A similar but much weaker trend was detected for reversals. The observed evolutionary trend of parallel changes is explained in terms of the covarion model of molecular evolution. As the overlap between the covarion sets in orthologous genes from different lineages decreases with time after divergence, the likelihood of parallel changes decreases as well.

Conclusion

The level of homoplasy observed here appears to be low enough to justify the utility of RGC_CAMs and other types of RGCs for resolution of hard problems in phylogeny. Parallel changes, one of the major classes of events leading to homoplasy, occur much more often in relatively recently diverged lineages than in those separated from their last common ancestor by longer time intervals of time. This pattern seems to provide the molecular-evolutionary underpinning of Vavilov's law of homologous series and is readily interpreted within the framework of the covarion model of molecular evolution.

Reviewers

This article was reviewed by Alex Kondrashov, Nicolas Galtier, and Maximilian Telford and Robert Lanfear (nominated by Laurence Hurst).
Double rupture of interventricular septum and free wall of the left ventricle, as a mechanical complication of acute myocardial infarction: a case report
Authors: Rentoukas Elias I , Lazaros George A , Kaoukis Andreas P , Matsakas Evangellos P
Published: March 2008

Introduction

Cardiac ruptures following acute myocardial infarction include rupture of the left ventricle free-wall, ventricular septal defects, and papillary muscle rupture. Double myocardial rupture is a rare complication of acute myocardial infarction (0.3 %) and the report of such cases is exclusively limited to a small series of autopsy studies.

Case presentation

In this report we present the unusual case of a 70-year-old woman with acute anteroseptal myocardial infarction, which was complicated by a combined rupture of the interventricular septum near the apex, and the free wall of the left ventricle with concomitant formation of a pseudoaneurysm. The double myocardial rupture was accidentally discovered 10 days later with echocardiography, when the patient, complaining only of mild exertional dyspnea, was hospitalized for a scheduled coronary angiography. The patient underwent successful surgical correction of the double myocardial rupture along with by-pass grafting.

Conclusion

This report highlights the importance of comprehensive noninvasive predischarge diagnostic evaluation of all postinfarct patients, since serious and potentially life-threatening complications might have not been suspected on clinical grounds.
Role of protease-activated receptors in inflammatory responses, innate and adaptive immunity
Authors: Shpacovitch V , Feld M , Hollenberg M D , Luger T A , Steinhoff M
Published: March 2008

Serine proteases are well known as enzymes involved in digestion of dietary proteins, blood coagulation, and homeostasis. Only recent groundbreaking studies revealed a novel role of serine proteases as signaling molecules acting via protease-activated receptors (PARs). Important effects of PAR activation on leukocyte motility, cytokine production, adhesion molecule expression, and a variety of other physiological or pathophysiological functions have been described in vitro and in vivo. The crucial role of PAR activation during disease progression was revealed in animal models of different gastrointestinal pathologies, neuroinflammatory and neurodegenerative processes, skin, joint and airway inflammation, or allergic responses. This review focuses on the findings related to the impact of PAR deficiency in animal models of inflammatory and allergic diseases. Additionally, we observe the role of PAR activation in the regulation of functional responses of innate and adaptive immune cells in vitro. Understanding the mechanisms by which PARs exert the effects of serine proteases on immune cells may lead to new therapeutic strategies in inflammation, immune defense, and allergy.
Psychological and Clinical Factors Implicated in Decision Making About a Trial of Low-Dose Tamoxifen in Hormone Replacement Therapy Users
Authors: Rondanina Gabriella , Puntoni Matteo , Severi Gianluca , Varricchio Clara , Zunino Anna , Feroce Irene , Bonanni Bernardo , Decensi Andrea
Published: March 2008

Purpose

To assess the sociodemographic, health-related, and psychological factors that influence the decision of women on hormone replacement therapy (HRT) to participate in a phase III trial of low-dose tamoxifen.

Patients and Methods

Clinical and psychological factors were assessed in 265 women who accepted and 192 women who refused to participate in a proposed trial. Health-related and sociodemographic factors included age, Gail risk, body mass index, education, current HRT use, regular mammographic screening, smoking habit, physical activity, alcohol use, concern about adverse effects, and physician recommendation. Psychological factors included breast cancer–related worry, absolute and comparative cancer risk perception, anxiety, and depression.

Results

The most frequent reasons for entry were willingness to participate in a research program (60%), the need/desire to receive frequent medical care (58%), and the desire to contribute to medical knowledge (44%); whereas reasons for refusal included fear of medication abuse (33%), concern about adverse effects (31%), and physician advice against enrollment (24%). In a logistic model, after adjusting for current HRT use, the trial participation was directly associated with satisfaction with clearly explained study objectives (odds ratio [OR] = 9.33; 95% CI, 4.04 to 21.55) and inversely associated with high breast cancer worry (OR = 0.15; 95% CI, 0.03 to 0.77) and age ≥ 60 years (OR = 0.40; 95% CI, 0.22 to 0.73).

Conclusion

Participation in a chemoprevention trial among HRT users is associated with a younger age, no breast cancer worry, and satisfaction with health care providers, suggesting a condition of psychological well-being as a promoting factor and emphasizing the importance of thorough counseling at study presentation.
Irinotecan/Fluorouracil Combination in First-Line Therapy of Older and Younger Patients With Metastatic Colorectal Cancer: Combined Analysis of 2,691 Patients in Randomized Controlled Trials
Authors: Folprecht Gunnar , Seymour Matthew T. , Saltz Leonard , Douillard Jean-Yves , Hecker Hartmut , Stephens Richard J. , Maughan Timothy S. , Van Cutsem Eric , Rougier Philippe , Mitry Emmanuel , Schubert Ute , Köhne Claus-Henning
Published: March 2008

Purpose

Uncertainty exists about whether elderly patients benefit to the same extent as younger patients from combination therapy with irinotecan in the first-line treatment of metastatic colorectal cancer (CRC).

Patients and Methods

Combined analysis was carried out with source data from the fluorouracil (FU)/folinic acid (FA) and the irinotecan/FU/FA arms of four first-line, phase III trials of CRC to investigate the efficacy and safety of combination and monotherapy in elderly (age ≥ 70 years; n = 599) compared with younger (age < 70 years; n = 2,092) patients.

Results

Response rates were improved with irinotecan-based combination therapy compared with FU/FA in patients both younger than 70 years and ≥ 70 years (46.6% v 29.0% P < .0001; and 50.5% v 30.3%, P < .0001, respectively). With irinotecan/FU/FA, progression-free survival was better for both younger (hazard ratio [HR], 0.77; 95% CI, 0.70 to 0.85; P < .0001) and elderly patients (HR, 0.75; 95% CI, 0.61 to 0.90; P = .0026). In younger patients, overall survival was improved with combination therapy (HR, 0.83; 95% CI, 0.75 to 0.92; P = .0003). The same trend was observed in elderly patients (HR, 0.87; 95% CI, 0.72 to 1.05; P = .15). There was no significant interaction between treatment arm and age in the regression analysis. The expected differences in toxicity between combination and monotherapy in elderly and younger patients were observed. A significant interaction between treatment and age (cutoff, 70 years) for vomiting and hepatotoxicity was not confirmed by analysis that used age as a continuous variable.

Conclusion

Patients older than 70 years of age who were selected for inclusion in phase III trials derived similar benefits as younger patients from irinotecan-containing chemotherapy, and the risk of toxicity was similar.
Analysis of Primary CD30+ Cutaneous Lymphoproliferative Disease and Survival From the Surveillance, Epidemiology, and End Results Database
Authors: Yu James B. , Blitzblau Rachel C. , Decker Roy H. , Housman Douglas M. , Wilson Lynn D.
Published: March 2008

Purpose

Primary CD30+ cutaneous lymphoproliferative disease (PCLPD) is a spectrum of indolent cutaneous T-cell lymphomas. The primary intention of the analysis of the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database was to report epidemiologic information and overall survival of patients with PCLPD.

Methods

We investigated the SEER database from 1973 to 2004 and performed univariable and multivariable survival analysis.

Results

A total of 268 cases of PCLPD were recorded from 1973 to 2004. Median age at diagnosis was 61 years (range, 5 to 98 years). Among cases, 58% were male, and 42% female. Race distribution was 87% white, 7% black, and 4% Asian/Pacific Islander. A total of 157 patients had primary, localized PCLPD. For the total population (N = 268), overall survival at 3 years was 81% (95% CI, 74% to 87%). Population-matched relative survival at 3 years was 87% (SE, 3.6%). Disease-specific survival at 5 years was 92% (95% CI, 86% to 95%). Head and neck skin site predicted for inferior overall survival in patients with primary, localized PCLPD on univariable analysis (hazard ratio [HR] = 4.4; P = .008; 95% CI, 1.5 to 13.2), and was suggestive of decreased overall survival on multivariate analysis (HR = 3.0; P = .06; 95% CI, 0.95 to 9.7).

Conclusion

Localized PCLPDs are rare diseases with an excellent overall survival and occur more frequently in whites and in men. Head and neck skin primary site may be associated with poorer survival. Conclusions regarding subsets demonstrating association with survival should be taken with caution, given the small number of deaths analyzed.
Phase I Study of Recombinant Interleukin-21 in Patients With Metastatic Melanoma and Renal Cell Carcinoma
Authors: Thompson John A. , Curti Brendan D. , Redman Bruce G. , Bhatia Shailender , Weber Jeffrey S. , Agarwala Sanjiv S. , Sievers Eric L. , Hughes Steven D. , DeVries Todd A. , Hausman Diana F.
Published: March 2008

Purpose

A phase I study of patients with metastatic malignant melanoma (MM) and renal cell carcinoma (RCC) evaluated the safety and maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of recombinant human interleukin-21 (rIL-21).

Patients and Methods

Patients who had one or fewer prior systemic treatments for metastatic MM or RCC were treated with rIL-21 administered for two 5-day cycles on days 1 through 5 and 15 through 19 of a treatment course; rIL-21 was administered by rapid intravenous infusion in an outpatient setting. Cohorts of patients received doses ranging from 3 to 100 μg/kg/dose, and an expanded cohort was treated at the MTD. Patients with stable disease (SD) or better could receive additional treatment cycles.

Results

Forty-three patients were treated (24 MM; 19 RCC), including 28 in the expanded cohort. Dose-limiting toxicities consisted primarily of transient grade 3 laboratory abnormalities. The MTD was estimated to be 30 μg/kg. The most common adverse events included flu-like symptoms, pruritus, and rash. Twelve patients received up to five additional two-cycle courses of treatment without cumulative toxicity, except for one patient with reversible grade 4 hepatotoxicity. Serum concentrations of rIL-21 increased in a dose-proportional manner. Dose-dependent increases in soluble CD25 reflected lymphocyte activation. Antitumor activity was observed in both MM (one complete response and 11 SD) and RCC (four partial responses, 13 SD).

Conclusion

Outpatient therapy with rIL-21 at 30 μg/kg was well tolerated, had dose-dependent pharmacokinetics and pharmacodynamics, and was associated with antitumor activity in patients with MM and RCC.
Phase II Study of Sunitinib Malate, an Oral Multitargeted Tyrosine Kinase Inhibitor, in Patients With Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane
Authors: Burstein Harold J. , Elias Anthony D. , Rugo Hope S. , Cobleigh Melody A. , Wolff Antonio C. , Eisenberg Peter D. , Lehman Mary , Adams Bonne J. , Bello Carlo L. , DePrimo Samuel E. , Baum Charles M. , Miller Kathy D.
Published: March 2008

Purpose

Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, stem cell factor receptor (KIT), and colony-stimulating factor-1 receptor. This phase II, open-label, multicenter study evaluated sunitinib monotherapy in patients with metastatic breast cancer (MBC).

Patients and Methods

Sixty-four patients previously treated with an anthracycline and a taxane received sunitinib 50 mg/d in 6-week cycles (4 weeks on, then 2 weeks off treatment). The primary end point was objective response rate. Plasma samples were obtained for pharmacokinetic and biomarker analysis.

Results

Seven patients achieved a partial response (median duration, 19 weeks), giving an overall response rate of 11%. Three additional patients (5%) maintained stable disease for ≥ 6 months. Median time to progression and overall survival were 10 and 38 weeks, respectively. Notably, responses occurred in triple negative tumors and HER2-positive, trastuzumab-treated patients. Thirty-three patients (52%) required dose interruption during ≥ 1 cycle, and 25 patients required dose reduction (39%). Thirty-six patients (56%) had dose modifications due to adverse events (AEs). Treatment was associated with increases in plasma VEGF and decreases in soluble VEGFRs and KIT. The most common AEs were fatigue, nausea, diarrhea, mucosal inflammation, and anorexia. Most AEs were mild to moderate (grade 1 to 2) in severity and were effectively managed with dose delays or reductions.

Conclusion

Sunitinib is active in patients with heavily pretreated MBC. Most AEs were of mild-to-moderate severity and manageable with supportive treatment and/or dose modification. Further studies in breast cancer are warranted.
A review of pressure-sensitive paint for high-speed and unsteady aerodynamics
Authors: Gregory J W , Asai K , Kameda M , Liu T , Sullivan J P
Published: March 2008

The current paper describes the development of pressure-sensitive paint (PSP) technology as an advanced measurement technique for unsteady flow fields and short-duration wind tunnels. Newly developed paint formulations have step response times approaching 1 μs, making them suitable for a wide range of unsteady testing. Developments in binder technology are discussed, which have resulted in new binder formulations such as anodized aluminium, thin-layer chromatography plate, polymer/ceramic, and poly(TMSP) PSP. The current paper also details modeling work done to describe the gas diffusion properties within the paint binder and understand the limitations of the paint response characteristics. Various dynamic calibration techniques for PSP are discussed, along with summaries of typical response times. A review of unsteady and high-speed PSP applications is presented, including experiments with shock tubes, hypersonic tunnels, unsteady delta wing aerodynamics, fluidic oscillator flows, Hartmann tube oscillations, acoustics, and turbomachinery. Flowfields with fundamental frequencies as high as 21 kHz have been successfully measured with porous PSP formulations.
Energy dissipation in spacecraft structures incorporating bolted joints with viscoelastic layers
Authors: Wang R , Crocombe A D , Richardson G , Underwood C I
Published: March 2008

The energy dissipation capacity of bolted joints with viscoelastic layers in a spacecraft structure was investigated. Initially, a linear spring dashpot model was used to represent the bolts in a satellite structure. A relationship was developed between the model parameters (stiffness and damping coefficient) and the viscoelastic material and geometric properties (shear modulus, loss factor, operating area, and thickness) of the actual bolted joint. This model was then developed into the non-linear domain. Experiments on bolted joints with viscoelastic layers were carried out to provide information for the non-linear joint model. These models were incorporated into a simple spacecraft model to investigate the effect on the spacecraft response. Based on these numerical analysis, it was found that the joints can dissipate much energy and the response of the spacecraft structure to vibrations during launch can be decreased significantly.
Nano-Scale Hydroxyapatite Coating on Macroscopic Silica Fiber Using Carbon Nanofibers as Templates
Authors: Wu Qiang , Ogihara Hitoshi , Uchida Hisaichiro , Sadakane Masahiro , Nodasaka Yoshinobu , Ueda Wataru
Published: March 2008

Starting from Ca(NO3)2–H3PO4–methanol precursor mixtures and using carbon nanofibers (CNFs) as templates, we have successfully coated nano-scale hydroxyapatite (HAp) layers on macroscopic silica fiber (diameter ca. 5 μm) surfaces. Under controlled experimental conditions, CNFs can be formed on silica fiber with variable yield, layer thickness, and diameters, and thus can be further used as different templates for HAp coating. XRD, FE-SEM, and cross-sectional TEM experimental results provided clear evidence that CNFs can act as effective templates for uniform nano-scale HAp coating on silica fiber. It turned out that heat-treatment at 923 K for 5 h is sufficient for complete removal of the CNFs templates and crystallization of the resulting nano-scale HAp. It was shown that the resulting HAp layer thickness was ca. 2–4 μm, the average crystallite size was ca. 20–40 nm, and the specific surface area was ca. 50–65 m2 g−1. In addition, it was clearly demonstrated that the average layer thickness and amount of HAp was controlled by the layer thickness of CNFs. Therefore, the coating mode of HAp could be reliably controlled through the selection of different kinds of CNFs templates.
The Role of Adsorption Species in the Formation of Ag Nanostructures by a Microwave-Polyol Route
Authors: Tsuji Masaharu , Matsumoto Kisei , Jiang Peng , Matsuo Ryoichi , Hikino Sachie , Tang Xin-Ling , Kamarudin Khairul Sozana Nor
Published: March 2008

The role of adsorption species in reaction solutions has been studied in microwave-polyol synthesis of silver (Ag) nanostructures. When Ag+ ions from AgNO3 were reduced in ethylene glycol by the addition of H2[PtCl6] and poly(vinylpyrrolidone) (PVP), a mixture of one-dimensional (1-D) nanorods and nanowires and 3-D spherical, cubic, and triangular-bipyramidal nanoparticles was obtained within three minutes. It has been previously believed that PVP acts as a surfactant and its selective adsorption on {100} facets results in pentagonal 1-D nanorods or nanowires and cubic and triangular-bipyramidal nanocrystals. We found here that these Ag products could also be formed without the addition of PVP in the presence of Cl− ions, though their yields were lower than those in the presence of PVP by a factor of ≈300. These results indicate that Cl− anions can also act as adsorption species to assist the formation of these Ag nanostructures. It is concluded that the difference in the adsorption ability of different species in solution on Ag nanostructures determines final shapes, sizes, and yields of formed Ag nanostructures.
An Unusual Iodinated 5′-Deoxyxylofuranosyl Nucleoside from an Okinawan Ascidian, Diplosoma sp.
Authors: Margiastuti Pulpi , Ogi Takayuki , Teruya Toshiaki , Taira Junsei , Suenaga Kiyotake , Ueda Katsuhiro
Published: March 2008

An unusual nucleoside, 4-amino-7-(5′-deoxy-β-d-xylofuranosyl)-5-iodopyrrolo[2,3-d]pyrimidine (1), was isolated from an ascidian, Diplosoma sp., and its structure was successfully determined by spectroscopic and chemical analysis. The known didemnenones 2–5 were also isolated. Compound 1 was found to inhibit the division of fertilized sea urchin eggs.
Convenient Synthesis of Angular Triquinane from 4-Alkenylfulvene via Thermal Cycloaddition Followed by Skeletal Rearrangement of the Resulting [4 + 2] Adduct
Authors: Inagaki Sho , Imura Keisuke , Morita Toshio , Yoshimi Yasuharu , Hatanaka Minoru , Kawano Tomikazu
Published: March 2008

Alkenylfulvene prepared by the annulation of allylidenetriphenylphosphorane with 1,4-ynedione proceeded thermal cycloaddition in a highly regio- and stereoselective manner to give [4 + 2] adduct which was then converted into triquinane derivative by the treatment with LHMDS-t-BuOK after hydrolysis of the enol ether group.
Red clover isoflavones are safe and well tolerated in women with a family history of breast cancer
Authors: Powles Trevor J , Howell Anthony , Evans D Gareth , Mccloskey Eugene V , Ashley Sue , Greenhalgh Rosemary , Affen Jenny , Flook Lesley Ann , Tidy Alwynne
Published: March 2008

Objective

To assess the safety and tolerability of a standardized 40 mg red clover isoflavone dietary supplement (Promensil®, Novogen) in women with a family history of breast cancer to evaluate the feasibility of using the supplement for prevention of breast cancer in healthy women.

Study design

Healthy women aged 35–70 years (n = 401) with at least one first-degree relative with breast cancer received red clover isoflavones or placebo for three years in a randomized, double-blind, placebo-controlled pilot trial. Participants were assessed clinically and blood samples taken for biochemical analysis every six months. In addition, study participants underwent mammography, bone density and transvaginal ultrasound (postmenopausal women only) once per year.

Results

No significant differences in breast density, endometrial thickness, serum cholesterol, follicle stimulating hormone levels and bone mineral density were detected between those taking red clover isoflavones and placebo. In postmenopausal women, some significant differences in bone marker levels were seen between active and placebo groups, at six months and at 12 months. The adverse event profile was similar across all red clover isoflavone and placebo groups.

Conclusion

This three-year study supports the growing body of evidence that treatment with red clover isoflavones is safe and well tolerated in healthy women. Supplements containing red clover isoflavones did not adversely affect breast density, skeletal strength or cardiovascular status. In postmenopausal women, endometrial status was not adversely affected. The adverse event profile was similar between red clover isoflavones, and placebo and endocrine status did not differ.
Quality of life in obese postmenopausal women
Authors: Jones G L , Sutton A
Published: March 2008

The aim of this review was to identify the ways in which obesity affects the health-related quality of life (HRQoL) of postmenopausal women. This was considered important because a growing body of literature has identified obesity as a significant predictor for a poor psychological wellbeing and negative HRQoL, particularly in women, and because during the transition through the menopause women tend to accumulate more body weight. After searching eight electronic databases, only nine papers appeared meaningful. Although a meta-analysis was not possible, we found that a body mass index (BMI) >30 kg/m2 was associated with a poor HRQoL in postmenopausal women; particularly in the areas associated with physical functioning, energy and vitality, and health perceptions. Thus, clinical management of obese postmenopausal women should focus on weight reduction and exercise in an attempt to improve wellbeing in these areas. However, the paucity of research, the different instruments chosen to measure HRQoL and the methodological limitations of the studies identified, prevented firm conclusions being made about whether the relationship between BMI and HRQoL is linear in postmenopausal women. Further research is needed to explore this relationship; particularly in comparison with underweight postmenopausal women and obese premenopausal women, where a few papers have identified these women as having a worse HRQoL than their obese postmenopausal counterparts. Other measures of central adiposity, including waist circumference and waist-hip ratio are recommended as useful supplemental measures to BMI in future studies.
Heart disease and gender in mass print media
Authors: Clarke Juanne
Published: March 2008

Heart disease is a major cause of death, disease and disability in the developed world for both men and women. Nevertheless, the evidence suggests that women are under-diagnosed both because they fail to visit the doctor with relevant symptoms and because doctors tend to dismiss the seriousness of women's symptoms of heart disease. This study examines the way that popular mass print media present the possible links between gender and heart disease. The findings suggest that the ‘usual candidates’ for heart disease are considered to be high achieving and active men for whom the ‘heart attack’ is sometimes seen as a ‘badge of honour’ and a symbol of their success. In contrast, women are less often seen as likely to succumb, but they are portrayed as if they are and ought to be worried about their husbands. Women's own bodies are described as so problematic as to be perhaps useless to diagnose, because they are so difficult to understand and treat.
Obesity and gynaecological cancer
Authors: Lane Geoffrey
Published: March 2008

Obesity is now considered to be a global epidemic. The problem of obesity has significant implications for the diagnosis and treatment of gynaecological cancer. The cancer most frequently associated with obesity is that of the endometrium. The risk of endometrial cancer is 2–3 times higher in overweight and obese women. Obesity also adversely affects survival in most studies. With regard to ovarian cancer the evidence is inconsistent. Obesity in young adulthood may be more important than that in later life. With regard to survival obesity has an adverse effect but not in early stage disease. Few data are available regarding cervical cancer and obesity. There is evidence that obesity is associated with adenocarcinoma rather than squamous carcinoma. Data on vulval cancer and obesity are scant.
Evidence for “Publication Bias” concerning Global Warming in Science and Nature
Authors: Michaels Patrick J.
Published: March 2008

The climate research community believes that published findings on global warming will have an equal probability of raising or lowering forecasts of climate change and its impact. This is a testable hypothesis based upon the recent literature and the assumption that extant forecasts are themselves unbiased. A survey of Science and Nature demonstrates that the likelihood that recent literature is not biased in a positive or negative direction is less than one in 5.2 × 10−16. This has considerable implications for the popular perception of global warming science, for the nature of “compendia” of climate change research, such as the reports of the United Nations' Intergovernmental Panel on Climate change, and for the political process that uses those compendia as the basis for policy.
Reducing Anthropogenic Atmospheric Carbon Loading
Authors: Villaire Louis A.
Published: March 2008

Higher energy use is closely linked to economic growth and social wealth. This “Viewpoint” puts forth the argument that it is not energy use as such that causes carbon-loading of the atmosphere. Higher energy use is not the problem, but rather one of the solutions to reducing anthropogenic CO2 emissions. Energy trends are examined and evidence is provided showing that the costs of producing energy from high-carbon fuels are rising while those of producing energy from low-carbon fuels are declining. The greatest challenge of increasing energy use is the protection of the integrity of the biosphere while improving quality of life. Both are possible with higher energy use.
Wind Turbine Mechanical Vibrations: Potential Environmental Threat
Authors: Dean W. Dixie
Published: March 2008

This Discussion Paper describes a significant but overlooked potential threat to the environment, community/business interests and land itself posed by wind turbine mechanical vibrations. Their power and frequencies have been measured, and in Ireland magnified similar vibrations caused significant harm. Given the nature of this problem the author is calling on relevant authorities to exercise increased caution when considering turbine installations until urgent threat assessment is completed.
Wind Micro-Turbines for Domestic Hydrogen Production?
Authors: Macleod Alasdair
Published: March 2008

A primary concern with some renewable energy sources is the intermittent nature of the supply and a consequent need for significant backup generation or storage capacity. Much has been made of the apparent correlation between the availability of wind energy and consumer demand, with the belief this type of renewable resource can be supplemented with only a moderate reserve of hydrogen generated at times of generation surplus. The assumption is tested through a case study that considers the backup storage needs for domestic applications in the Western Isles of Scotland, one of the windiest places in Europe. The results reflect the likely importance of storage when renewable energy generation levels reaches a significant portion of the national needs, and the degree of consideration that should be given to energy backup at this very early phase in the likely transition from fossil fuels to renewable energy sources.