bluuebunny/crossref_metadata_2025 huggingface dataset:
Neighbourhood deprivation, school disorder and academic achievement in primary schools in deprived communities in England
Authors: Barnes Jacqueline , Belsky Jay , Broomfield Kate A. , Melhuish Edward ,   & the National Evaluation of Sure Start (NESS) Research Team
Published: April 2006

There is growing concern about violent behaviour in schools, involving students, staff and/or parents. A survey of 1777 primary schools (for children aged 5 to 11) throughout England, most in areas of social and economic deprivation, found more disorder in neighbourhoods with greater deprivation. More disorder was also observed when there was more school-level disadvantage (e.g. students receiving free meals), larger school size and more children in need of special education services. Despite difficulties in drawing causal inferences from correlational data, the fact that more disorder significantly predicted lower school achievement for students at 7 and 11 in standardized English, mathematics and science assessments even once school characteristics and neighbourhood deprivation were taken into account is judged noteworthy. Potential confounding factors are considered in the discussion.
Social and experiential influences on the development of inheritance concepts
Authors: Williams Joanne M. , Smith Lesley A.
Published: April 2006

This study explored social and experiential differences in children's (aged 4 to 14 years) concepts of inheritance. The study utilized semi-structured interviews including four tasks that were designed to elicit judgements and explanations about different aspects of inheritance understanding. A variety of social and experiential factors were examined including, gender of participant, family composition, pet ownership, socio-economic status and urban/rural locale. The results indicated strong developmental changes and several social and environmental variations in children's knowledge of inheritance. Children from rural areas and from a higher socio-economic group showed a more sophisticated understanding of inheritance. Other variables including gender, owning a pet and having siblings had less impact on children's understanding of inheritance. Overall, children showed small variations in their inheritance concepts based on differences in experience and background. The precise causes of these differences remains an issue for future research.
Sensory motor inhibition as a prerequisite for theory-of-mind: A comparison of clinical and normal preschoolers differing in sensory motor abilities
Authors: Chasiotis Athanasios , Kiessling Florian , Winter Vera , Hofer Jan
Published: April 2006

After distinguishing between neocortical abilities for executive control and subcortical sensory motor skills for proprioceptive and vestibular integration, we compare a sample of 116 normal preschoolers with a sample of 31 preschoolers receiving occupational therapeutical treatment. This is done in an experimental design controlled for age (mean: 49 months), sex, SES, linguistic abilities, and intelligence. Inhibition and theory-of-mind are measured with test batteries. Results show that children having deficits in sensory motor inhibition are less competent in conflict inhibition and in theoryof-mind. Regression analyses reveal that in the clinical sample conflict inhibition is a significantly stronger predictor of theory-of-mind than in the control group. These results point at a basic sensory motor inhibitory ability as a prerequisite for the development of theory-of-mind.
Fertility Decline, Family Structure, and Support for Older Persons in Latin America and Asia
Authors: Glaser Karen , Agree Emily M. , Costenbader Elizabeth , Camargo Antonio , Trench Belkis , Natividad Josefina , Chuang Yi-Li
Published: April 2006

Objectives: To compare family structures and support for older persons in two Asian countries (Taiwan and the Philippines) and six urban areas in Latin America (Buenos Aires, São Paulo, Havana, Santiago, Mexico City, and Montevideo). Methods: Using the 1999 Survey of Health and Living Status of the Elderly in Taiwan, the 2000 Philippine Survey of the Near Elderly and Elderly, and the 2001 Pan American Health Organisation surveys on Salud, Bienestar y Envejecimiento en América Latina y el Caribe, descriptive tables show variations across countries in family structure, proximity, and transfers of support by the timing of the fertility transition in each location. Results: Older people in settings with earlier transitions had fewer children and more childlessness, higher levels of solitary living, and lower levels of coresidence with children. In earlier transition settings, receipt of family support was lower and provision higher. Discussion: The timing of the demographic transition has significant implications for kin availability and support.
How should the effectiveness of Social Stories to modify the behaviour of children on the autistic spectrum be tested?
Authors: Rust Jonathan , Smith Ailsa
Published: April 2006

Social Stories are an extensively used intervention to address behaviour difficulties of children on the autistic spectrum. This article summarizes what Social Stories are and sets out to determine whether there is any relevant literature demonstrating the effectiveness of this intervention. Whilst the existing literature suggests positive findings with respect to the effectiveness of Social Stories, there is considerable variability in the quality of research methodology, with no single study employing comprehensive, stringent standards. This article highlights the factors that should be considered and addressed when testing the effectiveness of Social Stories, as a means of informing future research.
Crossing fields: the case of a multi-disciplinary research team
Authors: Massey Claire , Alpass Fiona , Flett Ross , Lewis Kate , Morriss Stuart , Sligo Frank
Published: April 2006

There are increasing opportunities for researchers to work in multi-disciplinary research teams; however, the extensive literature on research practice barely refers to the challenges inherent in this approach. The article describes the experience of a multi-disciplinary team which was engaged in investigating the nature of technological learning in relation to productivity improvement in the dairy farming industry in New Zealand. The largely qualitative, multi-method approach taken to the project by the team is described, and the description supplemented by reflection on the factors that led to the key decisions in the research design process, and the consequences of these decisions.
Sharing the world: the researcher and the researched
Authors: Shah Sonali
Published: April 2006

This article explores the methodological opportunities and challenges I encountered, as a disabled researcher, while doing research on the educational experiences and career aspirations of a group of young disabled people, still in full-time mainstream or special education. While the key barriers facing disabled researchers are recognized, they are challenged in this article and rather seen as opportunities. Further, they are diluted by the ontological privileges that are at the disposal of the disabled researcher, including the use of empathy, which provides a way of understanding other people's experiences in the context of both similarities and differences between the researcher and the researched. This article focuses on three methods of qualitative enquiry – namely, classroom observation, forum theatre workshops and individual interviews. It explores how they were employed to ensure the voices of young disabled people were captured by the research process in ways that reflect their views and recognize them as active social agents who are able to make decisions about their own futures.
Trying similarity, doing difference: the role of interviewer self-disclosure in interview talk with young people
Authors: Abell Jackie , Locke Abigail , Condor Susan , Gibson Stephen , Stevenson Clifford
Published: April 2006

Advocates of semi-structured interview techniques have often argued that rapport may be built, and power inequalities between interviewer and respondent counteracted, by strategic self-disclosure on the part of the interviewer. Strategies that use self-disclosure to construct similarity between interviewer and respondent rely on the presumption that the respondent will in fact interpret the interviewer's behaviour in this way. In this article we examine the role of interviewer self-disclosure using data drawn from three projects involving interviews with young people. We consider how an interviewer's attempts to ‘do similarity’ may be interpreted variously as displays of similarity or, ironically, as indicators of difference by the participant, and map the implications that this may have for subsequent interview dialogue. A particular object of concern relates to the ways in which self-disclosing acts may function in the negotiation of category entitlement within interview interactions.
Comparison of two commercial interferon-γ assays for diagnosingMycobacterium tuberculosisinfection
Authors: Lee J. Y. , Choi H. J. , Park I-N. , Hong S-B. , Oh Y-M. , Lim C-M. , Lee S. D. , Koh Y. , Kim W. S. , Kim D. S. , Kim W. D. , Shim T. S.
Published: April 2006

The clinical usefulness ofex vivointerferon-γ assays may largely depend on the assay format and epidemiological status of tuberculosis (TB) in the region studied.

From July 2004 to June 2005 a prospective comparison study was undertaken at a tertiary referral hospital in South Korea. The results of tuberculin skin tests (TST) and the commercially available QuantiFERON-TB Gold (QFT-G) and T SPOT-TB (SPOT) assays were compared in an intermediate TB-burden country.

Of the 224 participants studied, results from all three tests (TST, QFT-G, and SPOT) were available in 218; 87 with active TB and 131 at a low risk for TB. Using 10 mm as a cut-off for TST, SPOT sensitivity (96.6%) was significantly higher than that seen for TST (66.7%) and QFT-G (70.1%). QFT-G showed superior specificity over TST (91.6versus78.6%). Although the specificity of QFT-G was higher than that of SPOT (91.6versus84.7%), the difference was not statistically significant.

Whilst some differences were found in the performance of the two commercialised interferon-γ assays, they seemed to be superior in their detection ofMycobacterium tuberculosisinfection compared with tuberculin skin tests. The most appropriate choice of interferon-γ assay to use may depend on the clinical setting.
Long-term clinical effects of interferon gamma-1b and colchicine in idiopathic pulmonary fibrosis
Authors: Antoniou K. M. , Nicholson A. G. , Dimadi M. , Malagari K. , Latsi P. , Rapti A. , Tzanakis N. , Trigidou R. , Polychronopoulos V. , Bouros D.
Published: April 2006

Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia is a deadly disease with no effective treatment. The purpose of this randomised prospective multicentric study was to characterise the clinical effects of interferon gamma (IFN-γ) 1b administered subcutaneously thrice weeklyversuscolchicine for 2 yrs. This study had no pre-specified end-points.

Fifty consecutive IPF patients were randomised. Patients with mild-to-moderate IPF were eligible for the study if they had histologically proven IPF, or, in the absence of surgical biopsy, fulfilled the European Respiratory Society/American Thoracic Society criteria.

In the intent-to-treat population, five out of 32 (15.6%) IFN-γ-1b patients and seven out of 18 (38.8%) colchicine patients died after a median follow-up period of 25 months Patients treated with IFN-γ 1b showed a better outcome after 2 yrs of therapy, and fewer symptoms, as assessed using the St George’s Respiratory Questionnaire, after 12 months of therapy. Also, the IFN-γ-1b group exhibited a higher forced vital capacity (percentage of the predicted value) after 24 months of treatment. No significant differences were detected in resting arterial oxygen tension, total lung capacity (% pred), transfer factor of the lung for carbon monoxide (% pred) and high-resolution computed tomographic scoring between the two treatment groups.

These data suggest that long-term treatment with interferon gamma 1b may improve survival and outcome in patients with mild-to-moderate idiopathic pulmonary fibrosis. Further studies are needed to verify these results.
Global burden of COPD: systematic review and meta-analysis
Authors: Halbert R. J. , Natoli J. L. , Gano A. , Badamgarav E. , Buist A. S. , Mannino D. M.
Published: April 2006

The aim of this study was to quantify the global prevalence of chronic obstructive pulmonary disease (COPD) by means of a systematic review and random effects meta-analysis.

PubMed was searched for population-based prevalence estimates published during the period 1990–2004. Articles were included if they: 1) provided total population or sex-specific estimates for COPD, chronic bronchitis and/or emphysema; and 2) gave method details sufficiently clearly to establish the sampling strategy, approach to diagnosis and diagnostic criteria.

Of 67 accepted articles, 62 unique entries yielded 101 overall prevalence estimates from 28 different counties. The pooled prevalence of COPD was 7.6% from 37 studies, of chronic bronchitis alone (38 studies) was 6.4% and of emphysema alone (eight studies) was 1.8%. The pooled prevalence from 26 spirometric estimates was 8.9%. The most common spirometric definitions used were those of the Global Initiative for Chronic Obstructive Lung Disease (13 estimates). There was significant heterogeneity, which was incompletely explained by subgroup analysis (e.g.age and smoking status).

The prevalence of physiologically defined chronic obstructive pulmonary disease in adults aged ≥40 yrs is ∼9–10%. There are important regional gaps, and methodological differences hinder interpretation of the available data. The efforts of the Global Initiative for Chronic Obstructive Lung Disease and similar groups should help to standardise chronic obstructive pulmonary disease prevalence measurement.
Nontuberculous mycobacterial disease and Aspergillus-related lung disease in bronchiectasis
Authors: Kunst H. , Wickremasinghe M. , Wells A. , Wilson R.
Published: April 2006

The aim of the present study was to determine whether patients with bronchiectasis and nontuberculous mycobacteria (NTM) have a higher prevalence of Aspergillus-related lung disease.

A series of 30 consecutive patients with bronchiectasis and NTM (cases) were compared with 61 patients with bronchiectasis and no evidence of NTM (controls). Aspergillus serology and computerised tomography of the thorax were used to identify Aspergillus-related lung diseases, including aspergilloma, allergic bronchopulmonary aspergillosis and chronic necrotising pulmonary aspergillosis.

The rate of positive Aspergillus serology was higher in cases with NTM disease compared with controls (10 out of 30versussix out of 61). The radiological features of Aspergillus-related lung disease were also more common among patients with NTM disease than controls (six out of 30versusnone out of 61). This association between NTM disease and Aspergillus-related lung disease remained significant after adjustment for confounding effects of age and lung function (adjusted odds ratio 5.1, 95% confidence interval 1.5–17.0).

Patients with bronchiectasis and nontuberculous mycobacterial disease have a higher prevalence of coexisting Aspergillus-related lung disease than patients with bronchiectasis and without nontuberculous mycobacteria. Identification of Aspergillus-related lung disease is important as prognosis amongst undetected cases is invariably poor.
Puzzling Out Slave Origins in Rio de Janeiro Port Unionism: The 1906 Strike and the Sociedade de Resistência dos Trabalhadores em Trapiche e Café
Authors: e Cruz Maria Cecília Velasco
Published: April 2006

Translated by Sabrina Gledhill.
Regulation of early lung morphogenesis: questions, facts and controversies
Authors: Cardoso Wellington V. , Lü Jining
Published: April 2006

During early respiratory system development, the foregut endoderm gives rise to the tracheal and lung cell progenitors. Through branching morphogenesis, and in coordination with vascular development, a tree-like structure of epithelial tubules forms and differentiates to produce the airways and alveoli. Recent studies have implicated the fibroblast growth factor, sonic hedgehog, bone morphogenetic protein, retinoic acid and Wnt signaling pathways, and various transcription factors in regulating the initial stages of lung development. However, the precise roles of these molecules and how they interact in the developing lung is subject to debate. Here, we review early stages in lung development and highlight questions and controversies regarding their molecular regulation.
Medakasimplet(FAM53B) belongs to a family of novel vertebrate genes controlling cell proliferation
Authors: Thermes Violette , Candal Eva , Alunni Alessandro , Serin Guillaume , Bourrat Franck , Joly Jean-Stéphane
Published: April 2006

The identification of genes that regulate proliferation is of great importance to developmental biology, regenerative medicine and cancer research. Using an in situ screen on a cortical structure of the medaka fish brain, we identified the simplet gene (smp), which is homologous to the human FAM53B gene. smp was expressed in actively proliferating cells of the CNS throughout embryogenesis. It belongs to a family of vertebrate-specific genes with no characterized biochemical domains. We showed that FAM53B bound 14-3-3 chaperones, as well as SKIIP proteins, adaptor proteins connecting DNA-binding proteins to modulators of transcription. smp inactivation with morpholinos led to delayed epiboly and reduced embryonic size. Absence of Smp activity did not induce apoptosis, but resulted in a reduced cell proliferation rate and enlarged blastomeres. Moreover, smp was shown to control the expression of the pluripotency-associated oct4/pou5f1 gene. We propose that smp is a novel vertebrate-specific gene needed for cell proliferation and that it is probably associated with the maintenance of a pluripotent state.
Diverse gap junctions modulate distinct mechanisms for fiber cell formation during lens development and cataractogenesis
Authors: Xia Chun-hong , Liu Haiquan , Cheung Debra , Cheng Catherine , Wang Eddie , Du Xin , Beutler Bruce , Lo Woo-Kuen , Gong Xiaohua
Published: April 2006

Different mutations of α3 connexin (Cx46 or Gja8) andα8 connexin (Cx50 or Gja8), subunits of lens gap junction channels, cause a variety of cataracts via unknown mechanisms. We identified a dominant cataractous mouse line (L1), caused by a missense α8 connexin mutation that resulted in the expression of α8-S50P mutant proteins. Histology studies showed that primary lens fiber cells failed to fully elongate in heterozygous α8S50P/+ embryonic lenses, but not in homozygous α8S50P/S50P, α8-/- andα3-/- α8-/- mutant embryonic lenses. We hypothesized that α8-S50P mutant subunits interacted with wild-typeα3 or α8, or with both subunits to affect fiber cell formation. We found that the combination of mutant α8-S50P and wild-type α8 subunits specifically inhibited the elongation of primary fiber cells, while the combination of α8-S50P and wild-type α3 subunits disrupted the formation of secondary fiber cells. Thus, this work provides the first in vivo evidence that distinct mechanisms, modulated by diverse gap junctions, control the formation of primary and secondary fiber cells during lens development. This explains why and how different connexin mutations lead to a variety of cataracts. The principle of this explanation can also be applied to mutations of other connexin isoforms that cause different diseases in other organs.
Interaction among three parallel cracks under a uniaxial cyclic load: A boundary element modelling
Authors: Yan X
Published: April 2006

This paper presents a numerical approach for modelling multiple-crack fatigue growth in a plane elastic infinite plate. It involves a generation of Bueckner's principle, a displacement discontinuity method with crack-tip elements (a boundary element method) proposed recently by the author, and an extension of Paris' equation to a multiple-crack problem under mixed-mode loading. Because of an intrinsic feature of the boundary element method, a general multiple-crack growth problem can be solved in a single region formulation. In the numerical simulation, for each increment of crack extension, remeshing of existing boundaries is not necessary. Crack extension is modelled conveniently by adding new boundary elements on the incremental crack extension to previous crack boundaries. As an example, interaction among three parallel cracks under cyclic load is investigated using the numerical approach. Many numerical results are given.
Displacements for an electromechanical integrated electrostatic harmonic drive
Authors: Xu L , Qin L , Zhu C
Published: April 2006

In this paper, using the displacement function, the basic equations of the displacements of the flexible ring for the drive are presented. The electromechanical coupled force between the flexible ring and stator for the drive is given. The electric field force and the displacement function are all defined in Fourier series form. Using the boundary condition of the flexible ring, undetermined coefficients of these equations are obtained, producing displacements of the flexible ring. The displacement distributions and the relationships between the average radial displacement and voltage are given. Changes of the displacements along with drive parameters are also analysed. Results show that periodical changes of radial displacement will cause periodical changes of capacity, which will create an electric field force to drive the flexible ring and make it rotate. In order to obtain a larger electric field force, the two free ends condition should be selected. In order to obtain a larger electric field force, a larger radius and width of the ring, smaller thickness and clearance, and proper voltage should be used. The results are useful in design and manufacture of the drive system.
Design and experimental investigations of a new type of casing treatment for an axial flow compressor
Authors: Zhu I , Chu W , Lu X
Published: April 2006

A new type of bend skewed groove casing treatment was designed on the basis of the test results of the axial skewed groove casing treatment. The influences of utilizing it on an isolated axial-flow rotor, as well as comparisons between it and the axial skewed groove, have been investigated experimentally. The effects on overall performance of the axial chord of the rotor exposed to the treated area have been examined, and the ideal axial position of the casing treatment relative to the rotor leading edge was found. For the tested rotor with the new casing treatment, experimental results showed that significant improvements in stall margin were observed without efficiency penalty (in some axial locations) at two different speeds. Compared with the axial skewed groove casing treatment, the new treated casing at the axial exposure does not increase the secondary circulation in the radial—circumferential plane based on x-wire, hot-wire measurements under the operating conditions near peak efficiency. This can be considered to be one of many factors that keep the rotor efficiency identical.
Tribological design of grinding wheels using X-ray diffraction techniques
Authors: Jackson M. J.
Published: April 2006

Grinding wheel wear is a significant problem when the wheel has to be continuously dressed in order to maintain high productivity and high-quality ground surfaces, especially during the manufacture of camshafts and crankshafts for certain automotive applications. This paper describes the use of X-rays to specifically engineer bonding systems for conventional abrasive grinding wheels so that the wheel wears considerably less during cylindrical grinding operations including the peculiarities associated with camshaft and crankshaft grinding. A significant factor associated with the wear of grinding wheels is the amount of free quartz that remains in heat-treated vitrified bonding systems. A number of quartz dissolution models have been developed that show how grinding wheel manufacturers can reduce the occurrence of bond fracture during grinding, and these models are compared with each other in this paper using X-ray diffraction techniques. This paper also explains how the use of X-rays can be used to develop the next generation of vitrified bonding systems that will allow grinding wheels to be cleaned and dressed with a laser without damaging the structure of the grinding wheel. A new method of dressing is reported that promotes preferred orientation of aluminium oxide abrasive grains that allows grinding wheels to operate in the roughing, finishing, and superfinishing grinding regimes.
Functional replacement of Trypanosoma brucei Argonaute by the human slicer Argonaute2
Authors: Shi Huafang , Tschudi Christian , Ullu Elisabetta
Published: April 2006

RNA interference (RNAi) is widespread throughout the eukaryotic lineage, from protozoa to man. Central to all RNAi phenomena is a member of the Argonaute protein family, and, in the case of dsRNA-triggered mRNA cleavage, the Ago protein functions as the RNAi endonuclease or slicer. However, at present there is no definite experimental evidence that slicer Argonautes can be interchanged between distantly related organisms. Here, we show that the human slicer Argonaute2 (HsAgo2), but not HsAgo1, functions in RNAi in the early divergent protozoan Trypanosoma brucei, thus mimicking the situation in mammalian cells. This finding indicates that the basic features of the RNAi mechanism are conserved from T. brucei to man.
The domain of the Bacillus subtilis DEAD-box helicase YxiN that is responsible for specific binding of 23S rRNA has an RNA recognition motif fold
Authors: Wang Shuying , Hu Yaoxiong , Overgaard Michael T. , Karginov Fedor V. , Uhlenbeck Olke C. , McKay David B.
Published: April 2006

The YxiN protein of Bacillus subtilis is a member of the DbpA subfamily of prokaryotic DEAD-box RNA helicases. Like DbpA, it binds with high affinity and specificity to segments of 23S ribosomal RNA as short as 32 nucleotides (nt) that include hairpin 92. Several experiments have shown that the 76-residue carboxy-terminal domain of YxiN is responsible for the high-affinity RNA binding. The domain has been crystallized and its structure has been solved to 1.7 Å resolution. The structure reveals an RNA recognition motif (RRM) fold that is found in many eukaryotic RNA binding proteins; the RRM fold was not apparent from the amino acid sequence. The domain has two solvent exposed aromatic residues at sites that correspond to the aromatic residues of the ribonucleoprotein (RNP) motifs RNP1 and RNP2 that are essential for RNA binding in many RRMs. However, mutagenesis of these residues (Tyr404 and Tyr447) to alanine has little effect on RNA affinity, suggesting that the YxiN domain binds target RNAs in a manner that differs from the binding mode commonly found in many eukaryotic RRMs.
Parathyroid Hormone Monitoring during Total Parathyroidectomy for Renal Hyperparathyroidism: Pilot Study of the Impact of Renal Function and Assay Specificity
Authors: Bieglmayer Christian , Kaczirek Klaus , Prager Gerhard , Niederle Bruno
Published: April 2006

Background: Commonly used assays for intact parathyroid hormone (iPTH) detect not only the biologically active 84–amino acid hormone [PTH(1–84)], but cross-react with an N-terminal–truncated fragment. Because iPTH assays often fail to predict success of parathyroidectomy in patients with renal hyperparathyroidism (rHPT), we compared results of a 3rd-generation PTH(1–84) assay (Bio-iPTH; Nichols Institute Diagnostics) with two 2nd-generation iPTH assays (from Nichols and Roche Diagnostics) by evaluating the PTH clearance kinetics during surgical treatment.

Methods: We collected blood samples in short time intervals from 35 consecutive surgical patients with rHPT. Three patients had to be excluded from further calculations; the remainder were grouped according to kidney function and postoperative outcome. All samples were analyzed with the 3 automated PTH assays, which have different specificities.

Results: Twenty minutes after removal of the last gland, the PTH(1–84) values decreased to within the reference intervals in all patients with total and subtotal resection; however, iPTH concentrations normalized in only one half of these patients. In patients with poor renal function, the half-life of PTH(1–84) was shorter than the half-lives obtained with the iPTH assays.

Conclusions: The accuracy of PTH monitoring during surgery for rHPT depends on renal function and assay specificity. All assays tested showed similar effectiveness in detecting missed glands, but the assay for PTH(1–84) gave more reliable results than the iPTH assays, which overestimated the concentration of PTH and hampered the intrasurgical diagnosis of resection sufficiency.
Effects of Glutaraldehyde Exposure on Human Health
Authors: Takigawa Tomoko , Endo Yoko
Published: April 2006

Effects of Glutaraldehyde Exposure on Human Health: Tomoko Takigawa,et al.Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences—Glutaraldehyde (GA) is widely used in the industrial, scientific and biomedical fields. Many adverse health effects on humans have been reported in association with biomedical uses of GA, with 2–3.5% aqueous GA solution generally used for cold sterilization and GA exposure ranges of 0.001 to 2.6 ppm for this type of use. GA is metabolized extensively to CO2, but urinary excretion of it is low. Sensory irritant effects, sensitization of skin and respiratory organs and other symptoms have been reported among endoscopy nurses and medical radiation technologists. The prevalence of chronic bronchitis and nasal symptoms in humans is significantly correlated with peak concentrations of GA exposure. The extent of primary skin irritation depends on the duration and site of contact, and the severity of symptoms is dose‐related. Chronic inhalation affects the nose and respiratory tract, and lesions become severe with prolonged duration of exposure. Increases in neither mortality nor tumor incidence have been found in workers with less than 0.2 ppm GA exposure, no evidence of carcinogenic activity has been obtained in experimental animal studies. There has been no clear evidence of genetic toxicity of GA in either in vitro or in vivo studies, and neither developmental nor reproductive toxicity has been found in humans or animals. To prevent hazards from GA exposure, use of closed‐system, fully automated washing machines is recommended, since numerous symptoms have been found in individuals with less than 0.05 ppm GA exposure, the recommended peak exposure limit in many countries.
Capecitabine Monotherapy: Safe and Effective Treatment for Metastatic Breast Cancer
Authors: Ershler William B.
Published: April 2006

Learning Objectives

After completing this course, the reader will be able to: Describe the pharmacology of capecitabine.Discuss the use of capecitabine as a single agent and in refractory disease.Discuss safety and dosing considerationsDescribe current adjuvant treatment with capecitabine.

Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com

Optimal management for metastatic breast cancer frequently involves cytotoxic chemotherapy. Over the years, several complex multidrug regimens have been developed that were based upon a rationale of synergistic antitumor activity and nonoverlapping toxicities. However, recently the clinical value of these complex regimens has been called into question as several drugs used alone (monotherapy) or in sequence (serial single agent) have been shown to be both efficacious and better tolerated. Capecitabine (an orally administered fluoropyrimidine carbamate) is one such agent that has been proven to be effective when used alone for metastatic breast cancer, metastatic colorectal cancer, and adjuvant colon cancer. In this review, published (or reported in abstract form) data examining various aspects of clinical response and tolerability with single-agent capecitabine for (primarily) first- and second-line metastatic breast cancer are examined. For the most part, response rates are comparable with those of the more complex regimens. Dose reductions from the labeled dose of 1,250 mg/m2 twice daily are relatively common. Toxicities (following dose reductions if needed) are generally manageable, even by more frail patients. Elderly patients are more likely to have impaired renal function or be receiving warfarin treatment, and special attention to these factors is warranted. Nonetheless, the drug administered alone is a reasonable choice when single-agent chemotherapy is entertained as a treatment option for metastatic breast cancer, including in the first-line setting.
Pegylated Liposomal Doxorubicin Consolidation Therapy after Platinum/Paclitaxel-Based Chemotherapy for Suboptimally Debulked, Advanced-Stage Epithelial Ovarian Cancer Patients
Authors: Rocconi Rodney P. , Straughn J. Michael , Leath Charles A. , Kilgore Larry C. , Huh Warner K. , Barnes Mack N. , Partridge Edward E. , Alvarez Ronald D.
Published: April 2006

Objective. To assess the feasibility of using pegylated liposomal doxorubicin (PLD) as a consolidation therapy in patients with advanced ovarian cancer who have attained a clinically defined complete response to initial platinum/paclitaxel-based chemotherapy.

Methods. Patients diagnosed with suboptimally debulked stage IIIC/IV epithelial ovarian cancer who attained a clinically defined complete response at the completion of platinum/paclitaxel-based chemotherapy were eligible for this protocol. Patients were treated with PLD at a dose of 40 mg/m2 every 28 days for four cycles. A survival analysis was calculated using the Kaplan-Meier method.

Results. Of the 30 patients enrolled, 29 were evaluable. Twenty-three patients (79%) completed all four cycles of consolidation therapy. Palmar-plantar erythrodysesthesia was the most common toxicity. Six patients remained clinically without evidence of disease with a median follow-up of 35 months from the completion of primary chemotherapy. The median progression-free interval was 15 months, and median overall survival time was 31 months, with 47% of patients achieving a 4-year survival.

Conclusions. Consolidation therapy with PLD chemotherapy administered to women with advanced epithelial ovarian cancer after initial chemotherapy appears feasible based on its toxicity profile. Considering the tolerability of this agent, further investigation is needed to depict the optimal dose and schedule needed for consolidation therapy.
Clinical Implications of EGFR Expression in the Development and Progression of Solid Tumors: Focus on Non-Small Cell Lung Cancer
Authors: Ettinger David S.
Published: April 2006

Learning Objectives

After completing this course, the reader will be able to: Describe the EGFR signaling pathway as a target for new anticancer agents.Characterize the various EGFR agents developed for the treatment of NSCLC.Identify the appropriate indications for the use of these new agents.

Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com

Dysregulation of the epidermal growth factor receptor (EGFR) signaling pathway is associated with the development and progression of malignancy, and EGFR-targeted therapies offer the promise of better treatment for many types of solid tumors, including non-small cell lung cancer. Anti-EGFR agents include monoclonal antibodies (mAbs) targeting the EGFR extracellular receptor domain and small-molecule tyrosine kinase inhibitors (TKIs) targeting the EGFR intracellular kinase domain. Both mAbs and TKIs have demonstrated encouraging results as monotherapies and in combination with chemotherapy and radiotherapy. This review provides a critical update on the status of these novel therapeutics.
Darbepoetin Alfa Administered Every Three Weeks Is Effective for the Treatment of Chemotherapy-Induced Anemia
Authors: Boccia Ralph , Malik Imtiaz A. , Raja Vinay , Kahanic Stephen , Liu Randall , Lillie Tom , Tomita Dianne , Clowney Billy , Silberstein Peter
Published: April 2006

Patients with cancer receiving chemotherapy often have chemotherapy-induced anemia (CIA) and reduced quality of life. Darbepoetin alfa can effectively treat CIA when administered at an extended dosing interval of once every 3 weeks (Q3W). Darbepoetin alfa administered Q3W may allow synchronization of darbepoetin alfa therapy with chemotherapy administered Q3W. This multicenter, open-label, 16-week study evaluated the effectiveness and safety of darbepoetin alfa administered as a fixed dose (300 μg) Q3W in patients with CIA. Eligible patients (≥18 years) were anemic (hemoglobin <11g/dl), had a nonmyeloid malignancy, and were receiving multicycle chemotherapy. This analysis includes 1,493 patients who received at least one dose of darbepoetin alfa. The effect of baseline hemoglobin (<10 or ≥10 g/dl) on clinical outcomes was evaluated. Patients in the ≥10-g/dl stratum achieved the hemoglobin target range (11–13g/dl)in less time than patients in the <10-g/dlstratum (3 weeks vs. 9 weeks). More patients in the ≥10-g/dl stratum achieved the hemoglobin target range (87% vs. 66%); however, similar proportions of patients in both strata maintained hemoglobin within the target range (73% vs. 71%). Fewer patients in the ≥10-g/dl stratum received RBC transfusions from week 5 to the end of the study (12% vs. 28%). Over 50% of patients in both strata reported clinically significant improvements (≥3-point increase) in Functional Assessment of Cancer Therapy–Fatigue score. Twenty-eight percent of patients reported serious adverse events; 3% of all patients had a venous or arterial thrombotic event. This study demonstrates that darbepoetin alfa Q3W is well tolerated and effective for treating CIA.
The influence of sex steroid hormones on ferrochelatase gene expression in Harderian gland of hamster (Mesocricetus auratus)
Authors: Vilchis F , Ramos L , Timossi C , Chávez B
Published: April 2006

Ferrochelatase (protohaem ferrolyase, EC 4.99.1.1), the terminal enzyme of the haem biosynthetic pathway, catalyses the insertion of ferrous iron into protoporphyrin IX to form protohaem. The Syrian hamster Harderian gland (HG) is known for its ability to produce and accumulate large amounts of protoporphyrins. In this species, the female gland contains up to 120 times more porphyrin than the male gland. Data from biochemical studies suggest that this gland possesses the enzymatic complex for haem biosynthesis but lacks ferrochelatase activity. The abundance of intraglandular haem proteins does not support this idea. To gain more insight into this process, we isolated cDNA for ferrochelatase from hamster liver, using the 5′- and 3′- rapid amplification of complementary DNA ends (RACE), and investigated its expression in HG from males and females. The full-length cDNA comprises an open reading frame of 1269 bp encoding a polypeptide of 422 amino-acid residues. Hamster DNA sequence exhibits 92% identity to mouse and 87% identity to human sequences. The predicted hamster enzyme was shown to have structural features of mammalian ferrochelatase, including a putative NH2- terminal presequence, a central core of about 330 amino-acid residues and an extra 30–50-amino-acid stretch at the carboxyl-terminus. RNA blotting experiments indicated that this cDNA hybridized to a liver mRNA of about 2.1 kb, while a weak hybridization signal was observed with mRNA from HG preparations. RT–PCR assays confirmed the expression of specific transcripts in both tissues. Male glands contained approximately twofold more enzyme mRNA than female glands. Likewise, the intraglandular content of mRNA varied during the oestrous cycle, with the highest levels found in the oestrous phase. These cyclic variations were less evident in liver. Ovariectomy plus treatment with progesterone or 17β-oestradiol plus progesterone increased ferrochelatase mRNA of the gland. In HG of short- or long-term castrated males, the administration of testosterone did not affect the ferrochelatase mRNA concentration. Based on mRNA expression levels, we conclude that Harderian ferrochelatase may play an active role in maintaining the physiological pool of haem required for processing cytochromes and other glandular haem proteins. Likewise, the sex-steroid hormones appear to have only a modest influence upon Harderian ferrochelatase.
Ghrelin enhances glucose-induced insulin secretion in scheduled meal-fed sheep
Authors: Takahashi H , Kurose Y , Kobayashi S , Sugino T , Kojima M , Kangawa K , Hasegawa Y , Terashima Y
Published: April 2006

The purpose of this study was to investigate the effects of physiologic levels of ghrelin on insulin secretion and insulin sensitivity (glucose disposal) in scheduled fed-sheep, using the hyperglycemic clamp and hyperinsulinemic euglycemic clamp respectively. Twelve castrated Suffolk rams (69.8 ± 0.6 kg) were conditioned to be fed alfalfa hay cubes (2% of body weight) once a day. Three hours after the feeding, synthetic ovine ghrelin was intravenously administered to the animals at a rate of 0.025 and 0.05 μg/kg body weight (BW) per min for 3 h. Concomitantly, the hyperglycemic clamp or the hyperinsulinemic euglycemic clamp was carried out. In the hyperglycemic clamp, a target glucose concentration was clamped at 100 mg/100 ml above the initial level. In the hyperinsulinemic euglycemic clamp, insulin was intravenously administered to the animals for 3 h at a rate of 2 mU/kg BW per min. Basal glucose concentrations (44± 1 mg/dl) were maintained by variably infusing 100 mg/dl glucose solution. In both clamps, plasma ghrelin concentrations were dose-dependently elevated and maintained at a constant level within the physiologic range. Ghrelin infusions induced a significant (ANOVA; P < 0.01) increase in plasma GH concentrations. In the hyperglycemic clamp, plasma insulin levels were increased by glucose infusion and were significantly (P < 0.05) greater in ghrelin-infused animals. In the hyperinsulinemic euglycemic clamp, glucose infusion rate, an index of insulin sensitivity, was not affected by ghrelin infusion. In conclusion, the present study has demonstrated for the first time that ghrelin enhances glucose-induced insulin secretion in the ruminant animal.
Effects of long-term treatment with resveratrol and subcutaneous and oral estradiol administration on pituitary function in rats
Authors: Böttner Martina , Christoffel Julie , Jarry Hubertus , Wuttke Wolfgang
Published: April 2006

Hormone replacement therapy (HRT) has been used for several decades to treat menopausal discomforts. However, in the light of recent studies that draw attention to the potential hazards of conventional HRT, various attempts have been undertaken to search for alternatives to classical HRT. Phytoestrogens are claimed to be capable of positively influencing menopausal symptoms, including hot flushes. We designed a long-term study of 3 months to assess the effects of subcutaneous and orally fed 17β-estradiol (E2), as well as the actions of resveratrol (RES) on pituitary function in female rats. Our results have demonstrated that RES binds with a 10-fold lower affinity to estrogen receptor (ER)-α than to ERβ. The data from the in vivo study revealed that a dosage of 5 μg and 50 μg RES/kg bodyweight per day given to ovariectomized (OVX) rats achieved serum levels of 1.0 and 8.1 μM respectively. Long-term treatment of OVX rats with RES revealed no estrogenic potential on pituitary function in vivo as assessed by LH and prolactin secretion and by regulation of mRNAs for LHα, LHβ, and GnRH receptor. Subcutaneous treatment with E2 in silastic capsules exerted stronger effects on LH and prolactin secretion, as well as on LHβ, LHα, GnRH receptor, and ERβ mRNA regulation compared with orally applied estradiol benzoate despite comparable serum levels. Levels of aryl hydrocarbon receptor (AhR) mRNA in the pituitary were increased following OVX and attenuated by long-term E2 treatment, whereas RES did not modulate AhR mRNA expression.
Ocimum sanctum leaf extracts stimulate insulin secretion from perfused pancreas, isolated islets and clonal pancreatic β-cells
Authors: Hannan J M A , Marenah L , Ali L , Rokeya B , Flatt P R , Abdel-Wahab Y H A
Published: April 2006

Ocimum sanctum leaves have previously been reported to reduce blood glucose when administered to rats and humans with diabetes. In the present study, the effects of ethanol extract and five partition fractions of O. sanctum leaves were studied on insulin secretion together with an evaluation of their mechanisms of action. The ethanol extract and each of the aqueous, butanol and ethylacetate fractions stimulated insulin secretion from perfused rat pancreas, isolated rat islets and a clonal rat β-cell line in a concentration-dependent manner. The stimulatory effects of ethanol extract and each of these partition fractions were potentiated by glucose, isobutylmethylxanthine, tolbutamide and a depolarizing concentration of KCl. Inhibition of the secretory effect was observed with diazoxide, verapamil and Ca2+ removal. In contrast, the stimulatory effects of the chloroform and hexane partition fractions were associated with decreased cell viability and were unaltered by diazoxide and verapamil. The ethanol extract and the five fractions increased intracellular Ca2+ in clonal BRIN-BD11 cells, being partly attenuated by the addition of verapamil. These findings indicated that constituents of O. sanctum leaf extracts have stimulatory effects on physiological pathways of insulin secretion which may underlie its reported antidiabetic action.
Geostopping With Resistivity-Forward Modeling to Prevent Drilling Into The Loss-Circulation Zone of a Prolific Carbonate Reservoir
Authors: Kok Keng H. , Pruimboom John , David Frank M. , Then Jit-Chiun
Published: April 2006

The field-development plan for a Sarawak Shell Bhd. operated gas field, located in the South China Sea offshore Sarawak, Malaysia, specified drilling of horizontal wells into the Tertiary-Miocene carbonate reservoir. The wells were planned as high-capacity producers with a big-bore, long-casing flow design.

The traditional well design dictated that before entering the reservoir a casing had to be installed to stabilize the hole in soft shale. The uncertainty of detecting the formation top resulted in a premature casing commitment of atleast 30 ft true vertical depth (TVD) above the top of the reservoir and the need to use an expandable liner to cover 300 ft of exposed shale above the reservoir.

To obviate this problem, the capability of one of the components in the logging-while-drilling (LWD) tool array, specifically the electromagnetic-wave-resistivity (EWR) forward-modeling technique, was used to detect the top of the carbonate formation (i.e., the top of reservoir),immediately before drilling into it. A standard LWD tool is configured to prioritize EWR forward-model response as the carbonate-formation top is approached. This configuration, together with an appropriately designed bottomhole assembly (BHA) and well trajectory, enabled the successful implementation of the plan to stop drilling approximately 1 ft TVD above the carbonate top.

At this point, a conventional 9⅝-in. casing string was set at an optimum depth. This eliminated potential well-control problems, costly remedial actions associated with lost circulation, and inferior cementation of the 9⅝-in. casing string.

There after, the wells were drilled horizontally in a conventional manner into the carbonate-gas reservoir.

This paper compares predrilling EWR forward modeling of the proposed well trajectory with the actual well data while drilling. The predrilling- and post-drilling-modeled data are presented.

The cost savings from employing this technique are variable, ranging from substantial—in the event of a well-control situation and attendant high losses—to moderate if the need to set an expandable liner is eliminated. Aminimum of U.S. $1 million per well was saved with this technique.