bluuebunny/crossref_metadata_2025 huggingface dataset:
Polymer nanocomposites formation by the use of sodium montmorillonite dispersion in alcohol and a cationic surfactant
Authors: Sasaki Akinobu , White James L.
Published: December 2003

To enhance the formation of nanocomposites, we pretreated montmorillonite clay with a high‐boiling‐point alcohol or a combination of the alcohol and a cationic surfactant prior to melt mixing. The polymer matrix was melt‐mixed with sodium montmorillonite treated with alcohol or a combination of the alcohol and a cationic surfactant, and then, the alcohol was removed. This new method was applied to polymethyl methacrylate, polystyrene, polyethylene, and polypropylene compounds. The dual use of a surfactant and an alcohol for the treatment of montmorillonite enabled a high degree of intercalation of montmorillonite layers by polymethyl methacrylate chains, which was not obtained in untreated clay or clay treated with either the surfactant or alcohol individually. The process was not as successful with the polyhydrocarbons. There was some evidence for slightly enhanced intercalation for polystyrene, but there was less evidence for polyethylene and polypropylene. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 1951–1957, 2004
Gas permeation performance of cellulose hollow fiber membranes made from the cellulose/N‐methylmorpholine‐N‐oxide/H2O system
Authors: Jie Xingming , Cao Yiming , Lin Bin , Yuan Quan
Published: December 2003

Cellulose hollow fiber membranes (CHFM) were prepared using a spinning solution containing N‐methylmorpholine‐N‐oxide as solvent and water as a nonsolvent additive. Water was also used as both the internal and external coagulant. It was demonstrated that the phase separation mechanism of this system was delayed demixing. The CHFM was revealed to be homogeneously dense structure after desiccation. The gas permeation properties of CO2, N2, CH4, and H2 through CHFM were investigated as a function of membrane water content and operation pressure. The water content of CHFM had crucial influence on gas permeation performance, and the permeation rates of all gases increased sharply with the increase of membrane water content. The permeation rate of CO2 increased with the increase of operation pressure, which has no significant effect on N2, H2, and CH4. At the end of this article a detailed comparison of gas permeation performance and mechanism between the CHFM and cellulose acetate flat membrane was given. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 1873–1880, 2004
Increased oxidative stress with aging reduces chondrocyte survival: Correlation with intracellular glutathione levels
Authors: Carlo Marcello Del , Loeser Richard F.
Published: December 2003

Objective

To examine the role of oxidative stress in mediating cell death in chondrocytes isolated from the articular cartilage of young and old adult human tissue donors.

Methods

Cell death induced by the oxidant SIN‐1 was evaluated in the alginate bead culture system using fluorescent probes to assess membrane integrity. Generation of peroxynitrite by the decomposition of SIN‐1 was confirmed by positive immunostaining of treated cells for 3‐nitrotyrosine. Determinations of oxidized glutathione (GSSG) and reduced glutathione (GSH) were performed in monolayer cultures using an enzyme‐ recycling assay. Cells were depleted of intracellular glutathione either by the addition of DL‐buthionine‐(S,R)‐sulfoximine or by removal of L‐cystine from the culture media. The activity of cellular antioxidant enzymes was determined spectrophotometrically by the decay of substrate from the reaction mixture.

Results

More chondrocytes (>2‐fold) from old donors (≥50 years) died after exposure to 1 mM SIN‐1 relative to those derived from young donors (18–49 years). Although autocrine production of insulin‐like growth factor 1 (IGF‐1) promotes chondrocyte survival, pretreatment with IGF‐1 could not prevent the cell death induced by SIN‐1 exposure. Cells isolated from old donors had a higher ratio of GSSG to GSH. Glutathione reductase is the principal enzyme involved in the regeneration of GSH from GSSG. Treatment of chondrocytes with SIN‐1 to induce oxidative stress in vitro resulted in the decreased activity of glutathione reductase and thioredoxin reductase, but not catalase. Cells depleted of intracellular glutathione were more susceptible to cell death induced by SIN‐1.

Conclusion

These results provide evidence that increased oxidative stress with aging makes chondrocytes more susceptible to oxidant‐mediated cell death through the dysregulation of the glutathione antioxidant system. This may represent an important contributing factor to the development of osteoarthritis in older adults.
Occurrence of Raynaud's phenomenon in children ages 12–15 years: Prevalence and association with other common symptoms
Authors: Jones Gareth T. , Herrick Ariane L. , Woodham Sarah E. , Baildam Eileen M. , Macfarlane Gary J. , Silman Alan J.
Published: December 2003

Objective

Although Raynaud's phenomenon (RP) in adults is frequently reported as having been present since childhood, there have been no studies on the prevalence of RP in children. This study was undertaken to ascertain the prevalence of RP in children ages 12–15 years and to determine whether, as with other commonly reported symptoms, there were any associations with adverse psychosocial factors.

Methods

A previously validated self‐administered RP questionnaire was distributed to 903 children ages 12–15 years, from 28 schools. The questionnaire also included questions on other common childhood symptoms and on adverse psychosocial factors.

Results

Seven hundred twenty children responded (80%), in whom the prevalence of RP was 15%. This was higher in girls (18% versus 12%) and increased with age. After adjustment for age and sex, there was an association with reporting of current pain, both in the arm/shoulder region and elsewhere in the body. There were no associations with psychosocial variables.

Conclusion

RP is frequent in children ages 12–15 years. Unlike other common childhood symptoms, RP showed no association with psychosocial factors in this study.
Reduction in the evolution of murine type II collagen–induced arthritis by treatment with rosiglitazone, a ligand of the peroxisome proliferator–activated receptor γ
Authors: Cuzzocrea Salvatore , Mazzon Emanuela , Dugo Laura , Patel Nimesh S. A. , Serraino Ivana , Di Paola Rosanna , Genovese Tiziana , Britti Domenico , De Maio Massimo , Caputi Achille P. , Thiemermann Christoph
Published: December 2003

Objective

The peroxisome proliferator–activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily of ligand‐dependent transcription factors related to retinoid, steroid, and thyroid hormone receptors. The thiazolidinedione rosiglitazone is a PPARγ ligand that modulates the transcription of target genes. The aim of this study was to investigate the effects of rosiglitazone on the inflammatory response in mice with collagen‐induced arthritis (CIA).

Methods

CIA was induced in DBA/1J mice by an intradermal injection of 100 μl of an emulsion of bovine type II collagen (CII; 100 μg) in Freund's complete adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Rosiglitazone (10 mg/kg/day) or vehicle (10% DMSO) was administered beginning on day 25 (arthritis onset) until day 35. Clinical, radiographic, histopathologic, and laboratory assessments were performed.

Results

Mice immunized with CII in CFA developed erosive arthritis of the hind paws. Macroscopic evidence of CIA first appeared as periarticular erythema and edema of the hind paws. The incidence of CIA was 100% by day 27 in the CII‐challenged mice, and the severity progressed over the 35‐day study period. Radiographic evaluation revealed focal resorption of bone. Histopathologic features of CIA included erosion of cartilage at the joint margins. Rosiglitazone treatment ameliorated the clinical signs on days 26–35 and improved the histologic findings in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in rosiglitazone‐treated mice, as indicated by elevation of malondialdehyde levels, formation of nitrotyrosine, and activation of poly(ADP‐ribose) polymerase. Plasma levels of the proinflammatory cytokines tumor necrosis factor, interleukin‐1β, and interleukin‐6 were also significantly reduced by rosiglitazone treatment.

Conclusion

These data demonstrate that rosiglitazone exerts an antiinflammatory effect on chronic inflammation and is able to ameliorate the tissue damage associated with CIA.
Development of autoimmune exocrinopathy resembling Sjögren's syndrome in adoptively transferred mice with autoreactive CD4+ T cells
Authors: Arakaki Rieko , Ishimaru Naozumi , Saito Ichiro , Kobayashi Masaru , Yasui Natsuo , Sumida Takayuki , Hayashi Yoshio
Published: December 2003

Objective

The pathologic mechanisms responsible for organ‐specific tissue damage in primary Sjögren's syndrome (SS) remain unclear, but it has been suggested that the pathology is mediated by autoreactive CD4+ T cells infiltrating the salivary and lacrimal glands. This study was undertaken to investigate whether α‐fodrin autoantigen–specific autoreactive CD4+ T cells are capable of inducing autoimmune lesions.

Methods

A total of 45 synthetic α‐fodrin peptides designed to be 20 amino acid residues in length were generated. To establish an autoreactive T cell line, limiting dilution analysis (LDA) was performed on lymph node cells (LNCs) in the presence of α‐fodrin peptides. The effects of adoptive transfer of autoreactive CD4+ T cells into normal syngeneic recipients were investigated.

Results

Autoreactive CD4+ T cell lines that recognize synthetic α‐fodrin peptide, which produced Th1 cytokines and showed cytotoxic activities, were established in a murine model for SS. T cell receptor Vβ usage and third complementarity‐determining region (CDR3) sequences indicated that in some cases Vβ6‐CDR3 genes matched between the tissue‐infiltrating T cells and the autoreactive T cell lines. Adoptive transfer of the autoreactive CD4+ T cells into normal syngeneic recipients induced autoimmune lesions quite similar to those of SS.

Conclusion

Our data help to elucidate the pathogenic mechanisms responsible for tissue destruction in autoimmune exocrinopathy and indicate that autoreactive CD4+ T cells play a pivotal role in the development of murine SS.
Splenectomy attenuates streptococcal cell wall–induced arthritis and alters leukocyte activation
Authors: Kimpel Donald , Dayton Tim , Fuseler John , Gray Laura , Kannan Krishnaswamy , Wolf Robert E. , Grisham Matthew
Published: December 2003

Objective

To investigate the role of the spleen in the pathogenesis of streptococcal cell wall (SCW)–induced arthritis and determine the impact of splenectomy on monocytes and T cells involved in the arthritis.

Methods

Female Lewis rats were separated into 4 groups: 1) saline‐injected, sham‐operated; 2) saline‐injected, splenectomized; 3) peptidoglycan–polysaccharide (PG‐PS)–injected, sham‐operated; and 4) PG‐PS–injected, splenectomized. After a 10‐day recovery period, rats received a single intraperitoneal injection of saline or PG‐PS (25 μg rhamnose/gm body weight). We evaluated the effect of splenectomy on joint inflammation, histopathology, leukocyte subtypes in blood and lymph nodes, cytokines, and cell surface expression of CD44 and CD45RC in the chronic phase of the disease (day 28).

Results

Splenectomy dramatically decreased chronic joint inflammation and histopathologic damage as well as altered cell types in lymph nodes and peripheral blood, as analyzed by flow cytometry. Nitric oxide (NO) production, levels of interleukin‐1β (IL‐1β), IL‐6, tumor necrosis factor α, and a biomarker of Th1 cell predominance correlated with the level of joint inflammation. Surprisingly, in splenectomized animals, increased expression of adhesion molecules thought to track T cells to inflamed tissue were observed in lymph nodes.

Conclusion

The result of splenectomy was attenuation of SCW‐induced arthritis and changes in mediators of inflammation, including T cell subsets, proinflammatory cytokines, and NO production. Splenectomy may remove an important antigen reservoir and alter immune cell activation in the SCW‐induced arthritis model.
Leflunomide use during the first 33 months after food and drug administration approval: Experience with a national cohort of 3,325 patients
Authors: Siva Chokkalingam , Eisen Seth A. , Shepherd Rebecca , Cunningham Francesca , Fang Meika A. , Finch William , Salisbury Don , Singh Jasvinder A. , Stern Richard , Zarabadi S. Alireza
Published: December 2003

Objective

To describe leflunomide (LEF) use in a national cohort of 3,325 veterans.

Methods

Prescriptions for LEF and 9 disease‐modifying antirheumatic drugs written between October 1998 and June 2001 at all Veterans Affairs (VA) medical centers were obtained from VA national databases.

Results

LEF was initiated with a loading dose of 100 mg daily for 3 days in 61% of patients, and 42% of patients discontinued LEF. LEF was more likely to be discontinued if a 3‐day 100‐mg loading dose was prescribed, patients were younger than 44 years or older than 75 years, or reported an annual family income <$60,000. Review of medical records of 291 discontinuers revealed that the most common reasons for discontinuation were inefficacy (30%), gastrointestinal symptoms (29%), medication noncompliance or lost to followup (14%), and elevated liver enzymes (5%).

Conclusion

LEF is relatively safe in clinical practice. The VA's national databases provide an excellent, inexpensive resource for postmarketing evaluation of rheumatologic medications.
Association of nitrate use with risk of new radiographic features of hip osteoarthritis in elderly white women: The study of osteoporotic fractures
Authors: Lane Nancy E. , Williams Elizabeth N. , Hung Yun‐Yi , Hochberg Marc C. , Cummings Steven R. , Nevitt Michael C.
Published: December 2003

Objective

To examine the association between nitrate medication use and the development of new radiographic findings of hip osteoarthritis (OA) in elderly women.

Methods

Pelvic radiographs were obtained at baseline and a mean of 8.3 years later in 5,987 women, age ≥65 years at the baseline examination of the Study of Osteoporotic Fractures. Atlas‐standardized individual radiographic features (IRFs) of OA were assessed and minimal joint space was measured on paired films. New radiographic findings of hip OA were defined as the development in hips free of these findings at baseline: 1) joint space narrowing (JSN), which consisted of either a MJS ≤1.5 mm or an IRF score indicating lateral JSN ≥2 or medial JSN ≥3; 2) an IRF score for osteophytes of ≥2 in any location; or 3) a summary grade of 2 or more (at least 2 IRFs present). Nitrate use was recorded by interview at years 6 and 8. Logistic and linear regression analyses were performed to determine the association of nitrate use with new radiographic findings of hip OA, adjusting for age, weight, height, bone mineral density, and estrogen.

Results

Compared with no reported use of nitrates, we found significant associations between use of nitrates at 1 clinic visit and new JSN (odds ratio [OR] 1.94, 95% confidence interval [95% CI] 1.18–3.17, P = 0.009), new osteophyte formation (OR 1.70, 95% CI 1.03–2.88, P = 0.04), and any new radiographic finding of hip OA or total hip arthroplasty for OA (OR 1.71, 95% CI 1.16–2.52, P = 0.007). Any nitrate use was associated with an increased risk of developing summary grade 3 or greater hip OA (OR 1.84, 95% CI 1.03–3.31, P = 0.041), but not with any other incident findings of OA.

Conclusion

Older women using nitrates may have an increased risk of developing new radiographic findings of hip OA.
Access to pediatric rheumatology care in the United States
Authors: Mayer Michelle L. , Mellins Elizabeth D. , Sandborg Christy I.
Published: December 2003

Objective

To describe rheumatology providers, depict their availability, and determine the extent to which internist rheumatologists may expand access to care for children with rheumatic diseases.

Methods

Using data from the American College of Rheumatology and the Bureau of Health Professions Area Resource File, we generated a national map of providers' practice locations and calculated distances between each county and the nearest rheumatologist. We also performed a logit analysis to identify provider and county characteristics that were associated with internist rheumatologists' willingness to treat children.

Results

Approximately 50% of the under 18 population in the United States live within 50 miles of a pediatric rheumatologist and nearly 90% live within 50 miles of a pediatric rheumatologist or an internist rheumatologist who treats children. Internist rheumatologists in private practice were 3 times as likely as those in medical schools to treat children (P < 0.001). Likewise, internist rheumatologists who live 200 or more miles from a pediatric rheumatologist were more than twice as likely to treat children as those who lived within 10 miles of a pediatric rheumatologist (P < 0.001).

Conclusions

Our analysis suggests that internist rheumatologists are more geographically diffuse than pediatric rheumatologists and act as substitutes for pediatric rheumatologists in those regions that lack such providers. Research is needed to understand the role of internist rheumatologists in caring for children with rheumatic diseases and the quality of the care that they provide to this population.
Factors contributing to possession and use of walking aids among persons with rheumatoid arthritis and osteoarthritis
Authors: Van der Esch M. , Heijmans M. , Dekker J.
Published: December 2003

Objective

To investigate the possession and use of walking aids among patients with rheumatoid arthritis (RA) or osteoarthritis (OA), and to identify factors contributing to possession and actual use of these aids.

Methods

A random sample of 640 patients with RA or OA was derived from a database of 6,500 registered patients. A total of 410 (64%) patients (223 RA, 187 OA) completed a questionnaire on possession and use of walking aids. Demographics, disease‐related characteristics, and information about possession and use were assessed. Logistic regression analyses were used to determine which factors are associated with the possession and use of walking aids.

Results

Forty‐nine percent of the RA patients and 44% of the OA patients owned a walking aid. Canes, forearm crutches, walkers, and orthopedic footwear were most frequently possessed. In the RA group, age, education, frequency of pain, and disability were associated with possessing a walking aid. In the OA group, age and disability were associated with possession. Approximately 30% of the owners did not use their walking aid. Factors associated with the actual use of an aid included higher age, a high intensity of pain, more disability, decrease in morning stiffness by the aid, and a positive evaluation of the aid.

Conclusion

Almost half of patients with RA or OA possess a walking aid. Disability, pain, and age‐related impairments seem to determine the need for a walking aid. Nonuse is associated with less need, negative outcome, and negative evaluation of the walking aid.
Validation of a Japanese version of the Stanford Health Assessment Questionnaire in 3,763 patients with rheumatoid arthritis
Authors: Matsuda Yuko , Singh Gurkirpal , Yamanaka Hisashi , Tanaka Eiichi , Urano Wako , Taniguchi Atsuo , Saito Terunobu , Hara Masako , Tomatsu Taisuke , Kamatani Naoyuki
Published: December 2003

Objective

To develop and validate a self‐administered instrument for measuring functional status in Japanese‐speaking rheumatoid arthritis patients.

Methods

We translated the Stanford Health Assessment Questionnaire (HAQ) into Japanese (original HAQ), and then made a tentative Japanese version of the HAQ (J‐HAQ) with culturally appropriate modifications of the arising, eating, and reach category questions. The questionnaire was then administered to 3,763 RA patients (82.6% female; mean age 58.0 years; mean onset age 47.4 years; mean disease duration 10.5 years).

Results

This instrument showed excellent internal reliability (Cronbach's α = 0.927), with a mean interitem correlation of 0.60. For the arising category question, the J‐HAQ asks about arising from a futon in addition to a bed because futons are still common in Japanese culture. Arising from a futon is generally more difficult for disabled individuals than is arising from a bed, so the arising score was higher in the J‐HAQ (mean score 0.82) than in the original HAQ (0.48). The average scores for the eating and reach categories were virtually identical for the original HAQ and the J‐HAQ, with correlation coefficients of 0.979 and 0.926, respectively. Thus, the overall disability index (average of the scores for all functional areas) was higher in the J‐HAQ (0.81) than in the original HAQ (0.76), although the correlation coefficient was high (0.993). The test‐retest reliability value (0.92), studied at a 1‐week interval, revealed identical disability index scores measured on the 2 occasions.

Conclusion

The final version of the J‐HAQ is a valid and reliable instrument for measuring functional status in Japanese‐speaking RA patients.
Participatory patient–physician communication and morbidity in patients with systemic lupus erythematosus
Authors: Ward Michael M. , Sundaramurthy Saigeetha , Lotstein Debra , Bush Thomas M. , Neuwelt C. Michael , Street Richard L.
Published: December 2003

Objective

To examine associations between active patient–physician communication and measures of morbidity in patients with systemic lupus erythematosus (SLE).

Methods

Audiotapes of routine visits between 79 women with SLE and their rheumatologists were coded for active patient participation and the degree of patient‐centered communication of the physician, using a validated coding scheme. Measures of SLE activity, functional disability, and permanent organ damage were recorded at the same visit. Permanent organ damage was reassessed in 68 patients after a median of 4.7 years.

Results

Patients who participated more actively in their visits had less permanent organ damage, as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, and tended to accrue less organ damage over time. There were no associations between either active patient participation or physicians' patient‐centered communication scores and measures of SLE activity or functional disability.

Conclusions

Patients with SLE who participated more actively in their visits had less permanent organ damage, suggesting that involving patients more in their care may decrease morbidity.
Enhanced Web document retrieval using automatic query expansion
Authors: Shamim Khan M. , Khor Sebastian
Published: December 2003

The ever growing popularity of the Internet as a source of information, coupled with the accompanying growth in the number of documents made available through the World Wide Web, is leading to an increasing demand for more efficient and accurate information retrieval tools. Numerous techniques have been proposed and tried for improving the effectiveness of searching the World Wide Web for documents relevant to a given topic of interest. The specification of appropriate keywords and phrases by the user is crucial for the successful execution of a query as measured by the relevance of documents retrieved. Lack of users' knowledge on the search topic and their changing information needs often make it difficult for them to find suitable keywords or phrases for a query. This results in searches that fail to cover all likely aspects of the topic of interest. We describe a scheme that attempts to remedy this situation by automatically expanding the user query through the analysis of initially retrieved documents. Experimental results to demonstrate the effectiveness of the query expansion scheme are presented.
Information search performance and research achievement: An empirical test of the Anxiety‐Expectation Mediation model of library anxiety
Authors: Onwuegbuzie Anthony J. , Jiao Qun G.
Published: December 2003

This study presents a test of the Anxiety‐Expectation Mediation (AEM) model of library anxiety. The AEM model contains variables that are directly or indirectly related to information search performance, as measured by students' scores on their research proposals. This model posits that library anxiety and self‐perception serve as factors that mediate the relationship between performance in writing a research proposal and other cognitive, personality, and demographic variables. The model was tested using 225 graduate students enrolled in several sections of an introductory‐level course at a midsouthern university. Structural equation modeling techniques supported the AEM model. In particular, library anxiety and research achievement were reciprocally related. Furthermore, library anxiety mediated the relationship between research performance and the following variables: age, grade point average, learning style, academic procrastination, and self‐perception. The path analysis also revealed a direct, positive path from self‐perception to research performance. In addition, self‐perception moderated the relationship between research achievement and academic procrastination, perfectionism, and hope. The AEM model of library anxiety suggests that Wine's (1980) Cognitive‐Attentional‐Interference theory, Onwuegbuzie, Jiao, and Bostick's (in press) ILP model of library anxiety, and Bandura's (1977) self‐efficacy theory can be applied to the library and information context. Findings are discussed within the framework of current social‐psychological models of educational achievement.
Literature growth, journal characteristics, and author productivity in subject indexing, 1977 to 2000
Authors: Tsay Ming‐yueh
Published: December 2003

This study employed the Perl program, Excel software, and some bibliometric techniques to investigate growth pattern, journal characteristics, and author productivity of the subject indexing literature from 1977 to 2000, based on the subject search of a descriptor field in the Library and Information Science Abstracts (LISA) database. The literature growth from 1977 to 2000 in subject indexing could be fitted well by the logistic curve. The Bradford plot of journal literature fits the typical Bradford‐Zipf S‐shaped curve. Twenty core journals making a significant contribution could be identified from the Bradford‐Zipf distribution. Four major research topics in the area of subject indexing were identified as: (1) information organization, (2) information processing, (3) information storage and retrieval, and (4) information systems and services. It was also found that a vast majority of authors (76.7%) contributed only one article, which is a much larger percentage than the 60% of original Lotka's data. The 15 most productive authors and the key concepts of their research were identified.
Valproate‐induced neural tube defects in folate‐binding protein‐2 (Folbp2) knockout mice
Authors: Spiegelstein Ofer , Merriweather Michelle Y. , Wicker Ned J. , Finnell Richard H.
Published: December 2003

BACKGROUND

Folate is an important B vitamin that is transported into cells by way of folate‐binding proteins and transporters. Folate‐binding protein‐2 nullizygous (Folbp2−/−) mice develop normally; however, we have found them to be more susceptible to the teratogenic effects of arsenate exposure than wild‐type control mice.

METHODS

In the current study, we wanted to extend our findings and test the hypothesis that Folbp2−/− mice are more susceptible to the teratogenic effects of valproic acid (VPA), a commonly used antiepileptic drug that is known to induce neural tube defects (NTDs) in both humans and laboratory animals.

RESULTS

Folbp2−/− mice had higher VPA‐induced frequencies of embryonic lethality and exencephaly than did the wild‐type control mice during folate supplementation and a control diet, respectively. All other differences in response between the two genotypes were short of reaching statistical significance. Folate supplementation of wild‐type, but not Folbp2−/− dams reduced embryonic lethality of VPA‐treated wild‐type embryos compared to the folate‐deficient diet.

CONCLUSIONS

Unlike our previous findings with arsenate, enhanced susceptibility of Folbp2−/− mice to in utero VPA exposure was demonstrated in some dietary folate regimens. Thus, our data indicate a relatively frail relationship between Folbp2 and VPA‐induced NTDs. Birth Defects Research (Part A) 67:000–000, 2003. © 2003 Wiley‐Liss, Inc.
Möbius sequence in children exposed in utero to misoprostol: Neuropathological study of three cases
Authors: Marques‐Dias Maria Joaquina , Gonzalez Claudette H. , Rosemberg Sergio
Published: December 2003

Background

Misoprostol exposure in the first trimester of pregnancy has been related to congenital malformations, particularly the Möbius sequence and terminal transverse limb defects. CASES: Neuropathological findings of three patients with Möbius sequence related to misoprostol are reported. No previous pathological studies have shown these abnormalities to be associated with misoprostol exposure in utero. The brain stem was cut serially, from the rostral mesencephalum to the caudal aspect of the medulla, and all fragments were stained with hematoxylin‐eosin and cresyl violet. Old ischemic‐anoxic foci of gliosis, with necrosis and calcification, dorsally situated, were present from the pons to the medulla, involving some cranial nerve nuclei (especially the IV, VII, and XII) that were partially or completely depopulated of neural cells.

CONCLUSIONS

The findings suggest a circulatory mechanism to the Möbius sequence, with vascular disruption involving the territory of the subclavian artery, occurring in a critical period of embryonic life between six to eight weeks postconception. These cases add further evidence of the role of misoprostol as a teratogen. Birth Defects Research (Part A) 67:000–000, 2003. © 2003 Wiley‐Liss, Inc.
Das Rezept als literarische Form. Zum multifunktionalen Gebrauch des Rezepts in der deutschen Literatur
Authors: Telle Joachim
Published: December 2003

In the medical writing of antiquity the recipe, a basic form of scientific writing, was considered a literary genre with conventions of its own. In texttype‐linguistics, however, the recipe plays only a minor role; in studies on the history of literary short texts it is hardly ever mentioned and, furthermore, it has come to the conclusion that the recipe's function has lain solely in the curing of the sick. The present study focuses on the its multifunctional character. A collection of widely scattered and hardly accessible recipes shows that the recipe adopted functions beyond giving technical directives. Its multifunctionality in the German literature of early modern times is manifest in medical and cooking jocular recipes, cooking recipes in minnesang, mock recipes aimed at physicians and astrologers, recipes of spiritual‐religious content, recipes containing art and literary criticism as well as recipes in a moral‐satirical or a political‐agitative vein.
Wem gehört Adam Smith? Gedanken zur Auseinandersetzung um das geistige Erbe des schottischen Philosophen und Ökonomen
Authors: Volkmann Laurenz
Published: December 2003

Smith's appropriation by neoliberal theorists as the progenitor of economic liberalism and capitalism has recently been challenged by a phalanx of counter‐positions. In a concerted effort ‚to salvage the real Smith’︁, they rediscover the enlightenment philosopher who was very critical of ostentatious display of wealth and envisioned a society based on moral concerns rather than on the pursuit of self‐interest. This article discusses recent developments in the battle over the economist's and philosopher's heritage.
Experimental Design and Statistical Inference for Cluster Point Processes – with Applications to the Fruit Dispersion of Anemochorous Forest Trees
Authors: Näther W. , Wälder K.
Published: December 2003

This paper deals with experimental design and statistical inference for cluster point processes. The results are applied to fruit dispersion models of forest trees where the corresponding design of experiments is given by the positions of the traps containing the collected fruits. It is shown that consideration of anisotropic behaviour can lead to more realistic models. Modelling interactivity effects between trees seems to be of great interest. It is shown that an approach based on ordered weighted averages yields an notable improvement of model quality. The mathematical background of such models (Choquet integral, fuzzy measures) is sketched in the appendix. Finally, results for choosing a D‐optimal sub‐design are presented.
Direct and Indirect Classification in Clinical Research
Authors: Peters A. , Lausen B.
Published: December 2003

We investigate if the use of a priori knowledge allows an improvement of medical decision making. We compare two frameworks of classification – direct and indirect classification – with respect to different classification errors: differential misclassification, observed misclassification and true misclassification. We analyze general behaviors of the classifiers in an artificial example and furthermore as being interested in the diagnosis of early glaucoma we adapt a simulation model of the optic nerve head. Indirect classifiers outperform direct classifiers in certain parameter situations of a Monte‐Carlo study. In summary, we demonstrate that indirect classification provides a flexible framework to improve diagnostic rules by using explicit a priori knowledge in clinical research.
Blinded Sample Size Recalculation for Normally Distributed Outcomes Using Long‐ and Short‐term Data
Authors: Wüst K. , Kieser M.
Published: December 2003

Clinical trials are often planned with high uncertainty about the variance of the primary outcome variable. A poor estimate of the variance, however, may lead to an over‐ or underpowered study. In the internal pilot study design, the sample variance is calculated at an interim step and the sample size can be adjusted if necessary. The available recalculation procedures use the data of those patients for sample size recalculation that have already completed the study. In this article, we consider a variance estimator that takes into account both the data at the endpoint and at an intermediate point of the treatment phase. We derive asymptotic properties of this estimator and the relating sample size recalculation procedure. In a simulation study, the performance of the proposed approach is evaluated and compared with the procedure that uses only long‐term data. Simulation results demonstrate that the sample size resulting from the proposed procedure shows in general a smaller variability. At the same time, the Type I error rate is not inflated and the achieved power is close to the desired value.
Validation of Surrogate Markers in Multiple Randomized Clinical Trials with Repeated Measurements
Authors: Alonso Ariel , Geys Helena , Molenberghs Geert , Kenward Michael G. , Vangeneugden Tony
Published: December 2003

Part of the recent literature on the validation of biomarkers as surrogate endpoints proposes to undertake the validation exercise in a multi‐trial context which led to a definition of validity in terms of the quality of both trial level and individual level association between the surrogate and the true endpoints (Buyse et al., 2000). These authors concentrated on continuous univariate responses. However, in many randomized clinical studies, repeated measurements are encountered on either or both endpoints. When both the surrogate and true endpoints are measured repeatedly over time, one is confronted with the modelling of bivariate longitudinal data. In this work, we show how such a joint model can be implemented in the context of surrogate marker validation. In addition, another challenge in this setting is the formulation of a simple and meaningful concept of “surrogacy”. We propose the use of a new measure, the so‐called variance reduction factor, to evaluate surrogacy at the trial and individual level. On the other hand, most of the work published in this area assume that only one potential surrogate is going to be evaluated. We also show that this concept will let us evaluate surrogacy when more than one surrogate variable is available for the analysis. The methodology is illustrated on data from a meta‐analysis of five clinical trials comparing antipsychotic agents for the treatment of chronic schizophrenia.
Measuring Differences of Trait Distributions Between Populations
Authors: Gregorius Hans‐Rolf , Gillet Elizabeth M. , Ziehe Martin
Published: December 2003

A measure of difference between populations for a trait should reflect not only the differences in the relative frequencies of the trait states but also the trait differences between the states. Common approaches to measuring differences between populations rely on distance, probability, or variance concepts. To overcome conceptual problems of these approaches, a new difference measure Δ is presented that is based on both frequency and trait differences. For two populations, Δ expresses the degree to which the frequency distribution of the trait states within one population must be transformed in order to make it match the distribution in the other population. This is done by shifting the relative frequency excesses of trait states to other trait states of deficient frequency, where shifts occur between as similar states as possible. Δ equals the minimum sum of the shifted frequencies weighted by the respective trait differences. Its bounds are functions of the difference measure d0, which considers only differences in relative frequency. The computer program DeltaS applies an algorithm from operations research to calculate Δ. The effect of including trait differences is demonstrated by the topological differences observed between Δ‐ and d0‐dendrograms constructed from microsatellite allele frequencies in four riparian stands of black poplar (Populus nigra), where the trait difference between two alleles equals the difference in numbers of tandem repeats. Δ is applicable to all traits for which trait differences are measurable, and it is shown to have elementary linearity properties that considerably simplify its interpretation.
Bayesian Estimation of Hunting Success Rate and Harvest for Spatially Correlated Post‐stratified Data
Authors: Woodard R. , He C. Z. , Sun D.
Published: December 2003

We consider the estimation of success rate and harvest under post survey stratification at the sub‐domain (county) level. Often in this situation, the population size for the sub‐domain is unknown and the random mechanism that dictates the sample size for sub‐domains is ignored. Finding good estimators of success rate and harvest is very important for wildlife abundance. A Bayesian hierarchical model is developed to estimate both success rate and harvest simultaneously. The model includes a random sub‐domain sample size correlated with the number of successes in the sub‐domain, fixed week effects, random geographic effects, and spatial correlations between neighboring sub‐domains. The computation is done by Gibbs sampling and adaptive rejection sampling techniques. The method developed is illustrated using data from the Missouri Turkey Hunting Survey. The estimation of success rate is improved by treating the the sub‐domain sample size as a random variable instead of a fixed constant. The Bayesian model yields a reasonable harvest estimation. The spatial pattern of the estimated harvest matches the pattern of the check station data.
Kinetics of Aquation and Anation of Ruthenium(II) Arene Anticancer Complexes, Acidity and X‐ray Structures of Aqua Adducts
Authors: Wang Fuyi , Chen Haimei , Parsons Simon , Oswald Iain D. H. , Davidson James E. , Sadler Peter J.
Published: December 2003

The aqua adducts of the anticancer complexes [(η6‐X)Ru(en)Cl][PF6] (X=biphenyl (Bip) 1, X=5,8,9,10‐tetrahydroanthracene (THA) 2, X=9,10‐dihydroanthracene (DHA) 3; en=ethylenediamime) were separated by HPLC and characterised by mass spectrometry as the products of hydrolysis in water. The X‐ray structures of the aqua complexes [(η6‐X)Ru(en)Y][PF6]n, X=Bip, Y=0.5 H2O/0.5 OH, n=1.5 (4), X=THA, Y=0.5 H2O/0.5 OH, n=1.5 (5 A), X=THA, Y=H2O, n=2 (5 B), and X=DHA, Y=H2O, n=2 (6), are reported. In complex 4 there is a large propeller twist of 45° of the pendant phenyl ring with respect to the coordinated phenyl ring. Although the THA ligand in 5 A and 5 B is relatively flat, the DHA ring system in 6 is markedly bent (hinge bend ca. 35°) as in the chloro complex 3 (41°). The rates of aquation of 1–3 determined by UV/Vis spectroscopy at various ionic strengths and temperatures (1.23–2.59×10−3 s−1 at 298 K, I=0.1 M) are >20× faster than that of cisplatin. The reverse, anation reactions were very rapid on addition of 100 mM NaCl (a similar concentration to that in blood plasma). The aquation and anation reactions were about two times faster for the DHA and THA complexes compared to the biphenyl complex. The hydrolysis reactions appear to occur by an associative pathway. The pKa values of the aqua adducts were determined by 1H NMR spectroscopy as 7.71 for 4, 8.01 for 5 and 7.89 for 6. At physiologically‐relevant concentrations (0.5–5 μM) and temperature (310 K), the complexes will exist in blood plasma as >89 % chloro complex, whereas in the cell nucleus significant amounts (45–65 %) of the more reactive aqua adducts would be formed together with smaller amounts of the hydroxo complexes (9–25 %, pH 7.4, [Cl−]=4 mM).
A Functionalized Noncovalent Macrocyclic Multiporphyrin Assembly from a Dizinc(II) Bis‐Porphyrin Receptor and a Free‐Base Dipyridylporphyrin
Authors: Iengo Elisabetta , Zangrando Ennio , Alessio Enzo , Chambron Jean‐Claude , Heitz Valérie , Flamigni Lucia , Sauvage Jean‐Pierre
Published: December 2003

The bis‐porphyrin system ZnP2, in which two zinc porphyrins are connected by a phenanthroline linker in an oblique fashion, acts as a bifunctional receptor towards the complexation of free‐base meso‐5,10‐bis(4′‐pyridyl)‐15,20‐diphenylporphyrin (4′‐cis DPyP). In solution, NMR spectroscopy evidenced quantitative formation of the tris‐porphyrin macrocyclic assembly ZnP2(4′‐cis DPyP), in which the two fragments are held together by two axial 4′‐N(pyridyl)–Zn interactions. The remarkable stability of the edifice (an association constant of about 6×108 M−1 was determined by UV/Vis absorption and emission titration experiments in toluene) is due to the almost perfect geometrical match between the two interacting units. The macrocycle was crystallized and studied by X‐ray diffraction, which confirmed the excellent complementarity of the two components. Photoinduced energy transfer from the singlet excited state of the zinc porphyrin chromophores to the free‐base porphyrin occurs with an efficiency of 98 % (ken=2×1010 s−1 in toluene, ambient temperature) with a mechanism consistent with a dipole–dipole process with a low orientation factor.
Unique Guest‐Inclusion Properties of a Breathing Ionic Crystal of K3[Cr3O(OOCH)6(H2O)3][α‐SiW12O40]⋅16 H2O
Authors: Uchida Sayaka , Mizuno Noritaka
Published: December 2003

A microstructured ionic crystal, K3[Cr3O(OOCH)6(H2O)3][α‐SiW12O40]⋅16 H2O (1) was synthesized by the complexation of the Keggin‐type polyoxometalate of [α‐SiW12O40]4− with a macrocation of [Cr3O(OOCH)6(H2O)3]+. Compound 1 possessed a straight channel, with an opening of approximately 0.5×0.8 nm, which contained the water of crystallization. The use of the macrocation with large size (0.7 nm) and small charge (+1) reduced the anion–cation interaction and was essential for the channel formation. The molecular structures of the polyoxometalate and the macrocation in 1 were retained under vacuum at 473 K. Analogues of 1 were synthesized with [α‐PVW11O40]4− or [Fe3O(OOCH)6(H2O)3]+. The water of crystallization in 1 was removed under vacuum at room temperature to form the closely packed guest‐free phase 2. Compound 2 reversibly and repeatedly included water and polar organic molecules with two carbon atoms or less. Guest inclusion was highly selective and a difference of even one methylene group in the organic guest molecule was discriminated by the host. Polar organic molecules with longer methylene chains and nonpolar molecules such as dinitrogen and methane were completely excluded. The guest‐inclusion properties could be explained by the ion–dipole interaction between the host and the guest, which is proportional to the dipole moment of the guest molecule and inversely proportional to the ion–dipole (host–guest) distance. Thus, small polar molecules were selectively absorbed. These distinctive guest‐inclusion properties were successfully applied to the oxidation of methanol from a mixture of C1 and C2 alcohols. These results show unique guest inclusion and catalysis by rationally designed ionic crystals.
2‐Phosphanylphenolate Nickel Catalysts for the Polymerization of Ethylene
Authors: Heinicke Joachim , Köhler Martin , Peulecke Normen , He Mengzhen , Kindermann Markus K. , Keim Wilhelm , Fink Gerhard
Published: December 2003

The previously unknown methallylnickel 2‐diorganophosphanylphenolates (RPh,cHex) were synthesized and found to catalyze the polymerization of ethylene. To explore the potential for ligand‐tuning, a variety of P‐alkyl‐ and P‐phenyl‐2‐phosphanylphenols was synthesized and allowed to react with [Ni(cod)2] (cod=1,5‐cyclooctadiene) or with NiBr2⋅DME and NaH. The complexes formed in situ with [Ni(cod)2] are generally active as ethylene polymerization catalysts with all the ligands tested, whereas the latter systems are inactive when 2‐dialkylphosphanylphenols are applied.Mwvalues, ranging from about 1000 to about 100 000 g mol−1, increase for various R2P groups in the order RPh<Et≈tBu<iPr<cHex, while aryloxy substituents usually diminish the molecular weights. Increasing basicity of P‐ or aryloxy substituents usually leads to increasing turnover numbers. The polymers are high density polyethylene (HDPE) with low methyl and sometimes low long‐chain branching. Investigation of the influence of the solvent shows that the catalysts are stabilized by some oxygen‐containing Lewis bases as well as by olefins. The catalysts are tolerant to water, in particular the 2‐dicyclohexylphosphanylphenolate nickel catalyst, which in THF–water (1:1) gives HDPE withMw=39 000,Mn=14 500 g mol−1. Additives of tetrahydrothiophene or pyridine do not inhibit the catalyst, but decrease the reaction rate and the molecular weight of the polymers.
Theoretical Study of Rhodium(I) Carbene Complexes: The Structural Versatility of Phosphino‐ Compared with Aminocarbenes
Authors: Miqueu Karinne , Despagnet‐Ayoub Emmanuelle , Dyer Philip W. , Bourissou Didier , Bertrand Guy
Published: December 2003

Density functional calculations are reported for complexes of general formula [(carbene)RhClL2] featuring model phosphino‐ and aminocarbenes. Both the cis and trans isomers of the rhodium(I) η1‐complexes (1–9) were investigated, and the influence of the rhodium co‐ligands (L=ethylene, phosphine, or carbon monoxide) was evaluated. In the case of phosphinocarbenes and carbon monoxide as a ligand, a somewhat unusual coordination mode was observed, in which a significant intramolecular Cl→Ccarbene interaction is present. The propensity of phosphino‐ and aminocarbenes to behave as four electron donors was also investigated both structurally and energetically on the related η2‐complexes 10–18. These results as a whole emphasize the structural versatility of phosphino‐ compared with aminocarbene complexes.