bluuebunny/crossref_metadata_2025 huggingface dataset:
Proliferation of AI Tools: A Multifaceted Evaluation of User Perceptions and Emerging Trend
Authors: Marquis Yewande Alice , Oladoyinbo Tunbosun Oyewale , Olabanji Samuel Oladiipo , Olaniyi Oluwaseun Oladeji , Ajayi Samson Abidemi
Published: January 2024

The rapid advancement of artificial intelligence (AI) technologies, epitomized by tools like ChatGPT, Claude, Bard, Copilot, and Copy AI, has significantly reshaped various professional landscapes. This study aimed to assess the impact of these AI tools on professional performance, job dynamics, and societal perceptions. Amidst their benefits in enhancing efficiency and introducing novel capabilities, these tools also pose challenges concerning job displacement, ethical implications, and societal balance. Data from 1623 professionals across diverse industries were analyzed to assess AI tool utilization, functionality, user satisfaction, and perceived impacts. The results indicate that AI tools substantially enhance professional efficiency and are vital in diverse tasks including data analysis and decision-making. However, they also significantly affect traditional job roles, underscoring the urgency for workforce adaptation and skill development. Notably, the study unveils a generational gap in AI adoption, with younger users showing higher engagement compared to older cohorts, suggesting a digital divide. The study’s novelty lies in its comprehensive analysis of AI tool impacts across multiple professions, highlighting ethical and societal challenges. Concerns about AI-induced job displacement, privacy, and ethical use were evident, calling for responsible AI integration. The study advocate for targeted reskilling programs to equip the workforce for an AI-driven future and ethical guidelines to ensure AI tools' responsible development and use. This research contributes to the understanding of AI’s role in modern professional settings and offers strategic insights for policymakers, educators, and industry leaders. Emphasizing a balanced approach, the study urges for AI deployment that maximizes benefits while addressing potential risks and societal concerns.
Circulating Serotypes of Group A Rotavirus Identified in the Faeces of Children Aged 0-56 Months with Gastroenteritis
Authors: Tondé I. , Kambiré D. , Ky-Ba A. , Drabo D. C. , Gampiné M. T. , Tranchot-Diallo J. , Savadogo H. , Tamboura M. , Kam M. , Sanou M. , Ouédraogo A. S. , Sanou I. , Sangaré L. , Ouédraogo-Traoré R.
Published: January 2024

Gastroenteritis is a public health problem in developing countries such as Burkina Faso. The introduction of the RotaShield rotavirus vaccine in the early 1980s had the side-effect of causing acute intestinal invaginations, which led to the introduction of surveillance. The aim of this study is to review the serotypes of rotavirus identified. This retrospective study consisted in collecting data on group A rotavirus serotypes identified from stool samples using a rapid diagnostic test, confirmed by an ELISA test and then serotyped by real-time multiplex RT-PCR. A total of 840 suspect stools were collected between December 2013 and December 2017. Confirmed cases represented an average of 37.7%. Genotyping identified the P6(59.6%) and P8(40.4%) types of the P genotype in the VP4 genotype and G12 which predominates with 66% in the VP7 genotype followed by G3 23.4%. The genotypes most involved in gastroenteritis are serotypes P6 and P8 of the P genotype and serotypes G1, G2, G3, G9 and G12 of the G genotype in this study showed that.
Factor V Leiden mutation carriership and venous thromboembolism in polycythemia vera and essential thrombocythemia
Authors: Ruggeri Marco , Gisslinger Heinz , Tosetto Alberto , Rintelen Claudia , Mannhalter Christine , Pabinger Ingrid , Heis Navide , Castaman Giancarlo , Missiaglia Edoardo , Lechner Klaus , Rodeghiero Francesco
Published: October 2002

Polycythemia Vera (PV) and Essential Thrombocythemia (ET) are chronic myeloproliferative disorders complicated by a high incidence of thrombotic complications. Extensive coagulation studies failed to demonstrate a consistent pattern of abnormalities associated with thrombosis. Recently, a poor anticoagulant response to activated protein C (APC), due to a mutation of factor V (FV Leiden), has been identified as the most frequent hereditary disorder associated with venous thrombophilia. We investigated in 304 patients with PV and ET whether the presence of FV Leiden could be a risk factor for thrombosis. FV Leiden was found in 14/304 patients (4.6%) and was associated with venous thromboembolism (VTE) occurred before and at diagnosis (5/27,16%, with a significant difference of prevalence in comparison of that observed in asymptomatic patients, 9/263, 3%, p = 0.003). Carriership of FV Leiden was associated with VTE relapse, with a prevalence of 3.6% in asymptomatic patients, 6.9% in patients with a single episode of VTE and 18.1% in patients with recurrent VTE. The prevalence of FV Leiden in patients with and without arterial thrombosis was similar (5/79, 6% and 9/211, 4%, respectively, p = 0.337). This study indicates that the prevalence of the FV Leiden mutation in patients with PV and ET is comparable with that observed in the general population. FV Leiden mutation is a risk factor for VTE before and at time of diagnosis and for VTE recurrences. Screening for FV Leiden may be considered to identify PV and ET patients at higher risk of recurrences. Am. J. Hematol. 71:1–6, 2002. © 2002 Wiley‐Liss, Inc.
Resolution of psoriasis following allogeneic bone marrow transplantation for chronic myelogenous leukemia: Case report and review of the literature
Authors: Kanamori Heiwa , Tanaka Masatsugu , Kawaguchi Hiroshi , Yamaji Satoshi , Fujimaki Katsumichi , Tomita Naoto , Fujisawa Shin , Ishigatsubo Yoshiaki
Published: October 2002

We describe a case of a 49‐year‐old man with chronic myelogenous leukemia (CML) whose coincidental psoriasis resolved following allogeneic bone marrow transplantation (BMT). The patient had suffered from psoriasis for 20 years and was treated with corticosteroid ointment. He was diagnosed as having CML in 1998, and his psoriasis deteriorated following interferon therapy. In March 1999, he received a BMT from an HLA‐identical sister after undergoing a conditioning regimen involving busulfan, cytosine arabinoside, and cyclophosphamide. Prophylaxis of acute graft‐versus‐host disease was done using short‐term methotrexate and cyclosporin A. His psoriasis improved immediately and disappeared completely on day 70 after BMT. For 2.5 years, his CML remains in remission and he is free of psoriasis without undergoing immunosuppressive therapy. This case suggests the potential benefits of the treatment of immune‐mediated diseases with allogeneic BMT. Am. J. Hematol. 71:41–44, 2002. © 2002 Wiley‐Liss, Inc.
Exclusion mapping of the genetic predisposition for cervical artery dissections by linkage analysis
Authors: Grond‐Ginsbach Caspar , Klima Bernhard , Weber Ralf , Striegel Johannes , Fischer Christine , Hacke Werner , Brandt Tobias , Hausser Ingrid
Published: October 2002

Skin biopsies from a patient with a dissection of the left internal carotid artery and from four of his children were analyzed by electron microscopy. The index patient and three children showed mild but regular electron microscopic connective tissue aberrations. They were considered as carriers of an unknown autosomal dominant mutation. Thirty‐four candidate genes involved in the biosynthesis of the extracellular matrix were excluded by genetic linkage analysis as possible sites of a disease‐causing mutation in this family (logarithm of odds [LOD]‐score less than −2.0).
Impaired chemosensitivity to hypoxia is a marker of multiple system atrophy
Authors: Tsuda Takehide , Onodera Hiroshi , Okabe Shinichi , Kikuchi Yoshihiro , Itoyama Yasuto
Published: October 2002

Sudden death is common in patients with multiple system atrophy (MSA). In its early stages, the cerebellar presentation MSA‐C can be indistinguishable from idiopathic late‐onset cerebellar ataxia. We studied the hypoxic ventilatory response in MSA‐C and idiopathic late‐onset cerebellar ataxia patients. Six patients with idiopathic late‐onset cerebellar ataxia that later evolved to MSA had impaired hypoxic ventilatory response when minimal autonomic failure was still present, whereas for patients with unimpaired hypoxic ventilatory response their diagnosis remained idiopathic late‐onset cerebellar ataxia. The demonstration of impaired hypoxic ventilatory response appears to be a good marker enabling earlier diagnosis of MSA in patients presenting with idiopathic late‐onset cerebellar ataxia.
Aggregation behavior of 3,6‐O‐carboxymethylated chitin in aqueous solutions
Authors: Chen Lingyun , Du Yumin
Published: October 2002

The aggregation behavior of 3,6‐O‐carboxymethylated chitin (3,6‐O‐CM‐chitin) in aqueous solutions was investigated by viscometry, gel permeation chromatography (GPC), and GPC combined with laser light scattering (GPC‐LLS) techniques. 3,6‐O‐CM‐chitin has a strong tendency to form aggregates in NaCl aqueous solutions with the apparent aggregation number (Nap) of about 27. There were three kinds of aggregates corresponding to different cohesive energies, the aggregates with low cohesive energy were first dissociated at 60°C, the aggregates with middle cohesive energy were then dissociated at 80 to 90°C, and the aggregates with high cohesive energy were difficult to be disrupted by heating. Decreasing polysaccharide concentration (cp) or increasing NaCl concentration (cs) reduced the content of the aggregates. At the critical cp of 2.5 × 10−5 g/mL, the aggregates were dissociated into single chains completely. The change of aggregation and disaggregation of 3,6‐O‐CM‐chitin in water–cadoxen mixtures occurred from 0.1 to 0.4 of vcad, and were irreversible. Intermolecular hydrogen bonding can be ascribed as main driving force for aggregation. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1838–1843, 2002
Influence of molecular weight and syndiotacticity on the structure of high‐performance poly(vinyl alcohol) fibers prepared by gel spinning
Authors: Suzuki Masayosi , Tanigami Tetuya , Matsuzawa Shuji , Yamaura Kazuo
Published: October 2002

Atactic and syndiotactic‐rich poly(vinyl alcohol) fibers were prepared by gel spinning using ethylene glycol as a solvent. The mechanical properties of the fibers were independent of the degree of polymerization, although they were dependent on syndiotacticity. The amounts of tie molecules and the difference between the amounts of hydrogen bonds and microvoids determine the mechanical properties. The mechanical properties depended on the orientation of the segments in the amorphous parts. The entangled segments produced in the amorphous parts as a consequence of the difficulty of drawing were considered to form the voids and cracks, which grow to a banded structure. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1970–1977, 2002
Novel approach to fibrillation of LCP in an LCP/PP blend
Authors: Lee M. W. , Hu X. , Yue C. Y. , Li L. , Tam K. C. , Nakayama K.
Published: October 2002

A novel concept of improving shear‐induced fibrillation of liquid crystalline polymer (LCP) in LCP/thermoplastic blend systems was introduced. Silica fillers (SiO2) were added to an LCP/polypropylene (PP) system to serve as a viscosity thickening agent and to improve the fibrillation of the LCP phase. The formation of LCP fibrils was found to enhance with the incorporation of 5–15 wt % of fillers. The presence of LCP fibrils improved the flow properties of the LCP/PP/SiO2 composites. It was evident from the rheological and morphological studies that the addition of silica led to an increase of the aspect ratio of the LCP fibrils, which, in turn, should improve their effectiveness as reinforcements and/or toughening agents. Substantial improvement in LCP aspect ratio was achieved by the introduction of hydrophobic SiO2 fillers in the PP/LCP blends. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 2070–2078, 2002
Collaboration, conservation and the changing face of limnology
Authors: Wishart M.J. , Davies B.R.
Published: October 2002

The fauna of inland waters has the highest rates of imperilment of any ecosystems as a result of human demands and catchment manipulations. Thus, the conservation of these systems requires multi‐disciplinary and international collaboration.

In order to examine patterns of change in collaborative research we examined eight of the leading limnological journals over a 10 yr period, with another two journals examined over 5 yr.

Of the 9758 surveyed papers, single‐authored papers were proportionally the second most commonly published (N=2523: 25.86%) while dual‐authored papers accounted for the greatest number of papers (N=3517: 36.04%). There was a significant increase in collaboration and a decline in the relative proportion of single‐ (r2=0.71; P=0.00) and dual‐authored (r2=0.54; P=0.00) papers.

Collaboration between authors from different countries was recorded for 827 of the 8636 (9.58%) papers examined. While there was an annual average of 864 (8.57%) papers involving international collaboration, the range varied from 464 (5.60%: 1990) to 1374 (12.66%: 1995). There was a significant increase (r2=0.59; P=0.01) in the number of papers involving international collaboration.

‘Third World’ contributions constituted an average of 7.64% of papers published annually, ranging from 5.32% of all papers in 1987 to 9.31% in 1994.

Roughly equal proportions of lentic, lotic and marine papers were published over the survey period. Taxonomic and estuarine research was poorly represented probably due to the many specialist journals available for such publications. The data do not support the assertion that there has been an increase in lotic research at the expense of lentic research. Indeed, our data show a significant decrease in the number of papers published relating to lotic systems (r2=0.51; P=0.02).

The future of collaborative research conducted by multi‐institutional and multi‐disciplinary teams and its significance in terms of the management and conservation of aquatic ecosystems globally is discussed.

Copyright © 2002 John Wiley & Sons, Ltd.
Wilcoxon‐type rank‐sum precedence tests: large‐sample approximation and evaluation
Authors: Ng H. K. T. , Balakrishnan N.
Published: October 2002

Wilcoxon‐type rank‐sum precedence tests are useful alternatives to the precedence life‐test proposed for testing the hypothesis that two lifetime distribution functions are equal. In this paper, we first derive the exact power function under the Lehmann alternative for these tests. We also note that the large‐sample normal approximation for the null distribution is not satisfactory in case of small or moderate sample sizes. Then, we develop an Edgeworth expansion to approximate the significance probabilities. Comparison of normal approximation and Edgeworth approximation for various sample sizes are provided. Finally, an example is presented for illustration. Copyright © 2002 John Wiley & Sons, Ltd.
Importance of entero‐salivary recirculation in paracetamol pharmacokinetics
Authors: Schaiquevich Paula , Niselman Ada , Rubio Modesto
Published: October 2002

The contribution of an entero‐salivary recirculation (salivary secretion—swallowed—reabsorption of drug from the gastrointestinal tract) to the values of the pharmacokinetic parameters of paracetamol was studied in a two‐way crossover design. Five healthy volunteers took a tablet of Paracetamol (500 mg) in two occasions separated by a washout period. The difference between the two treatments consisted of saliva that was allowed or not to be swallowed during the 4 h of study. No statistically significant differences were found in the values of the pharmacokinetic parameters between treatments.

The half‐life time calculated from salivary levels was similar to the values previously reported by other authors. The percent of the oral dose excreted in saliva during 4 h of study was very low (0.1%). Secondary peaks appeared in 8 of 10 profiles. The lack of influence of salivary secretion on the pharmacokinetic parameters of Paracetamol and the low percent secreted in this fluid suggests that entero‐salivary recirculation is a possible physiological phenomenon undergoing after oral administration, but it is not one of the principal phenomenon that defines the pharmacokinetic of the drug. We confirm that working with salivary samples in pharmacokinetic studies of paracetamol is a useful tool. Copyright © 2002 John Wiley & Sons, Ltd.
Osteogenic growth peptide: From concept to drug design
Authors: Bab Itai , Chorev Michael
Published: October 2002

Recently, the osteogenic growth peptide (OGP) and its C‐terminal pentapeptide H–Tyr–Gly–Phe–Gly–Gly–OH [OGP(10–14)] have attracted considerable clinical interest as bone anabolic agents and hematopoietic stimulators. They are present in mammalian serum in micromolar concentrations, increase bone formation and trabecular bone density, and stimulate fracture healing when administered to mice and rats. In cultures of osteoblastic and other bone marrow stromal cells, derived from human and other mammalian species, OGP regulates proliferation, alkaline phosphatase activity and matrix mineralization via an autocrine/paracrine mechanism. In vivo it also regulates the expression of type I collagen and the receptor for basic fibroblast growth factor. In addition, OGP and OGP(10–14) enhance hematopoiesis, including the stimulation of bone marrow transplant engraftment and hematopoietic regeneration after ablative chemotherapy. Apparently, the hematopoietic effects of these peptides are secondary to their effect on the bone marrow stroma. Detailed structure–activity relationship study identified the side chains of Tyr10 and Phe12 as the principal pharmacophores for OGP‐like activity. Recently, it has been demonstrated that several cyclostereoisomers of OGP(10–14), including the analogue retro–inverso (Gly–Gly–D‐Phe–Gly–D‐Tyr), share the full spectrum of OGP‐like bioactivities. Taken together, OGP represents an interesting case of a “housekeeping” peptide that plays an important role in osteogenesis and hematopoiesis, and interacts with its putative macromolecular target via distinct pharmacophores presented in a specific spatial organization. © 2002 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 66: 33–48, 2002
Thermal stabilization of the DNA duplex by adducts of aflatoxin B1
Authors: Giri Indrajit , Stone Michael P.
Published: October 2002

The trans‐8,9‐dihydro‐8‐(N7‐guanyl)‐9‐hydroxyaflatoxin B1 cationic guanine N7 adduct of aflatoxin B1 thermally stabilizes the DNA duplex, as reflected in increased Tm values upon adduction. The magnitude of the increased Tm value is characteristically 2–3°C. The major rotamer of the neutral guanine N7 adduct trans‐8,9‐dihydro‐8‐(2,6‐diamino‐4‐oxo‐3,4‐dihydropyrimid‐5‐yl‐formamido)‐9‐hydroxy aflatoxin B1 (the FAPY major adduct) exhibits a 15°C increase in Tm in 5′‐d(CTATFAPYGATTCA)‐3′‐5′‐d(TGAATCATAG)‐3′. Site‐specific mutagenesis experiments reveal the FAPY major adduct induces G→T mutations in Escherichia coli at a frequency six times higher than that of the cationic adduct (Smela, M. E.; Hamm, M. L.; Henderson, P. T.; Harris, C. M.; Harris, T. M.; Essigmann, J. M. Proc Natl Acad Sci USA, 99, 6655–6660). Thus, the FAPY major lesion may account substantially for the genotoxicity of AFB1. Structural studies for cationic and FAPY adducts of aflatoxin B1 suggest both adducts intercalate above the 5′‐face of the modified deoxyguanosine and that in each instance the aflatoxin moiety spans the DNA helix. Intercalation of the aflatoxin moiety, accompanied by favorable stacking with the neighboring base pairs, is thought to account for the increased thermal stability of the aflatoxin cationic guanine N7 and the FAPY major adducts. However, the structural basis for the large increase in thermal stability of the FAPY major adduct in comparison to the cationic guanine N7 adduct of aflatoxin B1 is not well understood. In light of the site‐specific mutagenesis studies, it is of considerable interest. For both adducts, the intercalation structures are similar, although improved stacking with neighboring base pairs is observed for the FAPY major adduct. In addition, the presence of the formamido group in the aflatoxin B1 FAPY major adduct may enhance duplex stability, perhaps via intrastrand sequence‐specific hydrogen bonding interactions within the duplex. © 2002 Wiley Periodicals, Inc. Biopolymers (Nucleic Acid Sci) 65: 190–201, 2002
Proposed modifications to metabolic model for glycogen‐accumulating organisms under anaerobic conditions
Authors: Zeng Raymond , Yuan Zhiguo , van Loosdrecht Mark C. M. , Keller Jürg
Published: October 2002

Filipe et al. (2001) proposed an anaerobic metabolic model for glycogen‐accumulating organisms (GAO) in which the succinate–propionate pathway was used to describe the production of propionyl‐CoA. However, propionyl‐CoA is only an intermediate product in the above pathway. Stopping at propionyl‐CoA instead of propionate (the end product of the pathway) results in the consumption of one ATP from succinate to succinyl‐CoA, which was not accounted for in the model of Filipe et al. (2001). This resulted in significant errors in the stoichiometric coefficients in the final metabolic model. A modified model is presented in this communication and is shown to fit the experimental data significantly better than the original model. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 277–279, 2002.
Teaching and learning iterative methods for solving linear systems using symbolic and numeric software
Authors: Cariaga E. A. , Nualart M. C.
Published: October 2002

An integral approach is presented to strengthen the teaching and learning processes in the environment of the undergraduate course Numerical Analysis (NA) for engineering, examining tha advantages of combining the symbolic and numeric paradigms. In particular, the methodology is illustrated with the iterative methods: Gauss–Seidel (GS) and Conjugated Gradient (CG), for the numeric solution of Linear Systems (LS). The computer tools MATLAB and MAPLE are used in a pedagogic model that requires the explicit definition of Prospective Learnings and Activities of Learning. © 2002 Wiley Periodicals, Inc. Comput Appl Eng Educ 10: 51–58, 2002; Published online in Wiley InterScience (www.interscience.wiley.com.); DOI 10.1002/cae.10008
An exploratory study of the perceptions and experiences of further education amongst the young long‐term unemployed
Authors: Bolam Bruce , Sixsmith Judith
Published: October 2002

The aim of this study was to explore, in depth, the perceptions and experiences of Further Education (FE) amongst the young long‐term unemployed. Semi‐structured interviews were conducted with 16 long‐term unemployed youths of 18–25 years of age divided into three groups: those with no experience of FE; those having recently dropped out of FE; and those currently studying in FE. Grounded theoretical analysis highlighted the importance of both responses to and institutional aspects of unemployment. The impact of unemployment, poor previous educational experience and perceived irrelevance of FE are key barriers to learning. Those that enter FE may drop out as a result of both material and psychosocial factors. Those that stay on commonly emphasize both social support and personal agency in decision‐making alongside positive evaluations of FE. In conclusion, limitations of the findings, policy and practical recommendations for successful widening of participation in FE amongst this group are considered. Copyright © 2002 John Wiley & Sons, Ltd.
From genotype to phenotype: linking bioinformatics and medical informatics ontologies
Authors: Holloway Ele
Published: October 2002

A small group of around 40 people came together at the Chancellors Conference Centre in Manchester for the Ontologies Workshop, chaired by Alan Rector and Robert Stevens. The workshop was, rather strangely, spread over 2 half days. In hindsight, this programme worked very well as it gave people the opportunity to chat over a drink on the Saturday evening and share ideas, before launching into the second half on the following day. The participants were from various walks of life, all with a common interest in finding out more about ontologies and promoting collaborations between the medical informatics and bioinformatics ontology communities. Copyright © 2002 John Wiley & Sons, Ltd.
Clinical and survival covariates of eight classes of childhood supratentorial neuroglial tumors
Authors: Gilles Floyd H. , Leviton Alan , Tavaré C. Jane , Adelman Lester , Rorke Lucy B. , Sobel Eugene L. , Hedley‐Whyte E. Tessa , Davis Richard L. ,   The Childhood Brain Tumor Consortium
Published: October 2002

BACKGROUND

In the current study, the authors investigated clinical, surgical, and histologic characteristics (covariates) and their interactions in eight previously identified classes of childhood supratentorial neuroglial tumors. The classes resulted from 5 factor score profiles on 703 supratentorial neuroglial tumors in the Childhood Brain Tumor Consortium database.

METHODS

The Cox proportional models were used to identify class survival covariates.

RESULTS

Age was found to be a survival covariate only in Class 1, in which older age increased the 5‐year survival rate 73% from the first year (0.49) to the tenth year (0.85). A greater amount of tumor removed improved survival in Classes 2 and 4 only. Rosenthal fibers improved survival in Class 2 and overrode the negative effects of high Proliferative factor scores and pleomorphic nuclei. Survival for Class 3 children with high Proliferative factor scores improved from 0.60 to 0.95 as the Spongy factor scores increased. Survival in Class 4 increased from 0.17 to 0.39 with total tumor removal. Irregular nuclei and glomeruloid capillaries improved survival in Class 5 patients. Class 6 survival improved with low cell density. Macrocysts in tumors in Classes 1 and 5 were found to improve survival.

CONCLUSIONS

As a result of the current study, the authors conclude that survival covariates differ with tumor class and may modify prognosis considerably. Cancer 2002;95:1302–10. © 2002 American Cancer Society.

DOI 10.1002/cncr.10815
Role of 5‐aminolevulinic acid in the detection of urothelial premalignant lesions
Authors: Zaak Dirk , Hungerhuber Edwin , Schneede Peter , Stepp Herbert , Frimberger Dominic , Corvin Stefan , Schmeller Nikolaus , Kriegmair Martin , Hofstetter Alfons , Knöchel Ruth
Published: October 2002

BACKGROUND

The authors evaluated the role of 5‐aminolevulinic acid (5‐ALA)‐induced fluorescence endoscopy (AFE) in the detection of flat urothelial lesions in light of the suggestions made for flat neoplastic lesions within the 1999 World Health Organization (WHO) classification of urinary bladder tumors.

METHODS

From 1995 to 2000, 713 patients underwent 1414 AFE procedures for the detection of transitional cell carcinoma of the bladder (TCCB). Fluorescence imaging was performed with an incoherent light source (D‐light; 380–440 nm) that was filtered for efficient protoporphyrin IX excitation and with cystoscopes partially blocking reflected excitation light to enable fluorescence evaluation by a red/blue color contrast 2–3 hours after 50 mL of a 3% solution of 5‐ALA was instilled into the bladder. In total, 3834 biopsy specimens (mean, 2.7 specimens per AFE procedure) were taken.

RESULTS

Malignant disease was found in 1250 (32.6%) of all biopsies, with 304 biopsies (24.3%) showing carcinoma in situ (cis) and dysplasia II° (dys II) according to the previous diagnostic criteria of the WHO. Under prior conventional white‐light endoscopy, 30.3% of specimens with dys II and 52.8% of specimens with cis had been missed.

CONCLUSIONS

The current results suggest that 5‐ALA may be more effective in the detection of flat urothelial lesions than the current diagnostic devices. Cancer 2002;95:1234–8. © 2002 American Cancer Society.

DOI 10.1002/cncr.10821
Patterns of multiple recurrences of superficial (Ta/T1) transitional cell carcinoma of bladder and effects of clinicopathologic and biochemical factors
Authors: Yan Yan , Andriole Gerald L. , Humphrey Peter A. , Kibel Adam S.
Published: October 2002

BACKGROUND

Although multiple sequential recurrences are one of the most important characteristics of superficial transitional cell carcinoma (TCC) of the bladder, few studies have examined multiple sequential recurrence patterns and the clinicopathologic and biochemical factors associated with these patterns.

METHODS

Two hundred seventy superficial TCC bladder carcinoma patients were followed. Clinical, pathologic, and tumor marker (p53, MIB‐1, bcl‐2, c‐erb B‐2, and epidermal growth factor receptor) data were collected at baseline and during followup. The Kaplan‐Meier (KM) method was used to describe multiple recurrences. The Wei, Lin, and Weissfeld (WLW) marginal proportional hazards model was used to assess the effects of clinicopathologic and immunohistochemic factors on multiple recurrences.

RESULTS

Among the 270 patients, 126 (46.7%) had one or more recurrences, 38 (14.1%) had two or more recurrences, and 14 (5.2%) had three or more recurrences during the followup. The median times for the first, the second, and the third recurrences were 23 months, 15 months, and 13 months, respectively. In KM analysis, Stage T1, higher grades, and Ki‐67 stain positivity were associated with the first recurrence, and p53 stain positivity was marginally significant. Other markers were not significant. For the second recurrence, only p53 stain positivity was significant. In multivariate analysis (WLW method), stage was significantly associated with the first recurrence (risk ratio [RR] = 2.03), and Ki‐67 was marginally significant (RR = 1.49). For the second recurrence, only p53 positivity was statistically significant (RR = 2.73).

CONCLUSIONS

Among superficial TCC bladder carcinoma patients, multiple recurrences are common phenomena. The time for recurrence becomes shorter as the number of recurrences increases. In addition to tumor stage and grade, Ki‐67 can be used to identify patients at high risk for a first recurrence; and p53 can be used to identify patients at high risk for a second recurrence. Cancer 2002;95:1239–46. © 2002 American Cancer Society.

DOI 10.1002/cncr.10822
Prognostic significance of positive surgical margins in patients with extraprostatic carcinoma after radical prostatectomy
Authors: Kausik Sankar J. , Blute Michael L. , Sebo Thomas J. , Leibovich Bradley C. , Bergstralh Erik J. , Slezak Jeff , Zincke Horst
Published: October 2002

BACKGROUND

A significant number of prostate adenocarcinoma patients undergoing radical prostatectomy are found to have microscopic extraprostatic disease extension. A majority of these patients have focal extraprostatic extension limited to one or both sides of the prostate. In addition, positive surgical margins are a common pathologic finding in this patient subgroup. In the current study, the authors evaluated the impact of positive surgical margins as an independent predictive factor for prostate specific antigen (PSA) progression in patients with pT3a/b N0M0 carcinoma.

METHODS

The Mayo Clinic prostate cancer registry list provided 1202 patients with pT3a/b NO prostate carcinoma (no seminal vesicle or regional lymph node involvement) who underwent a radical prostatectomy between 1987–1995. To reduce confounding variables, patients who received preoperative therapy or adjuvant therapy were excluded, resulting in 842 patients who were eligible for analysis.

RESULTS

A total of 354 patients (42%) had ≥ 1 positive surgical margins whereas 488 patients (58%) demonstrated no margin involvement. The sites of margin positivity were as follows: apex (n = 163), base (n = 47), posterior prostate (n = 227), and anterior prostate (n = 11). A total of 111 patients had ≥ 2 positive surgical margins. The 5‐year survival free of clinical recurrence and/or biochemical failure (postoperative PSA level > 0.2 ng/mL) for patients with no positive surgical margins was 76% and was 65% for patients with 1 positive surgical margin (P = 0.0001). There was no significant difference in biochemical disease progression between patients with 1 versus those with ≥ 2 surgical margins (65% vs. 62%). Multivariate analysis revealed that positive surgical margins were a significant predictor (P = 0.0017) of clinical disease recurrence and biochemical failure (relative risk, 1.55; 95% confidence interval, 1.18–2.04) after controlling for preoperative PSA, Gleason score, and DNA ploidy.

CONCLUSIONS

In the current study, positive surgical margins were found to be a significant predictor of disease recurrence in patients with pT3a/b NO prostate carcinoma, a finding that is independent of PSA, Gleason score, and DNA ploidy. The benefit of adjuvant therapy in optimizing recurrence‐free survival remains to be tested. Cancer 2002;95:1215–9. © 2002 American Cancer Society.

DOI 10.1002/cncr.10871
Central projections of the utricular nerve in the gerbil
Authors: Newlands Shawn D. , Purcell Ian M. , Kevetter Golda Anne , Perachio Adrian A.
Published: October 2002

The central projections of primary afferent fibers in the utricular nerve, which convey linear head acceleration signals to neurons in the brainstem and cerebellum, are not completely defined. The purpose of this investigation was twofold: 1) to define the central projections of the gerbil utricular afferents by injecting horseradish peroxidase (HRP) and biotinylated dextran amine (BDA) into the utricular macula; and 2) to investigate the projections of individual utricular afferents by injecting HRP intracellularly into functionally identified utricular neurons. We found that utricular afferents in the gerbil projected to all divisions of the vestibular nuclear complex, except the dorsal lateral vestibular nucleus. In addition, terminals were observed in the interstitial nucleus of the eighth nerve, nucleus Y, external cuneate nucleus, and lobules I, IV, V, IX, and X of the cerebellar vermis. No projections appeared in the flocculus or paraflocculus. Fibers traversed the medial and intermediate cerebellar nuclei, but terminals appeared only occasionally. Individual utricular afferents collateralize extensively, projecting to much of the brainstem area innervated by the whole of the utricular nerve. This study did not produce complete filling of individual afferent collateral projections into the cerebellar cortex. J. Comp. Neurol. 452:11–23, 2002. © 2002 Wiley‐Liss, Inc.
Targeting Alzheimer's disease: Is there a light at the end of the tunnel?
Authors: Gurwitz David
Published: October 2002

The prevalence of Alzheimer's disease (AD) is on the rise in developed nations as a consequence of longer human lifespan. Current costs to society are alarming, and are projected to become even more demanding on future health budgets. Considering the relative success of Parkinson's disease pharmacotherapy, the success of AD therapy has been disappointing. Quite a few novel and promising AD drug targets are presented in this special issue of Drug Development Research. These are built on countless research studies, by many bright minds, carried out over the last several decades. However, the answer to the growing AD threat must include reliable and accurate tools, presently lacking, for its early diagnosis in at‐risk individuals. Drug Dev. Res. 56:45–48, 2002. © 2002 Wiley‐Liss, Inc.
Pharmacogenomic approaches in Alzheimer's disease drug development
Authors: Aerssens Jeroen
Published: October 2002

The basic principle of pharmacogenomics, namely, the search for a genetic basis that might explain the interindividual variation in drug response, has been around for a long time. Thanks to some recent biotechnological developments and the deliveries of the Human Genome Project, significant progress can now be made. Of particular interest for pharmacogenomics research is the availability of a large number of genetic markers in the human genome that have been identified and can now efficiently be screened for. In addition to new scientific and laboratory tools, successful pharmacogenomics projects also require high‐quality phenotypic data, for which clinical trials provide a unique resource. This review describes how pharmacogenomic approaches can be applied during the discovery and clinical development of new drugs for Alzheimer's disease. Drug Dev. Res. 56:67–73, 2002. © 2002 Wiley‐Liss, Inc.
Immunological concept in the treatment of Alzheimer's disease
Authors: Solomon Beka
Published: October 2002

More and more evidence shows that Alzheimer's disease, one of the most perplexing medical problems, belongs to a large group of etiologically diverse neurodegenerative disorders, so‐called ‘conformational’ diseases. Pathology of Alzheimer's disease (AD) shows significant correlation between β‐amyloid peptide (AβP) deposition and the clinical severity of dementia. For many years efforts have been focused on the development of selective inhibitors of amyloid formation to reduce the extent of its deposition and related neurotoxic effects. We developed a new concept showing that site‐directed antibodies may modulate the conformation of β‐amyloid peptide, thus leading to immunological treatment of Alzheimer's disease as well as of other conformation related diseases. Indeed, antibodies toward the EFRH sequence, located between amino acids 3–6 of the N‐terminal region of Alzheimer's AβP, found to be a key position in protein conformation modulation, suppress formation of β‐amyloid and dissolve already formed fibrillar amyloid. Performance of such anti‐β‐amyloid antibodies in transgenic mice models of AD showed that they are delivered to the central nervous system (CNS), preventing formation of β‐amyloid and dissolving real plaques. These data support the hypothesis that AβP plays a central role in AD, and antibodies that modulate Aβ conformation may lead toward immunotherapy of the disease. Drug Dev. Res. 56:163–167, 2002. © 2002 Wiley‐Liss, Inc.
Cytosolic protein‐protein interactions that regulate the amyloid precursor protein
Authors: Sabo Shasta L. , Ikin Annat F.
Published: October 2002

Alzheimer disease (AD), a progressive neurodegenerative disease, is the most common cause of dementia in the elderly and is among the leading causes of death in adults. AD is characterized by two major pathological hallmarks, amyloid plaques and neurofibrillary tangles. For a number of reasons, amyloid plaque accumulation is widely thought to be the probable cause of AD. The amyloid plaque core is largely composed of an approximately 4‐kDa peptide referred to as Aβ. Aβ is derived from its precursor, the Alzheimer amyloid protein precursor (APP), by endoproteolytic processing. APP is a type I integral membrane protein, with a long extracellular domain, one transmembrane domain, and a short (≈50 amino acid) cytoplasmic tail. Despite intense efforts to decipher the function of APP, its normal physiological role has remained elusive. The carboxy‐terminus of APP contains the sequence YENPTY, which is absolutely conserved across APP homologues and across species. The YENPTY sequence is important for regulation of APP processing and trafficking. Given the importance of the cytoplasmic domain in APP physiology, a number of laboratories have hypothesized that proteins that bind to the YENPTY sequence in the cytoplasmic domain of APP might regulate APP processing, trafficking, and/or function. In this article, we will discuss data revealing which proteins bind to the cytoplasmic domain of APP, how these binding‐proteins regulate APP metabolism and function, and why such protein‐protein interactions provide an exciting new target for therapeutic intervention in AD. Drug Dev. Res. 56:228–241, 2002. © 2002 Wiley‐Liss, Inc.
Anti‐amyloidogenic activity of cholinergic agents
Authors: Beach Thomas G. , Walker Douglas G. , Roher Alex E. , Potter Pamela E.
Published: October 2002

Overproduction of the peptide amyloid β (Aβ) is thought to be a critical pathogenic event in Alzheimer's disease (AD), leading to the formation of senile (amyloid) plaques, which in turn lead to neurofibrillary tangles, neuronal and synaptic loss, and dementia. Mendelian inheritance of AD, which occurs in a very small proportion of cases, is caused by mutations in the genes for β‐amyloid precursor protein (β‐APP), presenilin 1 or presenilin 2; the mutations are thought to be pathogenic because they result in increased Aβ production. The majority of AD is not inherited in a Mendelian fashion, and is therefore termed sporadic. The cause or causes of this common form of AD is unknown, although it is assumed that overproduction of Aβ is also the critical event. Recent animal experiments suggest that Aβ overproduction in aging and sporadic AD may be the result of cortical cholinergic deafferentation, which occurs as part of normal human aging. Decreasing Aβ production may therefore slow or halt the progression of AD, and cholinergic agents may be particularly suitable for this role. In vitro work has indicated that cholinergic muscarinic M1 receptor agonists may reduce the cellular production of Aβ. In vivo experiments have shown that both muscarinic agonists and acetylcholinesterase inhibitors lower central nervous system (CNS) Aβ concentrations. These results suggest that cholinergic agents may be particularly well suited to a preventative role in AD therapy by limiting the initial accumulation of Aβ. Drug Dev. Res. 56:242–247, 2002. © 2002 Wiley‐Liss, Inc.
Role of amyloid β peptides in the regulation of central cholinergic function and its relevance to Alzheimer's disease pathology
Authors: Kar S.
Published: October 2002

The neuropathological features associated with Alzheimer's disease (AD) brain include the presence of extracellular neuritic plaques composed of amyloid β protein (Aβ), intracellular neurofibrillary tangles containing hyperphosphorylated tau protein, and the loss of basal forebrain cholinergic neurons that innervate regions such as the hippocampus and the cortex. Studies of the pathological changes that characterize AD and several other lines of evidence indicate that Aβ accumulation in vivo may initiate and/or contribute to the process of neurodegeneration and thereby the development of AD. However, the mechanisms by which Aβ peptide influences/causes degeneration of the basal forebrain cholinergic neurons and/or the cognitive impairment characteristic of AD remain obscure. A number of recent studies indicate that physiological concentrations of soluble Aβ‐related peptides, under acute conditions, can negatively regulate various steps of acetylcholine (ACh) synthesis and release without inducing any apparent toxicity, suggesting a possible neuromodulatory role for the peptide in the regulation of central cholinergic functions. Chronic exposure to μM concentrations of Aβ peptides, on the other hand, evokes toxicity in cholinergic neurons, possibly via hyperphosphorylation of tau protein. Activation of selected cholinergic receptors has been shown to influence the processing of amyloid precursor protein as well as modulation of tau phosphorylation. More recently, a direct interaction between nicotinic ACh receptor and Aβ peptides have been demonstrated using a variety of approaches. This review focuses on the role of Aβ‐related peptides in the regulation of function/survival of central cholinergic neurons and its relevance to the cholinergic deficits observed in AD brains. Drug Dev. Res. 56:248–263, 2002. © 2002 Wiley‐Liss, Inc.
A numerical study of the behaviour of a gas–liquid interface subjected to periodic vertical motion
Authors: Valha J. , Lewis J. S. , Kubie J.
Published: October 2002

A numerical study has been undertaken to examine the behaviour of a gas liquid interface in a vertical cylindrical vessel subjected to a sinusoidal vertical motion. The computational method used is based on the simplified marker‐and‐cell method and includes a continuum surface model for the incorporation of surface tension. The numerical results indicate that the surface tension has very little effect on the period and amplitude of oscillations of the interfacial waves. The stability of the interfacial waves has been found to depend on the initial pressure pulse disturbance, and exponential growth of the interfacial wave has been observed in some cases. The influence of the amplitude and frequency of the forcing oscillations has also been investigated. The results are in good agreement with available experimental and analytical solutions. Copyright © 2002 John Wiley & Sons, Ltd.
Course of minimal dementia and predictors of outcome
Authors: Jelle Visser Pieter , Verhey Frans R. J. , Jolles Jellemer , Jonker Cees
Published: October 2002

Background

Previous studies have indicated that not all subjects who meet the CAMDEX criteria of ‘minimal dementia’ progress to dementia. In the present study, predictors of outcome in minimally demented subjects were tested.

Methods

Forty‐five subjects with minimal dementia who were participating in a population‐based study were followed‐up for on average 2.3 years. Variables tested as predictors of outcome were age, the apolipoprotein E (APOE) genotype, and the baseline scores on the MMSE, CAMCOG memory subscale, and fluency. Depression at baseline was tested as a predictor of reversible minimal dementia.

Results

At follow‐up, minimal dementia turned out to be reversible in 11 subjects (24%), and persistent in ten subjects (22%). Twenty‐four subjects (53%) had become demented. Predictors of outcome in multivariate analyses were age, score on the CAMCOG memory subscale, and the APOE genotype. Depression was not associated with reversible minimal dementia.

Conclusions

Subjects who meet the CAMDEX criteria of minimal dementia form a heterogenous group with respect to clinical outcome. Age, the score on the CAMCOG memory subscale, and the APOE genotype can improve predictive accuracy in these subjects. Copyright © 2002 John Wiley & Sons, Ltd.
Alcoholism in older Korean men: prevalence, aetiology, and comorbidity with cognitive impairment and dementia in urban and rural communities
Authors: Kim Jae‐Min , Shin Il‐Seon , Stewart Robert , Yoon Jin‐Sang
Published: October 2002

Background

Alcoholism in the elderly has received little research, particularly outside ‘Western’ cultures.

Objectives

This study aimed to investigate the prevalence and aetiology of alcoholism, and its comorbidity with cognitive impairment and dementia in an older Korean population.

Methods

1134 urban and rural community residents aged 65 or over were surveyed in Kwangju, South Korea. Alcoholism was identified by a culturally validated screening scale.

Results

Alcoholism was present in 16% of men and 2% of women. In men (n = 457), alcoholism was positively associated with manual occupation and negatively with religions encouraging temperance. In the urban sample, alcoholism was associated with higher education and with dementia. In the rural sample, it was associated with lower education and less strongly with dementia.

Conclusions

The prevalence of alcoholism was high in this population. Associated factors and urban/rural differences reflect traditional attitudes toward drinking. Copyright © 2002 John Wiley & Sons, Ltd.
The national context for reform
Authors: Daves, G. Doyle
Published: October 2002

Today's challenges, like those of the Sputnik era almost fifty years ago, require a visible and persistent national commitment to educational renewal and reform.
Investing in faculty
Authors: Project Kaleidoscope  , Core Institution Task Force
Published: October 2002

A clear understanding of why to invest in faculty and how must be an integral part of the strategic planning process.
A perspective on campus planning
Authors: Lidsky Arthur J.
Published: October 2002

Imagining new spaces for science can be a defining moment in the life of an institution, as the campus community addresses fundamental questions about how a major investment in science facilities is an investment in the future of their college or university.