bluuebunny/crossref_metadata_2025 huggingface dataset:
A study of Holocene floodplain particle size characteristics with special reference to palaeochannel infills from the upper Severn basin, Wales, UK
Authors: Taylor Mark Patrick , Brewer Paul A.
Published: August 2002

Multiple sedimentary units from floodplain reaches at Welshpool on the upper River Severn and at the confluence of the Afon Tanat and Afon Vyrnwy (mid‐Wales, UK) were examined to ascertain if they have distinctive particle size characteristics. Changes in particle size characteristics and their possible relationship to known human and climatic impacts are also discussed. Ellipse plots of particle size characteristics from the River Severn floodplain at Welshpool show that coarse‐grained outwash deposits can be clearly discriminated from channel margin or palaeochannel sediments. In contrast, at the Afon Tanat–Vyrnwy study reach, this discrimination is not seen so clearly. The relationships between age and particle size characteristics from the most sampled sedimentary environment, palaeochannel infills, were also examined. The data from the River Severn floodplain at Welshpool show that palaeochannel sediments reveal a gradual but clear increase in particle size from the mid‐ to late Holocene towards the present day. Sediments deposited in the period 90–160 years BP are markedly coarser. It is suggested that these changes may be related to the combined effect of land‐use changes, metal mining impacts and changes in flood frequency and magnitude that occurred at this time within the upper Severn basin. In contrast, the particle size characteristics of post Late Devensian/Early Holocene units from Tanat–Vyrnwy palaeochannels were random with no discernible age–size patterns. It is suggested that the non‐systematic grain size distribution may be due to the steeper valley gradients of the Tanat–Vyrnwy system (and by inference higher stream powers) and its relatively narrow valley form enabling more effective coupling between coarser outwash deposits found on and at the edges of hillslopes and the valley floor. Although the two study reaches have undergone comparable environmental change during the Holocene and lie in the piedmont zone of their catchments, palaeochannel units of the same age possess distinctly different characteristics. Intrinsic reach‐scale geomorphic factors would appear to preclude the uniform application of particle size characteristics to determine alluvial response to environmental change. Consequently, care needs to be applied to the use of such data for environmental discrimination because the phenomenon of equifinality means that a specific set of sediment characteristics is not necessarily exclusive to specific fluvial environments in either space or time. Copyright © 2001 John Wiley & Sons, Ltd.
Electrical coupling between glial cells in the rat retina
Authors: Ceelen Paul W. , Lockridge Amber , Newman Eric A.
Published: August 2002

The strength of electrical coupling between retinal glial cells was quantified with simultaneous whole‐cell current‐clamp recordings from astrocyte–astrocyte, astrocyte–Müller cell, and Müller cell–Müller cell pairs in the acutely isolated rat retina. Experimental results were fit and space constants determined using a resistive model of the glial cell network that assumed a homogeneous two‐dimensional glial syncytium. The effective space constant (the distance from the point of stimulation to where the voltage falls to 1/e) equaled 12.9, 6.2, and 3.7 μm, respectively for astrocyte–astrocyte, astrocyte–Müller cell, and Müller cell–Müller cell coupling. The addition of 1 mM Ba2+ had little effect on network space constants, while 0.5 mM octanol shortened the space constants to 4.7, 4.4, and 2.6 μm for the three types of coupling. For a given distance separating cell pairs, the strength of coupling showed considerable variability. This variability in coupling strength was reproduced accurately by a second resistive model of the glial cell network (incorporating discrete astrocytes spaced at varying distances from each other), demonstrating that the variability was an intrinsic property of the glial cell network. Coupling between glial cells in the retina may permit the intercellular spread of ions and small molecules, including messengers mediating Ca2+ wave propagation, but it is too weak to carry significant K+ spatial buffer currents. GLIA 35:1–13, 2001. © 2001 Wiley‐Liss, Inc.
The progression of cognitive impairment in dementia with Lewy bodies, vascular dementia and Alzheimer's disease
Authors: Ballard C. , O'Brien J. , Morris C. M. , Barber R. , Swann A. , Neill D. , McKeith I.
Published: August 2002

Background

Little is known about the rate of progression or associations of cognitive impairment in dementia with Lewy bodies (DLB), or the associations of accelerated decline.

Method

Dementia patients from a case register were evaluated at baseline and 1 year follow‐up using the Cambridge Assessment for Mental Disorders in the Elderly, section B (CAMCOG) and the Mini‐Mental State Examination (MMSE) to determine the rate of cognitive decline. Operationalized clinical diagnoses were applied (NINCDS ADRDA for Alzheimer's disease (AD), NINCDS AIRENS for vascular dementia (VaD) and consensus criteria for DLB).

Results

One hundred and ninety‐three patients completed annual MMSE schedules (AD, 101; DLB, 64; VaD, 38), of whom 154 completed the CAMCOG. The magnitude of cognitive decline (MMSE, 4–5 points; CAMCOG, 12–14 points) was similar in each of the dementias. The strongest predictor of accelerated cognitive decline in DLB was the apolipoprotein E4 allele (17.5 vs 8.3 points decline on the CAMCOG).

Conclusion

Over 1 year, DLB, VaD and AD patients had similar rates of cognitive decline overall. Apolipoprotein E4 may be an important predictor of more rapid decline in DLB. Copyright © 2001 John Wiley & Sons, Ltd
Visual detection of motion speed in humans: spatiotemporal analysis by fMRI and MEG
Authors: Kawakami Osamu , Kaneoke Yoshiki , Maruyama Koichi , Kakigi Ryusuke , Okada Tomohisa , Sadato Norihiro , Yonekura Yoshiharu
Published: August 2002

Humans take a long time to respond to the slow visual motion of an object. It is not known what neural mechanism causes this delay. We measured magnetoencephalographic neural responses to light spot motion onset within a wide speed range (0.4–500°/sec) and compared these with human reaction times (RTs). The mean response latency was inversely related to the speed of motion up to 100°/sec, whereas the amplitude increased with the speed. The response property at the speed of 500°/sec was different from that at the other speeds. The speed‐related latency change was observed when the motion duration was 10 msec or longer in the speed range between 5 and 500°/sec, indicating that the response is directly related to the speed itself. The source of the response was estimated to be around the human MT+ and was validated by functional magnetic imaging study using the same stimuli. The results indicate that the speed of motion is encoded in the neural activity of MT+ and that it can be detected within 10 msec of motion observation. RT to the same motion onset was also inversely related to the speed of motion but the delay could not be explained by the magnetic response latency change. Instead, the reciprocal of RT was linearly related to the reciprocal of the magnetic response latency, suggesting that the visual process interacts with other neural processes for decision and motor preparation. Hum. Brain Mapping 16:104–118, 2002. © 2002 Wiley‐Liss, Inc.
Reductive dimerization and reduction of imines using lanthanum metal
Authors: Nishino Toshiki , Nishiyama Yutaka , Sonoda Noboru
Published: August 2002

The treatment of N‐benzylideneaniline (1a) with a half‐equivalent of lanthanum metal and a catalytic amount of iodine gave the reductive dimerization product of 1a, a vic‐diamine, in good yield. Various vic‐diamines were synthesized from aldimines in this manner in moderate to good yields. Our findings suggest that electrons of a zero‐valent lanthanum metal were efficiently utilized in this reductive dimerization. In the reaction of ketimines, however, a similar reductive dimerization did not take place, and the corresponding amines were formed as the sole products. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:131–135, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10007
The Integrated Postsecondary Education Data System
Authors: Schuh John H.
Published: August 2002

This chapter discusses the Integrated Postsecondary Education Data System as a tool for collecting data to be used in benchmarking studies.
Neonatal health care costs related to smoking during pregnancy
Authors: Kathleen Adams E. , Miller Vincent P. , Ernst Carla , Nishimura Brenda K. , Melvin Cathy , Merritt Robert
Published: August 2002

Research objective: Much of the work on estimating health care costs attributable to smoking has failed to capture the effects and related costs of smoking during pregnancy. The goal of this study is to use data on smoking behavior, birth outcomes and resource utilization to estimate neonatal costs attributable to maternal smoking during pregnancy.

Study design: We use 1995 data from the Center for Disease Control's (CDC) Pregnancy Risk Assessment Monitoring System (PRAMS) database. The PRAMS collects representative samples of births from 13 states (Alabama, Alaska, California, Florida, Georgia, Indiana, Maine, Michigan, New York (excluding New York City), Oklahoma, South Carolina, Washington, and West Virginia), and the District of Columbia. The 1995 PRAMS sample is approximately 25 000. Multivariate analysis is used to estimate the relationship of smoking to probability of admission to an NICU and, separately, the length of stay for those admitted or not admitted to an NICU. Neonatal costs are predicted for infants ‘as is’ and ‘as if’ their mother did not smoke. The difference between these constitutes smoking attributable neonatal costs; this divided by total neonatal costs constitutes the smoking attributable fraction (SAF). We use data from the MarketScan™ database of the MedStat™ Corporation to attach average dollar amounts to NICU and non‐NICU nursery nights and data from the 1997 birth certificates to extrapolate the SAFs and attributable expenses to all states.

Principal findings: The analysis showed that maternal smoking increased the relative risk of admission to an NICU by almost 20%. For infants admitted to the NICU, maternal smoking increased length of stay while for non‐ NICU infants it appeared to lower it. Over all births, however, smoking increased infant length of stay by 1.1%. NICU infants cost $2496 per night while in the NICU and $1796 while in a regular nursery compared to only $748 for non‐NICU infants. The combination of the increased NICU use, longer stays and higher costs result in a positive smoking attributable fraction (SAF) for neonatal costs. The SAF across all states is 2.2%. Across the states, the SAF varied from a low of 1.3% in Texas to a high of 4.6% in Indiana.

Conclusions: These results further confirm the adverse effects of smoking. Among mothers who smoke, smoking adds over $700 in neonatal costs. The smoking attributable neonatal costs in the US represent almost $367 million in 1996 dollars; these costs vary from less than a million in smaller states to over $35 million in California. These costs are highly preventable since the adverse effects of maternal smoking occur in the short‐run and can be avoided by even a temporary cessation of maternal smoking. These cost estimates can be used by managed care plans, state and local public health officials and others to evaluate alternative smoking cessation programs. Copyright © 2002 John Wiley & Sons, Ltd.
A one‐year study of the Rostherne Mere ecosystem: seasonal dynamics of water chemistry, plankton, internal nutrient release, and implications for long‐term trophic status and overall functioning of the lake
Authors: Krivtsov Vladimir , Sigee David , Bellinger Edward
Published: August 2002

A study of Rostherne Mere (Cheshire, UK) was undertaken to reveal relationships among various ecosystem components and assess the progress in lake recovery following sewage diversion. An intensive monitoring programme included measurements of dissolved oxygen, T, pH, electric conductivity, K, Mg, Ca, Si, N and P species, Secchi depth, suspended solids, chlorophyll‐a, phyto‐ and zooplankton counts. Recorded changes and the results of correlation analysis broadly confirmed to the classic limnoecological theory and allowed detailed interpretation of the dynamics observed. The Si level was used to estimate the amount of diatom detritus produced in spring. Chemical profiles were used to estimate the amount of nutrients accumulated in the hypolimnion during the stratified period. These estimates were compared with simulations made using the model of exponential decay, which showed a good performance in the case of Si but considerable underestimation in the case of P. The differences between the values simulated by the model and estimates based on field observations resulted from the additional P release from the sediments. This release could have been stimulated by a combination of factors, including the development of anoxic layers on the sediment–water interface and Si‐induced desorption from Fe, Al and Mn oxides. Internal P loading during the stratified period was thus estimated at about 4–9 g/m2, suggesting that rapid changes in the lake's trophic status are at present unlikely. Certain aspects of this work (including interpretation of interrelationships between ecosystem components, estimation of the decomposition constant, analysis of factors controlling nutrient accumulation in the hypolimnion, and a low‐cost method to estimate internal P release) may be useful for studies of other aquatic systems and have, therefore, general limnological applicability. Copyright © 2001 John Wiley & Sons, Ltd.
TP53 mutation pattern of esophageal squamous cell carcinomas in a high risk area (Southern Brazil): Role of life style factors
Authors: Pütz Arno , Hartmann Antonio A. , Fontes Paulo R.O. , Alexandre Claudio O.P. , Silveira Daniela A. , Klug Stefanie J. , Rabes Hartmut M.
Published: August 2002

In an attempt to correlate the TP53 mutation pattern of squamous cell carcinomas of the esophagus (ESCC) and life style factors of patients from the high risk area Rio Grande do Sul, Brazil, 135 ESCC were analyzed, after prescreening by p53 immunohistochemistry, by SSCP and DNA sequencing of TP53, exon 5–9. Forty‐nine somatic TP53 mutations (and 1 case with p53 polymorphism) were identified as missense (n = 39), frameshift (n = 6), silent (n = 1), amber (n = 1) or intron border mutations (n = 2) that cause splicing aberrations. They were preferentially found in exon 5 (36.7%) and exon 8 (32.7%). Several mutations were located in the mutation hot spot codons 248, 273 and 282, mainly at CpG sites. Transition mutations were observed in 53.1% (among them 50% G > A), transversion mutations in 34.7% (among them 47.1% G > T) and frameshifts in 12.2%, the latter 2 mainly in smokers and alcohol drinkers. Transitions were more prevalent in females than in males (p < 0.05). TP53 mutations, mainly transversions, were more frequently found in heavy smokers (p = 0.03), with the same tendency after chronic alcohol consumption. Comparison with the worldwide IARC database disclosed differences in the TP53 mutation pattern of the Brazilian tumors, with a higher accumulation of TP53 mutations in exon 8 and a higher prevalence of transition mutations. Mutations at the reported hot spot codon 176 were missing. Although difficult because of the documented coexposure to various life style risk factors in most patients of this series, the hypothesis is proposed that besides smoking and alcohol drinking the commonly consumed hot mate tea in this high risk area for ESCC is responsible for this different pattern of TP53 mutations because of chronic hyperthermic irritation and inflammation in the esophagus with an endogenous formation of radicals or carcinogenic factors that lead to a higher prevalence of transition mutations. © 2001 Wiley‐Liss, Inc.
Intratumoral immunotoxin treatment of human malignant brain tumors in immunodeficient animals
Authors: Engebraaten Olav , Hjortland Geir Olav , Juell Siri , Hirschberg Henry , Fodstad Øystein
Published: August 2002

Treatment of malignant brain tumors remains a clinical challenge. New treatment modalities are under investigation and among these are intratumoral infusion of immunotoxins that bind to specific cell surface molecules on the malignant cells. We have compared the efficacy of the 425.3‐PE immunotoxin (which targets the epidermal growth factor [EGF] receptor) with the well‐known immunotoxin Tfn‐CRM107 (which targets the transferrin receptor), for the treatment of subcutaneous and intracranial human gliomas in nude animals. Bolus intratumoral administration of 1 μg Tfn‐CRM107 or 425.3‐PE into sc U87Mg tumors in nude mice reduced the tumor volume to 29 and 79%, respectively, of that in the control group 18 days after start of treatment. Higher doses of Tfn‐CRM107 were toxic to the animals, whereas 425.3‐PE was tolerated, with a dose‐response relationship of up to 8 μg, a dose that reduced the tumor volume to 2% of control. In nude rats, treatment of intracerebral U87Mg tumors with Tfn‐CRM107 proved ineffective and doses above 10 ng/animal were toxic to tumor‐bearing rats. In contrast, intratumoral administration of 4 μg 425.3‐PE increased symptom‐free survival from 23 days to 40 days, with 2/9 surviving more than 90 days. We have recently shown that immunodeficient rats inoculated intracerebrally with precultured glioblastoma biopsy specimens develop highly infiltrative brain tumors. Direct interstitial infusion of immunotoxins into such tumors reduced the number of animals with detectable tumors at autopsy after 3 months, from 8/9 in the control animals to 4/6 and 2/6 in animals treated with Tfn‐CRM107 and 425.3‐PE, respectively. In conclusion, the anti‐EGF receptor immunotoxin 425.3‐PE exhibited promising efficacy, comparable to or better than that of Tfn‐CRM107, an immunotoxin that in early clinical trials has been found to give responses in patients with brain tumors. © 2001 Wiley‐Liss, Inc.
Tumor‐specific CD8+ T lymphocytes derived from the peripheral blood of prostate cancer patients by in vitro stimulation with autologous tumor cell lines
Authors: Housseau Franck , Langer Daniel A. , Oberholtzer Samuel D. , Moorthy Anitha , Levitsky Hyam I. , Pardoll Drew M. , Topalian Suzanne L.
Published: August 2002

To identify tumor‐associated antigens as putative targets for developing immunotherapies against prostate cancer, we investigated the ability of T cells derived from the peripheral blood lymphocytes of prostate cancer patients to recognize autologous tumor cells. The technical challenge of growing in vitro carcinoma cell lines from small prostate cancer samples was previously addressed by immortalization of early epithelial cell cultures with the HPV16 transforming proteins E6 and E7 and by genetic characterization of the carcinoma and normal prostate cell lines. In our study, peripheral blood lymphocytes were stimulated in vitro using autologous IFNγ‐treated prostate carcinoma cells transduced with the B7.1 molecule as a source of T‐cell costimulation. Tumor‐specific CD8+ T lymphocytes were obtained from 3 of 6 prostate cancer patients tested and included T cells restricted by classical and nonclassical HLA molecules. In 1 case, we demonstrated that the prostate cancer‐reactive T cells were TCRα/β+ and recognized autologous tumor cells but not autologous normal cells in the context of HLA‐B or ‐C molecules. These results validate the approach of in vitro stimulation of peripheral blood lymphocytes from prostate cancer patients with autologous tumor cell lines to isolate prostate cancer‐specific T cells and demonstrate the existence of a functionally diverse immune response against prostate cancer. Published 2001 Wiley‐Liss, Inc.
A phase I‐II study of docetaxel‐ifosfamide‐cisplatin (DIP) combination chemotherapy regimen in advanced nonsmall cell lung cancer
Authors: Kosmas Christos , Tsavaris Nicolas B. , Makatsoris Thomas , Onyenadum Adimchi , Vadiaka Maria , Stavroyianni Niki , Sepsas Evangelos , Dimitropoulos Dimitris , Rokana Sofia , Kalofonos Haralambos P.
Published: August 2002

In an attempt to develop more effective chemotherapy regimens in advanced nonsmall cell lung cancer (NSCLC), we evaluated docetaxel‐ifosfamide‐cisplatin (DIP) based on our previous experience with paclitaxel‐ifosfamide‐cisplatin. Patients with advanced NSCLC (stages III‐IV), WHO‐PS≤2, no prior chemotherapy and unimpaired hematopoietic and organ function were eligible. Chemotherapy was administered in successive dose levels (DLs) and included docetaxel (80–100 mg/m2 day 1), ifosfamide (4–5 g/m2) and cisplatin (80–100 mg/m2), both divided over days 1 and 2 every 21 days. G‐CSF (lenograstin) was administered from days 4–13. Fifty‐five patients were accrued (phase I: 15; phase II: 40) and all are evaluable for response and toxicity: median age = 58 (40–72); PS = 1 (0–2); gender = 48 males, 7 females; stages IIIA = 8, IIIB = 19, IV = 28; and histologies were adenocarcinoma (29), squamous (20), large cell (6). Metastatic sites at diagnosis included lymph nodes (33), bone (8), liver (6), brain (6), lung nodules (9), adrenals (7) and soft tissue (1). The dose‐limiting toxicity (DLT) was reached at DL4 (Docetaxel: 100 mg/m2‐Ifosfamide: 5 g/m2‐Cisplatin: 100 mg/m2) consisting of 2 cases of febrile neutropenia (FN), and DL3 (Docetaxel: 100 mg/m2‐Ifosfamide: 5 g/m2‐Cisplatin: 80 mg/m2) was considered as the maximum tolerated dose (MTD) and recommended for further phase II testing. Among evaluable patients in phase II, 31/46 (67%; CI = 54–81%) responded; 4 were complete responses, 27 partial responses, 12 with stable disease and 3 with progressive disease. The median response duration was 7 months (2–21+), median time to progression (TTP) 8 months (1–23+) and median overall survival (OS) 13 months (2–23+). The 1‐year survival was 57%. Grade (Gr) 3/4 toxicities included neutropenia 39/46 with 27 developing Gr4 (≤7 days) and 20% FN managed successfully with broad‐spectrum antibiotics, thrombocytopenia Gr3 3/46‐Gr4 1/46, no Gr3 neuropathy, Gr1‐2 CNS toxicity in 12, no renal toxicity, 15 Gr2 myalgias, 17 Gr2 diarrhea and 10 Gr3 vomiting. In the present phase I‐II study, DIP appears highly active and tolerable in advanced NSCLC in the outpatient setting. Randomized comparisons to current standard 2‐drug regimens will be warranted. © 2001 Wiley‐Liss, Inc.
Inhibition of metalloproteinases enhances the internalization of anti‐CD30 antibody Ki‐3 and the cytotoxic activity of Ki‐3 immunotoxin
Authors: Hansen Hinrich P. , Matthey Bärbel , Barth Stefan , Kisseleva Tatiana , Mokros Thilo , Davies Stephen J. , Beckett R. Paul , Foelster‐Holst Regina , Lange Hans H. , Engert Andreas , Lemke Hilmar
Published: August 2002

CD30 is selectively expressed on the tumor cells of a variety of malignant disorders of the immune system and can therefore be used as a target for an anti‐CD30 antibody‐based immunotherapy. However, CD30 is cleaved at the cell surface by tumor necrosis factor‐α converting enzyme (TACE). This metalloproteinase releases the soluble ectodomain of CD30 (sCD30), which is able to neutralize immunotherapeutic agents before these reach their target cells. Such constitutive CD30 cleavage is enhanced after binding of most anti‐CD30 antibodies, leading to a downregulation of CD30 and an increase of sCD30 in the cell environment. Here, we demonstrate that CD30 shedding from the cell line Karpas 299 could effectively be blocked by the hydroxamic acid‐based metalloproteinase inhibitors BB‐3644 (IC50 = 180 nM), BB‐2116 (IC50 = 230 nM), BB‐94 (batimastat, IC50 = 230 nM) and BB‐2516 (marimastat, IC50 = 1 μM). This inhibition reduced the concentration of sCD30 in the cell environment to the background level, prolonged the persistence of the anti‐CD30 antibody Ki‐3 on Karpas 299 cells and favored its internalization. Moreover, a nontoxic concentration of the inhibitor BB‐3644 significantly increased the cytotoxic activity of the anti‐CD30 ricin A‐chain immunotoxin Ki‐3.dgA towards the CD30+ Hodgkin‐derived cell line L540. Hence, the metalloproteinase inhibitor BB‐3644 may be a promising compound to improve the immunotherapy of CD30+ malignancies. © 2001 Wiley‐Liss, Inc.
Human papillomavirus 16 load in normal and abnormal cervical scrapes: An indicator of CIN II/III and viral clearance
Authors: van Duin Mark , Snijders Peter J.F. , Schrijnemakers Henri F.J. , Voorhorst Feja J. , Rozendaal Lawrence , Nobbenhuis Marielle A.E. , van den Brule Adriaan J.C. , Verheijen René H.M. , Helmerhorst Theo J. , Meijer Chris J.L.M.
Published: August 2002

The relation between human papillomavirus type 16 (HPV 16) viral load in cervical scrapes and development of high‐grade cervical intraepithelial neoplasia (CIN II or III) was studied in a nested case‐control study of women with normal cytology (group A) and in a cohort of women with abnormal cytology (group B). HPV 16 DNA load was determined using a quantitative real‐time PCR assay. In group A, case women (women with CIN II/III, n = 12) had a significantly higher viral load than control women (women with CIN ≤ I, n = 47). This resulted in an increased relative risk of women with the 50% highest viral load for development of CIN II/III (OR 7.7; CI 1.6–33). In group B, women with CIN II/III (n = 38) had a significantly higher viral load than women with CIN ≤ I (n = 25). Women with the 50% highest viral load had an increased relative risk of CIN II/III (OR 3.2; CI 1.1–9.3) and a decreased chance of both viral clearance and cytologic regression. Our data suggest that in women with normal cytology an increased HPV 16 load confers an increased risk of developing a CIN lesion. A sustained high viral load is subsequently informative for progression to a high‐grade CIN lesion. © 2002 Wiley‐Liss, Inc.
Invasive bladder carcinoma: A pilot study of conservative treatment with accelerated radiotherapy and concomitant cisplatin
Authors: Zouhair Abderrahim , Ozsahin Mahmut , Schneider Dominique , Bauer Jean , Jichlinski Patrice , Roth Arnaud , Douglas Pelham , Miralbell Raymond
Published: August 2002

From November 1992 to December 1997, 25 patients (inoperable or refusing cystectomy) were included in a prospective study to assess the feasibility, tolerance, and curative potential of accelerated radiotherapy (RT) and concomitant cisplatin. Median age was 74 years (range 49–86). Stage distribution was as follows: 1 T1, 10 T2, 8 T3, and 6 T4. Two patients had clinically positive pelvic nodes. The goal was to deliver a total dose of 40 Gy to the whole pelvis and bladder in 4 weeks using a concomitant boost of 20 Gy to the tumor or to the whole bladder during the third and fourth weeks (total dose 60 Gy), with daily cisplatin (6 mg/m2) before RT for patients with creatinine clearance > 50 ml/min. All but one patient completed the RT protocol. Daily cisplatin was sucessfully delivered in 18 patients. One patient presented with grade III ototoxicity. Diarrhea was scored grade III in two and grade IV in two patients. Acute urinary toxicity was scored grade III in one patient. Posttreatment late effects included bladder grade II and grade III in two patients and one patient, respectively; large bowel grade III in one; urethral grade III in one; and femoral head radionecrosis in one. Four‐year overall and disease‐specific survival rates were 23% and 35%, respectively. The latter was 60% for patients with T2 tumors. The 4‐year actuarial locoregional control rate for all patients was 61%. In summary, accelerated RT and concomitant cisplatin is feasible with acceptable tolerance even in relatively old patients. Although outcome was better for patients with low‐stage tumors, local control and survival rates appeared similar to those of standard RT schedules for a similar patient population. © 2001 Wiley‐Liss, Inc.
Loss of heterozygosity on chromosome 10q is associated with earlier onset sporadic colorectal adenocarcinoma
Authors: Fawole Adeshina S. , Simpson David J. , Rajagopal Ramesh , Elder Jackie , Holland Tracey A. , Fryer Anthony , Deakin Mark , Elder James B. , Farrell William E.
Published: August 2002

Recent studies have shown that loss of heterozygosity (LOH) on chromosome 10q is a frequent event in a number of tumour types including colorectal cancers. Because previous studies have used markers located mainly distally on chromosome 10, we have examined 114 sporadic colorectal adenocarcinomas for LOH using a panel of 9 highly polymorphic microsatellite markers spanning the long arm of chromosome 10. Using microdissected tumour material, LOH of one or more chromosome 10q markers was a frequent event (75 of 114; 66%). The highest frequency of loss (42 of 96; 44%) was observed at the marker D10S1790 located at 10q21.1. The mean age of presentation, of patients with LOH of D10S1790 was significantly (p = 0.0006) lower (67.1 years) compared to patients with retention of this marker (73.5 years). When we compared frequency of loss at this marker in patients presenting before 70 years of age (68%) to those above 70 years (23%) we observed a significant difference (p < 0.0001). Statistical analysis between loss, or instability at other markers and clinicopathological features did not show any significant associations. In addition LOH at D10S1790 was infrequent in adenomas (2 of 20; 10%) compared to adenocarcinomas (42 of 96; 44%) (p = 0.0047), suggesting that loss within this region is a late event in colorectal tumorigenesis. The association of loss at D10S1790 and an earlier age of presentation in adenocarcinomas suggests that this locus may harbor a tumour suppressor gene(s), which affects the rate of colorectal tumour progression. Identification of this region of genetic loss further refines our understanding of the paradigm in this tumour type of multiple‐steps responsible for initiation and progression. © 2002 Wiley‐Liss, Inc.
Removal of acetaldehyde from saliva by a slow‐release buccal tablet of L‐cysteine
Authors: Salaspuro Ville , Hietala Jaana , Kaihovaara Pertti , Pihlajarinne Liisa , Marvola Martti , Salaspuro Mikko
Published: August 2002

High alcohol intake is an independent risk factor for upper gastrointestinal (GI)‐tract cancers. There is increasing evidence that acetaldehyde, the first metabolite of ethanol, might be responsible for ethanol‐associated carcinogenesis. Especially among Asian heavy drinkers with the ALDH2‐deficiency gene, i.e., a genetic inability to remove acetaldehyde, the risk of digestive tract cancers is markedly increased. Local acetaldehyde production from ethanol either by oral microbes, mucosal cells or salivary glands is a plausible carcinogenic agent in the saliva. The aim of our study was to examine whether is it possible to bind carcinogenic acetaldehyde from saliva with L‐cysteine, which is slowly released from a special buccal tablet. Nine healthy male volunteers took part in our study, and each subject served as his own control. A placebo or L‐cysteine‐containing tablet was fastened under the upper lip. Thereafter the volunteers ingested 0.8 g/kg of body weight of 10% (v/v) ethanol, and saliva samples were collected at 20 min intervals for 320 min. Salivary acetaldehyde and ethanol levels were analysed by headspace gas chromatography. The mean reduction of acetaldehyde concentration of the saliva with the L‐cysteine tablet compared to placebo was 59% (CL95% 43%, 76%). Area under the curve (AUC0–320min) with the L‐cysteine and placebo tablet were 54.3 ± 11 μM × hr and 162 ± 34.2 μM × hr (mean ± SEM), respectively (p = 0.003). After alcohol intake, up to two‐thirds of carcinogenic acetaldehyde can be removed from saliva with a slow‐releasing buccal L‐cysteine drug formulation. Thus, a buccal cysteine tablet could potentially be used to prevent upper GI‐tract cancers, especially among high‐risk individuals. © 2001 Wiley‐Liss, Inc.
Channelling and filtering migration: Hungary's bilateral labour migration agreements
Authors: Hárs Ágnes
Published: August 2002

New forms of mobility are being shaped in Europe which both challenge traditional explanations of mobility and contribute to popular fears of mobility. But what makes people move, and which economic indicators effectively explain migration? Does the projected migration pressure from Central/Eastern Europe actually exist? The answer to this question is often posed in terms of mainstream economic arguments concerning wage/income differences, but this offers only a partial explanation of migration. This paper considers attempts to control migration, channelling foreign labour from the countries of Central and Eastern Europe through different bilateral agreements, under different conditions, to European Union countries, as a way of admitting selected types of labour while excluding others. Surprisingly little is known about such programmes, and the paper considers who is attracted to these programmes, and the nature of the engine of this channelled labour migration? A statistical, socio‐demographic, labour‐market analysis of participants in these schemes, with special emphasis on the Hungarian case, is presented. The question is posed as to whether such bilateral agreements offer a means to control the expected European migration ‘shock’, and concludes that this is not the aim of these schemes. Copyright © 2002 John Wiley & Sons, Ltd.
Lessons learned from study of the developmental impact of parental alcohol use
Authors: Carmichael Olson Heather , O'Connor Mary J. , Fitzgerald Hiram E.
Published: August 2002

This overview outlines the magnitude of the impact of parental substance abuse on children's development. The aim of this special issue is described: to encourage research productivity by promoting integration between two traditionally separate literatures with quite different theoretical perspectives: (1) the effects of prenatal substance exposure; and (2) the impact on children of postnatal rearing by parents addicted to substances. Because study of the developmental impact of parental alcohol use has a long research tradition, lessons learned can guide the field. Thus, this overview focuses on the role of maternal drinking in the emergence of childhood psychopathology, a topic of interest to infant mental health. As an example, this article features multiple findings from O'Connor's programmatic research, which is built upon current models of development and integrated theoretical perspectives, and includes both lower and higher risk samples. These data show that women in a middle‐class sample who drank more heavily during pregnancy had infants with higher levels of negative affect and insecure attachments. At ages 5–6, a greater percentage of these alcohol‐exposed children showed significant levels of depression than expected for their age. Prenatal alcohol exposure and maternal depression both contributed significantly to prediction of preschoolers' depression, and findings could not be explained by mother's current drinking. Congruent results from a higher risk sample show how cumulative risk can exacerbate problems, and extend earlier data by documenting the mother–child interplay that can maintain or reduce the deleterious effects of prenatal alcohol exposure over time. Results are discussed in light of current theory about the early emergence of internalizing disorders, with implications for research and intervention. This overview ends by introducing the articles in this special issue, and how each contributes to advancing its aim. ©2001 Michigan Association for Infant Mental Health.
Work Plans
Authors: Zemsky Robert , Shaman Susan , Shapiro Daniel B.
Published: August 2002

This chapter provides a set of rules and tools for helping institutional leaders and researchers succeed at being market smart in order to remain mission centered.
The current state of paddy agriculture in Japan1
Authors: Sato Hitoshi
Published: August 2002

This document is a published version of the keynote speech made at the Asian Regional Workshop on Sustainable Development of Irrigation and Drainage for Rice Paddy Fields held in Tokyo in July 2000, hosted by the Japanese National Committee of the ICID.

This report outlines the current state of paddy agriculture in Japan, focusing on the history of paddy field development, current status of paddy field improvements, the formation of rules on water use, and the roles of land improvement districts, which form the basis of managing agricultural water in Japan. It also highlights the present situation of agriculture in Japan, directions of relevant efforts and initiatives, and the importance of enhancing multiple functions of paddy agriculture for the national livelihood as well as securing a stable food supply.

Paddy agriculture is an effective way of achieving both agricultural production and environment conservation functions in the Asian monsoon region. However, in the face of limited land and water resources as well as rapidly increasing population, a stable food supply will be difficult to attain in the future without the development and the establishment of irrigation and drainage technologies for paddy fields, and the dissemination and sharing of these technologies. Copyright © 2001 John Wiley & Sons, Ltd.
Controlled drainage effects on water quality under semi‐arid conditions in the western delta of Egypt
Authors: Wahba M.A.S. , El‐Ganainy M. , Abdel‐Dayem M.S. , Gobran Atef. , Kandil H.
Published: August 2002

Field experiments were conducted for two years in the Western Delta of Egypt to investigate the effects of controlled drainage on the quality of subsurface drainage outflows. Two water table management methods were applied in the 2.54 ha experimental field: free conventional subsurface drainage and controlled drainage. Controlled drainage was applied at 60 cm depth during both seasons. Drain discharge volumes and nitrate‐N and orthophosphate‐phosphorus concentrations were monitored during the growing seasons. The controlled drainage (CD) treatment significantly reduced the total drainage outflow by 68% during the summer season and by 28% during the winter of 1999–2000 at 99% confidence level, compared to free conventional drainage (FD) treatment. The CD also reduced the total nitrate‐N in drainage water by 73%, and 32% during the summer and the winter seasons respectively, compared to the FD treatment.

The CD treatment reduced the total orthophosphate‐phosphorus losses by 77% during summer of 1999 and by 30% during winter of 1999–2000 compared to the FD treatment; however, in general the total mass loss was low in both treatments. The results of the experiment showed the potential environmental and economic benefits with the application of controlled drainage in semi‐arid regions. Copyright © 2001 John Wiley & Sons, Ltd.
Evaluating business credit risk by means of approach‐integrating decision rules and case‐based learning
Authors: Stefanowski Jerzy , Wilk Szymon
Published: August 2002

This research utilizes a new approach which uses a hybrid learning system that combines two representations of knowledge: the first in a form of decision rules referring to general knowledge, and the other of single cases corresponding to exceptions or untypical situations. The Explore algorithm was chosen as a tool for inducing general rules. It generates all simple and sufficiently strong general rules from a given data set. Examples discovered by these rules are then used to identify exceptions and untypical cases. The paper discusses problems connected with tuning parameters of this approach and introduces a new procedure for this task. This methodology is applied to solve the problem of evaluating the risk of business credit applications in a Polish commercial bank. Using information about business credit applications, as described by 35 economic parameters and using five groups of banking risk, a knowledge base consisting of 70 decision rules and 15 specific cases was induced. Testing this model in the standard ‘leaving‐one‐out’ way we achieved the best classification accuracy of 81%. A comparative study showed that results obtained by other machine‐learning algorithms resulted in significantly worse classification accuracy. Copyright © 2001 John Wiley & Sons, Ltd.
Quasi‐fixed inputs and long‐run equilibrium in production: a cointegration analysis
Authors: Kim H. Youn , Lee Junsoo
Published: August 2002

This paper proposes a cointegration approach to testing the validity long‐run equilibrium in production, where capital and labour are taken as quasi‐fixed inputs. Previous studies consider only capital as the quasi‐fixed input and do not take account of the time series properties of the variables, assuming implicitly that they are stationary. The canonical cointegrating regressions (CCR) procedure is employed to test for cointegration in both the single‐equation and the seemingly unrelated regressions framework, and long‐run equilibrium conditions are tested. The evidence from US manufacturing reveals that capital and labour are not fully adjusted to their long‐run optimal values, casting doubt on the long‐run equilibrium hypothesis. Copyright © 2001 John Wiley & Sons, Ltd.
A flexible parametric GARCH model with an application to exchange rates
Authors: Wang Kai‐Li , Fawson Christopher , Barrett Christopher B. , McDonald James B.
Published: August 2002

Many asset prices, including exchange rates, exhibit periods of stability punctuated by infrequent, substantial, often one‐sided adjustments. Statistically, this generates empirical distributions of exchange rate changes that exhibit high peaks, long tails, and skewness. This paper introduces a GARCH model, with a flexible parametric error distribution based on the exponential generalized beta (EGB) family of distributions. Applied to daily US dollar exchange rate data for six major currencies, evidence based on a comparison of actual and predicted higher‐order moments and goodness‐of‐fit tests favours the GARCH‐EGB2 model over more conventional GARCH‐t and EGARCH‐t model alternatives, particularly for exchange rate data characterized by skewness. Copyright © 2001 John Wiley & Sons, Ltd.
Role of heat shock protein 60 (HSP60) on paraquat intoxication
Authors: Kaetsu Akihiko , Fukushima Tetsuhito , Inoue Seigou , Lim Heejin , Moriyama Masaki
Published: August 2002

The possibility of establishing a new method of treatment against pulmonary fibrosis caused by acute paraquat intoxication, which takes into consideration the role of heat shock protein 60 (HSP60), was investigated in paraquat‐exposed rat lung mitochondria. In polyacrylamide electrophoresis, mitochondrial protein bands appeared, especially in the range of molecular weight 60 kDa and higher, whereas protein bands disappeared in the 20–40 kDa range on the 4th day after paraquat exposure. The protein profile was normalized on the 7th day and no remarkable changes were seen thereafter up to the 56th day. The changes seen during the observation period were thought to reflect the course of paraquat‐induced dysfunction and subsequent repair. The malondialdehyde concentration in mitochondria decreased until the 7th day but subsequently increased and recovered to normal levels by the 56th day. The relative density of HSP60 increased until the 7th day but subsequently decreased and recovered to normal levels by the 56th day. These two parameters therefore showed symmetrical changes. The change in the malondialdehyde concentration was thought to reflect the course of activation of the antioxidation function in mitochondria and the progression of repair. The change in the relative density of HSP60 was thought to have increased to repair the proteins affected by the paraquat radical and to have normalized with the progression of healing. These results suggest that HSP60 may play an important role in preventing the progression of pulmonary fibrosis induced by paraquat. Copyright © 2001 John Wiley & Sons, Ltd.
Fabrication of porous hydroxyapatite bodies by a new direct consolidation method: starch consolidation
Authors: Rodríguez‐Lorenzo L. M. , Vallet‐Regí M. , Ferreira J. M. F.
Published: August 2002

A new direct consolidation method known as “starch consolidation” was developed especially for the fabrication of porous ceramics, as adopted to prepare hydroxyapatite (OHAp) bodies with different pore sizes and pore volume fractions. The method is based on the swelling ability of starch when it is heated to 80°C in the presence of water. An OHAp powder prepared by a precipitation method and heat treated at 900°C to obtain an appropriate specific surface area for colloidal processing was used in the present work. Wet ball milling was required to deagglomerate the powder and improve its processing ability. Different starch volume fractions and starch particle sizes were added to the OHAp slurries, which were then heat treated to promote consolidation by starch gelification. A linear relationship between the planned and measured porosity values was observed. SEM pictures reveal the presence of interconnected pores with shape and sizes corresponding to starch granules used. Flexural strength varied from about 2 to 15 MPa, for pore volume fractions of ∼70 and 45%, respectively. A degradation study in an acellular synthetic body fluid (SBF) has shown that the prepared bodies keep their integrity under physiological conditions during the studied time. The method offers possibilities of manufacturing materials that can be used as scaffolds engineering and/or systems for controlled delivery of drugs. © 2002 John Wiley & Sons, Inc. J Biomed Mater Res 60: 232–240, 2002; DOI 10.1002/jbm.10036
Force spectroscopy study of the adhesion of plasma proteins to the surface of a dialysis membrane: Role of the nanoscale surface hydrophobicity and topography
Authors: Conti Matteo , Donati Gabriele , Cianciolo Giuseppe , Stefoni Sergio , Samorì Bruno
Published: August 2002

A mechanochemical study of the process of adhesion of plasma proteins to the surface of dialysis membranes was carried out with a scanning force microscope (SFM) in the force spectroscopy mode. Three representative blood plasma proteins (fibronectin, fibrinogen, and albumin) covalently were grafted to a SFM probe, and the adhesion forces of these proteins to cellulosic and synthetic dialysis membranes were measured. The experiment was tailored to apply a controlled load on the protein molecules adsorbed onto the surface in order to simulate the squeezing forces exerted on them during blood filtration. The de‐adhesion forces, measured using this new approach for studying the interaction between a protein and dialysis membranes, suggest that the membrane's topography, at a nanometer scale, plays a critical role in the adhesion process. This result was strongly supported by parallel experiments performed on a flattened glass surface with the same dominant hydrophilic character as dialysis membranes. In contrast, a hydrophobic polystyrene surface led to de‐adhesion forces at least one order of magnitude greater, overwhelming any possible shape recognition process between the protein molecules and the surface. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 370–379, 2002