bluuebunny/crossref_metadata_2025 huggingface dataset:
Trastuzumab plus docetaxel in HER‐2/neu‐positive prostate carcinoma
Authors: Lara Primo N. , Chee Karen Giselle , Longmate Jeff , Ruel Christopher , Meyers Frederick J. , Gray Carl R. , Edwards Regina Gandour , Gumerlock Paul H. , Twardowski Przemyslaw , Doroshow James H. , Gandara David R.
Published: April 2004

BACKGROUND

Overexpression of the HER‐2/neu oncoprotein has been reported to occur in ≤ 60% of patients with prostate carcinoma and to correlate with shortened survival. Trastuzumab is a humanized monoclonal antibody to the HER‐2 receptor and has activity against HER‐2–positive breast carcinoma, more so when combined with a taxane. The authors screened for HER‐2 overexpression in patients developing hormone‐refractory prostate carcinoma (HRPC) and conducted a Phase II trial of trastuzumab plus docetaxel in HER‐2–positive patients.

METHODS

Paraffin‐embedded tumor specimens from potentially eligible patients were screened for HER‐2 expression by immunohistochemistry (IHC) and/or amplification by fluorescent in situ hybridization (FISH). Shed HER‐2 was also assessed by enzyme‐linked immunoradsorbent assay (ELISA). Patients with HER‐2–positive tumor specimens (IHC 2+ or 3+ or FISH ratio > 2) were initially randomized to receive either single‐agent trastuzumab or docetaxel. After two treatment cycles, nonresponding patients received the trastuzumab/docetaxel combination. Treatment was comprised of 30 mg/m2 of docetaxel weekly for 6 weeks followed by a 2‐week break and 4 mg/kg of trastuzumab intravenously during Week 1 then 2 mg/kg per week thereafter. The cycle length was 8 weeks.

RESULTS

One hundred patients with HPRC were screened. IHC results were as follows: 3+ (n = 1), 2+ (n = 6), 1+ (n = 26), 0 (n = 39), and insufficient tissue specimen/not tested (n = 28). Only 3 of 37 patients had elevated shed HER‐2 by ELISA (> 15 mg/mL). None overexpressed HER‐2 by IHC. FISH amplification was found in 0 of 34 tissue samples. Of seven patients with IHC 3+ or 2+, four were tested by ELISA and two by FISH. None were abnormal. Age and Gleason score did not correlate with IHC status. Of the seven patients eligible for the Phase II study, only four agreed to participate. The trial was thus closed for nonfeasibility (the overall HER‐2 positivity rate was < 20%). No patient responded to trastuzumab alone. The median survival was not reached and the median progression‐free survival was 7 months.

CONCLUSIONS

HER‐2 overexpression by IHC in archival prostate carcinoma specimens was infrequent. There was no apparent correlation among IHC, ELISA, and FISH, although the sample size was limited. Conclusions regarding the predictive value of HER‐2 status on outcome after trastuzumab‐based therapy were not reached and were only drawn after larger‐scale screening efforts. The authors estimated that 1000 patients need to be screened to complete accrual to a 40‐patient efficacy trial. Cancer 2004. © 2004 American Cancer Society.
Ultrasound‐guided fine‐needle aspiration biopsy remains a valid approach in the evaluation of nonpalpable breast lesions
Authors: Liao Jim , Davey Diane D. , Warren Graham , Davis Joseph , Moore Angela R. , Samayoa Luis M.
Published: April 2004

The use of ultrasound‐guided fine‐needle aspiration (FNA) biopsy for nonpalpable breast lesions varies considerably. This retrospective study stresses the role of breast FNA in evaluating sonographically suspicious nonpalpable breast masses using a probabilistic reporting system. One hundred and eight consecutive ultrasound‐guided FNA biopsies diagnosed as positive (32), suspicious (8), atypical (11), benign (55), and unsatisfactory (2) were analyzed and correlated with 61 subsequent surgical specimens. All positive cytologies showed carcinoma on histology; suspicious cases were followed by 5 carcinomas, 2 fibroadenomas, and 1 papillary lesion. Follow‐up of atypical cases included 4 carcinomas, 3 fibroadenomas, and 2 papillary lesions, while all 10 biopsies following benign cytology showed fibrocystic changes. Two cases with suspicious sonographic findings but unsatisfactory cytology had lobular carcinoma. The remainder of the benign and atypical cases were followed clinically and radiographically for at least 10 months and had no evidence of carcinoma. Positive predictive values were positive, 100%; suspicious, 63%; atypical, 36%; benign, 0%. Most (40/43; 93%) carcinomas were invasive. In conclusion, ultrasound‐guided FNA for nonpalpable breast lesions is highly accurate, and probabilistic reporting helps direct patient management. Diagn. Cytopathol. 2004;30:325–331. © 2004 Wiley‐Liss, Inc.
Immunotherapy with OX40L‐Fc or anti‐CTLA‐4 enhances local tissue responses and killing of Leishmania donovani
Authors: Zubairi Soombul , Sanos Stephanie L. , Hill Sue , Kaye Paul M.
Published: April 2004

Enhancing granuloma development and effector function, but without inducing the pathology associated with excess granulomatous inflammation, poses a major challenge for immunotherapeutic intervention against diseases such as visceral leishmaniasis (VL). Here, we demonstrate that a chimeric fusion protein (OX40L‐Fc) which stimulates T cells through OX40 and a monoclonal antibody which blocks CTLA‐4, an inhibitory receptor on T cells, both enhanced the rate of granuloma maturation, CD4+ T cell proliferation, and killing of Leishmania. Costimulation‐based therapy induced no adverse fibrotic or necrotic reactions, and had no significant effect on the levels of endogenous anti‐inflammatory cytokines (IL‐10 and TGF‐β). Furthermore, both OX40L‐Fc and anti‐CTLA4could be co‐administered with conventional anti‐leishmanial drugs. Until now, enhancing T cell immunity by the manipulation of costimulatory pathways has only received serious attention for cancer immunotherapy, but our data provide a compelling argument for the evaluation of this approach in human VL and other infectious diseases.
Vanadyl Phosphate Intercalated with Diethyl Ether
Authors: Melánová Klára , Beneš Ludvík , Zima Vítězslav , Trchová Miroslava , Dybal Jiří
Published: April 2004

Vanadyl phosphate intercalated with diethyl ether has been prepared by replacing 2‐propanol molecules in the corresponding VOPO4 intercalate with diethyl ether. The intercalate contains one diethyl ether molecule per formula unit. The guest molecules are anchored to the host layers by an O−V donor−acceptor bond. The local structure and interactions in the intercalate have been suggested on the basis of quantum chemical calculations. The intercalate is thermally stable. Its diffractogram does not change up to 100 °C. A new phase with lower basal spacing appears at 130 °C. The intercalate is very moisture‐sensitive; the diethyl ether molecules are easily replaced by water molecules. The replacement of diethyl ether in the vanadyl phosphate intercalate by the water molecules has been monitored by infrared spectroscopy. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Bismuth(III) Triflate in Organic Synthesis
Authors: Gaspard‐Iloughmane Hafida , Le Roux Christophe
Published: April 2004

Bismuth(III) triflate is a new, cheap and environmentally friendly Lewis acid. The research presented in this microreview is devoted to the evaluation of the scope of the uses of bismuth(III) triflate in organic synthesis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Estimation of mass transfer and kinetics in operating trickle‐bed bioreactors for removal of VOCS
Authors: Barton John W. , Davison Brian H. , Klasson K. Thomas , Gable C. Chris
Published: April 2004

Long‐term, stable operation of trickle‐bed bioreactors remains desirable but is difficult to achieve for industrial processes, which generate continuous streams of dilute gaseous hydrocarbons. Mass transfer and kinetics parameters are difficult to measure, complicating predictive estimates. Two methods are presented which were used to predict the importance of mass transfer versus kinetics limitations in operating trickle‐bed biofilters. Both methods altered the overall activity of the biofilter and estimated the effective mass transfer coefficient (KLa) by varying the VOC (volatile organic contaminant) loading rate and concentration. The first method altered the total bed temperature of a well‐established biofilter to effect a change. The second method, used with developing biofilters possessing low biomass, involved addition of cultured biomass to the recirculating liquid to effect an overall change in VOC removal capacity. Results and modeling from these experiments are presented for a mixed culture trickle‐bed bioreactor that is capable of consuming sparingly soluble alkanes, such as pentane and isobutane. Methods to control overgrowth are discussed which were used to operate one reactor continuously for over 24 months with sustained degradation of volatile alkanes with a rate of 50 g h–1 m–3.
Demonstration of pilot‐scale pervaporation systems for volatile organic compound removal from a surfactant enhanced aquifer remediation fluid II. Hollow fiber membrane modules
Authors: Abou‐Nemeh I. , Majumdar S. , Saraf A. , Sirkar K. K. , Vane L. M. , Alvarez F. R. , Hitchens L.
Published: April 2004

Pilot‐scale demonstration of pervaporation‐based removal of volatile organic compounds from a surfactant enhanced aquifer remediation (SEAR) fluid has been conducted at U.S. EPA's Test & Evaluation Facility using hollow fiber membrane modules. The membranes consisted of microporous hydrophobic polypropylene fibers having a thin plasmapolymerized silicone layer on the outside surface. The SEAR fluid was allowed to flow through the fiber bores at 35–45° C, while vacuum was pulled on the shell side. The SEAR fluid was obtained from a pilot‐scale demonstration at Hill Air Force Base, Layton, Utah, and contained trichloroethylene (TCE) at 3,000 mg/L, 1, 1, 1‐trichloroethane (TCA) at 450 mg/L and tetrachloroethylene (PCE) at 400 mg/L along with 2.5 wt % anionic surfactant, 1.5 wt % isopropyl alcohol, 1 wt % salt and a small amount of nonvolatile oil/grease. The hollow fiber modules were run at flow rates of 0.25‐1 gpm for a period of 8‐10 hours every day for a total of six weeks along with a continuous 40‐hour run using the SEAR fluid. The modules were never washed with any fluid. The performance of the hollow fiber modules was stable and satisfactory vis‐à‐vis VOC removal and pressure drop considerations.
Effectiveness of very thin soil layers in chemical release from bed sediment
Authors: Talbert Bryan , Thibodeaux Louis J. , Valsaraj Kallait T. T.
Published: April 2004

The chemical containment effectiveness of both the natural recovery and the “particle broadcasting” processes for remediating contaminated bed‐sediments depend upon very thin soil and/or sand layers millimeters in depth. Conventional capping for in situ chemical containment of bed‐sediment or dredged material typically involves thick layers of 30 to 90 centimeters in depth. Few studies have been conducted with thin layers of candidate natural materials. A steady‐state benzoic acid dissolution test apparatus and procedure, devised to realistically simulate bed‐sediment chemo‐dynamic conditions, was used to measure chemical flux through thin layers (1 to 8 mm) of soil, sand, and ideal porous media. The thin layers were found to be very effective. Flux reductions ranged from 81 to 96%, with fine sand being slightly better than top soil. Design algorithms developed for the thick layers used in conventional capping design will under predict the flux through very thin layers. Advective flow induced by surface roughness is proposed to explain the higher average measure d‐to‐predicted flux ratio of 1.67.
Eliminating a sulfuric acid mist plume from a wet caustic scrubber on a petroleum coke calciner
Authors: Brown Charles A. , Hohne Paul A.
Published: April 2004

Reducing sulfuric acid mist emissions and eliminating the visible plume that remained after steam dissipation were the objectives of a project recently completed for a petroleum coke calciner. The coke calciner produces flue gas containing SO2 that is treated with a wet caustic scrubber. The scrubber is extremely efficient at removing most of the SO2, but some oxidizes to SO3, catalyzed by vanadium in the coke dust that collects in the waste heat boiler. Submicron droplets of H2SO4 form when the flue gas is quenched by the scrubber liquor, and makes its way through the scrubber. This paper describes the installation of, and performance test results for, a wet electrostatic precipitator (WESP), as well as SO2 scrubber modifications that were re q u i red to make room for the WESP. The successful project significantly reduced sulfuric acid mist emissions, eliminating the visible plume while maintaining a very low SO2 outlet concentration, even after removing one of three gas‐liquid contactors.
Long‐term evaluation of an industrial‐scale biofilter for odor control at a large metropolitan wastewater treatment plant
Authors: Zhuang Lian , Keener Tim C. , Siddiqui Kaniz F.
Published: April 2004

The efficiency of H2S removal by an industrial scale biofilter using a wood‐based mulch at a large publicly owned wastewater treatment plant has been evaluated for over a one‐year time period. The research consisted of developing sampling and analytical methods, validation of experimental methods, and the evaluation of the biofilter's performance. The study showed that removal efficiency strongly depends on the inlet H2S concentration. The elimination capacity increases as inlet loading increases until full elimination is achieved. The H2S removal efficiency was constantly higher than 95% during the one‐year period of this study. The removal efficiency was higher than 99% when the inlet H2S concentration was lower than 100 ppmv, and it dropped sharply when the inlet concentration was higher than 100 ppmv. The removal efficiency dropped from 99% to 95% when the inlet H2S concentration reached about 250 ppmv. At lower H2S concentrations (< 100 ppmv), the elimination capacity equaled the inlet H2S loading. The maximum elimination capacity was determined to be 14 g H2S/m2 hr. The seasonal temperature dependency of H2S production was also investigated based on ambient temperature data. Maximum levels of H2S production corresponded to periods of highest average ambient temperature.
SO2 scrubbing technologies: A review
Authors: Srivastava Ravi K. , Jozewicz Wojciech , Singer Carl
Published: April 2004

Electricity generating units may use sulfur dioxide (SO2) scrubbers to meet the requirements of Phase II of the Acid Rain SO2 Reduction Program. Additionally, the use of scrubbers can reduce mercury emissions. It is timely, therefore, to review the commercially available flue gas desulfurization (FGD) technologies that have an established record of performance. Data on worldwide applications reflect that wet FGD technologies have been used at most of the installations, 522 out of 668, completed through 1998.

In reviewing the SO2 removal performance of scrubbers, data reflect that most wet limestone and lime spray drying installations appear to be capable of about 90% SO2 removal. Advanced, state‐of‐the‐art wet scrubbers can provide removal in excess of 95%. This paper also reviews recently reported advances in SO2 scrubbing technologies. Some of these advances have been aimed at improving the performance and cost‐effectiveness of established processes. Others, like wet ammonia FGD, have focused on developing new processes. Costs associated with limestone forced oxidation (LSFO) technology are analyzed.
Non‐Thermal organic waste destruction: Characterization of the CerOx system 4
Authors: Varela Juan A. , Oberg Steven G. , Neustedter Thomas M. , Nelson Norvell
Published: April 2004

The first commercial system for the CerOx Process Technology for destruction of liquid organic hazardous waste materials has been installed at the Environmental Health and Safety Department (EH&S) at the University of Nevada, Reno, (UNR). A non‐thermal alternative to incineration, CerOx is an electrochemically‐driven, aqueous phase process that oxidizes organic materials at near ambient temperatures and atmospheric pressure in a fully contained tank system consistent with the provisions of 40 CFR 260.10 Subpart J. The tank system classification exempts the CerOx Process from RCRA regulation while its electrochemical basis allows for scaling to accommodate on‐site waste processing ranging from less than a drum per day to plant size applications. The addition of the CerOx System 4 to the UNR waste management program allows the University to reduce the quantity of organic hazardous wastes shipped off‐site for disposal.

The data presented in this report were used to show that the operation of the CerOx Process is in compliance with the Washoe County Air District and with the Reno‐Sparks POTW, the governing air and water regulatory agencies for the UNR location. The report covers two series of verification tests that were conducted before and after a major equipment upgrade which included a significant design improvement in the electrochemical cells. The after process releases to the atmosphere, as regulated by the Washoe County Air District, and to the Reno‐Sparks publicly‐owned treatment works(POTW) were well within their defined limits.
An electrocoagulation unit for the purification of soluble oil wastes of high COD
Authors: Calvo L. Sánchez , Leclerc Jean‐Pierre , Tanguy G. , Cames M. C. , Paternotte G. , Valentin G. , Rostan A. , Lapicque F.
Published: April 2004

In spite of abundant literature on the topic, the efficiency of electrocoagulation for a specific effluent cannot be predicted in advance. Prior to designing an industrial wastewater treatment unit, preliminary treatment tests have to be done using different soluble oil wastes with a very high chemical oxygen demand (COD). The influence of various parameters can then be assessed. Coagulant dose, linked to the electrical charge passed and the nature of the waste, seem to be the controlling parameters of process efficiency. The results obtained at the laboratory‐scale have been confirmed in a small pilot cell, and an industrial unit has been designed. A preliminary economic study shows that electrocoagulation may be competitive with current treatment technologies. From knowledge gained at bench‐scale, we concluded that electrocoagulation appears to be a suitable process for treatment of soluble oily wastes with high COD.
Life cycle management as a business strategy for sustainability
Authors: Saur Konrad
Published: April 2004

Today's business climate demands signifcant shzfts in how organizations deliver products and services to customers. Firms in many industrial sectors are effectively using management systems and life cycle assessments to understand and improve their operations, products, and services. But, a more comprehensive approach is needed to significantly reduce the pressure on natural systems, and to successfully respond to the increased complexity of business decision‐making in the 21st centuly. This paper discusses life cycle management as an effective business strategy that can continually respond to these unique new challenges.
LCC—The economic pillar of sustainability: Methodology and application to wastewater treatment
Authors: Rebitzer Gerald , Hunkeler David , Jolliet Olivier
Published: April 2004

Industrial applications of supply chain cost management, along with life cycle costing of goods and services, are increasing. Several industrial sectors, in particular the automotive, electronics, and primary materials, have engaged in programs to coordinate upstream and downstream activities to reduce environmental burdens. At the same time, there is an increasing need to pass on information on product, material, and energy flows along the supply chain, as well as to provide data on the use and end‐of‐life phases of goods and services. Therefore, methods to analyze, assess, and manage these flows, from an economic as well as an environmental perspective, are of essential importance, particularly in established large‐scale industries where suppliers are increasingly challenged to provide comprehensive cost and environmental information. In this context, a life cycle costing analysis (LCC), conducted as part of life cycle management activities, can provide important opportunities. Therefore, this paper focuses on a life cycle assessment (LCA)‐based LCC method, which utilizes an LCA model as a basis for cost estimations in product development and planning. A case study on life cycle costing of wastewater treatment illustrates the practical use and benefits of the method.
Implementing life cycle assessment in product development
Authors: Bhander Gurbakhash Singh , Hauschild Michael , McAloone Tim
Published: April 2004

The overall aim of this paper is to provide an understanding of the environmental issues involved in the early stages of product development, and the capacity of Life Cycle Assessment (LCA) techniques to address these issues. The paper aims to outline the problems for the designer in evaluating the environmental benignity of a product from the outset, and to provide a framework for decision support based on the performance evaluation at different stages of the design process. The barriers that prevent product developers from using LCA are presented, as well as opportunities for introducing environmental criteria in the design process by meeting the designer's information requirements at the different life cycle stages. This can lead to an in‐depth understanding of the attitudes of product developers towards the subject area, and an understanding of possible future directions for product development.

This paper introduces an Environmentally Conscious Design method, and presents trade‐offs between design degrees of freedom and environmental solutions. Life cycle design frameworks and strategies are also addressed. The paper collects experiences and ideas around the state‐of‐the‐art in eco‐design, from literature and personal experience, and provides eco‐design life cycle assessment strategies. The end result of this presentation is to define the requirements for performance measurement techniques, and the environment needed to support life cycle evaluation throughout the evaluation of early stages of a product system.
Resistance to tearing of calf and ostrich pericardium: Influence of the type of suture material and the direction of the suture line
Authors: Páez José María García , Carrera Antonio , Jorge Eduardo , Millán Isabel , Cordon Angeles , Maestro María A. , Rocha Aurora , Castillo‐Olivares José Luis
Published: April 2004

The tearing of the valve leaflet of a cardiac bioprosthesis can cause early failure of this device, which is employed to replace a diseased native valve. This report involves the study of the behavior of 312 tissue samples (152 of calf pericardium and 160 of ostrich pericardium) treated with glutaraldehyde and subsequently subjected to tear testing. The samples were cut in the two principal directions: longitudinally, or root to apex, and transversely. They included a series of control samples that were left unsutured, and the remaining samples were repaired with the use of two different suture techniques: a running suture in the direction of the load and a telescoping suture perpendicular to the load. Four commercially available suture materials were employed: Pronova®, nylon, Gore‐Tex®, or silk. The unsutured control samples of both types of pericardium exhibited a similar anisotropic behavior in the tear test. The mean resistance to tearing of the calf pericardium was 24.29 kN m in samples cut longitudinally and 34.78 kN m in those cut transversely (p = .03); the values were 28.08 kN m and 37.12 kN m (p = .002), respectively, in ostrich pericardium. The series repaired with the telescoping suture always exhibited greater resistance to tearing, with values that ranged between 44.34 and 64.27 kN for the samples of calf pericardium and from 41.65 to 47.65 kN for those obtained from ostrich. These assays confirm the anisotropic behavior of calf and ostrich pericardium treated with glutaraldehyde when subjected to tear testing, as well as the loss of this behavior in ostrich pericardium after suturing. Suturing techniques, such as the telescoping model, that provide a greater resistance to tearing should be studied for use in the design of the valve leaflets of cardiac bioprostheses made of biological materials. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 69B: 125–134, 2004
Long‐term strength of ceramics for biomedical applications
Authors: Zhang Yu , Lawn Brian
Published: April 2004

The influence of slow crack growth on the initiation of radial cracks at the lower surfaces of ceramic layers bonded to polymeric substrates is studied, with particular relevance to biomechanical systems, e.g., dental crowns and hip replacement prostheses. Critical loads are measured as a function of loading rate (dynamic fatigue) for model bilayers fabricated by epoxy‐bonding selected clinical ceramics to polycarbonate bases. Radial crack initiation is observed in situ by viewing from below the transparent base during loading. Declines in the critical loads with diminishing load rate are consistent with slow crack growth of intrinsic flaws prior to radial crack pop in. A simple fracture mechanics relation incorporating a crack velocity function is used to analyze the data. Extrapolation beyond the data range enables long‐lifetime (10 yr) estimates of sustainable loads. The procedure provides a basis for ranking ceramic types, and in particular for eliminating vulnerable candidate materials, for use in biomechanical systems. While slow crack growth is an important factor in failure, other mechanisms could operate in concert and even dominate under severe testing conditions, especially under cyclic loading. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 69B: 166–172, 2004
Chitosan membrane as a wound‐healing dressing: Characterization and clinical application
Authors: Azad Abul Kalam , Sermsintham Niwet , Chandrkrachang Suwalee , Stevens Willem Frans
Published: April 2004

Chitosan prepared from natural biopolymer chitin and cast into membranes has been tested as wound dressing at the skin‐graft donor site in patients. Bactigras, a commonly used impregnated tulle gras bandage, served as a control. Chitosan membrane, prepared with a 75% degree of deacetylation and a thickness of 10 μm, was used in nonmesh or mesh form. The progress in wound healing was compared by clinical and histological examination. Itching and pain sensitivity of the wound dressed area was scored with the use of a visual analogue scale. Mesh chitosan membrane in contrast to the nonmesh membrane allowed blood to ooze into the surrounding gauze. After 10 days, the chitosan‐dressed area had been healed more promptly as compared with the Bactigras dressed area. Moreover, the chitosan mesh membrane showed a positive effect on the re‐epithelialization and the regeneration of the granular layer. The data confirm that chitosan mesh membrane is a potential substitute for human wound dressing. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 69B: 216–222, 2004
C2 monitoring of cyclosporine in de novo liver transplant recipients: The clinician’s perspective
Authors: Villamil Federico , Pollard Stephen
Published: April 2004

Adjusting cyclosporine (CsA) dose based on blood concentration at 2 hours after dose (C2) has been shown in prospective clinical trials to reduce the risk of rejection compared with conventional trough monitoring. In addition, it provides equivalent efficacy to tacrolimus in liver transplant patients, with a favorable safety profile. Target C2 should be defined on an individual basis depending on adjunctive therapy and the level of exposure required. It appears less critical to achieve target C2 in the first few days after liver transplantation than was previously believed. Achieving target C2 exposure in the initial period after transplant requires that changes in the proportion of cyclosporine absorbed from the gut be taken into account to avoid risk of overexposure. In addition, if a starting dose of 10-15 mg/day is used, it is advisable to delay increasing the dose until a trend in C2 level indicates this to be necessary. Immediate dose reduction is required if C2 exceeds target range. In patients with low C2 values, cyclosporine concentration at a later time point should be measured to establish whether the patient is a poor absorber or a delayed absorber of C2, and dose adjustments should be undertaken accordingly. In conclusion, this more flexible approach to C2 monitoring allows the dose of cyclosporine to be individualized effectively for each patient, which results in significant efficacy benefits while minimizing the risk of toxicity. (Liver Transpl 2004;10:577-583.)
Estimation of liver size for liver transplantation: The impact of age and gender
Authors: Choukèr Alexander , Martignoni André , Dugas Martin , Eisenmenger Wolfgang , Schauer Rolf , Kaufmann Ines , Schelling Gutav , Löhe Florian , Jauch Karl-Walter , Peter Klaus , Thiel Manfred
Published: April 2004

In general, the liver is considered to be larger in males than in females. In the present study, data on liver weight from 728 legal autopsies were analyzed with respect to gender, age, body height (BH), body weight (BW), body mass index (BMI), and body surface area (BSA). Descriptive statistics revealed that liver weight increases with age, reaching maximum values between 41 and 50 years in men and between 51 and 60 years in women. Thereafter, liver weight decreases again. Because this loss in liver weight starts earlier in men while liver weight continues to rise in women, the difference in liver weight between men and women is lost above the age of 50. Thus, this age defines a threshold value below which gender is expected to be a critical factor in the calculation of liver weight. When demographic data mentioned above were subjected to multiple stepwise linear regression analysis, liver weight (LW) was best predicted in younger people (16-50 years) by body weight, age, and gender: LW (g) = 452 + 16.34 × BW + 11.85 × age − 166 × gender (r2 = 0.381; “gender”: 1 = female, 0 = male). In contrast, in elderly people (51-70 years) LW was best predicted by BW and age only. Gender was not a significant factor. LW (g) = 1390 + 15.94 × BW − 12.86 × age (r2 = 0.35). When these formulas were applied to demographic data from 97 organ donors and compared to published formulas (which, however, do not consider the age-dependent effects of gender), the new formulas best predicted male to female liver weight ratios in younger and elderly donors. In conclusion, the new formulas might better predict liver weight in organ donors and transplant recipients to avoid liver size mismatch. (Liver Transpl 2004;10:678-685.)
Liver transplantation for neuroendocrine tumors: Progress and uncertainty†
Authors: Rosado Barbara , Gores Gregory J.
Published: April 2004

Metastases from neuroendocrine tumors (NET) of the gastrointestinal tract, carcinoids, and endocrine pancreatic tumors (EPT) can be limited to the liver for long periods and may have slow growth. The symptoms are often related to hormone overproduction, and debulking surgery—for example, liver resection—is recommended to achieve tumor remission or symptom palliation. If liver resection is not feasible, hepatectomy and orthotopic liver transplantation (OLT) have been proposed. For EPT where the primary tumor is located in the head of the pancreas it may be advantageous to resect the primary tumor and the liver metastases en blocand perform a multivisceral transplantation (MVTx). (Transplant Proc 2003;35:809-810.)
Prediction of protein‐protein interactions based on surface patch comparison
Authors: Carugo Oliviero , Franzot Giacomo
Published: April 2004

A method to predict if two proteins interact, based on their three‐dimensional structures, is presented. It consists of five steps: (i) the surface of each protein, represented by the solvent accessible atoms, is divided into small patches; (ii) the shape of each patch is described by the atom distributions along its principal axes; (iii) the shape complementarity between two patches is estimated by comparing, through contingency table analysis, their atom distributions along their principal axes; (iv) given protein A, with nA surface patches, and protein B, with nB surface patches, nA×nB shape complementarity values are obtained; and (v) the distribution of the latter allows one to discriminate pairs of interacting and of noninteracting proteins. Only a few seconds are necessary to predict if two proteins interact, with accuracy close to 80%, sensitivity over 70% and specificity close to 50%.
Proteomic analysis of mouse mammary terminal end buds identifies axonal growth cone proteins
Authors: Morris Joanna S. , Davies Claire R. , Griffiths Matthew R. , Page Martin J. , Bruce James A. , Patel Thakor , Herath Athula , Gusterson Barry A.
Published: April 2004

Ductal morphogenesis in the mouse mammary gland occurs mainly postnatally and is driven by specialized structures at the ends of the developing ducts, the terminal end buds (TEBs), which later regress once ductal growth is complete. To identify proteins that are specifically associated with migration of TEBs we developed a novel method of isolating TEBs, which eliminated the mammary stroma. The protein expression profile of the TEBs was then compared with that of isolates taken from the 4th inguinal mammary gland of adult virgin mice using two‐dimensional (2‐D) gel electrophoresis and mass spectrometry (MS) analysis (matrix‐assisted laser desorption/ionization and quadrupole time of flight). Following construction of an integrated protein expression database, 44 protein features which showed differential expression levels between the two sets were chosen for MS analysis. Of these, 24 gave protein annotations whereas the other 20 produced unidentified peptides. Fourteen unequivocal proteins were identified from these 24, whereas the remaining 10 matched more than one protein within a single 2‐D gel feature. Several of the identified proteins were associated with the cytoskeleton and have previously been reported in axonal growth cones, suggesting that they may influence cell shape and motility within the advancing TEBs, in a similar fashion to migrating axons.
Prediction of the subcellular localization of eukaryotic proteins using sequence signals and composition
Authors: Reczko Martin , Hatzigerrorgiou Artemis
Published: April 2004

A tool called Locfind for the sequence‐based prediction of the localization of eukaryotic proteins is introduced. It is based on bidirectional recurrent neural networks trained to read sequentially the amino acid sequence and produce localization information along the sequence. Systematic variation of the network architecture in combination with an efficient learning algorithm lead to a 91% correct localization prediction for novel proteins in fivefold cross‐validation. The data and evaluation procedure are the same as the non‐plant part of the widely used TargetP tool by Emanuelsson et al. The Locfind system is available on the WWW for predictions (http://www.stepc.gr/~synaptic/locfind.html).
Effects of d‐wave symmetry in high‐TC grain boundary Josephson junctions
Authors: Barone Antonio , Lombardi Filomena , Monaco Antonia , Sarnelli Ettore , Tafuri Francesco , Testa Gianluca
Published: April 2004

Recent experimental results on the physics of high temperature superconductivity (HTS) related to coherent phenomena and unconventional pairing symmetry are discussed. Some consequences of the d‐wave order parameter symmetry on the phenomenology of HTS junctions of different type are investigated. The attention is focused on recent experiments based on biepitaxial YBa2Cu3O7−δ Josephson structures where junctions with a π shift in the phase have been reproducibly obtained. Anisotropy measurements confirm the relevance of effects of d‐wave order parameter symmetry on the properties of the junctions, and prove that intrinsic d‐wave effects can be predominant over extrinsic effects. The possibility to obtain some kind of tunnel‐like barriers and to tune d‐wave effects through a suitable geometry has been demonstrated opening some perspectives towards novel device concepts within the framework of π circuitry and “quiet qubit”. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Coexistence of superconductivity and magnetism in low dimensional conductors
Authors: BenAli A. , Charfi‐Kaddour S. , Pasquier C. , Bennaceur R. , Héritier M.
Published: April 2004

Coexistence of superconductivity and antiferromagnetism in low dimensional conductors can be explained by a phase segregation scenario: (i) In quasi 1D or 2D conductors in which the (T, pressure) phase diagram exhibits a border line between superconducting and spin density wave (SDW) phases, it is favourable to create a phase segregation in the direct space by forming alternatively superconducting and magnetic slabs (ii) a phase segregation may also occur in reciprocal space. A d‐wave superconducting order is established, with lines of zero gap on the Fermi surface, as in cuprates. In the node region, superconductivity is weak enough to leave room for a confined SDW gap. These models can explain consistently various recent experimental data observed in low dimensional conductors
Sampled‐data iterative learning control with well‐defined relative degree
Authors: Sun Mingxuan , Wang Danwei , Wang Youyi
Published: April 2004

This paper addresses the problem of iterative learning control with well‐defined relative degree. The solution is a family of sampled‐data learning algorithms using lower‐order differentiations of the tracking error with the order less than the relative degree. A unified convergence condition for the family of learning algorithms is derived and is proved to be independent of the highest order of the differentiations. In the presence of initial condition errors, the system output is ensured to converge to the desired trajectory with a specified error bound at each sampling instant. The bound will reduce to zero whenever the bound on initial condition errors tends to zero. Numerical examples are provided to illustrate the tracking performance of the proposed learning algorithms. Copyright © 2004 John Wiley & Sons, Ltd.
Robust control from data in presence of input saturation
Authors: Canale M.
Published: April 2004

In this paper, conditions are given for internal model control (IMC) structures to be robustlyL2stable with respect toH∞bounded model uncertainty and in presence of input saturation. This conditions are used for the design robust controllers that are the bestH∞approximation to ‘perfect’ linear control among all controllers guaranteeingL2stability in presence of actuator saturation. The cases of both ‘standard’ and enhanced IMC structures are considered. Copyright © 2004 John Wiley & Sons, Ltd.
Predisposing Factors and Situational Triggers: Exclusionary Reactions to Immigrant Minorities
Authors: SNIDERMAN PAUL M. , HAGENDOORN LOUK , PRIOR MARKUS
Published: April 2004

This paper examines the bases of opposition to immigrant minorities in Western Europe, focusing on The Netherlands. The specific aim of this study is to test the validity of predictions derived from two theories—realistic conflict, which emphasizes considerations of economic well-being, and social identity, which emphasizes considerations of identity based on group membership. The larger aim of this study is to investigate the interplay of predisposing factors and situational triggers in evoking political responses. The analysis is based on a series of three experiments embedded in a public opinion survey carried out in The Netherlands (n=2007) in 1997–98. The experiments, combined with parallel individual-level measures, allow measurement of the comparative impact of both dispositionally based and situationally triggered threats to economic well-being and to national identity at work. The results show, first, that considerations of national identity dominate those of economic advantage in evoking exclusionary reactions to immigrant minorities and, second, that the effect of situational triggers is to mobilize support for exclusionary policies above and beyond the core constituency already predisposed to support them.
Realism, Narrative, and Happenstance: Thucydides' Tale of Brasidas
Authors: HEILKE THOMAS
Published: April 2004

Neorealism and some versions of realism seek to furnish nomothetic theories of the international system at the same time that they also strive to prescribe policy for political leaders. Insofar as practical advice is insufficiently articulated by means of either nomothesis or the structural theoretical framework that (neo-)realist paradigms supply, these two aspirations seem contradictory. This essay is an examination of what contemporary realism and, especially, neorealism require to make practical wisdom available for practitioners. It argues that narrative, which is exemplified in the so-called classical realism of Thucydides, remains a crucial component of practical realism and neorealism.
Newell's list
Authors: Agassi Joseph
Published: April 2004

Newell wanted a theory of cognition to abide by some explicit criteria, here called the Newell Test. The test differs from the Turing Test because it is explicit. The Newell Test will include the Turing Test if its characterization of cognition is complete. It is not. Its use here is open-ended: A system that does not pass it well invites improvement.
Rapid decrease in total magnetic field F at Antarctic stations - its relationship to core–mantle features
Authors: Rajaram Girija , Arun T. , Dhar Ajay , Patil A.G.
Published: April 2004

The Indian Institute of Geomagnetism (IIG) in 1982, 1986, and 1996, operated a Proton Precession Magnetometer (PPM) at its Antarctic stations Dakshin Gangotri/Maitri (located at ∼70°S, ∼12°E). Comparison of the average quiet-time value of total intensity F for these years with values of F obtained at the same geographic location (interpolated from iso-intensity contours of F on World Magnetic Charts and IGRF Maps) for earlier years, suggested that over the last 75 years at this location, F has dropped from ∼49 000 nT in 1922, to ∼40 000 nT in 1996 i.e. ∼120 nT per year. Further inspection at nearby Antarctic stations reveals a drop of ∼108 nT yr−1 at Novolazarevskaya, ∼100 nT yr−1, at Georg Forster and ∼95 nT yr−1 at Syowa; Mawson situated still further away shows a drop of ∼72 nT yr−1, while Dumont d'Urville located very near the magnetic pole showed a drop of ∼50 nT yr−1 until 1994. A study of the observed F values over the past five decades at 23 observatories from the Antarctic and sub-Antarctic regions indicates that contours of yearly decrease in F follow a definite pattern, with maximum decrease lying in a belt encompassing Maitri. These observations are of importance in the light of modelling works at the Earth's Core–Mantle boundary pointing to two prominent regions of reverse magnetic flux (RMF) occurring beneath South America, South Africa and a large part of Antarctica, and which may merge sometime to cause reversal of the present geomagnetic field polarity. The importance of continuous monitoring of F at various locations in Antarctic and sub-Antarctic regions is brought out in this work. It is equally important to understand the cause behind this rapid decrease in F.
Involvement of endogenous CCK and CCK1 receptors in colonic motor function
Authors: Varga Gábor , Bálint András , Burghardt Beáta , D'Amato Massimo
Published: April 2004

Cholecystokinin (CCK) is a brain‐gut peptide; it functions both as a neuropeptide and as a gut hormone. Although the pancreas and the gallbladder were long thought to be the principal peripheral targets of CCK, CCK receptors are found throughout the gut. It is likely that CCK has a physiological role not only in the stimulation of pancreatic and biliary secretions but also in the regulation of gastrointestinal motility. The motor effects of CCK include postprandial inhibition of gastric emptying and inhibition of colonic transit. It is now evident that at least two different receptors, CCK1 and CCK2 (formerly CCK‐A and CCK‐B, respectively), mediate the actions of CCK. Both localization and functional studies suggest that the motor effects of CCK are mediated by CCK1 receptors in humans. Since CCK is involved in sensory and motor responses to distension in the intestinal tract, it may contribute to the symptoms of constipation, bloating and abdominal pain that are often characteristic of functional gastrointestinal disorders in general and irritable bowel syndrome (IBS), in particular. CCK1 receptor antagonists are therefore currently under development for the treatment of constipation‐predominant IBS. Clinical studies suggest that CCK1 receptor antagonists are effective facilitators of gastric emptying and inhibitors of gallbladder contraction and can accelerate colonic transit time in healthy volunteers and patients with IBS. These drugs are therefore potentially of great value in the treatment of motility disorders such as constipation and constipation‐predominant IBS.

British Journal of Pharmacology (2004) 141, 1275–1284. doi:10.1038/sj.bjp.0705769
Successful Surgical Excision of a Gigantic Cerebral Hydatid Cyst
Authors: Menkü A. , Kulaksızoglu O. , Tucer B. , Kurtsoy A. , Akdemir H.
Published: April 2004

In this study, an extremely rare case of a gigantic cerebral hydatid cyst is presented. A right frontotemporal hydatid cyst was detected by computed tomography and magnetic resonance imaging. This lesion was extirpated successfully with intact contents with the aid of a neuronavigation system. The literature is reviewed and possible postoperative complications are discussed with the published reports.
Fibrin depletion decreases inflammation and delays the onset of demyelination in a tumor necrosis factor transgenic mouse model for multiple sclerosis
Authors: Akassoglou Katerina , Adams Ryan A. , Bauer Jan , Mercado Peter , Tseveleki Vivian , Lassmann Hans , Probert Lesley , Strickland Sidney
Published: April 2004

In multiple sclerosis, in which brain tissue becomes permeable to blood proteins, extravascular fibrin deposition correlates with sites of inflammatory demyelination and axonal damage. To examine the role of fibrin in neuroinflammatory demyelination, we depleted fibrin in two tumor necrosis factor transgenic mouse models of multiple sclerosis, transgenic lines TgK21 and Tg6074. In a genetic analysis, we crossed TgK21 mice into a fibrin-deficient background. TgK21fib-/-mice had decreased inflammation and expression of major histocompatibility complex class I antigens, reduced demyelination, and a lengthened lifespan compared with TgK21 mice. In a pharmacologic analysis, fibrin depletion, by using the snake venom ancrod, in Tg6074 mice also delayed the onset of inflammatory demyelination. Overall, these results indicate that fibrin regulates the inflammatory response in neuroinflammatory diseases. Design of therapeutic strategies based on fibrin depletion could potentially benefit the clinical course of demyelinating diseases such as multiple sclerosis.