bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic acidosis developing during cardiopulmonary bypass is related to a decrease in strong ion difference
Authors: Alston R Peter , Cormack Laura , Collinson Catherine
Published: June 2004

Metabolic acidosis is a frequent complication of cardio-pulmonary bypass (CPB). Commonly, its cause is ascribed to hypoperfusion; however, iatrogenic causes, related to the composition and volume of intravascular fluids that are administered, are increasingly being recognized. The aim of this study was to determine if metabolic acidosis during CPB was associated with hypoperfusion, change in strong ion difference (SID) or haemodilution. Forty-nine patients undergoing cardiac surgery using CPB in the Royal Infirmary of Edinburgh (RIE) or the HCI, Clydebank were included in the study. Arterial blood samples were aspirated before induction of anaesthesia and the end of CPB. Samples were subjected to blood gas analysis and measurement of electrolytes and lactate. Changes in concentrations were then calculated. Change variables that were found to be significant (p B-0.1) univariate correlates of the change in hydrogen ion concentration were identified and entered into a multivariate regression model with hydrogen ion concentra tion at the end of CPB as the outcome variable (r2=0.65, p<0.001). Change variance in hydrogen ion concentration was created by first entering the baseline hydrogen ion concentration into the model. Next, any variance resulting from the respiratory component of acidosis was removed by entering the change in arterial carbon dioxide tension (regression coefficient (β)=0.67, p<0.01). Change in SID (β=-0.34, p<0.01) and surgical institution (β=-0.40, p<0.01) were then found to be predictors of the remaining variance whilst change in concentration of lactate (β in=0.16, p=0.07) and volume of intravascular fluid that was administered (β=-0.07, p=0.52) were rejected from the model. These findings suggest that the metabolic acidosis developing during CPB is partially the result of iatrogenic decrease in SID rather than hypoperfusion, as estimated by lactate concentration, or haemodilution.
What time human geography?
Authors: Jones Rhys
Published: June 2004

This paper seeks to contribute to the debate concerning the current and future state of human geography by focusing on its changing treatment of the past. I argue that, while contemporary human geography has experienced a welcomed explosion in terms of its thematic breadth, it has also suffered from a considerable narrowing of the time periods that inform its empirical and conceptual studies. The paper begins by demonstrating the changing temporal focus of the subdiscipline over the past 50 years, drawing particular attention to its temporal narrowing over the past 20 years. Following this, I seek to suggest possible reasons for the foreshortening of the times studied in the subdiscipline. I then illustrate the benefits of extending our temporal frame of reference to discuss earlier times. I conclude by arguing that the project of lengthening the timeframes that we use to structure our geographical research has the potential to enable us to tell different stories about the geographical past and present.
World music: deterritorializing place and identity
Authors: Connell John , Gibson Chris
Published: June 2004

Music has been neglected in geography, yet the rise of ‘world music’ exemplifies the multiple ways in which places are constructed, commodified and contested. Music from distant and ‘exotic’ places has long entered the western canon, yet the pace of diffusion to the west accelerated with the rise of reggae and the marketing of Paul Simon's Graceland (1986), which pointed to the modification and transformation of distant, ‘other’ musics for western tastes and markets. Fusion and hybridity in musical styles emphasized both the impossibility of tracing authenticity in musical styles and the simultaneous exoticism and accessibility of distant musics. ‘Strategic inauthenticity’, romanticization and the fetishization of marginality were central to the search for and marketing of purity and novelty: simplistic celebrations of geographical diversity and remoteness. The formal arrival of world music in 1987 was as a marketing category with commerce and culture entangled and inseparable, in a form of appropriation for western, cosmopolitan audiences. Yet, for musicians, world music was an expressive project, which created identities that fused the local and global, traditional and modern. For some, international success required artistic compromise, essentialized identities and the resources of transnational companies. Others simply resisted categorization. The expansion of world music exemplifies the deterritorialization of cultures and emphasizes how the rise of a particular cultural commodity (world music) is primarily a commercial phenomenon, but could not have occurred without the construction and contestation of discourses of place and otherness.
Study conduct, monitoring and data management in a trinational trial: the OPTIMA model
Authors: Kyriakides Tassos C , Babiker Abdel , Singer Joel , Piaseczny Mirek , Russo John
Published: June 2004

The OPTions In Management with Antiretrovirals (OPTIMA) Trial, a collaboration between three governmental agencies in the USA, UK and Canada is a large-scale, multicenter, randomized controlled trial designed to compare the relative efficacy of different therapeutic strategies in HIV disease. The collaboration of three coordinating centers introduced unique data management issues including: a) use of different data systems for managing “country” trial data; b) two-way data transfer between the coordinating centers and the center where OPTIMA data is merged and analysis files are generated; and c) translation of certain data forms (mainly patient completed questionnaires) into French and Spanish. The involvement of three data centers provided a challenge in planning, designing and executing data management procedures in OPTIMA. Processes were implemented to ensure the trial's successful execution at the trinational level, without disregarding countryspecific requirements and regulations. The OPTIMA model required a significant time and resource investment on behalf of all agencies involved, but allowed for autonomy and a sense of joint ownership of data in different countries.
Small group processes relevant to data monitoring committees in controlled clinical trials: an overview of reviews
Authors: Walker Anne E , McLeer Sharon K ,   DAMOCLES group
Published: June 2004

Background The quality of the decisions reached by data monitoring committees (DMCs) is crucial. The aim of this paper is to identify factors that may make errors more or less likely in small, task-oriented, decision-making expert groups and to consider the implications of these factors for data monitoring committees.

Methods A systematic overview was carried out of reviews of empirical studies of small group processes and decision errors in small, task-oriented decision-making groups in laboratory or real-world settings, published between 1950 and 2002 (n = 57 included reviews).

Results These reviews suggest that a number of factors may increase the likelihood that small groups will make poor and potentially erroneous decisions. The most important of these, in terms of empirical support, are: biased or overly directive leadership, expression of a limited range of opinions during group discussion, poor procedures for identifying or appraising the available information, and presentation of the available information in a way that is likely to result in biased perception of it.

Conclusions The main implications for DMCs relate to membership, the role of the chairperson, the information provided for DMCs and training for DMC members. Selection methods that encourage a degree of diversity within the DMC are recommended. Chairs of DMCs should be experienced members, who have the skills to facilitate a discussion, can manage conflict effectively and can be impartial. Adherence to a prespecified analysis plan is recommended to reduce the risk of error associated with strong evidence or excess information. Training in the use of methodical decision-making procedures, education about the factors that influence decision quality and an opportunity to participate in mock DMC discussions may be of benefit for new members.
Covariate-based constrained randomization of group-randomized trials
Authors: Moulton Lawrence H
Published: June 2004

Group-randomized study designs are useful when individually randomized designs are either not possible, or will not be able to estimate the parameters of interest. Blocked and/or stratified (for example, pair-matched) designs have been used, and their properties statistically evaluated by many researchers. Group-randomized trials often have small numbers of experimental units, and strong, geographically induced between-unit correlation, which increase the chance of obtaining a “bad” randomization outcome. This article describes a procedure – random selection from a list of acceptable allocations – to allocate treatment conditions in a way that ensures balance on relevant covariates. Numerous individual- and group-level covariates can be balanced using exact or caliper criteria. Simulation results indicate that this method has good frequency properties, but some care may be needed not to overly constrain the randomization. There is a trade-off between achieving good balance through a highly constrained design, and jeopardizing the appearance of impartiality of the investigator and potentially departing from the nominal Type I error.
Bayesian estimation of vaccine efficacy
Authors: Chu Haitao , Halloran M Elizabeth
Published: June 2004

Protective vaccine efficacy, VES, is measured as one minus the incidence rate ratio (IRR) or the relative risk (RR) in the vaccinated group compared with the unvaccinated group. In this paper, we systematically present Bayesian estimation of protective vaccine efficacy based on the Poisson and binomial distributions. We also propose a new tool, the vaccine efficacy acceptability curve, to represent the uncertainty for the estimate of the vaccine efficacy graphically. It is very useful, especially when there is no universal agreement on the acceptable vaccine efficacy. The vaccine efficacy acceptability curve is defined as the posterior probability that the measure of vaccine efficacy VES ≥ k for each acceptable value k. When a vaccine is highly efficacious, the number of vaccinated susceptibles being infected is likely to be very small or even zero. Then the assumptions of normality and log-normality of IRR or RR usually do not hold well. Although frequentist exact methods provide good estimates of the confidence interval, they are overly conservative and are computationally difficult to extend to estimate the vaccine efficacy acceptability curve. In this paper, our focus is on Bayesian estimation of protective vaccine efficacy, its highest probability density credible set, and the vaccine efficacy acceptability curve through Markov chain Monte Carlo (MCMC) methods. We illustrate the methods using the data from two pertussis vaccine studies and the H. influenza Type B preventive trial.
Factorial designs: a graphical aid for choosing study designs accounting for interaction
Authors: Byth Karen , Gebski Val
Published: June 2004

The presence of possible treatment interaction when designing a factorial study can be either greeted with dismay (for an antagonistic or negative interaction) or can be welcome (in the case of a synergistic effect). The type of potential interaction may greatly influence the choice of study design. Depending on the magnitude of an expected additive or multiplicative interaction, a three-arm study, instead of a 2 × 2 factorial, may yield greater statistical power. A graphical aid for examining the loss of power due to the presence of such interaction is developed. The technique can also be applied to designing studies where prespecified subgroup analyses are of particular interest. Tests for interaction effects between subgroups are usually underpowered, even if the subgroups have been prespecified in the protocol. The technique can be used to determine the appropriate sample sizes in the subgroups to ensure adequate power to detect potential interaction effects. The method is illustrated with respect to a published 2 × 2 factorial study. In this study, interaction reduced the power of the final analysis to detect significant main effects.
Methodologic issues in terminating enrollment of a subgroup of patients in a multicenter randomized trial
Authors: Lee Shing M , Wise Robert , Sternberg Alice L , Tonascia James , Piantadosi Steven ,   National Emphysema Treatment Trial Research Group
Published: June 2004

The National Emphysema Treatment Trial (NETT) was a multicenter randomized controlled trial comparing medical treatment plus lung-volume-reduction surgery (LVRS) to medical treatment alone for the treatment of severe emphysema. The primary outcomes specified for the trial were mortality from all causes and change in functional status as indicated by the change in maximum exercise capacity measured two years after randomization. A secondary objective of the trial was to define criteria to identify subgroups of patients at risk of harm or benefit from LVRS. Stopping guidelines for safety and efficacy based on 30-day mortality and a combination of overall mortality and functional status at two years were specified at the inception of the trial. Although specific subgroups of patients likely to benefit were not identified in advance, several clinical factors were specified as likely to be important in defining subgroups with differential outcome. In May 2001, with 40% of expected deaths accrued, the Data and Safety Monitoring Board determined that a subgroup of patients was at significantly higher risk of 30-day mortality from LVRS without counterbalancing evidence of functional benefit, and recommended that the protocol be modified to exclude further randomization of such patients. The trial's sponsor, the National Heart, Lung and Blood Institute, accepted the recommendation, which was rapidly communicated to participating clinics. This paper describes the operational aspects of identification of the subgroup and implementation of the recommendation to continue the trial, but to terminate enrollment of new patients in the subgroup. These aspects include notification of the investigators, the institutional review boards, the Research Group, the patients and the medical community. We also describe the repercussions of the publication and the misinterpretations of the results based on media coverage.
A reporting tool for real-time assessment of study data availability
Authors: Bosch Ronald J , Pierce Casey , Spritzler John , Kendall Michelle A , Jacobson Jeffrey M , Schock Barbara , Siminski Suzanne
Published: June 2004

A simple framework for assessing and reporting data availability in an ongoing clinical trial is described. Protocol requirements, visit schedules and data availability are combined into a simple report to track the progress of a study.
Carbon dioxide removal via a membrane system in a natural gas combined-cycle plant
Authors: Carapellucci R , Milazzo A
Published: June 2004

Gas separation using polymeric membranes is generally believed to be poorly suited for CO2 capture from gas turbine based power plants, because the high air-to-fuel ratios produce large amounts of exhaust gas containing strongly diluted CO2. The driving force for selective permeation is obtained by compressing the entire exhaust stream, resulting in a significant energy penalty. Additional energy is required for permeate compression, which is impaired by the other gases emitted with CO2. In spite of these difficulties, the present study is concerned with membrane systems, which the authors believe warrant further investigation. The attention was focused on natural gas combined cycles (NGCC), so as to have a starting point with high energy efficiency and low baseline emissions. To reduce the exhaust gases and to concentrate the CO2, the NGCC is fitted with a flue gas recirculation system, which has proven to leave plant performance substantially unaffected. The energy requirements for exhaust gas compression are reduced by introducing a heat exchanger between the compressed and residual exhaust gas and recovering heat from the latter. The membrane separator has been modeled using conservative data reported in the literature. Various configurations, such as multiple compression-expansion and multistage membrane units, are considered. Permeate compression is also modeled, so as to highlight the influence of permeate purity on this process. The results show a rather moderate performance penalty. A specific emission of 100 g CO2/kWh corresponds to 48 percent efficiency. Admittedly a CO2 separator for a power plant would be larger than any other membrane system designed for other purposes. However, the system appears technically feasible and would offer valuable benefits in terms of emissions.
Performance of a centrifugal pump running in inverse mode
Authors: Fernández J , Blanco E , Parrondo J , Stickland M. T. , Scanlon T. J.
Published: June 2004

This paper presents the functional characterization of a centrifugal pump used as a turbine. It shows the characteristics of the machine involved at several rotational speeds, comparing the respective flows and heads. In this way, it is possible to observe the influence of the rotational speed on efficiency, as well as obtaining the characteristics at constant head and runaway speed. Also, the forces actuating on the impeller were studied. An uncertainty analysis was made to assess the accuracy of the results. The research results indicate that the turbine characteristics can be predicted to some extent from the pump characteristics, that water flows out of the runner free of swirl flow at the best efficiency point, and that radial stresses are lower than in pump mode.
Recent developments in gas turbine component temperature prediction methods, using computational fluid dynamics and optimization tools, in conjunction with more conventional finite element analysis techniques
Authors: Dixon J. A. , Verdicchio J. A. , Benito D , Karl A , Tham K. M.
Published: June 2004

Accurate temperature predictions are essential to the optimization of gas turbine component design. This paper provides an update on the application of recent developments in heat transfer boundary condition derivation and finite element model validation. Computational fluid dynamics (CFD) is increasingly being used to determine cooling flow distributions and convective heat fluxes on a range of components. Validation of the CFD methodology for internal cavity heat transfer is also a key focus of major research programmes. In this paper, further results are presented for selected engine and rig cavities. A fully coupled CFD/finite element thermal model solution is also demonstrated. Increasingly, the application of optimization techniques to the thermal model calibration process is showing that significant savings in analysis time can be achieved for a given accuracy of ‘match’. The optimization process is described and sample results are presented from the calibration of a typical thermal model. Finally, the impact of these new analysis techniques on the derivation of thermal boundary conditions in gas turbine component cavities and the implications for compliance with Airworthiness Authority regulations are summarized with respect to offering an improved temperature prediction validation strategy.
Simulation of discharge pressure pulsation within twin screw compressors
Authors: Wu Huagen , Xing Ziwen , Peng Xueyuan , Shu Pengcheng
Published: June 2004

Even in the absence of self-acting valves, flow through the discharge port of a twin screw compressor is oscillatory in nature. This unsteady but periodic flow variation at the discharge port excites the pressure pulsation, which is the main source of noise and vibration. In this paper, a mathematic model based on the one-dimensional unsteady gas flow equations is established to describe the discharge pressure pulsation, which considers the effects of friction and heat transfer between the gas and the pipe. The boundary conditions of the discharge pressure pulsation model are given in detail. The two-step Lax—Wendroff scheme is applied to solve the one-dimensional unsteady gas flow equations. In order to verify the theoretical analysis, the discharge pressure pulsations under various working conditions are measured and compared. It is shown that the model established in this paper is a useful tool to obtain a better understanding of the behaviour of the pressure pulsation in discharge pipe. It is found that the most important factor that affects the discharge pressure pulsation is the pressure difference between the pressure upstream of the discharge port in the compression chamber and the pressure in the discharge line some way downstream. The minimum fluctuation occurs when the discharge pressure is equal to the pressure corresponding to the built-in volume ratio. For a constant discharge pressure, the pressure pulsation amplitude increases with the rotational speed.
Heavy Metals in Marine Coastal Sediments: Assessing Sources, Fluxes, History and Trends
Authors: Frignani Mauro , Bellucci Luca Giorgio
Published: June 2004

Examples are presented from the Adriatic Sea, the Ligurian Sea and the Venice Lagoon to illustrate different approaches to the study of anthropogenic metals in marine coastal sediments. These examples refer to studies of areal distribution and transport mechanisms, individuation of the sources, sediment dating, chronology of the fluxes, present and past trends. In particular, some of the findings achieved in studying the Venice Lagoon are discussed from the point of view of anthropogenic changes both in sediment composition and contaminant fluxes.
Importance and Difficulties of Research on Metal Speciation in the Aquatic Ecosystem: an Ecologist's Viewpoint
Authors: Ravera Oscar
Published: June 2004

Post‐war research on the role of heavy metals in the environment was stimulated by a new sensitivity towards nature, the increasing impact of human activities on the environment, continuous progress in analytical chemistry and the development of radioecology. Nowadays, very low concentrations of total metal can be quantified in the various compartments of the ecosystem (e.g. water, sediment, suspended particles, plants and animals), and the physical and chemical forms of the metal identified. A current difficulty is how to evaluate the role of the various metal forms in the natural ecosystem. The major issues to be tackled are: variations over time of metal species in relation to the influence of environmental variables; the fact that the availability of the metal varies with the plant and animal species; the ability of the organism to select the metals and their forms; the influence of suspended particles and chelating substances on metal uptake, detoxification strategies and synergic and antagonistic effects. The advantages and disadvantages of monitoring using bioaccumulator organisms are discussed.
FT‐IR Spectroscopy and Chemometrics as a Useful Approach for Determining Chemical‐Physical Properties of Gasoline, by Minimizing Analytical Times and Sample Handling
Authors: Pavoni Bruno , Rado Nadia , Piazza Rossano , Frignani Silvano
Published: June 2004

Since recently Mid‐Infrared Spectroscopy is being used in the petrol industry for determining important chemical‐physical properties of gasoline. This technique enables to achieve results similar to those obtainable with standard methods at shorter times, lower costs and safer sample handling. This can be obtained by employing multivariate regression models in the framework of a chemometric analytical approach. In the present work some gasoline properties including density, Reid vapor pressure, Research Octane Number, aromatic hydrocarbons content and fraction recovered at 70 °C were determined with standard methods (ISO, CEN, ASTM) on 93 samples of unleaded gasoline produced in an oil refinery. The same samples were also analyzed by FT‐IR spectrophotometry, recording absorptions of seven characteristic bands. The obtained values of chemical‐physical and spectroscopic properties were used to develop and validate a multivariate regression model. This established an experimental correlation between these two sets of variables derived from the same gasoline samples. The model was able to correctly predict the chemical physical properties of a set of unknown gasoline samples produced in the same refinery starting from the spectroscopic ones.
Spectrophotometric Studies on the Complexation Equilibria of Ni and Pb with 2‐Carboxy‐2‐Hydroxy‐5'‐Sulfo‐Formazylbenzene. Simultaneous Determination of Trace Amounts of Ni and Pb
Authors: Hashem Elham Y. , Abu‐Bakr Mohamed S. , Hussain Sawsan M.
Published: June 2004

Spectrophotometric studies have been made to investigate the reaction of Nickel and Lead with 2‐carboxy‐2'‐hydroxy‐5'‐sulfoformazyl‐benzene (zincon) in 50%(v/v) ethanol‐water at 25 °C and an ionic strength of 0.1 M NaClO4. A complete picture of the complexation equilibria in the pH range (4.2‐12.0) for nickel and (1.9‐11.5) for lead are presented. Simple, rapid, selective and sensitive methods for the spectro‐photometric determination of nickel and lead has been developed based on the color reaction of their complexes with zincon. The methods allow the determination of 4.69 μg mL‐1 of nickel at pH = 6.3 (λmax = 665 nm) and 10.3 μg ml‐1 of lead at pH = 5.6 (λmax = 610 nm). The apparent molar absorptivities were ε = 1.3 × 104 L mol‐1 cm‐1 for nickel and ε = 0.6 × 104 L mol‐1cm‐1 for lead. The interference of a large number of foreign ions and complexing agents has been studied. Thiosulphate, as masking agent allows the simultaneous determination of nickel and lead in the presence of high concentrations of copper. Ascorbic acid, sodium cyanide and or sodium fluoride provide the elimination of many other interferences. The methods have been applied successfully to the simultaneous determination of nickel and lead in an aluminium and non‐ferrous alloy
Synergistic Extraction of Cobalt (II) by β Hydroxy Naphthaldoxime and Neutral Donors
Authors: Banerjee Shrabanti , Basu Sukalyan
Published: June 2004

Liquid — liquid extraction of Cobalt (II) from aqueous hydrochloric acid medium by the use of oxime derivative of β‐hydroxy naphthaldehyde in o‐xylene medium is being reported. The ligand was synthesized and characterized in our laboratory. The typical pH range of extraction of Co (II) by the ligand — donor combination was seen to be between 8 — 9. The effect of different donors like dimethyl sulphoxide (DMSO), trioctyl phosphine oxide (TOPO) and bis(2‐ethylhexyl) phosphonate and the effect of various diluents on the extraction of Co(II) by the present method were studied in detail. The binary adduct formation constant (log kex) in the organic phase was found to be 3.182. The overall equilibrium constant (log K) for the ternary species [Co(A)(DMSO)(Cl)], [Co(A)(TOPO)(Cl)] and [Co(A)(phosphonate)(Cl)] were estimated to be 6.42, 6.22 and 6.25 respectively. The trend in equilibrium constants were in accordance with their basic character, i.e., (DMSO > TOPO ≅ phosphonate). The results were extrapolated in the determination of Cobalt in pharmaceutical drugs and cobalt bearing ore samples.
Ferroelectric, Electroactive, and Dielectric‐Relaxation Behavior of Fluoropolymers
Authors: Ang C. , Yu Z.
Published: June 2004

The discovery of piezoelectricity in poly(vinylidene fluoride) polymers and related co‐ and terpolymers has led to much interest in the physics of these materials because of their great potential for many actuator applications. The electroactive strain, ferroelectric polarization, and dielectric behavior of an irradiated poly(vinylidene fluoride–trifluoroethylene) (P(VDF–TrFE)) copolymer and non‐irradiated poly(vinylidene fluoride–trifluoroethylene–chlorotrifluoroethylene) (P(VDF–TrFE–CTFE)) terpolymer are reported here, with special attention given to the analysis of the complex permittivity.
Fabrication of Two‐Dimensional Arrays of CdSe Pillars Using E‐Beam Lithography and Electrochemical Deposition
Authors: Su Y.‐W. , Wu C.‐S. , Chen C.‐C. , Chen C.‐D.
Published: June 2004

Two‐dimensional arrays of high refractive index structures can be fabricated using a combination of e‐beam lithography for pattern definition and electrochemical deposition for structure formation. The potential of this method is demonstrated for CdSe, where nanopillars, mushrooms (see Figure), walls, and crosses are prepared. Such arrays have potential in optical device applications such as photonic crystals and waveguides.
Room Temperature Electrochemical Opening of Carbon Nanotubes Followed by Hydrogen Storage
Authors: Skowroński J.M. , Scharff P. , Pfänder N. , Cui S.
Published: June 2004

An electrochemical method is used to open multi‐walled carbon nanotubes at a room temperature. HRTEM analysis (see Figure, arrows indicate openings) and cyclic voltammetry were undertaken and showed that, owing to the oxidation reactions occurring preferably at the end regions of nanotubes, an enhanced amount of hydrogen is stored in the nanotubes, which, during the cathodic reduction, is reversibly recovered.
Customization of Poly(dimethylsiloxane) Stamps by Micromachining Using a Femtosecond‐Pulsed Laser
Authors: Wolfe D.B. , Ashcom J.B. , Hwang J.C. , Schaffer C.B. , Mazur E. , Whitesides G.M.
Published: June 2004

A femtosecond‐pulsed Ti:sapphire laser is used to generate surface features in slabs of poly(dimethylsiloxane) with minimum dimensions of 1 μm—smaller than those available by rapid‐prototyping techniques using transparency masks. The fabrication of magnetic field concentrators and the addition of custom features to a generic microfluidic channel (see Figure) demonstrate the utility of the technique.
Uniform Emulsion‐Templated Silica Beads with High Pore Volume and Hierarchical Porosity
Authors: Zhang H. , Hardy G.C. , Rosseinsky M.J. , Cooper A.I.
Published: June 2004

A new type of porous silica bead (see Figure) with a narrow size distribution, useful for applications such as catalysis, biomolecule immobilization, and chromatographic separation, can be synthesized via a novel emulsion templating/sedimentation polymerization route. This method might be scaled up for the synthesis of significant quantities of beads, or extended to make, e.g., metal and metal oxide beads with high surface area and macropore volume.
π‐Stacked Conjugated Polymers: The Influence of Paracyclophane π‐Stacks on the Redox and Optical Properties of a New Class of Broken Conjugated Polythiophenes
Authors: Salhi F. , Collard D.M.
Published: June 2004

Bis(3‐octyl‐2‐thienyl)‐[2.2]paracyclophane is subjected to oxidative polymerization to afford a soluble redox‐active polymer (see Figure) consisting of conjugated tetraarenes held in permanent cofacial stacks by cyclophane linkages. The influence of p‐stacking of the conjugated units along the polymer chain and the effect of stacking on the extended delocalization and conjugation of excitons and charge carrier is investigated.
Costello syndrome with growth hormone deficiency and hypoglycemia: A new report and review of the endocrine associations
Authors: Gregersen Nerine , Viljoen Denis
Published: June 2004

We describe an 18‐month‐old boy with Costello syndrome (CS) with proven partial growth hormone (GH) deficiency and hypoglycemic episodes. The hypoglycemia is deemed to be due to cortisol deficiency. This report represents the second published case of cortisol deficiency in the CS. A brief review of the endocrine disturbances in the syndrome is provided. We highlight the need for careful endocrinological evaluation of individuals with CS. © 2004 Wiley‐Liss, Inc.
Paternal transmission of fragile X syndrome
Authors: Zeesman Susan , Zwaigenbaum Lonnie , Whelan Donald T. , Hagerman Randi J. , Tassone Flora , Taylor Sherryl A.M.
Published: June 2004

We present a family in which a fragile X mosaic male, who carries both premutation and full mutation alleles in his peripheral blood leukocytes, has a daughter with both premutation and partially methylated full mutation alleles and a significant developmental disability. To our knowledge, this is the first report of such an occurrence and it challenges current thinking about the expansion and transmission of unstable FMR1 alleles from men to their daughters. It is currently accepted that neither males with premutations nor full mutations are at risk for having daughters with full mutations and fragile X syndrome. The sperm cells of full mutation males are thought to carry only premutation alleles. These alleles, when transmitted through a male, regardless of his cognitive status, are thought to be unable to expand to full mutations in the next generation. In effect, the expansion from premutation to full mutation has only been observed through female meioses. The sperm cells in the father in this family have been shown to contain only alleles in the premutation range. Since his daughter has both premutation and full mutation alleles the expansion to full mutation in this case must have occurred postzygotically. © 2004 Wiley‐Liss, Inc.
Worry about ovarian cancer risk and use of screening by high‐risk women: How you recruit affects what you find
Authors: Andersen M. Robyn , Nelson Judy , Peacock Sue , Giedzinska Antoinette , Dresher Charles , Bowen Deborah , Urban Nicole
Published: June 2004

Several studies have described the characteristics of women at high‐risk for ovarian cancer who are participating in registry studies and high‐risk screening programs. These studies have found high‐risk women to report high levels of perceived risk and worry about their risk for ovarian cancer. In contrast, population based studies have found that while high‐risk women did report high levels of perceived risk, they did not report high levels of worry about their risk. In this study, we examine reports of perceived risk, worry about ovarian cancer, and use of screening by high‐risk women recruited to participate in a survey from several recruitment sources. These sources include self‐, physician‐, and affected patient relative‐referral, a fundraising mailer, and a mass mailing to a commercial mailing list. High‐risk women recruited via mass mailing were less likely than those recruited via physicians or affected relatives to report either worry about their risk or use of ovarian cancer screening tests. © 2004 Wiley‐Liss, Inc.
Association between the neurofibromatosis‐1 (NF1) locus and autism in the Japanese population
Authors: Marui Tetsuya , Hashimoto Ohiko , Nanba Eiji , Kato Chieko , Tochigi Mamoru , Umekage Tadashi , Ishijima Michiko , Kohda Kazuhisa , Kato Nobumasa , Sasaki Tsukasa
Published: June 2004

Autistic patients have a 100 to 190‐fold increased risk of neurofibromatosis compared to the general population. This suggests that the two diseases may share a common etiological background. Recently, a new allele (or the six‐repeat allele) of the (AAAT)n repeat polymorphism in an Alu sequence in the neurofibromatosis‐1 (NF1) gene was observed exclusively in severe autistic patients, not in controls, in Caucasians of French ancestry. This suggests a role of the NF1 gene in the development of autism. We investigated three microsatellite polymorphisms within the intron‐27b and intron‐38 of the NF1 region, including the (AAAT)n and two (CA)n repeat polymorphisms, in Japanese subjects with autism (n = 74) and controls (n = 122). The six‐repeat allele of the (AAAT)n polymorphism was not found either in patients or controls, possibly indicating an ethnic difference in the polymorphism. However, significant differences were observed in the allele distributions of the (AAAT)n and a (CA)n, which were located at intron‐27b, between patients and controls, although an association was not significant between autism and another polymorphism at intron‐38. This may suggest an involvement of the NF1 locus in susceptibility to autism, although further investigations are recommended. © 2004 Wiley‐Liss, Inc.
L‐3‐hydroxyacyl‐CoA dehydrogenase II protects in a model of Parkinson's disease
Authors: Tieu Kim , Perier Celine , Vila Miquel , Caspersen Casper , Zhang Hui‐Ping , Teismann Peter , Jackson‐Lewis Vernice , Stern David M. , Yan Shi Du , Przedborski Serge
Published: June 2004

The neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) impairs mitochondrial respiration and damages dopaminergic neurons as seen in Parkinson's disease (PD). Here, we report that L‐3‐hydroxyacyl‐CoA dehydrogenase type II/amyloid binding alcohol dehydrogenase (HADH II/ABAD), a mitochondrial oxidoreductase enzyme involved in neuronal survival, is downregulated in PD patients and in MPTP‐intoxicated mice. We also show that transgenic mice with increased expression of human HADH II/ABAD are significantly more resistant to MPTP than their wild‐type littermates. This effect appears to be mediated by overexpression of HADH II/ABAD mitigating MPTP‐induced impairment of oxidative phosphorylation and ATP production. This study demonstrates that HADH II/ABAD modulates MPTP neurotoxicity and suggests that HADH II/ABAD mimetics may provide protective benefit in the treatment of PD. Ann Neurol 2004;56:51–60
Sequence‐dependent and independent inhibition specific for mutant ataxin‐3 by small interfering RNA
Authors: Li Yi , Yokota Takanori , Matsumura Ryusuke , Taira Kazunari , Mizusawa Hidehiro
Published: June 2004

In Machado–Joseph disease (MJD) gene, there is a C/G polymorphism immediately after the CAG repeat; the expanded CAG repeat tract is exclusively followed by C, whereas about half of wild‐type alleles are followed by G. Using this C/G polymorphism, we have engineered the small interfering RNA (siRNA) which decreased the expression of mutant ataxin‐3, Q79C, by 96.0%, whereas there was minimal reduction on that of the wild type, Q22G (5.9%). Furthermore, unexpectedly, the expression of another wild‐type allele, Q22C, was also much less suppressed (22.5%) by this siRNA possibly due to difference of the secondary structure of the target RNA. This is the first report of sequence‐independent discrimination of mutant and wild‐type alleles by siRNA. Ann Neurol 2004;56:124–129
Increased susceptibility of S100B transgenic mice to perinatal hypoxia‐ischemia
Authors: Wainwright Mark S. , Craft Jeffrey M. , Griffin W. Sue T. , Marks Alexander , Pineda Jose , Padgett Kyle R. , Van Eldik Linda J.
Published: June 2004

S100B is a glial‐derived protein that is a well‐established biomarker for severity of neurological injury and prognosis for recovery. Cell‐based and clinical studies have implicated S100B in the initiation and maintenance of a pathological, glial‐mediated proinflammatory state in the central nervous system. However, the relationship between S100B levels and susceptibility to neurological injury in vivo has not been determined. We used S100B transgenic (Tg) and knockout (KO) mice to test the hypothesis that overexpression of S100B increases vulnerability to cerebral hypoxic‐ischemic injury and that this response correlates with an increase in neuroinflammation from activated glia. Postnatal day 8 Tg mice subjected to hypoxia‐ischemia showed a significant increase in mortality compared with KO and wild‐type mice. Tg mice also exhibited greater cerebral injury and volume loss in the ischemic hemisphere after an 8‐day recovery, as assessed by histopathology and magnetic resonance imaging. Measurement of glial fibrillary acidic protein and S100B levels showed a significant increase in the Tg mice, consistent with heightened glial activation and neuroinflammation in response to injury. This is the first demonstration to our knowledge that overexpression of S100B in vivo enhances pathological response to injury. Ann Neurol 2004;56:61–67
B‐lymphocyte and plasma cell clonal expansion in monosymptomatic optic neuritis cerebrospinal fluid
Authors: Haubold Kurt , Owens Gregory P. , Kaur Paramjit , Ritchie Alanna M. , Gilden Donald H. , Bennett Jeffrey L.
Published: June 2004

The CD19+ B‐lymphocyte and CD138+ plasma cell repertoires in cerebrospinal fluid from four patients with monosymptomatic optic neuritis (ON) were analyzed by single‐cell reverse transcriptase polymerase chain reaction. Amplified heavy (H)– and light (L)–chain antibody segments were sequenced and used to identify the rearranged germline and J segment of closest homology. Both the B‐cell and plasma cell repertoires from ON cerebrospinal fluid demonstrated significant clonal expansion. Up to 75% of the amplified H‐ and L‐chain sequences were contained in overrepresented populations and were somatically mutated, consistent with an antigen‐targeted response. The relationship between clonal populations within the CD19+ B lymphocyte and CD138+ plasma cell populations suggests ongoing mutational pressure to refine antigen binding. Our observations demonstrate that an antigen‐driven clonal B‐lymphocyte and plasma cell response is prominent in the initial stages of central nervous system demyelination and suggest that detection of the disease‐relevant antigens in ON may bear on the inciting antigens in chronic inflammatory disorders such as multiple sclerosis. Ann Neurol 2004;56:97–107
Abnormal lysosomal and ubiquitin‐proteasome pathways in 19p13.3 distal myopathy
Authors: Di Blasi Claudia , Moghadaszadeh Behzad , Ciano Claudia , Negri Tiziana , Giavazzi Alessio , Cornelio Ferdinando , Morandi Lucia , Mora Marina
Published: June 2004

We describe a second large Italian kindred with autosomal dominant vacuolar myopathy characterized by variable severity, adult‐onset weakness of distal limb muscles, and no cardiac involvement. At least 19 individuals over four generations are affected. Histopathological and immunochemical features of the vacuoles, present in many fibers, indicate protein degradation abnormalities with dysregulation of the lysosomal pathway and activation of the ubiquitin‐proteasomal pathway. Linkage analysis localized the defect to the 19p13.3 locus in a region with no known genes. We speculate that the primary defect may be an abnormality in the lysosomal degradation pathway or related components. Ann Neurol 2004;56:133–138
Medial temporal lobe function and structure in mild cognitive impairment
Authors: Dickerson Bradford C. , Salat David H. , Bates Julianna F. , Atiya Monika , Killiany Ronald J. , Greve Douglas N. , Dale Anders M. , Stern Chantal E. , Blacker Deborah , Albert Marilyn S. , Sperling Reisa A.
Published: June 2004

Functional magnetic resonance imaging (fMRI) was used to study memory‐associated activation of medial temporal lobe (MTL) regions in 32 nondemented elderly individuals with mild cognitive impairment (MCI). Subjects performed a visual encoding task during fMRI scanning and were tested for recognition of stimuli afterward. MTL regions of interest were identified from each individual's structural MRI, and activation was quantified within each region. Greater extent of activation within the hippocampal formation and parahippocampal gyrus (PHG) was correlated with better memory performance. There was, however, a paradoxical relationship between extent of activation and clinical status at both baseline and follow‐up evaluations. Subjects with greater clinical impairment, based on the Clinical Dementia Rating Sum of Boxes, recruited a larger extent of the right PHG during encoding, even after accounting for atrophy. Moreover, those who subsequently declined over the 2.5 years of clinical follow‐up (44% of the subjects) activated a significantly greater extent of the right PHG during encoding, despite equivalent memory performance. We hypothesize that increased activation in MTL regions reflects a compensatory response to accumulating AD pathology and may serve as a marker for impending clinical decline. Ann Neurol 2004;56:27–35
POMGnT1 gene alterations in a family with neurological abnormalities
Authors: Vervoort Virginie S. , Holden Kenton R. , Ukadike Kennedy C. , Collins Julianne S. , Saul Robert A. , Srivastava Anand K.
Published: June 2004

Muscle‐eye‐brain disease (MEB), is caused by mutations in the POMGnT1 gene. We describe a white family with two siblings affected with congenital hypotonia early‐onset glaucoma, and psychomotor delays. Brain magnetic resonance images (MRIs) showed hydrocephalus, bilateral frontal polymicrogyria, abnormal cerebellum, and characteristic flattened dystrophic pons. We identified novel POMGnT1 gene alterations in this family. Both affected siblings were found to be compound hetrozygotes and carried two missense changes inherited from their mother and one missense change (p.R442C) inherited from their father. Our findings further define the phenotypic spectrum of MEB and its occurrence in the US population. Ann Neurol 2004;56:143–148
Titelbild: Multivalency in the Gas Phase: The Study of Dendritic Aggregates by Mass Spectrometry (Angew. Chem. 27/2004)
Authors: Broeren Maarten A. C. , van Dongen Joost L. J. , Pittelkow Michael , Christensen Jørn B. , van Genderen Marcel H. P. , Meijer E. W.
Published: June 2004

Das entfaltete Massenspektrum auf dem Titelbild stammt von einem Poly(propylenimin)‐Dendrimer der dritten Generation, an das ein bis acht Gastmoleküle gebunden sind – der Komplex mit vier Gastmolekülen ist am häufigsten. Jedes Aggregat kann gezielt ausgewählt werden, um die Gäste schrittweise durch stoßinduzierte Fragmentierung zu entfernen. Wie diese Ergebnisse zum Verständnis von wichtigen sekundären Wechselwirkungen in der Gasphase beitragen, erfahren Sie in der Zuschrift von E. W. Meijer et al. auf S. 3641 ff.
Cover Picture: Multivalency in the Gas Phase: The Study of Dendritic Aggregates by Mass Spectrometry (Angew. Chem. Int. Ed. 27/2004)
Authors: Broeren Maarten A. C. , van Dongen Joost L. J. , Pittelkow Michael , Christensen Jørn B. , van Genderen Marcel H. P. , Meijer E. W.
Published: June 2004

The deconvoluted mass spectrum shown in the cover picture of a third‐generation poly(propylene imine) dendrimer to which one to eight guest molecules are bound indicates that the complex with four guest molecules is the most abundant. Each of these aggregates can be selected, and the guests can be removed one by one by collision‐induced dissociation (CID). The results provide new insight into the role of important secondary interactions in the gas phase. For more information, see the Communication by E. W. Meijer and co‐workers on page 3557 ff.
Quantification of mechanical deformations induced by an electric field in a semicrystalline organic insulator
Authors: Mamy P. R. , Martinez‐Vega J. , Dupre J. C. , Bretagne N.
Published: June 2004

We studied mechanical deformations induced when an insulating material was subjected to a gradual increase in a direct‐current electric field. Poly(ethylene terephthalate) film was studied with an optical technique, which was nondestructive and involved no physical contact. The experimental results indicated that the level of the induced mechanical deformation depended on the strength of the applied electric stress, the linear dimensions of the area under study, and the thickness of the film. When the studied area was relatively small, the level of the mechanical deformation seemed to be more important. The relationship between the induced mechanical deformation and the electric conduction phenomenon was also examined. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 2313–2321, 2004