bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical Genetic Algorithms—Evolutionary Optimization of Binary-to-Real-Value Translation in Genetic Algorithms
Authors: Suzuki Hideaki , Sawai Hidefumi , Piaseczny Wojciech
Published: December 2005

A chemical genetic algorithm (CGA) in which several types of molecules (information units) react with each other in a cell is proposed. Not only the information in DNA, but also smaller molecules responsible for the transcription and translation of DNA into amino acids, are adaptively changed during evolution, which optimizes the fundamental mapping from binary substrings in DNA (genotype) to real values for a parameter set (phenotype). Through the struggle between cells containing a DNA unit and small molecular units, the codes (DNA) and the interpreter (the small molecular units) coevolve, and a specific output function, from which a cell's fitness is evaluated, is optimized. To demonstrate the effectiveness of the CGA, it is applied to a set of variable-separable and variable-inseparable problems, and it is shown that the CGA can robustly solve a wide range of optimization problems regardless of their fitness characteristics. To ascertain the optimization of the genotypeto-phenotype mapping by the CGA, we also conduct analytical experiments for some problems while observing the basin size of a global optimum solution in the binary genotype space. The results show that the CGA effectively augments the basin size, makes it easier for evolution to find a path to the global optimum solution, and enhances the GA's evolvability during evolution.
A Comprehensive Overview of the Applications of Artificial Life
Authors: Kim Kyung-Joong , Cho Sung-Bae
Published: December 2005

We review the applications of artificial life (ALife), the creation of synthetic life on computers to study, simulate, and understand living systems. The definition and features of ALife are shown by application studies. ALife application fields treated include robot control, robot manufacturing, practical robots, computer graphics, natural phenomenon modeling, entertainment, games, music, economics, Internet, information processing, industrial design, simulation software, electronics, security, data mining, and telecommunications. In order to show the status of ALife application research, this review primarily features a survey of about 180 ALife application articles rather than a selected representation of a few articles. Evolutionary computation is the most popular method for designing such applications, but recently swarm intelligence, artificial immune network, and agent-based modeling have also produced results. Applications were initially restricted to the robotics and computer graphics, but presently, many different applications in engineering areas are of interest.
A Control System for a Flexible Spine Belly-Dancing Humanoid
Authors: Or Jimmy
Published: December 2005

Recently, there has been a lot of interest in building anthropomorphic robots. Research on humanoid robotics has focused on the control of manipulators and walking machines. The contributions of the torso towards ordinary movements (such as walking, dancing, attracting mates, and maintaining balance) have been neglected by almost all humanoid robotic researchers. We believe that the next generation of humanoid robots will incorporate a flexible spine in the torso. To meet the challenge of controlling this kind of high-degree-of-freedom robot, a new control architecture is necessary. Inspired by the rhythmic movements commonly exhibited in lamprey locomotion as well as belly dancing, we designed a controller for a simulated belly-dancing robot using the lamprey central pattern generator. Experimental results show that the proposed lamprey central pattern generator module could potentially generate plausible output patterns, which could be used for all the possible spine motions with minimized control parameters. For instance, in the case of planar spine motions, only three input parameters are required. Using our controller, the simulated robot is able to perform complex torso movements commonly seen in belly dancing as well. Our work suggests that the proposed controller can potentially be a suitable controller for a high-degree-of-freedom, flexible spine humanoid robot. Furthermore, it allows us to gain a better understanding of belly dancing by synthesis.
Eco‐efficiency Trends in the UK Steel and Aluminum Industries
Authors: Dahlström Kristina , Ekins Paul
Published: January 2006

Measures of eco‐efficiency—broadly understood as “getting more from less”—often include an economic and an environmental variable. The latter is often seen as the more problematic variable, particularly when used in relation to impacts of public concern. But an analysis of resource and value trends in the U.K. steel and aluminum industries over the last 30 yr showed that there are significant problems associated with using economic variables in measures of eco‐efficiency at the sectoral level.

The research found that the U.K. steel and aluminum industries have improved the effectiveness with which they use natural resources, but that this has been accompanied by a decline in the economic output (value added) per unit of material or energy consumed. These seemingly contradictory results can be explained by the fall in the price of metals in real terms, and by the competitive pressures that necessitate the cutting of production costs and indirectly lead to a fall in the measure of economic output of the relevant industry.

The research also suggests a logical terminology to bring consistency and coherence to the broad field of eco‐efficiency indicators, with an important distinction made between measures that examine the value output per unit of physical input, and measures that examine the physical output per unit of physical input. Both these types of indicators are important, as they highlight different aspects of eco‐efficiency.
Eulerian Available Energetics in Moist Atmospheres
Authors: Bannon Peter R.
Published: January 2006

A new derivation of local available energy for a compressible, multicomponent fluid that allows for frictional, diabatic, and chemical (e.g., phase changes) processes is presented. The available energy is defined relative to an arbitrary isothermal atmosphere in hydrostatic balance with uniform total chemical potentials. It is shown that the available energy can be divided into available potential, available elastic, and available chemical energies. Each is shown to be positive definite.

The general formulation is applied to the specific case of an idealized, moist, atmospheric sounding with liquid water and ice. The available energy is dominated by available potential energy in the troposphere but available elastic energy dominates in the upper stratosphere. The available chemical energy is significant in the lower troposphere where it dominates the available elastic energy. The total available energy increases with increasing water content.
Variability in the Southerly Flow into the Eastern Pacific ITCZ*
Authors: de Szoeke Simon P. , Bretherton Christopher S.
Published: January 2006

During boreal summer and fall, there is a strong southerly boundary layer flow across the equator into the east Pacific intertropical convergence zone (ITCZ). The modulation of this flow on synoptic to seasonal time scales is studied using an index of meridional pressure difference between the equator and the ITCZ along 95°W. Two complementary datasets from the East Pacific Investigation of Climate (EPIC) are used to study eastern Pacific variability. Daily measurements of sea level pressure (SLP) from Tropical Atmosphere Ocean (TOA) array buoys from May to November 2001 provide temporal coverage, and eight flights by a C-130 aircraft during September to October 2001 document the associated modulation of lower tropospheric vertical structure.

The principal mode of variability of the perturbation SLP along 95°W from 1°S to 12°N, derived by principal component analysis from either the eight flights (PC1C-130) or from daily TAO buoy observations (PC1), explains 77% of the meridional pressure gradient variability. The pressure anomalies at 1.6 km are similar to those at the surface. The time series of the first mode of the TAO observations shows that most of the variance is in the 2–7-day range. Low pressure at 12°N is associated with southerly and westerly surface wind anomalies, and enhanced precipitation in the ITCZ. The depth of ITCZ convection is more strongly correlated to meridional wind above the planetary boundary layer (PBL) than to meridional wind within the PBL. There is little correlation of PBL meridional flow across the equator with ITCZ convection.

Regression of PC1C-130 against the 95°W cross sections observed by dropwinsondes released during the eight C-130 flights shows correlations of westerlies to positive PC1C-130 (low pressure at 12°N). Between the equator and 4°N, statistically significant northerlies just above the PBL at 1–2-km height and southerlies at 4 km are correlated with negative PC1C-130, having high SLP at 12°N, an anomalously weak meridional SLP gradient, and suppressed convection in the ITCZ.

PC1 is bandpass filtered and correlated with reanalysis fields to identify the structures that modulate meridional pressure gradients along 95°W. Most of the variability at periods less than 15 days is related to easterly waves. Seasonal trends in PC1 during May–October 2001 reflect the seasonal evolution of the sea and land surface temperatures. After the seasonal trend is removed, a geostrophic westerly jet at 12°N—probably related to the Madden–Julian oscillation—dominates PC1 variability on time scales longer than 15 days.
Pharmacokinetic/Pharmacodynamic Relationships for Otamixaban, a Direct Factor Xa Inhibitor, in Healthy Subjects
Authors: Paccaly Anne , Frick Annke , Ozoux Marie‐Laure , Chu Valeria , Rosenburg Ronald , Hinder Markus , Shukla Umesh , Jensen Bradford K.
Published: January 2006

Direct pharmacokinetic/pharmacodynamic relationships for otamixaban were investigated after rising doses in healthy subjects using mixed‐effect modeling. Activated partial thromboplastin time, prothrombin time, dilute prothrombin time, and Russell's viper venom—induced clotting time (RVVT) related linearly, whereas Heptest clotting time (HCT) followed a sigmoidal Emax model. The pharmacokinetic/pharmacodynamic response (slope) and their corresponding interindividual variability (seconds per ng/mL, [% coefficient of variation]) were 0.263 (29%) for Russell's viper venom—induced clotting time, 0.117 (10%) for dilute prothrombin time, 0.058 (19%) for activated partial thromboplastin time, and 0.021 (11%) for prothrombin time. For Heptest clotting time, the parameter estimates with their corresponding interindividual variability (% coefficient of variation) were 71 ng/mL (30%) for EC50, 186 seconds (64%) for Emax, and 17 seconds (16%) for E0. The model predicted otamixaban plasma concentrations to double the clotting times that were close to those observed. These pharmacokinetic/pharmacodynamic relationships, together with the predictable pharmacokinetics, allowed the anticoagulant effect at given doses of otamixaban to be foreseen in healthy subjects.
Rethinking Community Economic Development
Authors: Shaffer Ron , Deller Steve , Marcouiller Dave
Published: January 2006

In this article, the authors present arguments for a more interdisciplinary approach to community economic development. Building an alternative paradigm that includes six elements—resources, markets, institutions, society, decision making, and space—they rethink the framework that links economic theory to the practice of community economic development. Major attention is paid to the integration of economic and noneconomic factors in the practice of community economic development. In the end, the goal of this new paradigm is to more directly link the practice of community economic development to its solid interdisciplinary theoretical foundation.
Management of Hepatitis C Infection in the HIV-Infected Patient
Authors: McNelis Kelly
Published: January 2006

Morbidity and mortality associated with HIV infection have rapidly decreased with the introduction of highly active antiretroviral therapy. Of recent concern is the increase of unusual opportunistic infections, particularly hepatitis C virus in this population. Because of the shared route of transmission, a significant number of HIV-infected patients are also coinfected with hepatitis C virus. HIV infection has been demonstrated to increase the rate of hepatitis C virus disease progression. New data on the use of pegylated interferon plus ribavirin indicate that while cure of hepatitis C virus in the coinfected patient is a clinical challenge, it is possible. Aggressive management of anemia, drug-induced depression, and drug interactions increase the opportunity for clinical response and positive patient outcomes.
Highlights From the 7th International Family Nursing Conference: Plenary Address: The “Hard Spots” of Family Nursing
Authors: Doane Gweneth Hartrick , Varcoe Colleen
Published: January 2006

The focus of this discussion is how nurses might more effectively work within the “hard spots” of family nursing to connect across difference. Taking a pragmatic stance toward knowledge, the practical consequences of ideas and theories informing definitions of family and family nursing practice are examined. The authors propose that the provision of competent, ethical, and culturally safe nursing care could be greatly enhanced by a relational view. In particular it is suggested that understanding family as a relational experience, understanding nursing and culture as relational processes and conceptualizing difference as a basis for connection can provide a foundation for more effectively working across differences. Using this relational view the authors outline processes that have the potential to foster more equitable, just, and compassionate family nursing practice.
Measuring Service Quality in E-Retailing
Authors: Collier Joel E. , Bienstock Carol C.
Published: January 2006

To managers of companies with a Web presence, an awareness of how customers perceive service quality is essential to understanding what customers value in an online service transaction. Previous research in e-service quality has primarily focused on the interaction of the consumer and the Web site while missing the big picture that e-service quality is composed of more than Web site interactivity. The goal of this article is to extend the work on e-service quality to encompass not only Web site interactivity or process quality but also outcome quality and recovery quality. A conceptual framework of e-service quality is proposed and empirically tested that combines process, outcome, and recovery dimensions. Contrary to previous service quality studies, formative instead of reflective indicators are used to conceptualize e-service quality. This study found empirical support for the use of formative indicators and the three-dimensional approach to conceptualizing e-service quality.
Belgian Football
Authors: Dejonghe Trudo , Vandeweghe Hans
Published: January 2006

The Belgian football league declined, after the Bosman case, to a secondary level and became a “stepping stone” for players from outside the European Union. The transformation of professional football into a media-corporations-merchandising-markets model throughout Europe resulted in a decline of Belgian competition. The market in Belgian was too small to be competitive, and the old-fashioned Royal Belgian Football Association rejected adaptation to the new environment. Currently, clubs in Belgium can no longer compete with the European elite, and many small teams have been fighting for their existence year after year. The result is the increasing importation of inferior foreign players. A new phenomenon is that many clubs sell their players when they are sure of their prolongation in the first division.
Fetomaternal cross talk in the placental vascular bed: control of coagulation by trophoblast cells
Authors: Sood Rashmi , Kalloway Shawn , Mast Alan E. , Hillard Cecilia J. , Weiler Hartmut
Published: December 2005

Humans and rodents exhibit a peculiar type of placentation in which zygote-derived trophoblast cells, rather than endothelial cells, line the terminal maternal vascular space. This peculiar aspect of the placental vasculature raises important questions about the relative contribution of fetal and maternal factors in the local control of hemostasis in the placenta and how these might determine the phenotypic expression of thrombophilia-associated complications of pregnancy. Using genomewide expression analysis, we identify a panel of genes that determine the ability of fetal trophoblast cells to regulate hemostasis at the fetomaternal interface. We show that spontaneous differentiation of trophoblast stem cells is associated with the acquisition of an endothelial cell–like thromboregulatory gene expression program. This program is developmentally regulated and conserved between mice and humans. We further show that trophoblast cells sense, via the expression of protease activated receptors, the presence of activated coagulation factors. Engagement of these receptors results in cell-type specific changes in gene expression. Our observations define candidate fetal genes that are potential risk modifiers of maternal thrombophilia-associated pregnancy complications and provide evidence that coagulation activation at the fetomaternal interface can affect trophoblast physiology altering placental function in the absence of frank thrombosis.
Relationship of 99mtechnetium labelled macroaggregated albumin (99mTc-MAA) uptake by colorectal liver metastases to response following Selective Internal Radiation Therapy (SIRT)
Authors: Dhabuwala Atul , Lamerton Prue , Stubbs Richard S
Published: December 2005

Background

SIRT is an emerging treatment for liver tumours which relies on the selective uptake by tumour of 90Y microspheres following hepatic arterial injection. Response rates of around 90% are reported. Hepatic arterial injection of MAA gives an indication of the expected distribution of 90Y microspheres within the liver. This study sought to determine if the MAA scan could be predictive of subsequent tumour response.

Methods

58 patients with colorectal hepatic metastases received SIRT. All had pre-treatment MAA planar images and CT scans which were retrospectively reviewed. Tumours were qualitatively considered "cold", "equivocal" or "hot" based on MAA uptake and the ratio of uptake in tumour and normal liver tissue was calculated (TNR). Following SIRT (which included the administration of hepatic arterial Angiotensin 2) tumour response was assessed by CEA changes one to two months after treatment and by serial CT.

Results

Uptake was classified as "hot" in 37 patients (Group 1) and "equivocal" or "cold" in 21 (Group 2). CEA levels fell dramatically in over 90% of patients. The falls were not significantly different between the groups. There was no correlation between TNR and tumour response based on CEA changes (r2 = 0.004). CT responses after 3 months were not different in the 2 Groups.

Conclusion

The pattern of MAA uptake by colorectal liver tumours after arterial injection is not a predictor of tumour response after treatment by SIRT. The results suggest the doses of 90Y microspheres used may be greater than is necessary.
HIV Prevalence among Aboriginal British Columbians
Authors: Hogg Robert S , Strathdee Steffanie , Kerr Thomas , Wood Evan , Remis Robert
Published: December 2005

Context

There is considerable concern about the spread of HIV disease among Aboriginal peoples in British Columbia.

Objective

To estimate the number of Aboriginal British Columbians infected with HIV.

Design and setting

A population-based analysis of Aboriginal men and women in British Columbia, Canada from 1980 to 2001.

Participants

Epidemic curves were fit for gay and bisexual men, injection drug users, men and women aged 15 to 49 years and persons over 50 years of age.

Main outcome measures

HIV prevalence for the total Aboriginal population was modeled using the UNAIDS/WHO Estimation and Projection Package (EPP). Monte Carlo simulation was used to estimate potential number infected for select transmission group in 2001.

Results

A total of 170,025 Aboriginals resided in British Columbia in 2001, of whom 69% were 15 years and older. Of these 1,691 (range 1,479 – 1,955) men and women aged 15 years and over were living with HIV with overall prevalence ranging from 1.26% to 1.66%. The majority of the persons infected were men. Injection drug users (range 1,202 – 1,744) and gay and bisexual men (range 145, 232) contributed the greatest number of infections. Few persons infected were from low risk populations.

Conclusion

More than 1 in every 100 Aboriginals aged 15 years and over was living with HIV in 2001. Culturally appropriate approaches are needed to tailor effective HIV interventions to this community.
SW-620 cells treated with topoisomerase I inhibitor SN-38: gene expression profiling
Authors: Souza Vinicius , Dong Yan Bin , Zhou H Sam , Zacharias Wolfgang , McMasters Kelly M
Published: December 2005

Background

The goal of this study was to evaluate changes in gene expression in SW-620 cells in response to SN-38 in order to further elucidate the mechanisms by which SN-38 causes apoptosis and cell cycle arrest.

Methods

We used a quantitative gene expression microarray assay to identify the genes regulated by SN-38 treatment in colon cancer cells and confirmed our results with RT-PCR. By gene expression profiling, we first screened a proprietary list of about 22,000 genes.

Results

Treatment with SN-38 cells resulted in two-fold or greater alteration in the level of expression of 192 genes compared to control treatment. Most of the affected genes were not known to be responsive to SN-38 prior to this study. SN-38 treatment of these cells was found to affect the expression of various genes involved in DNA replication, transcription, signal transduction, growth factors, cell cycle regulation, and apoptosis, as well as other genes with unknown function. Changes in expression of 14 genes were confirmed by quantitative real-time polymerase chain reaction (RT-PCR).

Conclusion

This study leads to an increased understanding of the biochemical pathways involved in SN-38-induced apoptosis and possibly to the identification of new therapeutic targets.
Characterization of a monoclonal antibody with specificity for holo-transcobalamin
Authors: Orning Lars , Rian Anne , Campbell Andrew , Brady Jeff , Fedosov Sergey N , Bramlage Birgit , Thompson Keith , Quadros Edward V
Published: January 2006

Background

Holotranscobalamin, cobalamin-saturated transcobalamin, is the minor fraction of circulating cobalamin (vitamin B12), which is available for cellular uptake and hence is physiologically relevant. Currently, no method allows simple, direct quantification of holotranscobalamin. We now report on the identification and characterization of a monoclonal antibody with a unique specificity for holotranscobalamin.

Methods

The specificity and affinity of the monoclonal antibodies were determined using surface plasmon resonance and recombinant transcobalamin as well as by immobilizing the antibodies on magnetic microspheres and using native transcobalamin in serum. The epitope of the holotranscobalamin specific antibody was identified using phage display and comparison to a de novo generated three-dimensional model of transcobalamin using the program Rosetta. A direct assay for holotrnscobalamin in the ELISA format was developed using the specific antibody and compared to the commercial assay HoloTC RIA.

Results

An antibody exhibiting >100-fold specificity for holotranscobalamin over apotranscobalamin was identified. The affinity but not the specificity varied inversely with ionic strength and pH, indicating importance of electrostatic interactions. The epitope was discontinuous and epitope mapping of the antibody by phage display identified two similar motifs with no direct sequence similarity to transcobalamin. A comparison of the motifs with a de novo generated three-dimensional model of transcobalamin identified two structures in the N-terminal part of transcobalamin that resembled the motif. Using this antibody an ELISA based prototype assay was developed and compared to the only available commercial assay for measuring holotranscobalamin, HoloTC RIA.

Conclusion

The identified antibody possesses a unique specificity for holotranscobalamin and can be used to develop a direct assay for the quantification of holotranscobalamin.
Effects of local gene transfer of VEGF on neointima formation after balloon injury in hypercholesterolemic rabbits
Authors: Dulak Jozef , Schwarzacher Severin P , Zwick Ralf H , Alber Hannes , Millonig Gunda , Weiss Caecilia , Hügel Heike , Frick Matthias , Jozkowicz Alicja , Pachinger Otmar , Weidinger Franz
Published: December 2005

Enhancement of the generation of nitric oxide (NO) and vascular endothelial growth factor (VEGF) are suggested to prevent restenosis after angioplasty. Accordingly, we tested whether the local delivery of L-arginine (L-Arg), a substrate for NO generation and the VEGF gene, alone or in combination, can influence neointima formation in hypercholesterolemic rabbits. Balloon injury of the iliac arteries was performed in 24 New Zealand White rabbits fed a 1% cholesterol diet for 3 weeks followed by a local infusion of: (1) pSG5VEGF165 plasmid alone (1000 μg); (2) pSG5VEGF165 (1000 μg) with L-Arg (800 mg); (3) L-Arg (800 mg) alone; and (4) L-Arg (800 mg) with naked pSVβ-gal plasmid (1000 μg). The animals were kept on the hypercholesterolemic diets for a further 28 days, when vessels were taken for morphometric analysis and immunocytochemistry. Endogenous rabbit VEGF concentration in the plasma increased significantly at 7 days after injury (17.06 ± 1.57 vs 23.01 ± 1.9 pg/ml; p < 0.02) and remained elevated for up to 28 days (28.46 ± 5.24; p < 0.01). Injured arteries exhibited strong immunocytochemical staining for rabbit VEGF. Rabbits that received a VEGF gene transfer revealed more prominent neointima formation, whereas treatment with L-Arg was associated with significantly less intimal thickness ( p < 0.05). Local transfer of the VEGF gene does not inhibit neointima formation in hypercholesterolemic rabbits. Our results suggest that VEGF gene therapy applied locally in atherosclerotic arteries may not be beneficial.
Vascular compliance versus flow-mediated vasodilation: correlation with cardiovascular risk factors
Authors: Nair Nandini , Oka Roberta K , Waring Laurel D , Umoh Eva M , Taylor C Barr , Cooke John P
Published: December 2005

Cardiovascular risk factors are associated with impaired endothelium dependent vasodilation and reduced vascular compliance. In this study, the correlation with cardiovascular risk factor score of two common techniques for assessing vascular function was compared. Risk factors and vascular function were evaluated in a study population of 122 people with peripheral arterial disease (PAD) or with risk factors for PAD (73 men and 49 women; mean age 69 years). A risk factor score was determined using Framingham criteria. Vascular compliance was assessed by pulse waveform analysis and simultaneous blood pressure measurement. Flow-mediated vasodilation of the brachial artery was measured using duplex ultrasonography. Participants with a high risk factor score had significantly reduced vascular compliance of large and small vessels. By contrast, the difference in flow-mediated vasodilation between those with a high or low risk factor score did not reach statistical significance. There was a significant negative correlation between vascular compliance and risk factor score. There was a similar trend between flow-mediated vasodilation and risk factor score, but this did not reach statistical significance. A measure of vascular compliance was more significantly correlated with cardiovascular risk factor score than was a measure of flow-mediated vasodilation in the study population. Neither technique provided values that were highly correlated with risk factor burden. Although flow-mediated vasodilation is a preferred research tool for assessing vascular function, technical limitations and biological variability may reduce its clinical application in assessing individual cardiovascular risk.
Extended enoxaparin monotherapy for acute symptomatic pulmonary embolism
Authors: Kucher Nils , Quiroz Rene , McKean Sylvia , Sasahara Arthur A , Goldhaber Samuel Z
Published: December 2005

We investigated the efficacy and safety of extended enoxaparin monotherapy in symptomatic patients with acute pulmonary embolism (PE). We randomized 40 patients in a 1:1 allocation to enoxaparin monotherapy (1 mg/kg twice daily for 10-18 days, and then 1.5 mg/kg once daily until day 90) ( n = 20) or to enoxaparin 1.0 mg/kg twice daily as a bridge to warfarin with a target international normalized ratio of 2.0-3.0 for 90 days (at least 10 doses of enoxaparin overlapping with warfarin for at least 4 days) ( n = 20). All patients underwent echocardiography, cardiac troponin I (TnI), and brain natriuretic peptide testing to identify patients with an increased likelihood of adverse clinical outcomes. The end-points were newly diagnosed deep venous thrombosis (DVT) or PE and bleeding events through day 90. In 15 patients on extended enoxaparin therapy, we used repeated measure analysis of variance (ANOVA) to investigate differences in anti-Xa levels obtained at 2, 4, 8 and 12 weeks. The patients’ mean age was 52 ± 17 years; the most common comorbidities were obesity (58%), hypertension (30%), concomitant DVT (30%) and cancer (15%). Twelve (30%) patients had elevated cardiac TnI >0.1 mg/l and 11 (28%) had moderate or severe right ventricular dysfunction on echocardiography. Ten (25%) patients received thrombolysis with a continuous infusion of 100 mg alteplase prior to randomization. During a 90-day follow-up, one patient from the enoxaparin monotherapy group suffered symptomatic distal DVT; one from the warfarin group had recurrent symptomatic PE (p= 1.0). None of the study patients had major hemorrhage; two warfarin group patients had minor bleeding compared with none in the enoxaparin monotherapy group (p= 0.49). Repeated measure ANOVA did not reveal significant differences in anti-Xa levels over time (p= 0.217). In patients with acute symptomatic PE, extended enoxaparin monotherapy is feasible and warrants further investigation in a large clinical trial.
The association between smoking and the prevalence of intermittent claudication
Authors: Jensen Svein A , Vatten Lars J , Nilsen Tom IL , Romundstad Pål R , Myhre Hans O
Published: December 2005

The objective of this study was to investigate the association between smoking and the prevalence of intermittent claudication (IC). Between 1995 and 1997, all residents aged 20 years or older in Nord-Trøndelag County, Norway, were invited to take part in the Nord-Trøndelag Health Study (Helseundersøkelsen i Nord-Trøndelag: HUNT 2). A total of 19 748 participants aged 40-69 years attended. Responses to 12 questions on IC (including a Norwegian translation of the Edinburgh Claudication Questionnaire) had been previously tested against the ankle-brachial pressure index (ABPI < 0.9), and an algorithm of the best test properties was used to identify people with IC. Using logistic regression analysis we computed age-adjusted prevalence odds ratios (OR) for the association between smoking and IC. Both current (ORmen = 3.8, confidence interval (CI) 2.1-6.7, ORwomen = 2.2, CI 1.4-3.4) and former smokers (ORmen = 1.7, CI 0.9-3.2, ORwomen = 1.7, CI 1.1-2.7) had a higher prevalence of IC compared with those who had never smoked, and individuals who had stopped smoking more than 20 years previously had a substantially lower prevalence of IC (ORmen = 0.2, CI 0.1-0.5, ORwomen = 0.4, CI 0.2-0.8) than current smokers. We found no association between passive smoking and IC in either men or women. Current and previous smoking habits were positively associated with the prevalence of IC, and smoking cessation was negatively associated in men and women. Passive smoking was not associated with IC in this study.
A pilot study of l-arginine supplementation on functional capacity in peripheral arterial disease
Authors: Oka Roberta K , Szuba Andrzej , Giacomini John C , Cooke John P
Published: December 2005

Peripheral arterial disease (PAD) impairs walking capacity and is often associated with a profound endothelial vasodilator dysfunction, characterized by reduced bioactivity and/or synthesis of endothelium-derived nitric oxide (NO). Previous studies have suggested that dietary supplementation of L-arginine, the precursor of NO, improves endothelium-dependent vasodilation, limb blood flow and walking distance. However, these studies have been small, and have used large intravenous doses of L-arginine. The optimal dose of L-arginine has not been determined. Accordingly, this pilot study was conducted to establish the lowest effective oral dose of L-arginine to improve walking distance in preparation for the definitive study. Patients with PAD and intermittent claudication ( n = 80) participated in this study. Eligibility criteria included: (1) ankle-brachial index (ABI) at rest ≤0.90; (2) post-exercise reduction in ABI ≥25%; and (3) difference in absolute claudication distance of ≤25% between two consecutive treadmill tests. Treadmill testing was performed using the Skinner-Gardner protocol and community-based walking was assessed using the walking impairment questionnaire. Patients were randomly assigned to oral doses of 0, 3, 6 or 9 g of L-arginine daily in three divided doses for 12 weeks. Treadmill testing was performed prior to administration of the study drug and again after 12 weeks of treatment. The study drug was well tolerated, with no significant adverse effects of L-arginine therapy. The safety laboratory studies were unremarkable, except for a statistically significant reduction in hematocrit in the L-arginine-treated groups. There was no significant difference observed in absolute claudication distance between the groups. However, a trend was observed for a greater increase in walking distance in the group treated with 3 g L-arginine daily, and there was a trend for an improvement in walking speed in patients treated with L-arginine. This pilot study provided data for safety, for power calculation and for dosing for the larger definitive trial that is now underway.
Mechanisms of Raynaud’s disease
Authors: Cooke John P , Marshall Janice M
Published: December 2005

Raynaud's phenomenon is due to transient cessation of blood flow to the digits of the hands or feet. An attack of Raynaud’s phenomenon is classically manifested as triphasic color changes. The white phase is due to excessive vasoconstriction and cessation of regional blood flow. This phase is followed by a cyanotic phase, as the residual blood in the finger desaturates. The red phase is due to hyperemia as the attack subsides and blood flow is restored. An attack is frequently associated with pain and/or paresthesia due to sensory nerve ischemia. Variants of Raynaud’s phenomenon include acrocyanosis and primary livedo reticularis, each of which is associated with reduced skin blood flow, exacerbated by cold or emotional upset. Raynaud’s phenomenon in the absence of other disorders is primary Raynaud’s phenomenon, or Raynaud’s disease. The mechanisms of Raynaud’s disease include increased activation of the sympathetic nerves, in response to cold or emotion; an impaired habituation of the cardiovascular response to stress may contribute. In addition, there appears to be a local fault, which is likely multifactorial. This local fault is due to an alteration in vascular function rather than vascular structure. The alteration in vascular function may be related to increased sensitivity to cold of the adrenergic receptors on the digital artery vascular smooth muscle. In some cases, locally released or systemically circulating vasoconstrictors may participate, including endothelin, 5-hydroxytryptamine and thromboxane. A deficiency or increased degradation of nitric oxide, possibly due to increased oxidative stress, may be involved in some cases. These recent pathophysiological insights may lead to new therapeutic options.
Atheromatous embolization
Authors: Liew Yin Ping , Bartholomew John R
Published: December 2005

Atheromatous embolization is a multisystem disease complicating advanced atherosclerosis. It occurs most often as a complication of angiography, an endovascular procedure or cardiovascular surgery. Atheromatous embolization can present in a subtle manner where it is often under-recognized, or with catastrophic results including myocardial infarction, strake or acute renal failure. It may mimic other disease processes and often goes underdiagnosed and undertreated. A high clinical suspicion is the key to diagnosis. Atheromatous embolization results in significant morbidity and mortality; therefore, early recognition followed by aggressive management may help to prevent end-organ damage and improve overall clinical outcomes. Management strategies should include risk factor modification, prevention of further insults by discontinuing or avoiding predisposing factors, supportive treatment and interventional or surgical approaches to remove the atheroembolic source. Atheromatous embolization is expected to increase as our population ages and the epidemics of diabetes mellitus and obesity increase.
Paediatric chest drains: past, present and percutaneous
Authors: Parslow PM , Sandell JM
Published: December 2005

The authors present a review of the pathophysiology of pneumothoraces, the indications and the procedures required for the insertion of chest drains, and review paediatric practice using the recently developed Seldinger-style percutaneous chest drains.
The immuno-inflammatory response to trauma
Authors: Tzioupis Christopher C , Katsoulis Stathis , Manidakis Nick , Giannoudis Peter V
Published: December 2005

The systemic inflammatory response syndrome is a well recognized physiological entity being part of our homeostatic mechanisms. It represents the cascade of inflammatory reactions initiated in the immediate aftermath following trauma reflecting the state of alertness that our body undergoes in order to fight for survival. A variety of inflammatory mediators and cellular elements are involved during this process interacting amongst each other. This allows communication between the different organ systems and thus regulating local and systemic responses. We have just begun to characterize and quantify the immuno-inflammatory response to trauma and this has opened new horizons in the way we understand the pathophysiological response to injury. As our knowledge evolves new therapeutic agents and innovative treatment plans will be developed contributing to increased survival rates in patients with multiple injuries.
The limping child
Authors: Gibbons Paul
Published: December 2005

A limp suggests an underlying pathology causing the abnormal gait pattern. There is a long list of possible causes. The challenge for the physician is to identify the cause and act accordingly. The purpose of this article is to instruct on the assessment of a child with a limp.
‘Spot the difference’: the importance of recognizing symmetrical trauma
Authors: Rutherford Elizabeth E , Sampson Madeleine A
Published: December 2005

The eye can play tricks on us and optical illusions are commonly used to illustrate the fact that the brain interprets perceived images according to what it ‘expects’ to see. When viewing trauma imaging, we tend to subconsciously use the body’s symmetry as a reference point and therefore symmetrical injuries can easily be overlooked, even when gross. In this article, we will illustrate this phenomenon with examples of imaging from trauma cases and suggest how recognition of typical patterns of injury in addition to knowledge of some common pitfalls in trauma radiology can help us avoid the misinterpretation of bilateral symmetrical abnormalities.
Injuries caused by seatbelts
Authors: Smith JE , Hall MJ
Published: December 2005

Seatbelts save lives. However, they may cause injury to adjacent structures and when they malfunction can cause injury to the abdominal viscera, bony skeleton and vascular structures. The motor industry has attempted to reduce these injuries by modification of vehicle design and safety equipment. This paper discusses the patterns of injury caused by seatbelts and the methods by which the motor industry attempts to reduce their incidence.
Injuries of the acromioclavicular joint and current treatment options
Authors: Rollo J , Raghunath J , Porter K
Published: December 2005

The acromioclavicular joint is involved in four out of ten shoulder injuries. The joint is prone to injury due to its anatomy and relative lack of soft tissue cover. Sportsmen involved in contact sports are likely to suffer damage to the joint during their professional careers. Most subluxations of the joint can be treated nonoperatively whilst dislocations are generally treated operatively except in those individuals at significant risk of re-injury, for example, rugby players. This article looks at the anatomy and physiology of the acromioclavicular joint, injury classification and presents the current evidence regarding treatment options for these injuries.
A general formulation for a one-sided group sequential design
Authors: Moser Barry K , George Stephen L
Published: December 2005

Background A major contribution to the statistical literature on group sequential designs was provided by Pampallona and Tsiatis who developed closed form functions that can be used to iteratively calculate the boundary points of a family of popular group sequential designs [1]. A related area of interest is the use of conditional probability calculations to make interim decisions in stochastic curtailment procedures.

Purpose The purpose of the paper is to develop group sequential designs based on conditional probabilities, to compare our results to the general closed form family of designs developed by Pampallona and Tsiatis, and to relate these to commonly used stochastic curtailment procedures.

Methods The problem and its solution are formulated and derived mathematically. A graphical interpretation of the results provides the reader with an alternative mechanism to understand the results and their significance.

Results One-sided group sequential design boundary points, as closed form functions, are derived from conditional probability statements. These conditional probability statements can be interpreted as the probability, at the final analysis, of reversing the conclusion reached at an interim state. Under mild constraints, these boundary points are identical to the Pampallona and Tsiatis boundary points. At any interim stage when a boundary point is attained or surpassed we suggest a graphical approach to examine the conditional probability of reversing the interim decision at the final stage versus a range of possible parameter values. For stochastic curtailment procedures, we recommend relaxing (increasing) the conditional probability levels to at least 0.50 so that early stopping is at least as likely as for the O'Brien-Fleming procedure.

Limitations The results are limited to one-sided group sequential designs.

Conclusions Conditional probabilities of reversing interim decisions provides a useful concept to develop group sequential designs and to evaluate stochastic curtailment procedures.
Monitoring event times in early phase clinical trials: some practical issues
Authors: Thall Peter F , Wooten Leiko H , Tannir Nizar M
Published: December 2005

Background In many early phase clinical trials it is scientifically inappropriate or logistically infeasible to characterize patient outcome as a binary variable. In such settings, it often is more natural to construct early stopping rules based on time-to-event variables. This type of design may involve a variety of complications, however.

Purpose The purpose of this paper is to illustrate by example how one may deal with various complications that may arise when monitoring time-to-event outcomes in an early phase clinical trial.

Methods We present a series of Bayesian designs for a phase II clinical trial in kidney cancer. Each design includes a procedure for monitoring the times to a severe adverse event, disease progression and death. The first design, which is the simplest, is based on the time to failure, defined as any of the three events, assuming exponentially distributed failure times with an inverse gamma prior on the mean. This design is compared by simulation to the CMAP design (Cheung and Thall, Biometrics, 2002; 58: 89–97). The model and monitoring procedure are then extended successively to accommodate several common practical complications, and we also study the method's robustness.

Results Our simulations show that 1) one may apply the monitoring rule periodically, rather than continuously, without a substantive degradation of the design's reliability; 2) it is very important to account for interval censoring due to periodic evaluation of disease status; 3) it is important to account for the effect of disease progression on the subsequent death rate; 4) conducting a randomized trial presents little additional difficulty and provides unbiased comparisons; and 5) the exponential-inverse gamma model is surprisingly robust in most cases.

Limitations The methods discussed here do not account for patient heterogeneity. This is an important but complex issue that may be dealt with by extending the models and methods given here to accommodate patient covariates and treatment-covariate interaction.

Conclusions Bayesian procedures for monitoring time-to-event outcomes offer a practical way to conduct a variety of early phase trials. Considerable care must be given, however, to modeling the important aspects of the trial at hand, and to calibrating the prior and the design parameters to ensure that the design will have good operating characteristics.
Identifying methodologies in the assessment of treatment effects on the repeated occurrences of hot flashes in postmenopausal women
Authors: He Weili , Deng Weiping
Published: December 2005

Background Two methods that are commonly used in most clinical trials for evaluating the effect of treatment on hot flashes are frequency only and severity score methods. However, in these crude methods, composite recurrent hot flash data on a patient are reduced to a one-dimensional summary measure, an approach which may not be optimal. In addition, the duration of a hot flash event provides additional information, which is not accounted for in the two methods mentioned above.

Purpose We propose two new methods in the analysis of hot flash data in this paper.

Methods The first method utilizes a generalization of the continuation ratio model to model the severity of a hot flash event. The model accounts for individual random effects and dependence of recurrent events within an individual. The other method that accounts for the duration of a hot flash event is a 3-Dimensional (3D) score method, which incorporates hot flash information on frequency, severity, and duration.

Results Simulation studies were conducted to evaluate the properties of our proposed methods. The results indicate that our proposed generalized continuation ratio model has appreciably high power in detecting small treatment effects on severity compared with the two commonly used methods. The proposed 3D score, on the other hand, is sensitive in detecting treatment effects on both frequency and duration, but has low power in detecting treatment effects on severity alone.

Conclusions Our proposed generalized continuation ratio model approach provides a valuable and powerful alternative to the two commonly used methods in the analysis of treatment effects on hot flash severity. Our proposed 3D score method incorporates the additional information hot flash duration provides, and is another analysis option for the practitioners to employ.