bluuebunny/crossref_metadata_2025 huggingface dataset:
A final reconstruction approach for a unified global illumination algorithm
Authors: Granier Xavier , Drettakis George
Published: July 2004

In the past twenty years, many algorithms have been proposed to compute global illumination in synthetic scenes. Typically, such approaches can deal with specific lighting configurations, but often have difficulties with others. In this article, we present a final reconstruction step for a novel
unified approach
to global illumination that automatically detects different types of light transfer and uses the appropriate method in a closely-integrated manner. With our approach, we can deal with difficult lighting configurations such as indirect nondiffuse illumination. The first step of this algorithm consists in a view-independent solution based on hierarchical radiosity with clustering, integrated with particle tracing. This first pass results in solutions containing directional effects such as caustics, which can be interactively rendered. The second step consists of a view-dependent final reconstruction that uses all existing information to compute higher quality, ray-traced images.
A framework and tool support for the systematic testing of model-based specifications
Authors: Miller Tim , Strooper Paul
Published: July 2004

Formal specifications can precisely and unambiguously define the required behavior of a software system or component. However, formal specifications are complex artifacts that need to be verified to ensure that they are consistent, complete, and validated against the requirements. Specification testing or animation tools exist to assist with this by allowing the specifier to interpret or execute the specification. However, currently little is known about how to do this effectively.This article presents a framework and tool support for the systematic testing of formal, model-based specifications. Several important generic properties that should be satisfied by model-based specifications are first identified. Following the idea of mutation analysis, we then use variants or mutants of the specification to check that these properties are satisfied. The framework also allows the specifier to test application-specific properties. All properties are tested for a range of states that are defined by the tester in the form of a testgraph, which is a directed graph that partially models the states and transitions of the specification being tested. Tool support is provided for the generation of the mutants, for automatically traversing the testgraph and executing the test cases, and for reporting any errors. The framework is demonstrated on a small specification and its application to three larger specifications is discussed. Experience indicates that the framework can be used effectively to test small to medium-sized specifications and that it can reveal a significant number of problems in these specifications.
LinkSelector
Authors: Fang Xiao , Sheng Olivia R. Liu
Published: July 2004

As the size and complexity of Web sites expands dramatically, it has become increasingly challenging to design Web sites where Web surfers can easily find the information they seek. In this article, we address the design of the portal page of a Web site, which serves as the homepage of a Web site or a default Web portal. We define an important research problem---hyperlink selection: selecting from a large set of hyperlinks in a given Web site, a limited number of hyperlinks for inclusion in a portal page. The objective of hyperlink selection is to maximize the efficiency, effectiveness, and usage of a Web site's portal page. We propose a heuristic approach to hyperlink selection, LinkSelector, which is based on relationships among hyperlinks---structural relationships that can be extracted from an existing Web site and access relationships that can be discovered from a Web log. We compared the performance of LinkSelector with that of the current practice of hyperlink selection (i.e., manual hyperlink selection by domain experts), using data obtained from the University of Arizona Web site. Results showed that LinkSelector outperformed the current manual selection method.
Why reform the U.S. patent system?
Authors: Samuelson Pamela
Published: July 2004

Considering three important reforms to improve the current system.
A parallel direct solver for large sparse highly unsymmetric linear systems
Authors: Duff Iain S. , Scott Jennifer A.
Published: July 2004

The need to solve large sparse linear systems of equations efficiently lies at the heart of many applications in computational science and engineering. For very large systems when using direct factorization methods of solution, it can be beneficial and sometimes necessary to use multiple processors, because of increased memory availability as well as reduced factorization time. We report on the development of a new parallel code that is designed to solve linear systems with a highly unsymmetric sparsity structure using a modest number of processors (typically up to about 16). The problem is first subdivided into a number of loosely connected subproblems and a variant of sparse Gaussian elimination is then applied to each of the subproblems in parallel. An interface problem in the variables on the boundaries of the subproblems must also be factorized. We discuss how our software is designed to achieve the goals of portability, ease of use, efficiency, and flexibility, and illustrate its performance on an SGI Origin 2000, a Cray T3E, and a 2-processor Compaq DS20, using problems arising from real applications.
Algorithm 835
Authors: Zeng Zhonggang
Published: July 2004

MultRoot is a collection of Matlab modules for accurate computation of polynomial roots, especially roots with non-trivial multiplicities. As a blackbox-type software, MultRoot requires the polynomial coefficients as the only input, and outputs the computed roots, multiplicities, backward error, estimated forward error, and the structure-preserving condition number. The most significant features of MultRoot are the multiplicity identification capability and high accuracy on multiple roots without using multiprecision arithmetic, even if the polynomial coefficients are inexact. A comprehensive test suite of polynomials that are collected from the literature is included for numerical experiments and performance comparison.
Decreased affinity for oxygen of cytochrome-c oxidase in Leigh syndrome caused by SURF1 mutations
Authors: Pecina Petr , Gnaiger Erich , Zeman Jiří , Pronicka Ewa , Houštěk Josef
Published: July 2004

Mutations in the gene SURF1 prevent synthesis of cytochrome- c oxidase (COX)-specific assembly protein and result in a fatal neurological disorder, Leigh syndrome. Because this severe COX deficiency presents with barely detectable changes of cellular respiratory rates under normoxic conditions, we analyzed the respiratory response to low oxygen in cultured fibroblasts harboring SURF1 mutations with high-resolution respirometry. The oxygen kinetics was quantified by the partial pressure of oxygen (Po2) at half-maximal respiration rate (P50) in intact coupled cells and in digitonin-permeabilized uncoupled cells. In both cases, the P50 in patients was elevated 2.1- and 3.3-fold, respectively, indicating decreased affinity of COX for oxygen. These results suggest that at physiologically low intracellular Po2, the depressed oxygen affinity may lead in vivo to limitations of respiration, resulting in impaired energy provision in Leigh syndrome patients.
Cardiac neuronal hierarchy in health and disease
Authors: Armour J. Andrew
Published: July 2004

The cardiac neuronal hierarchy can be represented as a redundant control system made up of spatially distributed cell stations comprising afferent, efferent, and interconnecting neurons. Its peripheral and central neurons are in constant communication with one another such that, for the most part, it behaves as a stochastic control system. Neurons distributed throughout this hierarchy interconnect via specific linkages such that each neuronal cell station is involved in temporally dependent cardio-cardiac reflexes that control overlapping, spatially organized cardiac regions. Its function depends primarily, but not exclusively, on inputs arising from afferent neurons transducing the cardiovascular milieu to directly or indirectly (via interconnecting neurons) modify cardiac motor neurons coordinating regional cardiac behavior. As the function of the whole is greater than that of its individual parts, stable cardiac control occurs most of the time in the absence of direct cause and effect. During altered cardiac status, its redundancy normally represents a stabilizing feature. However, in the presence of regional myocardial ischemia, components within the intrinsic cardiac nervous system undergo pathological change. That, along with any consequent remodeling of the cardiac neuronal hierarchy, alters its spatially and temporally organized reflexes such that populations of neurons, acting in isolation, may destabilize efferent neuronal control of regional cardiac electrical and/or mechanical events.
Tetanization-induced pelvic-to-pudendal reflex plasticity in anesthetized rats
Authors: Lin Tzer-Bin
Published: July 2004

Reflex plasticity between pelvic afferent and pudendal efferent nerve fibers was examined in anesthetized rats. Brief high-frequency electric stimulation (300 pulses at 100 Hz) of the pelvic nerve afferent fiber produced a long-lasting potentiation of the pelvic-to-pudendal reflex (PPR). This tetanization-induced potentiation was abolished by a selective N-methyl-d-aspartate (NMDA) receptor antagonist and attenuated by a non-NMDA excitatory amino acid receptor antagonist. However, the GABAA-receptor antagonist had no effect on this potentiation. Both intrathecal glutamate (0.1 mM, 2–5 μl it) and NMDA (0.1 mM, 2–5 μl it) induced a potentiation of PPR similar to that of tetanization. Agonist-induced potentiation was shorter than tetanization-induced potentiation. The duration of the contraction wave of intraurethral pressure, elicited by PPR, was elongated by tetanization-induced potentiation, whereas the peak pressure was not affected. All these results demonstrate that brief high-frequency stimulation of the pelvic nerve afferent fiber can induce a distinct and long-lasting modulation in PPR activity and this change may be involved in nociceptive C afferent-induced obstructive urinary dysfunctions.
Quantifying the Ontogeny of Optokinetic and Vestibuloocular Behaviors in Zebrafish, Medaka, and Goldfish
Authors: Beck James C. , Gilland Edwin , Tank David W. , Baker Robert
Published: July 2004

We quantitatively studied the ontogeny of oculomotor behavior in larval fish as a foundation for studies linking oculomotor structure and function with genetics. Horizontal optokinetic and vestibuloocular reflexes (OKR and VOR, respectively) were measured in three different species (goldfish, zebrafish, and medaka) during the first month after hatching. For all sizes of medaka, and most zebrafish, Bode plots of OKR (0.065–3.0 Hz, ±10°/s) revealed that eye velocity closely followed stimulus velocity (gain > 0.8) at low frequency but dropped sharply above 1 Hz (gain < 0.3 at 3 Hz). Goldfish showed increased gain proportional to size across frequencies. Linearity testing with steps and sinusoids showed excellent visual performance (gain > 0.8) in medaka almost from hatching; but zebrafish and goldfish exhibited progressive improvement, with only the largest equaling medaka performance. Monocular visual stimulation in zebrafish and goldfish produced gains of 0.5 versus <0.1 for the eye viewing a moving versus stationary stimulus pattern but 0.25 versus <0.1 in medaka. Angular VOR appeared much later than OKR, initially at only high accelerations (>200°/s at 0.5 Hz), first in medaka followed by larger (8.11 mm) zebrafish; but it was virtually nonexistent in goldfish. Velocity storage was not observed except for an eye velocity build-up in the largest medaka. In summary, a robust OKR was achieved shortly after hatching in all three species. In contrast, larval fish seem to be unique among vertebrates tested in their lack of significant angular VOR at stages where active movement is required for feeding and survival.
Motor-Unit Coherence and Its Relation With Synchrony Are Influenced by Training
Authors: Semmler John G. , Sale Martin V. , Meyer François G. , Nordstrom Michael A.
Published: July 2004

The purpose of the study was to quantify the strength of motor-unit coherence from the left and right first dorsal interosseous muscles in untrained, skill-trained (musicians), and strength-trained (weightlifters) individuals who had long-term specialized use of their hand muscles. The strength of motor-unit coherence was quantified from a total of 394 motor-unit pairs in 13 subjects using data from a previous study in which differences were found in the strength of motor-unit synchronization depending on training status. In the present study, we found that the strength of motor-unit coherence was significantly greater in the left compared with the right hand of untrained right-handed subjects with the largest differences observed between 21 and 24 Hz. The strength of motor-unit coherence was lower in both hands of skill-trained subjects (21–27 Hz) and the right (skilled) hand of untrained subjects (21–24 Hz), whereas the largest motor-unit coherence was observed in both hands of strength-trained subjects (3–9 and 21–27 Hz). A strong curvilinear association was observed between motor-unit synchronization and the integral of coherence at 10–30 Hz in all motor-unit pairs ( r2 = 0.77), and was most pronounced in strength-trained subjects ( r2 = 0.90). Furthermore, this association was accentuated when using synchronization data with broad peaks (>11 ms), suggesting that the 10- to 30-Hz coherence is due to oscillatory activity in indirect branched common inputs. The altered coherence with training may be due to an interaction between cortical inhibition and the number of direct common inputs to motor neurons in skill- or strength-trained hands.
Differential Roles of Neuronal Activity in the Supplementary and Presupplementary Motor Areas: From Information Retrieval to Motor Planning and Execution
Authors: Hoshi Eiji , Tanji Jun
Published: July 2004

We explored functional differences between the supplementary and presupplementary motor areas (SMA and pre-SMA, respectively) systematically with respect to multiple behavioral factors, ranging from the retrieval and processing of associative visual signals to the planning and execution of target-reaching movement. We analyzed neuronal activity while monkeys performed a behavioral task in which two visual instruction cues were given successively with a delay: one cue instructed the location of the reach target, and the other instructed arm use (right or left). After a second delay, the monkey received a motor-set cue to be prepared to make the reaching movement as instructed. Finally, after a GO signal, it reached for the instructed target with the instructed arm. We found the following apparent differences in activity: 1) neuronal activity preceding the appearance of visual cues was more frequent in the pre-SMA; 2) a majority of pre-SMA neurons, but many fewer SMA neurons, responded to the first or second cue, reflecting what was shown or instructed; 3) in addition, pre-SMA neurons often reflected information combining the instructions in the first and second cues; 4) during the motor-set period, pre-SMA neurons preferentially reflected the location of the target, while SMA neurons mainly reflected which arm to use; and 5) when executing the movement, a majority of SMA neurons increased their activity and were largely selective for the use of either the ipsilateral or contralateral arm. In contrast, the activity of pre-SMA neurons tended to be suppressed. These findings point to the functional specialization of the two areas, with respect to receiving associative cues, information processing, motor behavior planning, and movement execution.
Mouse MRI: Concepts and Applications in Physiology
Authors: Pautler Robia G.
Published: July 2004

The purpose of this review is to provide an introduction to the rapidly expanding field of mouse magnetic resonance imaging (MRI). It is by no means meant to be all-inclusive but rather to provide a brief introduction to the basics of MRI theory, provide some insight into the basic experiments that can be performed in mice by using MRI, and bring to light some factors to consider when planning a mouse MRI experiment.
AMP-Activated Protein Kinase Inhibits Angiotensin II–Stimulated Vascular Smooth Muscle Cell Proliferation
Authors: Nagata Daisuke , Takeda Ryo , Sata Masataka , Satonaka Hiroshi , Suzuki Etsu , Nagano Tetsuo , Hirata Yasunobu
Published: July 2004

Background—

AMP-activated protein kinase (AMPK) is a stress-activated protein kinase that works as a metabolic sensor of cellular ATP levels. Here, we investigated whether AMPK signaling has a role in the regulation of the angiotensin II (Ang II)-induced proliferation signal in rat vascular smooth muscle cells (VSMCs).

Methods and Results—

Aminoimidazole-4-carboxamide-1-β-ribofuranoside (AICAR) activated AMPK in rat VSMCs and inhibited Ang II-induced extracellular signal-regulated kinase 1/2 phosphorylation but not that of p38 MAPK or Akt/PKB. Although Ang II activated AMPK, this activation was significantly inhibited by catalase,
N
-acetylcysteine, and diphenyleneiodonium chloride, an NADPH oxidase inhibitor. Moreover, the observation that AMPK was activated by H
2
O
2
suggests that AMPK is redox sensitive. The Ang II type 1 receptor antagonist valsartan but not the Ang II type 2 receptor antagonist PD123319 significantly inhibited Ang II-induced AMPK activation, suggesting that Ang II-induced AMPK activation was Ang II type 1 receptor dependent. Whereas
3
H-thymidine incorporation by VSMCs treated with Ang II was significantly inhibited when the cells were pretreated with 1 mmol/L AICAR, the inhibition of AMPK by dominant-negative AMPK overexpression augmented Ang II-induced cell proliferation. Subcutaneous injection of AICAR (1 mg/g body weight per day) for 2 weeks suppressed neointimal formation after transluminal mechanical injury of the rat femoral artery.

Conclusions—

Our findings indicate that Ang II-induced AMPK activation is synchronized with extracellular signal-regulated kinase signaling and that AMPK works as an inhibitor of the Ang II proliferative pathway. AMPK signaling might serve as a new therapeutic target of vascular remodeling in cardiovascular diseases.
C-Reactive Protein, the Metabolic Syndrome, and Prediction of Cardiovascular Events in the Framingham Offspring Study
Authors: Rutter Martin K. , Meigs James B. , Sullivan Lisa M. , D’Agostino Ralph B. , Wilson Peter W.F.
Published: July 2004

Background—

Inflammation (assessed by C-reactive protein [CRP]) and the metabolic syndrome (MetS) are associated with cardiovascular disease (CVD), but population-based data are limited.

Methods and Results—

We assessed the cross-sectional relations of CRP to the MetS (National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Adult Treatment Panel III definition) in 3037 subjects (1681 women; mean age, 54 years) and the utility of CRP and the MetS to predict new CVD events (n=189) over 7 years. MetS (≥3 of 5 traits) was present in 24% of subjects; mean age-adjusted CRP levels for those with 0, 1, 2, 3, 4, or 5 MetS traits were 2.2, 3.5, 4.2, 6.0, or 6.6 mg/L, respectively (
P
trend <0.0001). In persons with MetS, age-adjusted CRP levels were higher in women than men (7.8 versus 4.6 mg/L;
P
<0.0001). MetS and baseline CRP were individually related to CVD events (for MetS: age-sex-adjusted hazard ratio [HR], 2.1; 95% CI, 1.5 to 2.8; for highest versus lowest CRP quartile: HR, 2.2; 95% CI, 1.4 to 3.5). Greater risk of CVD persisted for MetS and CRP even after adjustment in a model including age, sex, MetS (HR, 1.8; 95% CI, 1.4 to 2.5), and CRP (HR, 1.9; 95% CI, 1.2 to 2.9). The c-statistic associated with the age- and sex-adjusted model including CRP was 0.72; including MetS, 0.74; and including CRP and MetS, 0.74.

Conclusions—

Elevated CRP levels are related to insulin resistance and the presence of the MetS, especially in women. Although discrimination of subjects at risk of CVD events using both MetS and CRP is not better than using either phenotype alone, both CRP and MetS are independent predictors of new CVD events.
Cardiac Memory Evolves With Age in Association With Development of the Transient Outward Current
Authors: Plotnikov Alexei N. , Sosunov Eugene A. , Patberg Kornelis W. , Anyukhovsky Evgeny P. , Gainullin Ravil Z. , Shlapakova Iryna N. , Krishnamurthy Ganga , Danilo Peter , Rosen Michael R.
Published: July 2004

Background—

Calcium-insensitive transient outward current (
I
to
) is important to the development of cardiac memory (CM), which itself reflects the capacity of the heart to remodel electrophysiologically. We used cardiac pacing to test the hypothesis that CM evolution can be explained by developmental maturation of
I
to
.

Methods and Results—

Acutely anesthetized dogs from 1 day old to adult were paced from the left ventricle (VP, n=29) or left atrial appendage (AP, n=12) to induce CM. T-wave vector displacement (TVD) obtained during VP was greater than with AP (adults, 0.39±0.06 mV; neonates, 0.04±0.01 mV;
P
<0.05). TVD began to increase at ≈40 days of age, reaching adult levels by ≈200 days. Microelectrode studies performed in 18 dogs (ages 3 to 94 days) after completing the CM protocol and 20 additional dogs (1 day old to adult) revealed that the epicardial action potential notch was absent in neonates, became apparent in the young, and was deepest in adults. The relationship between TVD and epicardial notch was such that as notch magnitude increased, TVD increased (
r
=−0.65,
P
<0.05). KChIP2 and Kv4.3 mRNA (measured via reverse transcription–polymerase chain reaction) also increased with age.

Conclusions—

The inducibility of CM gradually increases with age in association with evolution of the epicardial action potential notch and mRNA expression for KChIP2 and Kv4.3. This suggests that the capacity of the heart to remodel electrophysiologically and to manifest memory during development depends in part on evolution of the determinants of
I
to
.
Loading With 600 mg Clopidogrel in Patients With Coronary Artery Disease With and Without Chronic Clopidogrel Therapy
Authors: Kastrati Adnan , von Beckerath Nicolas , Joost Alexander , Pogatsa-Murray Gisela , Gorchakova Olga , Schömig Albert
Published: July 2004

Background—

It is not known whether further suppression of platelet function can be achieved with clopidogrel beyond that provided by currently recommended loading and maintenance doses. We performed a comparative assessment of the antiplatelet effects of a 600-mg loading dose of clopidogrel given to patients with and without chronic clopidogrel therapy.

Methods and Results—

Those eligible for this prospective study were aspirin-treated patients with suspected or documented coronary artery disease admitted to hospital for coronary angiography. Two series of 20 consecutive patients each were assessed in this study. The first series included patients who had never received clopidogrel (first-use group); the second series included patients on chronic therapy with a daily dose of 75 mg clopidogrel for ≥1 month (chronic therapy group). Blood samples were drawn before and 6 hours after oral administration of 600 mg clopidogrel for aggregometry and flow cytometry studies. In the first-use group, loading with 600 mg clopidogrel inhibited ADP 5 μmol/L–induced platelet aggregation from 90±9% to 51±19% (
P
<0.001). In the chronic therapy group, loading with 600 mg clopidogrel yielded further inhibition of ADP 5 μmol/L–induced platelet aggregation in addition to that achieved by the maintenance dose of 75 mg/d, from 52±14% to 33±12% (
P
<0.001). In both groups, 600 mg clopidogrel loading significantly inhibited ADP-induced expression of glycoprotein IIb/IIIa and P-selectin receptors.

Conclusions—

Further platelet inhibition can be achieved with clopidogrel in addition to that provided by currently recommended loading and maintenance doses. Higher doses may be warranted after assessment of their clinical efficacy and safety.
Cellular-Free Magnesium Depletion in Brain and Muscle of Normal and Preeclamptic Pregnancy
Authors: Resnick Lawrence M. , Barbagallo Mario , Bardicef Mordechai , Bardicef Orit , Sorokin Yoram , Evelhoch Jeffrey , Dominguez Ligia J. , Mason Brian A. , Cotton David B.
Published: July 2004

Preeclampsia is a pregnancy disorder of unknown origin, characterized by vasospasm, elevated blood pressure, and increased neuromuscular irritability, features common to syndromes of magnesium deficiency. Evidence of serum and ionized magnesium metabolism disturbances have been observed in women with preeclampsia. This and the therapeutic utility of magnesium in preeclampsia led us to investigate the extent to which an endogenous tissue magnesium deficiency might be present in and contribute to its pathophysiology. We used
31
P nuclear magnetic resonance spectroscopy to noninvasively measure in situ intracellular-free magnesium levels in brain and skeletal muscle of fasting nonpregnant women (n=12), and of third trimester women with uncomplicated pregnancies (n=11) and preeclampsia (n=7). Compared with nonpregnant controls (brain 519±59 μmol/L; muscle 604±34 μmol/L), brain and skeletal muscle intracellular magnesium levels were significantly lower in both normal pregnant (brain 342±23 μmol/L; muscle 482±40 μmol/L;
P
=0.05 for both tissues) and preeclamptic women (brain 229±17 μmol/L; muscle 433±46 μmol/L;
P
=0.05 for both tissues). Brain intracellular magnesium was further reduced in preeclamptics compared with normal pregnant subjects (
P
=0.05). For all pregnant subjects, blood pressure was significantly and inversely related to the concomitantly measured intracellular magnesium level in brain (systolic,
r
=−0.59,
P
=0.01; diastolic,
r
=−0.52,
P
=0.02) but not in muscle. Cellular magnesium depletion is characteristic of normal pregnancy and may be one factor contributing to the pathophysiology of preeclampsia. Furthermore, the influence of central nervous system factors on blood pressure may be mediated, at least in part, by ambient intracellular magnesium levels.
Visceral Fat in Hypertension
Authors: Sironi Anna Maria , Gastaldelli Amalia , Mari Andrea , Ciociaro Demetrio , Postano Vincenzo , Buzzigoli Emma , Ghione Sergio , Turchi Stefano , Lombardi Massimo , Ferrannini Ele
Published: July 2004

Preferential visceral adipose tissue (VAT) deposition has been associated with the presence of insulin resistance in obese and diabetic subjects. The independent association of VAT accumulation with hypertension and its impact on insulin sensitivity and β-cell function have not been assessed. We measured VAT and subcutaneous fat depots by multiscan MRI in 13 nondiabetic men with newly detected, untreated essential hypertension (blood pressure=151±2/94±2 mm Hg, age=47±2 years, body mass index [BMI]=28.4±0.7 kg · m
−2
) and 26 age-matched and BMI-matched normotensive men (blood pressure=123±1/69±2 mm Hg). Insulin secretion was measured by deconvolution of C-peptide data obtained during an oral glucose tolerance test, and dynamic indices of β-cell function were calculated by mathematical modeling. For a similar fat mass in the scanned abdominal region (4.8±0.3 versus 3.9±0.3 kg, hypertensive subjects versus controls,
P
=0.06), hypertensive subjects had 60% more VAT than controls (1.6±0.2 versus 1.0±0.1 kg,
P
=0.003). Intrathoracic fat also was expanded in patients versus controls (45±5 versus 28±3 cm
2
,
P
=0.005). Insulin sensitivity was reduced (10.7±0.7 versus 12.9±0.4 mL · min
−1
· kg
ffm
−1
,
P
=0.006), and total insulin output was proportionally increased (64 [21] versus 45 [24] nmol · m
−2
· h, median [interquartile range],
P
=0.01), but dynamic indices of β-cell function (glucose sensitivity, rate sensitivity, and potentiation) were similar in the 2 groups. Abdominal VAT, insulin resistance, and blood pressure were quantitatively interrelated (ρ’s of 0.39 to 0.47,
P
<0.02 or less). In newly found, untreated men with essential hypertension, fat is preferentially accumulated intraabdominally and intrathoracically. Such visceral adiposity is quantitatively related to both height of blood pressure and severity of insulin resistance, but has no impact on the dynamics of β-cell function.
Is the Failing Heart Energy Starved?
Authors: Ingwall Joanne S. , Weiss Robert G.
Published: July 2004

The requirement of chemical energy in the form of ATP to support systolic and diastolic work of the heart is absolute. Because of its central role in cardiac metabolism and performance, the subject of this review on energetics in the failing heart is ATP. We briefly review the basics of myocardial ATP metabolism and describe how this changes in the failing heart. We present an analysis of what is now known about the causes and consequences of these energetic changes and conclude by commenting on unsolved problems and opportunities for future basic and clinical research.
Myocardial Protection at a Crossroads
Authors: Bolli Roberto , Becker Lance , Gross Garrett , Mentzer Robert , Balshaw David , Lathrop David A.
Published: July 2004

Over the past 30 years, hundreds of experimental interventions (both pharmacologic and nonpharmacologic) have been reported to protect the ischemic myocardium in experimental animals; however, with the exception of early reperfusion, none has been translated into clinical practice. The National Heart, Lung, and Blood Institute convened a working group to discuss the reasons for the failure to translate potential therapies for protecting the heart from ischemia and reperfusion and to recommend new approaches to accomplish this goal. The Working Group concluded that cardioprotection in the setting of acute myocardial infarction, cardiac surgery, and cardiac arrest is at a crossroads. Present basic research approaches to identify cardioprotective therapies are inefficient and counterproductive. For 3 decades, significant resources have been invested in single-center studies that have often yielded inconclusive results. A new paradigm is needed to obviate many of the difficulties associated with translation of basic science findings. The Working Group urged a new focus on translational research that emphasizes efficacy and clinically relevant outcomes, and recommended the establishment of a system for rigorous preclinical testing of promising cardioprotective agents with clinical trial-like approaches (ie, blinded, randomized, multicenter, and adequately powered studies using standardized methods). A national preclinical research consortium would enable rational translation of important basic science findings into clinical use. The Working Group recommended that the National Institutes of Health proactively intervene to remedy current problems that impede translation of cardioprotective therapies. Their specific recommendations include the establishment of a preclinical consortium and the performance of 2 clinical studies that are likely to demonstrate effectiveness (phase III clinical trials of adenosine in acute myocardial infarction and cardiac surgery).
Spatial Constraint Method: A New Approach to Real-Time Haptic Interaction in Virtual Environments
Authors: Hirota Koichi , Hirayam Masaki , Tanaka Atsuko , Kaneko Toyohisa
Published: July 2004

In this paper, we propose an approach to real-time haptic interaction based on the concept of simulating the constraining propertes of space. Research on haptic interaction has been conducted from the points of view of both surface and volume rendering. Most approaches to surface rendering—such as the constraint-based god-object method, the point-based approach, and the virtual proxy approach—have dealt only with the interaction with an object surface. Whereas, in volume rendering approaches, algorithms for representing volume data through interactions in space have been investigated. Our approach provides a framework for the representation of haptic interaction with both surface and space. We discretize the space using a tetrahedral cell mesh and associate a constraining property with each cell. The interaction of the haptic interface points with a volume is simulated using the constraining properties of the cells occupied by this volume. We implemented a fast computation algorithm that works at a haptic rate. The algorithm is robust in that any sudden or quick motion of the user does not disturb the computation, and the computation time for each cycle is independent of the complexity of the model as a whole. To demonstrate the performance of the proposed method, we present experimental results on the interaction with models of varying complexity. Also, we discuss some problems that need to be solved in future work.
The Irony of Vietnam: The Johnson Administration's Tentative Bridge Building to China, 1965–1966
Authors: Lumbers Michael
Published: July 2004

Drawing on recently declassified American documents, this article traces the shift in U.S. policy toward the People's Republic of China (PRC) initiated by the Johnson administration in 1965–1966. During the first two years of his presidency, Lyndon Johnson resisted proposals to adopt a more flexible stance toward China, owing in large part to his suspicion that Beijing was encouraging and supplying the Communist insurgency in South Vietnam. This perception remained intact for the duration of the Johnson years and stifled major changes in policy toward China. Yet ironically, the Vietnam War itself led to a reappraisal of long-standing strategy toward the PRC. Johnson's determination to head off the threat of Chinese intervention in Vietnam and to sustain public support for the war yielded a relaxation of travel restrictions, the promotion of unofficial contacts between the two countries, and a striking change in rhetoric.
Storehouses and Systems At Persepolis
Authors: Aperghis
Published: July 2004

The Achaemenid financial administration at Persepolis controlled a network of commodity storehouses. This paper demonstrates how the Fortification Tablets from this location reveal the method of operation of the storehouses and the functions of the responsible officials. There were two main branches of the administration, a regional one of storehouses where the commodity tax was collected, and a super-imposed flexible system of work-groups and animal management under the control of apportioners. The key to understanding the procedures adopted is a comprehensive analysis of seal use on the tablets.
Definitions and Paradigms: Laches' First Definition
Authors: Rabbås Øyvind
Published: July 2004

Laches' first definition is rejected because it is somehow formally inadequate, but it is not clear exactly how this is so. On my interpretation, the failure of this definition cannot be explained by reference to the distinction between universals and particulars. Rather, it provides a paradigm of courage, which is inadequate because it fails to make clear how it is to be projected into other, non-paradigmatic cases. The definition is interesting because it articulates essential elements of the dominant moral tradition, including both its normative content (it is is too conservative and aristocratic) and its form (it is sustained by a certain limited canon of ideals, idols, and images of excellence). Socrates' elenchus of this definition thus amounts to a challenge to this tradition.
Rofecoxib for dysmenorrhoea: meta-analysis using individual patient data
Authors: Edwards Jayne E , Moore R Andrew , McQuay Henry J
Published: July 2004

Background

Individual patient meta-analysis to determine the analgesic efficacy and adverse effects of single-dose rofecoxib in primary dysmenorrhoea.

Methods

Individual patient information was available from three randomised, double blind, placebo and active controlled trials of rofecoxib. Data were combined through meta-analysis. Number-needed-to-treat (NNT) for at least 50% pain relief and the proportion of patients who had taken rescue medication over 12 hours were calculated. Information was collected on adverse effects.

Results

For single-dose rofecoxib 50 mg compared with placebo, the NNTs (with 95% CI) for at least 50% pain relief were 3.2 (2.4 to 4.5) at six, 3.1 (2.4 to 9.0) at eight, and 3.7 (2.8 to 5.6) at 12 hours. For naproxen sodium 550 mg they were 3.1 (2.4 to 4.4) at six, 3.0 (2.3 to 4.2) at eight, and 3.8 (2.7 to 6.1) at 12 hours. The proportion of patients who needed rescue medication within 12 hours was 27% with rofecoxib 50 mg, 29% with naproxen sodium 550 mg, and 50% with placebo. In the single-dose trial, the proportion of patients reporting any adverse effect was 8% (4/49) with rofecoxib 50 mg, 12% (6/49) with ibuprofen 400 mg, and 6% (3/49) with placebo. In the other two multiple dose trials, the proportion of patients reporting any adverse effect was 23% (42/179) with rofecoxib 50 mg, 24% (45/181) with naproxen sodium 550 mg, and 18% (33/178) with placebo.

Conclusions

Single dose rofecoxib 50 mg provided similar pain relief to naproxen sodium 550 mg over 12 hours. The duration of analgesia with rofecoxib 50 mg was similar to that of naproxen sodium 550 mg. Adverse effects were uncommon suggesting safety in short-term use of rofecoxib and naproxen sodium. Future research should include restriction on daily life and absence from work or school as outcomes.
Complementary and alternative medical therapies for chronic low back pain: What treatments are patients willing to try?
Authors: Sherman Karen J , Cherkin Daniel C , Connelly Maureen T , Erro Janet , Savetsky Jacqueline B , Davis Roger B , Eisenberg David M
Published: July 2004

Background

Although back pain is the most common reason patients use complementary and alternative medical (CAM) therapies, little is known about the willingness of primary care back pain patients to try these therapies. As part of an effort to refine recruitment strategies for clinical trials, we sought to determine if back pain patients are willing to try acupuncture, chiropractic, massage, meditation, and t'ai chi and to learn about their knowledge of, experience with, and perceptions about each of these therapies.

Methods

We identified English-speaking patients with diagnoses consistent with chronic low back pain using automated visit data from one health care organization in Boston and another in Seattle. We were able to confirm the eligibility status (i.e., current low back pain that had lasted at least 3 months) of 70% of the patients with such diagnoses and all eligible respondents were interviewed.

Results

Except for chiropractic, knowledge about these therapies was low. Chiropractic and massage had been used by the largest fractions of respondents (54% and 38%, respectively), mostly for back pain (45% and 24%, respectively). Among prior users of specific CAM therapies for back pain, massage was rated most helpful. Users of chiropractic reported treatment-related "significant discomfort, pain or harm" more often (23%) than users of other therapies (5–16%). Respondents expected massage would be most helpful (median of 7 on a 0 to 10 scale) and meditation least helpful (median of 3) in relieving their current pain. Most respondents indicated they would be "very likely" to try acupuncture, massage, or chiropractic for their back pain if they did not have to pay out of pocket and their physician thought it was a reasonable treatment option.

Conclusions

Most patients with chronic back pain in our sample were interested in trying therapeutic options that lie outside the conventional medical spectrum. This highlights the need for additional studies evaluating their effectiveness and suggests that researchers conducting clinical trials of these therapies may not have difficulties recruiting patients.
Algorithms for optimizing drug therapy
Authors: Wanger Peter , Martin Lene
Published: July 2004

Background

Drug therapy has become increasingly efficient, with more drugs available for treatment of an ever-growing number of conditions. Yet, drug use is reported to be sub optimal in several aspects, such as dosage, patient's adherence and outcome of therapy. The aim of the current study was to investigate the possibility to optimize drug therapy using computer programs, available on the Internet.

Methods

One hundred and ten officially endorsed text documents, published between 1996 and 2004, containing guidelines for drug therapy in 246 disorders, were analyzed with regard to information about patient-, disease- and drug-related factors and relationships between these factors. This information was used to construct algorithms for identifying optimum treatment in each of the studied disorders. These algorithms were categorized in order to define as few models as possible that still could accommodate the identified factors and the relationships between them. The resulting program prototypes were implemented in HTML (user interface) and JavaScript (program logic).

Results

Three types of algorithms were sufficient for the intended purpose. The simplest type is a list of factors, each of which implies that the particular patient should or should not receive treatment. This is adequate in situations where only one treatment exists. The second type, a more elaborate model, is required when treatment can by provided using drugs from different pharmacological classes and the selection of drug class is dependent on patient characteristics. An easily implemented set of if-then statements was able to manage the identified information in such instances. The third type was needed in the few situations where the selection and dosage of drugs were depending on the degree to which one or more patient-specific factors were present. In these cases the implementation of an established decision model based on fuzzy sets was required. Computer programs based on one of these three models could be constructed regarding all but one of the studied disorders. The single exception was depression, where reliable relationships between patient characteristics, drug classes and outcome of therapy remain to be defined.

Conclusion

Algorithms for optimizing drug therapy can, with presumably rare exceptions, be developed for any disorder, using standard Internet programming methods.
Color Doppler imaging of cervicocephalic fibromuscular dysplasia
Authors: Arning Christian , Grzyska Ulrich
Published: July 2004

Background

Fibromuscular dysplasia (FMD) is a possible cause of stroke, especially in middle-aged women. However, only few reports are available on ultrasonographic detection and monitoring.

Methods

Among the 15,000 patients who underwent color Doppler imaging (CDI) of the cervicocephalic arteries during the study period, all cases fulfilling ultrasound criteria of FMD were included into the case series. Criteria of FMD were: 1. Segmental string-of-beads pattern, 2. Localization in the distal extracranial part of internal carotid artery (ICA) or vertebral artery (VA), and 3. (optional): Direct and/or indirect criteria of stenosis.

Results

CDI detected FMD in 39 vessels (37 ICA and 2 VA segments) of 21 patients. 16 patients had bilateral manifestation on ICA, one of those also on VA, bilaterally. CDI disclosed 4 symptomatic high-grade ICA stenoses, 3 of them underwent endovascular treatment. 5 patients with moderate symptomatic ICA stenoses got medical treatment. In 6 patients FMD was the most likely cause of headache and in one patient FMD was diagnosed as a cause of vertigo.

Conclusions

CDI may be used for detection of cervicocephalic FMD. Due to the unfavourable localisation of FMD for CDI, the sensitivity of CDI is lower in comparison to angiography. However, high-grade FMD stenoses that require invasive treatment can be recognized on the basis of indirect hemodynamic criteria.
Cardiotoxicity in rats induced by methidathion and ameliorating effect of vitamins E and C
Authors: Yavuz Turhan , Altuntas Irfan , Delibas Namik , Yildirim Bekir , Candir Ozden , Corâ Ahmet , Karahan Nermin , Ibrisim Erdogan , Kutsal Ali
Published: July 2004

We have examined the effect of subchronic methidathion (MD) administration on heart damage, and have evaluated possible ameliorating effects of a combination of vitamins E and C against MD toxicity. The experimental groups were: control group, rats treated with 5 mg/kg MD and rats treated with 5 mg/kg body weight MD plus vitamin E and vitamin C (MD+Vit). The groups were given MD by gavage 5 days a week for four weeks at a dose level of 5 mg/kg/day (MD and MD+Vit) by using corn oil as the vehicle. Vitamin E and vitamin C were injected at doses of 50 mg/kg i.m. and 20 mg/kg i.p., respectively, after the treatment with MD in the MD+Vit group. The levels of malondialdehyde (MDA) were determined in the heart tissue, and the levels of cardiac troponin I (TnI) in serum. An autoanalyser was used to determine the serum activities of cholinesterase (ChE). Histopathological examination was carried out in the heart tissue. MDA significantly increased in the MD group as compared to controls (P <0.01). When MD was given concurrently with vitamins E and C, the increase in MDA was significantly less (P <0.01). ChE activity significantly decreased in the MD group as compared to controls (P <-0.01). When MD was given concurrently with vitamins E and C, the decrease in ChE activity was significantly higher (P <-0.05). The serum TnI levels significantly increased in the MD group as compared to controls (P <-0.01). When MD was given concurrently with vitamins E and C, the increase in the serum TnI was significantly less (P <-0.01). MD caused the diffuse loss of striation and myocytolysis of the cardiomyocytes, whereas the combination of vitamins E and C caused a significant decrease in these effects of MD. In conclusion, subchronic MD administration caused heart damage and, in addition, treatment with a combination of vitamins E and C after the administration of MD reduced heart damage caused by MD.
Four children with colchicine poisoning
Authors: Ataş Bülent , Çaksen Hüseyin , Tuncer Oğuz , Kirimi Ercan , Akgün Cihangir , Odabaş Dursun
Published: July 2004

Colchicine poisoning is a rare event. It is characterized by multiorgan involvement and by poor prognosis associated with overdose. In this article we present four children with colchicine poisoning to emphasize that colchicine poisoning has a large spectrum in childhood. The children's ages ranged between 1 year and 3.5 years. The ingested dosage of colchicine was between 0.37 and 1.72 mg/kg. Most of the findings of colchicine poisoning such as gastrointestinal symptoms, hepatotoxicity, cardiotoxicity, bone marrow suppression, hypocalcaemia and hair loss were diagnosed in our patients. Two children receiving 0.37 mg/kg and 1 mg/kg colchicine and admitted 13 and 19 hours after poisoning, respectively, died. Our findings suggest that in addition to amounts of the drug, mortality was also related to the duration between drug ingestion and admission to hospital.