bluuebunny/crossref_metadata_2025 huggingface dataset:
Worksite health promotion using individual counselling and the effectiveness on sick leave; results of a randomised controlled trial
Authors: Proper K I , van der Beek A J , Hildebrandt V H , Twisk J W R , van Mechelen W
Published: February 2004

Aims:To investigate the effectiveness of a worksite health promotion programme by individual counselling on sick leave.

Methods:Three municipal services of Enschede, the Netherlands, participated in this trial. A total of 299 civil servants were measured at baseline and were randomised by cluster into the intervention (n = 131) or the control group (n = 168). During nine months, subjects in the intervention group received a total of seven consultations, particularly aimed at increasing their physical activity level and improving their dietary habits. Both the intervention and the control subjects received written information as to several lifestyle factors. Sick leave data regarding the nine month intervention period (from May until January) were collected from each municipal service’s personnel department. In addition, sick leave data concerning the nine month period pre- and post-intervention were collected. Sick leave data were analysed using multilevel analysis.

Results:For both groups, the mean sick leave rate during the intervention increased compared to before the intervention. After the intervention period, the control group increased even more (from 22.9 to 27.6 days), whereas the intervention group slightly decreased (from 21.5 to 20.5 days). Median values of sick leave rate decreased for both groups. No statistically significant intervention effect was found. In both groups, the mean sick leave frequency slightly decreased over time (intervention effects were not significant).

Conclusions:Results showed no significant effect of individual counselling on sick leave. Continued research investigating the effectiveness of this individual counselling programme on several health related outcomes is useful to clarify the trend observed in sick leave.
Occupations and exposures in the work environment as determinants for rheumatoid arthritis
Authors: Olsson Å Reckner , Skogh T , Axelson O , Wingren G
Published: February 2004

Background and Aims:Several occupational categories have been associated with rheumatoid arthritis (RA); this study was conducted to further evaluate these associations.

Methods:Lifelong occupational history together with exposure experiences were collected through a postal questionnaire answered by 293 incident cases and 1346 population based referents. Occupational determinants were evaluated through stratified and multivariate analyses; pooled analyses with previously gathered data on 422 prevalent cases and 858 referents were also performed.

Results:In both materials, significantly increased logistic odds ratios (LORs) were seen for male conductors, freight and transport workers (LOR 17.8, 95% CI 1.5 to 207.8 and LOR 4.7, 95% CI 1.4 to 16.3, respectively), and farmers and farm workers (LOR 2.4, 95% CI 1.1 to 5.2, and LOR 2.2, 95% CI 1.3 to 3.5, respectively). Among women, increased LORs were seen in the separate and the pooled material for printmakers and process engravers (LOR 5.5, 95% CI 0.9 to 32.6, and LOR 3.0, 95% CI 0.9 to 10.3, respectively). Increased risks were seen in both materials for men exposed to asbestos (LOR 2.5, 95% CI 1.0 to 6.8, and LOR 1.6, 95% CI 0.8 to 3.3, respectively), and vibrations (LOR 2.0, 95% CI 0.9 to 4.4, and LOR 2.2, 95% CI 1.3 to 3.8, respectively). The risk for RA increased with increasing duration of exposure to vibrations and mineral dust, respectively.

Conclusions:There was evidence of a causal relation between exposures to vibrations and mineral dust and development of RA among men. Occupational factors seem to be aetiologically more important for men, and most occupations at risk involve multiple exposures. Several exposures associated with an increased risk for RA are frequent among farmers, and some of the occupations at risk include exposure to organic dust.
Cumulative exposure to dust and gases as determinants of lung function decline in tunnel construction workers
Authors: Bakke B , Ulvestad B , Stewart P , Eduard W
Published: February 2004

Aims:To study the relation between lung function decrease and cumulative exposure to dust and gases in tunnel construction workers.

Methods:A total of 651 male construction workers (drill and blast workers, tunnel concrete workers, shotcreting operators, and tunnel boring machine workers) were followed up by spirometric measurements in 1989–2002 for an average of six years. Outdoor concrete workers, foremen, and engineers served as a low exposed referent population.

Results:The between worker component of variability was considerably reduced within the job groups compared to the whole population, suggesting that the workers within job groups had similar exposure levels. The annual decrease in FEV1in low-exposed non-smoking workers was 21 ml and 24 ml in low-exposed ever smokers. The annual decrease in FEV1in tunnel construction workers was 20–31 ml higher than the low exposed workers depending on job group for both non-smokers and ever smokers. After adjustment for age and observation time, cumulative exposure to nitrogen dioxide showed the strongest association with a decrease in FEV1in both non-smokers, and ever smokers.

Conclusion:Cumulative exposure to nitrogen dioxide appeared to be a major risk factor for lung function decreases in these tunnel construction workers, although other agents may have contributed to the observed effect. Contact with blasting fumes should be avoided, diesel exhaust emissions should be reduced, and respiratory devices should be used to protect workers against dust and nitrogen dioxide exposure.
SQUARK AND SLEPTON MASSES AS PROBES OF SUPERSYMMETRIC SO(10) UNIFICATION
Authors: ANANTHANARAYAN B. , PANDITA P. N.
Published: February 2004

We carry out an analysis of the non-universal supersymmetry breaking scalar masses arising in SO(10) supersymmetric unification. By considering patterns of squark and slepton masses, we derive a set of sum rules for the sfermion masses which are independent of the manner in which SO(10) breaks to the Standard Model gauge group via its SU(5) subgroups. The phenomenology arising from such non-universality is unaffected by the symmetry breaking pattern, so long as the breaking occurs via any of the SU(5) subgroups of the SO(10) group.
FLAVOR MIXING AND CP VIOLATION OF MASSIVE NEUTRINOS
Authors: XING ZHI-ZHONG
Published: February 2004

We present an overview of recent progress in the phenomenological study of neutrino masses, lepton flavor mixing and CP violation. We concentrate on the model-independent properties of massive neutrinos, both in vacuum and in matter. Current experimental constraints on the neutrino mass spectrum and the lepton flavor mixing parameters are summarized. The Dirac- and Majorana-like phases of CP violation, which are associated respectively with the long-baseline neutrino oscillations and the neutrinoless double beta decay, are discussed in detail. The seesaw mechanism, the leptogenesis scenario and the strategies to construct lepton mass matrices are briefly described. The features of flavor mixing between one sterile neutrino and three active neutrinos are also explored.
REVIEW OF THE PHENOMENOLOGY OF NONCOMMUTATIVE GEOMETRY
Authors: HINCHLIFFE I. , KERSTING N. , MA Y. L.
Published: February 2004

We present a pedagogical review of particle physics models that are based on the noncommutativity of space–time, [Formula: see text], with specific attention to the phenomenology these models predict in particle experiments either in existence or under development. We summarize results obtained for high energy scattering such as would occur, for example, in a future e+e-linear collider with [Formula: see text], as well as low energy experiments such as those pertaining to elementary electric dipole moments and other CP violating observables, and finally comment on the status of phenomenological work in cosmology and extra dimensions.
COLOR CONFINEMENT AND FINITE TEMPERATURE QCD PHASE TRANSITION
Authors: PANDEY H. C. , CHANDOLA H. C. , DEHNEN H.
Published: February 2004

We study an effective theory of QCD in which the fundamental variables are dual magnetic potentials coupled to the monopole field. Dual dynamics are then used to explain the properties of QCD vacuum at zero temperature as well as at finite temperatures. At zero temperature, the color confinement is realized through the dynamical breaking of magnetic symmetry, which leads to the magnetic condensation of QCD vacuum. The flux tube structure of SU(2) QCD vacuum is investigated by solving the field equations in the low energy regimes of the theory, which guarantees dual superconducting nature of the QCD vacuum. The QCD phase transition at finite temperature is studied by the functional diagrammatic evaluation of the effective potential on the one-loop level. We then obtained analytical expressions for the vacuum expectation value of the condensed monopoles as well as the masses of glueballs from the temperature dependent effective potential. These nonperturbative parameters are also evaluated numerically and used to determine the critical temperature of the QCD phase transition. Finally, it is shown that near the critical temperature (Tc≃0.195 GeV ), continuous reduction of vacuum expectation value (VEV) of the condensed monopoles caused the disappearance of vector and scalar glueball masses, which brings a second order phase transition in pure SU(2) gauge QCD.
HAMILTON–JACOBI TREATMENT OF CONSTRAINED SYSTEMS
Authors: NAWAFLEH KHALED I. , RABEI EQAB M. , GHASSIB HUMAM B.
Published: February 2004

One approach for solving mechanical problems of constrained systems using the Hamilton–Jacobi formulation is examined. The Hamilton–Jacobi function is obtained in the same manner as for regular systems. This is used to determine the solutions of the equations of motion for constrained systems.
Interactions in hypoxic and hypercapnic breathing are genetically linked to mouse chromosomes 1 and 5
Authors: Tankersley Clarke G. , Broman Karl W.
Published: February 2004

The genetic basis for differences in the regulation of breathing is certainly multigenic. The present paper builds on a well-established genetic model of differences in breathing using inbred mouse strains. We tested the interactive effects of hypoxia and hypercapnia in two strains of mice known for variation in hypercapnic ventilatory sensitivity (HCVS); i.e., high gain in C57BL/6J (B6) and low gain in C3H/HeJ (C3) mice. Strain differences in the magnitude and pattern of breathing were measured during normoxia [inspired O2fraction (FiO2) = 0.21] and hypoxia (FiO2= 0.10) with mild or severe hypercapnia (inspired CO2fraction = 0.03 or 0.08) using whole body plethysmography. At each level of FiO2, the change in minute ventilation (V̇e) from 3 to 8% CO2was computed, and the strain differences between B6 and C3 mice in HCVS were maintained. Inheritance patterns showed potentiation effects of hypoxia on HCVS (i.e., CO2potentiation) unique to the B6C3F1/J offspring of B6 and C3 progenitors; i.e., the change in V̇e from 3 to 8% CO2was significantly greater ( P < 0.01) with hypoxia relative to normoxia in F1 mice. Linkage analysis using intercross progeny (F2; n = 52) of B6 and C3 progenitors revealed two significant quantitative trait loci associated with variable HCVS phenotypes. After normalization for body weight, variation in V̇e responses during 8% CO2in hypoxia was linked to mouse chromosome 1 (logarithm of the odds ratio = 4.4) in an interval between 68 and 89 cM (i.e., between D1Mit14 and D1Mit291). The second quantitative trait loci linked differences in CO2potentiation to mouse chromosome 5 (logarithm of the odds ratio = 3.7) in a region between 7 and 29 cM (i.e., centered at D5Mit66). In conclusion, these results support the hypothesis that a minimum of two significant genes modulate the interactive effects of hypoxia and hypercapnia in this genetic model.
Vehicle trajectory control using the fuzzy logic controller
Authors: Cho H , Yi S-J
Published: February 2004

When the driver suddenly depresses the brake pedal under critical conditions, the desired trajectory of the vehicle can be changed. In this study, the vehicle dynamics and fuzzy logic controller are used to control the vehicle trajectory. The dynamic vehicle model consists of the engine, the rotational wheel, chassis, tyres and brakes. The engine model is derived from the engine experimental data. The engine torque makes the wheel rotate and generates the angular velocity and acceleration of the wheel. The dynamic equation of the vehicle model is derived from the top-view vehicle model using Newton's second law. The Pacejka tyre model formulated from the experimental data is used. The fuzzy logic controller is developed to compensate for the trajectory error of the vehicle. This fuzzy logic controller individually acts on the front right, front left, rear right and rear left brakes and regulates each brake torque. The fuzzy logic controlling each brake works to compensate for the trajectory error on the split-μ road conditions to maintain the desired trajectory.
Injector control logic for a liquid-phase liquid petroleum gas injection engine
Authors: Cho Sungwoo , Min Kyoungdoug
Published: February 2004

Fuel in a liquid-phase liquefied petroleum gas (LPG) injection engine is di cult to meter finitely because of LPG fuel characteristics such as flash boiling and variations in fuel composition, injection pressure and density. This study presents an injector control logic for a liquid-phase LPG injection engine; the control logic was developed through a series of experiments. A procedure was conceived using a gas analyser to calibrate the injection quantity promptly and precisely. Injectors are calibrated with four fuel compositions under various temperatures and injection pressures. A mathematical flowrate model is developed on the basis of the calibration data. This model is converted into an injector control logic, which is finally programmed into an electronic control unit (ECU). The verification experiment showed that the logic could precisely control the air-fuel ratio, regardless of fuel composition, fuel temperature and injection pressure.
The impact of adaptive cruise control systems on highway safety and traffic flow
Authors: Wang J , Rajamani R
Published: February 2004

This paper deals with the design of new adaptive cruise control (ACC) systems that can improve traffic flow while at the same time ensuring safe operation on today's highways. ACC systems are commonly designed to maintain a constant time-gap (CTG) between vehicles during vehicle- following. In this paper, a new inter-vehicle spacing policy in which the inter-vehicle spacing is a non-linear function of vehicle speed is developed. The new spacing policy, referred to as a variable time-gap (VTG) policy, is shown analytically to lead to better traffic flow and a higher highway capacity. Practical advantages of using the new spacing policy are demonstrated through traffic simulations. However, a detailed analysis of safety shows that the traditional CTG policy is superior in several scenarios. The VTG policy is then modified by explicitly taking inter-vehicle relative velocity into account in the definition of desired spacing. The resulting new spacing policy is shown to retain the advantages of stable traffic flow and a higher capacity while providing the same level of safety as the CTG policy.
Impact of thin-walled high-strength steel structural sections
Authors: Schneider F , Jones N
Published: February 2004

An experimental programme is reported which examines the progressive collapse behaviour of some thin-walled closed-section structural sections made from high-strength steels under quasi- static and impact axial loads. A comparison is made with theoretical formulae, which have been used successfully for predicting the behaviour of mild steel thin-walled structures.

Ten quasi-static crush tests and 46 impact tests were conducted on spot-welded top-hat and laser- welded square sections. The thin-walled sections were made from two different types of high-strength steel and one mild steel, the mechanical properties of which were determined experimentally from quasi-static and dynamic tensile tests. Although no specific change in the collapse mode was observed, the limited weight-specific energy absorption e ciency of the high-strength steels under dynamic loadings hinders the weight-reduction potential of crashworthy designs. An unexpected difference in the structural effectiveness of spot-welded top-hat sections made from mild steels and high-strength steels was identified, but was not present for similar square sections. This difference further accentuated the loss in the advantage of high-strength steels over mild steels, especially for spot-welded top-hat sections, and led to differences in the agreement between the experimental results and the theoretical predictions.
Performance benchmarks of pressure and fibre optics sensors for natural gas engine control
Authors: Nwagboso C O , Pendlebury M A , Mukarram S K
Published: February 2004

Traditionally, the automotive industry has been using piezoelectric transducers for measuring cylinder pressure due to their higher frequency and relatively small size. However, there is the need to develop sensors that are capable of measuring other combustion parameters. An optical fibre sensor can give accurate readings of combustion characteristics (e.g. combustion species concentrations) with high temporal resolution within each engine cycle. Engine control systems incorporating these sensors can reduce harmful emissions levels and improve fuel economy as well as performing parametric monitoring for predicting emission levels. A strategic combination of the fibre optic sensor as part of the control system can be deployed in order to provide these benefits.

This paper presents the design of a novel sensing scheme with a fibre optic sensory system capable of monitoring the combustion event as part of the natural gas engine control system with a minimal invasive technique. The robustness of the optical sensory system is compared with a pressure sensory signal and is used to analyse mass fraction burn and heat release. An integrated ignition controller is presented that will enable the ignition angle to be modified based on the measured optical combustion signal with a control technique to provide an optimal management of the engine performance. The technique presented in this paper was developed as part of a research and development programme. However, the results will also make a significant contribution to further deployment of the technology in production vehicles.
The effect of air-fuel ratio control strategies on nitrogen compound formation in three-way catalysts
Authors: Defoort M , Olsen D , Willson B
Published: February 2004

The ability of three-way catalysts (TWCs) to effectively remove CO and NOx from the exhaust is directly controlled by the air-fuel ratio at which the accompanying engine is operated. In a stoichiometric engine, small variations in the air-fuel ratio have large effects on the catalyst performance. These effects include wide variations in removal efficiencies and catalytic production of ammonia. The effect of the air-fuel ratio on catalysts has been well studied on automotive engines; these studies show the importance of maintaining an air-fuel ratio close to stoichiometric conditions. In automotive systems a ‘dithering’ technique is used in which the air-fuel ratio is modulated to widen the window of control. The effect of dithering on industrial engines has not been studied. A research programme was conducted to evaluate the effects of the air-fuel ratio on the performance of three-way catalysts operating on natural gas-fuelled industrial engines, the test programme aims at optimizing the engine based on the performance of the catalyst. This project has shown that dithering is an effective technique for enhancing the performance of TWCs on industrial engines. These results show that the allowable air-fuel ratio deviations are much larger with dithering and that the production of ammonia is significantly reduced.
Imaging molecular interactions by multiphoton FLIM
Authors: Peter Marion , Ameer‐Beg Simon M.
Published: February 2004

Summry— The spatio‐temporal localisation of molecular interactions within cells in situ and in particular in vivo is of great importance in elucidating the key mechanisms in regulation of fundamental process within the cell. Measurements of such near‐field localisation of protein complexes may be achieved by the detection of fluorescence (or Förster) resonance energy transfer (FRET) between protein‐conjugated fluorophores. The use of fluorescence lifetime imaging microscopy (FLIM) to determine both intra‐ and intermolecular FRET has become an important and powerful technique for investigating biological systems. In this review we focus on the time‐domain‐based fluorescence lifetime sensing, using time‐correlated single photon counting multiphoton microscopy. We give a description of the technique, including data acquisition and analysis, and discuss the different biological applications of this technology.
Heart rate variability in severe right or left heart failure: the role of pulmonary hypertension and resistances
Authors: Fauchier Laurent , Babuty Dominique , Melin Alexandre , Bonnet Pierre , Cosnay Pierre , Fauchier Jean Paul
Published: February 2004

Background:

The decrease in heart rate variability (HRV) might be related to the hemodynamic status in heart failure. However, HRV in patients with severe isolated right heart failure has not been extensively studied.

Aims:

This study compared HRV in patients with congestive heart failure (CHF) and in patients with isolated right heart failure.

Methods:

Time and frequency domain analysis of HRV on 24‐h ECG recording was assessed in 15 healthy subjects and in two groups of patients with severe heart failure awaiting heart or heart/lung transplantation. These were 15 patients with CHF due to idiopathic dilated cardiomyopathy (IDC) and 10 patients with isolated right heart failure due to primary pulmonary hypertension (PPH).

Results:

Measurement of HRV were significantly decreased in both groups of patients compared with the control group. Patients with IDC had higher pulmonary capillary wedge pressure than patients with PPH (P=0.04) but lower pulmonary artery pressure and lower pulmonary vascular resistance (PVR) (P<0.0001). However, all the measurements of HRV were significantly lower in patients with IDC than in patients with PPH (range 22–77%, P<0.05 to P<0.01). None of the HRV measurements correlated with filling pressure measurements.

Conclusions:

The increase in pulmonary vascular resistance in heart failure is not the main causal factor behind a decrease in HRV.
QT dispersion correlates to myocardial viability assessed by dobutamine stress echocardiography in patients with severely depressed left ventricular function due to coronary artery disease
Authors: Bountioukos Manolis , Schinkel Arend F.L. , Poldermans Don , Rizzello Vittoria , Vourvouri Eleni C. , Krenning Boudewijn J. , Biagini Elena , Roelandt Jos R.T.C. , Bax Jeroen J.
Published: February 2004

Background:

T dispersion is prolonged in numerous cardiac diseases, representing a general repolarization abnormality.

Aim:

To evaluate the influence of viable myocardium on QT dispersion in patients with severely depressed left ventricular (LV) function due to coronary artery disease.

Methods and results:

103 patients with ischemic cardiomyopathy (LV ejection fraction [EF]: 25±6%) were studied. Patients underwent 12‐lead electrocardiography to assess QT dispersion, and two‐dimensional echocardiography to identify segmental dysfunction. Dobutamine stress echocardiography (DSE) was then performed to detect residual viability. Resting echo demonstrated 1260 dysfunctional segments; of these, 476 (38%) were viable. Substantial viability (≥4 viable segments on DSE) was found in 62 (60%) patients. QT dispersion was lower in these patients, than in patients without viability (55±17 ms vs. 65±22 ms, P=0.012). Viable segments negatively correlated to QT dispersion (r=−0.333, P=0.001). In contrast, there was no correlation between LVEF and QT dispersion (r=−0.001, P=NS).

Conclusions:

There is a negative correlation between QT dispersion and the number of viable segments assessed by DSE. Patients with severely depressed LV function and a low QT dispersion probably have a substantial amount of viable tissue. Conversely, when QT dispersion is high, the likelihood of substantial viability is reduced.
Left–right asymmetric ventricular expression of CARP in the piglet heart: regional response to experimental heart failure
Authors: Torrado Mario , López Eduardo , Centeno Alberto , Castro‐Beiras Alfonso , Mikhailov Alexander T.
Published: February 2004

Background and aim:

Cardiac ankyrin repeat protein (CARP), whose expression is down‐regulated in response to doxorubicin (Dox) in vitro, has been proposed to be a marker of experimentally‐induced cardiac hypertrophy in rodent models. In piglets, the rapid hypertrophy rate of the left ventricle (LV) as compared to that of the right ventricle (RV) represents a natural model of asymmetric ventricular enlargement. We tested whether CARP expression correlates with postnatal ventricular hypertrophy and to what extent CARP can be sensitive to Dox treatment in vivo.

Methods:

CARP mRNA and protein levels were quantified (by Northern blot hybridization, semi‐quantitative RT‐PCR and Western blot) in the piglet heart, both during early postnatal development and upon Dox‐induced cardiomyopathy (Dox‐CM).

Results:

The study revealed: (1) significantly augmented CARP mRNA and protein levels in the LV compared to the RV resulting in left vs. right asymmetry in ventricular CARP expression throughout early postnatal development; (2) dose‐ and chamber‐dependent CARP mRNA and protein enrichment in ventricular myocardium in response to Dox; and (3) abolishment of asymmetric patterns of ventricular CARP expression at heart failure resulting from Dox‐CM.

Conclusions:

(1) CARP is differentially regulated in the LV and RV during both postnatal development and disease; and (2) monitoring of ventricular CARP expression patterns can be used for further analysis of transition from compensated to overt heart failure.
Beneficial effects of carvedilol on angiotensin‐converting enzyme activity and renin plasma levels in patients with chronic heart failure
Authors: Solal Alain Cohen , Jondeau Guillaume , Beauvais Florence , Berdeaux Alain
Published: February 2004

Objective:

To assess the effects of carvedilol treatment on the renin–angiotensin system in patients with chronic heart failure (CHF).

Background:

Carvedilol improves survival of patients suffering from CHF but the effects of the drug on angiotensin‐converting enzyme (ACE) activity, renin and aldosterone are not well characterized in patients receiving an ACE inhibitor.

Methods:

A randomized, multicenter, double‐blind, 6‐month, placebo‐controlled study of carvedilol vs. placebo was conducted in 64 CHF patients. Circulating levels of ACE activity, active renin and aldosterone as well as left ventricular diameters and ejection fraction by echography were assessed.

Results:

During the study, left ventricular ejection fraction increased from 25±11% to 31±12% with carvedilol and from 27±12% to 28±12% with placebo (P=0.03). This beneficial effect was associated with marked blunting of active renin secretion (−53% in the carvedilol group vs.−13% in the placebo group, P=0.04). ACE activity was reduced by 30% in the carvedilol group (P=0.07 vs. placebo). Aldosterone was not changed.

Conclusion:

Carvedilol markedly reduced the increase in active renin observed with time despite ACE‐inhibitors and tended to decrease ACE activity. These findings may in part explain the beneficial actions of carvedilol and highlights the profound effect of betablockade on renin in patients already receiving ACE‐inibitors.
Biological variation of the natriuretic peptides and their role in monitoring patients with heart failure
Authors: Wu Alan H.B. , Smith Andrew
Published: February 2004

Background:

B‐type natriuretic peptide (BNP) and the inactive metabolite NT‐proBNP are proven tests for diagnosis and staging of severity for patients with heart failure. However, the utility of these biomarkers for monitoring the success of drug therapy remains to be determined. Results of longitudinal studies on serial blood testing must be linked to overall patient morbidity and mortality outcomes. We previously determined the 8‐week biological variability (BV) of BNP and NT‐proBNP assays in healthy subjects and the 1‐day BV for BNP alone in patients with compensated and stable heart failure. From these studies, the percent statistical change in serial samples of approximately 100% difference was estimated (95% confidence).

Methods:

We applied the biological variability concepts to the serial results of BNP and NT‐proBNP collected from patients with heart failure and compared the performance of these two markers.

Results:

While there are minor differences in the results between the assays from one time period to another, the overall interpretation of results are essentially identical. Moreover, the majority of individual serial time points are not significantly different from the previous value.

Conclusion:

Frequent testing (e.g. daily) for BNP and NT‐proBNP to monitor therapy for patients with CHF is not indicated, as overall changes require several days to become evident.
N‐terminal probrain natriuretic peptide (NT‐proBNP) in the emergency diagnosis and in‐hospital monitoring of patients with dyspnoea and ventricular dysfunction
Authors: Bayés‐Genís Antoni , Santaló‐Bel Miquel , Zapico‐Muñiz Edgar , López Laura , Cotes Carlos , Bellido Jesús , Leta Rubén , Casan Pere , Ordóñez‐Llanos Jordi
Published: February 2004

Objective:

To evaluate the utility of NT‐proBNP in the emergency diagnosis and in‐hospital monitoring of patients with acute dyspnoea and ventricular dysfunction.

Background:

Misdiagnosis of heart failure (HF) is common in the urgent care setting using clinical diagnostic tests. Reports show that BNP is useful to diagnose HF in patients with acute dyspnoea.

Methods:

Prospective study of 100 patients attending the Emergency Department (ED) for acute dyspnoea. Final diagnosis was determined on the basis of ED data sheets, echocardiography and pulmonary function tests. NT‐proBNP levels were obtained on admission, at 24 h and at day 7.

Results:

Patients with ventricular dysfunction were sub‐classified into decompensated HF and masked HF, defined as HF with concomitant signs of pulmonary disease. Decompensated and masked HF patients had significantly higher NT‐proBNP values than patients with non‐cardiac dyspnoea (normal ventricular function) (920±140 and 978±363 vs. 50±15 pmol/L; P<0.001 and P<0.01, respectively). The mean area under the ROC curve for NT‐proBNP was 0.957 (95% CI, 0.918 to 0.996, P<0.001). In multiple logistic‐regression analysis NT‐proBNP>115 pmol/l was the strongest independent predictor of ventricular dysfunction (odds ratio 45.4; 95% CI: 4.5–452.3). At day 7, a significant and similar reduction in NT‐proBNP was observed in the two groups of patients with ventricular dysfunction (P<0.001 vs. admission values), but complete clinical resolution was less frequent in masked HF patients (P<0.05 vs. decompensated HF).

Conclusions:

NT‐proBNP is a new candidate marker for the detection and exclusion of ventricular dysfunction in patients attending the ED for acute dyspnoea. NT‐proBNP may also serve to monitor outcome during hospitalization.
Reduced readmission rate for alternating diagnoses of heart failure and pulmonary disease after implementation of B‐type natriuretic peptide testing
Authors: Wu Alan H.B. , Harrison Alex , Maisel Alan S.
Published: February 2004

Background:

Patients with heart failure (HF) or pulmonary diseases (PD) present with similar symptoms. Effective disease management requires an accurate diagnosis. B‐type natriuretic peptide (BNP) is increased in patients with HF and is normal in PD patients without cardiac involvement.

Objective:

To determine if the readmission rate for patients with either HF or PD who later present with the alternate diagnosis (PD or HF) is decreased with the implementation of BNP testing at one hospital.

Methods:

We retrospectively determined the impact of BNP testing on reducing diagnostic ambiguities for patients admitted to an emergency department (ED) with these diseases. We compared a HF DRG (Diagnostic Related Group) (#428) and PD DRGs (#480–496) before vs. 1 and 2 y after implementation of BNP testing.

Results:

In a 12‐month period before BNP, there were 42 total visits (15 cases) where a patient presented with a HF DRG and returned within 6 months with a PD DRG, and 41 visits (14 cases) where there was a PD→HF readmission. One year after BNP implementation, the corresponding number of visits decreased 52% to 20 visits (15 cases) for HF→PD, and 73% to 11 visits (8 cases) for PD→HF readmissions. A similar reduction in readmissions was observed in the second year after BNP testing. The total number of HF and PD cases in 1999 (1029 patients) was similar to 2001 (985), and was higher in 2002 (1350) during these time intervals. The ED length‐of‐stay (LOS) was slightly higher for the HF→PD cases with BNP testing, whereas there was no change in LOS for the PD→HF cases.

Conclusion:

We hypothesize that prior to BNP implementation, there may have been diagnostic ambiguities in the initial diagnosis of HF or PD, which contributed to a repeat visit for the alternate diagnosis (PD or HF). With BNP testing, the apparent number of inappropriate visits decreased. Reducing unnecessary ED admissions helps justify the costs for implementing BNP testing in the hospital.
Essential biochemistry and physiology of (NT‐pro)BNP
Authors: Hall Christian
Published: February 2004

Brain natriuretic peptide (BNP) is a 32 amino acid cardiac natriuretic peptide hormone originally isolated from porcine brain tissue. The human BNP gene is located on chromosome 1 and encodes the prohormone proBNP. The biologically active BNP and the remaining part of the prohormone, NT‐proBNP (76 amino acids) can be measured by immunoassay in human blood. Cardiac myocytes constitute the major source of BNP related peptides. The main stimulus for peptide synthesis and secretion is myocyte stretch. Recently, cardiac fibroblasts have also been shown to produce BNP. Other neurohormones may stimulate cardiac BNP production in different cardiac cell types. In contrast to atrial natriuretic peptides (ANP/NT‐proANP), which originate mainly from atrial tissue, BNP related peptides are produced mainly from ventricular myocytes. Ventricular (NT‐pro)BNP production is strongly upregulated in cardiac failure and locally in the area surrounding a myocardial infarction. In peripheral organs BNP binds to the natriuretic peptide receptor type A causing increased intracellular cGMP production. The biological effects include diuresis, vasodilatation, inhibition of renin and aldosterone production and of cardiac and vascular myocyte growth. In mice BNP gene knockout leads to cardiac fibrosis, gene over‐expression to hypotension and bone malformations. BNP is cleared from plasma through binding to the natriuretic peptide clearance receptor type C, but it seems relatively resistant to proteolysis by neutral endopeptidase NEP 24.11. Clearance mechanisms for NT‐proBNP await further study. While the plasma concentration of NT‐proBNP and BNP is approximately equal in normal controls, NT‐proBNP plasma concentration is 2–10 times higher than BNP in patients with heart failure. This relative change in peptide levels may be explained by shifts in cardiac secretion and/or clearance mechanisms.
N‐terminal pro brain natriuretic peptide in arterial hypertension—a marker for left ventricular dimensions and prognosis
Authors: Hildebrandt Per , Boesen Mikael , Olsen Michael , Wachtell Kristian , Groenning Bjoern
Published: February 2004

In arterial hypertension risk factor evaluation, including LV mass measurements, and risk stratification using risk charts or programs, is generally recommended. In heart failure NT‐proBNP has been shown to be a marker of LV dimensions and of prognosis. If the same diagnostic and prognostic value is present in arterial hypertension, risk factor evaluation would be easier. In 36 patients with arterial hypertension, electrocardiographic LV hypertrophy and preserved left ventricular function, NT‐proBNP was eight‐fold higher than in healthy subjects. The log NT‐proBNP correlated with LV mass index (R=0.47, P=0.0002) measured by magnetic resonance imaging. In other subjects with arterial hypertension a significant but weak correlation to diastolic properties has been demonstrated. As for prognosis, a recent study in patients with hypertension, electrocardiographic left ventricular hypertrophy and preserved LV function demonstrated that NT‐proBNP was a very strong prognostic marker, especially combined with a history of cardiovascular disease. Patients with high NT‐proBNP and known cardiovascular disease had a seven‐fold increase in CV events compared to patients with low NT‐proBNP and no CV disease, while patients with either high NT‐proBNP or CV disease had a three–four‐fold increased risk. In conclusion NT‐proBNP predicts LV mass in hypertensive patients and is a very strong prognostic marker in these patients. This could indicate a use of NT‐proBNP in the future for risk stratification and perhaps monitoring of treatment in patients with arterial hypertension.
Brain and other natriuretic peptides: molecular aspects
Authors: Vanderheyden Marc , Bartunek Jozef , Goethals Marc
Published: February 2004

Natriuretic peptides have emerged as important candidates for development of diagnostic tools and therapeutic agents in cardiovascular disease. The family contains of three major peptides—ANP, BNP, CNP—that participate in cardiovascular and cardiorenal homeostasis. Each of these natriuretic peptides binds differentially to specific receptors that signal through different mechanisms. They are cleared enzymatically by neutral endopeptidase as well as by receptor‐mediated endocytosis. Because of its fast induction and specific expression in overt heart failure, BNP seems the most promising natriuretic peptide. It is predominantly synthesized in the cardiac ventricles, released as pre‐proBNP and then enzymatically cleaved to BNP and the N‐terminal portion of BNP(NT‐proBNP). Blood measurements of BNP and NT‐proBNP have been shown to identify patients with LV dysfunction. This review focuses on the physiology of natriuretic peptides as a group and brain natriuretic peptide in more detail, its structure and regulation as well as its effects at the cellular level.
Can natriuretic peptides be used for the diagnosis of diastolic heart failure?
Authors: Dahlström U.
Published: February 2004

Many patients with heart failure have stiff hearts with an increased wall thickness and small volumes leading to diastolic dysfunction. Different definitions for diastolic heart failure have been proposed but today there is no generally accepted definition and there are few large controlled studies telling us how it should be managed. Natriuretic peptides (BNP or NT‐proBNP) might be used to detect patients with diastolic dysfunction especially in those patients having a restrictive filling pattern or pseudo‐normalised mitral flow pattern and in those, who are symptomatic. However, patients with relaxation abnormalities and mild symptoms or asymptomatic may have normal levels of the natriuretic peptides indicating no or only slight elevation of the left ventricular filling pressures. Thus low levels cannot be used as a rule out diagnosis of diastolic dysfunction.
Natriuretic peptides for risk stratification of patients with acute coronary syndromes
Authors: Galvani Marcello , Ferrini Donatella , Ottani Filippo
Published: February 2004

Natriuretic peptides (BNP and NT‐proBNP) have been shown to be useful tools for risk stratification of patients with acute myocardial ischemia encompassing the whole spectrum of acute coronary syndromes (ACS), particularly for prediction of mortality. Both BNP and NT‐proBNP possess several characteristics of the ideal biomarker, showing independent and incremental prognostic value above traditional clinical, electrocardiographic, and biochemical (particularly troponin) risk indicators. Specifically, in ACS patients, BNP and NT‐proBNP have powerful prognostic value both in patients without a history of previous heart failure or without clinical or instrumental signs of left ventricular dysfunction on admission or during hospital stay. They can also be easily and rapidly measured in an emergency context. We have performed a meta‐analysis of available studies concerning the prognostic value of natriuretic peptides. Our results show that the prognostic value of natriuretic peptides is similar: (1) both at short‐ and long‐term; (2) when natriuretic peptides are measured at first patient contact or during hospital stay; (3) for BNP or NT‐proBNP; and (4) in patients with ST elevation myocardial infarction or no ST elevation ACS. These data suggest that natriuretic peptide measurement should be integrated into routine evaluation of patients with an ACS.
An exploratory study of performance measurement systems and relationships with performance results
Authors: Evans James R
Published: February 2004

The design of an effective performance measurement system, which includes the selection of appropriate measures and approaches for analyzing results, is central to aligning an organization’s operations with its strategic direction. Despite its importance, this is one area that many organizations fail to address effectively. This paper reports exploratory empirical results, obtained from an on‐line survey, on the relative emphasis and types of performance measurements and analysis approaches used by organizations in manufacturing, service, and not‐for‐profit (including education and health care) sectors. The results suggest that organizations with more mature performance measurement systems report better results in terms of customer, financial, and market performance.
Short interfering RNA‐mediated gene targeting in the zebrafish
Authors: Dodd Andrew , Chambers Stephen P. , Love Donald R.
Published: February 2004

Short interfering RNAs (siRNAs) have proved to be a useful tool in studying gene function in plants, invertebrates and mammalian systems. Here we report the use of siRNAs for targeting the zebrafish dystrophin gene. This study demonstrates the efficacy of siRNA‐based gene silencing in this vertebrate model species, and illustrates the potential of this approach for determining the roles of multiple protein products expressed by a single gene during the early stages of development. In addition this study illustrates the usefulness of zebrafish as a model for muscle disease, and highlights the potential of siRNA‐based gene targeting for disease analysis in this model organism.
Cholera toxin induces expression of ion channels and carriers in rat small intestinal mucosa
Authors: Flach Carl-Fredrik , Lange Stefan , Jennische Eva , Lönnroth Ivar
Published: February 2004

Cholera toxin causes cyclic adenosine monophosphate (cAMP)‐induced electrolyte and water secretion in the small intestine. The toxin‐induced change in gene expression in rat small intestine was evaluated with microarray technique and the results were confirmed by semiquantitative polymerase chain reaction (PCR). The transporter CNT2 for nucleosides was upregulated between 6 and 18 h after challenge, whereas the level of GLUT1 transporter for glucose became elevated at 6 h. Both changes probably facilitate uptake of these nutrients in the gut. At 18 h, the major chloride channel in the villus, ClC2, was upregulated. Aquaporin 8 was downregulated at 6 h and two mucin‐producing genes were upregulated 18 h after toxin challenge. The expression was back to normal after 72 h, which is the turnover time for intestinal epithelial cells.
Essential role of the family‐22 carbohydrate‐binding modules for β‐1,3‐1,4‐glucanase activity of Clostridium stercorarium Xyn10B
Authors: Araki Rie , Ali Mursheda K , Sakka Makiko , Kimura Tetsuya , Sakka Kazuo , Ohmiya Kunio
Published: February 2004

Clostridium stercorarium Xyn10B is a modular enzyme comprising two family‐22 carbohydrate‐binding modules (CBMs), a family‐10 catalytic module of glycoside hydrolases, a family‐9 CBM, and two S‐layer homologous modules consecutively from the N‐terminus. To investigate the role of the family‐22 CBMs, truncated proteins were constructed: a recombinant catalytic module polypeptide (rCD), a CBM polypeptide composed of two family‐22 CBMs (rCBM) and a polypeptide composed of the family‐22 CBMs and the catalytic module (rCBM‐CD). We found that rCBM‐CD was highly active toward β‐1,3‐1,4‐glucan; however, rCD was negligibly active toward the same substrate. The V
max/K
m value of rCBM‐CD for β‐1,3‐1,4‐glucan was 7.8 times larger than that for oat‐spelt xylan, indicating that rCBM‐CD should be specified as a β‐1,3‐1,4‐glucanase rather than a xylanase despite the fact that family‐10 catalytic modules are well‐known xylanase modules. These results indicate that the family‐22 CBMs in rCBM‐CD are essential for hydrolysis of β‐1,3‐1,4‐glucan.
Comparison of the anti‐allodynic and antinociceptive effects of systemic; intrathecal and intracerebroventricular morphine in a rat model of central neuropathic pain
Authors: Yu W. , Hao J‐X. , Xu X‐J. , Wiesenfeld‐Hallin Z.
Published: February 2004

The present study has assessed the efficacy and potency of systemic, intrathecal (i.t.) and intracerebroventricular (i.c.v.) morphine in alleviating a chronic mechanical allodynia‐like behaviour in a rat model of central pain after spinal cord injury. The anti‐allodynic potency of morphine was compared to its antinociceptive potency in both spinally injured and normal rats. Systemic (intraperitoneal or subcutaneous) morphine did not significantly relieve allodynia up to 3 mg/kg cumulative dose, which was sedative. Mechanical allodynia‐like behaviour was only significantly relieved by 10 mg/kg morphine which caused severe sedation. Low doses of i.c.v. morphine abolished vocalization of allodynic rats to von Frey hair stimulation. However, other components of abnormal reactions to innocuous mechanical stimulation, such as agitation, jumping and avoidance, were only relieved by i.c.v. morphine at high, sedative doses. In contrast, i.t. morphine dose dependently reversed all components of the allodynic reactions without causing sedation. Morphine administered by all three routes produced powerful antinociception in the tail flick test in normal rats. The antinociceptive potency of morphine was reduced after systemic, i.t. and, particularly, i.c.v. administration in allodynic rats.

These results indicated that i.t. morphine relieved the mechanical allodynia‐like responses in spinally injured rats, whereas systemic or i.c.v. morphine only increased the response threshold to innocuous mechanical stimulation at high doses, which was associated with sedation, making it difficult to assess the anti‐allodynic effect. However, i.c.v. morphine may be particularly effective for the affective component of pain in the present model. The antinociceptive potency of morphine was also reduced in spinally injured rats. It is suggested that morphine may be differentially effective against different types of pain after different routes of administration. Spinal morphine may be a therapeutic alternative in treating central pain after spinal cord injury.