[Vision on man, vision on addiction: a multiple view of problems and recovery]. / Visie op de mens, visie op verslaving: een meervoudige kijk op problematiek en herstel.

BACKGROUND: The way we look at addiction has changed dramatically over the past decades. Currently, the brain disease model is the leading model in the biomedical scientific literature. However, this model has been severely criticized and seems to apply mostly to people with a chronic form of addiction. When the ideas of the recovery movement are applied to the current understanding of addiction, the biopsychosocial (bps) model seems the most fitting. On the other hand, while 'meaningful existence' (or 'sense of meaning') is a focal element the model of recovery, this concept is not included in the bps model.
AIM: To explore whether addition of the concept of meaning to the bps model is usefull.
METHOD: Discussion of a case and evaluation of selected literature.
RESULTS: We advocate the addition of the concept 'sense of meaning' to the bps model, making it the bpsm model. A matter still to be resolved is whether this concept would become a fourth domain or considered either subjacent to or above the other three domains. We suggest that, while sense of meaning is not new in addiction care, adding this concept would underline the importance of the personal story behind the addiction.
CONCLUSION: Addition of the concept meaning to the bps model is Usefull in addiction care.

Multicentre evaluation of the new ORTHO VISION® analyser.

BACKGROUND: Implementation of fully automated analysers has become a crucial security step in the blood bank; it reduces human errors, allows standardisation and improves turnaround time (TAT). OBJECTIVES: We aimed at evaluating the ease of use and the efficiency of the ORTHO VISION® Analyser (VISION) in comparison to the ORTHO AutoVue® Innova System (AutoVue) in six different laboratories. METHODS: After initial training and system configuration, VISION was used in parallel to AutoVue following the daily workload, both automates being based on ORTHO BioVue® System column agglutination technology. Each participating laboratory provided data and scored the training, system configuration, quality control, maintenance and system efficiency. A total of 1049 individual samples were run: 266 forward and reverse grouping and antibody screens with 10 urgent samples, 473 ABD forward grouping and antibody screens with 22 urgent samples, 160 ABD forward grouping, 42 antibody screens and a series of 108 specific case profiles. RESULTS: The VISION instrument was more rapid than the AutoVue with a mean performing test time of 27·9 min compared to 36 min; for various test type comparisons, the TAT data obtained from VISION was shorter than that from AutoVue. Moreover, VISION analysed urgent STAT samples faster. Regarding the ease of use, VISION was intuitive and user friendly. CONCLUSIONS: VISION is a robust, reproducible system performing the most types of analytical determinations needed for pre-transfusion testing today, thus accommodating a wide range of clinical needs. VISION brings appreciated new features that could further secure blood transfusions.

Maximum likelihood estimation of structure parameters from high resolution electron microscopy images. Part I: a theoretical framework.

This paper is the first part of a two-part paper on maximum likelihood (ML) estimation of structure parameters from electron microscopy images. In principle, electron microscopy allows structure determination with a precision that is orders of magnitude better than the resolution of the microscope. This requires, however, a quantitative, model-based method. In our opinion, the ML method is the most appropriate one since it has optimal statistical properties. This paper aims to provide microscopists with the necessary tools to apply this method so as to determine structure parameters as precisely as possible. It reviews the theoretical framework, including model assessment, the derivation of the ML estimator of the parameters, the limits to precision and the construction of confidence regions and intervals for ML parameter estimates. In a companion paper [Van Aert et al., Ultramicroscopy, this issue, 2005], a practical example will be worked out.

Maximum likelihood estimation of structure parameters from high resolution electron microscopy images. Part II: a practical example.

This paper is the second part of a two-part paper on maximum likelihood (ML) estimation of structure parameters from electron microscopy images. In order to show the practical applicability of the theoretical methods described in the first part of this two-part paper, an experimental study of an aluminium crystal is presented. In this study, structure parameters, atom column distances in particular, are estimated from high-resolution transmission electron microscopy (HRTEM) images using the ML method. The necessary steps to be made in the application of this method will be worked out one by one, including model assessment, the computation of the ML parameter estimates, and the construction of confidence intervals for these parameter estimates.

Fluvastatin reduces the 4-year cardiac risk in patients with multivessel disease.

BACKGROUND: To evaluate the impact of the extent of coronary disease (single- or multivessel) and of fluvastatin treatment on the incidence of long-term cardiac atherosclerotic complications in the Lescol Intervention Prevention Study (LIPS). METHODS: A total of 1063 patients with single-vessel disease and 614 patients with multivessel disease were randomized to receive fluvastatin (40 mg bid) or placebo for at least 3 years following a first successful percutaneous coronary intervention. The incidence of cardiac atherosclerotic events (cardiac death, non-fatal myocardial infarction, and coronary re-interventions not related to restenosis) was evaluated. RESULTS: Patients with multivessel disease tended to be older and presented a higher prevalence of associated risk factors and cardiovascular antecedents. The presence of multivessel disease markedly increased the risk of cardiac atherosclerotic events compared with single-vessel disease among patients allocated to placebo (RR 1.67 [95% CI: 1.24-2.25]; p<0.001). In patients treated with fluvastatin, however, no significant differences in long-term outcomes were observed between patients with multivessel disease and patients single-vessel disease (RR 1.28 [95% CI: 0.90-1.81]; p=0.2). CONCLUSIONS: Multivessel coronary disease impaired the 4-year outcomes after percutaneous intervention. However, the hazardous effect of multivessel disease was significantly reduced by long-term fluvastatin treatment.

The red cell revisited--matters of life and death.

An erythrocyte-fractionating method combining volume and subsequent density separation is described. Iron isotope (59Fe)-validation proved this combination of methods to be complementary. By deploying HbA1c as cell age marker, obtained fractions demonstrated that circulating erythrocytes lose 20% of hemoglobin and membrane by shedding vesicles. Vesiculation from older cells proved to be facilitated by the spleen. Animal studies revealed that such vesicles are rapidly removed from the circulation by scavenger receptors on Kupffer cells with phosphatidylserine acting as the principal ligand. These studies reveal the existence of an alternative pathway of erythrocyte breakdown. This means that the premortal substrate of 20% of any erythrocyte is at our disposal. As this kind of vesiculation takes place during the entire erythrocyte lifespan, loss and sometimes reutilisation of marker substances limits the usefulness of isotope studies to the first half of the erythrocyte lifespan, thereby putting the dogmatic lifespan of 120 days into question. Furthermore, these studies add to the understanding of hemoglobin A1c (HbA1c) metabolism and the origin of the wide variation of erythrocyte parameters in peripheral blood. Removal of old erythrocytes from the circulation and from donor blood may open new ways into the treatment of both bilirubin and secondary iron overload.

Is atomic resolution transmission electron microscopy able to resolve and refine amorphous structures?

Atomic resolution transmission electron microscopy, even with an aberration free microscope, is only able to resolve and refine amorphous structures at the atomic level for very small foil thicknesses. Then, a precision of the order of 0.01 A is possible, but this may require long recording times, especially for light atoms. For larger thicknesses, amorphous structures can in principle only be resolved and refined using electron tomography.

Feasibility of a new in vitro approach to evaluate cellular damage following co-infusion of red blood cell concentrates and intravenous drug solutions.

INTRODUCTION: Transfusion guidelines may result in unwanted delay in infusion schemes, as simultaneous infusion of blood components and drug solutions is universally prohibited. The aim of this study was to measure possible damage to red cells by drug solutions, as manifested by haemolysis, using a dynamic model that resembles the clinical setting. METHODS: Stored filtered and irradiated RBC concentrates and drug solutions were co-infused in an in vitro dynamic model. Also, incubation in a static model was performed. The haemolytic potency of the drug solutions was measured by determining free haemoglobin (fHb) levels. RESULTS AND DISCUSSION: Neither in the dynamic tests nor in the static tests did fHb levels exceed the maximally acceptable standard for filtered RBC concentrates according to Dutch specification guidelines. In the static test model, fHb levels were slightly elevated compared with those of control samples, as well as those in the dynamic test model. CONCLUSION: A novel in vitro dynamic infusion system appears to represent a useful technique to calculate possible damage to RBCs resulting from co-infused drug solutions. Co-infusion of the drug solutions tested with filtered and irradiated RBC concentrates did not produce fHb levels above the levels accepted by the Dutch national guidelines. Apart from haemolysis, other parameters reflecting RBC damage should be investigated in future studies.

High-resolution electron microscopy and electron tomography: resolution versus precision.

The performance of high-resolution electron microscopy and electron tomography is usually discussed in terms of two-point resolution, expressing the possibility of perceiving separately two image points of an object. However, the concept resolution obtains another meaning if one uses prior knowledge about the object and the imaging procedure in the form of a parametric model describing the expectations of the observations. The unknown parameters, such as the positions of the components in an object, can be measured quantitatively by fitting this model to the observations. Due to the statistical nature of the experiment, the resulting solutions for the positions of the components and therefore for the distance between the components will never be exact. An alternative to resolution is then the precision with which the distance can be measured. In the present paper, it is shown that the precision depends on the size of the components, the distance between the components, the resolution of the instrument, and the number of electron counts. For electron tomography, it also depends on the orientation of the object with respect to the rotation axis.

Optimal experimental design of STEM measurement of atom column positions.

A quantitative measure is proposed to evaluate and optimize the design of a high-resolution scanning transmission electron microscopy (STEM) experiment. The proposed measure is related to the measurement of atom column positions. Specifically, it is based on the statistical precision with which the positions of atom columns can be estimated. The optimal design, that is, the combination of tunable microscope parameters for which the precision is highest. is derived for different types of atom columns. The proposed measure is also used to find out if an annular detector is preferable to an axial one and if a C(s)-corrector pays off in quantitative STEM experiments. In addition, the optimal settings of the STEM are compared to the Scherzer conditions for incoherent imaging and their dependence on the type of object is investigated.

Angiographic and clinical one-year follow-up of the Cordis tantalum coil stent in a multicenter international study demonstrating improved restenosis rates when compared to pooled PTCA and BENESTENT-I data: the European Antiplatelet Stent Investigation (EASI).

The Cordis tantalum coil stent was assessed in a nonrandomized multicenter trial: 275 patients with stable or unstable angina were entered. Clinical follow-up was for 1 year, with repeat angiography at 6 months. The major adverse cardiac event rates (MACE) were 3%, 14%, and 17% at 1, 7, and 13 months, respectively. The procedural success rate was 96% and the subacute occlusion rate 1.5%, in a group of patients over 60% of whom had ACC/AHA type B2 or C lesions. The binary restenosis rate at 6 months was 17.3%. Minimum lumen diameter increased from 1.07 +/- 0.28 mm preprocedure to 2.93 +/- 0.34 mm poststenting and at 6 months was 1.99 +/- 0.69 mm. These results demonstrate that the Cordis tantalum stent can be used to treat complex lesions with good procedural success and low rates of subacute thrombosis and restenosis at 6 months.

Does a monochromator improve the precision in quantitative HRTEM?

This paper addresses the question as to what extent the incorporation of a monochromator in an electron microscope can enhance the performance of high resolution transmission electron microscopy (HRTEM). The monochromator will reduce the chromatic aberration, and hence the information limit, at the expense of beam current, leading to a decrease in signal intensity and a corresponding decrease in signal-to-noise ratio (SNR). Both aspects, information limit and SNR, have been included in a quantitative evaluation based on the statistical precision with which the position of an atom column can be estimated. It is shown that the effect of a monochromator on the attainable precision depends on the microscope and monochromator parameters, as well as on the characteristics of the object.

Beta blockade in neurocardiogenic dysfunction: results of a clinical study.

BACKGROUND: Few placebo-controlled studies with ß-blockers have been performed in patients suffering from neurocardiogenic syncope. METHODS: We investigated the efficacy of metoprolol in 26 patients with recurrent syncope, suspected to be of neurocardiogenic origin, and positive tilt table test (TTT) outcome in a single-centre, double-blind, placebo-controlled, crossover study, with treatment periods of two weeks. Therapeutic efficacy was defined as a negative TTT after metoprolol and a positive TTT after placebo. Therapeutic failure was defined as a positive TTT after metoprolol and a positive or negative TTT after placebo. Patients with a negative TTT test after both metoprolol and placebo comprised the third group. RESULTS: The 24 patients who completed the study consisted of 14 females and 10 males, mean age 53 years, range 18-75 years. Therapeutic efficacy was observed in nine patients, therapeutic failure in eight patients and seven patients had a negative TTT after both placebo and metoprolol. According to the exact binomial test for paired proportions, the 95% confidence interval is 12 to 38% and p<0.01 in favour of treatment with metoprolol. CONCLUSION: These findings indicate a favourable effect of metoprolol.

Auto-calibration and -compensation of a capacitive pressure sensor using multilayer perceptrons

Using multilayer perceptrons (MLPs), a smart model for a capacitive pressure sensor (CPS) is proposed. When the ambient temperature changes, the nonlinear response characteristics of a CPS may vary widely. Under such conditions, calibration of the sensor and compensation of the nonlinear sensor characteristics to obtain correct readout becomes a difficult task. The proposed MLP model can provide automatic nonlinear compensation and calibration of the CPS characteristics. A microcontroller unit (MCU)-based implementation scheme for this model is also considered. Simulation results show that this model can estimate the pressure with a maximum full-scale error of +/- 1% over a variation of temperature from -50 to 150 degrees C.

Modeling of an intelligent pressure sensor using functional link artificial neural networks.

A capacitor pressure sensor (CPS) is modeled for accurate readout of applied pressure using a novel artificial neural network (ANN). The proposed functional link ANN (FLANN) is a computationally efficient nonlinear network and is capable of complex nonlinear mapping between its input and output pattern space. The nonlinearity is introduced into the FLANN by passing the input pattern through a functional expansion unit. Three different polynomials such as, Chebyschev, Legendre and power series have been employed in the FLANN. The FLANN offers computational advantage over a multilayer perceptron (MLP) for similar performance in modeling of the CPS. The prime aim of the present paper is to develop an intelligent model of the CPS involving less computational complexity, so that its implementation can be economical and robust. It is shown that, over a wide temperature variation ranging from -50 to 150 degrees C, the maximum error of estimation of pressure remains within +/- 3%. With the help of computer simulation, the performance of the three types of FLANN models has been compared to that of an MLP based model.

Aberration and the Strehl ratio.

An exact expression is derived for the Strehl ratio as a function of the minimum root-mean-square aberration value that may produce it. The result is applicable to any aperture and is shown to imply a similar expression for the Strehl ratio as a function of the minimum amplitude range of the aberration.

Macrophage specific overexpression of the human macrophage scavenger receptor in transgenic mice, using a 180-kb yeast artificial chromosome, leads to enhanced foam cell formation of isolated peritoneal macrophages.

Macrophage scavenger receptors class A (MSR) are thought to play an important role in atherogenesis by mediating the unrestricted uptake of modified lipoproteins by macrophages in the vessel wall leading to foam cell formation. To investigate the in vivo role of the MSR in this process, a transgenic mouse model expressing both isoforms of the human MSR was generated. A 180-kb yeast artificial chromosome (YAC) containing the human MSR gene (MSR1) with 60- and 40-kb flanking sequence at the 5' and 3' end, respectively, was obtained by reducing the size of a 1050-kb YAC by homologous recombination. This 180-kb YAC was microinjected into mouse oocytes. In the resulting transgenic mice, high levels of mRNA for both type I and type II human MSR1 were detected in peritoneal macrophages and trace levels in other organs, known to contain macrophage-derived cells. Using an antibody against the human MSR, the Kupffer cells in the liver were shown to contain the MSR protein. In vivo clearance of acetyl-LDL was not changed in the MSR1-transgenic mice. However, in vitro studies using peritoneal macrophages from the transgenic mice showed a two-fold increased degradation of acetyl-LDL and cholesterolester accumulation concomitant with a four-fold increase in foam cell formation, as compared to wild-type macrophages. Thus, macrophage specific overexpression of the MSR may lead to increased foam cell formation, which is one of the initial and crucial steps in atherogenesis.