Unleashing NK- and CD8 T cells by combining monalizumab and trastuzumab for metastatic HER2-positive breast cancer: Results of the MIMOSA trial.

The large majority of patients with HER2-positive metastatic breast cancer (MBC) will eventually develop resistance to anti-HER2 therapy and die of this disease. Despite, relatively high levels of stromal tumor infiltrating lymphocytes (sTILs), PD1-blockade has only shown modest responses. Monalizumab targets the inhibitory immune checkpoint NKG2A, thereby unleashing NK- and CD8 T cells. We hypothesized that monalizumab synergizes with trastuzumab by promoting antibody-dependent cell-mediated cytotoxicity. In the phase II MIMOSA-trial, HER2-positive MBC patients were treated with trastuzumab and 750 mg monalizumab every two weeks. Following a Simon's two-stage design, 11 patients were included in stage I of the trial. Treatment was well tolerated with no dose-limiting toxicities. No objective responses were observed. Therefore, the MIMOSA-trial did not meet its primary endpoint. In summary, despite the strong preclinical rationale, the novel combination of monalizumab and trastuzumab does not induce objective responses in heavily pre-treated HER2-positive MBC patients.

Homogeneous water nucleation in carbon dioxide-nitrogen mixtures: Experimental study on pressure and carrier gas effects.

New homogeneous nucleation experiments are presented at 240 K for water in carrier gas mixtures of nitrogen with carbon dioxide molar fractions of 5%, 15%, and 25%. The pulse expansion wave tube is used to test three different pressure conditions, namely, 0.1, 1, and 2 MPa. In addition, a restricted series of nucleation experiments is presented for 25% carbon dioxide mixtures at temperatures of 234 and 236 K at 0.1 MPa. As pressure and carbon dioxide content are increased, the nucleation rate increases accordingly. This behavior is attributed to the reduction in the water surface tension by the adsorption of carrier gas molecules. The new data are compared with theoretical predictions based on the classical nucleation theory and on extrapolations of empirical surface tension data to the supercooled conditions at 240 K. The extrapolation is carried out on the basis of a theoretical adsorption/surface tension model, extended to multi-component mixtures. The theoretical model appears to strongly overestimate the pressure and composition dependence. At relatively low pressures of 0.1 MPa, a reduction in the nucleation rates is found due to an incomplete thermalization of colliding clusters and carrier gas molecules. The observed decrease in the nucleation rate is supported by the theoretical model of Barrett, generalized here for water in multi-component carrier gas mixtures. The temperature dependence of the nucleation rate at 0.1 MPa follows the scaling model proposed by Hale [J. Chem. Phys. 122, 204509 (2005)].

Homogeneous water nucleation: Experimental study on pressure and carrier gas effects.

Homogeneous nucleation of water is investigated in argon and in nitrogen at about 240 K and 0.1 MPa, 1 MPa, and 2 MPa by means of a pulse expansion wave tube. The surface tension reduction at high pressure qualitatively explains the observed enhancement of the nucleation rate of water in argon as well as in nitrogen. The differences in nucleation rates for the two mixtures at high pressure are consistent with the differences in adsorption behavior of the different carrier gas molecules. At low pressure, there is not enough carrier gas available to ensure the growing clusters are adequately thermalized by collisions with carrier gas molecules so that the nucleation rate is lower than under isothermal conditions. This reduction depends on the carrier gas, pressure, and temperature. A qualitative agreement between experiments and theory is found for argon and nitrogen as carrier gases. As expected, the reduction in the nucleation rates is more pronounced at higher temperatures. For helium as the carrier gas, non-isothermal effects appear to be substantially stronger than predicted by theory. The critical cluster sizes are determined experimentally and theoretically according to the Gibbs-Thomson equation, showing a reasonable agreement as documented in the literature. Finally, we propose an empirical correction of the classical nucleation theory for the nucleation rate calculation. The empirical expression is in agreement with the experimental data for the analyzed mixtures (water-helium, water-argon, and water-nitrogen) and thermodynamic conditions (0.06 MPa-2 MPa and 220 K-260 K).

Delivery of Nutritious Meals to Elderly Receiving Home Care: Feasibility and Effectiveness.

BACKGROUND/OBJECTIVES: Elderly with functional disabilities are at increased risk of inadequate dietary intake. Little is known about the effectiveness of interventions aimed at improving their dietary intake and nutritional status, nor about the determinants of successful implementation. We performed a feasibility study to evaluate the implementation and effectiveness of a home delivery service providing nutritious meals. DESIGN: Quasi-experimental, with participants allocated to treatment group based on municipality of residence. SETTING AND PARTICIPANTS: Functionally disabled home-dwelling elderly receiving home care. INTERVENTION: Three-month daily meal service consisting of dinner and snacks (intervention). The control group sustained habitual food intake. MEASUREMENTS: Data on satisfaction and problems regarding the meal service were collected by structured interviews. Dietary intake (2-day estimated food diary), nutritional status (anthropometry), handgrip strength, and quality of life (questionnaire-based) was measured at baseline, three months (end of intervention), and six months (follow-up). RESULTS: Forty-four elderly were included (intervention group: 25, control group: 19). For most aspects of the meal service, approximately 90% of participants indicated being satisfied, and the large majority (70%) was interested in receiving a similar meal service in the future. At the end of the 3-month intervention, the intervention group showed a greater increase than the control group in body weight (P< 0.005), body mass index (P< 0.005), upper leg circumference (P< 0.01) and fat free mass (FFM, P< 0.03). Three months post-intervention, only the increase in FFM remained statistically significant (P< 0.05). Except for calcium intake, no positive intervention effect was observed for any of the other outcomes. CONCLUSION: Our study stresses the feasibility as well as the potential of healthy and tasteful meals to support home-dwelling elderly, by showing that a high-quality meal service was highly appreciated and had a rapid effect on FFM.

On the effect of pressure and carrier gas on homogeneous water nucleation.

Homogeneous nucleation rates of water droplets were measured at a nucleation temperature close to 240 K in a Pulse-Expansion Wave Tube (PEWT). Several measures were taken to improve the data obtained with the PEWT. For instance, the molar water vapor fraction was determined with three independent techniques. The resulting standard uncertainty of the supersaturation was within 1.8%. Results are given for water nucleation in helium at 100 kPa and at 1000 kPa and in nitrogen at 1000 kPa. Two trends were observed: (i) the values of the nucleation rate of water in helium at 1000 kPa are slightly but significantly higher (factor 3) than its values at 100 kPa and (ii) nucleation rates of water in nitrogen at 1000 kPa are clearly higher (factor 10) than in helium at the same pressure. It is argued that the explanation of the two observed trends is different. For case (i), it is the insufficient thermalization of the growing water clusters in helium at the lowest pressure that has a reducing effect on the nucleation rate, although a full quantitative agreement has not yet been reached. For case (ii), thermal effects being negligible, it is the pressure dependency of the surface tension, much stronger for nitrogen than for helium, that explains the trends observed, although also here a full quantitative agreement has not yet been achieved.

Combined isometric and vibration training does not enhance strength beyond that of isometric training alone.

AIM: Research considering combined vibration and strength training is extensive yet results are equivocal. However, to date there appears no research which has considered the combination of both direct vibration and whole-body vibration when used in an isometric deadlift position. The aim of this study was to compare groups performing isometric training with and without direct and whole-body vibration. METHODS: Twenty four participants (19-24 years) were randomly divided into: isometric training with vibration (ST+VT: N.=8), isometric training without vibration (ST: N.=8), and control (CON: N.=8). Within the training groups participants trained twice per week, for 6 weeks, performing 6-sets of maximal isometric deadlift contractions, increasing in duration from 30 seconds to 40 seconds (weeks 1-6). Hip and knee angle was maintained at 60° and 110°, respectively for both testing and training. Training sessions for ST+VT were identical to ST with the addition of a direct vibratory stimulus through hand-held straps and whole-body vibration via standing on vibration a platform. The amplitude remained constant (2 mm) throughout the intervention whilst the frequency increased from 35Hz to 50Hz. Pre- and post-test isometric strength was measured using an isometric deadlift dynamometer. RESULTS: Results revealed significant increases in isometric strength for both ST+VT (P<0.001, 23.8%) and ST (P<0.001, 32.5%) compared to CON, with no significant differences between ST+VT and ST training groups. CONCLUSION: The present study provides evidence to suggest that there are no greater gains to be incurred by the addition of a vibratory stimulus to traditional strength training.

Combined isometric and vibration training does not enhance strength beyond that of isometric training alone.

Research considering combined vibration and strength training is extensive yet results are equivocal. However, to date there appears no research which has considered the combination of both direct vibration and whole---body vibration when used in an isometric deadlift position. The aims of this study were to compare groups performing isometric training with and without direct and whole---body vibration. Twenty four participants (19---24 years) were randomly divided into: isometric training with vibration (ST+VT: n=8), isometric training without vibration (ST: n=8), and control (CON: n=8). Within the training groups participants trained twice per week, for 6 weeks, performing 6---sets of maximal isometric deadlift contractions, increasing in duration from 30 seconds to 40 seconds (weeks 1---6). Hip and knee angle was maintained at 60° and 110°, respectively for both testing and training. Training sessions for ST+VT were identical to ST with the addition of a direct vibratory stimulus through hand---held straps and whole---body vibration via standing on vibration a platform. The amplitude remained constant (2mm) throughout the intervention whilst the frequency increased from 35Hz to 50Hz. Pre--- and post---test isometric strength was measured using an isometric deadlift dynamometer. Results revealed significant increases in isometric strength for both ST+VT (p < 0.001, 23.8%) and ST (p < 0.001, 32.5%) compared to CON, with no significant differences between ST+VT and ST training groups. The present study provides evidence to suggest that there are no greater gains to be incurred by the addition of a vibratory stimulus to traditional strength training.

Dietary patterns and fatty acids levels of three European populations. Results from the IMMIDIET study.

BACKGROUND AND AIMS: Differences in blood fatty acids (FAs) profile among populations with different lifestyle have partly been attributed to differences in food intake. A holistic approach in dietary guidance through dietary patterns is essential. This study aimed at evaluating the main plasma and red blood cell (RBC) FAs in three European populations and assessing the role of dietary patterns in explaining variation in their levels. METHODS: In the framework of the IMMIDIET Project, 1604 subjects (802 male-female pairs) aged 26-65 years were enrolled in Italy, Belgium and UK. Plasma and RBC FAs were measured. One year recall food frequency questionnaires were used to evaluate dietary habits of each individual. RESULTS: Italian cohort showed lower plasma and RBC n-3 levels than participants of the other two populations (P<0.001). Both plasma and RBC arachidonic acid were higher in Italian cohort as compared to Belgian and English. Reduced rank regression analysis indicated two dietary patterns explaining 35% and 17% of the total variation of the sum of plasma and RBC n-3, respectively. In a holistic dietary analysis, neither fish nor mollusks intake seemed to contribute to n-3 variation as compared to vegetable oils and polyphenol-rich foods. CONCLUSION: The Italian cohort presented significant lower plasma and RBC n-3 FA levels compared to Belgians and English. A holistic approach in dietary analysis seemed to explain a relatively high proportion of plasma and RBC n-3 FAs variability. Dietary pattern analysis may contribute to the study of the association of human diet with FAs levels.

Characterization of a standardized glucagon challenge test as a pharmacodynamic tool in pharmacological research.

The aim of this study was to characterize a glucagon challenge test as a tool in diabetes research by assessing the inter- and intra-individual variability, and investigating the activity of the autonomic nervous system (ANS) during the challenge, as this might have an indirect impact on glucose homeostasis. The study was performed in 24 healthy volunteers separated in 2 groups. The first group of 12 volunteers underwent a 5-h glucagon challenge during a pancreatic clamp procedure with infusion of [6,6-2H2]-glucose infusion in combination with heart rate variability measurements. In the second group, 12 other healthy volunteers underwent two 6-h glucagon challenges separated by 6 weeks, and fat biopsies were taken for analysis of glucagon receptor expression. Serum glucose rose rapidly after glucagon infusion, and reached a plateau at 90 min. The time profiles suggested rapid development of tolerance for glucagon-induced hyperglycemia. During the glucagon challenge intra- and inter-individual variabilities for hepatic glucose production, the rate of disappearance of glucose, and plasma glucose were approximately 10-15% for all variables. Hyperglucagonemia did not affect heart rate variability. Human adipose tissue had a low, but variable, expression of glucagon receptor mRNA. This standardized glucagon challenge test has a good reproducibility with only limited variability over 6 weeks. It is a robust tool to explore in detail the contribution of glucagon in normal and altered glucose homeostasis and can also be used to evaluate the effects of drugs antagonizing glucagon action in humans without confounding changes in ANS tone.

Crystal structures of manganese and cobalt dichloride monohydrate and deuteration effects on magnetic behavior.

This work reports the long sought crystal structures of the title members of the intriguing series of 3d transition metal dichloride monohydrates. The double chain structure which results from rearrangement of the well-known pseudo-octahedral coordination geometry and single chains in the corresponding metal chloride dihydrate is extremely unusual. MnCl2·H2O and CoCl2·H2O each crystallize in orthorhombic space group Pnma with Z = 4 and lattice parameters a = 9.0339(1), 8.8207(3); b = 3.68751(5), 3.5435(1); c = 11.5385(2), 11.2944(4) all in Å and for Mn, Co, respectively. Results are reported also for both fully deuterated systems; the structures remain the same with lattice parameter changes typically much less than 0.1%. Various magnetic properties of MnCl2·D2O and CoCl2·D2O are reported. For the latter, there are no apparent differences, qualitatively or quantitatively, from the previously measured properties of CoCl2·H2O. Interestingly, for the former some differences with respect to MnCl2·H2O are apparent, principally a lower Tmax = 3.10(10) K about which a broad antiferromagnetic maximum is centered, and a larger value χmax = 0.336(3) emu/mol. However, antiferromagnetic ordering appears to occur at essentially the same 2.18(2) K. Results of fits to susceptibilities of MnCl2·D2O and CoCl2·D2O are compared with those obtained before for MnCl2·H2O and CoCl2·H2O. Structural considerations serve to rationalize the physical properties, especially the lower dimensional magnetism of monohydrates.

Recombinant human serum amyloid P in healthy volunteers and patients with pulmonary fibrosis.

PRM-151, recombinant human Pentraxin-2 (PTX-2) also referred to as serum amyloid P (SAP), is under development for treatment of fibrosis. A First-in-Human (FIH) trial was performed to assess the safety, tolerability, and pharmacokinetics of single ascending intravenous doses of PRM-151 administered to healthy subjects, using a randomized, blinded, placebo controlled study design. Each cohort included three healthy subjects (PRM-151:placebo; 2:1). SAP levels were assessed using a validated ELISA method, non-discriminating between endogenous and exogenous SAP. At a dose level of 10 mg/kg, at which a physiologic plasma level of SAP was reached, two additional healthy volunteers and three pulmonary fibrosis (PF) patients were enrolled enabling comparison of the pharmacokinetic SAP profile between healthy volunteers and PF patients. In addition, the percentage of fibrocytes (CD45+/Procollagen-1+ cells) in whole blood samples was assessed to demonstrate biological activity of PRM-151 in the target population. PRM-151 administration was generally well tolerated. In two pulmonary fibrosis patients non-specific, transient skin reactions (urticaria and erythema) were observed. PRM-151 administration resulted in a 6-to 13-fold increase in mean baseline plasma SAP levels at dose levels of 5, 10, and 20 mg/kg. The estimated t1/2 of PRM-151 in healthy volunteers was 30 h. Pharmacokinetic profiles were comparable between healthy volunteers and PF patients. PRM-151 administration resulted in a 30-50% decrease in fibrocyte numbers 24 h post-dose. This suggests that administration of PRM-151 may be associated with a reduction of fibrocytes in PF patients, a population for which current pharmacotherapeutic options are limited. The pharmacological action of PRM-151 should be confirmed in future research.

Evaluation of the EndoPAT as a Tool to Assess Endothelial Function.

Endothelial dysfunction is a potential target for (pharmaceutical) intervention of several systemic pathological conditions. We investigated the feasibility of the EndoPAT to evaluate acute changes in endothelial function with repeated noninvasive measurements and assessed its discriminating power in different populations. Endothelial function was stable over a longer period of time in renally impaired patients (coefficient of variation 13%). Endothelial function in renally impaired and type 2 diabetic patients was not decreased compared to healthy volunteers (2.9 ± 1.4 and 1.8 ± 0.3, resp., versus 1.8 ± 0.5, P > 0.05). The EndoPAT did not detect an effect of robust interventions on endothelial function in healthy volunteers (glucose load: change from baseline 0.08 ± 0.50, 95% confidence interval -0.44 to 0.60; smoking: change from baseline 0.49 ± 0.92, 95% confidence interval -0.47 to 1.46). This suggests that at present the EndoPAT might not be suitable to assess (changes in) endothelial function in early-phase clinical pharmacology studies. Endothelial function as measured by the EndoPAT could be physiologically different from endothelial function as measured by conventional techniques. This should be investigated carefully before the EndoPAT can be considered a useful tool in drug development or clinical practice.

Gender differences in copper, zinc and selenium status in diabetic-free metabolic syndrome European population - the IMMIDIET study.

BACKGROUND AND AIMS: The European 'IMMIDIET' study was designed to evaluate the effect of genetic and dietary habit interactions on cardiovascular disease risk factors in non-diabetic subjects. Copper, zinc and selenium are involved in redox balance and modifications of their homeostasis could be associated with metabolic syndrome. Because few studies have dealt with trace element status in metabolic syndrome with conflicting results, we aimed at investigating the relationships between plasma copper, zinc and selenium concentrations and metabolic syndrome in the IMMIDIET population. METHODS AND RESULTS: Male-female couples born and living in Abruzzo, Italy (n = 271); Limburg, Belgium (n = 267), southwest part of London, England (n = 263) and 205 Italian-Belgian mixed couples living in Belgium were enrolled. Data on medical history, hypertension and blood lipid profile, medication use, smoking and alcohol habits, physical activity and socioeconomic status were collected using a standardised questionnaire. Anthropometric, blood pressure, glucose, insulin, lipid profile and copper, zinc and selenium measurements were performed. Participants were classified in two groups according to the presence of metabolic syndrome (Yes/No). Comparison between these two groups, performed separately in men and women, indicated no association in men whereas, in women, metabolic syndrome was associated with higher plasma selenium concentrations (odds ratio (OR) = 1.55(1.28-1.89)); this association remained significant after adjustment for age, group, social status, physical activity, energy intake, alcohol consumption, smoking and hormonal status (OR = 1.33 (1.06-1.67)). CONCLUSION: Our results indicate gender differences in the association between plasma selenium concentration and metabolic syndrome without diabetes and may suggest a sub-clinical deleterious effect of high selenium status in women.

Validation of the IMMIDIET food frequency questionnaire in an adult Belgian population: a report from the Belgian case-control study on bladder cancer risk.

We evaluated the performance of the IMMIDIET food frequency questionnaire (FFQ) used to collect dietary data for the Belgian case-control study on bladder cancer. Thirty-seven men and women aged 50 years and older were recruited from the University Hospital in Leuven, Belgium. Participants completed the IMMIDIET FFQ, a 7-day diet diary and a 24-hour diet recall. Median intakes and inter-quartile ranges were calculated for 27 foods and nutrients from each dietary assessment method. All dietary factors were log-transformed and adjusted for energy using the nutrient density method. Pearson correlation coefficients were used to compare the different dietary assessment methods. Bland-Altman plots were also used to assess levels of agreement between the dietary methods. Energy, fruit and vegetable intake estimates were higher from the IMMIDIET FFQ compared with the two reference methods.The highest deattenuated correlations between the FFQ and 7-day diary were meat (0.58), bread (0.44), fruit (0.38) and fish (0.38). The highest deattenuated correlations between the FFQ and 24-hour recall were for fruit (0.72), fat (0.48), alcohol (0.44), cholesterol (0.42), monounsaturated fatty acid (0.42) and polyunsaturated fatty acid (0.41). Generally, correlation was lower for the micro-nutrients except for phosphorus (0.42), vitamin C (0.41) and calcium (0.40). The IMMIDIET FFQ is an appropriate instrument to measure usual dietary intake for the Belgian case-control study on bladder cancer risk. Further investigation of nutritional assessment methods is necessary.

The relationship between visual field loss in glaucoma and health-related quality-of-life.

PURPOSE: to investigate the relationship between visual field loss and health-related quality-of-life (HRQOL) in patients with ocular hypertension (OHT) or primary open-angle glaucoma (POAG). METHODS: we conducted a cross-sectional study among 537 OHT and POAG patients from seven hospitals in The Netherlands. Clinical information was obtained from medical files. Patients completed a questionnaire, containing generic HRQOL instruments (EQ-5D and Health Utilities Index mark 3), vision-specific National Eye Institute Visual Functioning Questionnaire (VFQ-25), and glaucoma-specific Glaucoma Quality-of-Life questionnaire (GQL-15). The impact of visual field loss on HRQOL scores was analysed with multiple linear regression analyses. RESULTS: a relationship between mean deviation (MD) and HRQOL was found after adjusting for age, gender, visual acuity, medication side effects, laser trabeculoplasty, and glaucoma surgery. We found interaction between MD in both eyes for GQL and VFQ-25 scores. The relationship between MD and utility was non-linear, with utility only affected at MD-values below -25 dB in the better eye. Visual acuity, side effects, and glaucoma surgery independently affected HRQOL. Binocular MD and MD in the better eye had similar impacts on HRQOL, whereas MD in the worse eye had an independent effect. HRQOL was affected more by binocular defects in the inferior than in the superior hemifield. CONCLUSION: visual field loss in progressing glaucoma is independently associated with a loss in both disease-specific and generic quality-of-life. It is important to prevent progression, both in early and in advanced glaucoma, especially in patients with inferior hemifield defects and severe defects in either eye.

Homogeneous water nucleation and droplet growth in methane and carbon dioxide mixtures at 235 K and 10 bar.

Homogeneous nucleation rates and droplet growth rates of water in pure methane and mixtures of methane and carbon dioxide were measured in an expansion wave tube at 235 K and 10 bar. The nucleation rate in pure methane is three orders of magnitude higher than literature nucleation rates of water in low-pressure helium or argon. Addition of carbon dioxide to the carrier gas mixture increases the rates even more. Specifically, rates in a mixture of methane and 3% carbon dioxide are a factor of 10 higher than the rates in pure methane. With 25% carbon dioxide, the rates are four orders of magnitude higher than the rates in pure methane. An application of the nucleation theorem shows that the critical cluster consists of 22 water molecules and 5 methane molecules, for nucleation in pure methane. Growth rates of water droplets were measured in methane and in methane-carbon dioxide mixtures at 243 K and 11.5 bar. At equal temperature, pressure and water vapor fraction, the growth rate of the squared droplet radius is about 20% lower in the mixture with 25% carbon dioxide than in pure methane. The lower growth rate is caused by a smaller diffusion coefficient of water in the mixture with carbon dioxide; the difference of the diffusion coefficients is qualitatively reproduced by the empirical Fuller correlation combined with Blanc's law.

Effects of snack consumption for 8 weeks on energy intake and body weight.

BACKGROUND: Consumption of snacks might contribute to the obesity epidemic. It is not clear how the moment of consumption and energy density of snacks can influence the compensatory response to consumption of snacks in the long term. OBJECTIVE: To investigate the effects of snack consumption for 8 weeks on changes in body weight, emphasizing on moment of consumption and energy density. DESIGN: In total, 16 men and 66 women (mean age 21.9 years (s.d. 0.3 year), mean body mass index 20.7 kg m(-2) (s.d. 0.2 kg m(-2))) were randomly assigned to one of four parallel groups in a 2 x 2 design: snacks consumed with or between meals and snacks having a low (<4 kJ g(-1)) or high (>12 kJ g(-1)) energy density. For 8 weeks, subjects consumed mandatory snacks that provided 25% of energy requirements on each day. Body weight, body composition, physical activity level (PAL) and energy intake were measured in week 1 and week 8. RESULTS: There were no differences in changes in body weight between the four groups. Moment of consumption (P=0.7), energy density (P=0.8) and interaction (P=0.09) did not influence body weight. Similarly, there were no differences in changes in body composition, PAL and energy intake between the four groups. CONCLUSIONS: Body weight after 8 weeks of snack consumption was not affected by moment of consumption and energy density of snacks. This finding suggests that consuming snacks that are high or low in energy density does not necessarily contribute to weight gain. Healthy, nonobese young adults may be able to maintain a normal body weight through an accurate compensation for the consumption of snacks.

Comparison between solutions of the general dynamic equation and the kinetic equation for nucleation and droplet growth.

A comparison is made between two models of homogeneous nucleation and droplet growth. The first is a kinetic model yielding the master equations for the concentrations of molecular clusters. Such a model does not make an explicit distinction between nucleation and droplet growth. The second model treats nucleation and growth separately, fully ignoring stochastic effects, and leads to the continuous general dynamic equation (GDE). Problems in applying the GDE model are discussed. A numerical solution of the kinetic equation is compared with an analytic solution of the GDE for two different cases: (1) the onset of nucleation and (2) the nucleation pulse. The kinetic model yields the thickness of the condensation front in size space as a function of supersaturation and dimensionless surface tension. If the GDE is applied properly, solutions of the GDE and the kinetic equation agree, with the exception of very small clusters, near-critical clusters, and the condensation front.

C reactive protein and its determinants in healthy men and women from European regions at different risk of coronary disease: the IMMIDIET Project.

AIM: Differences in C-reactive protein (CRP) levels and its determinants in three European populations at different risk of coronary artery disease (CAD) were studied. METHODS: Subjects were recruited randomly in Limburg (Belgium), Abruzzo (Italy) and south-west (SW) London (England). RESULTS: Ten-year risk of fatal coronary events (estimated using risk equations provided by the SCORE Project) was lower both in men and women from Abruzzo, intermediate in people from Limburg and higher in subjects from SW London. Within each country, high sensitivity (hs)-CRP levels were higher in the high-risk class in men but not in women. Men from Abruzzo had higher hs-CRP levels than those from Limburg and SW London. Women always had higher hs-CRP levels than men. The strongest hs-CRP determinant was body mass index (BMI, R(2) = 0.14) in women and waist circumference (WC, R(2) = 0.046) in men. The highest hs-CRP levels were observed in subjects with both high BMI and high WC. Metabolic syndrome was associated with high levels of CRP both in men and women, even after adjustment for confounders. DISCUSSION: Difference in CRP levels cannot explain the European gradient of CVD risk, although CRP levels are associated with the calculated SCORE risk of fatal coronary events within each country.