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SUMMARY In this study, we investigate the correlation between the residuals of a neGMM (non-ergodic Ground Motion Model) and the physics-based parameters obtained using a non-parametric GIT approach (Generalized Inversion Technique) to lay the groundwork for the implementation of an ad-hoc FAS (Fourier Amplitude Spectra) neGMM for the Central Italy region. This region is particularly suitable for data-driven methodologies as those applied in this work because of the large amount of available data due to the recent multiple main shock–aftershock sequences occurred in this area. Both neGMM and GIT models are developed for Fourier spectra in the frequency range between 0.5 and 25 Hz and using the same reference sites. The comparison of the non-ergodic terms with the source, path and site spectral parameters provides interesting results. First, we find a strong correlation between the source parameters, stress drop Δσ and decay ${k}_{\mathrm{ source}}$ and the source neGMM corrective terms (the combination of the between-event δBe and the location-to-location terms δL2L). This correlation is frequency dependent and, at high frequency, is remarkably positive for Δσ and negative for ${k}_{\mathrm{ source}}$. Concerning the attenuation terms, the path-to-path residuals (δP2P) are clearly associated with the deviations from the regional Q estimates obtained from GIT analysis. This indicates that the neGMM properly captures the properties of the anelastic attenuation and that the corrective terms δP2P can be used to account for differences in travel paths across different crustal domains. Finally, adopting the same reference sites for neGMM and non-parametric GIT, we observe that the systematic site terms (δS2Ss) and the GIT-derived amplification functions are in good agreement. The next step for an appropriate modelling is to identify the physical parameters (e.g. VS,30 and ${k}_0$) describing the empirical amplification curves to be introduced as explanatory variables in the ground motion model.

We investigate the preparatory phase of the 2009, Mw 6.1 L’Aquila earthquake in central Italy by analysing the temporal evolution and spatial distribution of the seismic moment, M0, to radiated energy, ES. Our approach focuses on monitoring the deviations of the scaling between M0 and ES with respect to a model calibrated for the background seismicity. The temporal evolution of these deviations, defined as Energy Index, EI, identifies the onset of the activation phase one week before the mainshock. We show that foreshocks are characterized by a progressive increase in slip per unit stress, in agreement with the diffusion of highly pressurized fluids before the L’Aquila earthquake proposed by previous studies. Our results suggest that the largest events occur where EI is highest, in agreement with the existing link between EI and the mean loading stress.

The first mainshock (Mw 6.0) of the 2016 Central Italy seismic sequence, severely struck the Amatrice village and the surrounding localities. After few days, some Italian Institutions, coordinated by the "Center for Seismic Microzonation and its applications", carried out several preparatory activities for seismic microzonation of the area. A temporary seismic network was installed that monitored about 50 sites in epicentral area. The network produced a huge amount of records in a wide range of magnitude up to Mw 6.5. For about half of the recording stations, detailed site characterization was undertaken, encompassing singlestation noise measurements and S-wave velocity profiles. The geological and geophysical data together with the collected dataset of seismic signals were exploited to investigate the site response of selected stations. Significant amplifications are found in correspondence of several sites that experienced high level of damage (Imcs >IX), mainly at short and intermediate periods.

In atopic individuals, exposure to allergens is followed by recruitment of blood eosinophils in the target tissue. We investigated whether allergen inhalation challenge could result in depletion of blood eosinophils overexpressing adhesion molecules involved in eosinophil migration.Blood eosinophils were isolated from seven atopic asthmatic patients and seven control subjects and the "at baseline" expression of lymphocyte function-associated antigen-1 (LFA-1), macrophage antigen-1 (Mac-1) and very late antigen-4 (VLA-4) was assessed by monoclonal antibody staining and flow cytometry analysis. Asthmatic patients underwent allergen challenge and the expression of LFA-1, Mac-1 and VLA-4 by blood eosinophils was again evaluated 3 h and 24 h after allergen challenge.As compared to controls, eosinophils from atopics showed at baseline enhanced LFA-1 expression (P=0.0012), but similar Mac-1 or VLA-4 expression (P0.1, each comparison). In atopics, the percentage and absolute number of blood eosinophils were significantly decreased 3 h after allergen challenge (P=0.001 and P=0.022, respectively) but returned to similar values to prechallenge values after an additional 21 h (P0.1). Allergen challenge was also followed by a significant decrease in LFA-1 expression by eosinophils, at 3 h (P=0.002) and at 24 h (P=0.038), while no changes in Mac-1 and VLA-4 were observed. A significant correlation between postchallenge decrease in LFA-1 expression and in blood eosinophilia, both expressed as percentage (r=0.88; P0.01) or absolute number (r=0.87; P0.01) was demonstrated at 3 h (r=0.88; P0.01) but not at 24 h (r=0.64, P0.05 and r=0.11; P0.05, respectively).In allergic asthma, an early recruitment of blood eosinophils overexpressing LFA-1 occurs in the first hours after allergen challenge.

Summary. Airway nitric oxide (NO) production can be measured by chemiluminescence analyzer in children able to perform a single low exhalation. The aim of the present study was to evaluate whether exhaled NO (e-NO) peaks (first part of the exhalation) were as useful as e-NO plateaus (last part of the exhalation) in evaluating e-NO production in asthmatic children and in detecting responses to inhaled steroid treatment. E-NO peak, plateau, and rate of production values were measured in 100 atopic asthmatic children using a chemiluminescence analyser. Thirty-seven patients (mean age, 11.1 ± 0.7 years) were receiving inhaled steroids (flunisolide, 0.8–1 mg daily) or beclomethasone (0.2–0.4 mg daily), while the remaining 63 (mean age, 12.0 ± 0.4 yrs) were-steroid naive and treated only with inhaled β2-agonists on an as-needed basis. Fifteen out of the 63 steroid-naive patients were reevaluated after a short course (3 weeks) of inhaled corticosteroid treatment (flunisolide, 0.8–1 mg daily, or beclomethasone, 0.2–0.4 mg daily). Regardless of the type of data analysis (peak , plateau, or rate of production), the e-NO values of the steroid-naive patients were significantly higher than those of inhaled steroid-treated patients (P

The goals of this work are to review the Northern-Italy ground-motion prediction equations (GMPEs) for amplitude parameters and to propose new GMPEs for frequency content and duration parameters. Approximately 10,000 weak and strong waveforms have been collected merging information from different neighboring regional seismic networks operating in the last 30 yr throughout Northern Italy. New ground-motion models, calibrated for epicentral distances ≤100 km and for both local (ML) and moment magnitude (Mw), have been developed starting from a high quality dataset (624 waveforms) that consists of 82 selected earthquakes with ML and Mw up to 6.3 and 6.5, respectively. The vertical component and the maximum of the two horizontal components of motion have been considered, for both acceleration (peak ground horizontal acceleration [PGHA] and peak ground vertical acceleration [PGVA]) and velocity (peak ground horizontal velocity [PGHV] and peak ground vertical velocity [PGVV]) data. In order to make comparisons with the most commonly used prediction equations for the Italian territory (Sabetta and Pugliese, 1996 [hereafter, SP96] and Ambraseys et al. 2005a,b [hereafter, AM05]) the coefficients for acceleration response spectra (spectral horizontal acceleration [SHA] and spectral vertical acceleration [SVA]) and for pseudovelocity response spectra (pseudospectral horizontal velocity [PSHV] and pseudospectral vertical velocity [PSVV]) have been calculated for 12 periods ranging between 0.04 and 2 sec and for 14 periods ranging between 0.04 and 4 sec, respectively. Finally, empirical relations for Arias intensities (IA), Housner intensities (IH), and strong motion duration (DV) have also been calibrated. The site classification based on Eurocode (hereafter, EC8) classes has been used (ENV, 1998, 2002). The coefficients of the models have been determined using functional forms with an independent magnitude decay rate and applying the random effects model (Abrahamson and Youngs, 1992; Joyner and Boore, 1993) that allow the determination of the interevent, interstation, and record-to-record components of variance. The goodness of fit between observed and predicted values has been evaluated using the maximum likelihood approach as in Spudich et al. (1999). Comparing the proposed GMPEs with SP96 and AM05, it is possible to observe a faster decay of predicted ground motion, in particular for distances greater than 25 km and magnitudes higher than 5.0. The result is an improvement in fit of about one order of size for magnitudes spanning from 3.5 to 4.5.

To investigate whether the state of activation of circulating T-cells in childhood asthma could be related to serum IgE levels and/or to blood eosinophilia.Seventeen atopic asthmatic children, sensitized to Dermatophagoides pteronyssinus (Der p), in stable condition at the time of the study and 15 sex-matched and age-matched controls were studied. The expression of activation surface markers (HLA-DR and CD25) on peripheral blood mononuclear cells (PBMCs) was tested by monoclonal antibodies and FACS analysis, while the PBMC proliferative response to Der p antigens was measured by tritiated thymidine (3HTdR) incorporation.As compared to controls, atopic children showed higher eosinophil counts (P.01), similar lymphocyte counts (P.1, each comparison) but higher proportion of HLA-DR+ and CD25+ T-lymphocytes (P.05, each comparison). A significant Der p allergen-induced PBMC proliferation was observed in atopic children (P.01) but not in controls (P.1). Both in controls and in atopic children, no correlations were found between lymphocyte counts and eosinophil counts or total or allergen-specific IgE levels (P.1, each comparison). In contrast, weak correlations were detected between the degree of allergen-induced PBMC proliferation and: a) allergen-specific IgE levels in serum (P.05) and b) eosinophil counts (P.05).These data support the concept that the degree of activation of allergen-specific T-lymphocytes in blood may reflect the intensity of allergic sensitization in childhood asthma.

Sinusitis is a common complication of non-allergic and allergic rhinitis, and can trigger lower respiratory diseases, such as bronchitis and asthma. Standard radiography is unable to give any data about the underlying pathological mechanisms (infectious or allergic) involved and infectious rhinosinusitis is very common in pediatric age, even in allergic patients. We investigated the possibility of obtaining more useful diagnostic information, performing nasal brushing (NB) on 117 children with recurrent respiratory symptoms. The following hypothesis were evaluated: (1) whether NB neutrophil/eosinophil percentages and/or NB culture could predict the radiological evidence of maxillary sinusitis; and (2) whether differences between nonallergic and allergic patients could be detected. In the total patient group and in the nonallergic group, the comparison of NB neutrophil percentages in patients with and without maxillary sinusitis showed a statistically significant difference (median 2 and 18%, respectively; P0.001). In the nonallergic group, a NB neutrophil rateor = 5% was chosen as a cut-off between positive and negative NB diagnosis of rhinosinusitis and NB data were compared with radiological investigations. The results obtained showed that NB was fairly sensitive (91%) and predictive (84%). In allergic patients, neither neutrophil nor eosinophil percentages significantly correlated with the presence of sinusitis. Microbiological studies showed that, even if the presence of bacteria in NB resulted associated with sinusitis, a negative culture was not predictive of the absence of the disease. We therefore suggest that NB describes the present inflammatory status of the upper airways, hence, it is more suitable to describe the inflammation related to ongoing upper respiratory tract infections rather than chronic inflammation due to allergic rhinitis, characterized by relapsing episodes of acute inflammation. In conclusion, we propose to consider NB a reliable tool in the diagnosis of rhinosinusitis, particularly in nonallergic pediatric patients. Compared to standard radiological techniques, NB makes it possible to avoid radiation exposure and gives information about the pathological mechanisms involved in the single patient.

Increased levels of nitric oxide have been found in expired air of patients with asthma, and these are thought to be related to the airway inflammatory events that characterize this disorder. Since, in adults, bronchial inflammatory changes are present even in mild disease, the present study was designed to evaluate whether a significant proportion of children with mild-intermittent asthma could have increased exhaled air NO concentrations. Twenty-two atopic children (aged 11.1+/-0.8 yrs) with mild-intermittent asthma, treated only with inhaled beta2-adrenoreceptor agonists on demand and 22 age-matched controls were studied. NO concentrations in orally exhaled air, measured by chemiluminescence, were significantly higher in asthmatics, as compared to controls (19.4+/-3.3 parts per billion (ppb) and 4.0+/-0.5 ppb, respectively; p0.01). Interestingly, 14 out of 22 asthmatic children had NO levels8.8 ppb (i.e.2 standard deviations of the mean in controls). In asthmatic patients, but not in control subjects, statistically significant correlations were found between exhaled NO levels and absolute number or percentage of blood eosinophils (r=0.63 and 0.56, respectively; p0.01, each comparison). In contrast, exhaled NO levels were not correlated with forced expiratory volume in one second (FEV1) or forced expiratory flows at 25-75% of vital capacity (FEF25-75%) or forced vital capacity (FVC), either in control subjects, or in asthmatic patients (p0.1, each correlation). These results suggest that a significant proportion of children with mild-intermittent asthma may have airway inflammation, as shown by the presence of elevated levels of nitric oxide in the exhaled air. The clinical relevance of this observation remains to be established.

In allergic asthma, there is convincing evidence that changes in eosinophil and lymphocyte state of activation in blood may reflect disease activity. We evaluated whether simple blood eosinophil or lymphocyte counts in atopic children with asthma could reflect the degree of allergic sensitization. Seventy-six asthmatic children, sensitized to house dust mites (HDM), in stable conditions at the time of the study, and 53 sex- and age-matched controls (CTR) were studied. As compared to CTR, allergic patients showed higher eosinophil numbers and percentages (p0.001) but similar lymphocyte numbers and proportions (p0.1). Both in CTR and in allergic patients, eosinophil counts did not correlate with lymphocyte counts (p0.05; each comparison) but positive correlations were observed between eosinophil numbers and percentages and paper radio immunosorbent test (PRIST) levels or radio-allergo sorbent test (RAST) classes (p0.001; each comparison). When allergic asthmatic individuals were subdivided according to their age into two subgroups (Gr), no differences were found in eosinophil and lymphocyte counts and in PRIST levels and RAST values between Gr1 (or =5 years old [preschool children]) and Gr2 (5 years old [school children]) (p0.05; each comparison). Interestingly, although positive correlations between eosinophil counts and PRIST levels were found in both subgroups (p0.05; each comparison), only in Gr2 did eosinophil counts correlate positively with RAST classes (p0.001). No correlations between lymphocyte counts and PRIST levels or RAST classes were demonstrated (p0.05; each comparison). These data suggest that although blood eosinophilia was similar in preschool and in allergic asthmatic school children sensitized to HDM, only in the oldest children did blood eosinophil counts appear to be related to the degree of HDM-specific sensitization.

Summary Difficulties to comply with prescribed therapy can be cause of failure to establish and/or maintain asthma control. All current guidelines recommend regular long-term treatment in patients with persistent asthma. This includes the administration of inhaled corticosteroids combined, when necessary, with long-acting bronchodilators and/or systemic steroids, administering inhaled short-acting β2-agonists only on a prn basis. It is becoming clear that in addition to therapy: a) education for an active partnership with patients remains the cornerstone of asthma management; b) education should be carried out by health care providers involved in asthma care; c) education to asthma self-management should be tailored to the needs of each individual patient.

Although atopic asthma symptoms often seem to disappear around puberty, subjects in this age group may experience unexpected, often severe, asthma attacks. This may be related to persistence of untreated airway hyperresponsiveness/inflammation in a life period characterized by low perceptiveness of disease-related symptoms. This study was designed to evaluate the prevalence and the severity of bronchial hyperreactivity and the exhaled nitric oxide (FENO) levels in a group of steroid-naive asthmatic adolescents. Fifty-two patients with mild-intermittent asthma were studied, ages 12 to 16, sensitized to house dust mites; 22 age-matched controls, were also studied. Asthma patients showed FEV1, FEF25-75%, and FVC values not significantly different from controls, (p0.05, each comparison). By contrast, although none of the control subjects showed bronchial hyperreactivity, increased airway responsiveness to methacholine (MCh) was demonstrated in the majority of the patients and found to be severe in 36.5% (MCh PD20or = 400 microg or accumulative doseor = 1220 microg) and moderate in 32.7% (MCh PD20 400-1400 microg or accumulative dose 1220-4620 microg). In addition, FENO concentrations were significantly higher in asthmatics, as compared with controls (20.4 +/- 5.3 ppb and 4.4 +/- 0.7 ppb, respectively; p0.01) and 83% of the patients had FENO levels higher than 8.9 ppb (i.e.,2 standard deviations of the mean in control subjects). A positive, statistically significant correlation was found between FEF25-75% values and MCh PD20 (r = 0.358; p0.01) or MCh accumulative dose (r = 0.355; p0.05). No correlations were demonstrated between MCh responsiveness and FVC or FEV1 values or FENO levels and between FENO levels and pulmonary function parameters (p0.05). The high incidence of bronchial hyperresponsiveness to MCh and of airway inflammation (as demonstrated by the elevated FENO levels) in adolescents with mild asthma suggests the need for more accurate evaluation and, possibly, for early intervention with antiinflammatory drugs in a significant proportion of patients in this age group.

Orally exhaled nitric oxide (NO) levels are increased in children with asthma and thought to reflect the local inflammatory events in the airways. NO production in the lower respiratory airway is reflected in the plateau values of the NO curve, recorded while the patient is performing a slow vital capacity manoeuvre. In young patients, however, plateau values may be difficult to obtain, because the slow vital capacity manoeuvre is often terminated prematurely. In the present study, 60 steroid-naive atopic asthmatic children and 17 normal age-matched controls were asked to perform a slow vital capacity manoeuvre, during which fractional exhaled NO (FEno) levels were measured and evaluated as: a) FEno plateau levels of last part of exhalation (NO plateau); b) FEno peak values, c) area under the FEno curve (AUC). Thirteen out of the 60 steroidnaive patients were reevaluated after a short course of inhaled corticosteroid treatment. Independently of the type of data analysis, FEno values of asthmatics were significantly higher than those observed in normal controls (P0.001, each comparison). In addition, possibly because of upper airway NO contamination, FEno peak values were significantly higher than FEno plateau levels in asthmatic patients and in control subjects (P0.001, each comparison). Both in asthmatics and controls, highly positive correlations were observed between: a) FEno plateau and peak values (r0.7, P0.01, each correlation), b) FEno plateau and AUC values (r0.7, P0.01, each correlation) and c) FEno peak and AUC values (r0.9, P0.001, each correlation). In asthmatic patients, the three types of data analysis were equally sensitive in detecting the decrease in FEno levels induced by inhaled steroid therapy (P0.05, each comparison), with a good correlation between the three data analyses (r0.5, P0.05, each correlation). Thus, although quantitatively different, comparable data reflecting airway inflammation can be obtained evaluating FEno plateau, FEno peak, and area under the curve, on account of possible upper airway contamination in FEno peak, FEno plateau should be preferred to measure lower airway NO production.

SUMMARY. Airway nitric oxide (NO) production can be measured by chemiluminescence analyzer in children able to perform a single low exhalation. The aim of the present study was to evaluate whether exhaled NO (e-NO) peaks (first part of the exhalation) were as useful as e-NO plateaus (last part of the exhalation) in evaluating e-NO production in asthmatic children and in detecting responses to inhaled steroid treatment. E-NO peak, plateau, and rate of production values were measured in 100 atopic asthmatic children using a chemiluminescence analyser. Thirty-seven patients (mean age, 11.1 +/- 0.7 years) were receiving inhaled steroids (flunisolide, 0.8-1 mg daily) or beclomethasone (0.2-0.4 mg daily), while the remaining 63 (mean age, 12.0 +/- 0.4 yrs) were-steroid naive and treated only with inhaled beta(2)-agonists on an as-needed basis. Fifteen out of the 63 steroid-naive patients were reevaluated after a short course (3 weeks) of inhaled corticosteroid treatment (flunisolide, 0.8-1 mg daily, or beclomethasone, 0.2-0.4 mg daily). Regardless of the type of data analysis (peak, plateau, or rate of production), the e-NO values of the steroid-naive patients were significantly higher than those of inhaled steroid-treated patients (P0.01, each comparison). Similarly, in the subgroup of steroid-naive patients, the three methods were able to detect a decrease in e-NO levels by inhaled steroid therapy (P0.001, each comparison). Plotting the difference between e-NO peak and e-NO plateau values against their average, the peak e-NO concentrations were higher than e-NO plateau values. This difference was independent of the absolute e-NO concentration. The results of the two types of data analysis seems to agree more closely in steroid-naive patients than in steroid treated patients, or in the subgroup of steroid-naive patients who received a short course treatment with inhaled steroids. In steroid-treated subjects, the differences were up to five times higher for peak than plateau e-NO values. These data suggest that both e-NO plateau and e-NO peak values are useful in detecting airway NO production in atopic asthmatic children, but they cannot be used interchangeably. Because of possible nasal contamination in e-NO peak measurement, we prefer e-NO plateau levels for evaluating lower airway e-NO production.

Immunoglobulin binding on eosinophil surface receptors results in activation of these cells. Evaluating blood eosinophils from atopic subjects, it was investigated whether ligation of immunoglobulin E low-affinity receptor (FcepsilonRII/ CD23) with specific monoclonal antibodies (Mabs) resulted in enhanced eosinophil migration and adhesion molecule expression. Eosinophils from 20 subjects with allergic asthma (atopic individuals) and nine nonatopic normal individuals (controls) were purified using Percoll gradients. The effect of antihuman CD23 Mabs on: 1) eosinophil migration through human umbilical vein endothelial cells (HUVECs); and 2) eosinophil expression of the adhesion molecules leukocyte function-associated antigen-1 (LFA-1, CD11a/CD18), macrophage antigen-1 (Mac-1, CD11b/CD18) and very late activation antigen-1 (VLA-4, CD49d/CD29) was evaluated by specific Mab staining and flow cytometric analysis. As compared to controls, freshly isolated eosinophils from atopic individuals showed enhanced migration through HUVECs (p0.05) and increased LFA-1 expression (p0.01), but similar Mac-1 and VLA-4 expression (p0.1 for both). In both controls and atopic individuals, eosinophil incubation with antihuman CD23 Mabs induced a dose-dependent increase in cell migration through HUVECs, significant at antihuman CD23 Mab concentrations of 5 microg x mL(-1) (p0.05 for all). Similarly, incubation of the cells with antihuman CD23 Mabs induced dose-dependent upregulation of LFA-1 and Mac-1 expression, whereas no changes in VLA-4 expression were observed (p0.1). Finally, the enhanced eosinophil migration induced by antihuman CD23 Mab stimulation was significantly inhibited by antihuman LFA-1 (84+/-14% (mean+/-SEM); p0.01) and VLA-4 Mabs (47+/-15%; p0.05) but not by antihuman Mac-1 Mabs (p0.1). In both atopic and control subjects, immunoglobulin E, low-affinity receptor stimulation induces functional changes in eosinophils characterized by increased eosinophil migration associated with enhanced late function antigen-1 and Mac-1 expression.

In this paper, we present and comment on the results of a tomographic inversion of P arrival times of local earthquakes to better understand the structure and features of the Ligurian Sea, an oceanic basin originated in the Oligocene–Miocene. This tomographic inversion is the last step in a long and careful revision of the data available for the Ligurian Sea. An accurate catalogue derived from a controlled compilation of data from the numerous stations monitoring seismic activity in this young oceanic basin has been used for computation of a one dimensional (1D) reference model. A high-quality subset of the new catalogue has been used for the non-linear 3D tomographic inversion by iteratively solving the coupled hypocenter-velocity problem in a least square sense. Careful analysis of the resolution capability of the used data set has revealed the better-resolved features for interpretation. The resulting 3D model shows a high-velocity layer extending from the northeastern side of the model, where it lays about 30 km deep, to the southwestern part where it shallows to 15 km. The shallow part of this high-velocity body is located near the original area of the opening of the Ligurian Sea that took place between the Oligocene and early Miocene. Its velocity is comparable with that of an oceanic Moho (around 7.8 km/s). A lens-shaped high-velocity body, about 25 km long, located at a depth of 8–15 km, is interpreted as a series of ophiolitic bodies intruded into the upper crust.

OBJECTIVE: To test in vitro and in vivo the hypothesis that sodium nedocromil could modulate the expression of surface molecules on airway epithelial cells. METHODS: Human bronchial epithelial cells, obtained from surgically resected bronchi, were cultured and stimulated with recombinant IFN-gamma in the presence of sodium nedocromil. The intensity of the expression of surface molecules HLA-DR and ICAM-1 molecules on bronchial epithelial cells in vitro, was quantified by specific antibody staining and flow-cytometry analysis. Furthermore, we studied the effect of the drug on airway inflammation in vivo and on allergic rhinitis patients sensitized to house dust mites. Nasal epithelial cells were collected by brushing, at baseline and 2 to 3 weeks after treatment with sodium nedocromil. The expression of HLA-DR and ICAM-1 molecules was measured by flow-cytometry, and the proportions of neutrophils and eosinophils "contaminating" the epithelial cells evaluated by light microscopy examination of nasal brushings. RESULTS: The enhanced HLA-DR and ICAM-1 expression, induced by IFN-gamma, was effectively downregulated, in a dose-dependent manner, by sodium nedocromil. At all the concentrations tested (10(-9) to 10(-4) M), the inhibitory activity of the drug was stronger on HLA-DR than on ICAM-1 expression (P.05) on nasal epithelial cells, and higher proportions of nasal eosinophils (P.05), and induced a mild, but not statistically significant, decrease of nasal eosinophilia (P>.05). CONCLUSION: These data demonstrate that the antiinflammatory activity of sodium nedocromil may include modulation of surface molecule expression on airway epithelial cells.

Microzonation studies aim to estimate amplification differences of the ground motion at close sites. To evaluate site responses several techniques have been utilized and compared in recent studies (e.g., Field and Jacob, 1995, Riepl et al., 1998). Two of the proposed methods, the Reference Site Method (RSM) (Borcherdt, 1970) and the Receiver Function Technique (RFT or H/V) (Langston, 1977; Lermo and Chavez-Garcia, 1993) are based on a spectral ratio scheme. In both these techniques the source and path contributions are removed from the seismic recordings by means of a deconvolution operation using a function free of site effects. An alternative method to calculate site responses is the Generalized Inversion Technique (GIT) (Andrews, 1986; Castro et al., 1990; Boatwright et al., 1991). The site responses, the source spectra and the quality factor Q are simultaneously obtained by inverting the shear wave spectra in the framework of the parametric approach introduced by Castro et al. (1990). Generally, GIT methods are applied to data recorded by regional seismic network and few studies deal with the small interstation distance characterizing the microzonation analyses. In this work, the reliability of the results obtained by applying the GIT to site responses estimate is assessed by means of numerical simulations. The synthetic data are generated looking at a real case. We concern with five sites in Fabriano (central Italy) and we use the data recorded during 11 day experiment in the contest of the UMBRIA-MARCHE microzonation Project (see http://seism.irrs.mi.cnr.it). Four stations were placed on soft soil and one on rock site. The interstation distance ranged between 100m and 1400m, even if the maximum distance between the stations on soft soil was 600m about. The synthetic data are computed solving the forward problem, considering the same source-station geometry of the real case and assuming a simplified model for the source functions and the Q factor. Moreover, we adopt the site effects detected by applying the H/V spectral ratio to the real data set. Finally, the synthetic data are perturbed with a 10% random noise. The inversions are performed by using three different methods: Simultaneous Reconstruction Technique (SIRT), Singular Value Decomposition (SVD) and Least Squares Method (LSQ). The results obtained with the synthetic data show that GIT provide reliable estimate of the site effects. Furthermore, the site amplification relevant to the three considered inversion scheme are very similar. If no a priori information about a reference site are available, a frequency independent scaling factor is unresolved. If this is the case, only relative amplification levels between close site can be retrieved. The GIT are also applied to the real data-set. The recorded events are corrected for attenuation using a Q(f) function obtained with a coda-Q analysis (Aki and Chouet, 1975; Sato 1977). The achieved results are compared with those obtained by the reference site method and the receiver function technique.

Allergic asthma is characterized by eosinophil migration in the airways, which is strictly dependent on the expression of adhesion molecules. This study investigated whether the expression of adhesion molecules on eosinophils is increased and associated with disease activity in allergic asthma. Twenty atopic asthmatic (AA) subjects and nine controls were studied and the expression of lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18), Mac-1 (CD11b/CD18) and very late antigen-4 (VLA-4; CD49d/CD29) on blood eosinophils was evaluated by specific monoclonal antibody (Mab) staining and flow-cytometric analysis. Compared with controls, eosinophils from AA showed increased expression of LFA-1 (p0.1). In addition, LFA-1 expression correlated positively with blood eosinophil number (r=0.792, p0.1). Thus, the expression of lymphocyte function-associated antigen-1 by blood eosinophils is increased in atopic asthmatics and seems to modulate the enhanced eosinophil migration observed in allergic asthma.

It has long been noticed that the effects of geology on ground shaking is an important aspect of earthquake engineering. In general site response estimate from instrumental recordings is accomplished by removing the source and the path effects from recorded seismograms using information relevant to bedrock ground motion. When ground motion recordings at the base of the soil layers (e.g. down-hole array) are not available, simplified tecniques that only requieres recordings at the top of the layers could be used. Basically these methods may be divided in to two main categories (Bard, 1994): the 'Reference Site' and the 'Non Reference Site' techniques. In this study we adopted a non reference site technique which requires to take the speetral ratio between the horizonthal and the vertical components (WV) of the signal recorded at surface. Many authors agree that this method, when applied to earthquake data (Receiver function method (Langston, 1977)) provide a reliable estimation of the site response. Nevertheless it seems to underestimate the absolute level of amplification with respect to those inferred by the reference site or down hole recording methods. Differently, other authors pointed out that WV ratio applied to microtremors (Nakamura method, (Nakamura, 1989)) allows a reliable evaluation of the fundamental resonance frequencies of soft deposit, but it fails in providing higher harmonies, Moreover the obtained amplitude value is generally lower with repsect to the amplification measured with other techniques. In this study we utilize short period recordings as weIl as microtremors to examine frequency dependent site effects. Data were recorded by a temporary network layed out during the earthquake sequence occurred in Central Italy (Umbria Marche) in september 1997. The emphasis of this preliminary analysis is both on a comparison of the results obtained by Nakamura and Receiver function methods and on assessing the influence of different deconvolutive approaches to estimate the speetral ratio.

OBJECTIVE--To investigate whether during acute asthma episodes a decrease in blood eosinophil count could correlate with the severity of the disease. DESIGN--Prospective study on paediatric asthmatic patients admitted for acute asthma exacerbation between January 1992 and August 1993. All patients were regularly followed up in an outpatient clinic and had had a complete clinical evaluation < 1 month before admission. SETTING--Pulmonary division of the G Gaslini paediatric research institute, Genoa, Italy. SUBJECTS--21 asthmatic patients, 59 (SEM 9) months of age, admitted for acute asthma exacerbation. On the basis of clinical evaluation and the results of blood and microbiological tests performed during acute asthma exacerbations, patients were divided into two subgroups: infected (n = 13) and non-infected (n = 8). RESULTS--All but one of the patients showed a marked decrease in blood eosinophil count during the acute asthma episode, in comparison with recent count (< 1 month before admission) obtained in clinically stable conditions: 662 (116) v 210 (54) eosinophils/mm3, p < 0.0003. The decrease in the eosinophil count was more pronounced in the infected patients than in the non-infected patients, but the difference was not statistically significant (p > 0.05). Similarly, transcutaneous arterial oxygen pressure (PaO2) values measured during acute asthma exacerbations tended to be lower in infected patients, without, however, reaching statistical significance: 8.6 (0.7) v 10.1 (0.9) kPa, p > 0.05). The correlation between the decrease in blood eosinophil count and PaO2 during the acute asthma exacerbations was significant in all the patients (r2 = 0.235, p = 0.022) and in the non-infected patients (r2 = 0.653, p = 0.015), but not in infected patients. In this latter subgroup, a significant negative correlation was found between blood neutrophil counts during acute asthma exacerbations and PaO2 (r2 = 349, p = 0.026). CONCLUSIONS--During acute asthma exacerbations in atopic patients without clinical evidence of infection, the decrease in blood eosinophil count correlates significantly with the decrease in PaO2, further supporting the role of eosinophils in allergic asthma.

Exhaled nitric oxide levels are elevated in asthmatic children and decrease after inhaled steroid treatment. We evaluated the time-dependent changes in fractional exhaled nitric oxide concentration (FENO) and pulmonary function parameters following inhaled steroid therapy. Thirty-nine steroid-naive atopic patients (age 11.92+/-0.48 years) with mild intermittent asthma and 22 age-matched healthy controls were enrolled in the study; pulmonary functions and FE(NO) levels were measured. Low doses of inhaled steroids were prescribed to all asthmatic patients who were reevaluated in a second visit (between 10 and 40 days after the beginning of the treatment). At the enrolment, asthmatic patients had similar forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) values (p0.05) but reduced forced expiratory flows at 25-75% of the vital capacity (FEF(25-75%)) values, as compared to controls (p0.05). In addition, FE(NO) levels were significantly higher in asthmatics with respect to control subjects (30.8+/-3.0 and 4.0+/-0.5 ppb, respectively; p0.01). All asthmatics had FE(NO) levels higher than 8.8 ppb (i.e.,2 standard deviations of the mean in controls). After steroid treatment, patients showed significant improvement of FEV1, FVC, and FEF(25-75%) (p = 0.0001; each comparison) and a reduction of FE(NO) levels (p = 0.0001). A weak significant correlation was found between percent decrease in FE(NO) levels and percent increase in FEV1 (r = 0.33, p = 0.04) or in FEF(25-75%) (r = 0.4, p = 0.01) after treatment. When changes in FE(NO) levels and in pulmonary function parameters were corrected for days of treatment, significant correlations were still present between percent decrease in FE(NO) levels and percent increase in FEV1 (r = 0.57, p = 0.0004) or percent increase in FEF(25-75%) (r = 0.45, p = 0.006). Sixteen of the 39 asthmatic patients were evaluated on two occasions after the beginning of treatment, at days 10 and 40. The significant reduction in FE(NO) levels (p0.01) and the significant increase in FEV1 and FEF(25-75%) values observed (p0.05) after 10 days did not further improve at day 40. These data show that it is possible to demonstrate early effects of low-dose inhaled steroids in asthmatic children using objective measurements of airway caliber and inflammation.