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Variable levels of methane in the martian atmosphere have eluded explanation partly because the measurements are not repeatable in time or location.We report in situ measurements at Gale crater made over a 5-year period by the Tunable Laser Spectrometer on the Curiosity rover.The background levels of methane have a mean value 0.41 ± 0.16 parts per billion by volume (ppbv) (95% confidence interval) and exhibit a strong, repeatable seasonal variation (0.24 to 0.65 ppbv).This variation is greater than that predicted from either ultraviolet degradation of impact-delivered organics on the surface or from the annual surface pressure cycle.The large seasonal variation in the background and occurrences of higher temporary spikes (∼7 ppbv) are consistent with small localized sources of methane released from martian surface or subsurface reservoirs., The authors thank the reviewers for constructive comments that greatly improved the manuscript. The research described here was carried out in part at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (NASA). Funding: Funding from NASA’s Planetary Science Division is acknowledged by authors C.R.W., P.R.M., S.K.A., G.J.F., C.M., C.P.M., M.H.W., M.G.T., A.S., D.A., C.H.H., R.V.G., A.P., J.L.E., D.P.G., J.C.P., D.K., L.E.C., J.P.-G., S.C.R.R., M.D.S., D.M.H., M.L., J.C., R.W.Z., and A.R.V. R.N.-G. acknowledges funding from the National Autonomous University of Mexico and Consejo Nacional de Ciencia y Tecnología. J.E.M. and C.L.S. acknowledge funding from the Canadian Space Agency MSL participating scientist program. S.P.Sc. acknowledges funding from the UK Space Agency. A.-M.H. acknowledges funding from the Finnish Academy under grant 310509. J.P.-G. acknowledges funding from the Spanish Ministry of Economy and Competitiveness under contract ESP2016-79612-C3-1-R. Author contributions: C.R.W. and P.R.M. performed TLS-SAM instrument design, build, and testing (IDBT); surface operations (SO); test-bed activities (TBA); data analysis (DA); data correlations (DC); and science interpretation (SI). G.J.F. and C.M. performed IDBT, SO, TBA, and DA. S.K.A., J.E.M., C.P.M., C.L.S., A.S., D.A., B.S., P.J.C., C.F., P.-Y.M., R.V.G., C.H.H., A.P., J.L.E., D.P.G., S.P.Sa., and R.W.Z. performed SI. J.C. and A.R.V. performed SO. J.C.P., D.K., and L.E.C. performed IDBT. G.M., J.M.-T., J.G.-E., M.-P.Z., M.G.T., S.P.Sc., R.N.-G., A.V.-R., H.K., D.V.-M., M.D.S., A.-M.H., M.G., D.M.H., and M.L. performed DC. J.P.-G. and S.C.R.R. performed DC and SI. Competing interests: No potential conflicts of interest exist for any of the listed authors. Data and materials availability: The data described in this paper are publicly available from NASA’s Planetary Data System (PDS) under an arrangement with the Mars Science Laboratory (MSL) project at http://pds-geosciences.wustl.edu/missions/msl/sam. htm, under the run numbers given in table S2.

The effects of dextropropoxyphene on the steady-state kinetics of oxcarbazepine and its metabolites were investigated in eight patients with epilepsy or trigeminal neuralgia. One patient dropped out of the study, presumably due to side-effects of dextropropoxyphene. Dextropropoxyphene did not affect the plasma levels of the principal active metabolite, 10, 11-dihydro-10-hydroxy-carbamazepme. Since dextropropoxyphene is known to increase the plasma levels of carbamazepine, leading to toxicity, the findings of this study suggest that oxcarbazepine is a useful alternative to carbamazepine when concomitant dextropropoxyphene therapy is required.

A final market image (FMI) tablet formulation of oxcarbazepine was compared with the marketed formulation (current market formulation (CMF)) and with the clinical trial formulation (CTF) tablet used during clinical efficacy and safety studies. The goal of the study was to compare the bioavailability after single doses and at steady state of the FMI versus CMF and CTF as well. Additionally, the effect of food was evaluated on the final market formulation. The study was an open-label, single-center, 4-way crossover trial. Each treatment period consisted of a single dose of 600 mg OXC on Day 1. From Day 4 up to including Day 7, 600 mg b.i.d. were administered. A final dose of 600 mg was administered in the morning on Day 8. Blood samples were taken on Day 1 before and on Day 7 (predose) and on Day 8 (morning dose). Plasma concentrations of MHD (the main metabolite of OXC) were determined by using a validated HPLC assay. FMI as test formulation was compared with the CMF and CTF as reference formulations. FMI under fed conditions was also compared with FMI under fasting conditions. These comparisons were made using data following single-dose administration and steady state conditions. Plasma AUC for single dose or AUC(0-12h) for steady state, and plasma Cmax, log-transformed (natural base), were used for the assessment of bioequivalence. The 90% confidence interval (CI) approach was used for testing bioequivalence. Bioequivalence was accepted if the CI was contained within the region (0.8, 1.25). At steady state under fed conditions, tested formulation (FMI) was bioequivalent to CTF and with the reference marketed formulation (CMF) with regard to AUC and Cmax. After single dose under fed conditions, FMI and CTF were bioequivalent with regard to AUC and Cmax, and FMI and CMF were equivalent with regard to AUC but not Cmax. Food had no effect on the bioavailability of the FMI. These results clearly support the switch from the current market formulation (CMF) to the final market image tablet in the countries where Trileptal is or was already registered.

A 39-year-old woman presented in the first month of pregnancy with reflex sympathetic dystrophy involving both lower legs. Symptoms became so severe that she could not walk unassisted, and the pain worsened after delivery. Radiographs showed patchy reduction in apparent density in the tarsal bones and around the ankles and knees. Uptake was increased in these areas on technetium methylene diphosphonate bone scan. Bone density (dual-energy X-ray absorptiometry) was reduced in the spine, hip, and radius. Biochemical tests were normal except for an increase in urinary excretion of the N-telopeptide cross-linking region of type I collagen (NTx). Because the patient wanted to continue breast-feeding, intravenous pamidronate was administered at monthly intervals. Breast milk was collected for 48 h after the infusion. The pain began to decrease soon after drug administration was initiated, and it was virtually gone by 6 months. NTx excretion fell by 78% and bone density increased by as much as 18.9% over the 6-month treatment interval. The baby was healthy and grew normally. Milk expressed after the first treatment was assayed for pamidronate content by high-performance liquid chromatography with fluorescence detection. None was detected (limit of quantitation, 0.4 micromol/liter). This case shows that pamidronate may be considered for treatment of lactating women.

Objective: The pharmacokinetics of orally and intravenously administered valsartan were determined in two studies. In a first pilot study, three i.v. doses of valsartan were given in an ascending manner (5, 10 and 20 mg) to evaluate tolerability and basic pharmacokinetics of the i.v. formulation. In a second study, the absolute bioavailability of 80 mg valsartan from a capsule and a buffered solution was compared with a 20 mg i.v. dose. Methods: The concentrations of valsartan in plasma and urine were measured using HPLC. The disposition of valsartan after an i.v. dose was characterized by biphasic decay kinetics, with a distribution phase (half-life 1.0 h), followed by a longer elimination phase (half-life 9.5 h). The volume of distribution at steady state was 16.9 l, and the total body clearance 2.2 l · h−1. 29% of the i.v. dose was recovered unchanged in the urine. Results: Plasma levels peaked 2 h after oral administration of the 80 mg capsule. Thereafter, plasma levels declined biexponentially with a terminal t1/2 of 7.0 h. Cmax was reached 1 h after administration of the solution, and t1/2 was 7.5 h. On average 7.3% (capsule) and 12.6% (solution) of the dose was excreted in the urine as the unchanged drug. The fraction of dose absorbed and systemically available after oral administration was 0.23 for the capsule and 0.39 for the solution, based on AUC. Absorption appeared to follow two first-order processes. The first phase was rapid, with a half-life of 0.5 h and 0.9 h for solution and capsule, respectively. The slower absorption phase was characterized by a half-life of 6.5 h for the solution and 3.5 h for the capsule. Most of the drug was absorbed during the period 0.4 h to 3 h post-dosing, and 90% of the fraction absorbed from the capsule was absorbed within 5 h.

The aim of the study was to determine whether the concentration of CGP 53437 measured in the sera of normal volunteers following oral administration of a single dose, had retained its anti-HIV activity; and whether such results could be of predictive value for future clinical antiviral efficacy studies. CGP 53437 is an inhibitor of HIV-1 protease that suppresses HIV-1 replication in human lymphocytes in vitro at 100 nM. The in vitro anti-HIV activity of human sera obtained from CGP 53437-treated individuals was compared with that of sera spiked with known concentrations of CGP 53437 (in the presence or absence of α-1 acid glycoprotein). It was found that the concentration of the compound measured in the sera from treated individuals provided the expected in vitro anti-HIV activity. These results not only validate our analytical method for detection of CGP 53437, but also support the notion that interaction of CGP 53437 with plasma proteins does not significantly affect its antiviral activity (shift of the ED90 by a factor of three). In conclusion, ex vivo anti-HIV activity determinations of sera containing an HIV protease inhibitor, in conjunction with the pharmacokinetic evaluation during Phase I clinical studies, can provide valuable information regarding the suitability of such inhibitors for further clinical studies.

To determine if iron chelation therapy has activity against human malaria, we administered desferrioxamine B in amounts of 100 mg/kg per day by continuous 72-hour subcutaneous infusions to 28 volunteers with asymptomatic Plasmodium falciparum infection in a randomized, double- blind, placebo-controlled crossover trial. Peripheral blood concentrations of P falciparum ring forms were determined at 12-hour intervals in all subjects and serum concentrations of desferrioxamine B + ferrioxamine (the iron complex of desferrioxamine B) were measured in 26 subjects. Geometric mean concentrations of asexual intraerythrocytic parasites decreased with both chelator and placebo treatment, but the decrement with desferrioxamine B was significantly greater than that with placebo (P less than .006) during both the initial and crossover periods. Compared with placebo, desferrioxamine B treatment was associated with an almost 10-fold enhancement of the rate of parasite clearance during both phases of the trial (P less than .007). Mean +/- SEM steady state concentrations of desferrioxamine B + ferrioxamine were 6.90 +/- 0.60 mumol/L at 36 hours and 7.72 +/- 0.68 mumol/L at 72 hours; in vitro, the ID50 has been reported to be approximately 4 to 20 mumol/L. No drug toxicity was detected. Parasitemia recurred in 19 of 24 participants followed-up over 1 to 6 months. We conclude that desferrioxamine B enhances the clearance of P falciparum parasitemia and that iron chelation may provide a new strategy to be developed for the treatment of malaria.

To determine if iron chelation therapy has activity against human malaria, we administered desferrioxamine B in amounts of 100 mg/kg per day by continuous 72-hour subcutaneous infusions to 28 volunteers with asymptomatic Plasmodium falciparum infection in a randomized, double- blind, placebo-controlled crossover trial. Peripheral blood concentrations of P falciparum ring forms were determined at 12-hour intervals in all subjects and serum concentrations of desferrioxamine B + ferrioxamine (the iron complex of desferrioxamine B) were measured in 26 subjects. Geometric mean concentrations of asexual intraerythrocytic parasites decreased with both chelator and placebo treatment, but the decrement with desferrioxamine B was significantly greater than that with placebo (P less than .006) during both the initial and crossover periods. Compared with placebo, desferrioxamine B treatment was associated with an almost 10-fold enhancement of the rate of parasite clearance during both phases of the trial (P less than .007). Mean +/- SEM steady state concentrations of desferrioxamine B + ferrioxamine were 6.90 +/- 0.60 mumol/L at 36 hours and 7.72 +/- 0.68 mumol/L at 72 hours; in vitro, the ID50 has been reported to be approximately 4 to 20 mumol/L. No drug toxicity was detected. Parasitemia recurred in 19 of 24 participants followed-up over 1 to 6 months. We conclude that desferrioxamine B enhances the clearance of P falciparum parasitemia and that iron chelation may provide a new strategy to be developed for the treatment of malaria.

Oxcarbazepine (trileptal) oral suspension has been reformulated and a study was performed to compare the bioavailability after single doses and at steady state of the current and former oral suspension versus the marketed film-coated tablets and to compare the bioavailability of the current and former oral suspension. The results support the switch from the former oral suspension to the current oral suspension and also from both oral suspensions to the film-coated tablet and vice versa. The study was an open-label, single-center, 3-way crossover trial. Each treatment period consisted of a single dose of 600 mg oxcarbazepine on Day 1, 600 mg oxcarbazepine b.i.d. repeated administration from Day 4 up to including Day 7, and a final dose of 600 mg oxcarbazepine administered on the morning of Day 8. Blood samples were taken on Day 1, Day 7 and Day 8 (pre-dose). Plasma concentrations of the main metabolite of oxcarbazepine (MHD) were determined using a validated HPLC assay. The 2 oral suspensions were compared with the film-coated tablet as reference formulation under fasted conditions. Also the current oral suspension was compared with the former oral suspension. These comparisons were made using data following single dose administration and under steady state conditions. Plasma AUC for single dose and AUC(0-12h) at steady state and plasma Cmax, log-transformed (natural base) were used for the assessment of bioequivalence. The 90% confidence interval (CI) approach was used for testing bioequivalence. Bioequivalence was accepted if CI was contained within the region (0.8, 1.25). At steady state, both the former and the current oral suspensions showed bioequivalence with the film-coated tablet with respect to AUC and Cmax. The current oral suspension was also bioequivalent when compared to the former oral suspension with respect to AUC and Cmax. After single dose, the former oral suspension was bioequivalent when compared to the film-coated tablet with respect to both AUC and Cmax. However, the current oral suspension was bioequivalent to both the film-coated tablet and the former oral suspension with respect to AUC but not to Cmax.

Objective: This was a randomised, open, three-way crossover study in 12 healthy male volunteers to determine the effect of a single oral dose of cimetidine on the pharmacokinetics of a single oral dose of the angiotensin II receptor antagonist valsartan – and vice versa. The volunteers received either valsartan alone (160 mg), or cimetidine alone (800 mg), or valsartan 1 h after cimetidine. The study was designed primarily to detect a possible influence of cimetidine on the rate and extent of absorption of valsartan. Methods: Plasma concentrations of valsartan and cimetidine, measured by means of high-performance liquid chromatography, were used to calculate pharmacokinetic parameters. The rate of absorption of valsartan and the fraction of the dose absorbed and systemically available after oral administration were calculated using data from an i.v. study with valsartan in healthy young volunteers. Results: The pharmacokinetics of cimetidine – area under curve (AUC0–48 h), maximum concentration (Cmax), time to reach Cmax (tmax) and apparent terminal plasma half-life (t1/2) – was not changed by co-administration of valsartan. For valsartan, the AUC0–48 h increased by 7% and the Cmax by 51% (ratio of geometric means) with co-administration of cimetidine. The higher value for Cmax was attributed to the initial increase in the rate of absorption of valsartan: ka was increased 2.7-fold and another indicator for the rate of absorption, Cmax/tmax, 2.2-fold. This effect was ascribed to inhibition of acid secretion by cimetidine, which leads to a higher gastric pH, thereby increasing the solubility of valsartan; the t1/2 of valsartan was not changed. After valsartan alone, 19% of the dose was absorbed, 23% with co-administration of cimetidine. It was estimated that only 2.2% of the possible change in AUC might be missed by giving a single high dose of cimetidine instead of multiple doses, with the aim to optimally inhibit formation of the inactive metabolite of valsartan. Cimetidine-related changes in the rate of elimination of valsartan were not anticipated, since the clearance from plasma occurs mainly by biliary excretion of unchanged valsartan; metabolism and renal excretion are only minor contributors. Therefore, even in the clinically relevant situation with multiple doses of valsartan and cimetidine, notable changes in the pharmacokinetics of valsartan, except for an increase in Cmax, are not to be expected. This increase in Cmax appears to be of no clinical significance. Valsartan alone and in combination with cimetidine was well tolerated by healthy subjects.

Pharmacokinetics, pharmacodynamic effects and tolerability of 200 mg valsartan, once-daily for 8 days, were investigated in 16 healthy, normotensive volunteers on a normal sodium diet.This was a double-blind, placebo-controlled, randomized crossover study. Drug concentrations in plasma and urine, angiotensin II (Ang II) concentrations in plasma, systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR) in the supine position and 3 min after passive head-up tilting, as well as safety parameters (ECG, clinical chemistry and hematology, renal water and electrolyte excretion) were measured over 24 h after the first dose (day 1) and at steady state on day 8.Absorption and distribution of valsartan were rapid (Cmax, 2 h; t1/2 lambda 11 h), followed by a slower terminal elimination phase (t1/2 lambda 2, 6 h) on days 1 and 8, with little accumulation in plasma (increase of 20% on day 8). Less than 10% of the dose was excreted unchanged in urine. The increase in plasma Ang II (Cmax, 6 h) was significantly enhanced at steady state. Supine SBP and DBP significantly decreased on day 8 only, by an average of -3.6 and -2.4 mmHg, respectively, versus placebo, without a concomitant increase in HR. Upon passive tilting, the increase in DBP, normally reinforced by sympathetic renin release, was slightly but significantly blunted on day 1 (-2.0 mmHg) and day 8 (-4.0 mmHg) of treatment with valsartan versus placebo. The orthostatic reflex increase in HR was slightly enhanced compared with placebo by an average of 2.8 beats min-1 on day 1 and by 2.9 beats.min-1 on day 8. Valsartan was well tolerated and had no influence on ECG, clinical laboratory parameters, and water, electrolyte and uric acid excretion.Pharmacokinetics of valsartan are unchanged after multiple once-daily dosing, with little (expected) accumulation in plasma. Effects of 200 mg valsartan on blood pressure in healthy subjects on a normal sodium intake are small and become more prominent after repeated dosing. Indirect evidence of AT1 blockade by valsartan is demonstrated by an increase of plasma Ang II and by a blunted DBP response to passive tilting. The decrease in blood pressure at steady state enhances the increase in plasma Ang II. Valsartan is well tolerated and is devoid of effects on water, electrolyte and uric acid excretion at 200 mg per day in healthy normotensive volunteers.

Pharmacokinetic and pharmacodynamic interactions between single oral doses of valsartan (160 mg) and furosemide (40 mg) were investigated in an open, randomized, three-period crossover study in twelve healthy male subjects.A washout period of one week was observed between treatments. Pharmacokinetic measurements included plasma concentrations of valsartan and furosemide, and urinary excretion of the latter. Plasma renin activity (PRA), plasma angiotensin II, blood pressure, heart rate, as well as urinary water and electrolyte excretion were determined as pharmacodynamic variables. Efficiency of furosemide for sodium and water excretion was calculated as the ratio of the measured pharmacodynamic effect and the urinary excretion of furosemide.Simultaneous administration of valsartan and furosemide did not modify the pharmacokinetics of valsartan. In contrast, Cmax, AUC, and urinary excretion of furosemide were significantly reduced following simultaneous treatment with valsartan. Inter- and intra-individual variability of the pharmacokinetic variables was high for both furosemide and valsartan. PRA and angiotensin II increased, and blood pressure decreased after all treatments. These effects were most pronounced after the combined treatment. The decrease in blood pressure was additive, at most, while the increase in PRA and angiotensin II appeared to exceed simple addition. No relevant effects on heart rate were observed. The diuretic effect of furosemide, as assessed by urinary water and electrolyte excretion, was unchanged after co-administration of valsartan, despite the lower bioavailability of furosemide after the combined treatment.

To evaluate dose proportionality and absolute bioavailability of a new enteric-coated pellet formulation of pamidronate disodium (AREDIA), nine females (aged 52–66 years) were given three different single peroral doses of pamidronate disodium (75, 150, and 300 mg) and an i.v. infusion of 15 mg over 30 minutes at constant infusion rate. Repeated peroral doses (75 and 150 mg) were administered to 12 females (aged 51–70 years) for 10 consecutive days. Urinary excretion of pamidronate after peroral and i.v. administration was used for estimation of pamidronate absorption. Renal excretion of pamidronate ranged from 0.01% to 0.35% of dose, with mean values of 0.11, 0.16, and 0.18% for 75, 150, and 300 mg, respectively. After i.v. infusion, the renal excretion of pamidronate was 26–53% of the dose, lower than for other bisphosphonates. The absolute bioavailability was 0.31% (range 0.08–0.7%) after 75 mg, 0.43% (0.01–1.20%) after the 150-mg dose, and 0.48% (0.07–1.06%) following 300 mg of pamidronate disodium. Urinary excretion after the 10th intake showed a significant increase (difference 0.07% (range -0.003-0.29%),P < 0.02) when compared with the first dose. In conclusion, intestinal uptake of pamidronate was low with high intraindividual variation, like other bisphosphonates.

Background: Pamidronate is a secondgeneration bisphosphonate used in the treatment of tumor-induced hypercalcemia and in the management of bone metastases from breast cancer, myeloma, or prostate cancer. The pharmacokinetics of pamidronate is unknown in cancer patients. Purpose: To determine the influence of the rate of administration and of bone metabolism, we studied the pharmacokinetics of pamidronate at three different infusion rates in 37 patients with bone metastases. Methods: Three groups of 11-14 patients were given 60 mg pamidronate as an intravenous infusion over a period of 1, 4, or 24 hours. Urine samples were collected in the three groups of patients. Plasma samples were obtained only in the 1-hour infusion group. The assay of pamidronate in plasma and urine was performed by high-performance liquid chromatography with fluorescence detection after the derivatization of pamidronate with fluorescamine. Results: The body retention (BR) at 0-24 hours of pamidronate represented 60%-70% of the administered dose and was not significantly modified by the infusion rate. In particular, the BR at 0-24 hours was not reduced at the fastest infusion rate. Among patients, a threefold variability in BR at 0-24 hours occurred, which was related directly to the number of bone metastases and, to some extent, to creatinine clearance. At 60 mg/hour, the plasma kinetics followed a multiexponential course characterized by a short distribution phase. The mean (±SD) half-life of the distribution phase was 0.8 hour (±0.3), the mean (±SD) of the area under the curve for drug concentration in plasma × time at 0-24 hours was 22.0 × 8.8 μmol/L × hours, and the mean (±SD) of the maximum plasma concentration was 9.7 μmol/L (±3.2). Pharmacokinetic variables remained unchanged after repeated infusions applied to four patients. Clinically, the three infusion rates were equally well tolerated without significant toxicity. Conclusions: The 1-hour infusion rate could be proposed as kinetically appropriate for the administration of pamidronate to patients with metastatic bone diseases. [J Natl Cancer Inst 84: 788-792, 1992]

Summary.-This investigation concerned a comparison of the opinions and attitudes of male felons incarcerated for homicidal or assaultive behavior and matched with subjects of a normal, control group. The 5 0 incarcerated and 50 control subjects were closely matched on age, sex, race, and education. A specially designed questionnaire of 330 items was administered one-to-one or in groups of rwo to five subjects. The felons were screened for current psychotic disturbance, heavy medication, and mental retardation. They were classified as either homicidal or assaultive by review of their official records and the judgment of two three-member panels of judges. The data were subjected ro one-way analysis of variance and an item analysis using the Lawshe and Baker technique for testing the significance of differences becween percentages. There have been some efforts, although not large scale ones to use psychological evaluations and psychometric scales to assess the traits of convicted felons. This effort is increasing; yet need for research continues. Notable has been the work of Megargee and Bohn (1979) in classifying criminal offenders. Studies have concerned differentiating between violent and nonviolent felons (Justice & Birkman, 1972; Wilds, 1973; Perdue & Lester, 1974; Justice, Justice, & Kraft, 1974; Lester, et dl., 1975; Hays, Roberts, & Solway, 1981; Wolfgang & Ferracuti, 1982 ) . METHOD An inmate group of aggressive felons was divided into two groups. Homicidal felons were 50 incarcerated men serving time for first-degree murder in a maximum security prison. These inmates were first identified by examination of their institutional records and then qualified by two panels of judges, one of three psychologists and the other of three experienced correctional officers who knew the felons. The assaultive felons were 50 men convicted for assaultive crimes other than murder. Examples would be assault, malicious cutting and wounding, or malicious shooting and wounding. These subjects were also classified on the basis of their official records. The normal control group of 50 male factory/industrial workers was comprised mostly of hourly employees and some college students with no previous record of a conviction for adult felony.

A dynamic method for the damage evaluation of large bridges is developed by BFVA and Technical University Graz. The method is a combination of dynamic in-situ tests and dynamic calculations and is also useful for the general improvement of mathematical modelling for static and dynamic calculations. Experiences with prestressed bridges were obtained. In general damages decrease the stiffness and increase damping. The structures are very large and the influences of cracks on dynamic parameters are very small. The basic concept of the method is to elaborate a dynamic model in the virgin state of the structure. Damages of the structure will lead to a certain pattern of deviations of dynamic parameters from the virgin state and can be used for localisation and quantification of damages in a global manner.