In each of these large series, one patient died soon after rituximab administration as a result of overwhelming disease, and the main adverse event seen in these patients was reactivation of KS, which is intriguing and may have been attributable to the rapid B-cell depletion that is observed during rituximab therapy, or an immune reconstitution inflammatory syndrome to hitherto latent antigens [47]. Bower et al. [48] demonstrated after successful rituximab therapy, a significant reduction from baseline of the CD19 B-cell count, and reductions in the levels of the inflammatory cytokines

IL-5, IL-6 and IL-10. In the largest study to date [49], Bower et al. Belnacasan nmr identified 61 HIV-positive patients with histologically confirmed MCD (median follow-up, 4.2 years). Since 2003, 49 patients with newly diagnosed http://www.selleckchem.com/products/AZD2281(Olaparib).html MCD have been treated with rituximab with (n = 14) or without (n = 35)

etoposide. With rituximab-based treatment, the overall survival was 94% (95% CI: 87–100%) at 2 years and was 90% (95% CI: 81–100%) at 5 years compared with 42% (95% CI: 14–70%) and 33% (95% CI: 6–60%) in 12 patients treated before introduction of rituximab (log-rank p < 0.001). Four of 49 rituximab-treated patients have died; three died as a result of MCD within 10 days of diagnosis, and one died as a result of lymphoma in remission of MCD. Eight of 46 patients who achieved clinical remission suffered symptomatic, histologically confirmed MCD relapse. The median time to relapse was 2 years, and all have been successfully re-treated and are alive in remission. The 2- and 5-year progression-free survival rates for all 49 patients treated with rituximab-based therapy were 85% (95% CI: 74–95%) and 61% (95% CI: 40–82%), respectively. Gerard et al. [50] compared the incidence of NHL between patients who had received rituximab or not over 4.2 years of follow-up. In the group that did not receive rituximab (n = 65), 17 patients developed patient developed NHL (incidence, 4.2 of 1000 person-years). Based on the propensity

score-matching method, a significant decrease in the incidence of NHL was observed in patients who had been treated with rituximab (hazard ratio 0.09, 95% CI: 0.01–0.70). Ten Kaposi sarcoma (KS) exacerbations and one newly diagnosed KS IKBKE were observed in nine patients after rituximab therapy. Rituximab was associated with an 11-fold lower risk of developing lymphoma. KS exacerbation was the most challenging adverse event after rituximab therapy. Data from Stebbing et al. [30] showing that rising levels of HHV8 predicted relapses, suggested that combination therapy including rituximab should be considered. For immunocompetent patients the chemotherapy regimens for MCD are based on lymphoma schedules such as CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) [51].

Phenotypic (Antivirogram®; Janssen Diagnostics BVBA, Mechelen, Belgium) and genotypic assays were performed by Janssen Diagnostics BVBA (Mechelen, Belgium) to assess the development of resistance in VFs. VF was defined as loss of (rebounders) or never achieving (never suppressed) HIV-1 RNA < 50 copies/mL. The TLOVR non-VF-censored algorithm was used as a basis for this analysis, with the following additional rules: patients who discontinued before

week 12 were not taken into account to determine VF because these patients did not have the full opportunity to show virological response; patients who had a single detectable last viral load measurement were considered VFs regardless of the reason for discontinuation. Initially, phenotypic and genotypic determinations were only performed on plasma samples with HIV-1 RNA ≥ 1000 copies/mL at screening, baseline, and weeks 24, Regorafenib order 48, 96 and 192 (or withdrawal). To better assess the relationship between VF and resistance, additional click here testing was also performed on samples from VFs with HIV-1 RNA ≥ 50 copies/mL. The development of a mutation was defined as the

detection of a mutation by population sequencing at endpoint that was not present at baseline or screening. Loss of phenotypic susceptibility to an antiretroviral drug was defined as having a fold-change value above the biological/clinical cut-off of the Antivirogram® at endpoint, but not at baseline. The ITT population was used for the safety analysis. The incidence and severity of AEs and laboratory abnormalities (Division of AIDS toxicity grading table) were recorded and causality was assessed by the investigator. Safety results were compared by Fisher’s exact tests. All conducted tests were two-sided. Of the 843 patients screened, 689 were randomized and treated with DRV/r 800/100 mg once daily (n = 343) or LPV/r 800/200 mg (n = 346). Of patients in the LPV/r group, 75.1% received LPV/r twice daily, 14.5% received LPV/r once daily and 10.4% switched from LPV/r twice daily to once daily. At the time of the week 192 analysis, 86.7% of patients had switched from the LPV/r capsule to tablet formulation, 11.6%

had started and remained on capsules and 1.7% selleck screening library had started and remained on tablets. In comparison, at the time of the week 48 analysis, 83% of patients had switched from the LPV/r capsule to tablet formulation, 15% had started and remained on capsules and 2% had started and remained on tablets [6]. Baseline characteristics, as described previously [6], were well balanced across treatment arms and stratification factors. At baseline, 34% of patients had HIV-1 RNA ≥ 100 000 copies/mL and 42% had CD4 cell count < 200 cells/μL. The overall discontinuation rate through week 192 was lower in the DRV/r arm than in the LPV/r arm. Of the 689 randomized patients receiving treatment, 85 (24.8%) and 114 (32.9%), respectively, discontinued by week 192 (P = 0.02; post hoc analysis).

A description of the phenomenon with the volume scattering function assumes

the single scattering model (a particular photon does not interact with more than one particle of emulsion). The correctness of such a description of a real phenomenon has been tested for light scattering at right angles in a Baltic crude oil – seawater emulsion ( Stelmaszewski et al. 2009). The spectral dependence of the calculated function for wavelengths from 380 nm to 730 nm was compared with the measured scattering spectrum. This test has shown that the scattering function β corresponds to experimental results and that the single scattering model does provide an adequate description of the phenomenon. Application of this model under natural conditions to the scattering of solar radiation in polluted seawater needs to take into consideration the fluorescence of the emulsions. selleckchem This is important because petroleum is a fluorescent medium. Emulsion particles are fluorescent objects

and, moreover, dissolving the fluorescent compounds can accompany emulsifying oil in water. The test mentioned above was carried out for monochromatic radiation (the scattered light measured had the same wavelength as the illuminating radiation), and fluorescence remained undetected in these measurements. In the case learn more of polychromatic radiation like natural sunlight, the separation of fluorescence from scattering appears Mannose-binding protein-associated serine protease to be impossible. The foregoing indicates that any investigation of light scattering in an oil-in-water emulsion should be supplemented by a study of its fluorescence properties. This is the subject of this paper: it discusses the fluorescence of emulsions of seven different oils representing the main petroleum types. These emulsions were tested in the spectral range from 220 nm to 720 nm. The important question was to determine how photoluminescence can influence light scattering measurements. To this end, fluorescence and scattering

spectra were measured and the intensities of these phenomena compared. The test was carried out on seven different types of petroleum: two crude oils of differing properties (Baltic and Romashkino), two fuels, as well as lubricating, hydraulic and transformer oils. Samples of each oil were emulsified in seawater. Because the water should be assumed to be a non- fluorescent and fully transparent medium, it was prepared by dissolving the principal sea salts in demineralized water to achieve an ionic composition similar to that of natural water of salinity 7.5 PSU. The emulsion was prepared as follows. An aliquot of oil (3 cm 3) was dissolved in n-hexane (2 cm 3), and this solution was stirred with water (3 dm3) in a stainless steel vessel at 600 rpm for 3 hours. The emulsion was then allowed to stabilize at 20°C for 24 hours.

This is particularly expressed in smaller cerebral vessels increasing the incidence of both – overt and silent lacunar infarctions. One of the modifiable risk factors is diabetes mellitus. Generally, vascular complications of diabetes can be separated into microvascular (diabetic nephropathy, neuropathy and retinopathy) and macrovascular (coronary disease, cerebrovascular disease, peripheral artery disease) complications. Atherosclerotic manifestations can be divided in early stages – endothelial dysfunction, increase in arterial stiffness, and increase of intima–media thickness. Later atherosclerotic of blood vessels stages can be recognized as atherosclerotic plaques

which provide different grade of vessel lumen stenoses [3]. In addition to atheroma formation, there is a strong evidence 5-Fluoracil concentration of increased platelet adhesion, hypercoagulability, impaired nitric

oxide generation and increased free radical formation as well as altered calcium regulation in diabetic patients. Cerebral autoregulation is the ability to maintain constant cerebral blood flow despite changes in the cerebral perfusion pressure. selleck chemicals llc Breath holding method was introduced in early 90s as reproducible, non-invasive screening method to study cerebral hemodynamic by means of Transcranial Doppler (TCD). It is accurate, specific and sensitive method for evaluation of cerebral vasoreactivity in comparison with other methods (functional magnetic resonance imaging – MR, positron Org 27569 emission tomography – PET, single photon emission computed tomography – SPECT). In our previous works we standardized breath holding index (BHI) values for different age and sex groups [3] and [4]. Recently pulse pressure amplification and arterial mechanics, most often explored as arterial stiffness (inversely related to arterial strain-measurement of arterial volume load and physiological

answer of the body to increased pressure load expressed as pulse pressure) are named as those with greatest sensitivity for vascular event prediction [5], [6] and [7]. E-tracking is new automatized software for evaluation of the vessel wall functions, it enables monitoring vessel wall biomechanical parameters and early detection of the subclinical extracranial vessel atherosclerotic changes [8] and [9]. The most efficient stroke management is primary and secondary prevention, optimal prevention would be to recognize atherosclerotic changes in their early subclinical stages. BHI would provide information about intracranial vessel function and arterial stiffness would provide information about extracranial arteries biomechanical characteristics. According to those findings we can recognize atherosclerosis in its subclinical stages and apply principles of primary and secondary prevention [10] and [11]. We included 60 volunteers in our study, 20 healthy volunteers and 40 diabetic type 2 patients – 20 with well controlled serum glucose levels and 20 with poor controlled serum glucose levels.

Animal care and

use procedures were conducted in accordance with NIH, USDA and institutional guidelines. An initial vector dose response study was carried out with a 1 month survival using 48 rats to determine the optimal dilution of AAV2/8-hSNCA and ratio of AAV2/8-hSNCA to silencing vector for use in efficacy experiments (Table S1). For the behavioral study, treatment groups were: AAV- hSNCA alone (n=16 at 1 month; n=11 at 2 months); AAV-hSNCA and AAV-NS (n=15 at 1 month and 10 at 2 months); AAV-hSNCA and AAV-mir30-SNCA (n=16 at 1 month and n=11 at 2 months). LBH589 cost At 1 month, rats were sacrificed for histological analysis of TH-IR fiber density in ST and Iba-1 in SN this website (n=5). The remaining rats were sacrificed at 2 month with half the rats prepared for histology and half for molecular analyses (n=5–6). A separate group of rats was injected for molecular analysis at 10 days (n=3). The skin overlying the skull of isoflurane-anesthetized rats was shaved. Stereotaxic surgeries were carried out using a Stoelting stereotaxic apparatus equipped with a Stoelting

quintessential stereotaxic injector holding a 10 µl Hamilton syringe with a 26 gauge needle. A hole was drilled in the skull over the appropriate injection site at stereotaxic coordinates, 5.5 mm posterior, −1.9 mm lateral and 7.4 mm ventral from Bregma (SN injection). The syringe was inserted into the brain at a speed of ~1 mm/min and then allowed to remain in place for 2 min before vector injection. 2 μl of each virus mixture was injected at a rate of 0.5 μl/min into one SN, and the needle was left in place for 5 min at the end of the injection in order to minimize diffusion up the needle track. The doses of each vector used for the dose response experiments are shown in Table S1. For the efficacy experiment, rats received 6.22×109 vg of AAV2/8-hSNCA alone or with either see more 3.51×1011 vg of AAV2/8-mir30-NS

or 3.26×1011 vg of AAV2/8-mir30-SNCA in a 2 μl volume. The syringe was withdrawn at a rate of ~1 mm/min. The drill hole was plugged with gel foam to control bleeding and Marcaine was spread around the surgical site. The skin was sutured and treated with topical antibiotic ointment and rats were returned to the vivarium upon recovery from anesthesia. Twenty-four hours after surgery, rats were transferred to a clean cage and the old bedding was autoclaved. Rats were placed inside of a plexiglass cylinder, partially surrounded by mirrors in a quiet, dark room. The activity of each rat was recorded on videotape under red light for a 10 min period. The number of times each paw was used for wall touches on the first 25 rearings of each rat was counted by an observer blinded to treatment group to determine forelimb use preference as previously published (Schallert et al.

Post-hoc FDA response for abdominal pain was significantly greater than placebo for the 100-mg eluxadoline group, and stool consistency response displayed a more dose-proportional response with superiority over placebo observed for the 200-mg eluxadoline group (P < .10 for the

100-mg eluxadoline group). The higher dropout rate in the 200-mg eluxadoline group and lack of data imputation for those dropouts may contribute to the failure of that dose to achieve superiority over placebo for the pain responses during the 12-week study interval used in the post-hoc analyses. The most common adverse events reported were those of the gastrointestinal system. Gastrointestinal adverse events, including nausea, vomiting, and abdominal pain, were more frequently reported

in the 200-mg eluxadoline group, suggestive this website of a continuum of eluxadoline’s Selisistat purchase local pharmacological effects on the gut. The higher incidence of abdominal pain reported in the 200-mg eluxadoline group might also contribute to the lack of efficacy seen for pain response in this dose group. Although the incidence rate of constipation was higher in the 100-mg eluxadoline group, the events were generally mild in intensity and were tolerated by the patients without requiring discontinuation of study drug. The most notable safety finding among patients receiving eluxadoline was infrequent reports of pancreatitis, including 2 cases that occurred after only 1 or 2 doses of study drug. Although 2 of the 4 total pancreatitis cases were confounded by mitigating factors (one patient with high blood alcohol level at the onset of the event and another patient who was off study drug for 2 weeks at the onset of the event), a possible relationship Baf-A1 to eluxadoline treatment could not be ruled out because of the known association between opioids and acute pancreatitis and the lack of any

such events among placebo-treated patients in this study.17 After the last case, the protocol was amended to exclude patients who might have been predisposed to pancreatitis, that is, those with histories of pancreatitis, biliary duct disease, sphincter of Oddi dysfunction, alcohol abuse, binge drinking, elevated serum lipase, or cholecystectomy. The rationale for excluding patients with sphincter of Oddi dysfunction was based on the knowledge that patients experiencing sphincter of Oddi dysfunction are sensitive to opioids and can experience severe abdominal pain and pancreatitis, even after a single dose of opioid-containing medications.18 Importantly, after implementation of the amendment, no additional events of pancreatitis were reported among the 210 patients enrolled. Future studies will need to prospectively evaluate the potential association between pancreatitis and eluxadoline treatment and also evaluate whether the exclusionary precautions implemented in the current study might minimize any potential risk.

Two were older than 12 years of age, and two were younger than 6 years of age at the time of their evaluation. Their full-scale intelligence quotients ranged from 62-88. We emphasize that the lowest full-scale intelligence quotient score (51) in the whole sample was observed in a child carrying a mutation affecting the expression of Dp140, but not the expression of Dp71. A more detailed analysis of the Wechsler subscales revealed some interesting and completely new differences in cognitive profiles in the two subgroups of patients with Duchenne muscular dystrophy (Fig

1). Patients in the Duchenne muscular dystrophy distal group scored significantly lower than patients of the Duchenne find more muscular dystrophy proximal group in Digit Span (t(26.83) = −3.627, P = 0.001), Picture Arrangement (t(32) = −2.419, P = 0.021), and Object Assembly (t(32) = −2.075, P = 0.046). Children in the Duchenne muscular dystrophy proximal group tended (albeit not significantly) to score

lower than those in the Duchenne muscular dystrophy distal group on Comprehension (t(38) = 1.777, P = 0.08). All these PR 171 differences tended to retain (for Digit Span, Picture Arrangement, and Object Assembly, P = 0.009, P = 0.025, and P = 0.064, respectively) or even improve (Comprehension subtest, P = 0.006) their significance when full-scale intelligence quotient was used as a covariate in the analysis (to assess the specific components of reported impairments). No Bonferroni correction was applied, because the variables are obviously intercorrelated. Compared (using t tests) with control subjects, patients in the Duchenne muscular dystrophy distal group scored significantly lower (P < 0.03) on all verbal subtests except on Comprehension, while patients in the Duchenne muscular dystrophy proximal group scored lower (P < 0.03) on all verbal subtests except Digit Span. In terms of Performance subtests, the children with distally mutated Duchenne muscular dystrophy performed significantly worse than control subjects in Picture Completion, Picture Arrangement, Block Design,

and Coding (P < 0.05), whereas the children with proximally mutated Duchenne muscular dystrophy did not differ from control subjects on any subtest (P > 0.05). Concerning scores obtained on language tests, comparisons Fludarabine between subgroups were repeated, controlling for the effect of full-scale intelligence quotient (set as a covariate in an analysis of variance). As depicted in Fig 2, both subgroups demonstrated deficits in all linguistic functions, with distally mutated patients obtaining generally lower scores than proximally mutated patients. Only scores in Grammatical Comprehension proved significantly different in the two subgroups (F (1.40) = 5.667, P = 0.02), and this difference was confirmed when intelligence quotient was entered as a covariate into the analysis (F (1.39) = 5.07, P = 0.03).

, 2006). Research was focused on, but not limited to, the pro-apoptotic ( Shankar et al., 2007 and Shankar and Srivastava, 2007a), anti-proliferative ( Bachmeier et al., 2010), anticancer ( Bar-Sela et al., 2010), antiviral ( Rechtman et al., 2010), antiarthritic ( Funk et al., 2006), anti-amyloid ( Ringman et al., 2005), antioxidant ( Glauert et al., 2010), anti-obesity ( Alappat and Awad, 2010) and anti-inflammatory ( Jurenka, 2009) properties of curcumin. The underlying mechanisms of these diverse effects are only poorly understood, however, they seem to involve the regulation of various molecular targets, including

transcription factors (nuclear factor-kB), growth factors (vascular endothelial cell growth factor), inflammatory cytokines (tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (mammalian target of rapamycin, mitogen-activated protein PKC inhibitor kinases, and Akt) and other enzymes (cyclooxygenase Vemurafenib mw 2 and 5 lipoxygenase) ( Aggarwal and

Sung, 2009 and Zhou et al., 2011). It is important to note that there are substantial controversies regarding the action of curcumin on HIV as well as inflammatory conditions ( Liu et al., 2005 and White and Judkins, 2011). Increasing evidence indicates that cation channels also serve as targets for curcumin, i.e. micromolar concentrations of curcumin inhibit Ca2+-release-activated Ca2+ channel (ICRAC) and K+ channels (Kv and SK4) in human T cells ( Shin et al., 2011), block the Cav3.2 T-type

Ca2+ current in bovine adrenal zona fasciculata (AZF) cells ( Enyeart et al., 2009), bTREK-1 K+ channels ( Enyeart et al., 2008) and the Kv1.4 voltage-gated K+ channel ( Liu et al., 2006) in bovine adrenocortical cells. Curcumin also seems to ameliorate pain Rolziracetam hypersensitivity in rats through a selective blockade of transient receptor potential vanilloid 1 (TRPV1) channels ( Yeon et al., 2010). In contrast to cation channels, which seem to be inhibited by curcumin, chloride channels seem to be activated by the substance. The open probability of the cystic fibrosis transmembrane regulator (CFTR) chloride channel was reported to be increased by curcumin in excised, inside-out membrane patches ( Berger et al., 2005). Accordingly, Wang et al. ( Wang et al., 2005 and Wang et al., 2007) found that curcumin (0.5–10 μm) stimulated ion currents mediated by both wild-type and ΔF508-CFTR in excised membrane patches. These authors pointed out that the structure of curcumin (two aromatic rings separated by a hydrocarbon spacer) is similar to that of 5-nitro-2-(3 phenylpropylamino)benzoic acid-AM (NPPB-AM), which is an uncharged form of the well-known chloride channel blocker NPPB and acts as a CFTR agonist by increasing the channel opening rate. Interestingly, curcumin was also shown to increase the activity of a CFTR mutant (G551D) with an extremely low open probability despite its normal trafficking to the plasma membrane ( Yu et al., 2011).

Moreover, the mentioned models are more

oriented towards ship design and also have limitations leading to particular uncertainties and biases. In the model by Ehlers and Tabri (2012), e.g. the bow shape of the striking vessel is simplified to only the bulbous bow, leading to uncertainty and bias in regards to the actual damage extents. In the model by Hogström (2012), the bow geometry is accounted for but the collision damage is calculated assuming a fixed vessel body, which leads to uncertainties related to the redistribution of kinetic energy into deformation energy, particularly for impacts in the bow or stern area (Ehlers and Tabri, 2012). The model by Chen and Brown (2002), which lays at the basis of the model

by van de Wiel and van Dorp (2011), is a simpler model in terms of collision energy SGI-1776 chemical structure and structural damage but accounts both for bow shape and external dynamics. The polynomial regression model by van de Wiel and van Dorp (2011) uses a set of predictor variables to link the impact scenario variables to the longitudinal and transversal damage extents. These predictor variables are representative of the impact scenario. An impact scenario can be described through the vessel masses m1 and m2, the vessel speeds v1 and v2, the impact angle φ, the relative damage location l and the striking ship’s bow half-entrance angle η, see Fig. 6. An additional variable is used EPZ015666 price as a scaling factor between the results of the small and the large tankers given in the set of damage cases ( NRC, 2001). This variable is set as the vessel length L or the vessel width B depending on whether longitudinal or transversal damage extents are calculated. As predictor variables, dimensionless variables xi are applied as follows: equation(14) x1=1-exp-ek,pβpαpx2=1-exp-ek,tβtαtx3=Beta(l∗+12|1.25,1.45)-Beta(-l∗+12|1.25,1.45)x4=CDF(η)x5=CDF(L)orCDF(B)where ek,p and ek,t are respectively the perpendicular and tangential collision L-NAME HCl kinetic energy, l* the relative impact location

with reference to midship and αp, βp, αt and βt parameters of a Weibull distribution for the predictor variables involving respectively the perpendicular and tangential kinetic energy. These are given in Table 4, along with the values for the empirical CDF of the bow half entrance angle η and the empirical CDF(L) and CDF(B).We write: equation(15) l∗=l-12 equation(16) ek,p=12(m1+m2)(v1sin(φ))2 equation(17) ek,t=12(m1+m2)(v2+v1cos(φ))2Using these predictor variables, a polynomial regression model is made for respectively the expected damage length yL and penetration depth yT: equation(18) yL=exp(hL(x|β^l)) equation(19) yT=exp(hT(x|β^t))with: equation(20) hL(x|β^l)=∑i=15β^0l+∑j=15β^i,jlxji equation(21) hT(x|β^t)=∑i=15β^0t+∑j=15β^i,jtxjiThe regression coefficients for the expressions hL and hT are given in Table 5.

However, the mean currents do not go into the open area west of Bornholm but either follow the coast

straight toward the west or go south into Bornholm. An interesting question is whether it is possible to calculate approximations of the measures from the statistics of the currents only without employing the computationally expensive technique of tracer ensemble simulations. This question is outside the scope of the present study. A certain asymmetry is visible in several places, e.g., east of Gotland, where the maximum is closer to Gotland than Latvia, or south of Bornholm, where the maximum is closer to Bornholm than Poland. The asymmetry south of Bornholm can be explained to a large extent by the small size of the island of Bornholm, which occupies a much narrower sector of directions than the Polish coast at the same distance. The same explanation cannot be applied to the asymmetry east of Gotland. For Instance, the isoline between yellow and buy VE-822 green in Fig. 4 is very close to Gotland but far away from the Latvian coast. However, the southerly currents close to Gotland (see Fig. 3) may explain the asymmetry. There are also northerly currents

along the opposite coast, but the bathymetry in the direction of the currents differs. Many of the investigations of the Gulf of Finland suggest asymmetries in the FK506 mw corresponding measures and in the locations of maritime routes (Viikmäe et al., 2011, Andrejev et al., 2011, Soomere et

al., 2011a and Soomere et al., 2011c). The Gulf of Finland is rather symmetrical. Hence, the asymmetries are explained by the patterns of the currents rather than by the bathymetry. For the northern Baltic proper, a very strong asymmetry toward the west is found by Viikmäe et al. (2011). This finding is in contrast to our results, which show a slight, if any, asymmetry toward the east. Viikmäe et al. (2011) attributed the strong asymmetry to the dominating west wind. However, as in Thymidylate synthase our study, Viikmäe et al. (2011) have not considered the direct impact of wind on an oil spill. In our study, there are no easterly current components (Fig. 3), which could be the result of preferably westerly wind. A more likely explanation of the asymmetry is provided by the southerly current in the western part of the area, as well as the fact that trajectories are not traced outside of the domain studied by Viikmäe et al. (2011). In Fig. 15, some examples of real routes of tankers carrying hazardous cargo are shown. The routes for these ships have been optimized with respect to fuel consumption and travelling time by considering forecasted currents, waves and wind. Environmental factors are considered only by taking into account areas prohibited by national maritime administration agencies. In general, real maritime routes use more direct paths than those calculated in our study, e.g., most routes go north instead of south of Bornholm.