Detail description of sampling sites.
\r\n\tThis book chapter’s main theme will be focused on transmission dynamics, pathogenesis, mechanisms of host interaction and response, epigenetics and markers, molecular diagnosis, RNA interacting proteins, RNA binding proteins, advanced development of tools for diagnosis, possible development of concepts for vaccines and anti drugs for RNA viruses, immunological mechanisms, treatment, prevention and control.
\r\n\t
World Health Organization explains a healthy city is one that is continually creating and improving those corporal and communal environments and expanding those community assets that enable people to mutually support each other in achieving all the purposes of life and in developing to their maximum potential. While the basic tasks of the urban environment are climate change, the wasteful use of natural resources, the health impacts of airborne pollutants and exposure to vast arrays of hazardous chemicals. These problems are bound up with the modern lifestyles and at the same time require attention and action of many different parts of society. Environmental awareness to people is at rise, as more and more individuals are search for higher living standards and a better living surroundings. Thus the development of sound environmental policy requires both scientific information about the linkages between pollutant emissions and human health effects and value judgments about the importance of these effects relative to other social concerns.
\nAsia is one of the significant part of the world in the view of atmospheric aerosol loading because of the presence of growing economies like India, China and other developed and developing countries. Mechanization, expansion, financial growth and connected increase of energy demands have resulted in profound deterioration of urban air quality [1, 2]. The developing countries like India have shifted their economics from manufacturing toward services that involve information technologies. Growth in information technology have amplified the quantity and extended the use of equipment used in proximity to office worker due to which electronic media used for entertainment, telecommunications and data processing have become widespread in daily life [3, 4]. Typical examples are television, audio-visual recorders, stereo systems, and CPUs with their peripherals such as monitors and printers, scanners and copiers. There is growing concern about the levels of potentially harmful pollutants that may be emitted from office and other commercial centers equipment. Office equipment has been found to be a source of ozone, particulate matter, volatile organic compounds (VOCs) and semi-volatile organic compounds (SVOCs) [5]. Several studies have revealed more consistent correlation for the concentration of fine (PM2.5) and inhalable (PM10) particles with health than any other air pollutant [6, 7]. In cities, a major fraction of ultrafine aerosol particles (particle diameter, Dp <100 nm) cause adverse health effects in sensitive human beings more than larger particles due to their increased lung deposition efficiency [8]. With possible adverse health effects, the question of the chemical characterization of the fine particles released by such devices is of special importance [9]. Trace elements associated with PM2.5 and below are nonvolatile in nature; they are less vulnerable to chemical alterations and remain in the form as they were emitted, even though they tend to undergo long range atmospheric transport [2, 10, 11]. Particulate metal components can have severe carcinogenic and toxic effects on occupants when inhaled in higher concentration. Short-term differences of atmospheric metal concentration have been observed in a day-to-day or even an hour-to-hour basis [1, 12]. Epidemiological studies show that these ultrafine particles cause more adverse health effects in sensitive human beings more than larger particles due to their increased lung deposition efficiency. Therefore the reduction of particulate and associated metal pollution to some acceptable levels is an important environmental issue. The objective of this study helps in pinpointing the integrated actions essential to reduce the particulate pollutant and eliminate the toxicological environment impacts of Indian urban environment. This can enhance the capacity of national environment within the city and which can be implemented to other towns and cities of India that can benefit health, quality of life and the economy.
\nThe city of Taj, Agra (27°10′N, 78°02′E) is located in the central part of northern India, about 204 km of south of Delhi in the Indian state of Uttar Pradesh. Agra is one of the most famous tourist spots of the country. The city is situated on the west bank of the river Yamuna 169 m above sea level. A part of the great northern Indian plains, Agra region experience a tropical climate. In winter the temperature ranges from 3.5 to 30.5°C and during summers which are hot and dry the temperature ranging from 32 to 48°C. The downward wind is south-southeast 29% and northeast 6% of the time in summer, and it is west-northwest 9.4% and north-northwest 11.8% of the time in winter. Agra has about 1.586 million population and the population density is about 1084 persons per square km (ORG, office of the registrar New Delhi, India: Ministry of Home Affairs, 2011). In this study real time series data for mass and number of coarse and fine particles were monitored in indoor environment of three different location (two shops, two commercial buildings and two offices) in different parts of Agra city (Figure 1A and B). Indoor PM5 was also collected from these sites for chemical characterization. The detailed description of these sites is shown in Table 1.
\n(A) Map of Agra city showing different sampling sites and (B) different sampling sites.
Sampling site/type | \nConditions | \nBuilding age (years) | \nHeight | \nWorking area (m2) | \nTraffic/greenery/trees | \nVentilation | \n
---|---|---|---|---|---|---|
Supermarket 1 | \nHigh population area, congested, made of iron, brick and cement | \n2 | \n5–10 | \n600 | \nHigh traffic with no greenery around, situated in congested commercial area | \nAir cooling system but mostly kept close | \n
Supermarket 2 | \nHigh population area, made of iron, brick and cement | \n3 | \n5–10 | \n550 | \nHigh traffic with no greenery around, situated in congested old market area | \nImproper ventilation system with no use of exhaust | \n
Shop 1 | \nCongested and very populated area of the city, made of bricks and cement | \n20 | \n5 | \n181 | \nHeavy traffic throughout the day with no greenery around, situated in congested commercial area | \nImproper ventilation | \n
Shop 2 | \nCongested and very populated area of the city, made of bricks and cement | \n20 | \n5.5 | \n192 | \nHeavy traffic throughout the day with no greenery around, situated in congested old market area | \nImproper ventilation | \n
Office 1 | \nCongested and very populated area of the city, made of bricks and cement | \n12 | \n6 | \n287 | \nHigh traffic with less greenery, situated in congested residential area | \nImproper ventilation with no use of exhaust | \n
Office 2 | \nCongested and very populated area of the city, made of bricks and cement | \n40 | \n5 | \n250 | \nHigh traffic with no greenery, situated in congested commercial area | \nImproper ventilation with no use of exhaust | \n
Detail description of sampling sites.
A short term study was conducted from September 2011 to November 2011 to determine number and mass concentration of coarse and fine particles, i.e., PM10, PM5.0, PM2.5, PM1.0, PM0.5, and PM0.25 in indoors of commercial centers, shops and offices in of Agra city. Chemical characterization in PM5 was also carried for heavy metal detection. A total of 36 samples (i.e., 18 samples each for PM mass and number concentration) and 36 samples for chemical characterization were collected from these sites at the same time. Grimm Aerosol Spectrometer model (1.109) (Figure 2) was selected for the monitoring of coarse and fine particles, it runs at a flow rate of 1.2 L/min ± 5% constant with controller for continuous measurement during the sampling period. It measures mass in (μg m−3) and number in (particles/m3). The sampler measures particles from 0.25 to 32 μm range in 31 channel sizes, each unit is certified by National Institute of Standards and Technology, monodisperse latex on the size of channels calibrated by www. GRIMM Aerosols.com. To improve the time resolution, the range was limited to 0.25–10 μm. The sampling equipment was housed such that it was as compact as possible and positioned indoors to cause minimal intrusion to the occupants. The instrument was generally positioned in the center of the rooms where people spent most of their time. Inlet heads were positioned as close as possible to head height. The instrument was set to average the data over 15 min to reduce the response time and to enable the identification of individual sources. The GRIMM particle measuring system is equipped with GRIMM 1174 Software for data acquisition.
\nGRIMM aerosol spectrometer (model: 1.109).
After sampling the filters were thrice weighted before and after sampling using four digit (Wenser, Model No. MAB 120) with sensitivity off 2 ± mg and in the 220–20 mg range. Before the samples were equilibrated in desiccators at 20–30°C and relative humidity of 30–40% in humidity controlled room for 24 h. Filters cassettes were used to carry weight filter papers to the sampling sites, there filters were transferred to filter holders and placed on the sampling plates. Exposed filters along with the holders were then wrapped with aluminum foil, and taken back to the laboratory and placed in the desiccators. Field blanks were collected with exposed filters, they were latter weighted and were stored in refrigerator at 4°C to prevent the evaporation of volatile components [13]. Handy sampler Model No. 821 (Envirotech, New Delhi make) (Figure 3) was used for PM5 chemical characterization which was maintained at a flow rate of 2 L/min and YES-IAQ monitor model No.206 (Figure 4) for recording the air exchange rate.
\nHandy sampler APM 821.
Handy sampler YES-206.
The exposed filter papers were digested in analytical grade (Merk) HNO3 and kept on hot plate at the temperature of 4–60°C for 90 min. The solution was diluted up to 50 ml with distilled deionized water and stored in polypropylene bottles at 4°C till analysis. Analysis for metals (Fe, Br, Pb, Ba, Zn, Sb, Cu, Cd, Hg) was done on AAS (AAnalyst 100, Perkin Elmer) (Figure 5) present in our departmental analytical lab. The tested suites of elements were related to specific combustion sources using Principal component analysis statistical techniques.
\nAtomic absorption spectrophotometer (Perkin Elmer, AAnalyst 100), with schematic diagram.
A total of 12 samples per month (i.e., six for mass concentration and six for number concentration) for PM10, PM5.0, PM2.5, PM1.0, PM0.5, and PM0.25 were collected from three different indoor microenvironments. Tables 2 and 3 gives the statistical summary of particulate mass and number concentrations along with temperature, CO2, humidity and air exchange rate during the total sampling days. During the campaign study the mean PM10, PM5.0, PM2.5, PM1.0, PM0.5 and PM0.25 mass concentration and standard deviation (SD) was 324.17 ± 46.70, 270.27 ± 42.66, 223.41 ± 48.19, 137.47 ± 23.43, 99.84 ± 20.39 and 52.34 ± 11.45 μg m−3 at supermarket sites, 324.57 ± 47.13, 271.30 ± 40.63, 225.44 ± 49.79, 137.89 ± 23.86, 99.41 ± 20.72 and 53.07 ± 11.36 μg m−3 at shop sites respectively and 327.00 ± 47.03, 272.98 ± 40.03, 227.44 ± 50.54, 139.17 ± 23.75, 101.33 ± 20.75 and 56.13 ± 11.58 μg m−3 at office sites respectively and for number concentrations for coarse and fine particles, mean values of PM10, PM5.0, PM2.5, PM1.0, PM0.5 and PM0.25 was 564,050 ± 915,78.43, 320,394 ± 393,85.52, 193,678 ± 17,880.25, 174,101 ± 23,865, 158,428 ± 29,089.22 and 73,378 ± 22,638 particles/L at supermarket sites, 589,882 ± 98,489.67, 349,888 ± 39,072.42, 206,648 ± 25,422.77, 181,495 ± 24,131.06, 166,050 ± 28,853.73 and 77,619 ± 22,858.65 particles/L at shop sites respectively and 622,352 ± 77,730.91, 352,319 ± 38,052.23, 232,186 ± 35,323.51, 193,769 ± 28,899.68, 178,172 ± 24,245.03 and 85,121 ± 24,879.46 particles/L at office sites respectively.
\nStatistical summary of mass concentration during the sampling duration at sampling sites.
On applying the one way ANOVA (SPSS 10.0) to the mean values of particulate concentrations at all the sites for each location significant values found for PM10, PM5.0, PM2.5, PM1.0, PM0.5 and PM0.25 were close to 1 or were approximately 1. For the supermarkets it varied from 0.931 to 0.997, for shops it varied from 0.942 to 0.998 and for offices they varied from 0.938 to 0.999, indicating that there is no significant difference between the concentrations of two types of similar microenvironment and thus have similar kind of sources which lead to the generation of particulate pollutant in their indoor environment. Due to the above reason, the discussion made in this report is explained on the basis of average concentration of two types of similar microenvironment rather than six places individually. The study period for mass and number concentration trend of PM10, PM5.0, PM2.5, PM1.0, PM0.5 and PM0.25 from September 2011 to November 2011 in supermarket, shops and offices are given in Figure 6A and B. On comparing with the standards given by WHO guidelines (24 h mean = 25 μg m−3, 50 μg m−3 for PM2.5 and PM10), PM2.5 exceeded 9 times and PM10 exceeded 6.5 times in all the indoor microenvironment (i.e., supermarkets, shops, and offices). On comparing with NAAQS standards (24 h mean = 60 μg m−3, 100 μg m−3 for PM2.5 and PM10), Coarse to fine particles exceeded 6 to 4 times at all the sampling locations. For coarse and fine particles similar kind of trend was obtained at all the different microenvironments. However, the mass and number concentration trends for coarse and fine particles were somewhat higher for all the particle sizes in the offices in comparison to shops and supermarkets. The higher concentration trend in the offices can be due to particle resuspension from vacuum cleaning, sweeping, low air exchange rate as or due to the movements of office workers [14, 15]. PM concentrations are also greatly affected in the offices by the use of printers and multitask devices [16]. During the campaign study a slight increase was notice in the PM concentrations during month of October in comparison to September and November. On applying the one way ANOVA (SPSS 10.0) to the mean values of particulate concentrations at all the working environment; significance values were found forPM10, PM5.0, PM2.5, PM1.0, PM0.5 and PM0.25 were close to 1 or approximately 1. They varied from 0.923 to 0.998 at two offices site, 0.918 to 0.993 at two shop sites and 0.920 to 0.987 at two commercial center sites indicating that there is no significant difference between the concentrations of same type of working environment and thus have similar kind of sources which lead to the generation of particulate pollutant in their environment.
\n(A) Mass concentration of PM10, PM5.0, PM2.5, PM1.0, PM0.5 and PM0.25 at supermarkets, shops and offices from September 2011 to November 2011, and (B) number concentration of PM10, PM5.0, PM2.5, PM1.0, PM0.5 and PM0.25 at supermarkets, shops, and offices from September 2011 to November 2011.
The diurnal trend of particulate number and mass concentration during the sampling duration has been monitored continuously throughout the night and day in indoors at the supermarket, shop and office (Figure 7A and B). Full-day variation trend of particulate pollutant around the clock covers all the indoor activities taking place. The highest mass and number concentration peaks were observed basically during the morning hours from 9:00 to 10:00 AM and late in the evening hours from 18:00 to 19:00 PM. The maximum concentrations of the particulate matter during this time can be due to resuspension generated by traffic and other human activities, as these sites are mostly adjacent to busy traffic roads of the city (Figure 1A). As a result concentrations reaches maximum during the rush hours in the evening and morning [17]. The low concentrations for all the particles are observed during 3:00–4:00 AM in the early morning hours. Whereas, during the working hours low concentrations were reported between 14:00 and 15:00 PM in the afternoon hours at all the microenvironments. All the coarse and fine particulate sizes showed similar trends.
\n(A) Full day variation in μg m−3 in different indoor microenvironment and (B) full day variation in particles/L in different indoor microenvironment.
Inter Particulate Ratios at sampling sites.
For better understanding of these particles in the different indoor environment, inter particulate ratios have also been evaluated and reported in Table 4. The average contribution of finer particles (i.e., PM0.25, PM0.50, PM1.0, and PM2.5) to coarse particles (i.e., PM5.0 and PM10) in indoors during the study period for September was around 44.7% at supermarket sites, 44.8% at shops sites and 47% at office sites. In October it was 45.7% at supermarket sites, 46.2% at shops sites and 47.9% at office sites. In November it was 37.1% at supermarket sites, 37.5% at shops sites and 38.0% at office sites. Particles especially PM2.5 and below are resuspended in air with high intensive activities during indoor activities when there is low ventilation rates due to closed doors and windows, which get reduced to some level during the infiltration from higher air exchange rates [18]. The shops are more ventilated in comparison to offices and supermarkets (Tables 2 and 3).
\nStatistical summary of Number concentration during the sampling duration at sampling sites.
At offices contribution of finer particles to coarse particles is 44% while at the shops and supermarket is around 42%. This suggests that office sites are more exposed to finer particles then in comparison to shops or supermarkets.
\nCharacterization of PM components, including inorganic elements, is of central importance in proposing mechanisms for health effects and in source apportionment studies [19, 20]. Data obtained by chemical analysis for seven metals in PM2.5 particulate size collected from 36 samples of different indoor environment of supermarkets, shops and offices sites is shown in Table 5. Observations on the basis of these tables are as follows:
\nMetal concentration (μg m−3) | \nZn | \nNi | \nCr | \nMn | \nCu | \nFe | \nPb | \n
---|---|---|---|---|---|---|---|
Average | \n0.60 | \n0.04 | \n0.09 | \n1.36 | \n0.07 | \n0.38 | \n0.17 | \n
SD | \n0.02 | \n0.02 | \n0.01 | \n0.13 | \n0.01 | \n0.04 | \n0.03 | \n
Maximum | \n0.62 | \n0.06 | \n0.10 | \n1.50 | \n0.08 | \n0.42 | \n0.20 | \n
Minimum | \n0.58 | \n0.03 | \n0.08 | \n1.24 | \n0.06 | \n0.35 | \n0.15 | \n
Average | \n0.62 | \n0.07 | \n0.10 | \n1.52 | \n0.09 | \n0.42 | \n0.21 | \n
SD | \n0.03 | \n0.02 | \n0.02 | \n0.13 | \n0.01 | \n0.03 | \n0.03 | \n
Maximum | \n0.65 | \n0.09 | \n0.12 | \n1.65 | \n0.10 | \n0.45 | \n0.25 | \n
Minimum | \n0.60 | \n0.06 | \n0.09 | \n1.40 | \n0.08 | \n0.40 | \n0.19 | \n
Average | \n0.67 | \n0.08 | \n0.12 | \n1.78 | \n0.13 | \n0.45 | \n0.25 | \n
SD | \n0.03 | \n0.02 | \n0.03 | \n0.15 | \n0.02 | \n0.03 | \n0.04 | \n
Maximum | \n0.70 | \n0.10 | \n0.15 | \n1.95 | \n0.15 | \n0.48 | \n0.29 | \n
Minimum | \n0.65 | \n0.07 | \n0.10 | \n1.66 | \n0.11 | \n0.42 | \n0.22 | \n
Statistical profile of metal concentrations in PM2.5 (N = 36).
At supermarket sites the sum of the average concentrations for fine particles were found to be 223.41 μg m−3 and ranged from 243.27 to 188.85 μg m−3 in indoors, at shops site the concentration was 225.44 μg m−3 and ranged from 238.17–192.93 μg m−3 in indoors and whereas at offices sites the concentration was found to be 227.44 μg m−3 and the range from 245.65 to 194.00 μg m−3 in indoor environment respectively. The total analyzed parameters contributed 65% at supermarket sites, 70% at shop sites while 75% at the offices site of the particulate concentration respectively. The trends in increasing order of metal concentrations at supermarket, shop and office sites are as follows:
\nA similar kind of trends were found for metal concentrations in all the three microenvironment, indicating one or more similar kind of sources contributing to these microenvironment, being present in similar kind of commercial areas of the city. Out of 0.14% contribution of analyzed metals in PM5 at supermarket percentage contribution of each metal is shown in Figure 8A while from the total contribution of 0.16% at shop sites and 0.20% at office sites percentage contribution of each metal is shown in Figure 8B and C. Global emissions reported shows that natural and anthropogenic sources can contribute to the principal aerosol classes, but values change according the local scenario (coarse and fine) of atmospheric particulate matter (PM). About 10–20% of the aerosols can be characterized as anthropogenic on a global scale [21], but these values may drastically change due to local scenarios, human activities, and the prevailing particle cutoff. The principal component analysis is the most common multivariate statistical methods applied in environmental studies. The SPSS software package version 10.0 was used for the multivariate analysis. The levels of various elements vary by different orders of magnitude and hence the principal component analysis was applied to the correlation matrix.
\n(A–C) Percent contribution of each metal at supermarket, shop, and office sites.
Principal component analysis (PCA) is a well-established tool for analyzing structure in multivariate data sets [22]. A varimax rotated factor analysis was performed to identify the major sources responsible for the particulate pollutants and the sampling sites. It is a statistical method; in which a set of multiple intercorrelated variables are replaced by small number of independent variables or factors by orthogonal transformations also called as rotations. This is achieved by analyzing the correlation matrix of the variable, i.e., by computing their Eigen values and the Eigen vectors. “Factor loadings” obtained after the varimax rotation give the correlation between the variables and the factors. Data which is included in the matrix only if their Eigen values of tat factor is bigger than 1. The varimax technique was adopted for rotation of the factor matrix to allocate the initial matrix into one that was easier to understand. For this SPSS version 10.0 was used to perform factor analysis. At supermarket, shop and offices sites we have mostly multistory modern types of construction, as they have been built recently; usually their outside environment is of high traffic during the day with both heavy and light motor vehicles. These are in the busy commercial places of the city with many kinds of other activities like major hospitals, hotels, railway station, big or small restaurants and banks etc.
\nAt supermarket sites indoors three sources identifying 90% of metal concentration were identified (Table 6). Zn, Ni, Cr and Mn represent the factor 1 with 36% variance. The common source attributed to the smoking of the occupants in the indoor environment [23]. Factor two is represented by Cu and Fe with 31% variance and was attributed to resuspension of dust due to indoor human activities [23]. Third factor is comprised of Pb with 24% and is attributed to emission of paints from wall, ceiling and furniture [24].
\nRotated component matrix at office sites | \n|||
---|---|---|---|
\n | 1 | \n2 | \n3 | \n
Zn | \n0.29 | \n0.43 | \n|
Ni | \n0.44 | \n0.30 | \n|
Cr | \n0.43 | \n0.19 | \n|
Mn | \n0.29 | \n0.48 | \n|
Cu | \n0.23 | \n0.22 | \n|
Fe | \n0.38 | \n0.45 | \n|
Pb | \n0.44 | \n0.31 | \n|
Total | \n2.51 | \n2.16 | \n2.14 | \n
% of variance | \n35.88 | \n30.79 | \n23.62 | \n
Cumulative % | \n35.88 | \n66.67 | \n82.29 | \n
Factor analysis at supermarket sites.
At shop sites indoors three sources identifying 93% of metal concentration were identified (Table 7). Zn, Cr and Mn represent the factor 1 with 37% variance. The common source attributed to the smoking of the occupants in the indoor environment [25]. Factor two is represented by Ni, Cu and Fe with 28% variance and was attributed to electrical wiring or appliances [1]. Third factor is comprised of Pb with 27% and is attributed to emission of paints from wall, ceiling and furniture [24].
\nRotated component matrix at office sites | \n|||
---|---|---|---|
\n | 1 | \n2 | \n3 | \n
Zn | \n0.47 | \n0.46 | \n|
Ni | \n0.48 | \n0.42 | \n|
Cr | \n0.33 | \n0.26 | \n|
Mn | \n0.34 | \n0.41 | \n|
Cu | \n0.44 | \n0.38 | \n|
Fe | \n0.39 | \n0.30 | \n|
Pb | \n0.42 | \n0.34 | \n|
Total | \n2.89 | \n1.99 | \n1.89 | \n
% of variance | \n37.28 | \n28.45 | \n26.99 | \n
Cumulative % | \n37.28 | \n69.73 | \n96.72 | \n
Factor analysis at shop sites.
At office sites indoors three sources identifying 92% of metal concentration were identified (Table 8). Zn, Ni, Cr and Mn represent the factor 1 with 30% variance. The common source attributed to the smoking of the occupants in the indoor environment [25]. Factor two is represented by Cu and Fe with 32% variance and was attributed to resuspension of dust due to indoor human activities [23]. Third factor is comprised of Pb with 30% and is attributed to emission of paints from wall, ceiling, and furniture [24].
\nRotated component matrix at office sites | \n|||
---|---|---|---|
\n | 1 | \n2 | \n3 | \n
Zn | \n0.47 | \n0.46 | \n|
Ni | \n0.38 | \n0.47 | \n|
Cr | \n0.62 | \n0.48 | \n|
Mn | \n0.47 | \n0.32 | \n|
Cu | \n0.41 | \n0.40 | \n|
Fe | \n0.39 | \n0.34 | \n|
Pb | \n0.32 | \n0.47 | \n|
Total | \n2.40 | \n2.24 | \n2.10 | \n
% of variance | \n30.22 | \n32.03 | \n29.99 | \n
Cumulative % | \n30.22 | \n66.25 | \n96.24 | \n
Factor analysis at office sites.
Excess cancer risks (ECRs) were calculated using the unit risk and the PM-bound concentration of the metals which represents the total concentration of the metals. ECRs can be calculated simply by using the formula given below [26, 27]:
\nThe information on the carcinogenic types and the unit risks of the metals was obtained from the US EPA database for IRIS (Integrated Risk Information System) [28]. Fine particles, PM2.5-bound metals such as Cd, Cr, Ni and Pb are the known carcinogenic metals which can cause serious health risks to occupants in these microenvironments. They are introduced to the occupants by exposure through the inhalation pathway [27]. Cadmium have been categorized as the B1 carcinogen, while Cr (VI) is classified as group A which indicates that it is a known human carcinogen by the inhalation route of exposure. Therefore, the concentration of Cr (VI) used for the carcinogenic risk assessment was calculated as one seventh of the total Cr concentration. Nickel also has been classified as group A materials, known human carcinogens. From the research findings it is evident that Ni was mainly emitted from tobacco or cigarette smoke and outdoor sources like the industrial or refinery emissions can contribute to it in an indoor environment [29]. Lead on the other hand is also a probable human carcinogen (group B2), but human evidence is inadequate and its unit risk is currently being amended by the US EPA.
\nPM2.5-bound metals such as Cd, Cr and Ni, respectively, based on PM concentrations. The particles whose diameters are less than 4 mm can penetrate into the trachea, bronchi and the alveoli [28, 29]. In Table 9, the estimated ECR of PM2.5-bound carcinogenic elements in the indoor environment for the average values and the 95th percentile values of Cd, Cr and Ni. The total ECRs based on the average values of Cd, Cr (VI) and Ni in PM2.5 in different indoor environment varied from 0.47 to 0.32 × 10_6, respectively. Ni had the highest ECRs followed by Cd and Cr in the different indoor environment. The results indicates that occupant exposure to toxic trace metals in indoor environments can easily get cancer in different indoor working environments. Thus, trace metals in airborne fine and ultrafine particles be used in order to more accurately assess environmental and health risks. Thus chemical speciation of metal is important and should become a routine analysis in future study of air pollution.
\nElements | \nConcentration (ng m_3) | \n\n | Inhalation unit risk (μg m_3)_1 | \nExcess cancer risk (μg m_3)_1 | \n\n |
---|---|---|---|---|---|
Offices | \nAverage | \n95th percentile | \n\n | Average | \n95th percentile | \n
Cd | \n0.08 | \n1.05 | \n1.8 × 10_3 | \n0.14 | \n2.51 | \n
Cr (VI) (=∑Cr/7) | \n0.11 | \n2.01 | \n1.2 × 10_2 | \n0.13 | \n2.43 | \n
Ni | \n0.07 | \n1.03 | \n2.4 × 10_4 | \n0.16 | \n2.76 | \n
Shops | \nAverage | \n95th percentile | \n\n | Average | \n95th percentile | \n
Cd | \n0.08 | \n1.04 | \n1.8 × 10_3 | \n0.14 | \n2.40 | \n
Cr (VI) (=∑Cr/7) | \n0.10 | \n1.95 | \n1.2 × 10_2 | \n0.12 | \n2.37 | \n
Ni | \n0.06 | \n1.02 | \n2.4 × 10_4 | \n0.14 | \n2.58 | \n
Commercial centers | \nAverage | \n95th percentile | \n\n | Average | \n95th percentile | \n
Cd | \n0.05 | \n1.01 | \n1.8 × 10_3 | \n0.09 | \n1.97 | \n
Cr (VI) (=∑Cr/7) | \n0.09 | \n1.82 | \n1.2 × 10_2 | \n0.10 | \n2.20 | \n
Ni | \n0.04 | \n1.00 | \n2.4 × 10_4 | \n0.09 | \n2.36 | \n
Excess cancer risks of carcinogenic elements in PM2.5 in different indoor environment.
Indoor air pollution in developing countries is recognized as a major source of health risk to the exposed population, thus there is a need to address the issue of particles, especially fine particles and their related toxicity in different indoor microenvironments. On comparing with the standards given by WHO and national standards, PM10 and PM2.5 concentrations exceeded many folds at all the sampling sites. These high values indicate the need to find strategies to control particulate pollution. Metal concentrations were determined using the positive matrix factorization in PM2.5 in different indoor working environments. The sources responsible for PM2.5 emissions are smoking, incense burning, anthropogenic activities and use of different mechanical and electrical apparatus like computers, printers and photocopiers, etc. in the work environment. Risk assessment related to particulate pollutant was evaluated on the basis of metal contamination. The values summarized in this study represent initial estimates of emissions and their implications, which can be a useful addition to the existing literature, in particularly for the developing countries like India; where such measurements are yet under represented.
\nSupport is duly acknowledged by Council of Science and Industrial Research (Project No. 8/109 (0010)/2011-EMR-I). I would like to thank Principal and Head of the Chemistry Department, St. John’s College Agra for providing necessary facilities.
\nGiant cell arteritis (GCA) is a primary (non-necrotizing granulomatous) vasculitis of autoimmune etiology, which especially affects extra cranial medium-sized arteries (branches of the external carotid arteries-ECAs-particularly the superficial temporal arteries-TAs) and sometimes large-sized arteries (aorta and its major branches). It is also recognized as Horton, temporal, or granulomatous arteritis. It causes narrowing of the artery, leading (by wall thickening) to partial (stenosis) or complete obstruction (occlusion) of local arterial blood flow, its clinical manifestations being expressed by signs of local ischemia [1, 2, 3, 4, 5, 6].
\nGCA is the most common form of vasculitis that occurs in adults and in the elderly, being diagnosed over the age of 50’s. Women are two to three times more affected than men. It is well known that the disease can occur in every racial group but is most common in Caucasians, especially people of northern European descent, and others in northern latitudes. [1, 2, 3, 4, 5, 6].
\nAccording to Hunder [7], and Jennette [8] a complete diagnosis of GCA requires the presence of American College of Rheumatology (ACR) classification modified criteria:
age over 50 years at the onset of the disease;
moderate, bitemporal, recently installed headache;
scalp tenderness, abnormal temporal arteries on inspection and palpation (Figure 1), reduced pulse, jaw claudication (pain in the jaw while/after chewing);
blurred vision or permanent visual loss in one or both eyes (since permanent visual loss due to ischemia is frequent, GCA should be considered an ophthalmic emergency requiring immediate management);
systemic symptoms (fatigue, weight loss, fever, pain in the shoulders and hips: polymyalgia rheumatica);
increased inflammatory markers (erythrocyte sedimentation rate greater than 50 mm/h, C reactive protein greater than 1,5 mg/dl);
representative histologic findings in temporal artery biopsy (TAB): mononuclear cell infiltration or granulomatous inflammation of the vessel wall, usually accompanied with multinucleated giant cells (Figure 2).
Giant cell arteritis (GCA) of the left superficial temporal artery (TA) shows a prominent, tender and nodular artery, that is also hypo pulsating on palpation [
The histopathological examination of the left superficial temporal artery biopsy (TAB) noted [
Several imaging techniques may be suitable in the diagnosis of GCA. [9] Compared to other imaging techniques, US is considered to be the most suitable in the evaluation of GCA patients, therefor it can easily be performed by the clinician (immediately after the general examination of patient), and it is significantly shortening the waiting period until another investigation is performed. [9, 10, 11, 12, 13, 14, 15, 16].
\nUltrasonography (US) is a safe, noninvasive, without radiations, widespread accessible, fast, and low-cost bedside screening technique which has the unique capacity of studying real-time hemodynamics. It presents the ability to evaluate the anatomy of vessel’s wall, identifying equally parietal abnormalities (wall thickening, hypoechoic plaques, clotting, parietal hematoma, dissections) and the external diameter of the artery; it can rule out both stenosis and occlusion. Therefore, the use of US is widespread in neurological clinical practice, mainly in the evaluation of arterial atherosclerotic process but also for monitoring other diseases such as medium/large-vessel vasculitis. [17, 18, 19].
\nOlah noted that for US imaging of extracranial vessels different modes are being used:
\n
The strength of the echo is recorded as a bright dot, while the location of different gray dots corresponds to the depth of the target. [17]
\n
It associates a B-mode gray-scale image with pulse-wave (PW) Doppler flow velocities measurements.
The B-mode image represents the anatomical localization of the vessels, indicating the zone of interest where a Doppler sample volume should be placed and where the velocities are measured.
The Doppler angle can be measured correctly when the blood is parallel to the direction of the vessel. [17]
\n
Measure mean frequency shift in each sample volume.
It represents color–coded velocity information, which is superimposed as a color flow map on a B-mode image.
In each sample volume, the color reflects the blood flow velocity in a semi quantitative manner, as well as the flow direction relative to the transducer. Blood flowing toward or away from the transducer is shown by different colors (red and blue). Moreover, fast flow is indicated by a lighter hue and slow flow by a deeper one.
The color flow map indicates the position and orientation of the vessels, as well as the site of turbulent flow or stenosis. Since color flow mapping is based on flow velocity measured by PW technology, aliasing occurs if the frequency shift is higher than half of the pulse repetition frequency (PRF). [17]
\n
Uses the signal intensity of the returning Doppler signal instead of frequency shift.
Power (intensity) of the signal is displayed as a color map superimposed on a B-mode image. Since the Doppler power is determined mainly by the volume rather than the velocity of moving blood, power Doppler imaging is free from aliasing artifacts and much more sensitive to detect flow, especially in the low-flow regions. However, it does not contain information about the flow direction or flow velocity. [17]
The advantages of US over other imaging techniques in GCA are represented by its safety, accessibility, tolerability, fast (may take about 15-20 minutes, if it’s conducted by an experienced sonographer) and the more important, its high resolution (a high –frequency probe offers both an axial and a lateral resolution of 0.1 mm) [19, 20, 21, 22, 23, 24, 25, 26, 27]. The smaller the vessel diameter, the more difficult is to appreciate the vessel wall damages, so that, in this case, the most informative US data are based on Doppler spectral evaluation. This is also valid for the assessment of medium to small vessel inflammation such as intracranial vasculitis. Small vessel vasculitis (the ANCA-associated or the immune complex vasculitis) are not a domain of ultrasound. [19].
\nFurthermore, US has a higher sensitivity than TAB, the last one evaluating only a restricted anatomical region in a systemic disease. Using US, we can reveal pathological characteristics in GCA: non-compressible arteries (compression sign), the wall thickening (“halo” sign), stenosis and vessel occlusion. A normal intima-media complex (IMC) of an artery is represented by US as a homogeneous, hypoechoic or anechoic echo structure delineated by two parallel hyperechoic margins. [19, 20, 21, 22, 23, 24, 25, 26, 27].
\nThere is imperative to underline the importance of establishing the arteries that should be routinely examined in a patient suspected for GCA and these are: the TAs, and axillary arteries. If US of these arteries does not reveal suggestive lesions, in the presence of a clear patient history and of an obvious clinical examination, other arteries should be examined: other branches of the ECAs (the internal maxillary, the facial, the lingual, the occipital arteries), the vertebral, the subclavian, the common carotid arteries-CCAs, and the internal carotid arteries-ICAs. [9, 19, 21].
\nRegarding the adequate US equipment for the diagnosis of GCA, modern high-resolution linear probes providing Doppler mode should be used, especially for examination of TAs. We should take into consideration that tissue penetration increases with lower frequencies and the resolution of US increases with higher frequencies. Probes that provide frequencies >20 MHz allow the clearly visualization of the normal IMC of TAs probes with frequencies ≥15 MHz are usually used for detection of minor wall thickening. [19, 21].
\nIn 2012, during the Chapel Hill Consensus Conference [19, 28], large vascular vasculitis (LVV) was well-defined as a vasculitis involving the aorta and its major branches, although any size of artery may be affected. This definition does not state that LVV mainly affects large vessels because in many patients, the number of medium and small arteries affected is greater than the number of large arteries involvement. For example, in GCA, only few branches of the ECAs may be affected when there is involvement of numerous small branches extending into the eye and orbit (e.g., central retinal artery, posterior ciliary arteries). [29, 30] Less frequently, the CCA and the ICA are also affected (Figures 3 and 4). [9].
\nLarge vessels GCA; CT-angiography- occlusion of the left CCA, ECA, and ICA [
Large vessels GCA, color Doppler ultrasound in transverse view of the right CCA. Hypoechoic wall swelling with right CCA occlusion [
As Sturzenegger pointed up, angiography is not able to illustrate the vessel wall, so as to diagnose the inflammation of the large cervical and cervico-brachial vessels (aorta and its supra-aortic branches), the US can be very useful, since it can define alterations of the vessel wall with the use of B-mode imaging, while Doppler spectral flow velocity evaluation can help identify the stenosis or occlusion of the vessel. [19].
\nColor Doppler Duplex sonography (CDDS) is an excellent device used in screening the large vessels involvement. Agreeing with different authors, including Sturzenegger, there are two ultra-sonographic hallmarks of large vessels GCA:
Vessel wall thickening, that typically is homogeneous, circumferential and over long segments (Figures 4 and 5);
Stenosis, typically revealing slickly tapered luminal tightening (hour glass like) [19, 20, 21, 22, 23, 24, 25, 26, 27]
Large vessel GCA, color Doppler ultrasound in longitudinal view of the right CCA with hypoechoic wall swelling [
Remarkably in some cases [9], the common carotid and the internal carotid arteries are also involved (large-vessel GCA) (Figures 3, 4, and 5).
\nExtracranial Duplex sonography investigates almost completely the whole length of the common superficial TAs, including the frontal and parietal branches, and founds that inflammation is segmental (intermittent arterial involvement) [19, 20, 21, 22, 23, 24, 25, 26, 27]. The common superficial TA derives from the ECA. It divides into the frontal and parietal ramus in front of the ear. The distal common superficial TA and the rami are localized between the two layers of the temporal fascia, which is like a bright band at ultrasound examination. [19, 20, 21, 22, 23, 24, 25, 26, 27].
\nHigh-resolution color Doppler US can illustrate the vessel wall and the lumen of the TAs. One should use linear probes with a minimum gray scale frequency of 8 Mhz. Color frequency should be about 10 Mhz. [19, 20, 21, 22, 23, 24, 25, 26, 27].
\nThe pulse repetition frequency (PRF) should be about 2.5 kHz as maximum systolic velocities are rather high (20-100 cm/s). Steering of the color box and the Doppler beam should be maximal as the rami are parallel to the probe. It is important that the color covers the artery lumen exactly. [19, 20, 21, 22, 23, 24, 25, 26, 27].
\nThe sonographer should perform at least 50 Duplex ultrasound of the TAs of subjects without GCA to be sure about the appearance of normal TAs before starting to evaluate patients with GCA. [19, 20, 21, 22, 23, 24, 25, 26, 27].
\nThe investigation should begin with the TA, using the longitudinal scan. The probe should then be moved along the course of the TA to the parietal ramus. On the way back one should delineate the TA in transverse scans. Using the transverse scan, one can find the frontal ramus, which should then be delineated in both scans (longitudinal and transverse). If the color signal indicates localized aliasing and diastolic flow, one should use the pw-Doppler mode to confirm the presence of stenosis. [19, 20, 21, 22, 23, 24, 25, 26, 27].
\nIn 1997 Schmidt et al. proved that the most specific (almost 100% specificity) and sensitive (73% sensitivity) sign for GCA was a concentric hypo-echogenic mural thickening, dubbed “halo”, which the authors interpreted as “vessel wall edema”. [24].
\nOther positive findings for GCA are the presence of occlusion and stenosis. [19, 20, 21, 22, 23, 24, 25, 26, 27].
\nIn conclusion, there are three important items in the ultrasound diagnosis of temporal arteritis:
“dark halo” sign – a typically homogeneous, hypoechoic, circumferential wall thickening around the lumen of an inflamed TA - which represents vessel wall edema and a characteristic finding in temporal arteritis/GCA. It is well delineated toward the lumen (Figure 6).
stenosis are documented by blood-flow velocities, which are more than twice the rate recorded in the area of stenosis compared with the area before the stenosis, with wave forms demonstrating turbulence and reduced velocities behind the area of stenosis (Figure 7).
acute occlusions, in which the US image is comparable to that of acute embolism in other vessels, showing hypoechoic material in the former artery lumen with absence of color signals. [19, 20, 21, 22, 23, 24, 25, 26, 27]
Color Doppler ultrasonography (CDUS) of the right TA shows a hypoechoic halo around the lumen in transverse view (arrow). The “halo sign” corresponds to edema of the artery wall. [
Longitudinal view of the right TA by color Doppler ultrasonography (CDUS) shows a hypoechoic halo of the TA and the presence of turbulent and weak flow, suggesting the presence of stenosis. The PSV is 1 m/s, that is double compared to the segment without stenosis. [
Related ultrasound patterns can be found in other arteries: the facial, the internal maxillary, the lingual, the occipital, the distal subclavian and the axillary arteries.
\nThe best time to perform ultrasound investigation is before initiating the corticosteroid treatment, or in the first 7 days of treatment, since with corticosteroid therapy the” halo” revealed by TAs ultrasound disappears within 2-3 weeks. The wall inflammation, stenosis, or occlusions of the larger arteries (CCA, ICA) remain for months, despite corticosteroid treatment. However, the diagnosis process should not postpone the initiation of therapy. Ultrasound may also detect inflamed TAs in patients with clinically normal TAs. Some patients with the clinical image of polymyalgia rheumatica, but with hidden TAs may be diagnosed using ultrasonography. [9, 10, 11, 12, 13, 14, 15, 16, 19, 20, 21, 22, 23, 24, 25, 26, 27].
\nIn 2010, Arida et al. [26] evaluated a number of studies that examined the sensitivity and specificity of the “halo” sign confirmed by TA ultrasound (US) for GCA diagnosis versus the American College of Rheumatology (ACR) 1990 criteria for the classification of this vasculitis (used as a reference standard). Only 8 studies involving 575 patients, 204 of whom received the final diagnosis of GCA, achieved the technical quality criteria for US. This meta-analysis disclosed a sensitivity of 68% and a specificity of 91% for the unilateral “halo” sign, as well as 43% and 100%, respectively, for the bilateral “halo” sign in TA US for GCA diagnosis when the 1990 ACR criteria are used as the reference standard. The authors established that the halo sign in US is of great utility in diagnosing GCA. [19, 20, 21, 22, 23, 24, 25, 26, 27].
\nIn the case of consistent clinical and sonographic results, temporal arteries biopsy (TAB) does not appear to be useful and justified. [19, 27].
\nSturzenegger affirmed that differential diagnosis with arteriosclerosis is important in patients over 50 years, taking into consideration that GCA with large vessels disease disturbs almost exclusively this category of patients. There are some characteristic features of the arteriosclerotic wall: the thickening usually appears less homogeneous; there are calcified arteriosclerotic plaques ulcers; stenosis extends over shorter segments, they are not concentric, not tapering, and location of lesions differs (e.g., mainly bifurcations). [19].
\nBesides, agreeing to Sturzenegger, differential diagnosis with the other LVV, especially Takayasu arteritis, has to be reflected:
Takayasu arteritis usually affects women below the age of 40 years;
symptoms like tender scalp or polymyalgia syndrome are exceptional;
the involvement of CCA is more frequent in Takayasu arteritis, while the involvement of temporal artery in Takayasu arteritis is not known;
US image of wall thickening (“halo”) is brighter in TA than in GCA probably due to a larger mural edema in GCA which is a more acute disease than TA. Reflected. [19, 20, 21, 22, 23, 24, 25, 26, 27]
Approximately 25% of patients with temporal artery biopsy (TAB) - proven GCA have ophthalmologic complications: usually unilateral visual loss (due to the vasculitic involvement of orbital vessels:
of posterior ciliary arteries (PCAs) - represented by arteritic anterior ischemic optic neuropathies (A-AION), or
of central retinal artery (CRA) - represented by central retinal artery occlusion (CRAO). [31, 32, 33, 34, 35]
Schmidt compared the results of TAs-US examinations with the occurrence of visual ischemic complications (A-AION, CRAO, branch retinal artery occlusion, diplopia, or amaurosis fugax) in 222 consecutive patients with newly diagnosed, active GCA. [21, 22, 23, 24].
\nHowever, findings of TAs US did not correlate with eye complications. [21, 22, 23, 24].
\nThis is the reason why we always have to exam the orbital (retrobulbar) vessels in GCA patients or in patients with unilateral abrupt visual loss [9, 10, 11, 12, 13, 14, 15, 16] (Figure 8A,B).
\nColor Doppler imaging (CDI) of orbital (retro-bulbar) vessels: (A). central retinal artery (CRA); (B). posterior ciliary arteries (PCAs) [
The ophthalmic artery (OA) branches in several arteries, including (Table 1):
the central retinal artery (CRA) (Figure 8 A), and
the posterior ciliary arteries (nasal and temporal branches-nPCAs, tPCAs) [28, 31, 32] (Figure 8B), (Table 1). [15, 28, 31, 32]
Parameter | \nOA | \nCRA | \nPCA (temporal) | \nPCA (nasal) | \nSOV (superior ophthalmic vein) | \n
---|---|---|---|---|---|
45,3 ± 10,5 | \n10,2 ± 3,8 | \n||||
11,8 ± 4,3 | \n4,3 ± 2,4 | \n||||
0,74 ± 0,07 | \n\n |
OA finishes in the a. supra-trohlearis and
Standard neurovascular ultrasound machines equipped with linear-array transducers emitting 6-12 MHz (up to 15 MHz) are adequate for identifying (by Color Doppler sonography), and measuring (by spectral analysis pulsed Doppler sonography) the blood flow in the orbital vessels: the OA, the CRA and central retinal vein (CRV), PCAs, and the superior ophthalmic vein (SOV). [28, 31, 32].
\nThe CRA, a distal branch of the OA, enters the optic nerve (ON) approximately 1-1.5 cm distal from the bulbus coming from the dorsolateral direction. Parallel to this is the CRV.
\nThe PCAs are located near the optic nerve (ON) (the nasal-nPCA and the temporal-tPCA branches). [28, 31, 32].
\nIf the vessels are difficult to display, the power should be elevated for a short time if the clinical question is important. [28, 31, 32].
\nThe optic nerve head (ONH) consists of (from anterior to posterior):
the surface nerve fiber layer - mostly supplied by the retinal arterioles. The cilioretinal artery, when present, usually supplies the corresponding sector of the surface layer. [36, 37, 38, 39, 40]
the prelaminar region - situated anterior of the lamina cribrosa. It is supplied by centripetal branches from the peripapillary choroid. [36, 37, 38, 39, 40]
the lamina cribrosa region - supplied by centripetal branches from the posterior ciliary arteries (PCAs), either directly or by the so-called arterial circle of Zinn and Haller (when is present). [36, 37, 38, 39, 40]
the retrolaminar region - is the part of the ONH that lies immediately behind the lamina cribrosa. It is supplied by two vascular systems: the peripheral centripetal and the axial centrifugal systems. The previous represents the main source of stream for this part. It is formed by recurrent pial branches arising from the peripapillary choroid and the circle of Zinn and Haller (when present, or the PCAs instead). In addition, pial branches from the central retinal artery (CRA) also supply this part. The latter is not present in all eyes. When present, it is formed by inconstant branches arising from the intraneural part of the CRA.
From the description of the arterial supply of the ONH given above, it is obvious that the PCAs are the main source of blood supply to the ONH. [36, 37, 38, 39, 40].
\nThe blood flow in the ONH depends upon [36, 37, 38, 39, 40]:
resistance to blood flow - depends upon the condition and caliber of the vessels supplying the ONH, which in turn are influenced by: the efficiency of auto-regulation of the ONH blood flow, the vascular variations in the arteries feeding the ONH circulation, and the rheological properties of the blood.
arterial blood pressure (BP) - both arterial hypertension and hypotension can influence the ONH blood flow in several ways. In an ONH, a fall of blood pressure below a critical level of auto-regulation would decrease its blood flow. Decrease of BP in the ONH may be due to systemic (nocturnal arterial hypotension during sleep, intensive antihypertensive medication, etc.) or local hypotension.
intra-ocular pressure (IOP) - there is an opposite relationship between intra-ocular pressure and perfusion pressure in the ONH.
The blood flow in the ONH is calculated by using the following formula:
\nPerfusion pressure = Mean BP minus intraocular pressure (IOP).
\nMean BP = Diastolic BP + 1/3 (systolic - diastolic BP) [6, 13].
\nAION is the consequence of an acute ischemic disorder (a segmental infarction) of the ONH supplied by the PCAs. Blood supply interruption can occur with or without arterial inflammation. Therefore, AION is of two types: non-arteritic AION (NA-AION) and arteritic AION (A-AION). The prior is far more common than the last, and they are distinct entities etiologically, pathogenically, clinically and from the management point of view. [36, 37, 38, 39, 40].
\nA history of amaurosis fugax before an abrupt, painless, and severe loss of vision of the involved eye, with concomitant diffuse pale optic disc edema is extremely suggestive of A-AION. None of these symptoms are found in NA-AION patients. [36, 37, 38, 39, 40].
\nIn acute stage, blood flow cannot be detected in the PCAs in the clinically affected eye of any of the GCA patients with A-AION. Low end diastolic velocities (EDV) and high resistance index (RI) are identified in all other orbital vessels (including the PCAs in the opposite eye) of all A-AION patients. [9, 10, 11, 12, 13, 14, 41].
\nOver 7 days, Spectral Doppler analysis of the orbital vessels highlights blood flow alterations in all A-AION patients even with a high-dose corticosteroids therapy. Severely reduced blood flow velocities (especially EDV) in the PCAs of the affected eye (both nasal and temporal branches), compared to the unaffected eye, are observed. An increased RI in the PCAs is noted (the RI is higher on the clinically affected eye as compared to the unaffected eye). [9, 10, 11, 12, 13, 14, 41] (Figure 9A,B).
\nCDI of the PCAs in A-AION: (A). Decreased EDV in the nasal PCAs of the clinically affected right eye, and (B) of the clinically unaffected left eye.
Fewer abnormalities are detected in the CRAs: high RI are measured in both sides, with decreased peak systolic velocities (PSV) in the CRA of the clinically affected eye. [9, 10, 11, 12, 13, 14, 41].
\nSimilar abnormalities are noted in the OAs: high RI are measured in both sides. [9, 10, 11, 12, 13, 14, 41].
\nAt 1 month, after treatment with high-dose corticosteroids, CDI examinations of orbital blood vessels reveals that blood flow normalization is slow in all A-AION patients. [9, 10, 11, 12, 13, 14, 41].
\nIn conclusion, the Spectral Doppler Analysis of the orbital vessels in A-AION indicates (after several days of corticosteroid treatment) low blood velocities, especially EDV, and high RI in all orbital vessels, in both orbits. These signs represent characteristic signs of the CDI of the orbital vessels in A-AION. [9, 10, 11, 12, 13, 14, 41].
\nIn contrast, the patients with NA-AION present the following characteristics in acute stage, and at 1 week of evolution:
minor reduction of PSV in PCAs (nasal and temporal) in the affected eye, compared to the unaffected eye.
slight decrease of PSV in CRA of the affected eye, due to papillary edema. [9, 10, 11, 12, 13, 14, 41]:
in OAs, PSV are variable: normal to decreased, according to ipsilateral ICAs status.
Severe ICA stenosis (≥70% of vessel diameter) combined with an insufficient Willis polygon led to diminish PSV in ipsilateral OA. [9, 10, 11, 12, 13, 14, 41].
\nIn 1 month, CDI examinations of orbital blood vessels reveal that blood flow normalization is reached. The exceptions are the cases with severe ipsilateral ICA stenosis/occlusion. [9, 10, 11, 12, 13, 14, 41].
\nIn conclusion, in NA-AION, blood velocities and RI in PCAs are preserved. Similar results were obtained in other studies. [9, 10, 11, 12, 13, 14, 41].
\nFluorescein angiogram and CDI of the orbital vessels data support the histopathological evidence of involvement of the entire trunk of the PCAs in the A-AION (impaired optic disc and choroidal perfusion in the patients with A-AION). On the other hand, in the NA-AION, the impaired flow to the optic nerve head (ONH) is distal to the PCAs themselves, possibly at the level of the para-optic branches (only 1/3 of the flow of the PCAs). [36, 37, 38, 39, 40].
\nThese branches supply the ONH directly (impaired optic disc perfusion, with relatively conservation of the choroidal perfusion). [36, 37, 38, 39, 40].
\nExtremely delayed or absent filling of the choroid has been depicted as a fluorescein angiogram characteristic of arteritic AION and has been suggested as one useful factor by which A-AION can be differentiated from NA-AION. [36, 37, 38, 39, 40].
\nCRAO is the result of an abrupt diminuation of blood flow in CRA, severe enough to cause ischemia of the inner retina. Due to the fact that there are no functional anastomoses between choroidal (PCAs) and retinal circulation (CRA), CRAO determines severe and permanent loss of vision. Therefore, it is very important to identify the cause of CRAO, in order to protect the contralateral eye. Frequently, the site of the blockage is within the optic nerve substance and for this reason, it is generally not visible on the ophthalmoscopy. The majority of CRAO are caused by thrombus formation due to systemic diseases, including GCA. For this reason, all patients with CRAO should undergo a systemic evaluation. [42, 43, 44].
\nThe patients with an unilateral CRAO present at the Spectral Doppler analysis of the retrobulbar vessels the following aspects [9, 15, 16]:
an elevated RI in the CRAs (the RI is higher on the affected side, than it is on the unaffected side); with severe diminished blood flow velocities (especially EDV) in the CRA.
fewer abnormalities are observed in the PCAs, and in the OAs (Figure 10).
CDI of orbital vessels revealed severely diminished EDV and high RI in both CRAs (a, b) despite the fact that the left eye had the normal aspect at ophthalmoscopy. Fewer abnormalities were observed in the PCAs (c, d). [
Other imaging techniques, such as high-resolution magnetic resonance imaging (MRI), magnetic resonance-angiography (MR-A), computer tomography angiography (CT-A), positron emission tomography (PET) provide valuable information regarding the structure of large vessels, highlighting with much greater precision the thoracic aorta, compared with US. [45, 46, 47].
\nThere are few studies that compared US with other imaging techniques. Some of them indicated that there is a good correlation between US and PET, even though PET might have a little more sensitivity for vertebral arteries examination. [45, 46] 18F-fluorodeoxyglucose-positron emission tomography/ computed tomography (FDG-PET/CT) has a higher sensitivity for detection of large arteries and aortic involvement - analysis of the arterial wall. [45, 46] The diagnostic power of high-resolution MRI and color-coded duplex US of extra-cranial arteries in detecting GCA are equivalent [47].
\nThe disadvantages of this techniques are: they are more expensive, hardly accessible, some of them are limited by invasiveness, nephrotoxicity (angiography) and exposure to high radiations (CT,PET), this is why they might be unnecessary (excepting those patients with exclusively thoracic aorta involvement) and are not accepted as diagnostic methods in GCA. They should only be used when interventions are required [45, 46, 47].
\nAll these imaging techniques should always be performed by well-trained specialists, using suitable equipment and operational protocols. [45, 46, 47].
\nNevertheless, US is particularly useful in examining the orbital vessels. [9, 10, 11, 12, 13, 14, 15, 16, 28, 31, 32, 41].
\nThe diagnostic work-up of AION benefits from the combined used of fluorescein angiography and noninvasive multimodal imaging, including CDI of the orbital vessels and structural Optical Coherence Tomography (OCT) of the optic nerve head (ONH) and OCT angiography [10, 48]. They provide very detailed information regarding the structural (retinal nerve fiber layer-RNFL-thickness/optic disc edema) and vascular impairments (microvascular defects-vessel tortuosity, and vessel density reduction) of the ONH, respectively [10, 48].
\nUS should be used as a first-line diagnostic investigation for patients presenting with clinical and biological features suggestive for GCA, taking into consideration that it has a high sensitivity to detect vessel wall thickening (dark hallo sign) in the case of large/medium vessels. In a few cases of our studies, the CCAs and the ICAs were also involved.
\nIn consequence, in our department, CCDS has emerged as a safe and reliable alternative to TAB as a point of care diagnostic tool in the management of temporal arteritis.
\nThe eye involvement in GCA is frequent and consists in A-AIONs or CRAO, with abrupt, painless, and severe loss of vision of the involved eye.
\nBecause findings of TAs US do not correlate with eye complications in GCA, CDI of the orbital vessels is of critical importance, in order to quickly differentiate the mechanism of eye involvement (arteritic, versus non-arteritic). This US tehnique may be helpful to detect the blood flow in the orbital vessels, especially in cases of opacity of the medium, or when the clinical appearance of ophthalmologic complications in temporal arteritis is athypical.
\nThe Spectral Doppler Analysis of the orbital vessels in GCA with eye involvement reveals low blood velocities, especially EDV, and high RI in all orbital vessels, in both orbits, for all patients (especially on the affected side).
\nA huge advantage of CDI of orbital vessels is that it provides immediate information that can be used to inform treatment decisions, including a potential reduction in loss of sight and avoidance of unnecessary long-term steroid treatment by early exclusion of mimics.
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\\n\\nBook: The publication as a collection of chapters compiled by IntechOpen including the Chapter. Chapter: The original literary work created by Corresponding Author and any Co-Author that is the subject of this Agreement.
\\n\\n2. CORRESPONDING AUTHOR'S GRANT OF RIGHTS
\\n\\n2.1 Subject to the following Article, the Corresponding Author grants and shall ensure that each Co-Author grants, to IntechOpen, during the full term of copyright and any extensions or renewals of that term the following:
\\n\\nThe aforementioned licenses shall survive the expiry or termination of this Agreement for any reason.
\\n\\n2.2 The Corresponding Author (on their own behalf and on behalf of any Co-Author) reserves the following rights to the Chapter but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Chapter as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world.
\\n\\nThe Corresponding Author confirms that they (and any Co-Author) are and will remain a member of any applicable licensing and collecting society and any successor to that body responsible for administering royalties for the reprographic reproduction of copyright works.
\\n\\nSubject to the license granted above, copyright in the Chapter and all versions of it created during IntechOpen's editing process (including the published version) is retained by the Corresponding Author and any Co-Author.
\\n\\nSubject to the license granted above, the Corresponding Author and any Co-Author retains patent, trademark and other intellectual property rights to the Chapter.
\\n\\n2.3 All rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the Corresponding Author's or any Co-Author’s specific approval.
\\n\\n2.4 The Corresponding Author (on their own behalf and on behalf of each Co-Author) will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Chapter as a consequence of IntechOpen's changes to the Chapter arising from translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits.
\\n\\n3. CORRESPONDING AUTHOR'S DUTIES
\\n\\n3.1 When distributing or re-publishing the Chapter, the Corresponding Author agrees to credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen. The Corresponding Author warrants that each Co-Author will also credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen, when they are distributing or re-publishing the Chapter.
\\n\\n3.2 When submitting the Chapter, the Corresponding Author agrees to:
\\n\\nThe Corresponding Author will be held responsible for the payment of the Open Access Publishing Fees.
\\n\\nAll payments shall be due 30 days from the date of the issued invoice. The Corresponding Author or the payer on the Corresponding Author's and Co-Authors' behalf will bear all banking and similar charges incurred.
\\n\\n3.3 The Corresponding Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Chapter worldwide for the full term of the above licenses, and shall provide to IntechOpen upon request the original copies of such consents for inspection (at IntechOpen's option) or photocopies of such consents.
\\n\\nThe Corresponding Author shall obtain written informed consent for publication from people who might recognize themselves or be identified by others (e.g. from case reports or photographs).
\\n\\n3.4 The Corresponding Author and any Co-Author shall respect confidentiality rights during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Corresponding Author and any Co-Author are confidential and are intended only for the recipient. The contents may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\\n\\n4. CORRESPONDING AUTHOR'S WARRANTY
\\n\\n4.1 The Corresponding Author represents and warrants that the Chapter does not and will not breach any applicable law or the rights of any third party and, specifically, that the Chapter contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy. The Corresponding Author warrants and represents that: (i) the Chapter is the original work of themselves and any Co-Author and is not copied wholly or substantially from any other work or material or any other source; (ii) the Chapter has not been formally published in any other peer-reviewed journal or in a book or edited collection, and is not under consideration for any such publication; (iii) they themselves and any Co-Author are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) they themselves and any Co-Author have not assigned and will not during the term of this Publication Agreement purport to assign any of the rights granted to IntechOpen under this Publication Agreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\\n\\nThe Corresponding Author also warrants and represents that: (i) they have the full power to enter into this Publication Agreement on their own behalf and on behalf of each Co-Author; and (ii) they have the necessary rights and/or title in and to the Chapter to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses expressed to be granted in this Publication Agreement. If the Chapter was prepared jointly by the Corresponding Author and any Co-Author, the Corresponding Author warrants and represents that: (i) each Co-Author agrees to the submission, license and publication of the Chapter on the terms of this Publication Agreement; and (ii) they have the authority to enter into this Publication Agreement on behalf of and bind each Co-Author. The Corresponding Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each such Co-Author.
\\n\\nThe Corresponding Author agrees to indemnify and hold IntechOpen harmless against all liabilities, costs, expenses, damages and losses and all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of or in connection with any breach of the aforementioned representations and warranties. This indemnity shall not cover IntechOpen to the extent that a claim under it results from IntechOpen's negligence or willful misconduct.
\\n\\n4.2 Nothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\\n\\n5. TERMINATION
\\n\\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co-Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\\n\\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\\n\\n6. INTECHOPEN’S DUTIES AND RIGHTS
\\n\\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Chapter attributing it to the Corresponding Author and any Co-Author.
\\n\\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Chapter and has the right to contact the Corresponding Author and any Co-Author until the Chapter is publicly available on any platform owned and/or operated by IntechOpen.
\\n\\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Chapter, IntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\\n\\n7. MISCELLANEOUS
\\n\\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\\n\\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\\n\\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\\n\\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\\n\\n7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
\\n\\n7.6 Severance: If any provision or part-provision of this Publication Agreement is or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\\n\\nAny modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\\n\\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\\n\\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
\\n\\nLast updated: 2020-11-27
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The Corresponding Author (acting on behalf of all Authors) and INTECHOPEN LIMITED, incorporated and registered in England and Wales with company number 11086078 and a registered office at 5 Princes Gate Court, London, United Kingdom, SW7 2QJ conclude the following Agreement regarding the publication of a Book Chapter:
\n\n1. DEFINITIONS
\n\nCorresponding Author: The Author of the Chapter who serves as a Signatory to this Agreement. The Corresponding Author acts on behalf of any other Co-Author.
\n\nCo-Author: All other Authors of the Chapter besides the Corresponding Author.
\n\nIntechOpen: IntechOpen Ltd., the Publisher of the Book.
\n\nBook: The publication as a collection of chapters compiled by IntechOpen including the Chapter. Chapter: The original literary work created by Corresponding Author and any Co-Author that is the subject of this Agreement.
\n\n2. CORRESPONDING AUTHOR'S GRANT OF RIGHTS
\n\n2.1 Subject to the following Article, the Corresponding Author grants and shall ensure that each Co-Author grants, to IntechOpen, during the full term of copyright and any extensions or renewals of that term the following:
\n\nThe aforementioned licenses shall survive the expiry or termination of this Agreement for any reason.
\n\n2.2 The Corresponding Author (on their own behalf and on behalf of any Co-Author) reserves the following rights to the Chapter but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Chapter as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world.
\n\nThe Corresponding Author confirms that they (and any Co-Author) are and will remain a member of any applicable licensing and collecting society and any successor to that body responsible for administering royalties for the reprographic reproduction of copyright works.
\n\nSubject to the license granted above, copyright in the Chapter and all versions of it created during IntechOpen's editing process (including the published version) is retained by the Corresponding Author and any Co-Author.
\n\nSubject to the license granted above, the Corresponding Author and any Co-Author retains patent, trademark and other intellectual property rights to the Chapter.
\n\n2.3 All rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the Corresponding Author's or any Co-Author’s specific approval.
\n\n2.4 The Corresponding Author (on their own behalf and on behalf of each Co-Author) will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Chapter as a consequence of IntechOpen's changes to the Chapter arising from translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits.
\n\n3. CORRESPONDING AUTHOR'S DUTIES
\n\n3.1 When distributing or re-publishing the Chapter, the Corresponding Author agrees to credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen. The Corresponding Author warrants that each Co-Author will also credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen, when they are distributing or re-publishing the Chapter.
\n\n3.2 When submitting the Chapter, the Corresponding Author agrees to:
\n\nThe Corresponding Author will be held responsible for the payment of the Open Access Publishing Fees.
\n\nAll payments shall be due 30 days from the date of the issued invoice. The Corresponding Author or the payer on the Corresponding Author's and Co-Authors' behalf will bear all banking and similar charges incurred.
\n\n3.3 The Corresponding Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Chapter worldwide for the full term of the above licenses, and shall provide to IntechOpen upon request the original copies of such consents for inspection (at IntechOpen's option) or photocopies of such consents.
\n\nThe Corresponding Author shall obtain written informed consent for publication from people who might recognize themselves or be identified by others (e.g. from case reports or photographs).
\n\n3.4 The Corresponding Author and any Co-Author shall respect confidentiality rights during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Corresponding Author and any Co-Author are confidential and are intended only for the recipient. The contents may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\n\n4. CORRESPONDING AUTHOR'S WARRANTY
\n\n4.1 The Corresponding Author represents and warrants that the Chapter does not and will not breach any applicable law or the rights of any third party and, specifically, that the Chapter contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy. The Corresponding Author warrants and represents that: (i) the Chapter is the original work of themselves and any Co-Author and is not copied wholly or substantially from any other work or material or any other source; (ii) the Chapter has not been formally published in any other peer-reviewed journal or in a book or edited collection, and is not under consideration for any such publication; (iii) they themselves and any Co-Author are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) they themselves and any Co-Author have not assigned and will not during the term of this Publication Agreement purport to assign any of the rights granted to IntechOpen under this Publication Agreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\n\nThe Corresponding Author also warrants and represents that: (i) they have the full power to enter into this Publication Agreement on their own behalf and on behalf of each Co-Author; and (ii) they have the necessary rights and/or title in and to the Chapter to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses expressed to be granted in this Publication Agreement. If the Chapter was prepared jointly by the Corresponding Author and any Co-Author, the Corresponding Author warrants and represents that: (i) each Co-Author agrees to the submission, license and publication of the Chapter on the terms of this Publication Agreement; and (ii) they have the authority to enter into this Publication Agreement on behalf of and bind each Co-Author. The Corresponding Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each such Co-Author.
\n\nThe Corresponding Author agrees to indemnify and hold IntechOpen harmless against all liabilities, costs, expenses, damages and losses and all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of or in connection with any breach of the aforementioned representations and warranties. This indemnity shall not cover IntechOpen to the extent that a claim under it results from IntechOpen's negligence or willful misconduct.
\n\n4.2 Nothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\n\n5. TERMINATION
\n\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co-Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\n\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\n\n6. INTECHOPEN’S DUTIES AND RIGHTS
\n\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Chapter attributing it to the Corresponding Author and any Co-Author.
\n\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Chapter and has the right to contact the Corresponding Author and any Co-Author until the Chapter is publicly available on any platform owned and/or operated by IntechOpen.
\n\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Chapter, IntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\n\n7. MISCELLANEOUS
\n\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\n\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\n\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\n\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\n\n7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
\n\n7.6 Severance: If any provision or part-provision of this Publication Agreement is or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\n\nAny modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\n\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\n\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
\n\nLast updated: 2020-11-27
\n\n\n\n
\n"}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[{id:"396",title:"Dr.",name:"Vedran",middleName:null,surname:"Kordic",slug:"vedran-kordic",fullName:"Vedran Kordic",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/396/images/7281_n.png",biography:"After obtaining his Master's degree in Mechanical Engineering he continued his education at the Vienna University of Technology where he obtained his PhD degree in 2004. He worked as a researcher at the Automation and Control Institute, Faculty of Electrical Engineering, Vienna University of Technology until 2008. His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. 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